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THE

Hlower Ueterinary Library

FOUNDED BY
ROSWELL P. FLOWER
for the use of the

N. Y. STATE VETERINARY COLLEGE
1897

 

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cooperation with Cornell University Libraries, 2007.
You may use and print this copy in limited quantity
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for revenue-generating or other commercial purposes.
CLINICAL DIAGNOSIS.

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CLINICAL DIAGNOSIS:

THE

BACTERIOLOGICAL, CHEMICAL, AND MICROSCOPICAL
EVIDENCE OF DISEASE.

BY

Dr. RUDOLF v. JAKSCH,

PROFESSOR OF SPECIAL PATHOLOGY AND THERAPEUTICS, AND DIRECTOR OF THE
MEDICAL CLINIC, IN THE GERMAN UNIVERSITY OF PRAGUE.

Granslated from the Third German Edition anv Enlarged by

JAMES CAGNEY, M.A., M.D.

MEMBER OF THE ROYAL COLLEGE OF PHYSICIANS OF LONDON ;
PHYSICIAN TO THE HOSPITAL FOR EPILEPSY AND PARALYSIS, REGENT’S PARK;
LATE DEMONSTRATOR OF ANATOMY, ST. MARY’S HOSPITAL MEDICAL SCHOOL,

With Mumerous Fllustrations (partly in Colours).

LONDON:

CHARLES GRIFFIN AND COMPANY, Limitep.
PHILADELPHIA : J. B. LIPPINCOTT COMPANY.

1893.
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Vorrede zur 2. englischen Ausgabe.

Die Edition einer 2. englischen Auflage dieses Buches, 2
Jahre nach dem Erscheinen der 1. Auflage, zeigt, dass es dem
Werke gelungen ist, auch in englischen Kreisen sich Freunde zu
erwerben. Indem ich dies mit Genugthuung feststelle, dringt
es mich, den Wunsch hinzufiigen, dass auch diese 2. Edition
bei den englischen Collegen dieselbe giinstige Beurtheilung finden
mége !

Herrn Dr. James Cagney sage ich fiir seine Miihewaltung
besten Dank.

Pror. R. v. JAKSCH.

PRAG, tm Oktober, 1892.

In the Second Edition of this book, as in the First, I have
endeavoured to adhere closely to the German text. The changes
are chiefly of form and arrangement, with here and there others
that have been made after consulting the original authorities. I
am indebted to Prof. v. Jaksch for his cordial co-operation. For
the new matter, which is in every case enclosed within square
brackets, I am alone responsible. It includes, however, a part
of that which was contributed by Prof. Stirling as an Appendix
to the First Edition. I have again to express my acknowledg-
ments to the publishers (Messrs. Griffin) for the assistance which
they have given me in putting the book through the press.

JAMES CAGNEY.

WIMPOLE STREET, November 1892.

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TABLE OF CONTENTS.

CHAPTER I.
THE BLOOD.

I. CoLour of THE BLoop
II. Reaction
III. Sprciric GRAVITY

IV. ae IN THE FORMED eee OF THE Engen
. Oligocythemia
(a. ) Thoma-Zeiss apparatus for counting blood-cor rpuseles
(b.) Gowers’ hemacytometer :
(c.) Bizzozero’s chromocytometer
(d.) V. Fleischl’s hamometer
é.) Hénocque’s heematoscope
(f.) Hedin’s hematocrite
. Leucocytosis
. Leukeemia ‘
. Anemia infantum pseudo- leukzemica
Melanzmia
. Microcytheemia
. Poikilocytosis
. Changes in the formed elements of the blood in chlorosis
! Changes in the formed elements of the blood in pernicious
anemia :
. Changes in the for med elements of the blood with haemorrhage
and the infectious fevers (secondary anzemia)

O ON ANEW YN

=
°

V. THe PaRAsiTEs oF THE BLoop
A, Vegetable Parasites :
Method of examining the blood for micro-organisms
1. Bacillus of anthrax ;
Spirillum of relapsing fever
Bacillus of tubercle
Bacillus of glanders
Bacillus of typhoid fever
Streptococci.
Micro-organisms of the blood in ‘hy drophobia
Bacillus of tetanus : : ;

BL. A ee Parasites Gane
ne oa ,
. Parasites of feran ague .
2. Parasites of quartan ague
. Parasites of acyclical and anomalous forms of ague
i Methods of examining the blood for the parasites
of malaria . : : :

pet Gena

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vili CONTENTS.

a a mes .

. Distoma heamatoninan
2. Filaria sanguinis hominis .

VI. Tue CHEmicaL CHANGES IN THE BLoop

1. Colouring-matter of the blood
1. Blood changes in dyspnoea
Blood changes in carbonic oxide poisoning
Blood changes in poisoning with sulphuretted hydr ogen
Blood changes i in prussic acid poisoning :
. Blood changes in poisoning with chlorate of potash
Blood changes in Dee with nitrobenzol
; Hemoglobinzmia :
Recognition of changes in the colouring- matter of the
blood : : :
. Proteids .
. Urea”. ;
: Dine acid and xanthin substances .
. Uric acid
2. Xanthin bases
. Carbohydrates (melithemia)
I. Grape-sugar
2. Glycogen
Ba: ellulose
. Organic acids (lipacideemvia)
. Lipemia ‘
. Cholemia
. Ureemia .
. Ammonizemia
. Acetonzemia
. Changes in the salts of the blood

CN AW Os

fw N

Wn

N= OW ON O

HOH

CHAPTER IL.
THE BUCCAL SECRETION.

I. Nakep-EyE APPEARANCES OF THE SALIVA
II. MrcroscopicaL APPEARANCES
1. Salivary corpuscles
2. Red blood-corpuscles
3. Epithelium
4. Fungi

III. CuHrmican Consumonton OF THE Bea AL SECRETION
IV. Constitution or MoRBID SALIVA IN GENERAL
V. THE SULPHOCYANIDE OF THE SALIVA

VI. Tuer Sativa In Spectan DIsEASES
1. Catarrhal stomatitis : : :
2. Other forms of stomatitis (mercurial, scorbutic, &c.)
3. Thrush . : , : :

VII. Deposit on TEEtH
VIII. Coatine oF tHE TonNGUE
IX. ee OF THE TONSILS

LU and diphtheritic Poneillitie
. Pharyngomycosis leptothricia

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CONTENTS. 1x

CHAPTER III.

THE NASAL SECRETION.

PAGE
I. Nakep-Eye and MicroscopicaAL CHARACTERS—CHEMICAL Con-
STITUTION : ‘ : : : : . 90
I]. THE SECRETION IN AFFECTIONS OF THE N ASAL ee ITIES, . . 90
CHAPTER IV.
‘THE SPUTUM.
I. NakED-Eyr CHARACTERS OF THE SPUTUM. 4 : : os
Il. MicroscoptcaL EXAMINATION OF THE SPUTUM. ; : . 94
1. White blood-corpuscles . ; 3 ; : : : > Ol
2. Red blood-corpuscles . : : : : ; : od)
3. Epithelium . : : : : : ; 5 : s 15
4. Elastic fibres s : 3 : : ; : Oy
5. Spirals . : ; : ; : : : : OS
6. Fibrinous coagula . : : : ‘ : : , . 100
7. Connective tissue . : 2 : e ; : . 100
8. Corpora amylacea . : ; : ; : : : . 101
9. ee : : : : é J s ; : Lon
. Fungi. : ; ; : : ! LOM
(a.) Non- pathogenic ‘ . : : . oe
1. Moulds : , : : 3 : Loe,
2. Yeasts : : : ; : : > nes)
Bs Sou aes : : ; : : Los)
. Sarcina pulmonis . : : : OR
2. Leptothrix . ; ; : . 103
3. Bacilli and Micrococei : 3 > Koss)
(b.) Pathogenic . : : : : O38}
1. Tuberele-bacillus . : , a 103)
Detection of tuberele-bacillus . . . 104
2. Pneumonia-microbes . : : : PLOT,
3. Actinomyces : : : ! ; OO)
2. Infusoria : ; : 3 : : : A . 109
Vermes . : 2 5 3 z : ‘ : . 10
TO. prea : : : 4 : : . 110
1. Charcot-Ley den cry stals : : ’ : ; . 10
2. Hematoidin crystals. : s : : : ey
3. Cholesterin crystals 2 . : : 5 Serta
4. Fat-crystals (margarine needles) : : : : 5 We)
5. Tyrosin crystals. : : : : : >
6. Oxalate of lime. : } : : ; : Li
7. Triple phosphate . E : } : : : unS
Ill. Carmican EXAMINATION : : ; 3 \ : : ua
1. Proteids and allied substances ; : : : 3 rts
2. Volatile fatty acids es : : : ; 1}
3. Glycogen : 4 ; ; ; : ; ; : . II4
o Ferment é : i : : : : . iid
5. Inorganic constituents : : : : : ; peel)

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CONTENTS.

IV. THr CHARACTER AND CONSTITUTION OF THE SPUTUM IN THE
PrIncrpAL DISEASES OF THE LUNGS AND BRONCHI
MV ee of the bronchi
. Acute bronchitis
. Chronic bronchitis and bronchiectasis
A Putrid bronchitis
4. Plastic bronchitis
2 ee of the lung tissue

. Tuberculosis

(a.) Miliary tuberculosis :
(b.) Acute tubercular infiltration .
(c.) Chronic pulmonary tuberculosis

0 MHI OMNI bv

. Chronic (non-tubercular) inflammation of the lung
. Croupous pneumonia :

. Pulmonary abscess

Gangrene of lung .

. Pulmonary edema

. Hemoptysis .

. Hemorrhagic infarction

. Pneumoconiosis

(a.) Anthracosis of the lung
(b.) Siderosis pulmonum
(c.) Mason’s lung

CHAPTER V.

THE GASTRIC JUICE AND VOMIT.

I. EXAMINATION OF THE GASTRIC JUICE
1. Naked-eye characters
2, Formed elements .
3. To obtain the gastric juice
4. Chemical constituents of the gastric juice

1. Pepsin .

(a.) Detection
(b.) Estimation

. Acids

Q NX

. Milk-curdling ferment ;

(a.) Acidity
(6.) Hydrochloric acid :
Als eee of Free Hydr ochloric cia}

2,

2

. Mohi’s tests
Aniline-dye tests
(a.) Methyl-aniline v iolet reaction
(b.) Tropeolin
(c.) Fuchsin .
(d.) Emerald-green
e.) Congo-red
(f.) Phloro- glucin and vanillin
(q.) Benzo-purpurin :
Uffelmann’s tests

a Ultramarine and zine sulphide :

B. Quantitative Estimation of Free Hydrochloric
Acid : : : :
1. Leo’s method
2. Sjoqvist’s method.
3. V. Jaksch’s modification of Sjoavist’s

method .

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a
NWNHNNYNNNNNNNNN LN

ODCOONN DADDAUIUN Ss
CONTENTS.

3. Acids (continued)—
B. Quantitative Estimation (continued)—
4. A. Braun’s method
5. Hoffman’s method
C. The Quantity of Hydrochloric “Acid ‘Physiolo i
cally Active in the Gastric Juice, and tts
Diagnostic Import
). Organic Acids of the Gastric Juice
1. Lactic acid
(a.) Qualitative tests
(6.) Quantitative estimation
2. Butyric and acetic acids
(a.) Qualitative tests
(b.) Quantitative estimation
4. Proteids
5. Urea
6. Ammonia.
7. Carbohydrates é
5. Estimation of the rate of absorption of the gastric contents .
6. To determine the contractile activity of the stomach
7. Asummary of the chemical examination of the gastric con-
tents
Il. Tae Inrestinan Jvurce
. Naked-eye characters
. Formed elements .
. To obtain the intestinal juice
4. Chemical constitution of the intestinal j juice

III. ExaMINnavtion oF THE VOMIT
1. Moulds .
2. Yeasts
3. Fission-fungi
Acute gastritis
Chronic gastritis .
Chronic ulcer of the stomach
Carcinoma of the stomach
Dilatation of the stomach
Parasitic affections of the stomach
. Croup and diphtheria .
. Fecal substances in the vomit
Pus :
. Animal parasites :
: Cee of the vomit in poisoning
. Poisoning with acids
(a.) Detection of sulphuric acid .
(b.) Detection of nitric acid
(c.) Detection of oxalic acid
. Poisoning with alkalies .
3. Poisoning with metals and metalloids
(a.) Poisoning with salts of lead .
(b.) Poisoning with salts of mercury
(c.) Poisoning with salts of copper
(d.) Arsenic poisoning :
(e.) Phosphorus poisoning .
4. Poisoning with alkaloids
(a.) Morphia poisoning
(6.) Poisoning with nicotin
(¢.) Poisoning with atropin
(d.) Poisoning with ptomaines and toxalbumins.

wn

OS ORCo SOS Oa

N

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157
X1l CONTENTS.

. Poisoning with ethylic alcohol

. Poisoning with chloroform

3 Poisoning with carbolic acid .

Poisoning with nitrobenzol and aniline
: Poisoning with prussic acid .

0 ON Dur

CHAPTER VI.
THE FACES.

I. Naxep-EvYE CHARACTERS OF THE Fa&cES .

II. MicroscopicaL CHARACTERS OF THE FACES

1. Constituents derived from the food
(a.) Vegetable cells
(b.) Muscle fibres
(c.) Elastic fibres
(d.) Areolar tissue
(¢.) Fat. :
(f.) Starch granules :
(g.) Coagulated proteids
a Hepacd elements derived from the intestinal tract
. Red blood-corpuscles
2. Leucocytes
3. Epithelium
4. Detritus
3. Parasites f . ;
A, Veg eae Parasites
. Non-pathogenic fungi
1. Moulds
2. Yeasts :
Fission-fungi .
_ Pathogenic fungi
. Cholera-bacillus
2. Bacillus of cholera nostras
Spirillum of cheese
3. Bacillus of typhoid fever
4. Tubercle-bacillus
B. Animal Parasites .
1. Protozoa.
1. Rhizopoda
(a.) Monadines
(b.) Ameeba coli
2. Sporozoa .
Ba Se
. Cercomonas intestinalis
Trichomonas intestinalis .
Paramecium coli

AW NA

. Vermes
Chass i Plntodes
(a.) Cestodes
1. Teenia saginata .
. Teenia solium
. Tenia nana
. Tenia flav opunetata .
. Tenia cucumerina .
. Bothriocephalus latus

OmbwWhy

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3-

CONTENTS.

B. Animal Parasites (continued)—
Crass I. Platodes (continwed)—
(b.) Trematodes :
1. Distoma hepaticum :
2. Distoma lanceolatum
3. Distoma Rathonisi
ie II. Annelides
. Order Nematodes qommce w Bre
(a.) eons Ascarides
_ Ascaris lumbricoides
2. Ascaris mystax
3. Oxyuris vermicularis
(f.) Family Strongylides.
Anchylostoma duodenale
(y.) Family Trichotrachelides
1. Trichocephalus dispar
2. Trichina spiralis
(6.) Rhabdonema strongyloides
Insects .

4. Crystals

4

OO SYDNEY H

. Charcot- Mevden eee

Heematoidin crystals
Cholesterin

Fat crystals

Oxalate of lime
Carbonate of lime .

. Sulphate of calcium

. Phosphate of lime .

. Triple phosphate .

. Sulphide of bismuth crystals

I1I. CurmicaL EXAMINATION OF THE FacEs
A. Organic Substances

4

Il.
12.

113}:

ODM W YN A

90 ON

. Mucin
. Albumin
. Peptone

Urea

. Carbohydr ates

Acids

(a.) Bile acids.

(B.) Volatile fatty acids
Phenol . ; ;

. Indol and skatol .
. Cholesterin, fats, and non- volatile « organic acids
] Sepa as matters ;

_ Urobilin.
. Blood colouring- matter
Bile pigment .
Taegan gases
Ptomaines
Ferments

B. Inorganic Substances

IV. EXAMINATION OF THE MECONIUM .

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205
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206
xiv CONTENTS.

YV. CHARACTER OF THE FXCES IN CERTAIN INTESTINAL AFFECTIONS .

. Acute intestinal catarrh

. Chronic intestinal catarrh
Ulcerative enteritis
Typhoid fever

. Dysentery

Cholera

Hemorrhagic stools

. Acholic stools

COI DEW NA

CHAPTER VII.
EXAMINATION OF THE URINE.

I. Nakep-Eyr InspEcTION OF THE URINE

Quantity
Specific gravity
Colour .
Reaction

BYP om

IJ. MicroscoricaL EXAMINATION OF THE URINE

. Cellular constituents (organised sediments) of ihe urine
1. Red blood-corpuscles :
. Leucocytes
. Epithelium
Casts
. Spermatozoa . :
. Fragments of tumours
: pe
1. Fungi
(a.) Non- pathogenic
(b.) Pathogenic
. Infusoria
. Vermes .
1. Distoma haematobium
2. Filaria sanguinis hominis
3. Echinococci
4. Eustrongylus gigas
5. Ascarides
. Crystalline and amorphous deposits (ongiganisell rekmeney
A, Sediments from Acid Urine
(a.) Be ystalline deposits
. Uric acid.
Oxalate of lime
Bilirubin and hematoidin
. Triple phosphate :
Basic phosphate of magnesia
Neutral phosphate of lime
Calcium sulphate
. Hippuric acid .
. Cystin
Xanthin . :
. Tyrosin and leucin .
. Soaps of lime and magnesia

NAW ON

GN

a
PASO SY OMEY YS

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207
207

208
208
209
209
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NNNNNNNNNNNNNNN

G2 Ga Ga G2 G2 G2 G2 G2 Go Ga G Od Ga NY
COO ONIN NN £ Oo) 2 Wo

NN N
w
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LER
0000

b

241
242
242
242
242
243
244
244
246
CONTENTS.

(b.) Amorphous deposits

Urates

_ Oxalate of lime

. Calcium sulphate

. Brown and yellow concretions
eel atiee

4

WEN

B. Seuirnents from Alkaline Urine.

(a.) Crystalline deposits

. Triple ee

. Indigo :

: Urate of ammonia

. Phosphate of Aenea
. Cholesterin

m

wWeEwWhd

>

(b.) Amorphous deposits

. Urate of ammonia .

. Basic phosphatic earths

. Carbonates of the alkaline earths
. Carbonate of lime

. Indigo

WMEwnN

3. Urinary pemore ore ,
4. Foreign bodies in the urine .

III. CaHremican EXAMINATION OF THE URINE
A, Organic Substances
I. eects

. Albuminuria .
(a.) Renal albuminuria
(b.) Accidental albuminuria
Determination of albumin (serum- albumin) .
(a.) Detection ; :
(B.) Estimation .
Peptonuria :
. Albumosuria .
Globulinuria .
Fibrinuria
. Heematuria
. Hemoglobinuria
. Mucinuria

ON ANEW N

2. Carbohydrates

Aun &

21s cosuria
a.) Physiological glycosuria
(>) Pathological glycosuria
(a.) Transitory glycosuria
(.) Persistent glycosuria ;
Determination of grape-sugar
(a.) Detection ;
(B.) Estimation .
Leevulosuria :
Lactosuria
Dextrin .
Animal gum
. Choluria
. Urobilinuria .
Heemato-porphyrinuria .
. Ather-sulphuric acids and their derivatives (indigo- blue,
skatol, phenol, parakresol, pyrocatechin, hydro-
chinon) and the aromatic oxyacids :

Ph

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Xvl

ae

8.

9.

Io.

Il.

12.
13.

14.

15.
16.
Nei
18.
19.
20.
Que

CONTENTS.

(a.) Indicanuria . :
Detection of indican .
Estimation

(b.) Skatoxyl-sulphuric atid :

(c.) Parakresol-, phenol-zther sulphuric acid
Detection of ether-sulphuric acids
Estimation of eether-sulphuric acids .
Estimation of phenols 3

(d.) Pyrocatechin .

(e.) Hydrochinon . f

(f.) The aromatic oxyacids .

Detection .
Estimation

Alkaptonuria
Inosituria

Melanuria

Acetonuria
Diaceturia
Lipaciduria

Lipuria .

Chyluria

Oxaluria

Cystinuria

Uric acid diathesis
Urea

Kreatinin

Ptomaines (putrefaction bases)
Ferments of the urine

B. Inorganic Substances

=

ON Qu BW WV

. Chlorides

. Sulphates

. Phosphates

. Carbonates

_ Nitrates and nitrites

. Sulphuretted hydrogen (hy drothionuria)
. Peroxide of hy: drogen é
. Gases of the urine .

IV. CHARACTERS OF THE URINE IN DISEASE

. The urine in febrile states d
‘The urine in disorders of the circulation (congestion) :
3. The urine in diseases of the urinary organs .

1. Renal affections

Vor Ey yp

(a.) Acute nephritis
(b.) Chronic nephritis
(c.) Contracted kidney
(d.) Amyloid kidney
(e.) Ureemia
Pyelitis calculosa .
Cystitis .
Tuberculosis of urinary organs

. Calculus and tumours of the bladdex

Catarrhal urethritis

. Gonorrheeal urethritis

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301
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315

G2 Go
ae
On

Nu
oO

MONI DOU VD

G2 G2 G2 Gd Gd Gd GI LD OO
wWwWKN HN HN YN

Go
N
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‘Oo

G2 Gd G2 G3 Gd Ld Wo U2 Gd GI LI Ud Ld Lo
WOW OOOIWO YN NWN
OWND HHH OUO

G
rs
CONTENTS. xvii

PAGE

4. The urine in diseases of the alimentary canal : meses
5. The urine in hepatic affections . : : : ; . 335
6. The urine in diabetes mellitus. : : : j £336
7. The urine in diabetes insipidus . : : : : Peso 7
8. The urine in anemia . : : : ; 3 7.
g. The urine of toxic states 2 : : } y esgo
1. Poisoning with acids. , : : : : . 338

Dp Poisoning with alkalies . : : F : Esso

3. Poisoning with metals and metalloids . : ; . 338

(a.) Lead salts. : : : A : : . 338

(b.) Salts of mercury . 3 ; : : : . 338

(c.) Salts of copper. : é : ; : » 339

(d.) Arsenic : : ; : p ; : . 340

(¢.)) Phosphorus . : ; : s i ; . 340

4. Poisoning with alkaloids : : ! ; é 340

5. Poisoning with ethylic alcohol . : : : . 341

6. Poisoning with chloroform , : : ; : . 341

7. Poisoning with carbolic acid . : : . 341

8. Poisoning with nitro-benzol and aniline : é - 342

9. Poisoning with carbonic oxide gas : : . 342

VY. Tae Detection or Certain DRUGS IN THE URINE. ; - 343
1. Iodoform and salts of iodine and bromine . : : . 343
2. Salicylates . 343
3. Quinine, kairin, antipyrin, thallin, antifebrin, and phenacetin 344
4. Chrysophanic acid : : : : ; « 345
5. Santonin ; : : : : 3 ; : - 346
6, Tannin. : : : . : : 4 2 : . 346
7. Naphthalin . : : : : : : y ‘ . 346
8. Copaiba balsam. : : : : ; : s . 346

CHAPTER VIII.

INVESTIGATION OF EXUDATIONS, TRANSUDATIONS,
AND CYSTIC FLUIDS.

A. Exudations . bhi : : : : ; : : meg 47,
1. Purulent exudations ; : : : : 3 5 aly
I. Naxep-Eye APPEARANCES . : : 3 A aed7,
II. MrcroscoricAL CHARACTERS : » 348
. White and red blood- sree id ee eliiren . 348
5, Fungi. : : : : : ; . 348
I. ‘Mieroeocei : : : : : : . 348
2. Tubercle-bacillus . : ; : ; - 349
3. Bacillus of syphilis . : : ’ : - 349
4. Actinomyces . : 2 : é ess
5. Bacillus of glanders ; : : ; ees 5
6. Bacillus of anthrax . : : : : 5a
7. Bacillus of leprosy . : . : : Begs
8. Bacillus of tetanus . ; : : : 55
g. Bacillus of influenza ; : . : . 356
b

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XVIil CONTENTS.

3. Protozoa
4. Vermes .
5. rae :
. Cholesterin er ystals
2. Heematoidin
3. Fat needles
4. Triple phosphate cr ystals

III. CapmicaLt ExaMINATION OF Pus
Sero-purulent exudations

Putrid exudations

Hemorrhagic exudations

Serous exudations

Chylous exudations

DALEY

B. Transudations

C. Contents of Cysts .
1. Hydatid cysts
2. Ovarian cysts
3. Cystic kidney
4. Pancreatic cysts

D. Secretions from Fistule

CHAPTER IX.
THE SECRETIONS OF THE GENITAL ORGANS.

I. Tue Seminan Fivuip
1: Naked-eye appearances of fhe semen
2, Microscopical examination of the semen
3. Chemical examination of the semen

II. SkcRETIONS OF THE SEXUAL ORGANS OF THE FEMALE .
1. Mammary secretion (the milk)
2. Vaginal secretion . ‘
3. The uterine secretions .
1. Menstruation
2. The lochia

CHAPTER X.
METHODS OF BACTERIOLOGICAL RESEARCH.

I. Tur Microscope . : F
IJ. Tort Detection or Micro- Ones ISMS

III, Cuntivation or Micro-OrRGANISMS
A. Methods of Sterilisation
Sterilisation of instruments, fluids, and nutrient substances
B. Nutrient Substances :
1. Nutrient fluids
2. Solid nutrient substances
1. Blood serum .
2. R. Koch’s nutrient gelatine
3. Agar-agar
4. Potato
Stained nutrient substances

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CONTENTS.

C. Preparation of Koch’s Pure Cultivations

1. Plate cultivations .

2. Cultivation by deep inoculation
3. Cultivations on glass slides .
4. Cultivations in hanging drops
5. Cultivation by exclusion of air

IV. THE TRANSMISSION oF PuRE CULTIVATIONS TO ANIMALS
(a.) By the lungs
(6.) In the food .
(c.) By cutaneous inoculation
(d.) By subcutaneous inoculation and injection.

Y. ScHEME OF A BACTERIOLOGICAL INVESTIGATION

BIBLIOGRAPHY
INDEX

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385
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388

389
389
389
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389

599

301
441
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I
I
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I
I
2
2
2

LIST OF ILLUSTRATIONS.

IG.

1. Blood-plates from normal blood

2, Capillary tube :
3-5. Thoma-Zeiss apparatus for eames cea caramels

5 Gowers’ apparatus

7-10. Bizzozero’s chromo- eytometer

I. Von Fleischl’s hemometer

2-14. Hénocque’s hematoscope

5. Hedin’s hematocrite

6. Leukemic blood

7. Eosinophil cells . :

8. Blood in anemia infantum faeeude: Henleemien :

9. Melanzmic blood

0. Poikilocytosis

1. Blood in neGiee nee

2. Anthrax-bacilli from rabbit’s iricedl

23. Anthrax-bacilli from human blood

24. Spirilla of relapsing fever (Koch)

25. Tubercle-bacilli in blood

26. Bacilli of glanders in human blood :

27, 28, 29. Parasite of tertian ague (Golgi and others)

30. Parasite of quartan ague ((olg?)

31. Parasites of acyclical intermittent fever (C ella and Man One tn)
32. Parasites in Roman fever (Celli and Guarnieri)

33, 34. Blood in tertian ague

35. Distoma hematobium

2

36. Filaria sanguinis hominis lens Brol Lonckari)

37. Spectrum of oxyhemoglobin

38. Spectrum of reduced hemoglobin

39. Spectrum of hematin in alkaline solution
40. Spectrum of reduced hematin .

41. Teichmann’s hemin crystals

42. Spectrum of methemoglobin ;
43. Spectrum of carbonic oxide hemoglobin .
44. Hering’s spectroscope

45. Buccal secretion

46. Saliva of thrush

47. Leptothrix buccalis

48. Nasal mucus : F

5
5

49. Epithelium, recone nna poole of he eaten

o. Elastic fibres in the sputum
I, 52. Spirals from the sputum

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51; 52

54, 56

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20

26
29
30
34

35
36

43
43
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47

52

2

53

58
59
60
60
60
61,
61
62
63,
66.
80,
85
86
go
95.
97
98, 99
XXI1 LIST OF ILLUSTRATIONS.

rma, PAGE
53, 54. Fibrinous coagula from a case of pneumonia . i : ; . 100
55. Fibrinous coagula from a case of plastic bronchitis . ‘ : . 101
56, 57. Moulds from the sputum in pulmonary abscess : : ; . 102
58. Tubercle-bacilli from sputum . : : : : ; : ‘ . 106
59. Tubercle-bacilli, stained . : : : : : : : : . 108
60. Pneumonia-cocci . : : : . 108
61. Echinococcus hooklets dl mombratie of hydatid an ; , : . 109
62. Charcot-Leyden crystals . : : ; : : ‘ : : LLL
63. Microbe of pneumonia . : : : : ; . : : . 120
64. Collective view of vomited matter . : : 5 : : . 145
65. Mucous cylinder from feces . : 4 ‘ : ; ; : . 165
66. Collective view of the feces . : : : : : ; ‘ LOT,
67. Degenerated intestinal epithelium . ; : 2 ; : ; . 168
68. Bacilli from the feces. . . : ely 2
69. Nothnagel’s clostridia and stunted bacilli ‘ow the core : : 72)
70. Koch’s comma-bacillus . : ° : : ; ‘ : 74:
71. Finkler-Prior bacillus of cholera SORES, ; 3 : : : Eel 7i7)
72. Bacilliof typhoid . : ; j ‘ : : : , lS)
73. Organisms in stools. : ; : : ; : , ; : . 180
74. Cercomonads from the stools . s : : : ‘ ; ; . 181
75. Tenia saginata . ‘ : : 4 é 5 : , : aS
76. Tenia solium . : 5 , : : : : : : : ELS
77. Tenianana . 2 : : ; : : ; : : ; . 184
78. Tenia cucumerina . 3 j : : : 3 ; , : . 185
79. Bothriocephalus latus. : ; 2 3 : : : ; . 186
80. Distoma hepaticum : : : ; : ; : : : Sy,
81. Distoma lanceolatum . : ‘ : e : : : : . 188
82. Ascaris lumbricoides : : : : : : : 3 : . 189
83. Ascaris mystax : : : : : : : : : ; . 189
84. Oxyuris vermicularis . , : ; : : ; : : - 190
85. Anchylostoma duodenale . : : : ; : : F . 191
86. Trichocephalus dispar. : ’ ; ; : 2 : : . 192
87. Trichine . : : : : : , : : : ; . 193
88. Anguillula perce : : ; : : ; : : . . 194
89. Hematoidin crystals 7 : : ; ; : ; : 5 . 196
go. Acholic stools : : : ; , : : : ‘ . 196
gt. Sulphide of bismuth erates i 7 . 3 : ! : : . 198
92. Stenbeck’s sedimentator . : : ; c ; : : 3 . 218
93. Urinary epithelium . ; : : : 3 ; ; ; : 222,
94. Cast of urates . ; : : . : I : : : : 225
95. Epithelium cast e : 3 3 : : : : : . 226
96. Cast of shrunken blood- Corpuecles ; : : : : : i . 226
97. Cast formed of leucocytes 5 4 : 6 5 A ‘ . 226
98. Casts formed of leucocytes and Serene ; ; : : : . 226
gg. Granular cast in chronic nephritis . ; : ; . : . Suez 277)
1oo. Granular cast in acute nephritis . A A : ; , 5 . 227
1o1. Granular cast in chronic nephritis : 4 : 3 , ; . 228
102. Waxy casts. : : 5 : : : : : : 5 . 229
103. Granular and fatty casts : ; ; : : : : : . 230
104. Hyaline casts . ; : ; ; : ¢ : I A é . 230

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105.
106.
107.
108.
109.
110.
III.
112.
113.
114.
ne
116.
117.
118.
119.
. Soaps of lime and magnesia
121.
122.
T2e5
124.
1255
126.
127.
128.
129.
130.
131.
1ig2)
Tee.
134.
135.
136.
137.
138.
139.
140.
I4l.
142.
143.
144.
145.
146.
147.
148.
149.

LIST OF ILLUSTRATIONS.

Cylindroids from the urine

Micrococcus ures :

Sediment from fermenting diabetrd urine

Tubercle-bacilli from urinary sediment .

Distoma hematobium in sediment . :

Uric acid crystals from urine in congestion from sinphysema
Uric acid crystals from urine in congestion from heart-disease
Oxalates of urine from sediment in cystitis and pyelonephritis
Triple phosphate crystals from the sediment in chlorosis
Basic phosphate of magnesia .

Neutral phosphate of lime from the urine of liner meatinaits
Calcium sulphate

Crystals of hippuric acid :

Crystals after the use of benzoic acid in a case of Fhonmation
Tyrosin, leucin, and cystin

Triple phosphate crystals

Indigo crystals

Urate of ammonia

Cholesterin crystals

Carbonate of lime

Esbach’s albuminimeter .

Phenyl-glucosazon crystals

Flask for estimation of sugar by fermentation
Lippich’s polarimeter ; ,

Spectrum of urobilin in acid urine

Spectrum of urobilin in alkaline urine

Ludwig’s filter

Hiifner’s apparatus

Gonococci of urethritis

Gonococci (two days after infection)

Cocci from an empyema

Actinomyces granules

Actinomyces from pleural cavity

Actinomyces from peritoneum

Preparation from same case as last, cei
Bacillus of tetanus .

Pus from putrid empyema

Contents of an ovarian cyst

Microscopical appearance of human semen
Colostrum , , 0 : . : : , 0
Vaginal secretion in cancer

Microscope (made by Reichert)

Abbe’s condenser 4
The same, showing the collecting Pen of fentes

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CIA DEIR I,
THE BLOOD.

Every change in the quantity or the quality of the blood itself is apt to
be attended with serious disturbance of the system; further, the blood is
the carrier and distributer through the body of nearly all the poisons,
organic and inorganic, which act upon the latter. From this it follows
that the physiology and pathology of the blood represent a mass of
knowledge, at once immense and various. It is not our purpose, here,
however, to treat these subjects exhaustively, but merely to select from
them certain well-established facts which bear upon disease, and to point
out the way in which they may help in its diagnosis.

I. COLOUR.—Arterial and venous blood differ considerably as to
colour in health, the former being scarlet, and the latter a bluish red.
The distinction, however, belongs not to the fluid part of the blood, or
plasma, but to the colouring-matter, or hemoglobin, contained in the
red corpuscles, and it depends upon the chemical constitution of the
corpuscles, which, changing colour themselves, determine the tint of the
whole mass of the blood.

Thus, when the blood is rich in oxygen, the amount of hemoglobin
is increased, and the fluid is proportionately bright red. Again, where,
as is always the case with venous blood, oxygen is deficient, or where,
from physiological or pathological causes, arterial blood contains but
little oxyhemoglobin, the colour is darker, and this in a degree corre-
sponding to the condition which underlies it. In certain morbid states,
however, the blood may assume a brighter tint than that of healthy
arterial blood. In carbonic oxide poisoning, for instance, it is of a
bright cherry colour (see p. 63). [Venous blood, which appears dark
red by reflected light, is green by transmitted light. It is therefore
said to be dichroic. Arterial blood is monochroic.1]* The blood which
is taken from the finger for the purpose of microscopical examination by
means of a slight puncture is usually venous in character.

* The Numbers refer to the Bibliography at the end of the volume.
A

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dS

THE BLOOD.

Il. THE REACTION of healthy blood, like that of nearly all the
tissue fluids, is alkaline. [It is due to the presence of disodic phos-
phate, Na,HPO,, and bicarbonate of soda.] Still, this reaction is lable
to considerable variation under certain conditions of health as well as
in disease.

The alkalinity of the blood diminishes when it has been with-
drawn from the influence of living blood-vessels. Hence we find
that an acid reaction is one of the phenomena of coagulation, and
that this becomes more pronounced the longer the blood is allowed
to stand. [The change depends upon the formation of an acid derived,
probably, from the decomposition of the colouring-matter of the red
corpuscles. |

To test the reaction of the blood, Liebreich ? employs plates of plaster
of Paris or clay soaked in neutral litmus solution. A few drops of the
blood to be examined are placed upon this, and washed off again with
water.* If the blood was alkaline, the spot upon which it has fallen
exhibits a blue, but if acid, a red colour.

For the same purpose Zuntz® uses glazed litmus paper soaked in a
solution of common salt or sulphate of soda; this he dips several times
in the blood to be tested, and again washes in the salt solution. The
same thing may be done by allowing a drop of the blood to fall on the
litmus paper, and then quickly washing it off again, as in Liebreich’s
method.

For the comparative estimation of the alkalinity of the blood in
animals, Lassar* has devised a process, which, however, cannot be
applied to the case of human beings, where the requisite quantity of
blood is not available. On the other hand, the plan which Landois°
recommends is very suitable for clinical purposes.

The author has obtained useful results in a large series of observations
by proceeding according to the following method (a modification of that
of Landois), for the quantitative estimation of the alkalinity of the
blood :—

A mixture is made of a concentrated solution of sulphate of soda with
1/100 and 1/tooo normal solution of tartaric acid (I.) in various propor-
tions ; and in this way a series of test-fluids is obtained, the members
of which contain varying quantities of acid to the cubic centimetre. +

* [The reaction of the blood with ordinary litmus paper is obscured by the red
colour of the fluid, and the various expedients for its determination are directed to
overcome this difficulty.]

+ The fluids are prepared thus: 7.5 grms. of pure tartaric acid are dissolved
in a litre of water, and a normal solution (1/10 of the acid) results. By appro-
priate dilution of this, the other normal solutions (1/100 and 1/1000) may be
obtained.®

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DETERMINATION OF ALKALINITY. 3

Experience shows that eighteen such test-solutions of varying acidity
are needed. And of these :—

I. contains in 1 ce, 0.9 ce, of 1/100 normal solution of acid and o.1 ce.

a

. °
Wit, 5 inI cc. 0,8cc. of 1/100 _,, ae of 02, /3 4
and so on, 23
- 2 n
IX, “3 in Ice, 0.1 cc, of 1/100 ——4, 2 a 99 | oH
dG 35 in I ce. 0.9 ce, of 1/1000 ,, ie ” oI ,, 2 2
and so on, Se

> , f a
XIV. SS in I cc. 0.5 ce. of 1/1000 ,, 5 “4 ONG 3 =
and so on, gn

XVIII. 7 in I ce. 0.1 ce, of 1/1000 ,, a - 0.9) 55 =

The experiment is conducted in the following manner :—The proper
quantities of the acid and sulphate of soda solutions are placed in a
series of watch-glasses, by means of a pipette graduated in o.1 cc.,*
and a number of strips of very sensitive blue and red litmus paper are
prepared. The blood is usually taken by means of cupping-glasses from
the patient’s back, and before it coagulates, 0.1 ce. of the blood is added
to each ec. of the fluids described above, well mixed in each case, and the
resulting mixtures tested with the litmus papers until one is found to
exhibit a neutral reaction, 7.2, leaving the red and blue litmus paper
unchanged. This will show what quantity of the acid is required to
neutralise o.1 cc. of the blood in question. In order to arrive at an
accurate result, it is necessary to proceed very quickly, and as a rule it
may be laid down that not more than 14 minutes should be allowed to
elapse between the taking of the blood and the conclusion of the experi-
ment, having regard to the rapid diminution of alkalinity after the blood
is withdrawn from the living vessels.

For the sake of clearness the following example may be taken :—

In the case of a man who suffered from tuberculosis and tabes dorsalis, it was

found that 0.4 cc. of 1/100 normal tartaric acid solution was required to neutralise
0.1 cc. of blood.
1 cc. of 1/100 normal solution of the acid corresponds to 0.0004 grm. NaOH.
OI » 95 ” c6 mi 0.00004 ,, 5
0.4 " in 68 9 » 0.00016 ,, 3
The alkalinity of the blood may, therefore, be expressed by 0.00016 grm. NaOH
for 0.1 cc., or .160 grm. NaOH for 100 ce.

Haycraft and Williamson’s Method.

[The method recently introduced by Haycraft and Williamson’ is very suitable
for clinical purposes, since by its means the alkalinity of the blood may be deter-
mined quantitatively from a single drop of the fluid.

A number of red litmus papers is prepared, containing varying quantities of
oxalic or some other acid. One of these is such as is found by experiment barely
to give a reaction with normal blood, and this is made the basis of a series of test

* For this purpose also the automatic pipettes (see p. 19) containing 0.1 cc. will

serve yery well.

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4 THE BLOOD.

papers answering to different degrees of alkalinity. The strength of each is esti-
mated by means of a solution of caustic potash of known concentration. The
papers are glazed, and dipped for a second or two in liquid paraftin and then
dried. In conducting the experiment a drop of blood is drawn from the finger
(previously well cleansed) and placed upon a paper of medium strength. There
it is allowed to rest for ten seconds. Sufficient of the plasma has then soaked in.
The blood is washed off, and the reaction, if any, is at once apparent. Should
this be so, a paper containing more acid is employed ; but if there be no reaction,
a weaker oneis taken. Suppose, now, it is found that the blood will give a reac-
tion with the sixth and not with the seventh paper, the former is then taken as

the expression of its alkalinity. But it is known that an = solution of an alkali

will give the same reaction, therefore the alkalinity of the blood will be =
“‘This is perhaps not absolutely true, for probably the blood plasma does not
percolate so readily into the litmus paper as does a watery solution of an alkali.
In this case, however, the error will be uniform,” and will not vitiate the con-
clusion in a series of comparative investigations. *]

It is true, as H. Meyer ® has shown, that the results to be obtained in
this way are open to error. This, indeed, we should expect, since the
final reaction varies in each specimen with the colour of the blood and
the quantity of CO, which it contains. The method has been described
here, faulty and unsatisfactory as it is, because by means of it certain
information has been obtained as to the character of the blood in
disease.?

The author’s experiments! have led him to the conclusion that the
alkalinity of 100 cc. of healthy human blood corresponds to 260-300
mgrms. of NaOH. Canard, who adopts a similar method, gives the
equivalent as 203-276 mgrms. NaOH ; while Mya and Tassinari,!2 from
experiments upon blood drawn from the veins, quote very much higher
figures (516 mgrms.) The alkalinity of the blood is often diminished
in fever. The author has invariably found it reduced considerably in
uremia, as well as in certain toxic states, as carbonic oxide poisoning.
[It is also reduced in persistent vomiting.] In organic disease of the
liver, leukemia, pernicious anemia, and diabetes, the author has found
such a diminution as was capable of being expressed in figures, and in
this (the condition of the blood in chlorosis alone excepted) he is borne
out by the researches of Girdber.15 His conclusions have also been con-
firmed by Pedper 14 and Rumpf. The results obtained by Kraus 16 with
another method are substantially the same. AJemperer!” has proceeded
also on the principle of estimating the proportion of CO,. He has found
that the diminished alkalinity of the blood in fever is not affected by

* [I am indebted to the courtesy of Dr. J. B. Haycraft for a personal communica-
tion on the subject discussed in the text. He informs me that he has already derived
important clinical inferences from the application of his method. By means of it he

has ascertained that the reaction of the blood in different conditions may vary as
widely as that of the urine.—(ED.)]

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SPECIFIC GRAVITY OF THE BLOOD. 5

the administration of anti-pyretic remedies. Cantani 8 is of opinion
that the blood in cholera may exhibit an acid reaction even during life.

Kraus’ Method.

The blood is taken by a lancet, and its content of carbonic acid determined by
weighing. This method is probably accurate ; but from the quantity of blood
which it demands, and the inexpediency of employing the lancet for clinical pur-

poses, it is not to be preferred to the other methods, which in general have yielded
the same results.

III. SPECIFIC GRAVITY OF THE BLOOD.—The specific gravity
of healthy human blood has been stated at 1.045-1.075 by Landois,!
and 1.035-1.068 by Lloyd Jones.2° It is usually lower in women than
in men; and the last-mentioned authority has shown that it is highest
at birth, falls gradually during the first few years of life, and reaches
its lowest point in man at 35-45 years of age. [It is diminished by
hunger, in pregnancy, by the ingestion of solid or liquid food, or by
gentle exercise.?1]

To estimate the specific gravity of the blood, Roy's method may be
adopted. ' This requires a series of test-tubes, holding a mixture of
glycerine and water in different proportions, so that the sp. gr. of these
shall range between 1.040 and 1.080. The test-tubes should have a
diameter of 4 cm. and should hold from 80-100 ce.

The proceeding is as follows :**—A drop of blood is drawn from the
finger by pricking it with an aseptic needle ; a capillary tube of glass,
bent at a right angle, and connected by a caoutchouc tube with the nozzle
of a Pravaz syringe is now taken, and the free pointed end of the tube is
placed in the centre of the exuding blood, some of which is drawn into
the tube by a slight movement of the piston. By gentle pressure on the
piston of the syringe a drop of blood is expelled into the middle of the
fluid in one of the test-tubes. There the blood will rise or sink according
to the density of the glycerine mixture, and successive trials are made
until a fluid is found in which the blood remains suspended. The
density of this fluid is that of the blood. The glycerine mixtures may
be preserved for future use by the addition of a little thymol, but their
sp. gr. must be verified before each investigation. [English observers
generally dispense with the syringe and employ the right-angled glass-
tube, which is pointed at one extremity and expanded at the other, where
it is closed by a caoutchouc cap, and by means of this the blood is drawn
in and again expressed in the test fluid. For purposes of comparison
the blood should be examined in the morning, and always at the same
hour, since Lloyd Jones®* has shown that its sp. gr. undergoes diurnal
variations, dependent probably upon the ingestion of food. Again, in
removing the blood for examination, it is important to avoid pressure on

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6 THE BLOOD.

the part from which blood is withdrawn (as by squeezing, or the applica-
tion of a ligature), since the sp. gr. is altered by such expedients. }
Hammerschiag’s?* method, and that of Schmaltz?® and Peiper,?® who
make use of a capillary pycnometer, seem to have no advantage over
that described here.

[Instead of glycerine Landois employs solutions of sulphate of soda
for the test fluids. The process is in other respects the same as Roy’s.””

Monckton Copeman?’ and Sherrington have investigated the sp. gr. of
the blood by a method founded on that of Roy. To prevent decomposi-
tion of the test fluids and consequent change in their density they are
derived from a stock fluid of glycerine and water saturated with boro-
elyceride and sulphate of magnesium, with a small quantity—1 in 1000
—of corrosive sublimate. Such a fluid will remain serviceable for more
than three years.] (See note on p. 78.)

Examination of the blood in the author’s clinic has shown that
intestinal hemorrhage, severe anemia, and prostration, are attended
with a fall in specific gravity. Siegl and Schmaltz have found that the
specific gravity varies with the proportion of hemoglobin, but not with
the total number of cellular elements. Hence it follows that a diminu-
tion in the number of red corpuscles may be inferred from a fall in
sp. gr., and the comparatively easy investigation of the latter may be
made in practice to replace the estimation of hemoglobin, which can be
effected only by the use of costly instruments.

IV. CHANGES IN THE FORMED ELEMENTS OF THE BLOOD.—
The blood contains red and white corpuscles, and recent observations
(Bizzozero) have shown the presence in it of a third class of formed
elements,—the blood-tablets (or blood-plates). The existence of these
bodies is now beyond dispute. To make them apparent in fresh blood,
it is necessary to fix the latter by the addition of some preserving fluid,
such as Hayem’s * solution, when it may be examined directly with an
oil-immersion lens and a narrow diaphragm.

The constitution of Hayen’s solution is as follows :—

1 grm. of chloride of sodium, 5 grms. of sodic sulphate, 0.5 germ. corrosive
sublimate, and 200 grms. distilled water.

The preparation will then show the bodies in question as minute
objects with a diameter less than half that of the red blood-corpuscles,
scattered singly, or in groups in the field. In the present state of our
knowledge, they possess no diagnostic importance. [They are supposed
to be most abundantly present in the blood of persons suffering from
chronic diseases ; and are said to increase in number during pregnancy
(Halla), in conditions of regeneration (Afanassiew), in febrile anemia
(Fusari), and to diminish in fever.?°]

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OLIGOCYTHAMIA. a

The physiology of the red and white blood-corpuscles is sufficiently
set forth in the Text-books of that science.

Pathologically, the corpuscles exhibit changes as to quantity and
character which are of the utmost importance in diagnosis. These
changes seldom occur separately, but are usually combinéd,—although
alterations of the structwre of the corpuscles may be more pronounced
in some cases, of their number in others. We shall consider :

1. The diminution in the number of the cellular elements of the
blood (oligocythcemia).

2. The increase in the number of the cellular constituents. An
absolute increase of this kind has not yet been proved to occur, but
a relative preponderance of white corpuscles is often met with. This
happens normally during digestion (physiological leucocytosis),—as a

 

Fia. 1.—Blood-plates from normal blood. (The blood had been fixed with Hayem’s solution.
Eye-piece III, objective Zeiss j,, homogeneous immersion).

transient phenomenon in a number of morbid states (pathological leu-
cocytosis), and as a persistent condition (/eukwmia).

3. Changes in the form of the blood-corpuscles (potkilocytosis, micro-
cythemia).

1. Oligocythemia.—Vierordt has computed that in health the
number of red blood-corpuscles is five millions in a man, and 44 millions
in a woman to the cubic millimetre of blood.* °° In disease the number
may diminish temporarily or permanently to two millions, or even sink
as low as 360,000 per cubic millimetre. Such a condition may occur as
a consequence of hemorrhage, whether of a traumatic origin, or due to
morbid changes in the blood-vessels, as when intestinal bleeding takes
place in typhoid fever. As a permanent state, it may be a phenomenon
of any disease which is attended with deficient regeneration of the blood.

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8 THE BLOOD.

[The number of the red corpuscles is lessened in chronic lead-poison-
ing, miasmatic conditions, and in syphilis. ]

Diagnosis of Oligocythemia.—The methods and apparatus employed
by physiologists to estimate a diminution of the red blood-corpuscles are
very many ; but of these a large number are useless for clinical purposes,
inasmuch as they require too great quantities of blood to work upon.

The apparatus which will serve our purpose is of two classes. One
is used to count the actual number of blood-corpuscles in a specimen
of blood ; the other, by estimating the quantity of hemoglobin present,
enables us to draw an inference as to changes in the blood. Both
methods have their advantages and supplement each other, since a
diminution in the hemoglobin is usually proportionate to a diminution
in the red corpuscles; thus, oligochromemia and oligocythemia mostly
occur together. Quite recently also, it has been found possible to take
account of the bulk of the red corpuscles (see p. 25), a point of some
value clinically.

When the oligocythemia is very pronounced, a glance through the
microscope will suffice to recognise it; and so with oldgochromemia—
diminution of hemoglobin—a little practice will enable us to detect it
by a simple examination of the blood in a very thin layer without the
addition of any fluid. To effect this, the end of the finger should be
washed in plain water, and pricked, and the first drops of blood allowed
to flow off. A glass slide should then be allowed to touch the summit
of the drop of blood on the skin without coming in contact with the
finger, quickly withdrawn, and a cover-glass placed over it.

In this way such impurities as epithelium, &c., are avoided.

The use of carbolic acid, ether, or alcohol, to wash the skin, is not to be
recommended, since these bodies are likely to produce changes in the appearance
of the corpuscles. When the object of the examination is the detection of micro-
organisms in the blood, the utmost care must be taken in cleansing the skin (see
p. 40).

Proceeding in this way in a case of oligocythemia, when the slide
is placed under the microscope, a marked diminution in the number of
blood-corpuscles will be noticed. The red corpuscles will also in most
cases be paler than normal ; their usual bi-concave shape less marked ;
they are somewhat flattened, and they tend less to run into rouleaux or
assume stellate forms. At the same time, they may be seen to have
undergone peculiar changes of shape (potkzlocytosis).

For many purposes it is well to fix the blood with some preserving
fluid before examination. A solution of common salt (0.8-1.0 per
cent.) or of sulphate of magnesium (5 per cent.) may be used (Gidiber).
Hayem’s or Pacini’s solution may be employed. Hayem’s has been
already described.

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ENUMERATION OF BLOOD-CORPUSCLES. 9

Pacini's solution is prepared thus :—A mixture is made of 1 part corrosive sub-
limate, 2 parts common salt, 13 parts glycerine, and 113 parts distilled water, and
the fluid is allowed to stand for at least two months. When about to be used, a
portion is diluted with three times its bulk of distilled water, and filtered through
blotting-paper.*#

When it is a question of a lesser degree of
oligocythemia, this proceeding will not suffice, and
we must have resort to special means of estimating
the precise number of the corpuscles or the relative
quantity of hemoglobin present. In recent times
a great many instruments have been constructed
with the firstnamed object—as those of Quinche,
Malassez, Hayem, Gowers, and Thoma and Zeiss.
The principle on which all these are constructed is
the same. A known quantity of blood is mixed in
definite proportion with some indifferent fluid (3
per cent. salt solution, &c.), a portion of the mix-
ture is placed upon a hollow slide of known con-
tents and graduated surface, and then the cor-
puscles are counted with the aid of the microscope.

(a.) The Thoma-Zeiss Apparatus for Counting
Blood-Corpuscles.—The simplest and best of these
instruments is that of Thoma and Zeiss. It con-
sists of a capillary tube of glass about ro centi-
metres long, expanding in its upper third to a bulb,
in which lies a small glass ball. The lower end of
the tube is furnished with a scale, graduated in
parts, numbered o.1, 0.5, 1, up to ror (fig. 2). With
this instrument is used a counting-chamber in-
vented by Abbe *® and Zeiss. This is a glass recep-
tacle cemented upon a glass slide (fig. 3); it is
exactly 0.1 mm. in depth, and its floor is marked

 

 

out into microscopic squares (fig. 4). The space
overlying each square = 1/4000 mm?* and the

 

squares are portioned out in groups of 16 by plainer yye, 2.—capillary Tube

7 Thoma-Zeiss Apparatus
s (fig. s). ( pp
line (fig 5) 5 tor Counting the Blood
Application of the Process.—A puncture is made Corpuscles).

in the tip of the finger, and in doing this the

precautions already indicated are taken. Blood from the summit of the
exuding drop is then sucked into the tube until it reaches the mark .5
or 1. The point of the tube is wiped, and a 3 per cent. solution of
common salt sucked in until the fluid has risen to the point marked rot.

* Mm ? = cubic millimetre.

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10 THE BLOOD.

For'some years the author has used Hayem’s fluid in this experiment
(see p. 6). Daland*” and Sadler *® prefer a 24 per cent. solution of
bichromate of potash. The contents of the tube are then thoroughly
mixed, and the column of fluid in the capillary tube is removed by
blowing into the tube, as the blood would not mix with the solution
of common salt. To neglect this precaution, therefore, would vitiate
the experiment.

The capillary tube must be carefully cleaned after use, by washing it with

distilled water, then with alcohol, and finally with zther, and a brisk current of
air blown through it. For the latter purpose Béhm’s air-pump is very suitable.

RW Quy WW a

 

 

Fic, 5.—Thoma-Zeiss Apparatus for Counting Blood-Corpuscles.

The hollow cell of the slide is next filled with the mixed blood-
and-salt-solution, care being taken to guard against the admission
of air-bubbles, and the cover-glass is accurately adjusted in such a
manner that Newton’s colour-rings are produced. The preparation
is left to stand for some minutes, so as to allow of an intimate ad-
mixture of its parts, after which it is placed under the microscope,
and looked at with a power of 30-70 diameters, when it will be seen
whether any air-bubbles or foreign bodies are present in it, and
whether the corpuscles are pretty evenly distributed through the fluid.

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ENUMERATION OF BLOOD-CORPUSCLES. IT

The latter are then counted under a high power. In doing this, the
number present in sixteen squares is counted, and from this the average
is estimated. The greater the number of the squares taken, the more
accurate will be the result attained. To count the corpuscles contained
in sixteen squares, Lyon and Thoma *® made the following suggestions :

The space overlying a vertical series of four of the squares is taken
as that the contents of which are to be estimated together. All the
cells which cover or impinge upon the upper boundary of the rectangle
formed by these four squares are to be reckoned, and that whether the
cells themselves are situated within or without the boundary-line in
question. So also are those which touch upon the line bounding the
field of four-squares on one (left) of its sides, and all that are entirely
included within its limits without being anywhere in contact with the
boundary.

The object-glass used in this investigation should be Ze7ss, C or D ;
Hartnack, 6; or Reichert, 7.

The estimation of the total number of corpuscles is conducted as
follows :—If the blood in the tube reached to the point 0.5, its propor-
tion in the mixed solution will be 1:200; if to the point 1.0, 1: 100.
Multiply the number of corpuscles counted in all the squares by 4000
aon being the cubic contents overlying a square), and the result by
100 or 200, according to the degree of dilution. Then divide the pro-
duct by the number of squares taken, and the result gives the number

 

of blood-corpuscles contained in a cubic millimetre of blood.

To estimate the number of white corpuscles in a specimen of blood,
Thoma * dilutes the latter with water containing one-third per cent.
glacial acetic acid in the proportion of 1:10. In this way the red cor-
puscles are destroyed, and the white alone remain in the field of vision.
In mixing the fluids, the same observer employs a mixing-glass speci-
ally devised by Zeiss for the purpose. The process may also be carried
out thus :—By means of a pipette of 1 ce. contents, and accurately
graduated in o.1 ec. units, 0.9 cc. of the acetic acid solution is measured
out into a watch-glass ; with another pipette holding exactly 0.1 cc., the
blood is added to this and the two well mixed. A drop of the mixture
is placed within the counting-chamber of the cytometer prepared as
before ; and now, since the number of corpuscles is relatively fewer,
the entire field, and not its marked-out divisions, is taken as the basis of
calculation, greater accuracy being so obtained. To the same end, a
lower power will be used, so as just to bring the marks in the floor of
the chamber clearly into view. Before beginning to count the corpus-
cles, however, it will be well to focus with the fine adjustment of the
microscope, and to make sure that the cells have all settled.

The cubie contents of that part of the chamber which corresponds

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12 THE BLOOD.

to the field of vision can be ascertained in the following way :—The
divisions of the chamber which appear in the field are first counted.
Each of these measures 4, mm. across (v. supra. the area= zo5 MM.”,
the cubic contents = z7455 mm.?). The diameter of the field, therefore,
is 4, mm. multiplied by the number of divisions which it contains.
Thus, for instance, if ten of the divisions are seen, the diameter of the
field =10 x A mm. or 39, and the radius=}?$ mm. The area of the
field, therefore = 7 (2°)? mm.®, and if the chamber is 0.100 mm. in depth,
its cubic contents=o.1 x (42)? = cubic mm. Hence we obtain the

following formula : *—
10xZ

UxQ
where M =the number of divisions under the microscope, Z = the
number of cells counted, Q=the cubic contents of the field (Q=o.1 =
R?, where R=the radius of the field in mm.), and where the blood is
diluted in the proportion of 1:10. The formula will give us the number
of cells contained in a cubic millimetre of undiluted blood. Where the
degree of dilution is 1 in 10, and where, as is usually convenient, 16
squares are taken, from the general formula results the following :—
10,000 x Z
314 2
or, if the degree of dilution be 1 in 20, the squares 16—
20,000 x Z
=e
z.e., the number of white corpuscles in 16 squares (Z) multiplied by
to,ooo for the 1 in ro solution, by 20,000 for the 1 in 20 solution, and
divided by 314, gives the number of white corpuscles in a cubic milli-
metre of blood.

When there is a very great increase in the number of leucocytes, as
in leukemia, their number can be estimated in the same manner as that
of the red corpuscles, and the relative proportion of the two can be de-
termined at the same time with sufficient accuracy, if only an adequate
number of squares is taken into account. Great assistance in such
experiments may be derived from the use of a 3 per cent. salt solution
coloured with gentian violet, in which the leucocytes are stained, and
become readily discernible from the red blood-corpuscles, which are
usually somewhat paler than normal. Yoison*#! employs for the pur-
pose a staining fluid of the following composition :—

Distilled water. , , 5 2 . 7 160 cc.
Glycerine r ; ‘ i : , : 4 30 cc.
Sulphate of soda . ; : : : : : 8 grms.
Chloride of sodium : : : P : : I erm.
Methyl-violet ; A : 3 : : - 0.025 grm.

 

7=3.1416. mm,?=square millimetre. mm.?=cubic millimetre.

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GOWER'S HAMACYTOMETER. 13.

For the same purpose, Mayet 42 recommends that the blood be mixed
with perosmic acid, glycerine, and water, which is said to confer upon
the coloured blood-corpuscles a beautiful red tint, whilst the white cor-
puscles remain unaffected by it.

[(b.) Gowers’ Hemacytometer.*—This instrument is the most commonly used
for clinical purposes in this country. ‘The hemacytometer (fig. 6) consists of :
(1.) A small pipette, which, when filled to the mark on its stem, holds exactly 995
cubic millimetres. It is furnished with an india-rubber tube and mouth-piece to
facilitate filling and emptying. (2.) A capillary tube marked to contain exactly
5 cubic millimetres, with india-rubber tube for filling, &c. (3.) Asmall glass jarin
which the dilution ismade. (4.) A glass stirrer for mixing the blood and solution
in the glass jar.t (5.) A brass stage-plate, carrying a glass slip, on which isa cell

 

 

 

 

Fic. 6.—Gowers’ Apparatus. A, pipette for measuring the diluting solution; B, capillary tube
for measuring the blood; C, cells with divisions on the floor, mounted on a slide; D,
vessel in which the dilution is made; E, glass stirrer ; F, guarded spear-pointed needle.

+ of a millimetre deep, The bottom of this is divided into 7, millimetre squares.
Upon the top of the cell rests the cover-glass, which is kept in its place by the
pressure of two springs proceeding from the ends of the stage-plate.”

The method of employing the instrument is as follows :—The diluting solution
used is a solution of sodic sulphate in distilled water, sp.gr. 1025, or the following :—

* For the above description and figure we are indebted to Landois and Stirling's
“Physiology,” vol. i. p. 5. Fourth edition.

{+ In practice error is apt to arise from variation in the depth of the cell, and it is
not easy to obtain one precisely} mm. Assuming that the same instrument is always
used by the observer, this is best corrected by ascertaining the true depth and allow-
ing for the error in mixing the solution. Suppose, for instance, the cell is found to
have a depth of 150 uw instead of 200 w, 5 parts of blood should be added to 945, of
the diluting fluid, instead of to955. The results so obtained will be absolutely accu-
rate (Z/art).]

Digitized by Microsoft®
14 THE BLOOD.

Sodic sulphate, 104 grains ; acetic acid, 1 drachm; distilled water, 4 .0z. ‘995
‘cubic millimetres of the solution are placed in the mixing jar; 5 cubic millimetres
of blood are drawn into the capillary tube from the puncture in the finger and
then blown into the solution. The two fluids are well mixed by rotating the
stirrer between the thumb and finger, and a small drop of this dilution is placed
in the centre of the cell, the covering-glass gently put upon the cell, and secured
by the two springs, and the plate placed upon the stage of the microscope. The
lens is then focussed for the squares. In a few minutes the corpuscles have sunk
to the bottom of the cell, and are seen at rest on the squares. The number in ten
squares is then counted, and this, multiplied by 10,000, gives the number in a

cubic millimetre of blood.” #3]
To estimate the COLOURLESS corpuscles only, mix the blood with ten parts of 0.5
per cent. solution of acetic acid, which destroys all the red corpuscles [Thoma].

The instruments of Bizzozero, v. Fleischl, Hénocque, and Gowers * in-
volve the second principle to which allusion has been made, viz., the
estimation of the quantity of hemoglobin in the blood.

Hedin’s*° instrument for measuring corpuscles in bulk (see p. 40) is
applicable to the same purpose.

Finally, mention must be made of v. Limbeck’s ** researches on the subject of
the resistance of the red corpuscles and the isotonic property of blood serum,

since they may find a practical application by-and-by. The same potential
importance attaches to Laker’s*” observations on the resistance of the blood-

corpuscles.

(¢.) Bizzozero’s Chromo-Cytometer [According to Bizzozero 48 a know-
ledge of the number of coloured blood-corpuscles is of less practical
value than.to know the quantity of hemoglobin, and, as a matter of
fact, the amount of the latter is not necessarily in direct proportion to
the number of the former. For the purpose of estimating the amount
of hemoglobin Bizzozero has invented a small, practical, and handy
instrument, which he calls a chromo-cytometer * (fig. 7).

By means of this instrument we can estimate the amount of hemo-
globin in the blood, and it can be used either as a cytometer or as a
‘chromometer. In both cases it is essentially an expedient for varying
the thickness of a stratum of blood.

To use it as a cytometer, the blood is mixed with a definite volume
(z:50) of an indifferent solution, e.y., normal saline solution (0.75
gramme of sodic chloride in 100 cc. water), so that the corpuscles
remain intact in the fluid. The quantity of hemoglobin is estimated by
the thickness of a layer of fluid through which one in a dark room can
distinctly see the edges of a candle-flame placed at a distance of 14 metres
from the instrument.

In using the instrument as a chromometer, the blood is mixed with
a known volume of water, which dissolves out the hemoglobin from
the corpuscles. The amount of hemoglobin is then calculated from the

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BIZZOZERO'S CHROMO-CYTOMETER. 15

thickness of the layer of this mixture, which yields a colour exactly
equal in intensity to that of a red-coloured glass supplied with the
instrument.

The chief part of the instrument consists of two tubes (ab, cd), work-
ing one within the other, and closed at the same end by glass dises
(figs. 7 and 8), while the other ends are open. The one tube can be
completely screwed into the other, so that both glasses touch. Con-
nected with the outer tube is a small open reservoir (7), from which fluid
can pass into the variable space between the two glass plates at the
ends of the tubes. By rotating the inner tube, the space between the
two glass plates can be increased or diminished, on the principle of
Hermann’s hematoscope, and the screw is so graduated as to indicate
the distance between the two plates, z.¢., the thickness of the layer of fluid
between them. Each complete turn of the screw = 0.5 mm., and the subdi-
visions on it are so marked—z5 to one turn (index, fig. 7, cd)—that each

SeeaNel e oO. bi .
subdivision of the index=°2=0.02 mm. When the inner tube is
2

screwed home and touches the glass disc in the outer tube, the index
stands at o on the scale. If the instrument is to be used merely as a
cytometer, these parts suffice; but if it is to serve as a chromometer,
the coloured glass is needed also. ‘The instrument is also provided with
small glass thimbles with flat bottoms, containing 2 and 4 cc. respec-
tively ; a pipette graduated to hold 4 and 1 ce., and another pipette for
to and 20 cmm., the latter provided with an india-rubber tube, to enable
the fluid to be sucked up readily ; a bottle to hold the saline solution,
and a glass stirrer.

Method of Using the Instrument as a Cytometer.—1. By means of the
pipette place .5 cc. of normal saline solution in a glass thimble.

2. With a lancet or needle puncture the skin of the finger at the edge
of the nail.

3. With the pipette suck up exactly 10 cmm. of blood, observing the
precautions already indicated at p. 8. Mix this blood with the .5 cc. saline
solution, and suck part of the latter several times into the capillary tube,
so as to remove every trace of blood from the pipette. Mix the fluids
thoroughly. Carefully cleanse the pipette with water.

4. Pour the mixture into the reservoir (7) of the instrument. Gradually
rotate the inner tube, and as the two glass discs separate, the fluid
passes into the space between them.

5. Ina dark room light a stearin candle, place it at a distance of 14
metres, and, taking the instrument in the left hand, bring the open end
of the tubes to the right eye. With the right hand rotate the inner
tube to vary the thickness of the column of fluid, and so adjust it until
the outlines of the upper three-fourths of the flame can be distinctly seen

Digitized by Microsoft®
16 THE BLOOD.

through the stratum of fluid. Vary the position of the inner screw so
as to determine accurately when this occurs. Read off on the scale the
thickness of the stratum of fluid.

Graduation of the Instrument as a Cytometer.—In this instrument
the graduation is obtained from the thickness of the layer of blood
itself, and the amount of hemoglobin is calculated directly from the
thickness of the layer of blood which is necessary to obtain a certain
optical effect, viz., through the layer of blood-corpuscles to see the out-
lines of a candle-flame placed at a certain distance.

From a number of investigations it appears that in healthy blood the

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 
 

b (a
a O-+Y
m
Fic. 7.—General view of the instrument. ab and Fic. 8.—Showing how ed fits into ab. zand
ed. Two tubes, the one fits inside the other; 7. 2’, Plates of glass closing the ends of ab and
Reservoir communicating with the space be- ed; other letters as in fig. 7.

tween ¢ and J when cd is screwed into ab;
cr. Milled head, and index-scale to the left of
it; y for ast of fig. 9; m. Handle.

outlines of the flame of a candle are distinctly seen through a layer of
; IIO : ;
the mixture of blood ——— mm. in thickness.
100

Let the number 110 correspond to 1, or, better still, 100 parts of
hemoglobin ; then it is easy to calculate the relative value of the sub-
divisions of the scale on the tube of the instrument. Let g = the
degree of the scale for normal blood; g’, that for the blood being inves-
tigated ; e, amount of hemoglobin in the former; and ¢’, the amount
sought for in the latter.

Assuming that the product of the quantity of hemoglobin and the
thickness of the stratum of blood is constant, so that

eg=eg.
Then

Digitized by Microsoft®
BIZZOZERO'S CHROMO-CYTOMETER. 17

Let us assume that the blood investigated gave the number 180;
then, using the above data :—

, _100.110 11,000
180 — 180

 

=61.1.

é

The blood, therefore, contains 61.1 hemoglobin. The following table
gives the proportion of hemoglobin, the normal amount of Taser loin
being taken as = 100 :—

Cytometer Scale. Hemoglobin. | Cytometer Scale. Heemoglobin.
110 : E . 100.0 170 5 2 OAS,
120 5 5 - 91.6 180 ‘ : ee Ore
130 : : . 84.6 190 : : - 57-9
140 5 5 7 O25) 200 5 0 - 55.0
150 - : - 73-3 210 : . « 52.4
160 ; ; - 68.7 220 , , + 50.0

If the instrument be used as a chromometer, the blood is mixed with a
known volume of water, whereby the hemoglobin is dissolved out of
the red corpuscles and the fluid becomes transparent. The quantity

GC

ANI

Fic. 9.—Coloured glass, 7, in a
blackened brass screen, 1 ; ast.
Stem for fixing itin y of fig. 7;
se. Brass tube in which f is se
fixed ; this is used when the
instrument is employed as a Ls
chromometer.

we

Oo

il

    
  
 

 

 
  

    

 

 

 

 

 

ast

 

 

Fic. ro.—Instrument seen from

above. Letters as in other

figs. (7, 8, 9).
of hemoglobin is calculated from the thickness of the stratum of fluid
required to correspond exactly to the colour-intensity of a tinted glass
which is attached to the instrument. The colour-intensity of the glass
is that of a definite solution of hemoglobin (fig. 9, /).

To use the Instrument as a Chromometer.—1. Place the coloured glass
with its brass frame in the instrument (ast of fig. 9 in y of fig. 7).

2. With the necessary precautions (p. 10) mix ro emm. blood with
.5 ce. distilled water, whereby in a few seconds a transparent solution
of hemoglobin is obtained.

3. Pour this solution into the reservoir (7), and rotate the inner tube
so that the fluid passes between the two glasses. Direct the mstrument
towards a white light or the sky, not towards the sun, and compare the
colour of the solution with the standard coloured glass, a proceeding
B

Digitized by Microsoft®
18 THE BLOOD.

which is facilitated by placing a milky glass between the source of light
and the layer of blood so as to obtain diffuse white light. When the
two colours appear to have as nearly as possible the same intensity, read
off on the scale the thickness of the layer of blood, and from this by
means of the accompanying table ascertain the corresponding amount of
hemoglobin.

This is done in the same way as for the cytometer, but the graduation
is different, as in the one case we have to do with a candle-flame, and
in the other with a coloured glass.

In very pronounced cases of anemia, even with a layer of blood 6 mm.
in thickness—the limit for which the instrument is constructed—the
intensity of the mixture of blood may be less than that of the coloured
glass. In such a case, instead of 10 cmm. of blood, use 20 cmm.

Graduation of the Chromometer.—As the coloured glass has not abso-
lutely the same intensity of colour in all chromometers, one must first
of all estimate the colour-intensity of the glass itself. This is most
easily done by ascertaining in a given specimen of blood what degree
of the chromometer corresponds to the scale of the cytometer of the
same blood.

Suppose that a specimen of blood by means of the cytometer gave r110,,
and by the chromometer 140; the number 110 of the cytometer = 100.
hemoglobin, so that the chromometer number 140 must also be = 100.
With the aid of the formula (p. 16) a similar table can be constructed
for the chromometer. Suppose the blood investigated = 280; then by
the aid of the formula and the data from normal blood :—

ef — 100.140 _ 14,000 _
280 280

 

 

50.

This blood, therefore, contains 50 parts of hemoglobin.
Example.—Blood gives 130 with the cytometer and 190 with the
chromometer ; what is the initial number of the chromometer gradua-
tion corresponding to too parts of hemoglobin ?
If 130 (cytometer) corresponds to 190 (chromometer), then r1o cyto-
meter (?.e., graduation corresponding to roo parts of hemoglobin) corre-
sponds to « chromometer graduation :

190.
130:190=I110:2.°..¢= 9 TT = 20,000 = 160.7.

130 130

 

Blood containing 100 parts hemoglobin will correspond to 160 of the
chromometer scale, and beginning with this number as a basis, with the
aid of our formula it is easy to construct a table showing the relation.
Whilst the value of the cytometer scale remains the same for every
instrument, the chromometer scale varies with each instrument, as the
colour-intensity of the glass is not necessarily the same in all. But

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VON FLEISCHL’'S HEMOMETER. 19

it is easy to construct a scale for each instrument by investigating a
specimen of blood and comparing it with the cytometer graduation as
indicated in the foregoing paragraph.

Precautions to be Observed in Using the Instrument.—In using the
instrument certain precautions must be observed. The exact quantity
of the several fluids must be carefully measured ; evaporation must be
prevented by covering the blood-mixture. Further, do not look at the
fluid too long at a time, as the eye becomes rapidly fatigued.

In cases of leukemia, where there is a large number of white cor-
puscles rendering the mixed fluid opaque, the corpuscles may be made
to disappear by adding a drop of very dilute caustic potash. If the
opacity does not disappear by the addition of this substance, then the
opacity is due to the presence of fatty granules in the blood, so that by
this means we can distinguish lipemia from leukemia.

Further, the operation must be. carried out not too slowly, as the
saline solution only retards the coagulation of the blood, and does not
arrest it.

Bizozero claims that when the instrument is used as a cytometer
the mean error is not greater than 0.3 per cent. | *

Sadler,5° working in the author’s clinic, has found that Bizzozero’s
instrument gives very accurate results.

(¢.) Von Fleischl’s Hemometer.t—The application of this instru-
ment (fig. 11) depends upon the principle that the colour of the blood
diluted with water may be compared with that of a glass wedge tinted
with Cassius’s golden-purple, or some such pigment.

Its essential part is the red glass wedge, which is mounted movably
beneath a platform like that of a microscope, with a circular opening in
its centre. Upon this the light from a gas or oil lamp (daylight is
not admissible) is projected by a plate of plaster of Paris. Above the
wedge, and exactly over the circular opening in the platform, is fixed a
metallic tube 14 cm. long, closed at the bottom with a plate of glass
and divided by a vertical metallic partition, so that one half of the
metallic tube receives its light through the red glass wedge, the other
directly from the white reflector. When the apparatus is in use, the
former of these compartments is filled with pure water, the other with
water mixed with a known quantity of blood.

To secure this known quantity, von Fleischl has designed an auto-
matic blood pipette of such a capacity that, when healthy blood is used,
the resulting mixture corresponds in colour to that derived from the
part of the red glass wedge which is marked roo. From this point to

* The instrument may be obtained from F. Koristka, Via Circo, 14, Milan, and

costs thirty-five lires.
+ Von Fleischl’s instrument is made by Reichert of Vienna, and sold for 35 florins.

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2© THE BLOOD.

its sharp edge (where o stands), the wedge is graduated in ten divisions,
which represent its diminishing thickness, the Nos. 90, 80, &c., being
marked on the apparatus.

The instrument is employed thus:—The blood is obtained from a
puncture in the finger, and placed by means of the pipette in the proper
compartment of the tube. Both compartments are then filled with
water, and the red glass wedge is moved until the two fluids show an
equal intensity of red colour. The number indicated on the scale is then
read off. Suppose this should be 80,—then the blood examined con-

 

Fic. 1r.—Von Fleischl’s Hemometer.

tains but 80 per cent. of the normal proportion of hemoglobin, or the
quantity of hemoglobin is to that of healthy blood as 80: 100. Now,
assuming that in a healthy man 14 grms.* may be taken as the amount
of hemoglobin in too grms. of blood, we can calculate the latter abso-
lutely for the specimen examined by means of the formula:
wig
100

 

* J. G. Otto states the normal quantity at 13.77 per cent. 14 is taken here (as
by Hénocque elsewhere) as a simpler expression for the purposes of the calculation.

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HENOCQUES HAMATOSCOPE. 21

Where
X =the quantity of hemoglobin in 100 grms of blood ;
R=the figure obtained with von Fleischl’s apparatus to express the
relative proportion of hemoglobin in the blood ; and

14=the normal quantity of hemoglobin in the blood of a healthy
adult.*

Although it must be conceded that the results obtained with this
instrument are not absolutely correct, it still supplies a simple and
ready means of estimating the hemoglobin in the blood, and has the
further advantage that it needs but little of the latter to work upon.
It has proved a useful adjunct to the Thoma-Zeiss apparatus, or that
of Gowers, in the investigation of changes in the blood for clinical
purposes.°!

(e.) Hénocque’s Hematoscope.*?—This instrument has the advantage
over others employed for a similar purpose, that while comparatively

i

 

Fic. 13.—Heénocque’s Heematoscope filled with Blood.

little fluid is needed for its application, this consists of pure blood
undiluted with artificial serums.

It consists essentially of two glass plates superimposed in such a
manner as to enclose a prismatic capillary space. The inferior of these
plates is the broader. Upon the upper part of its surface is engraved
a millimetre scale, o to 60, reading from left to right, and at either
extremity it carries a cap of nickelled metal, in which is a groove for
the reception of one end of the smaller (upper) plate. These grooves
are so placed that whilst the plates are in immediate contact at one end,
that opposite o of the scale, they are separated at the other by an in-
terval of 0.3 mm. The smaller plate can be made to slide in the grooves
under gentle pressure, and can thus be removed for the purpose of clean-

* This number is chosen here so as to afford a basis of comparison between the results

obtained with v. Fleischl’s instrument and those with Hénocque’s, which will be
described presently.

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22 THE BLOOD.

ing the instrument. From the above description it will be seen that a
layer of blood introduced within the capillary chamber has a thickness
varying uniformly from o on the left to 0.3 mm. under the mark 60
on the graduated scale ; and it also follows that its depth increases by
0.005 mm. for every mm. distance towards the right. Thus its depth
at any point may be known by multiplying the corresponding figure on
the scale by five, when the result is expressed in thousands of a milli-
metre or micron.

The prismatic chamber is filled with blood obtained by pricking the
finger, and this is done best by bringing the lower lamina on a level
with the puncture and permitting the issuing drops to flow upon it ata
gentle decline. The blood will then arrange itself in an even layer, and
if its continuity be interrupted by empty spaces or air-bubbles, these can
be extruded by slightly tapping the glass wall with the fingernail. Six
drops generally suffice. The edges of the instrument, when filled, are
wiped clean, and the examination may be begun.

This is conducted in two different ways :—

(a.) The first (procédé diaphanométrique), the readier and simpler, has
for its object to estimate the relative opacity of the blood, and so to infer
the proportion of hemoglobin which it contains.

For this purpose there is supplied with the hematoscope a plate of

 

O/C OOOO Oe
van ta ai

 

Memalosiope a Ninocque
15. 14. 18. 12. 11. 10. 9.8.7.6.5.4.

 

 

 

Fic. 14.—Enamelled Plate belonging to the Heematoscope.

white enamelled metal, bearing on its upper part a millimetre scale pre-
cisely similar to that engraved upon the lower of the two glass plates,
and below a descending series of figures, of which the first underlies the
8 mm. mark above. Then follow at constantly diminishing intervals the
figures 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4. The markings upon this
plate are traced throughout in black. When in use, it is placed behind
the hematoscope filled with blood, and held there in such a position
that like markings upon the millimetre scales accurately correspond.
It is evident that the portion of the blood layer which is thinner, and
therefore less deeply coloured, will be transparent, and will suffer the
marks beneath to be visible, while these disappear towards the thicker
end. The examination consists in noting the point at which the figures
(15-4) in the lower series cease to be visible ; and it is clear that this

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HENOCQUES HAIMATOSCOPE. 2B

point will be attained the sooner according as the blood is richer in
hemoglobin. :

Further, Hénocque has arranged the series so that the second figure
(14) expresses in grms. the quantity of oxyhemoglobin in 100 grms. of
blood, and this figure terminates the series as seen through a layer of
blood of normal constitution. With blood taken from a case of anemia,
on the other hand, the figure 8 or 7 may be legible, and this implies
that such blood contains in 100 grms. only 8 or 7 grms. of oxyhemo-
globin. Finally, the thickness of the stratum of blood at the point of
requisite opacity may be ascertained from the mm. scale in the manner
already indicated.*

Hellstrom, Loos,®* and the author have satisfied themselves that the
results obtained in this way are not to be relied upon, and that the
figures generally indicate too high a proportion of oxyhemoglobin.

(f.) In the second and more accurate mode of using the hematoscope
the enamelled plate is dispensed with, and a Browning’s spectroscope is
required. The instrument, filled with blood as before, is placed opposite
the cleft of the spectroscope, and the point is observed at which the
characteristic spectrum of oxyhemoglobin is first distinctly formed,—
when the corresponding point on the millimetre scale of the glass plate
is read off. The less hemoglobin in the blood, the thicker must be the
layer from which a spectrum is obtained. In order to secure a correct
reading from the scale, it is well to place the apparatus holding a stratum
of blood upon a sheet of white paper against a window so as to examine
it by bright and diffused daylight, and then directing the spectroscope
over 1 or 2 cm. of its surface, the observer should several times judge
for himself concerning the point of earliest definition of the spectrum.
Of the numbers obtained in this way (which will usually differ by an
amount expressing only two or three millimetres) the mean is taken,
and employed for the purpose of the calculation. It must be allowed
that the conclusion in this respect is always somewhat arbitrary, and
leaves room fora difference of opinion as to when precisely the spectrum
is formed ; but once the eye has become accustomed to look for a certain
clearness in the outline of the bands, it seeks for and easily appreciates
it in every instance. f

From the reading on the scale at the point where the spectrum is

* [Hénocque’s hematoscope may be obtained from M. Lutz, 82 Boulevard Saint-
Germain, Paris. The price is 12 francs, and the enamelled plate costs 5 francs
additional.—(ED.)]

+ [This difficulty may be further obviated by the use of Hénocque’s double
spectroscope, by means of which two persons are enabled to make the observation
at once. For a description of this instrument the reader is referred to the original

communication, ‘ L’Hémato-spectroscope.” Compt. Rend., Soc. de Biologie, October
1886. ]

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24 THE BLOOD.

thus seen, the thickness of the blood stratum, and the quantity of
oxyhemoglobin in a known quantity of blood, can be readily deter-
mined. In the case of normal blood, which contains 14 grms. of oxy-
hemoglobin in 100 grms. of the fluid, the absorption-bands are plainly
visible in the situation of the figure 14 on the mm. scale ; and from what
has been already said it follows that the thickness of the blood stratum
at this point is 14 x 0.005 mm.=o0.07 mm. Let it be assumed now that
in a given case the bands just become distinctly evident at a point cor-
responding to the division 20 on the index; then the thickness of the
layer which yields them is 20x 0.005 =0.r mm. From these data the
quantity of oxyhemoglobin in 100 grms. of the blood may be calculated
by the following equation :—
@:14=0.07 : 0.005.y

14 x 0.07
B=

 

©.005,4
In this formula :
x =the quantity of oxyhemoglobin sought.
14 =the quantity of oxyhemoglobin in roo grms. of healthy blood.
0.07 = the thickness of the blood stratum, which will make the absorp-
tion-bands plainly evident where the blood, as in normal blood, holds
14 grms. oxyhemoglobin in roo grms, of the fluid.
0.005 =the thickness of blood stratum corresponding to 1 mm.
y =the number of mm. read off at the point where the absorption-bands
become distinctly visible. From this results the simple expression :
_14X0.07__ 196
~ 0.005.y ¥ °
In the example chosen :
196

Y=20-. 55= 9.8,
z.e., the blood investigated contained 9.8 grms. of hemoglobin in
100 grms.

To obviate the necessity for making the calculation afresh in each
case Hénocque has compiled a table from which the quantity of hemo-
globin may be deduced directly from the depth of the blood stratum.

Comparisons which the author has instituted between the results
arrived at in this way with others derived by means of v. Fleischl’s ap-
paratus, have shown that the two are sufficiently in accord. Henschen,54
however, is of opinion that the latter are more accurate, and accounts
for this by pointing out that they are obtained from oxyhemoglobin,
whereas with Hénocque’s hematoscope that body is still within the cells.

The preference will usually be given to v. Fleischl’s apparatus, because
of the greater quantity of blood needed for the application of Hénocque’s
hematoscope ; but the latter is especially suitable for the observation

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HEDINS HMATOCRITE. 25

of such changes in the blood as the formation of methemoglobin, Wc.,
which can be recognised by spectrum-analysis. To detect such changes,
Hénocque has applied it in a very ingenious manner. He observed the
development of oxyhemoglobin-bands in transparent parts, such as the
lobe of the ear and the ungual phalanges of the finger, capable of being
illuminated by diffuse sunlight.* Then, in the case of the ungual
phalanx, the part was ligatured, and he noted the length of time required
for the appearance of the broad absorption-band of reduced hemoglobin.
Proceeding in this way, he found that with a normal proportion of oxy-
hemoglobin, reduction took place in the course of 70 seconds, while
with anemic blood the interval was shortened to 30-40 seconds.

As a result of his researches, Hénocque has arrived at the following formula,
which is applicable to clinical purposes :

M
E= DS
where
E=the energy of reduction ;
M=the mean proportion of hemoglobin ascertained by his method ;
D=the time in seconds in which reduction is accomplished.”

The formula is derived from the following considerations :—In a specimen of
blood holding 14 grms. oxyhemoglobin in 100 grms., reduction takes place in 70
seconds, and in another holding 13 grms. in roo, it takes place in 65 seconds.
Inspection of the figures shows that in both cases a fifth part of the quantity
of oxyhzmoglobin (in 100 grms.) is reduced. Hence, to obtain the value of E
(energy of reduction), the quantity of oxyhzmoglobin found is multiplied by 5,
and the product divided by the number expressing the time (in seconds) in which
reduction takes place. Experiments are now in progress under the author’s
supervision which have for their object to ascertain how far this method of in-
vestigation may be of use in diagnosis. The apparatus may be employed also
for the examination of milk, in the spectrum-analysis of urine and morbid fluids,
and for the aniline dyes of so much consequence in staining processes. It seems
to merit a description here on account of its extended utility ; and in any case,
in connection with the spectroscopic examination of the blood, it must be classed
with the apparatus of Thoma-Zeiss, Gowers, and y. Fleischl as a valuable addi-
tion to our resources.

(f.) Hedin’s Hematocrite.°—This instrument is of great value.
It enables one readily to estimate the volume of the red blood-corpuscles.
Its parts are: (1.) A capillary tube for measuring and mixing the blood.
Hedin uses a special contrivance for this purpose, but the mixing-glass
noticed on p. 11 for counting leucocytes serves equally well. To prevent
coagulation Hedin sucks Miiller’s fluid into the tube and then blood in
equal quantities. These are then expelled into a small platinum dish
and well mixed. Daland,*" in the authoyr’s clinic, has found that a 2.5
per cent. solution of bichromate of potash answers best.

* [In researches of this character the double spectroscope is specially recommended
by Hénocque.]

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26 THE BLOOD.

(2.) Two glass tubes, 35 mm. long, with a lumen 1 mm. in diameter
and graduated into 50 parts.

(3.) A metallic frame, terminating at either side in an angle to sup-
port a small cylindrical recess, of the same diameter as the tubes (2.),
and covered with a caoutchoue disc. From the middle of this metallic
frame there projects downwards a hollow metal cylinder, by means of
which it can be made to rotate on a vertical axis (fig. 15). Connected
with the central cylinder are two metallic springs, placed opposite each
other, and carrying each at their upper ends, on a level with the recesses

ha

 

Fic. 15.—Hedin’s Heematocrite.

mentioned above, a caoutchoue cap. Between the recess and this
caoutchoue cap on either side is placed one of the glass tubes which has
previously been filled with the mixture of blood and Miiller’s fluid
(or bichromate solution). In this position the tubes are closed by the
caoutchouc cap, which is held against them by the pressure of the springs.

(4.) A vertical support which can be made to rotate.

The instrument is used thus: With Hedin’s capillary tube, or the
mixer for estimating leucocytes, a mixture is made of blood and a 2.5
per cent. solution of bichromate of potash, and with this the tubes are
filled by plunging one end in the fluid, which is then drawn into the

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HEDINS H#MATOCRITE. Ov,

tube by the mouth applied to a piece of india-rubber tubing attached to
the other end. The tubes being filled in this way are placed in position
in the frame—the extremity towards the recess of the frame being first
adjusted, and the caoutchouc caps of the springs being then made to
press on the other extremity. The frame is then attached by its
vertical cylinder to the body of the instrument and made to rotate
rapidly. The red corpuscles, in virtue of the centrifugal action, sepa-
rate from the leucocytes and serum. After 50-70 seconds (where the
bichromate solution is used) the volume of the layer of red corpuscles
remains constant. The contents of the tubes are then arranged in three
parts ; at the distal end are ‘collected the red corpuscles, forming a
dense dark-coloured mass; next in order a small turbid band, con-
sisting of leucocytes, and in health of a whitish colour ; finally, the clear
serum, which is coloured a bright yellow by Miiller’s fluid. To guard
against error, a sheet of white paper is placed behind the tubes, and the
volume of the red corpuscles is read off on the scale. The corresponding
number multiplied by four gives the volume of red corpuscles in one
hundred parts of blood, as will appear from the following considerations.
The volume of red corpuscles as read upon the scale is that contained in
a mixture of equal parts of blood and bichromate solution, forming a
column 35 mm. long and divided into 50 equal parts. The proportion
of corpuscles in pure blood would be twice as great, and in 100 parts
(instead of 50) again twice as great ; therefore the percentage bulk may
be expressed by the figure read off the scale multiplied by 4.

The description given here applies to an instrument furnished by Sendling
Sandstrém of Lund, in Sweden, and differs somewhat from that published by
//edin himself.

This method is very serviceable in discriminating between the various
diseases which affect the blood, and it may be used in part to replace the
more difficult processes for counting the corpuscles. It may be substi-
tuted for these in conditions where the relative bulk of the red corpuscles
depends only upon their number, and not also (as in many diseases, ¢.7.,
pernicious anemia) upon their size. As to how far the results obtained
in this way tally with those arrived at by counting, and under what
circumstances the one method may supersede the other, the reader
should consult Daland’s notice. In the same way it is possible to
estimate approximately the relative proportion of red corpuscles and
leucocytes, as, for instance, in certain cases of persistent leucocytosis.
Observations made within the last year, in three cases of leukemia,
have satisfied the author that the method suffices to determine the
defective state of the blood in that disease. Further, it can be applied
to the purpose of studying the leucocytes in the blood, and for the
detection of micro-organisms therein.*®

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28 THE BLOOD.

2. Leucocytosis.—By this term is meant a condition in which the
number of white corpuscles in the blood is temporarily much increased.
Such an increase occurs in health as part of the process of digestion.®®
One to two hours after the principal meal the white corpuscles are
found in the blood in the proportion of 1 : 150 or even 1 : roo of red
corpuscles, diminishing soon after to 1 : 350 or 600, or, according to
Griber,©© between 1: 521 and 821. <A great number of observations,
conducted in the author’s clinic, give the proportion to leucocytes of red
corpuscles as 1 : 500-800 ®! in healthy adults. Reinecke’s ® figures are
1: 720.8 In new-born children the condition is different (Schiff ).°*
In the first three days of life the number of white corpuscles is very
great, and after that they diminish, as also do the red corpuscles, till the
proportion is 1: r88—1:168. Much greater degrees of leucocytosis,
which for the most part is transitory, are found in disease. Virchow
maintains that every affection in which the lymphatic glands are involved
leads to this condition. It invariably accompanies croupous pneumonia
(Tumas).°° The author has never failed to find it in the croupous
pneumonia of children. V. Limbeck and Pick confirm this. The former
observes that it always follows exudation processes, and he proposes to
give this form the name of inflammatory leucocytosis. [V. Jaksch ° has
quite lately observed that the prognosis in cases of acute pneumonia
running its course without an increase in the number of white blood
cells is very unfavourable.] Leucocytosis does not arise from typhoid
(v. Limbeck),°® but may occur in its course. When it does so, it seems
to point to a complication with some suppurative disorder (Sadler).

 

The condition occurs in connection with certain tumours,—sarcoma
(Sadler) ©° in pernicious anemia and chlorosis, and regularly in the
reaction stage resulting from the injection of Koch’s fluid.’

Leucocytosis can be readily diagnosed with a little practice by means
of the microscope alone. For the more precise estimation of its degree
the Thoma-Zeiss instrument may be used. It is necessary, above all
things, that the blood examined should not be rich in digestion-pro-
ducts, and on this account it should not be taken until some hours
after a meal. It is important to be able to recognise a pathological leuco-
cytosis. Its presence, taken in conjunction with the clinical symptoms,
will often serve to clear up the diagnosis of diseases,—as, for instance,
osteomyelitis,—which, without its light, would be very obscure.”

8. Leukeemia.—This condition, when well marked, may be recog-
nised from the naked-eye characters of the blood (Virchoww),™ which,
when allowed to flow from the finger, is light red in colour, and some-
what turbid and greasy, as though loaded with fatty matter.”

The reaction of the blood is alkaline (Mosler), not acid, as was
formerly thought, but its alkalinity is often considerably less than

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LEUKAEMIA. 29

normal (v, Jakseh). Microscopical examination shows an enormous
increase in the number of white corpuscles [J. H. Bennett]. Virchow
has found them in the proportion 2:3 of red corpuscles; J. Vogl, 1:3
to 1:2; Schredber, 2:3.7° In five cases recently treated in Nothnagel’s
clinic, the proportion was 1:3, 1:5, 1:8, 1:11, 1:12 (Gottlieb).

In a typical case of leukemia observed by the author in a child of
sixteen months, the figures were, 1:40, 1:50, and 1:18; and, in two
other cases they were respectively, 1:23, 1:20, 1:17, 1:12, 1:10, and
ae yale nGe

Another notable characteristic is the diminution of the cellular
elements of the blood in general. In the cases recorded above, their
number fell to 2-3 millions in the cubic millimetre of blood. By the
last examination in the child of sixteen months it was shown to be
2,440,000."6

The amount of hemoglobin in the blood is usually diminished in
leukeemia. In the case of the child recorded above it was shown by

     
 
 

   

   

OD
GE. o O
tte

Ai @dd

Fic. 16.—Leukzemic Blood from a case of Lym phatico-splenic Leukeemia (eye-piece III.,
objective 8a, Leichert).
y. Fleischl’s hemometer to be 6.4 grms., and sank with the progress of
the disease to 3.7 grms. In two other instances it was respectively
4.9—5.6 grms. and 1.2 grm.

It is important, further, to determine what is the prevalent character
of the leucocytes present in the blood. By observing this, the author
believes, in spite of Bizzozero’s™ assertion to the contrary, that it is
possible to ascertain with what form of the disease we have to deal. It
is usual to distinguish leukemia as splenic, lymphatic, and myelogenic,
according to the anatomical seat and clinical symptoms of the disease,
although probably an instance of true myelogenic leukemia has not yet
been observed.* [The existence of a myelogenic leukemia is not recog-

* Several years ago, the author had under observation ‘in Professor Nothnagel’s
clinic a case of nephritis in which the blood contained leucocytes of great size and
with unusually large nuclei, their proportion to the red corpuscles (as determined by

a single examination) being as 1:50. The autopsy revealed, in addition tu chronic
nephritis, changes in the medulla of the bones, like those described by Neumann in

connection with leukemia.

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30 THE BLOOD.

nised by Hayem."® Gowers™ left the question open. Since he wrote,
a case of undoubted myelogenic leukemia has been described by Dr.
Wallace Beatty ®° of Dublin. |

When large and small leucocytes—the latter preponderating
found in the blood, the leukemia is of a lymphatico-splenic character.
When, on the other hand, the larger cells alone are found, we are

 

are

justified in concluding that the disease is splenic, with but little in-
volvement of the lymphatic glands or marrow. If many corpuscles of
a transitional form are found, nucleated red cells, and especially large
white multinuclear corpuscles, there remains no doubt that the bone-
marrow is the seat of serious changes, and the disease is of the myelogenic
type.®!_ [Large and small leucocytes are found in every case of leukemia.
The smaller are most numerous in cases of moderate severity. When

Cry OHO2Z QDu PS Se
ae 3

gaia s

   

cS
o Ox
4 86 o
KH
DG
eS 95
RE &
A Yo
/Q aa

Fic. ee enie Ceils from Leukzemic Blood (ey e-piece III., objective Zeiss y',, homo-
geneous immersion ; Abe's mirror).

the disease tends rapidly to a fatal ending, very large hypertrophied
leucocytes and even giant cells occur (Hayem.8? See also paragraph on
anemia infantum below). Deviations from the normal in size are asso-
ciated with a loss of contractility. The very large leucocytes, and also
the smallest, fail to exhibit amzboid movements. Another peculiarity
noticed by Hayem is the fact that the leucocytes in this disease contain
some hemoglobin more commonly than they do in health,|** By means
of the staining processes noticed at p. 31 the various forms of leukemia
may be further distinguished.

Crystals are occasionally found in leukemic blood (Charcot, Robin,
Vulpian).8+ Newmann® attributes their origin to the marrow, and de-
scribes them as colourless, shining, oblong octahedrals (Ph. Schreiner).®6
They are seldom met with. The author has often sought, but never

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LEUKEMIA. 31

seen, them in freshly-drawn blood. It may be that they form only in
blood that has been allowed to stand.8? Prus§8 has observed them in the
freshly-shed blood, and Westphal®® in the living tissues of leukemic
patients.*

It should also be mentioned that the red blood-corpuscles commonly
undergo changes of form in leukemia, a condition which first received
the name of Poikilocytosis from Quincke.

An advanced stage of leukemia is readily recognised by the aid of
the microscope, but it is by no means easy to distinguish between
commencing leukemia and a pronounced leucocytosis; and this is a
task which the physician will often have to undertake. Magnus Huss
and others ® employ the term “leukemia” only when the white cor-
puscles are in a proportion not less than 1:20. That the diagnosis of
leukemia cannot be made to depend upon this fact alone, however, is
sufficiently proved by the author’s investigation of cases of anemia in
children, where the proportion of leucocytes to red corpuscles was as
1:12, 1:17, and 1:20.°! In another case where the patient was an
adult the proportion stood at 1: 8.1, and yet the condition was not one of
leukeemia.°?

We are indebted to P. Ehrlich ® for an excellent means by which we
may recognise an early stage of leukemia. By observing the “ granules ”
present in the protoplasm of the white corpuscles, he found that these
uniformly exhibited remarkable differences in their staining properties—
differences which have both a physiological and a pathological signi-
ficance. Upon this basis he distinguishes five several varieties of what
he called “granules,” classing them as « to € granules. In all cases of
acute leucocytosis, the mono- and poly-nuclear forms which furnish the
e granules are alone increased in number, whilst the « granules—which
are also styled “eosinophil,” from their property of taking up eosin—
are apparently fewer. Precisely the reverse of this, again, obtains at
the beginning of leukemia, and the fact provides us with a good means
of diagnosing that condition in its early stage. The method of examina-
tion is as follows:—The blood is spread in a very thin layer between
two cover-glasses, which are then grasped with forceps, dried in an
exsiceator, and heated upon plates of copper foil (for this purpose a dry-
ing chamber for temperatures beyond 100° C. will serve very well +) for
a considerable time (ro to 12 hours) at r20°-130° C. A drop of con-
centrated eosin-elycerine solution is then added to the preparation, the
colouring matter is washed off with water, and the preparation dried, and
examined in Canada balsam or oil of cloves.

* For the chemical constitution of these crystals, see Chapters IV., VI., and IX.
+ Hardening with absolute alcohol may also be employed ; then, of course, it will
be necessary to drive off the alcohol before staining.

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32 THE BLOOD.

According to Huber,** good results may also be obtained in the fol-
lowing manner :—Two germs. each of aurantia, indulin, and eosin are
dissolved in 30 erms. of glycerine, the resulting thick fluid well shaken
up, and the cover-glasses (dried and heated as above for several hours
at 120° C.) are immersed in it for a period varying from half an hour
to some days. When taken out, they are carefully washed with dis-
tilled water, dried in the air, and examined in Canada balsam or dammar
varnish. Should the case be one of early leukemia, the red blood-cor-
puscles in such a preparation are stained a reddish-yellow, the nuclei
of the white corpuscles have taken up the blue colouring matter, and in
addition there are seen large leucocytes (eosinophil cells) distended with
granules of a deep red tint (eosinophil granules). In such preparations
the latter are also commonly to be seen scattered separately or associated
uregularly in groups, together with large colourless cellular bodies of
oval shape, distended at their poles with similar particles.

Gabritschewsky ®® and Aldehoff®® stained blood-preparations made as
above with eosin. The latter employed a concentrated alcoholic (bluish)
solution of eosin, that known as No. 22 of Bayer’s factory at Elberfeld,
in the following way :—The preparation is submitted to the action of the
staining fluid for half an hour in the cold, or for two to three minutes
when heat is used ; the excess of colouring matter is then washed away
with distilled water, and the preparation is placed for a short time in a
concentrated watery solution of methylene-blue, dried and examined in
Canada balsam. Very beautiful specimens may be obtained in this way.

A series of observations which the author has made with the blood
of healthy and anemic persons, and especially of rickety children, has
shown that the appearances in question occur but rarely in normal blood
or in that of anemic states. In one case only, that of a patient with
tuberculosis, and who was not leukemic, were they to be seen in
abundance. Aldehof observed a large number of eosinophil cells in
the blood in three cases of malaria; so also did Dolega.%’ The author
has found such in healthy adults in pneumonia, and in anemia of all
kinds. Miller and Rieder ®S have had the same experience. ink
has described numerous leucocytes with eosinophil granules as present
in the blood of asthmatic patients.

It follows that the detection of eosinophil granules in increased
abundance has lost much of its weight as an evidence of commencing
leukemia. Still the interesting observations of Miller 1 afford room
for the belief that, by more accurate differentiation of eosinophil leuco-
cytes, further conclusions may be reached; and he has shown that in
leukemia there is probably but one form (Cornil’s “mark-zellen”) to
be found which does not occur also in healthy blood. The matter will
have acquired a diagnostic importance only when it has been proved

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ANAIMIA INFANTUM PSEUDO-LEUK2MICA. 33

conclusively that the bodies in question do exist in the blood of leukemia
alone, and do not exist in that of other forms of anemia. For the present
the assumption is not warranted. The author has observed leucocytes
similar to those described by Miiller in the blood in a case of sarcoma,
and Weiss 1! has reported in like manner. Nevertheless, where repeated
observation has shown the presence of these bodies, it is perhaps safe to
admit them as evidence of commencing leukemia.

In view of the great importance of Ehrlich’s” process for the investigation
of the blood, some further notice of his methods is called for. [1. Eosinophil
granules are those which stain with acid pigments, of which eosin is one. The
process for their detection has been already described. 2. Basophil granules
stain with basic aniline dyes, e.g., dahlia, gentian-violet, methyl-violet, methyl-
green, vesuvin, and fuchsin. 3. Meutrophil granules stain best with neutral dyes,
i.e., those composed of a coloured base and an acid. Of these, methyl-blue and
acid fuchsin are examples,}%]

[Dr. 8. Delépine divides the aniline dyes into two classes. (1.) Acid fuchsin may
be taken as a type of the first ; (2.) basic fuchsin as a type of the second. The
first class stains deeply the most differentiated parts of the cells; the second,
the least differentiated parts of the cells. Ina drop of blood, the red corpuscles
are most deeply stained by acid fuchsin, the leucocytes but faintly stained, while
the nuclei are not stained at all. If basic fuchsin be used, the nuclei are stained
most deeply, the body of the leucocytes to a less extent, and the red corpuscles
least of all.1°]

For the detection of neutrophil or e-granules, a fluid is required of the following
composition :—To five parts of a saturated solution of acid fuchsin one part of a
watery solution of methyl-blue, and five parts of distilled water are added ; the
mixture is allowed to stand for some days, then filtered, and the filtrate may be
employed for staining blood-preparations in the manner indicated above. The
leucocytes will then exhibit dense violet-coloured granules.

For the detection of basophil or y-granules (“ mast-zellen”” granules *) a fluid
is needed containing 50 cc. of a saturated alcoholic solution of dahlia and 10 cc.
of glacial acetic acid in 100 cc. of water.1

According to Ehrlich, basophil granules are absent from the blood in health.
It is probable that in the near future leucocytes may be further distinguished
according to their development, and the information so obtained may become
available for the purposes of diagnosis, as Einkorn’s! observations suggest. It
would be of great interest to ascertain which of the recognised varieties of
leucocytes occur in the blood in the conditions of leucocytosis mentioned above.
According to Einhorn, they would appear to be especially the polynuclear forms.

4. Anzemia Infantum Pseudo-Leukemiea.'"—The author has
described a-form of anemia of a very distinctive character, as occurring in
children, and the observations of Loos! in connection with the blood-
changes concerned, and of Luzet 1 in respect of its clinical history, furnish
sufficient warrant for regarding it as a separate disorder. Pathologically
the most striking fact is a very great diminution of the cellular elements

‘* [Mast-zellen” is the name given by German authors to certain bodies which
occur chiefly in connective tissue in the neighbourhood of blood-vessels. They are
round, nucleated, larger than leucocytes, and they have granules embedded in their

protoplasm. These granules stain deeply, and have been mistaken for micrococci.]

C
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34 THE BLOOD.

of the blood. In one case the red corpuscles numbered only 820,000,
the white 54,666. Leucocytes are always increased in number, but the
increase is not so great or so progressive as in leukemia. Further, the
leucocytes display a remarkable variety of form and attain to an unusual
size, The red corpuscles in freshly-shed blood exhibit a high degree of
poikilocytosis, and their contents are apt to be colourless—a condition
which is perhaps a form of poikilocytosis (compare figs. 20 and 21).

[Hayem™ has already commented upon the appearance in leukemic blood of
red corpuscles of pale colour and devoid of hemoglobin. These, he says, are not
merely stroma, and he inclines to the belief that they are stroma plus an
albuminoid material with which hemoglobin normally combines.]

Some of the leucocytes hold red corpuscles or fragments of the same
embedded in their substance, and amongst them are a few basophil, and

 

Fic, 18.—Appearance of the Blood from a Case of Anzmia Infantum Pseudo-leukzmica.
(Zeiss’s compensation eye-piece 4, achromatic objective »,, homogeneous immersion; <Abbe’s
mirror and open condenser. The blood was stained by Becker and Huber’s method.)

very large polynuclear neutrophil cells. Finally, nucleated red corpuscles
are also to be met with.

It is to be observed that none of the characters mentioned here as
belonging to the blood in anemia infantum pseudo-leukemica are
peculiar to that condition. Nucleated red corpuscles, for instance, are
found in leukemia, pernicious anemia, and purpura (Spietschka ™).

It is well known that the red corpuscles are all nucleated during early foetal
life, and, according to Hayem,? begin to be replaced by the coloured non-
nucleated erythrocytes or red cells only in the seventh month.

There are, however, clinical symptoms—enlarged spleen, &c.—a descrip-
tion of which would be out of place here, and these, together with the
character of the blood, sufficiently distinguish the disease.

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MELAN ZMIA—MICROCYTH £MIA. 35

It may be mentioned that the changes in the blood are very similar
to those found in leukemia, but in the latter the cellular elements and
the amount of hemoglobin are never reduced so much.

5. Melanzemia.'%—The microscopical appearance of the blood in
this very rare disease suffices for its recognition. There are to be seen
floating amongst the blood-corpuscles smaller or larger granules and
granulation masses, possibly pigment lumps, which are usually black,
more seldom brown and yellow. The granules are united to each other
by a substance which is soluble in acids and alkalies. The pigment
occurs also in the form of separate granules equal in size to leucocytes.
Finally (and this, in the author’s opinion, is the commonest case), the
pigment particles, both small and large, may be enclosed within cells
which occasionally resemble white blood-corpuscles, and sometimes differ
from them in being flask- or spindle-shaped. The pigment lumps are
very rarely observed ; but, on the other hand, the granules, and, more
commonly still, pigment-laden white corpuscles, are often temporarily

Fic. 19.—Melanwmic Blood (eye-piece ILI., objective 3a, Reichert), from a Case of
Malarial Cachexia.

present after a severe attack of ague and in relapsing fever. The pre-
paration (shown in fig. 19) was made from the blood of a man who had
suffered for a year from malarial disease which he had contracted in the
tropics. The appearances described here are usually associated with
oligochromemia and oligocythemia, and accompanied by the symptoms
of anemia.

6. Microcythzemia.—This condition was first described by Vanlair
and Masius.* It is characterised by the presence in the blood of small
hemoglobin-containing elements (mdcrocytes), which are probably derived
from the red blood-cells, and are generally smaller, but occasionally
larger (megaloblasts of Hayem and Lhrlich) than these.

Such bodies are found in many morbid states, and notably in toxic
states, infectious diseases, pronounced anemia, and in burns. Not-
withstanding that much has been written about them, there is really
but little known on the subject of microcytes, and their discovery is
of no assistance in diagnosis. Litten has shown that they may rapidly
appear in the blood, and as rapidly disappear from it. We may refer

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36 THE BLOOD.

here also to Bettelheim’s 5 observations on the subject of minute mobile
granules in the blood. Gram and Grdber 6 regard the microcytes as
the result of post-mortem changes in the blood. The latter believes that
they represent the final product of the rapid and uniform abstraction
of water from the corpuscles; and since such a process will take place
most readily in blood which contains but little water (and is, therefore,
relatively rich in albumin), the subject of microcythemia is invested,
by this theory, with a certain practical importance.

7. Poikilocytosis.—By this term it is usual to describe an affection
of the blood in which the red corpuscles exhibit a remarkable variety

 

Fic. 20.—Poikilocytosis from a Case of Amyloid Degeneration of the Kidney, Liver, Spleen,
and Intestine (eye-piece III., objective 8a, Reichert).

as to form and size.1!” The condition was first noticed in pernicious
anemia, and has been regarded by some authors as pathognomonic of
that disease. Cases, however, have been recorded (Grainger Stewart,
Lépine, Hermann Miiller) in which no such changes were found.

The appearance of the red blood-corpuscles in this condition exhibits
a remarkable variety. ‘Some are normal in shape and size, but amongst.

CCD

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Fia. 21.—Blood in Poikilocytosis (compensation eye-piece 4, Reichert’s apochromatic objective),
from a Case of Anzemia Infantum Pseudo-leukzemica,

them are seen smaller forms and others of great size (megaloblasts).
Some, again, are flask-shaped, and often tipped at one extremity with
a little knob; while others of irregular outline have been compared
to such different objects as an anvil, a biscuit, a goblet, or a kidney

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POIKILOCYTOSIS—CHLOROSIS. 37

(fig. 20). Friedreich and Mosler have seen ameeha-like processes on the
red corpuscles. The author has also observed similar appearances, and
inclines to the belief that the prominent features of poikilocytosis
depend upon the fact that the red corpuscles are endowed with an
abnormal power of contractility. This quality may also belong to the
contents of the red corpuscles 8 (see fig. 21), and it is possible that the
contained substances lately noted within them in cases of cancer may be
accounted for in this way.9 Quincie!2° has observed this condition,
and he has applied to the resulting appearances the name of “ cup-
shaped depressions in the red blood-corpuscles.” From the above
description it may be seen that poikilocytosis is easily distinguished
with the microscope. Such appearances are not confined to any one
disease, but are common to many in which the blood is greatly altered,
and especially in respect of the diminution of its cellular elements and
of the red corpuscles in particular.

The author has himself observed them in cases of chlorosis and severe
anemia of whatever kind, and typically developed in pernicious anemia,
and in anemia infantum pseudo-leukemica. He has also seen them in
the cancerous cachexia, in leukemia, and in amyloid degeneration of the
viscera. Griiber 1?! believes that the poikilocytes do not exist. in the
circulating blood ; a view which the author does not assent to in all cases.

8. Changes in the Formed Elements of the Blood in
Chlorosis.!22— Although the minute examination of the blood in
chlorosis commonly discloses few or none of the changes previously
described, it will prove both interesting and profitable to mark those
particulars in which it differs from simple oligocythemia on the one
hand, and from pernicious anemia on the other.

Chlorotic blood is especially characterised by its paler colour, not
necessarily accompanied by other changes in the physical properties of
its constituents. Microscopical examination shows usually that the red
corpuscles are abnormally pale without their number being markedly
diminished. The application of the methods for counting the corpuscles
and for estimating the amount of contained hemoglobin proves, in the
greater proportion of cases, that while the number of corpuscles is but
slightly altered, the blood is very deficient in hemoglobin. Generalising
somewhat, the conditions that obtain in chlorosis may be said to be :—
Diminution of the amount of hemoglobin, together with a less dimi-
nution of the cellular elements of the blood, and with or without an
accompanying relative increase of leucocytes. Poikilocytosis is a fre-
quent phenomenon in chlorotic blood, whilst microcytes and megalo-
blasts are also not of rare occurrence. In some cases of chlorosis the
number of red corpuscles is so greatly diminished that they approach the
character of pernicious anemia in this particular. Finally, according to

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38 THE BLOOD.

Peiper and Griiber, the alkalinity of the blood is always increased. The
author has noted a diminished alkalinity in three instances.

9. Changes in the Formed Elements of the Blood in Per-
nicious Anemia.!23—Very different is the condition witnessed in
pernicious anemia. The blood is thin, light-coloured, and shows all
the changes which have already been seen to belong to oligocythemia.
Under the microscope its cellular elements are seen to be enormously
diminished in quantity, a condition which is seldom or never observed
in the very worst forms of simple anemia. The number of blood-cells,
according to Laache, may fall so low as 360,000 to the cubic millimetre.
Further, the individual red cells are often larger than normal, and
exhibit in an exquisite manner the characteristics of poikilocytosis.
Eosinophil cells are also present in unusual number, and the characters
belonging to severe anemias generally and to anemia infantum pseudo-
leukeemica may be observed, except that the degree of leucocytosis is
never permanently so great as in the latter disease.

To estimate the diameter of the corpuscles, the method of “ dry
measurement” may be employed. It is founded upon the fact observed
by C. Schmidt, that red blood-corpuscles, when rapidly dried, retain
their form permanently. According to Laache’s directions, the pro-
ceeding is as follows :—A slide is gently heated and then swept quickly
and lightly over the surface of a very small drop of blood drawn from
the skin. The blood dries rapidly, and when placed under the micro-
scope, the corpuscles appear as bi-concave discs, lying apart from one
another, so that their diameter can easily be measured with the familiar
micrometrie apparatus (micrometer eye-piece). In the case of healthy
blood-corpuscles, the diameter ranges between 6.5 or 6.7 and 9.0 or 9.4 “.*
In the blood of pernicious anemia, red corpuscles are found of 10-15 4%
diameter. Microcytes are seldom found in the blood in this disease.

An important sign of pernicious anemia, as Hayem first showed, is
the fact that the number of red cells in the blood is inversely propor-
tional to the quantity of hemoglobin which they contain. Copeman 14
made the remarkable discovery that when the blood of pernicious
anemia is quickly dried, rhombic crystals of hemoglobin are sometimes
formed.

The presence of amorphous hzmatoidin in fresh blood is not a very rare occur-
rence. The author met with it in the case of a child of four months suffering
from hereditary syphilis and severe icterus.

We see then that the characteristic features of the blood in perni-
cious anemia are: a general diminution of its cellular constituents, with
a relative increase in the size of the red corpuscles and in the quantity

* The Greek letter « represents one-thousandth of a millimetre (u=0.001 milli-
metre), and is the sign of a micromillimetre or micron.

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ANAIMIA—BACTERIOLOGICAL METHODS. 39

‘of hemoglobin which they contain.!2 All these properties can he
shown by the methods described above.

[It is often important to have the means of comparing specimens of blood,
whether from different individuals or from the same individual at different times.
Dr. R. Muir 6 has adopted the following method for making permanent prepara-
tions of blood. A film of blood is obtained in the usual way upon a cover-glass,
and while it is still wet the latter is placed in a saturated watery solution of
corrosive sublimate, to which a little salt has been added, and is left there for
thirty minutes. It is then removed and the corrosive sublimate is washed off
with a # per cent. solution of common salt. The cover-glass is placed for a few
minutes in spirit, and afterwards in absolute alcohol. The specimen can then be
stained with eosin and logwood and is absolutely permanent. ]

10. Changes in the Formed Elements of the Blood after
Hemorrhage and in Infectious Diseases (Secondary Anemia).
—In these conditions, and also in chronic nephritis, anemia, with a
diminution in the corpuscular elements and of the colouring matter of the
blood, is of constant occurrence, but the other changes which have been
shown to accompany pernicious anemia, We., are absent. Nebert 12"
has shown that in pulmonary phthisis the amount of hemoglobin fre-
quently diminishes more rapidly than the number of corpuscles.

In myxedema, Krepelin!28 observed blood-changes similar to those
which belong to pernicious anemia, and the same microscopical appear-
ances have been found in cases of anemia due to the presence of
intestinal worms, as Bothriocephalus latus, Dochmius duodenalis (see
Chap. VI.), and in the course of syphilis.!?° The results of malarial
infection have been already noticed (p. 35).

V. THE PARASITES OF THE BLOOD.—Amongst these are mem-
bers both of the vegetable and of the animal kingdom.

A. Vegetable Parasites.—We shall follow the plan usually adopted
in clinical medicine, by which micro-organisms are divided into three
great groups—-(1.) Moulds; (2.) Yeasts (Saccharomycetes) ; and (3.)
Fission-fungi (Schizomycetes, bacteria). The third group alone concerns
us here, for to it belong, almost without exception, the parasites which
as yet have been found to infest the blood. Yeast cells, indeed, have
occasionally been seen in the blood of animals,!°° but not yet in that of
man, nor has any definite disease been attributed to their agency. We
have, therefore, to describe the bacilli of anthrax, of relapsing fever, of
tubercle, of glanders, and of typhoid. With reference to the bacillus of
tetanus, the recent investigations as to its occurrence and significance
are to be received with great reserve. In view of the researches of
Kitasato,!3! however, it is no longer possible to question the pathological
significance of this micro-organism. The statements concerning the

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40 THE BLOOD.

presence of Streptococci in the blood of certain diseases also need con-
firmation before they are made the basis of clinical inferences.

Methods of Examining the Blood for Micro-Organisms.—In certain
diseases (as, e.g. of relapsing fever and anthrax) no difficulty will be
found in determining the presence of bacilli in the blood by means of a
simple microscopical examination. In other instances (and especially
in miliary tuberculosis, typhoid, and glanders) we must resort to the
methods of Hoch and Ehrlich. In all alike the common process is to
dry the blood in a thin layer, so that the shape of the corpuscles is
lost without altering the appearance of the bacilli, and then to submit
it to the staining methods employed by Koch, Ehrlich, Weigert, &c.,1%?
and other investigators. The general principle of the methods is this,
that the fungi are deeply stained by the basic aniline dyes. To these
basic aniline dyes belong :—Bismarck-brown, vesuvin, aniline-brown,
fuchsin, methylene-blue, gentian-violet, and methyl-violet. It must be
observed, however, that other substances besides the micro-organisms are
‘coloured by these dyes. Thus, for instance, masses of protoplasm, cell-
nuclei, and the products of cellular disintegration stain readily with
them. This is true also of the y and 6 granules of Ehrlich, and, in fact,
they have over and over again been mistaken for fungi.

Preparation of Cover-Glasses.—The skin of the finger-tip from which
the blood is to be taken must first be thoroughly cleansed with soap
and water and a nail-brush, and washed with corrosive sublimate (z in
1000). All traces of the latter are removed by first rinsing the finger
with alcohol, and finally pouring ether upon it. A pretty deep punc-
ture is now made in it with a needle previously sterilised by heat. The
small instrument devised by Hauwaley 123 may be used instead of the
needle.

Scheurlen’s *+ process is, perhaps, safer, although, as a fragment of glass may
remain in the wound, it is not free from danger. Numerous observations have
shown that aseptic blood can be obtained in the ways mentioned here.

The first drops of blood that issue are swept away with a well-sterilised
platinum needle, and a cover-glass held in steel forceps, also sterilised,
is quickly brought in contact with the surface of the blood as it flows
freshly from the wound. To this cover-glass another is at once applied,
and the blood spread in a very thin layer between them. They are
then separated with the aid of two pairs of forceps, and placed to dry in
an'exsiccator or in a chamber free from draughts and dust. Care should
be taken that the cover-glasses employed are absolutely free from im-
purities, and to this end they should have been washed before use in
corrosive sublimate, alcohol, and ether. Not less care must be taken to
secure the cleanliness of the needles and forceps used. When dried in
this manner, the cover-glass, with the prepared surface upwards, is three

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BACTERIOLOGICAL METHODS. 41

times passed cautiously through the flame of a Bunsen’s burner, and
then kept for some hours at a temperature of 120°. After this a drop
of a strong watery solution of a basic aniline dye is applied to it by
means of.a pipette, allowed to rest on it for a short time—some minutes
at the longest—and then washed off with a gentle stream of sterilised
distilled water, directed so that it flows over, but not directly down
upon, the stained parts. With this object the cover-glass should be
held obliquely to the stream. The preparation can be examined whilst
wet. To mount it in Canada balsam, dammar varnish, or oil of cloves,
it is necessary to dry it again before placing it with a drop of one of
these substances on a slide.

If too concentrated a staining fluid has been used, and the specimen
proves too highly stained, the excess can be removed by the addition of
aleohol.* hrlich ™® claims for methylene-blue the advantage that, even
when submitted to its action for a long time, the preparation will not he
too deeply coloured.

Over-staining is less likely to oceur when alcohol, glycerine, or acetic
acid has been added to the water in which the dye is dissolved. It
must be mentioned, however, that vesuvin, Bismarck-brown, and aniline-
brown cannot be employed in alcoholic solution.

Further, it is a good plan, especially for the purposes of a provisional
inspection, to treat the cover-glass directly by placing upon it a drop of
a filtered alcoholic solution of an aniline dye, such as fuchsin or methyl-
violet, and then to wash off the superfluous staining fluid with alcohol,
when the preparation may be examined in the manner already described.

With reference to the staining fluid, it is advisable to prepare it
afresh each time it is required, because it readily decomposes when
allowed to stand ; and, besides, fungus vegetation is apt to thrive rapidly
in dilute solutions. To examine a dry cover-glass preparation of blood
for micro-organisms, the directions of Ldfler!*° may be followed with
advantage :—The cover-glasses, prepared as above, are left for 5-10
minutes in a staining fluid consisting of 30 cc. of a concentrated alco-
holic solution of methylene-blue, and 100 cc. of 1: 10,000 solution of
potash, then washed for 5-10 seconds in 4 per cent. solution of acetic
acid, treated with alcohol, dried, and mounted in oil of cloves or Canada
balsam.

Gram’s 37 method, which is also to be commended for the examination
of micro-organisms, is somewhat different. He prepares the cover-glass
in the manner described above, and places it for some minutes in an
Ehrlich-Weigert solution of gentian-violet and aniline-water (p. 105).
When sufficiently stained, he puts it into a solution of iodine and iodide

* Glycerine or dilute acetic acid will serve this purpose also.

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42 THE BLOOD.

of potassium (iodine 1.0, iodide of potass. 2.0, distilled water 300.0),
when a dull red-brown precipitate forms. It remains in the iodo-
potassic-iodide solution for two or three minutes. It is then put to
bleach in absolute alcohol, where it remains for some time. When
taken out and examined, all the cellular elements are seen to be colour-
less, while the micro-organisms are deeply stained a dark blue.

In Weiyert’s °8 modification of the same process the cover-glasses are
stained in a saturated aniline-water-gentian (or methyl-) violet solution,
washed with water or normal saline, and dried. A drop of Lugol’s fluid
is then applied. When this has taken effect, the preparation is once
more dried, and aniline-oil added, a drop at a time. The latter is then
thoroughly washed off with xylol and the preparation examined in the
usual way. By this method micro-organisms are stained a dark blue,
while fibrin particles have a pale colour.

Guinther’s method of investigation for the spirillum of relapsing fever
(see p. 45) is also applicable to the examination of blood for micro-
organisms. The microscope employed in these researches should be
provided with: an ‘oil-immersion lens, and an Abbe’s reflector and open
condenser (Chap. X.). The apochromatice objectives of Reichert, Zeiss,
and other instrument-makers serve still better (see Chap. X.).

1. Bacillus of Anthrax.—The presence of micro-organisms in the
blood of men and animals suffering from anthrax was pointed out
by Pollender, Brauell, and Davaine.® Many other observers (Buhl,
Waldeyer, E. Wagner, and W. Miiller 4°) have since described the
occurrence of the bacillus of this disease in human blood; but in all
cases the number as seen in man falls far short of that witnessed in the
case of the lower animals, and it varies according to the part from
which the blood is taken. It is found most abundantly in splenic blood.
When looked at through the microscope, the micro-organisms are seen
to be motionless, rod-like bodies, 5-12 » long,* and almost uniformly
1 p. broad, slightly thickened at the extremities, and occasionally having
the appearance of transverse segmentation towards the middle. Even
in unstained preparations they can be readily seen when they are present
in great numbers.

The blood is at the same time thin and of a dark red colour;
commonly, too, pronounced leucocytosis co-exists. Where typical an-
thrax bacilli are found in the blood, the diagnosis of the disease is estab-
lished “beyond -question ; but, on the other hand, it must be borne in
mind that the symptoms of anthrax may be well marked while no
bacilli are anywhere to be seen. In such a case the diagnosis may be
established by injecting some of the suspected blood into an animal

* 4=0.001 mm.

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BACILLUS OF ANTHRAX. 43

(mouse or guinea-pig), which, if anthrax be present, will shortly exhibit
symptoms of the disease, and its blood when examined will be found
to hold bacilli in profusion (fig. 22). The bacillus of anthrax does not
form into long threads either in the blood or in the living tissues,

 

Fic. 22.—Anthrax Bacilli from a Rabbit’s Blood ; from a preparation by Professor Weichselbaum
(eye-piece III., objective Reichert ;, homogeneous immersion; Abbe’s mirror and open con-

denser),

and it has no spores (R. Koch).41 It increases only by division. Fig.
22 represents bacilli from a rabbit’s blood.

Fig. 23 is from a preparation made from the blood of a man who had
died of anthrax (wool-sorter’s disease). A comparison of figs. 22 and
23 will enable the reader to recognise the bacilli.

\ \ z = 4 ‘
\ s Re eg Sate
. \
ane ; NN as Wee
~ 4 \
\ ee — \ y , \ ! \ a
\ ‘ \ i] \
“ “= \, \ J \
\ \ = /
\ " \ raw { x"
: \ 2
~ ae | / \ y ~
SNe ' / Ls, / j
‘ i
\ & \ j iS
\y / ety / \ INA
y 7 . | \
on fd /
f/f / f en
f Ne eae Nis = }
a / ‘\ i
4 A /
ae |
/ [- \ ‘et
/ oN
: / i Ee \ \
NG No \ Za N SRS.

Fic. 23.—Anthrax Bacilli from Human Blood (post-mortem); from a preparation by Professor
Eppinger (eye-piece III., objective Zeiss 4, homogeneous immersion; Abbe’s mirror and open

condenser).

The examination of the blood in anthrax is conducted in the manner

described above (for dry cover-glass preparations and staining with

basic aniline dyes). Léffler’s method is especially applicable to the

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44 : THE BLOOD.

purpose. It should be mentioned here that the affection known as
“wool-sorter’s disease,” the nature of which was formerly so obscure, is
now known (from the observations made by Eppinger and R. Paltauf 14?)
to be identical with anthrax, and when the clinical symptoms of that
disease come under observation, the physician should in all cases examine
the blood and pathological fluids (pleuritic exudation, &c.) for bacilli.

2. Spirillum of Relapsing Fever.—The spirillum was first noticed by
Obermeyer 13 in the blood of a patient suffering from relapsing fever.
It has since been seen by many observers, but most authorities are
agreed that it is to be found only during the paroxysms of the disease,
and that as the temperature falls the spirilla disappear.* When a
specimen of blood containing them is placed under the microscope, the
spirilla appear as long and very delicate unsegmented threads twisted
into spirals. Their average length is about six or seven times the
diaineter of a red blood-corpuscle. They have a brisk vibratile move-

®.
©O OF

 

Fic. 24.— Spirilla of Relapsing Fever, from a photograph by Koch.

ment in the direction of their long axis. This motion, when the blood
is examined with a low power, gives to the eye a peculiar impression of
disturbance, and will immediately lead the practised observer to look for
the presence of spirilla. If he then increases the power, and, still better,
if he employs an oil immersion-lens with Abbe’s condenser and a small
diaphragm, the spirilla come clearly into view. These bodies are ex-
tremely sensitive to reagents of all kinds. Even the addition of distilled
water will cause them to disappear.

The number of spirilla which are to be seen together in a specimen
of blood varies greatly, and often bears no relation to the intensity of
the fever.

If the blood is examined in the intervals of the disease, provided
another paroxysm be impending, it displays peculiar refractive bodies
resembling diplococci, which are especially numerous when the paroxysm

* In opposition to this view, see Naunyn, Centralbl. fiir Bacter. und Parasitenk.,
iv. 376, 1888.

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SPIRILLUM OF FEVER—TUBERCLE BACILLUS. 45

sets in; and just as it begins, they even seemed to the author in certain
cases to grow out, as it were, into short thick rods, from which the
spirilla were finally evolved. Before those of the author, similar obser-
vations had been made by Sarnow ; 144 and pending further confirmation,
it seems probable that these bodies are the spores of spirilla, which have
so long been sought for. In addition to spirilla, the blood, especially
after a paroxysm, contains pigment particles (melanin), either free or
incorporated with the leucocytes.

Since both the spirilla and the forms (? spores) just mentioned have
been met with as yet only in the blood of persons suffering from re-
lapsing fever,* their great importance as a clinical test is sufficiently
apparent.

It should be mentioned, however, that forms very similar to the
spirillum of relapsing fever are met with in the blood of malarial patients
(see p. 54) (v. Jaksch and Canalis). In such cases the two diseases
may be distinguished by attending to the other characters of the blood.
Moreover, when relapsing fever supervenes on an attack of ague, the
spirilla assume a modified shape, as it would appear from a very interest-
ing observation by Karlinshi.1

According to Sacharoff,48 the masses of protoplasm which have been seen in
the blood of relapsing fever constitute the specific hematozoon of that disease.
He believes that these develop in the red corpuscles, and that portions of their
nuclei give origin to the spirochete bodies. The writer in question attempts to
account in this way for certain resemblances between ague and relapsing fever.

For the purposes of research an unaltered specimen of blood serves
best, but dried preparations can also be made and stained most appro-
priately with fuchsin.

Guinther 4" has recently advocated the following plan :—The cover-
glasses, prepared in the usual manner, are immersed for ten seconds
in a5 per cent. solution of acetic acid, to destroy the colour of the red
corpuscles. The acetic acid is then removed as far as possible by
blowing upon the cover-glass, and its last traces neutralised by holding
the preparation surface over an open flask of strong ammonia solution
(shaken up previously). The preparation is next stained in the Ehrlich-
Weigert aniline-water gentian-violet solution, and the staining fluid
washed off. It is then mounted in Canada balsam or xylol before it
is inspected. This method is a very good one for the examination of
the blood for micro-organisms in general.

3. Tubercle Bacillus.—This was first described by Weichselbaum \46
as occurring post-mortem in a case of miliary tuberculosis. To one of
his pupils named Meisels 149 belongs the credit of its first discovery in

* Bodies resembling them are found in the buccal secretion (vide chapter on the
buceal fluids).

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46 THE BLOOD.

the same connection during life. Since then much knowledge on the
sub,ect has been derived from the labours of various observers (Lustig,
Sticker, Doutrelepont, Riitiémeyer.1°°

The assertion of Liebmann?*! that tubercle bacilli occur in the blood of
patients who have undergone tuberculin injection is not confirmed by Lhrlich,
Guttmann,'** Hamerle, and others (Kossel).

The number of tubercle bacilli found together is commonly small.
Indeed, when present, they are often so few as to baffle the most careful
investigation. It rarely happens that a specimen of blood is found so

 

Tic. 25.—Tubercle Bacilli in the Blood, from a preparation by Professor Weichselbaum (eye-
piece III., objective Zeiss ~, ; homogeneous immersion; Abbe’s mirror ; open condenser).

rich in bacilli as that represented in fig. 25; but, when detected, they
leave no doubt of the existence of general miliary tuberculosis.

The mode of research is the same as that detailed at p. 104 for the
examination of the tubercle-bacilli of the sputum, and the cover-glass is
prepared in the manner already described.

4. Bacillus of Glanders.—The bacillus of glanders was first dis-
covered by Ldffer + and Schiitz,*> and its association with the disease
has recently been confirmed by Jsrael©6 and Werchselbaum.15" The
bacilli are rod-like bodies, 2-3 « long and 0.3-0.4 u broad, often carry-
ing a spore at the extremity. They are found in the farcy buds and
ulceration of glanders, and also in the blood of persons suffering from
that disease. Fig. 26 represents the bacilli seen in a specimen of blood
taken from a case of glanders in the Vienna General Hospital. They
may be shown in the blood by means of the dried preparation, and they
are best stained by Loffler’s method for detecting these fungi. (See
Chapter VIIL.)

5. Bacillus of Typhoid Fever.—Bacilli have of late years repeatedly
been found inthe blood of typhoid patients, and they are doubtless the
exciting cause of the disease.8 Riitimeyer and Neuhauss 19 experi-
mented upon the blood taken from the roseolar spots of typhoid patients,
and succeeded in cultivating bacilli from it. Recent researches, as

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STREPTOCOCCI. 47

those of Janowshy,1°° show that the bacillus is very rarely present in
the blood during life, and that their detection should not be numbered
amongst the resources of diagnosis. Further information on this subject
will be found in the chapter on Feces.

6. Streptococci—V. Noorden 1! recently found streptococci in blood
taken from the body of a woman who had died of erysipelas. They
exhibited in their cultivation-properties the closest resemblance to the
well-known streptococci of Fehleisen and Rosenbach.

In like manner, Orthenberger,? by applying Weigert’s method to the
examination of the blood after death, has shown the presence in it of
pheumonicocci in six cases of uncomplicated lobar pneumonia.

In a series of cases in which the author examined the blood of pneumonia
patients, employing sterilised human blood-serum as the nutrient substance, he
failed altogether to obtain a cultivation of cocci.

Some years ago Klebs ascertained that micro-organisms existed in the
blood and endocardial vegetations of persons with endocarditis. In a

ees
ae ‘@

O

 

oOo -@
Fic. 26.—Bacilli of Glanders in Human Blood, from a preparation by Dr. Kolisko (eye-piece V.,
objective Zeiss j, homogeneous immersion ; Abbe’s mirror ; open condenser).

case of congenital heart-disease with endocarditis, Singer! has culti-
vated micro-organisms obtained from the blood during life. An instruc-
tive communication lately published by Weichselbawm 1** has also shown
that cultivations of cocci can be obtained from the blood during life in
cases of endocarditis. It is greatly to be desired that systematic investi-
gation of this subject should be made by means of Weigert’s method
and cultivation processes, with the object of establishing a secure stand-
point for clinical diagnosis. The researches of A. v. Hiselsberg, Levy,
and Brunner 1 encourage the hope that this may be accomplished. In
the clinic of Professor Chrobak at Vienna, the blood of patients in a
severe attack of puerperal fever has repeatedly been found to exhibit
micro-organisms of this class.1%

[Streptococcus Pyogenes.—A chain-forming micrococcus was described by Ogston
as occurring in abscesses. It was afterwards submitted to Koch’s cultivation
processes by Rosenbach, who gave it the name of Streptococcus pyogenes, and it
is now known to be associated with septic processes of all kinds, whether in men
or animals. It is apparently the same as Fehleisen’s 8. erysipelatis and Léfler’s

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48 THE BLOOD.

Diphtheriacoccus. It has been obtained from the pus of pyamic abscesses and
empyema, from the tissue-fluids in spreading gangrene, from the vesicles and
pustules of small-pox, and in contaminated calf’s lymph. It occurs in the blood-
vessels in certain cases of diphtheria, scarlet fever, puerperal septiczemia, measles,
and typhoid; but it must be regarded only as a secondary result of those affec-
tions. It may gain admission to the system in any disease attended with lesions
to the skin or mucous membrane, setting up destructive processes, when the
resistance of the tissues is greatly impaired by the working of a special virus
(Crookshank).187

Streptococcus of Scarlatina.—Dr. Klein has recently succeeded in separating a
micro-organism obtained from the blood of scarlatina patients, which he regards
as the contagium, virus, or actual cause of that disease. When cultivated by
inoculating the surface of nutrient gelatine with the post-mortem blood, the
micro-organisms bear a close resemblance to the Streptococcus pyogenes. Klein
is of opinion that the two are sufficiently distinguished, both morphologically
and by their pathogenic effects upon animals. The experiments upon which he
relies, however, are questioned by Crookshank,!® who maintains the identity of the
micro-organisms concerned. A Streptococcus which Klein believes to be the same
as that of scarlatina was found in the blood of cows in an outbreak of disease
amongst those animals at Hendon; and this, when inoculated upon calves, pro-
duced in them the post-mortem appearances of scarlatina. Moreover, the cow-
disease alluded to is thought to have caused an epidemic of scarlet fever amongst
men through the medium of the milk.1],

7. Micro-Organism of the Blood in Hydrophobia.—Bareggi!”° found constantly
present in the blood in hydrophobia a micro-organism which stained with
methylene blue. Placed on slices of potato at 25°-27° C., it developed in the
course of forty-eight hours in flattened hemispherical cultivations. of a colour
ranging between whitish-grey, yellow, and citron. In test-tube cultivations (see
the chapter on Bacteriological Methods) it behaved like the bacillus of Asiatic
cholera. Further research is needed to establish a connection between this micro-
organism and hydrophobia.

8. Bacillus of Tetanus.—Many authorities!" are of opinion that
tetanus is an infectious disease, produced by the agency of the ‘bristle-
bacillus” of Nikolaier. According to the observations of the latter
investigator, the bacilli in question are somewhat longer and thicker
than those of mouse-septicemia. They sometimes form in threads,
commonly in irregular heaps, and occasionally produce spores. The
bacilli themselves, or their spores, have been found in the blood (?)
(Hochsinger). They stain readily in dry cover-glass preparations, and
may be cultivated outside the system. The fact may be mentioned here
that from cultivations of the bacillus Brieger1” has isolated several
ptomaines—tetanin, tetanotoxin, and spasmotoxin—with which he has
induced tetanic poisoning symptoms in animals; and more recently the
same observer has obtained similar poisons from the blood of persons
who had died of tetanus.

Nissen 1"? also has experimentally demonstrated the presence of toxin
in the blood in cases of tetanus. [A. Bruschettini 1 has lately succeeded
in causing fatal tetanus in rats and rabbits by injecting the urine of

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PROTOZOA. AQ

patients suffering from that disease.] The researches of Aitasato!? in
Koch’s laboratory have definitely established the fact that the bacillus
is the specific cause of the disease. It is anzrobic, develops in pus
and forms spores there, but it is occasionally observed in the form of
rods free from spores, if the pus be examined in an early stage.176

B. Animal Parasites (Heematozoa).

1. Protozoa.—Under this heading are to be described the micro-
organisms of malaria,—parasites of very great interest, which occur in
the two principal varieties of Hamameba malarie and Laverania
malarie.

Historical.-—Alebs””" and Tommasi-Crudeli have described a bacillus which is
found in the soil of the Campagna, and they regard this as the specific cause of
malaria.

To Laveran,’8 who in 1880 observed flagellated organisms in the blood of
malaria patients, belongs the credit of the first step towards the ultimate patho-
logy of this disease ; but his discovery was too indefinite to lend itself to any
clinical purpose, and Marchiafava and Celli claim the honour of having first
distinguished and described the hamatozoon, which is the most abundant and,
clinically, the most important of this group of blood-parasites. These observers
detected amzboid bodies within the red corpuscles in the blood of persons
infected with malaria. The amzboid bodies (plasmodia) commonly contained
granules and particles of black pigment. They stain with methylene-blue. They
have not yet been cultivated outside the body,!*” but Marchiafuva and Celli, and
also Gerhardt,!8' by inoculation and intravenous injection with malarial blood
containing them, has succeeded in communicating the disease to other indi-
viduals, and the infected blood in its turn exhibited the plasmodia. The state-
ments of these authors are borne out by others.!**

[Fenton Evans has succeeded in obtaining pure cultivations of the hematozoen
outside the body by treating the nutrient media with living blood,—i.e., blood
taken before rigor mortis has set in. These cultivations, when inoculated upon
animals, produced a fatal disease, of which the symptoms were intermittent,
though not the same as those of classical intermittent fever. He believed also
that by altering the chemical composition of the media the hzmatozoon attained
a higher organisation. This statement is questioned by Dyer.!*3]

Metschnikof proposes to name the parasite Hematophyllum: malarie. TW.
Osler has examined the blood in seventy cases of malarial disease, and found
it present in all. It would appear from his researches, however, that the
organisms concerned assume a greater variety of forms than was previously
supposed.

Councilman,'* again, has recently supported the views of Laveran, Marchiafava,
and Celli. He describes several forms of the parasite, and opposes the doctrine
of Mosso,®> who sought to prove by his experiments that the plasmodium resolves
itself into degeneration types of the red blood-corpuscles ; and maintains that
similar appearances can be found in the blood apart from malaria. Finally,
L. Pfeiffer 1*° has also seen such in the blood after inoculation with vaccine and
in searlatina, Yommasi-Crudeli,'*’ on the other hand, regards the forms in ques-
tion rather as the result than as the cause of malarial disease, believing them to
be the product of the degeneration of the red blood-corpuscles, and further
maintains that the bacillus discovered by Klebs and himself is the true cause of
the disease.- This opinion is shared by Schiavuzzi,!8 who still more recently. has

D
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50 THE BLOOD.

succeeded in cultivating the micro-organism outside the system. ‘Ihe theory of
Danilewsky ® remains to be mentioned. That author supposes that the bodies
under discussion are identical with the hematozoa observed in the blood of many
birds. Ina recent communication he suggests for them the name of Polymitus
malariz, and from his researches, as well as those of Grassi, Felctti, Celli, and
Sanfelice,° it appears probable that birds are attacked by the same parasite
which is associated with malaria in man.

Observations which the author made in Rome in 1889 under the
direction of Marchiafava and Celli, and afterwards in his clinic at
Prague, have satisfied him that the blood in malaria contains specific
organisms, as Laveran first pointed out, and that these specific organisms
are the determining cause of the disease. The subject is thus invested
with great importance from the point of view of diagnosis ; but it must
be admitted that the micro-organisms in question display a great variety
of form, and many details of the life-history of this interesting parasite
remain yet to be discovered. For our purpose, it will suffice to mention
those particulars which at present admit of clinical application. The
following description is founded on the statements of Laveran, Marchia-
fava and Celli, Golgi, Celli and Guarnieri, Grassi and Calandraccio,
Canalis, R. Paltauf, Quincke, Dolega, Plehn, Chenzinshy, Rosenbach,
and Rosin, controlled by the author’s own observations.!®!_ Some of the
figures are borrowed from these writers.

The earlier researches of Laveran, which are so far confirmed by the
Italian observers, have established two facts—first, that the parasite of
malaria assumes a variety of forms in different cases, even within the
same locality ; and, secondly, that its form tends especially to vary with
the locality and with the clinical type of the disease. Hence the dis-
crepancies in the statements made by competent authorities, as by Laveran
on the one hand and Golg’ on the other, the former having had occa-
sion to see only or chiefly the spherical and crescentic bodies presently
to be noticed, while the amezboid parasite seldom came under his obser-
vation. 19?

We have it on the authority of Marchiafava, Celli, and Canalis,
and especially of Golgi and Canalis, that the hematozoon of malaria
occurs in three principal forms, each having a special relation to the
different clinical types of the disease—tertian and quartan ague, the
anomalous varieties, remitting and intermitting attacks, and cases of
fever with short periods of apyrexia (Febris perniciosa algida) (Marchia-
fava and Cellz), and that the development of the organism within the
system is intimately associated with the production of the various sets
of symptoms.

[Hehir 3 has very carefully investigated the blood of malaria patients
in India, and the results, which he has lately published, agree very closely

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PARASITES OF AGUE. 51

with the statements of Laveran and the Italian observers. He found
that there were constantly present in such blood eight different forms,
including the phagocytes, which may be observed to take an active
part in the morbid process. The micro-organisms are, in his opinion,
all varieties of a single polymorphous hematozoon, and in general they
correspond to Laveran’s description. The chief interest attaches to
a micro-organism with flagellated rapidly-vibrating processes, which was
very partial in its distribution through the body, was always most
abundant in the pyrexial period, and the vitality of which was controlled
by quinine. There was also found a spherical body with 3-6 well-
formed cilia-like processes. This is the Hematomonas malarie stellata. |

1. The Parasites of Tertian Ague.—A few hours after the
cessation of the febrile paroxysm the blood may be seen to contain

P

38 G yp aw

Fic. 27.—Parasite of Tertian Ague, as seen in the blood some hours after a paroxysm
(partly copied from other observers). 1%

very small movable bodies of a pale colour, and carrying from one to three
extremely delicate and pigmented thread-like processes (ektoglobular
parasite, fig. 27, on the left). Plehn and the author have observed
similar bodies during the fever-free period.

The parasite, as it is supposed, then invades, or has already invaded,
the red corpuscles (fig. 27, left), where it appears as an actively-moving
body, already, it may be, outlined, as it were, with a wall of melanin
granules. Within the corpuscle it grows in size, and as it does so, the

   

Fic. 28.—-Progressive Endoglobular Development of the Parasite during the Apyrexial
Interval (in part copied from Golgi).195

former becomes progressively despoiled of its hemoglobin. In this way
the parasite develops into a large freely-moving, deeply-pigmented mass
of protoplasm (Ameeba, see p. 53). The changes just described occur in
the fever-free period within twenty-four hours from the termination of
a paroxysm.

While the corpuscles which have been attacked rapidly lose their
colour (fig. 28), the newly-formed melanin accumulates towards their
centre, and the parasite comes to occupy the entire contents of the cor-
puscle. The parasite then undergoes segmentation, and from this result

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52 THE BLOOD.

the various forms described by Golgi, and represented in fig. 28. These

segmentation forms will be noticed at greater length presently.
The invaded corpuscle is disintegrated. Two more days are required

for this endoglobular development of the parasite. This terminates the

 

Fic. 29.—Parasite of Tertian Ague, at or just before the commencement of the attack (copied
from (Golgi).196 The figure shows the various segmentation forms of the parasite.

apyrexial period. A new generation of the parasite has matured, and
its presence in the blood determines a new paroxysm of fever.

The development of the parasite is often completed before the
paroxysm begins.

2. The Parasite of Quartan Ague.—The course of quartan ague
is marked by a development similar to that just described (Golgi).1%"
The endoglobular growth takes place in this case also during the fever-
free period. Its earlier phase is quite the same as that of tertian, only

paras O
a ae

 

Fic. 30.— Parasite of Quartan Ague. Various segmentation forms (from Golgi).1°8

the corpuscles are less rapidly decolorised, and the melanin granules
formed are of larger size.

The chief difference, however, is in the method of segmentation, the
resulting segments being much fewer in quartan than in tertian ague
(fig. 30). In the latter they may be as many as from 15-20 for each
plasmodium, whereas in the former they range from 6 to 12. Moreover,
the process of segmentation itself takes place in a more uniform manner

aes
Se O CO of
Fic. 31.—Parasites of Acyclical Intermittent Fever (from Celli and Marchiafava).

in quartan fever. The parasite requires three days for its development.
Golgi asserts that in quotidian fever the blood contains at once three
broods of the parasite of quartan, which mature successively at intervals
of one day.

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PARASITES OF AGUE. 53

3. The Parasites of Acyclical and Anomalous Forms of
Ague. — For a knowledge of these organisms we are indebted to
Celli and Marchiafava,'® and especially to Canalis. Marchiafava’s
observations were made with the blood of patients suffering from
the acyclic forms of intermittent fever which prevail at Rome in the
summer, autumn, and winter months. In Roman fever, just before the
paroxysm and at the end of the apyrexial period, the blood contains
small annular plasmodia, holding in their central part a mass of hemo-
globin or pigment granules ; also minute moving ameboid bodies with a
sinuous outline, and large round stationary forms which are almost
colourless, and which present at the centre or periphery a circular spot
of pigment. Unlike the parasites of tertian and quartan ague, the plas-
modia of the autumn and winter Roman fever are devoid of pigment
and retain their motility for a long time (Celli and Marchiafava).

In the varieties of Roman fever just noticed are often to be found
the crescentic and sickle-shaped bodies which were first described by

@) O
6 2
| f A 3 :
/ ie ) JR
fe a - a
| :

at oe

Fic. 32.—Crescentic and Falciform Bodies, and Free Organisms carrying Flagella
(Celli and Guarnieri 200),

Laveran. According to Celli and Guarniert the following forms may he
distinguished : Crescented or sickle-shaped bodies, others of a boat- or
spindle-shape, and again others with an oval or circular outline and pro-
vided with flagella (fig. 32).

‘Grassi and Feletti have urged that the name of Hemameeba malariz
should be appropriated to those forms of the plasmodium which have
been described as belonging to the recognised typical varieties of ague,
while the term Laverania malariz is reserved for the sickle-shaped micro-
organism. These writers are of opinion that the latter is associated with
recurring attacks and the malarial cachexia. Golgi holds the view that
the laverania occurs in cases of malarial fever, where the attacks are
separated by long and indeterminate intervals of immunity.

Canalis has directed his attention particularly to the study of the para-
sites which are to be found in cases where the successive febrile attacks
are separated by more or less considerable intervals, and which, for’ the
most part, result in the malarial cachexia. In this connection he has

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54 THE BLOOD.

described the life-history of two varieties of laverania ; and he also finds
that the period of maturation of one brood of the parasite coincides
with the development of fever.

Without entering into details, the author would observe that Canalis’ descrip-
tion applies to certain forms of the hematozoon which he himself has observed
in a case of reduplicated quartan ague with a very irregular course, and in certain
other particulars the observation is worthy of notice. Besides the usual amz-
boid forms, there were to be seen a remarkable number of pale, homogeneous,
red blood-corpuscles, and immediately after the febrile period—a double paroxysm
lasting for twelve hours—the blood contained free particles of protoplasm, en-
closing fine granular pigment and having attached long and well-formed flagella,
There were also present small round bodies segmented in the middle and pro-
vided with long, thick, freely-moving flagella, upon which black particles were
scattered. (See fig. 32.)

The most curious fact noticed was the presence, mostly towards the outer

   

eee OS r

Fic. 33-—lertian Ague; the Blood at the Commencement of the Attack. ‘he figure is com-
posed so as to represent the appearances observed in several cases. Zeiss’s compensation eye-
piece 4, apochromatic objective 2 mm., apert. 1.40, homogeneous immersion ; Abbe’s mirror,
and medium diaphragm.

boundary of the preparation, of spirally twisted bodies resembling the spirillum
of relapsing fever, but thicker and longer than the latter, and further distin-
guished by their outline being broken by very minute pigment particles. ‘These
bodies were actively mobile in the direction of their long axis. They never made
their appearance until some hours after the preparation had been mounted.2"2

Clinically, as has been said, the case was one of reduplicated quartan ague,
and pathologically it was found that distinct generations of the parasite matured
at separate intervals, their maturity corresponding with the access of fever.

Besides the parasites described here, the blood in malaria contains
pigmented leucocytes. These, however, are not characteristic of the
disease, occurring as they do in other febrile states, as, for instance, in
relapsing fever.

As the result of the foregoing description, it will be seen that the
parasite of malarial fever exhibits a singular variety of form.

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PARASITE OF MALARIA. 55

Notwithstanding, there are certain well-established facts available for
the diagnosis of the disease as it presents itself in European climates.
An examination of the blood at the outset, or during the period of fever,
will suffice to establish the nature of the disease in cases of tertian ague.
A number of the red corpuscles will be seen to be of a remarkably pale
colour, and within some of these pale corpuscles will be found freely-
moving colourless bodies, containing a fine granular pigment. Some of
the ved corpuscles are almost quite decolorised, and within these the
process of segmentation of the hemameba into 15-20 parts may be more
or less clearly distinguished. On the other hand, where this process can
be observed, and where the segments are fewer—6 to 8 in number—and
result in the characteristic marigold arrangement, the diagnosis of quartan
Jever may be made with equal certainty.

In view of the great importance of this subject, it is deemed advisable
to illustrate the foregoing remarks by a figure representing a specimen
of blood taken from a case of tertian fever at the commencement of the
paroxysm. The pale corpuscles contain the plasmodia (fig. 33).

This figure is drawn from appearances actually observed by the author
in three cases of tertian fever, and it will perhaps have an additional
value as affording a means of comparison with figs. 27-32, which were
partly borrowed from other sources, and in part merely diagrammatic.

In cases where the hemameeba is found in the blood, together with
the forms of laverania just described, the condition may be taken to be
one of atypical or anomalous intermittent fever.

It is unnecessary to dwell upon the great importance of these
researches. By their aid it has become for the first time possible to
distinguish malaria with absolute certainty by the result of an examina-
tion of the blood, and we have thus acquired an invaluable means of
discriminating other affections which closely resemble it, as obscure
sepsis, and certain cases of endocarditis and tuberculosis.?0?

4. Methods of Examining the Blood for the Parasites of
Malaria.—No more need be said to impress upon the reader the
expediency of being able to recognise the principal varieties of this
interesting parasite. For the purpose is needed an oil-immersion lens and
a moderately wide aperture of the diaphragm, or, still better, an apochro-

6 a RE His : et mao OMe: :
matic objective—as Zeiss’ apochromatic objective —— with compensating
1.40 - °

eye-piece IV. With such an instrument very little practice will secure
proficiency of observation ; indeed, the endoglobular pigmented parasite
can be discovered quite as readily as, for instance, the spirillum of re-
lapsing fever.

For the purposes of more precise investigation, and especially to avoid
the chance of being misled by the process of vacuolation in the red

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56 THE BLOOD.

corpuscles which has been noticed at p. 37, it is necessary to resort to
staining methods.

To distinguish the parasite of malaria from simple vacuolation it will suffice
to smear the under-surface of the slide upon which a preparation is mounted
with some blue fluid, as, for instance, a solution of aniline dye. The vacuoles
will then display the same colour as exists elsewhere in the field when not occu-
pied by corpuscles.?¢*

The parasite may be suitably stained in the following way :—

Methylene-blue is dissolved in normal (0.67%) salt solution until the
fluid is somewhat deeply coloured. The latter is then filtered, sterilised,
and set apart in small quantities in thoroughly sterilised test-tubes. The
point of the finger is then carefully cleansed, a drop of the staining fluid
applied to it, and through this the finger is pricked with a needle. The
flowing blood mixed with the staining fluid is brought in contact with a

 

Fic. 34.—The Blood in Tertian Ague at the Commencement of an Attack. Stained by Aldehoff’s
method; a. Plasmodia; b. Leucocytes; ¢. Eosinophil-leucocytes ; d. Blood-platelets (compen-
sation eye-piece VIII., apochromatic objective 2 mm., apert. 1.40, homogeneous immersion, Abbe's
mirror and open condenser).

cover-glass, and this is placed preparation-side downwards upon a slide
and examined. The preparation must be spread in a very thin layer,
and it is therefore necessary to guard against evaporation. This may be
done by sealing the edge of the cover-glass with paraftin-wax. It may
be examined first with a fairly wide aperture of the diaphragm, and
afterwards with an open condenser and a good oil-immersion lens.

The plasmodia, whether enclosed within the red corpuscles or lying
free in the blood, are stained a distinct blue of a light shade, and upon
this the pigment particles which they exhibit and the process of develop:
ment which they undergo may be easily discerned. It must be mentioned
that besides the plasmodia some red corpuscles which are free from them

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PARASITE OF MALARIA—VERMES. 57

may also take the stain, but with a little attention confusion will not
arise from this, since the corpuscles in question are stained uniformly
throughout. Instead of normal salt solution, diluted and _ sterilised
ascitic fluid may be employed for mixing the methylene-blue solution
(Guarnieri and Celli).

To mount a permanent preparation, the blood should be dried in a
very thin layer, the cover-glass heated for some time in the usual way,
and the preparation stained in eosin-methylene-blue solution (Chenzinshy,
Plehn).?o*

Plehn’s solution is as follows :—

A concentrated watery solution of methylene-blue . . 60 parts
3°/, solution of eosin in 75°/, alcohol . 2 : : . 20 parts
Distilled water . : : . 40 parts

To this is added 12 drops of a 20°/, solution of caustic potash.

The red corpuscles then appear a light red, leucocytes light blue, and
their nuclei a deep blue, the eosinophil granules of the leucocytes a
deep red; the parasites of malaria are stained blue. The method yields
good results.

The method of Aldehojf and Gabritschewsky for staining eosinophil
cells may also be applied for the detection of these parasites (fig. 34) in
the following manner :—

On cover-glasses prepared as laid down at p. 32, the blood is spread
out in a thin layer, and they are then immersed in a concentrated alco-
holic solution of eosin * for half-an-hour in the cold, or for 2-3 minutes
with heat, removed and washed with distilled water, then again stained
by dipping them once or twice into a concentrated watery solution of
methylene-blue, and finally well rinsed with distilled water. It is neces-
sary to obtain the blood rapidly, and to conduct the process without
undue delay. If this precaution be neglected, the blood-plates which
make their appearance (fig. 34 d) may be thought to have something to
do with the disease. R. Paltauf has directed attention to this as a
source of fallacy, and it may possibly explain the remarkable observa-
tions of Hochsinger.?°

It remains to be noticed that Loef and Pfeiffer °° have discovered in the blood

in SMALL-POX certain protozoa, to which they attribute a pathological signi-
ficance.

2. Vermes.—Under this heading we have to describe Distoma
hematobium and Filaria sanguinis hominis. Both are worms—the first
of the class Platodes and order Trematodes?® ; the second of the class
Annelides, order Nematodes, family Filariadew.

1. Distoma Hematobium (fig. 35).—Bilharz 28 has found this para-

* Kosin blaulich 22, Bayer, Elberfeld.

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58 THE BLOOD.

site in the main trunk and branches of the portal vein, in the splenic
and mesenteric veins, and in the venous plexuses of the bladder and
rectum. As the result of his investigations, he came to the conclusion
that more than half the adult Fellaheen and Coptic population of Egypt
suffered from it. Except in the blood, the eggs are more commonly
found than the parasite itself, and this in the liver, the lungs, the
bladder, the urethra, the large intestine, and the urine (see chapter on
Urine), giving rise to diarrhea, hematuria, and ulceration of the mucous
surfaces of these organs. Distoma hematobium has not yet, so far as
we know, been found in the peripheral blood-vessels, and on this account
it is seldom seen in the microscopic examination of the blood during life.
The parasite is of a white colour. The male and female are distinct
individuals. The former is from 12-14 mm. long, the latter 16-19 mm.
The male is thicker than the female. There are oral and abdominal
suckers anteriorly, and the genital opening in either sex lies close behind

 

Fic. 55.—Distoma Hematobium. Male and Female, with Eggs, from a preparation by
Dr. Schiess-Bey.

the latter. On the abdominal aspect of the male is a deep trench with
overlapping edges, which begins just behind the abdominal pore, and
serves for the reception of the female.

The eggs are slender bodies, about o.r2 mm. long and 0.04 mm.
broad, and furnished with a little spike, which projects from the
extremity or at the side.

Ringer *® discovered a new form of this worm at Tamsui in Formosa, and
Manson” found the eggs of the same species in the bloody sputa of a Chinese
who had lived for a long period in Formosa.

2. Filaria Sanguinis Hominis.—Waucherer 21 is said to have first
discovered this parasite in Bahia. Dr. Lewis”? of Calcutta, at all
events, was the first to describe it as occurring in the living body.

It is the larva of a filiform worm, which in the mature state measures
about 40 mm. in length. According to Bourne,?!3 the male is 1} in.
long, and carries two spicule. The larva, as it is found in the blood
of the living subject, is 0.0075 mm. in breadth and o-34 mm. long.
It has a short rounded head, with a tongue-like appendage, and a long
pointed tail. From the hinder extremity a ribbon-like proeess projects,
and when viewed with a high power of the microscope, this, like the
cephalic appendage, is seen to be the end of a closed sac in which the

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HEMOGLOBIN. 59

animal can coil or extend itself. This envelope is entirely structure-
less, but the contained parasite is seen under a very high power to be
transversely striated and very granular. In the blood the animal ex-
hibits for hours at a time the liveliest movements.2!4 At first it seems
to be homogeneous and transparent, but after some hours its motion
ceases, it assumes a darker tint, and the granular contents of its body
are easily discernible.

The parasite is rarely found elsewhere than in the blood and lymph
of persons who live, or have lived, in the tropics. It has recently, how-
ever, been met with in temperate climates.?)

It may infest the blood for months, or even years, without giving

 

Fig. 36.—Filaria Sanguinis Hominis (after Lewis and Leuckavt).

any sign of its presence ; but commonly, by blocking or perforation .of
capillaries and lymphatics, it leads to hematuria and chyluria, or to
hemorrhage and lymphatic exudation in different organs.

It would seem that the parasite is often conveyed by mosquito-bites.?16
Patrick Manson, Stephen Mackenzie, and others,? have shown that in
persons who suffer from the presence of Filaria sanguinis hominis, the
parasite is to be found in the blood only at certain periods, being absent
during the day, and abounding especially at night. Hence it is im-
portant that, when itis sought for, the blood should be taken from the
patient at night, and forthwith examined.

VI—CHEMICAL CHANGES IN THE BLOOD.

1. Colouring Matter.?!"—The most important constituent of the
blood is the Oxyhemoglobin—the combination of the colouring matter
with oxygen which is formed by the aération of the blood in the lungs.
The characteristic spectrum of dilute solutions of this body exhibits two
absorption-bands between D and E (of Fraunhofer’s lines). The band
nearest to D is darker, narrower, and more strongly marked ; that next
to E is less sharply defined and broader (fig. 37).

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60 THE BLOOD.

When submitted to the action of deoxidising substances, oxyhemo-
globin gives place to Reduced Hemoglobin. The spectrum of this body
is characterised by a single band, occupying a space about midway be-

tween the former two bands (fig. 38).

 

Red. Orange. Yellow. Green. Cyanblue.
—— —" 5 >
AGdBEC D Lb Ip

80 IO 100 116
pti

 

40 50
wlth tdi

 

 

 

 

 

 

 

 

Fic, 37. —Speetrum of Oxyhzemoglobin.

Under the action of acids of all kinds, of strong alkalies, and even of
CO,, hemoglobin is broken up into (1) a proteid resembling globulin,
and (2) the iron-containing body known as Hematin.

The spectrum of hematin in alkaline solution shows an absorption-

 

  

Red. Orange. Yellow. Green. Cyanblue.
AaB C D Eb F
0 50 80 90 100 110
ttt Gott the

 

 

  
 

 

 

 

 

 

 

 

 

 

Fic. 38.—Spectrum of Reduced Hemoglobin.

band lying between C and D of Fraunhofer’s lines (fig. 39). In an acid
solution its spectrum is identical with that of the methemoglobin acid
solution (fig. 42).

Hematin in alkaline solution, when treated with reducing agents,

 

Red. Oranye. Yellow. Green. Cyanbluc.
a a —— eee
AadBC D Eb FE

40 50 60 70 80 90 100 110

mob thot

fH
YY 4

Fic. 39.--Spectrum of Heematin in an Alkaline Solution.

 

 

    
  

 

 

 

 

 

 

 

 

 

yields Reduced Hematin. The spectrum of this body (fig. 40) exhibits
two absorption-bands between D and E. If the reduced solution be
shaken up with air or oxygen, these bands disappear again, and the

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TEICHMANN'S CRYSTALS. 61

spectrum shows once more the two absorption-bands of the alkaline
solution of hematin.

Hematin in combination with hydrochloric acid forms, even from
minute blood-traces, microscopic, highly characteristic, brown rhombic
crystals (fig. 41). These crystals were first discovered by Tetchmann.*!
They are of the utmost importance, inasmuch as their formation affords
an admirable test for blood-colouring matter under the most varied con-
ditions. We shall repeatedly have to revert to this later on.

To test for hemin crystals, the following plan may be adopted :—
The substance supposed to contain blood colouring-matter must be dried

Red. Orange. Yellow. Green. Cyanblue.

 

AaBeCe D Eb F
40 50 60 70 80 90 100 L10
ibid thy fbb drt

 

 

 
 

 

 

 

 

 

 

 

 

 

Fic. 40.—Spectrum of Reduced Hematin.

(if not already dry), powdered, and placed upon a slide. A crystal of
common salt is then added to it, and a cover-glass laid upon the pre-
paration. A few drops of glacial acetic acid are then allowed to flow
beneath the cover-glass. The whole is heated to a point below boiling,
and after a little while, if the substance contains blood colouring-matter,
hemin crystals (fig. 41) will be discernible by the microscope.

When an acid solution of hematin in alcohol is treated with reducing agents,
a series of colouring-matter derivatives are obtained. Of these, hwmatoporphyrin

 

Fic, 41.—Teichmann’s Hiemin Crystals (eye-piece III., objective 8a, Reichert).
(Hoppe-Seyler)° and heaahydro-hematoporphyrin (Nencki-Sieber)* have been
already isolated. If hzematoporphyrin be acted upon with tin and hydrochloric
acid in an alcoholic medium, it yields a body which cannot be distinguished
chemically or by its spectrum from urobilin (Hoppe-Seyler).?* According to C. le
Nobel,?"* however, this body is otherwise not identical with urobilin.

This substance can also be obtained from bilirubin by the action of sodium
amalgam (Maly).”4 There is another important derivative of hematin, which is
apparently identical with bilirubin. This is Hematoidin, a substance first dis-
covered by Virchow?” in extravasated blood. It was afterwards found in old

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62 THE BLOOD.

cerebral clots, in splenic infarctions, blood cysts, &c., and it has been met with
in human urine, in the sputum, and feces.*

From these facts, namely, that urobilin can be formed from hematin by the
action of reducing agents, and that this substance can also be formed from
bilirubin, Nencki and Sieber have established very simple relations between the
colouring matter of the blood and that of the bile. They have constructed a new
formula to express the constitution of hematin, and from this it would appear
that hematin is changed into bilirubin by the addition of two molecules of water
and the removal of one atom of iron, thus :—

Cy. Hz Ni O, Fe + 2H00 —- Fe = Cy Has Na Ob
———ae
Hematin. Bilirubin.

It follows from this, according to Nencki and Sicber, that bile pigment is JSormed
from the colouring matter of the blood, in that its molecules lose iron and take wp water.
Latschenberger 26 concludes, from experiments which he performed on animals,
that bile pigment, or rather its antecedents, to which he gives the name of Chole-
globin, results from the decomposition of blood colouring-matter, a dark-coloured
ferruginous pigment being formed at the same time. Choleglobin is elaborated
both in the tissues and in the interior of cells.

It seems to the writer not unimportant to consider these views here, in antici-
pation of much that will have to be said later on concerning the colouring-matters
of the blood and of the bile, in their relations to one another.

 

Red. Orange. Yellow. Green. Cyanblue.
Be ~—
AabBC D Eb F

40 50 na 70 80 90 100 ALO
titi tit

 

 
 

 

 

 

 

 

Fic. 42.--Spectrum of Methemoglobin in Acid and Neutral Solutions.

The colouring matter of the blood forms with oxygen another com-
pound, called Methemoglobin,??’ which is distinguished from oxyhemo-
globin by the more intimate union of the O with the Hb.

The spectrum of methemoglobin in acid and neutral solutions shows
four absorption-bands (fig. 42), one well marked (between C and D),
the other three in the yellow, green, and blue, being less easily seen.
This spectrum, as already said, is indistinguishable from that of acid
hematin in alcoholic solution. Any possibility of confounding these
two bodies is, however, excluded by the fact that when methemoglobin
is acted upon with sulphide of ammonium, its spectrum gives place, first,
to that of oxyhemoglobin (fig. 37), and after a while to that of reduced
hemoglobin (fig. 38); whilst, on the other hand, a solution of hematin
treated with ammonium sulphide yields a spectrum exhibiting two
absorption-bands between D and E (fig. 40). In alkaline solution, the

* See the chapters on these subjects.

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BLOOD-CHANGES IN DISEASE. 63

spectrum of methemoglobin shows three bands, viz., a narrow one
between C and D, but close to the latter, and two broader ones between
D and E (Jiderholm).2°8

1. Blood-changes in Dyspneea.—All conditions which interfere with
the giving off of CO, and the absorption of O in the lungs are attended
with certain characteristic changes in the blood.

The clinical symptoms of dyspnoea do not fall within our province.
They result directly from the condition of the blood, which shows itself
in the appearance of the patient. The arterial blood is laden with
carbonic acid, and in consequence has a darker colour, and this imparts
a bluish hue to the visible surfaces—cheeks, lips, nose, and finger-
tips. Microscopical examination of the blood shows no changes of a
special character. And further, in cases of the most severe dyspnoea
the blood is never so deficient in oxygen that its spectrum exhibits any
considerable change, such as, for instance, the disappearance of the oxy-
hemoglobin bands. v. Loos, by the application of Hénocque’s instru-
ment, has observed a notably diminished intensity in the oxyhemoglobin
bands in three cases of extreme cyanosis, while the proportion of con-
tained hemoglobin was approximately normal; and it is probable that,
with greater familiarity in the use of this method, we shall learn to
distinguish quantitative and qualitative spectroscopic changes as a result
of dyspnea.

2. Blood-changes in Carbonic Oxide Poisoning.—In carbonic oxide
poisoning the blood undergoes a change of colour which is appreciable

 

 

 

Red. Orange. Yellow. Green. Cyanblue.
—_— ——
AadBC D Eb F
40 50 60 70 80 90 100 140
pip bet ttt Ee

Fic. 43.—Spectrum of Carbonic Oxide Hemoglobin.

 

 

 

 

 

 

 

 

 

by the naked eye. It becomes of a bright cherry-red, alike in the
arteries and the veins. Spectrum-analysis shows the most important
change (fig. 43). The two absorption-bands of oxyhemoglobin are
replaced by two others between D and E, but placed slightly nearer to
the violet end of the spectrum. These bands indicate the union of the
hemoglobin with carbonic oxide,?*® and the most important quality of
this union is, that these bands cannot, as in the case of oxyhemoglobin,
be made to disappear by the action of deoxidising agents (ammonium
sulphide, Stokes’ fluid). Carbonic oxide hemoglobin in the blood of
the living subject may be recognised thus :—A few cubic centimetres of

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64 THE BLOOD.

blood are taken from the patient by means of a cupping-glass, and mixed
with water. Sulphide of ammonium is then added, and the solution is
placed in a glass vessel with parallel sides, or, still better, the blood
itself placed by means of Hénocque’s apparatus before the slit of the
spectroscope. If the specimen be one of blood poisoned with carbonic
oxide, the two absorption-bands will remain in spite of the admixture
with the reducing agent, sulphide of ammonium.

The presence of carbonic oxide in the blood can also be determined
by the following chemical test:—To a quantity of blood mixed with
water a 10 per cent. solution of caustic soda is added. When the mix-
ture is slowly warmed, a cinnabar-red colour appears. Under similar
circumstances a solution containing oxyhemoglobin will turn brownish-
green (Hoppe-Seyler, Otto).?°°

A modification of this test has been suggested by Salsozwsh?.251 The
blood to be examined is diluted with water to twenty times its bulk,
and a like quantity of a solution of caustic soda (sp. gr. 1.34) is added.
If the blood contains carbonic oxide, the fluid turns first white and
cloudy, and presently a bright red; when allowed to stand, red flakes
form and settle upon its surface. In the case of normal blood, when
treated in this way, a dirty brown colouration results. Kuniyost Kata-
yames method 78? is to add to the blood a little yellow sulphide of
ammonium and dilute acetic acid. The presence of carbonic oxide will
then be shown by the appearance of a beautiful red colour, whilst
normal blood so treated turns grey or greenish-grey.

Kunkel and Weizel 23° employ zinc chloride, or a very dilute solution of
platinum chloride. With these reagents carbonic oxide blood turns a
bright red, while normal blood becomes black. Other tests recom-
mended by Welzel are potassium ferrocyanide, acetic acid, and tannin.
Rubner *34 dilutes the blood with four to five times its bulk of acetate of
lead, which causes normal blood to take a chocolate-brown colour, while
if carbonic oxide be present it turns red.

3. Blood-changes in Poisoning with Sulphuretted Hydrogen (Hydvo-
thionemia).—The investigations of Hoppe-Seyler 23> tend to the conclu-
sion that hemoglobin will enter into combination with H,S, and form
a substance which that author has called Sulphide of Methemoglobin.
It is, however, noteworthy that in the severest cases of poisoning with
H,§, the two absorption-bands in the spectrum of oxyhemoglobin are
never known to disappear. In such cases, the blood becomes peculiarly
dark, and sometimes of a dull green tint. And it is further remarkable
that the distinction between venous and arterial blood entirely disap-
pears (Lewin).°°°

4. Blood-changes in Prussic Acid Poisoning.— Preyer 237 maintains
that hydrocyanic acid forms a crystalline compound with hemoglobin.

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BLOOD-POISONING—HAMOGLOBIN MIA. 65

However this may be, such a compound has not yet been found in the
blood of men or animals poisoned with the drug. According to Hoppe-
Seyler,”** the union of hydrocyanic acid with hemoglobin is of a very
unstable character, the resulting body readily decomposing when crys-
tallised or in presence of putrefaction.

5. Blood-changes in Poisoning with Chlorate of Potash. — Mai-
chand 8° discovered that when potassic chlorate was taken in great
quantities, the blood was profoundly altered, the most notable effect
being the formation of a sepia-like decomposition product, which was
afterwards shown to be identical with the methemoglobin of Hoppe-
Seyler mentioned above. Large doses of chlorate of potash cause the
production of methemoglobin itself in the blood, especially of children.
Stokvis and others 24° conclude from experiments upon rabbits that the
exhibition of the salt is not attended with the formation of methemo-
globin in the blood of the living subject ; while Marchand and Cahn*
have, in fact, obtained this result in certain animals, notably dogs.
The opinion of the latter observers finds support in a clinical notice
of Lenhartz, and also in a pathological observation recorded by JH.
Hammer?”

Chlorate of potash may be easily detected by spectrum-analysis
in fairly dilute solutions of hemoglobin, and the spectrum of methe-
moglobin, if present, will afford presumptive evidence of the poison.
Methemoglobin is produced also by the inhalation of nitrite of amyl
(Gamgee) and the injection of sodium nitrite into the blood-vessels 7#%
(Hoppe-Seyler), as well as by kairin, thallin, hydrochinon, pyrocatechin,
iodine, bromine, turpentine, ether, perosmic acid, permanganate of
potash (G. Hayem), and antifebrin (Fr. Miiller).** [The nitrites form
a compound with its oxygen, more firmly fixed than that of the oxygen
in oxyhemoglobin. They consequently tend to stop internal respira-
tion, but are more readily displaced by the products of asphyxia than
is carbonic oxide hemoglobin, and so again permit the aération of the
blood at the lungs. |

6. Poisoning with Nitrobenzol.—It has been asserted 74 that in dogs
poisoned with nitrobenzol the spectroscope has shown blood-changes
attributable to the presence of hematin. It would seem, then, that in
any case of suspected poisoning by this means in the human subject, the
blood should be examined in this direction by the spectroscope.

7, Hemoglobinemia.24°—By this term is meant the condition in
which hemoglobin is found dissolved in the blood. It is followed by
Humoglobinuria, whenever the spleen and the liver are unequal to the
task of eliminating the materials derived from the destruction of the red
blood-corpuscles within the vessels.

The presence of free colouring-matter in the blood may easily be

i
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66 THE BLOOD.

determined thus:—A little of the blood, drawn from the patient by
means of a cupping-glass, is placed immediately in a refrigerator, and
allowed to remain there for twenty-four hours. If the blood is normal,
perfectly clear yellowish-coloured serum will settle ; whereas, if heemo-
globinemia be established, there will be seen over the blood-clot a
beautiful transparent ruby-red stratum. The spectroscope shows in the
case of normal serum a feeble absorption-band in the blue part of the
spectrum (at /), said to be due to lutein (Thudicum) ;747 whilst with
serum containing colouring matter it shows the two absorption-bands of
oxyhemoglobin. The following method may also be employed :—Blood
serum is made to coagulate by heating it to 70°-80° C. If it contains
dissolved colouring matter it will appear of a more or less deep brown
colour, whereas healthy blood-serum when coagulated is light yellow and
of a milky turbidity. This method serves well for the detection of
heemoglobinemia.*48

8. Recognition of Changes in the Colouring Matter of the Blood.—
The changes in the character of the blood referred to above are chiefly
to be estimated by means of the spectroscope. Very perfect little

a b

é C

Fic. 44.—-Hering’s Spectroscope without Lenses,

 

 

instruments for clinical use have been invented by Desega of Heidel-
berg, Zeiss of Jena, and Hoffmann of Paris. Browning’s spectroscope
is also very suitable for the purpose.

To use one of these, artificial or day light is made to fall upon the
slit of the instrument. The telescopic tube attached to the apparatus
is focused until a spectrum is clearly defined, and if daylight be em-
ployed, the slit-like aperture is narrowed so as to bring Fraunhofer’s
lines clearly into view. The blood-solution to be tested is then fixed
between the aperture and the light. If the fluid be too concentrated,
it must be diluted beforehand. If the light be artificial, whether from
a lamp or some other source, it is well to place a little common salt or
some other salt of sodium in the flame, in order to define the situation
of the sodium line. Hénocque’s instrument is applicable to the same
purpose.

Very good results have been obtained in the investigation of blood
spectra with the aid of £. Hering’s 4° “ Lensless Spectroscope,” an instru-
ment which especially commends itself to the practitioner by reason
of its cheapness. It has been employed by the author together with

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PROTEIDS OF THE BLOOD. 67

Browning’s pocket-spectroscope, and shown itself to be quite as service-
able. The lensless spectroscope consists of two tubes, one sliding within
the other, and of about 24 cm. diameter. Of these, the outer one is
closed at its free end by a plate in which is a slit with a parallelogram
adjustment (fig. 44 c). The two parts of the plate which support this
parallel adjustment carry also a pair of clips destined to hold in posi-
tion a rectangular glass vessel or test-tube containing the fluid to be
examined.?6?

The tubes are lined with black, and the inner one (a) is provided at
(7) with a diaphragm to intercept reflected light. At that end of the
inner tube which is turned towards the observer, a prism (d) is fixed
in such a position that the spectrum is formed in a plane at right angles
to the proximal end of the tube, which is oblique, not vertical, in section.
In using the instrument, the eye must be directed at right angles to this
section, and not in the long axis of the tube. The tubes must also be
adjusted in such a manner that the spectrum is well defined and accu-
rately rectangular.

When this is done (by manipulation of the two tubes), a small but
very clear spectrum is obtained, in which the yellow is little developed,
but which very plainly exhibits absorption-bands such as those of oxy-
hemoglobin and urobilin. The instrument serves admirably for the
investigation of these bodies in blood and urine. Heénocque’s apparatus
is the most appropriate for the examination of undiluted blood.*

2. Proteids of the Blood.—The proteids of the blood are
diminished in all cases in which the total quantity of that fluid is
greatly lessened—temporarily, therefore, in hemorrhages of all kinds.
A permanent diminution of proteids occurs under such conditions as
disturb unfavourably the balance of waste and repair, whether of the
blood itself or of its contained albumin. Thus, in all diseases which
are attended with long-continued and excessive destruction of proteids
in the system, these bodies are found to be proportionally wanting in
the blood. It should be remarked, however, that such processes must
be long continued before this effect is reached, especially where the
digestive functions remain unimpaired. As a rule, a diminution of
proteids goes hand in hand with an unduly watery state of the blood
(hydreemia).

Hoppe-Seyler’s ?*! method is, perhaps, the best for determining the
proportion of proteids in the blood; but we shall not describe it
here, because it is very complicated, and its results are not altogether
accurate.

The occurrence of an absolute increase of proteids has not yet been

* This instrument can be had of Rothe, of Prague, for five florins.

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68 THE BLOOD.

established on satisfactory evidence. A relative increase is known to
happen in such diseases as are attended with the withdrawal of water
from the system more rapidly than it can be supplied, as in cholera and
acute diarvhcea.

In pneumonia and erysipelas there is an increase of fibrin. Hoppe-
Seyler 2 has devised a method for the estimation of the quantity of
fibrin in the blood, which is at once simple and adapted to clinical
purposes. It may be described as follows :—A beaker of about 80 ce.
capacity is provided with an india-rubber cap, perforated in the middle
by a close-fitting rod of whalebone. These are dried and weighed. Next,
30-40 cc. of blood, taken from the body of the patient with a cupping-
glass, are placed in the beaker, which is immediately covered by the
india-rubber cap and its whalebone rod. The blood is then defibrinated
by beating it up with the whalebone rod, allowed to cool, and weighed.
The cover is removed, and the beaker filled with water and beaten up
again. The fibrin is allowed to settle, washed with a solution of salt,
and placed upon a filter whose weight is known. Here it is again
washed with water until the fibrin is almost free from colouring matter.
It is next boiled with alcohol (to dissolve fat, lecithin, and cholesterin),
dried at r10°-120° C., then cooled, and weighed over sulphuric acid.

E. Ludwig? and the author have found peptones present in great
quantity in the blood in leukemia. Devoto, on the other hand, failed to
detect peptone in this condition, and Dr. Wagner (of Petersburg), by
examining fresh leukemic blood according to Devoto’s method, likewise
obtained a negative result. The same blood in a state of decomposition
showed abundance of peptone. In a second case in which the author
has applied Devoto’s method to the examination of leukemic blood no
peptone was found, and the same blood tested after death by this method
appeared also to be free from peptone, while Hoffmeister’s process showed
abundance of that body.

Further investigation is needed to explain the different results alluded to. It
is most likely that one or other of the two methods will serve for the detection
only of certain peptones. The observation of Devoto and Wagner, from which it
appears that Devoto’s method will not show the presence of peptone in leukzmic
blood which has been drawn during life, while in post-mortem blood it will, is of
much interest. In a third case—one of splenic leukamia—the author has lately
found much peptone by both methods in the blood during life.

To determine the presence of peptones in the blood, it is necessary
first to remove the other proteids by the action of metallic oxides, or by
coagulation with ammonium sulphate, and then to proceed in the manner
indicated in the chapter on Urine.

8. Urea.—Uvrea occurs only in traces in healthy blood (J. Picard)?

The following method will serve to detect its presence :—Blood is

 

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UREA. 69

diluted with 3-4 times its volume of alcohol, the mixture allowed to
stand for twenty-four hours, and filtered. The precipitate is washed
on the filter repeatedly with more alcohol, the filtrates are mixed, and
the alcohol distilled off. The residue is treated with nitric acid, and
the resulting crystalline pulp allowed to stand for some hours, when
the crystal masses which have formed are pressed between folds of
blotting-paper, dissolved in water, and treated with carbonate of baryta
until carbonic acid ceases to form, and dried on a water-bath ; the dry
residue is then extracted with boiling absolute alcohol. On evaporation,
the urea remains in long slender prismatic crystals belonging to the
rhombic system. If enough blood has been taken (at least 200-300 cc.),
or if the blood happens to contain urea in large quantities, the following
tests may be performed with the resulting crystals :—

t. Dissolve some crystals in a drop of water upon a slide, add a drop
or two of moderately strong pure nitric acid, and apply a cover-glass.
When looked at through the microscope, the characteristic hexagonal
plates of nitrate of urea will be seen.

2. To a somewhat saturated solution of the crystals add a little
metallic mercury and a drop of nitric acid, and heat; gas (CO, and N)
is rapidly evolved.

3. Heat the dried crystals in a test-tube, add a trace of caustic soda
and a drop of dilute solution of sulphate of copper. A violet colour
(biuret) indicates the presence of urea.

4. Over a erystal of urea pour a drop of fairly concentrated watery
solution of furfurol, and add immediately a drop of hydrochloric acid
of 1.10 sp. gr. A play of colours takes place from yellow through green
and blue to purple-red (Schiff).

This reaction does not occur with uric acid, but is yielded by allantoin, though

less promptly and clearly than by urea. It is given, moreover, by a number of
other bodies. 7°” :

 

When the above method* fails to exhibit the presence of urea—as,

indeed, usually happens in testing blood, on account of the very small
quantity of that body which it contains—resort must be had to the
more accurate process of Hoppe-Seyler,°> which can also be employed
whenever a quantitative analysis of urea is attempted.

[Haycraft?® recommends the following method :—20 ce. of blood are defibri-
nated and spread in a thin layer on a parchment-paper dialyser. This is then
floated on the surface of 50 cc. of absolute alcohol in a suitable vessel, where it
remains for twelve hours, the surface being kept moist by adding distilled water.
To the diffusate is added an equal bulk of concentrated oxalic acid solution, and
it is evaporated to dryness. To the residue is added naphtha-petroleum to remove

 

* The method has been described here because it serves well for the purpose of
examining the secretions and excretions generally for urea.

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70 THE BLOOD.

fats. The purified residue is then dissolved in a little water and barium car-
bonate added, next evaporated, the residue treated with boiling alcohol and
filtered. On concentrating the filtrate urea crystallises out, and may be sub-
mitted to the tests already described. ]

Dr. Miinzer has devised the following plan for the estimation of urea
in the blood :—The latter is treated with absolute alcohol and filtered,
&c., as above, the alcoholic extract evaporated, and the residue dissolved
in water. This is then submitted to Hufner’s process (see chapter on
Urine).

The method is not, perhaps, very exact, but by its means Miinzer has
determined the presence of great quantities of nitrogenous bodies in the
blood in cases of uremia.

Von Schroder’s method *° is, perhaps, the most delicate of all, but, on
account of its minute details, it is hardly applicable to clinical purposes.

Urea is found in increased quantity in the blood whenever its elimi-
nation is interfered with, either by disease of the kidneys or obstruction
of the urinary passages.

V. Schréder has shown that the formation of urea probably takes place in the
liver.

4. Urie Acid and Xanthin Substances.

1. Urie Acid.—Garrod found uric acid to the amount of 0.025-
0.175 in a thousand in the blood of persons suffering from gout. It
must be observed, however, that his method of testing for this substance
was far from exact.261

He took about 30-35 grms. of blood and allowed it to coagulate. Ten cc. of
the serum were then mixed with a dilute acetic acid solution in the proportion of
I: 10, and a delicate thread was placed in the fluid. When the blood contained
not less than 0.025 per 1000 uric acid, it was found that, after twenty-four to
forty-eight hours, the thread was covered with uric acid crystals.

In a few instances only did he precipitate from the blood with alcohol, and
apply the murexide test. 4 beles** has freed the blood from proteids by the
Schmidt-Mulheim process, and then tested for uric acid by Ludwig and Salkowski’s
method. Salomon? has observed an increase of uric acid in the blood during
the acute attack of gout.

For the detection of uric acid in the blood, the following procedure
may be adopted :?°4—roo—300 grms. of blood are removed by cupping,
and at once diluted with 3-4 times the bulk of water, heated on the
water-bath, and, when coagulation begins, treated with a few drops of
acetic acid (sp. gr. 1.0335 at 15° C.) until it has a feebly acid reaction.
It is left on the boiling water bath for 15-20 minutes, then removed
and filtered. The precipitate on the filter is repeatedly washed with
hot water and added to the filtrate. The fluid, which should now have
a slight yellow tinge, is again treated with a little acetic acid (sp. gr. as

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URIC ACID—-XANTHIN BASES. val

before), boiled over a flame, allowed to cool, and filtered. To the filtrate,
when cold, is added a little sodic phosphate, and it is then submitted to
the Ludwig-Salkowskt process. Should it happen that the pure blood
is deficient in salts, it may not coagulate on the water-bath so as to
yield a sufficiently clear filtrate. This may be remedied by the addition
of a little common salt.

The filtrate obtained by the Salkowski-Ludwig process, after the
addition of hydrochloric acid, is evaporated to the bulk of ro ec., and
allowed to stand for twenty-four hours; then, if visible crystals are
deposited, these ave obtained on an asbestos filter, washed first with
cold water and then with alcohol.?%©

1. Examine some of the crystals under the microscope. The character-
istic whetstone forms, and sometimes the rhombic tables, of urie acid
crystals are seen (figs. 110, IIT).

2. Some of the crystals may be submitted directly to the murexide
test (see below). If there should be no precipitate, or only a very slight
one, after the addition of nitric acid, the fluid containing hydrochloric
acid should be evaporated to dryness on a water-bath, pure nitric acid
added, and this again driven off by heat. To the residue is applied, by
means of pipettes, at one part a trace of ammonia, at another a little
caustic soda solution. If uric acid be present a red or purple coloration
develops at the spot touched by ammonia, and a blue round the soda
(murexide test). Nitric acid in the test may be replaced by bromine-
water, or chlorine-water, or nitrous acid (v. Jaksch).?°° The latter serves.
particularly well. The use of bromine-water or chlorine-water as re-
agents has for its object to distinguish between uric acid and the
xanthin bases.

The quantitative estimation of uric acid in the blood may be effected
in the same way. The blood is first freed from albumin, and Salkowshi
and Ludwig's process applied.?67

The blood in health does not contain uric acid in appreciable quantity.
Certain morbid states are marked by its appearance there. In croupous
pneumonia it may amount to 0.008 grm. in 100 grms. of blood. It is present
also in renal disease (acute and chronic nephritis and contracted kidney),
in severe anemia—finally, in all conditions which induce dyspnea,
notably in heart-disease and pleurisy. It is absent from the blood in
articular rheumatism and typhoid. It would appear that the febrile
state, as such, never leads to the production of uric acid in the blood.

From what has been said it follows that the presence of uric acid in
the blood is not characteristic of gout alone, and that it has not, there-
fore, the diagnostic significance imputed to it by Garrod.

2. Xanthin Bases.—Xanthin substances have been found in the
blood by various observers.?& They are closely allied to uric acid, and

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72 THE BLOOD.

the principal are xanthin and hypoxanthin. Very probably adenin,
paraxanthin, and guanin also occur. They may be detected in the
filtrate after the removal of uric acid in Salkowshkt and Ludwig’s process,
by the modified murexide test already described (p. 71), and by washing
the coloured residue after the application of the reagents mentioned
there (v. Jaksch).

5. Carbohydrates.

1. Grape-Sugar.—In health the blood contains a minute quantity
of sugar. To detect its presence there, the blood must first be freed
from proteids, and for this purpose the old method of Claude Bernard *°°
is the best. The blood is weighed, and its own weight of crystalline
sodic sulphate is added to it, and the mixture is boiled and filtered.
The filtrate may be tested for sugar as below. Another method for the
removal of proteids is to rub the blood in a mortar with solid ammonium
sulphate, and filter. In this case also the filtrate is free from proteids,
and the fact may be ascertained by testing it with alcoholic solution of
zine chloride (Abeles).

1. Moore’s test will serve where sugar exists in any quantity. (See
chapter on the Urine.)

2. Trommer’s test. (See chapter on the Urine.)

3. Lhe phenyl-hydrazin hydrochloride test is the best for detecting
slight traces of sugar in the blood. It is conducted as follows (v,
Jaksch) :?—

Add together two parts of phenyl-hydrazin hydrochloride and four ©
parts of acetate of soda ; add water and heat. Take 5 cc. of the proteid-
free filtrate (which is practically a saturated saline solution), obtained
by Claude Bernard’s process, and while still warm add it to 5 cc. of the
solution prepared as above. Place the mixture in a test-tube half filled
with water, heat it for half-an-hour on a water-bath, and allow it to
stand. Or a little of the phenyl-hydrazin salt and acetate of soda may
be added in a dry state to the warm proteid-free filtrate, and the process
conducted as described above. After it has cooled, when examined
under the microscope, it is seen to contain separately and in clusters the
characteristic yellow crystals of phenyl-glucosazon scattered amongst
colourless crystals of sulphate of soda. (See chapter on the Urine.)

To determine the percentage of sugar in the blood, Fehling’s fluid
may be employed (the blood having been previously freed from proteids)
in the manner afterwards to be recommended for testing for sugar in the
urine, and the polarimetric test* may be applied. It seldom happens,
however, that the filtrate contains sufficient sugar to be appreciable with

* See chapter on the Urine.

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GRAPE-SUGAR. 73

the polarimeters at present in use. Lippich’s instrument is the most
sensitive, and gives the best results in this connection.

[Pavey’s method, if somewhat tedious, serves well for the estimation of sugar
in moderately small quantity. The process may be divided into three parts :—1.
40 grms. of sodic sulphate are placed in a beaker, and 20 cc. of blood added,
The beaker and its contents are weighed ; the mixture is stirred, and about 30 cc.
of a hot concentrated solution of sodic sulphate added. The mixture is heated
till a coagulum forms, when the fluid is poured off, the coagulum washed, and
the washings added to the fluid in another vessel, which is then boiled and
filtered. 2, The filtrate is boiled, and an equal quantity of the copper test
solution added. The resulting suboxide of copper is collected on a glass-wool
filter and washed. It is then dissolved with a little peroxide of hydrogen and
nitric acid, boiled to drive off the excess of peroxide, and filtered through glass
wool, which latter must be carefully washed. ‘The filtrate contains the copper in
the form of nitrate. 3. The copper solution is placed in a vessel into which a
cylinder of platinum foil of known weight, connected with the negative pole of
a galvanic battery, is suspended. Within this a platinum spiral is made con-
tinuous with the positive pole of the battery. ‘he current is allowed to flow for
twenty-four hours, when the cylinder is removed, washed in distilled water and
alcohol, and weighed. The amount of copper deposited is the basis of a simple
calculation. One part of copper corresponds to .5678 parts of sugar; hence the
quantity of sugar in the blood used may be obtained by multiplying the weight
of copper deposited by this figure.

Claude Bernard’s "3 method :—Place 20 grms. of crystallised sodic sulphate in
each of six porcelain capsules, and to each add 20 grms. of the blood to be inves-
tigated. Mix the blood and salt together ; boil them till the froth above the clot
becomes white, and the clot itself is free from red specks; weigh again, and
make good the loss from evaporation by addition of water. The whole is then
placed in a small press, and the fluid part expressed, collected in a capsule, and
afterwards filtered. The filtrate is placed in a burette. Ina flask place 1 cc. of
Fehling’s solution, and to it add a few small pieces of caustic potash and 20 cc.
of distilled water. Boil this fluid, and from the burette allow the clear filtrate
of the blood to drop into the boiling dilute Febling’s solution until the latter
loses every trace of its blue colour. Asin all sugar estimations, the process must
be repeated several times to get accurate results. Hence the reason why several
capsules are prepared.

Read off the number of cc. used of the filtrate in the burette, ¢97., = n ce.
The formula

in grammes the weight of sugar per kilogramme of blood.

In Seegen’s method,” which may be taken as the type of the newer methods,
the proteids are precipitated by ferric acetate. The blood is diluted with 8-10
times its volume of water, acidulated with acetic acid, and heated. When the
precipitation of proteids commences, render the mixture strongly acid by the
addition of acetate of soda and perchloride of iron; then add sufficient sodic
carbonate until the mixture is faintly acid, and boil. Allow it to cool, and filter
it through a fine cloth filter, free from starch. The filtrate ought to be clear.
The residue on the filter is washed several times with water, and the remaining
fluid in it expressed by means of a small hand-press. The expressed fluid is then
mixed with the clear filtrate if the mixture has a slightly reddish tint from the

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74 THE BLOOD.

admixture of a small quantity of blood-pigment. Add a drop or two of per-
chloride of iron to precipitate the last traces of the proteids. Filteragain. The
sugar in the filtrate is estimated in the usual way by means of Fehling’s solution.]

In diabetes large quantities of grape-sugar are found in the blood.
Hoppe-Seyler 2” describes a case in which it reached as high as 0.9 per
cent. The researches of Freund 2° would make it appear that a deoxi-
dising substance—presumably sugar—exists in considerable quantity in
the blood in eases of carcinoma. This has been substantially confirmed
by Lrinkler.?7

2. Glycogen.—Salomon and Fr. v. Frerichs?"§ have studied the ques-
tion of glycogen in the white blood-corpuscles. Gabritschewshky?™ dis-
covered that this body occurs partly in the protoplasm of leucocytes, and
partly as free granules in the blood both of health and disease. For its
detection the blood is spread in a thin layer between two cover-glasses,
and dried in the air. A concentrated solution of gum arabic containing,
in roo grms., t grm. of iodine and 3 grms. of iodide of potassium, is
taken, and a drop is allowed to flow between the cover-glasses. The
presence of glycogen-containing leucocytes, which are the same as the
neutrophil cells described at p. 31, and also free granules of glycogen, is
made evident by a more or less deep brown coloration, whether of leu-
cocytes or granules. In health the blood examined after meals exhibits
little or no increase of glycogen. In diabetes and leukemia the glycogen
reaction is very pronounced (see Chaps. 1V., VIT., VIII.).

8. Cellulose.—According to Freund 8° the blood of tubercular
patients contains cellulose. For the detection of sugar, cellulose, and the
carbohydrates generally in the blood, the process of Baumann and
Udransky 8! may be employed with advantage. This is based upon
the fact that the carbohydrates are precipitated from their watery solu-
tions by the addition of benzoyl chloride and caustic potash, forming insol-
uble compounds. This combination of the carbohydrates with benzoyl
chloride when treated with sulphuric acid yields furfurol, a body which
may be recognised by its characteristic colour-reaction.

6. Organic Acids in the Blood (Lipacidemia). — Traces of
volatile fatty acids are sometimes present in the blood. The author has
frequently met with them. For their detection 20-30 erms. of blood
are taken from the patient by means of a cupping-glass, an equal
weight of sulphate of soda added, and the whole boiled and filtered.
The filtrate is evaporated to dryness, and the residue extracted with
absolute alcohol. The alcoholic extract in a large number of cases
contained no fatty acids, but, on the other hand, these occurred in
traces whenever looked for in fever and leukemia, and occasionally in
diabetes. *8?

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LIP MIA—CHOLAMIA. 75:

Lactic acid is also sometimes met with. Normal venous blood has
been said to contain 0.0079 per cent. of sarcolactic acid (Berlinerblau).
In regard to the latter and its tests, the reader may be referred to the
statements of Hoppe-Seyler and Berlinerblau.28* L. Hougouneng *** has.
found B-oxybutyric acid in the post-mortem blood of diabetes.

7. Lipgzemia.—The blood invariably contains small quantities of fat.
While digestion is in progress it abounds in this substance normally ;
but a permanent excess of fat is also a phenomenon of certain morbid
states. The blood in such cases is altered to the naked eye. It is.
turbid and usually paler than in health. Under the microscope a num-
ber of minute strongly-refracting globules are seen floating amongst
the proper cellular elements. The white corpuscles also often contain
fatty particles. [The lipemia of diabetes gives the blood a pink or
strawberry colour, and on standing a creamy layer collects on the
surface.] If any doubt remains in a given case as to the nature of these
particles, the addition of ether will settle the matter. If they are fatty,
a drop of ether poured upon the slide will dissolve them and cause them
to disappear.

Lipzmia has been met with in chronic alcoholism, chronic nephritis,
and severe cases of diabetes. It also occurs in wounds of the medullary
cavity of hones (embolic lipemia) when fluid fat passes into the blood.

8. Choleemia.—By this term is meant the condition in which the
constituents of the bile are found in the blood. In this connection the
biliary acids and colouring matters (bilirubin) are the points of chief
interest to the physician. And of these, again, the biliary acids must
probably be regarded as the real toxic agents, involving great possibili-
ties of mischief, leading to the disintegration of the red corpuscles, and,
as a consequence, to hemoglobinemia, disturbing the innervation of
the heart, and slowing the pulse. Even where such symptoms are
present, however, the quantity of biliary acids in the blood is always
very small—so small at times as to escape detection by the chemical
method presently to be detailed. This method, nevertheless, deserves
to be described, since it will serve where the biliary acids exist in com-
parative abundance in the blood, and in all cases where the secretions
are tested for bile. We shall, therefore, introduce it here :—

The blood 2° to be examined must first be freed from proteids by
precipitation with alcohol, or boiling it after dilution and filtering.
The proteid-free filtrate is treated with acetate of lead and ammonia.
The biliary acids combine with the lead and are precipitated as lead
salts. The precipitate is washed with water on a filter, boiled in
alcohol, and filtered. Carbonate of soda is added to decompose the lead
salt, The solution is again filtered, evaporated to dryness, and the
residue extracted by boiling with absolute alcohol. On evaporation, the

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70 THE BLOOD.

bile salts will crystallise out, or a dull amorphous substance may re-
main, from which the crystals can be derived by the addition of ether.
The amorphous substance itself may be tested for biliary acids by Petten-
kofer’s 86 method. This test depends upon the reaction of cholalic acid
in presence of cane-sugar and sulphuric acid. To apply it, dissolve
some of the crystalline or amorphous residue, obtained as above, in
water; add two-thirds its bulk of sulphuric acid slowly, so that the
temperature may not be raised above 60°. To the mixture now add a
few drops of a solution of cane sugar (1 to 5 of water), and a beautiful
violet colour indicates the presence of biliary acids. According to
Mylius,8" this test depends on the formation of furfurol from grape-
sugar, which then gives a play of colour with the bile acids. The
reaction may also, therefore, be well displayed with furfurol.?**

Mackay’s®*° physiological test may sometimes serve for the detection
of these substances in the blood. It depends upon the action of hile
acids, as observed in experiments, on the atropinised frog’s heart.

If a known quantity of blood be taken, the proportion of bile acids
in the blood may be determined in the manner described above. Efforts
have been made, unsuccessfully, to base an analytical test upon the
polarisation phenomena of biliary acids.

Bilirubin may be recognised by testing the serum obtained from
blood which has been allowed to coagulate on ice by any of the methods
described later on (wide chapter on the Urine). Huppert’s test is the
best for this purpose.

The same thing may be done more simply in a manner which the
author has recently adopted. Blood is taken from the patient with a
cupping-glass, sterilised in a fairly wide cylindrical glass, and allowed to
stand for an hour or two. The serum is then drawn off with a pipette
forced through an asbestos filter by means of an aspirator, and placed
in a test-tube. It is then shaken into froth. If bile pigment be present,
this froth is yellow. In all other cases (as, for instance, in hemoglobin-
emia, where the serum itself is tinted) the froth is quite colourless.2%°
Moreover, if more of the serum be now taken and left for three or four
hours in a warm chamber at 35° C., the development of an intense green
colour will mark the formation of biliverdin. A mere trace of bile pig-
ment will cause this green colour to appear, whereas normal serum
remains unchanged. A still simpler plan **! is to cause the blood-serum
to coagulate slowly at 70°-80° C. If normal, it will show a milky
yellowish tint; but if bile colouring matter be present, this is replaced
by a green colour of varying intensity, according to the proportion of
biliverdin formed from the bilirubin during the heating. In this way
the author has demonstrated bile pigment in the blood when none could
be found in the urine. He has also observed that in nearly every case

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URZMIA—AMMONIZMIA—ACETON AMIA. Taf

where urobilin exists in the urine, bilirubin may be found in the blood.
This is an unportant fact, as showing that bile pigment circulating in
the blood is transformed in the system—probably by the kidneys—into
urobilin.

The microscopical examination of jaundiced blood generally shows nothing un-
usual. According to Silbermann,2? this condition in newly-born infants is marked
by the following changes :—The red corpuscles are more or less disintegrated ;
they are often pale, or exhibit only round the pale centre of the corpuscle a ring
of hemoglobin of normal tint. Blood-plates, macro- and micro-cytes, and poik-
ilocytes are to be seen, together with nucleated red corpuscles and corpuscle-
holding cells. In a case which came under his own observation, however, the
author failed to find such appearances. ‘They are not to be regarded as constant
in jaundice.

9. Ureemia.**’—When urinary products accumulate in the blood,
the condition is termed Uremia. The retention of these products is
marked by certain well-defined phenomena, even though we are not at
present able to refer them to the action of any one substance in parti-
cular. The assumption that the poisonous material is urea, or carbonate
of ammonia resulting from its decomposition, has heen disproved. It is
now believed that the symptoms of uremia are due in general terms to
the excessive accumulation of fixed products in the blood. The interest-
ing researches of Bouchard *** go far to show that they may be referred
to the toxie effects of certain bodies resembling alkaloids (ptomaines)
normally existing in the urine. Stacdthagen, on the other hand, asserts
that no such substances can be found in the urine. Uremic blood
shows an increased quantity of urea and extractives. In a number of
cases reported by Horbaczewsk?,® no increase in salts was noted, even
in the salts of potash. The author himself, as also Pezper, has in
several instances observed that the alkalinity of the blood was greatly
less than normal,2%* and in some cases there was an excess of uric
acid.297 There are no other characteristic changes to be noticed as
occurring in the blood in uremia.

10. Ammonizemia.—Of this condition very little is yet known.
From observations hitherto made, it would appear that the poisonous
phenomena are due to the action of some hody—probably an alkaloid—
introduced into the system by absorption from the diseased bladder.
It would be essential in such cases to examine the blood for ptomaines
and toxalbumins.

11. Acetonzemia.—This term is applied to a condition in which
the blood is surcharged with acetone. Derehmiller and the author 2s
have succeeded, by extracting the blood with zther and subsequent dis-
tillation, in separating from it a substance which gives the reactions of
acetone. In many morbid states, and especially in fevers, it is found in
considerable quantity.

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78 THE BLOOD.

12. Changes in the Salts of the Blood.—The blood contains
about one-half per cent. of chloride of sodium,?® and this quantity
remains constant, whether much salt be taken with the food or not.
Moreover, Schen/:? has shown that in fevers, as, e.g., pneumonia,
where the chlorides disappear from the urine, the proportion of salt in
the blood is not notably altered.

In rickets and osteomalacia the salts are diminished.

The blood of tubercular patients, according to Freund,*° is relatively
deficient in sodium salts and phosphates, whilst at the same time the
salts of potash are increased.

The tests and methods for the qualitative and quantitative analysis
of the salts of the blood are to be found in the various text-books of
physiology and physiological chemistry.°°

[Note on the Specific Gravity of the Blood. —Hammerschlag’s method for determin-
ing the specific gravity of the blood is a modification of Roy’s, with the advantage
that it can be much more rapidly and conveniently applied. A mixture is made,
in a suitable vessel, of chloroform and benzol, two liquids of widely differing
specific gravity and which are freely miscible. In this mixture a drop of blood
is placed, and by the addition as required of more chloroform or benzol, the
density of the liquid is altered until the blood remains suspended in it. When
this point is reached, the specific gravity of the liquid is ascertained in the usual
way. ‘That of the blood is of course the same. Chloroform and benzol may be
supplied from two pipettes, and the whole proceeding may be accomplished in a
few seconds. This method has given the most satisfactory results ; and it dis-
penses with the troublesome necessity of preparing a series of solutions.?°?]

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CHAPTER II.

THH BUCCAL SHCRETION.

Tue saliva is a mixed secretion, derived in part from the mucous glands
within the mouth, and partly from the parotid, submaxillary, and sub-
lingual glands, which open by ducts within that cavity. Any dispro-
portionate activity, whether in health or disease, of one or other of these
glands will be attended with a corresponding modification of the physical
and chemical characters of the saliva.!

[To obtain the saliva fairly pure, the patient should be made to wash
his mouth with a warm solution of bicarbonate of soda, and afterwards
with cold water. The inside of the mouth should then be lightly
touched with a glass rod, moistened with dilute acid, and the secretion
collected. |

I. NAKED-EYE APPEARANCES OF THE SALIVA.—The saliva,
when freshly taken from the mouth, is a colourless or light blue fluid,
usually somewhat thick and stringy. When allowed to stand for some
time, it settles into two layers, of which the lower one is quite cloudy
and turbid, and contains in the greatest abundance the morphological
constituents presently to be described.

The reaction is distinctly alkaline. [The amount secreted daily is
variously stated at from 800 to 1500 grms.]

II. MICROSCOPICAL APPEARANCES.—The saliva, when examined
with the microscope, is seen to contain certain morphological elements
in varying proportions. These are :—

1. Salivary Corpuscles.—These bodies resemble white blood-cor-
puscles, but are larger, and their protoplasm is usually very granular.

2. Red Blood-Corpuscles.—These are seldom met with, and when
they occur are readily recognisable.

3. Epithelium.—Usually in the form of large irregular squamous
cells, derived from the mucous membrane of the mouth and tongue.
The quantity of epithelium to be found in the saliva varies greatly in
health ; and the cells exhibit much difference in shape, according as

79

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80 THE BUCCAL SECRETION.

they come from the superficial or the deeper layers of the mucous mem-
brane. They are, however, easily known by their polygonal shape and
relatively large size.

4. Fungi.—Mould- and yeast-fungi are very seldom seen in the saliva
in health ; when they occur, it is as an accidental constituent, probably
introduced with the food. In disease, however, their presence is frequent.
Fission-fungi, on the other hand, are met with in great number and
variety in healthy saliva. There are to be seen, thickly scattered through
the secretion, smaller or larger colonies of micrococci, of which some
possess the property of staining reddish in a solution of iodine and iodide
of potassium. W. D. Miller? describes four varieties, which he has
named Iodococcus magnus, parvus, vaginatus, &c. ; bacilli, too, of varying
size, which take a bluish red colour with the same reagent. There is
also an organism called the Spirochete buccalis, which occurs in ex-

    

Gb
wae
8 el
"No gone «*

Fic. 45.—Buccal Secretion, prepared by Friedliéinder’s and Giinther’s methods (eye-piece III.,
objective Reichert }, ; homogeneous immersion ; Abbe’s mirror; open condenser),

a, Epithelial cells. e. Spirochzete buccalis,

b. Salivary corpuscles. f. Comma bacilli of the oral cavity.
c. Fat drops. g. Leptothrix buccalis.

d. Leucocytes. h,i, k. Different forms of fungi.

tremely mobile spiral threads, very closely resembling the spirillum of
relapsing fever ; from this it is distinguished chiefly by its greater breadth
and by the smaller number of its coils. Forms resembling the comma
bacillus are frequently found in the saliva (Lewis, Miller).? They have
been obtained in considerable numbers from the secretion (Vignal).4
As many as twenty-one different micro-organisms have been separated
by the ordinary methods (see Chapter X.), and cultivated on plates and
by inoculation; and their behaviour in various food media observed.
Biondi® has recently been engaged in such research. According to
W. D. Miller,® the following list is a summary of the pathogenic fungi
which have hitherto been found in the buccal cavity, part of these
having also been isolated by cultivation methods :—Leptothrix buccalis,
Vibrio buccalis, Spirochete dentium, Micrococcus tetragenus, Micro-
coccus de la rage (Pasteui), Micrococcus of septicemic sputum, the

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FUNGI

 

CHEMISTRY OF SALIVA. SI

fungus designated § by Miller, the bacillus of decaying teeth, Bacillus
crassus sputigenus, Bacillus salivarius septicus, two pathogenic fission-
fungi not yet cultivated (Kreibohm), Staphylococcus pyogenes, albus and
aureus, and salivarius pyogenes, Coccus salivarius septicus, and Bacillus
septicus sputigenus.

Miller” has cultivated over fifty different fungi obtained from the
mouth. A special interest attaches to the presence in the mouth of
healthy persons of the bacillus of sputum-septicemia. Pure cultivations
of this bacillus have been made by Klein, Miller, and Friinkel,8 and
it would appear to be the same which the researches of Frdnkel and
Weichselbaum indicate as the specific cause of pneumonia (see pp. 120,
121). The observations of Léger and Velter® have shown that other
formidable parasites, as the bacillus of diphtheria, Staphylococcus, and
Streptococcus pyogenes are normally innocuous denizens of the mouth.

To show Spirochzte buccalis, a drop of pure saliva should be examined as it
is with a good oil-immersion lens, an Abbe’s condenser, and a narrow diaphragm.
It may be seen also in a preparation stained by Giinther’s process.

Under pathological conditions other pathogenic fungi are to be found
in affections of the mouth ; as, for instance, thrush-fungus, Actinomyces,
and the bacilli of tubercle. J rdnkel!® has obtained the bacillus of
typhoid from the lingual glands in a case of death from that disease,
and doubtless our acquaintance with such forms will extend with our
knowledge.

III. CHEMICAL CONSTITUTION OF THE BUCCAL SECRETION.
—This varies even in health with the activity of the different glands by
which the fluids are secreted. There are to be found traces of albumin
coagulable with heat, mucin, and occasionally sulphocyanide of potas-
sium (CNSK). The saliva contains, further, a ferment which changes
starch into sugar, and a trifling amount of salts. Oxygen, nitrogen, and
carbonic acid gases have been obtained from parotid saliva (Kuilz).U

It is seldom that opportunity offers for a chemical examination of the
saliva in disease. The quantity is then generally diminished rather
than increased ; and further, it is very difficult to obtain a pure secre-
tion from the patient.

Ptyalism (see below) is the only morbid state in which a large quan-
tity of pure saliva can be had. To examine the saliva, the patient
should be made to rinse the mouth with water carefully after each meal,
and the secretion collected for twenty-four hours in a clean vessel. The
reaction may be tested with litmus paper and the specific gravity taken.
It will be found to be alkaline, and of sp. gr. 1.002-1.006. A portion
of the fluid may next be tested for albumin in the manner to be described
in the chapter on Urine.

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82 THE BUCCAL SECRETION.

Another portion may be tested with solution of ferric chloride for
sulphocyanides. Should such be present, a bright red colour appears,
which does not disappear either with heat or on the addition of acid.
If the red colour is not thus obtained, roo ce. of the saliva should be
concentrated on a water-bath and tested as before. [Meconic acid yields
asimilar cherry-red colour with ferric chloride, and this may be obtained
from the saliva in cases of opium poisoning. The addition of mercuric
chloride causes the colour due to sulphocyanide to disappear, whilst that
from meconic acid is unaffected by it.] Colosanti advocates the fol-
lowing method :—The saliva is precipitated with alcohol and filtered.
The filtrate is evaporated on the water-bath, and the residue dissolved in
water. Cupric sulphate is then added. If sulphocyanide he present
an emerald-green colour develops.

Sugar may be tested for in the manner recommended for its detection
in blood, No. 3 (v. supra, p. 72).

The presence of diastatic ferment may be shown thus :—5 cc. of
saliva are mixed with 50 cc. of starch solution, and placed in a warm
chamber or in a water-bath heated to 40° C. When examined after one
hour, the fluid (which of course must have been tested beforehand to
ascertain the absence of sugar) will give all the reactions of grape-sugar
if amylolytic ferment be present.

Nitrites often occur in saliva. They may be detected by adding to
a little of the fluid a mixture of starch paste, iodide of potassium, and
dilute sulphuric acid, when, if nitrites be present, an intense blue colour
will be seen. A very useful test for nitrites has been suggested by
Greiss.14 Toa specimen of saliva diluted with five times its bulk of
water, a few drops of sulphuric acid are added, and then metadiamido-
benzol which melts at 63° C. The appearance of an intense yellow
colour shows the presence of nitrites.

IV. CONSTITUTION OF MORBID SALIVA IN GENERAL.—
The quantity of saliva is diminished during inflammation of the salivary
glands in febrile disorders and diabetes, and often also in nephritis.
[In high fever no saliva is secreted. That of moderate fever is thick
and scanty, and usually acid, and with the rise of temperature its dias-
tatic action is lessened. The secretion is arrested by certain drugs,
notably by belladonna.| It is increased in inflammations of the mouth,
by the action of certain poisons—as, e.g., pilocarpin and mercury /—
[in trigeminal neuralgia] and sometimes by the irritation of carious
teeth. The excessive secretion which attends poisoning by acids and
alkalies is rather due to irritation of the ducts than to any specific
action on the salivary glands. A long-continued flow of saliva will
sometimes occur without its being possible to ascribe it to any of the

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MORBID SALIVA. 83

causes mentioned. In such cases probably the disturbance is due to
some obscure changes in the innervation of the glands. Salivation has
occasionally been recorded as occurring in pregnancy (Schramm).1® [It
is frequently met with in hysterical women. ]

These are the cases (referred to above) which afford a favourable
opportunity for chemical analysis of the saliva.

In a case of ptyalism which the author observed, analysis of the saliva showed
that it contained 995.2 grms. of water and 4.8 grms. of solids. Its reaction was
alkaline. It held a small quantity of mucin, traces of serum-albumin, and some
sulphocyanides. The iodide of starch test showed the absence of nitrites ; and
no sugar was detected by phenyl hydrazin or other reagents (Salkowski).”

Certain diseases are attended with notable qualitative changes in the
saliva. [Its reaction may be acid in diabetes, acute rheumatism, and
mercurial poisoning.]18 In nephritis considerable quantities of urea
have been found in it by Wright, Picard, Rabuteau,!® and Fleischer.?°
For its detection Fleischer employs the following method :—An alcoholic
extract of the saliva is made and filtered, the filtrate evaporated, and
the residue dissolved in amylic-aleohol. Crystals of urea remain after
evaporation, and may be recognised by any of the tests described at
p. 70. Boucheron * found uric acid in the saliva of uremic patients by
employing the murexide test (p. 71). In such cases the author has
tested the saliva in the way described at p. 71, having previously pro-
moted its secretion by administering pilocarpin, and has never succeeded
in finding uric acid there.

Bile pigment and sugar have not yet been found in saliva. Even in that of
diabetic patients there seems to be no sugar. In three cases of diabetes the
author has carefully tested the secretion after the injection of pilocarpin, by
means of the phenyl-hydrazin test, but in each case without any result.

Certain drugs, and amongst them iodide and bromide of potassium, are readily
detected in the saliva soon after they have been taken into the system.”? (See
chapter on the Urine for the method of investigating this body.)

[The following method for the detection of mercury in the saliva is taken from
Ralfe.2 To the saliva secreted during twenty-four hours dilute HCl is added.
The mixture is heated for two hours in a water-bath, filtered, and the filtrate con-
centrated to half its bulk. The precipitate on the filter is placed in a beaker
three parts full of dilute HCl and heated, while small quantities of potassium
chlorate are added, and the mixture stirred to dissolve organic residue. It is then
filtered and the filtrate added to the previous one. The fluid is concentrated to
one-fourth its bulk. It containsall the mercury as bichloride. To test for this :—
1. Place a drop ona gold or copper coin and touch this with the blade of a knife ;
a bright silvery stain results. 2. Boil some of the fluid with pure copper foil ;
mercury is deposited on the foil, and may be volatilised in a test-tube.]

[V. THE SULPHOCYANIDE OF THE SALIVA.—The origin and
purpose of this salt in the economy have long been a subject of specula-
tion to physiologists. The researches of Dr. S. Fenwick ** have invested

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84 THE BUCCAL SECRETION.

the matter with a new interest, and their results go to prove that we
have in the variations of its quantity a valuable index to certain states
of the system. He has collected the records of a large number of cases
in which the saliva was examined, and the quantity of sulphocyanide
carefully compared. This was done by noting the colour produced by
adding to the secretion a certain quantity of a standard solution of per-
chloride of iron. For the purposes of comparison, the tint so obtained
with a mixture of the secretions from many healthy persons is taken
to indicate the normal amount of the salt, and a scale of colours. is pre-
pared by evaporating and diluting the fluid to certain proportions, and
copying the tints in each case.

As a result of his observations, Dr. Fenwick concludes that the sulpho-
cyanide of the saliva is a measure of the functional activity of the nutri-
tive organs, and that it is increased in general whenever an unusual
demand is made on them by the necessities of the system, provided those
organs are capable of responding to the call,—in the early stages of acute
inflammation, of cancer and phthisis, in acute congestion of the liver
from alcohol and over-feeding, in acute rheumatism, gout, and urticaria,
and in convalescence from typhoid and similar diseases. The quantity
is diminished in all conditions where the nutritive organs are unable to
supply the requirements of the system, in the later stages of phthisis
and malignant disease, in long-continued diarrhoea and dysentery, in
jaundice from obstruction, in lead-poisoning, and in ascites and similar
conditions impeding the portal circulation, and where the assimilation
of food is imperfectly performed. Where, in connection with articular
rheumatism, the sulphocyanide is greatly in excess, a tedious recovery is
to be expected, and frequent relapses may be feared.

Dr, Fenwick believes that the sulphocyanide is derived from the de-
composition of biliary compounds (? taurocholate of soda).

A more accurate method of ascertaining its amount is to collect the
saliva secreted during five minutes, add the tincture of perchloride of
iron in the proportion of one drop to a drachm, and filter. The colour
obtained in this way may then be compared with solutions of sulpho-
cyanide of iron carefully graduated. The bottles containing the tests,
and the solutions to be compared with them, should be of exactly equal
size. The flat-sided vessels or hematinometers used for the spectroscopic
examination of blood will serve well. |

VI. THE SALIVA IN SPECIAL DISEASES.

1. Catarrhal Stomatitis.—This affection is regularly attended with
a much-increased flow of saliva, which when examined microscopically
is found to contain an excess of epithelium and many leucocytes, but is
otherwise unaltered.” [Its reaction is acid. ]

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STOMATITIS—THRUSH. 85

2. Ulcerative Stomatitis (Mercurial, Scorbutic, §c.).—The saliva
is fetid, dark brown in colour, and strongly alkaline. It is loaded with
tissue débris, leucocytes, broken-down red blood-corpuscles, and various
forms of fungiin abundance. Friiiiwald ®6 believes that a specific bacillus
which he discovered has a special relation to ulcerative stomatitis. His
contention, however, remains to be proved.

8. Thrush.—The presence of this fungus in the mouth demands
a more detailed notice.** It occurs most frequently in children, but
is common also in adults, especially in association with tuberculosis.
Freundenberg *§ has detected it in healthy persons. It used to be taught
that the saliva of thrush is always acid ; but it is still a matter of doubt
whether the acidity is not due rather to the presence of other micro-

 

Fic. 46.—a. Thrush fungus; b. Conidia; c. Epithelial cells; d. Leucocytes ; ¢. Débris.
(From the mouth of a patient with a weak heart ; eye-piece III., objective 8a,
Reichert).

organisms than to the action of the thrush fungus. Kehrer has shown
that the latter parasite will thrive well in a medium where no free acid
exists, as in lactate of sodium or potassium. The outset of the disease
is marked by the formation of white patches on the mucous membrane,
and when examined microscopically, these patches are seen to enclose
sharp-bordered oval cells, each having one or two nuclei. The cells are
disposed in groups of two or three. After the lapse of some days the
patches run together, and form a membrane which may cover the entire
mucous surface of the mouth, and even line the fauces and cesophagus.
The membranes are at first firmly adherent, but later on loosen, and
may then be easily detached. When examined microscopically they are
seen to consist of epithelial cells, leucocytes, and débris, amongst which
the parasite appears as branching ribbon-like forms composed of long
segments. Each segment usually contains two strongly refractive nuclei

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86 THE BUCCAL SECRETION.

embedded in a clear substance, one at either end. The segments vary
_in length, and grow shorter towards the extremities of the parasite.
They are for the most part homogeneous, but occasionally finely granular.
There are also to be seen the oval bodies figured above, which are
thought to be the spores (conidia) of the fungus.

There is still much dispute as to the place of the thrush fungus in the vege-
table kingdom. Rees refers it to the yeast fungi; Grawitz*” supposes it to be
identical with the fungus studied by Cienkowsky; and Plaut* opposes this
view, regarding it (with both the above-named authors, and also Baginsky 3 and
Klemperer 33) as a yeast fungus.*4 According to the more recent investigations
of Plaut®* the thrush fungus is identical with the widely distributed Monilia
candida. :

The fungus can be easily examined by placing part of the loose mem-
brane with a little glycerine under the microscope.

 

Fic. 47.—Leptothrix buccalis.
The preparation was stained with iodo-potassic iodide solution (eye-piece III., objective 8a,
Reichert).

When pus containing Actinomyces has been discharged into the mouth,
the micro-organism can be found in the saliva. For its recognition,
see the chapter on Pus.

Fischer and Hauser*®® have repeatedly found sarcine in the buccal
mucus of wasting diseases.

VII. DEPOSIT ON THE TEETH.—TIf a little of the tartar be removed
from the teeth with a spatula and examined, it will be seen to abound
mainly in micro-organisms. These comprise :—

1. Spirochete buccalis (mentioned above), in small numbers.

2. Leptothrix buccalis.—Long bacilli, usually segmented and arranged
in large ribbon-like bundles. They stain bluish-red in iodine-potassic-
iodide solution (fig. 47). This micro-organism has been named Bacillus
maximus buccalis by Miller.27 He rejects the view that it has the

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DEPOSIT ON TEETH—COATING OF TONGUE. 87

power of penetrating dentine, but holds with other observers *> that
dental caries is brought about by various fungi, both cocei and bacilli,
which generate acids and destroy decalcified dentine. Mixed up with
‘the masses of Leptothrix are usually to be seen shorter bacilli, which do
not stain in the iodine solution.

3. Various forms of micrococci, occurring both separately and in
colonies.

4. A large number of leucocytes and epithelial cells, usually showing
advanced fatty degeneration (fig. 45).

VIII. COATING OF THE TONGUE.—1. In severe infectious dis-
eases the toneue is coated with a brownish fur, which consists partly of
the remains of food and partly of dried blood. Microscopical examina-
tion of the coating removed from the tongue exhibits, in such a case,
a profusion of epithelial cells and hosts of fungi of various forms. In
addition to these, there is a multitude of dark cellular bodies, derived
doubtless from the corneous and exfoliated epithelium of the part
(Bizzozero).

Schech,®*® again, has called attention to the occurrence of a black fur,
which is probably conditioned by the formation of pigmented papilla on
the tongue.*

2. The tongue of infants is normally coated with a white fur, and a
similar appearance is found in adults when the stomach is deranged.
Microscopical examination shows epithelium, a few salivary corpuscles,
and very many fungi.

[Dr. Dickinson ® has recently investigated the nature and significance of the
various morbid coatings of the tongue. He believes that a just conclusion can-
not be arrived at from the inspection of material scraped from the surface, and
his method was to obtain post-mortem sections through the substance of the
tongue, associating the microscopical with the naked-eye appearances during
life. Thus it is seen that the different varieties of coating distinguished as
‘« stippled,” ‘‘ coated,” “plastered,” ‘‘furred,” and “encrusted,” are all alike
derived from excess and alteration of the epithelial elements of the tongue;
the change, where most profound, extending first between the papille, and then
deeper, with hypernucleation of the deep cells of the corium and the diapedesis
of leucocytes. ‘The presence of non-pathogenic fungi is common to all, and may
be regarded as accidental ; even the thrush fungus occurs independently of the
grosser changes to which it commonly gives rise. The conditions of dryness
and moisture greatly modify both the character of the coat and its significance
as a symptom. ‘The colour of the encrusted brown variety is due to dryness
alone, while at the same time it must be mentioned that a profusion of micro-
organisms is especially associated with this form. Clinically the fact of most
importance is the thickness and exuberance of the coating, and a comparison
of instances has shown that such redundancy is especially connected with
pyrexia. ]

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88 THE BUCCAL SECRETION.

IX. COATING OF THE TONSILS.—The examination of morbid
deposits upon the tonsils is sometimes of the utmost importance in
diagnosis.

1. Croupous and Diphtheritic Tonsillitis. — The membrane
covering the tonsils both in croup and diphtheria is composed of glisten-
ing homogeneous fibrin, disposed in the form of a network, of which
the meshes vary in shape and size, and enclose epithelial cells, blood-
and pus-corpuscles, and micro-organisms of every description. The
differences between croupous and diphtheritic membrane cannot be dis-
tinguished by microscopic examination alone, as was formerly taught.
In both cases whitish layers are found on the tonsils. It should be
mentioned, however, that #. Wagner discriminates between croupous
and diphtheritic tonsillitis, in that the removal of the membrane in the
former affection leaves the underlying tissues simply hypereemic and
infiltrated with serum, while in the diphtheritie form a hemorrhagic or
even sero-purulent infiltration remains.

Hitherto even the newer bacteriological methods of investigation have
not thrown much light on the subject. The observations of Roux and
Versin, Zarnihko, Spronch, Wintgens, and van den Brink, Paltauf and
Kolisho, Escherich, Klein, and Bech, fully confirm the view that the
bacillus first discovered and described by Klebs and Liffler* is to be
regarded as the cause of diphtheria.

G. v. Hoffmann-Wellenhof “has shown that a micro-organism, morpho-
logically and in its life-history closely resembling the bacillus of A/ebs and
Léfler, occurs in the mucous membrane of diphtheria patients. This he
has named the pseudodiphtheria-bacillus. Kolisho and Paltauf, whose
observations have been confirmed by those of others, have again called
attention to a multiple infection in this disease—Strepto- and Botryo-
cocci being found in the interstices of the tissues, and diphtheria-bacilli
on the surface. These discoveries tend somewhat to discount the signifi-
cance of the diphtheria-bacillus as distinguished by Loffler’s indications.
More hopeful are the researches of 2oua and Versin, Brieger and
Frankel, Wassermann, Proskauer, which teach us that these fungi
elaborate proteid substances (toxalbumins) of a very poisonous nature.
When a method has been discovered by which it will be possible
to isolate these substances, either from pure cultivations of the fungi
or from the diseased tissues, we shall probably be in possession of
a more certain and simpler, and for that reason clinically more ser-
viceable, diagnostic resource than is afforded by the present cultivation
processes. Meanwhile, the method of d’Espine and A. de Marignac, as
adopted by Baginshy,*® serves the purpose. A portion of the diphther-
itic membrane is removed, washed in a 2 per cent. boracic acid solution,
and immersed in Loffler’s blood-serum. This consists of 3 parts blood,

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COATING OF THE TONSILS. 89

rt part bouillon, with 1 per cent. of peptone, common salt, and grape-
sugar. The resulting cultivations should then show the characters of
the diphtheria-bacillus ; and Baginsky is of opinion that this is twofold,
corresponding to two distinct clinical types of the disease. Of the latter
the more formidable is induced by the presence of Léffler’s bacillus,
while milder attacks are characterised by the presence within the tissues
of Streptococcus and Staphylococcus.

The author no longer has doubts as to the specific characters of the
diphtheria bacillus, and, with Kolisko and Paltauf, he would urge the
necessity of classing together, under the name of Synanche Contagiosa,
all those cases of ‘so-called croup and diphtheria in which the bacilli
mentioned above are to be found.

Peters*” discovered gregarina-like bodies (Coccidiwm oviforme ; see chapter on
the Feces) in diphtheritic membrane stained with alum-carmine and picric acid.
This fact is noteworthy, but further observation must show in what relation these
forms stand to the disease in man.

2. Pharyngomycosis leptothricia. — A special interest has
recently come to be attached to the nature of the plugs which block
the tonsillar crypts. They are found in almost every healthy person,
and consist of epithelial cells and of long seemented fungi, which stain
bluish-red with the iodo-potassic-iodide solution. In certain conditions
these micro-organisms extend outside the follicles, and cover the surface
of the tonsils with patches of varying size. They then give rise to
subjective symptoms, and their appearance may be mistaken for a com-
mencing attack of croupous or diphtheritic tonsillitis, They may be
readily recognised under the microscope by their reaction with the
iodine solution, as mentioned above, and the course of the disease will
afford a further indication of their nature (Zh. Hering).*8 O. Chiari?
is of opinion that this affection is not one sw generis, but should merely
be regarded as a modification of Angina follicularis, in which such
products are always found.

One or two minutes in the iodine solution suffice to develop the bluish-red
colour in a specimen containing leptothrix. This colour disappears in from
twenty-four to seventy-two hours.

Dr. O. Chiari has called the attention of the author to the fact that yellowish
plugs which do not contain leptothrix are often to be found in the crypts. Ina
very hard concretion from the tonsils, found on chemical examination to consist
of carbonates and silicates, the author met with splendid specimens of lepto-
thrix.

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CHAPTER III.

THE NASAL SECRETION.

I. NAKED-EYE AND MICROSCOPICAL CHARACTERS—
CHEMICAL CONSTITUTION.— Considering the great quantity of
glandular tissue with which the nasal passages is furnished, the secre-
tion in health is remarkably scanty.

Normal nasal mucus exhibits microscopically squamous and ciliated
epithelium in abundance, isolated leucocytes, and an enormous profusion
of fungi.

E. Weibel! has described a curved bacillus obtained from the nasal
secretion of healthy persons, which, when cultivated in nutrient gelatine

 

Fic. 48.—Nasal Mucus (eye-piece ILI., objective 8a, Reichert).
a, Ciliated epithelium ; b, Leucocytes; c. Encysted cocci; d. Bacilli; e. Micrococci.

and agar-agar, develops a spirillum-like body wound into several coils.
It is probable that further researches will show the presence of many
other forms. A great variety has been enumerated by Reimann.?

The normal nasal secretion is a thick fluid, faintly odorous, and of
an alkaline reaction. It abounds in mucin, but otherwise nothing
definite is known about its chemical constitution.

II. THE SECRETION IN AFFECTIONS OF THE NASAL CAVI-
TIES.—At the outset of an attack of acute nasal catarrh, the mucous
membrane is generally dry and much injected, and the secretion lessened

in quantity. Later on, however, there is a copious discharge of a thin
go

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SECRETION IN AFFECTIONS OF NASAL CAVITIES. gi

alkaline fluid, and this, when examined under the microscope, is seen to
consist of a great number of epithelial cells and fungi.

Where suppuration is in progress within the nose, the secretion par-
takes of the character of pus, and is seen microscopically to consist
almost entirely of pus cells. Occasionally, as in cases of wounds per-
forating the cranium and in brain tumours, cerebro-spinal fluid may be
discharged through the nose. Nothnagel® has reported a very inte-
resting case of this kind. Under such circumstances, chemical analysis
showing the absence of albumin and the presence of sugar, or, at least,
of a reducing substance, will determine the diagnosis. The import-
ance of the evidence so obtained in connection with cerebral tumours
is evident.

It is very necessary, in all cases of ulceration of the mucous membrane
of the nose, to look for certain of the pathogenic fungi already known
to us.

Thus, if it be a question whether a particular ulcer is tubercular or
not, a little of the discharge may be removed with the help of the nasal
speculum on a carefully sterilised platinum spatula, and examined for
tubercle bacillus in the manner indicated at p. 104.

Again, the discovery of the characteristic bacillus of glanders in such
a discharge will obviously determine the diagnosis of that disease.
This bacillus may be sought for in the same manner as in the examina-
tion of blood (p. 46). If this be not enough, fungi may be cultivated
on Koch’s plan (see Chapter X.) ; or, finally, in case of doubt, they may
be propagated in one of the lower animals, when a definite conclusion
will be arrived at.

LE. Frinkel* and Hajek ® observed various forms of fungi invariably
present in the discharge of the chronic ulcerative processes known as
ozena. Ldwenberg,® on the other hand, found that one large species of
diplococcus was almost the only form present in such discharge, and he
regards it as characteristic of ozena.

Tost" and Léwenberg® have shown that bodies resembling the pneu-
monia-coccus occur in the nasal secretion (fig. 48, c). H. v. Schrotter
and Winkler ® have isolated the Staphylococcus cereus flavus and another
similar micro-organism, which they designate albus, from the nasal dis-
charge in coryza. The discovery is obviously of no importance unless
it can be shown that these forms do not occur in health.

In a few cases, thrush-fungus and vegetations have been found in the
nose. Mould-fungi in this situation are another rare manifestation
(Schubert).0 Ascarides and other entozoa are very seldom seen there.
Proskauer ™ believes that he has found the embryo of Oxyuris. The
statement is very doubtful. Dipteral larvee are of most common occur-
rence (B. Frenkel).

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92 THE NASAL SECRETION.

The Charcot-Leyden crystals found in blood and sputum have also
been met with in the nasal secretion of an asthmatic patient. Leyden!
observed them associated with eosinophil cells in the nasal mucus in a
case of acute coryza, and Sticker 4 in blood discharged from the nose in
leukemia, after it had stood for some days. Lewy 5 has described them
in connection with nasal tumours (polypi).

Concretions (rhinoliths) occasionally form in the nasal cavities (0.
Chiari, Seifert).

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CHAPTER IV.
THE SPUTUM.

Unvber the term expectoration or sputum? are comprised all those sub-
stances which are removed from the air-passages by the mechanical effort
of coughing or hawking.

I. NAKED-EYE CHARACTERS OF THE SPUTUM.—The naked-
eye appearance of the sputum will often afford valuable information ; and
that this may be as accurate and exhaustive as possible, it is well to
collect the expectoration in glass vessels, after Mothnagel’s plan, and
then to examine it as to its quantity, specific gravity, reaction, colour,
smell, and tendency to stratification.

The quantity of expectoration discharged in twenty-four hours varies
within broad limits. Sometimes it does not exceed a few ce. ; in certain
conditions, on the other hand, as, e.g., where an empyema is discharging
into the lung, as much as 800 to 1000 ce. may be expectorated in twenty-
four hours.

H, Kossel? determines the specific gravity of the sputum in the
following manner :—The sputum is placed in a flask stoppered to pre-
vent evaporation, and gradually heated to 60° C. It is thus reduced to
a thinly-fluid state, and is placed in the pycnometer. The specific gravity
is seen to vary within very broad limits,—for mucous sputum, 1.0043-
1.0080; for purulent, 1.0155-1.0260; and for serous, 1.0375. The
question of density has in no case any clinical interest.

The reaction of the sputum is always alkaline.

In some diseases, as in abscess and gangrene of the lung, there is
marked stratification of its parts (see p. 121).

The colour of the sputum depends partly upon its microscopical and
partly upon its chemical character. When it consists entirely or chiefly
of mucin and a few cells, it is whitish. Green sputa are usually puru-
lent, but the presence of biliverdin or of pigment-forming bacteria may
also impart this colour.

The odour of the sputum is, for the most part, not characteristic ; but
in putrid bronchitis and gangrene of the lung it has a particularly
pungent and unpleasant smell.

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94 THE SPUTUM.

For many purposes it is convenient to collect the sputum in a cylin-
drical glass vessel containing water. In this way, for instance, the
nummular arrangement is made apparent. In other cases, again, cer-
tain constituents, as, e.g., spirals, fibrinous coagula, and shreds of tissue,
may be made more evident on a dark surface, such as that of a polished
black plate. A very suitable plate has been devised by Kroenzg.®

[The expedient of hardening the sputum and examining it in sections
was first adopted by Ad. Schmidt, and lately revived by Gabritschewshy.*
As fixing and hardening fluids the latter employs alcohol, Miiller’s fluid,
Flemming’s solution, picric acid, and sublimate in concentrated forms.
The hardened sputum is embedded in celloidin for cutting, and the
sections stained. This method is valuable for the detection of some of
the constituents of the sputum, which may be destroyed by pressure
under a cover-glass. |

Although much knowledge of a disease may be derived from a naked-
eye inspection of the sputa, it will never enable us to dispense with the
aid of the microscope, by means of which alone we can diagnose certain
affections—some forms of tuberculosis, for instance--with the utmost
certainty.

II. MICROSCOPICAL EXAMINATION OF THE SPUTUM.

1. White Blood-Corpuscles.—These bodies are always found in
large numbers in the sputum, commonly embedded in a viscid stringy
substance. Many of them are of large size and granular, and enclose
within them drops of fat and particles of pigment, such as carbon dust
and masses of hematoidin (see fig. 49, e). In cases where an abscess has
discharged into the lung, and in purulent bronchitis, such as is met
with in connection with emphysema, the sputum may consist entirely
of leucocytes.

2. Red Blood-Corpuscles.—These are also to be found in almost
all sputa, and their presence in small numbers is without significance.
In persons who smoke a great deal, or who spend much of their time in
an atmosphere of tobacco-fumes, the sputa are apt to be streaked with
blood in the morning. This blood, however, proceeds in most cases,
not from the lung-tissue proper, but from the bronchial mucous mem-
brane, and is due to catarrh.

When red blood-cells are present in very considerable quantity, the
sputa will be coloured by them. The individual cells are usually intact,
and in this they depart from the condition in which they are found in
urine and feces. In some cases, however, as in pneumonia, they are
altered and occur as pale discoidal bodies. Where blood has accumu-
lated for some time in the bronchial tubes, the red corpuscles may dis-
appear entirely and the pigment remain in the sputum either as irregular

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MICROSCOPICAL CHARACTERS. 95

particles or as red crystals of hematoidin (see fig. 49, e). The sputum of
pneumonia derives its colour from blood-pigment dissolved in it.

Finally, it is to be noted that in hemorrhage from the lungs the
sputum consists entirely of red corpuscles; in congestion the blood is
intimately mixed with mucus.

3. Epithelium.—The sputum abounds in epithelial cells. Squamous
cells (fig. 49, 2) come either from the mouth or from the surface of the
true vocal cords. Ciliated epithelium is less often scen, and occurs
chiefly in severe bronchial inflammation, when, too, it is probably derived
rather from admixture with nasal mucus® than from the surface of the
trachea, which, as is well known, is lined with ciliated epithelium. The
cells as found in the sputum are usually deprived of their cilia (fig. 49, ¢),
unless in quite recent expectoration, when cilia in active motion may

 

Fic. 49.—Epithelium, Leucocytes, and crystals of the Sputum (eye-piece III., objective 8a,
Reichert).
a, a, aw’, Alveolar epithelium. 6, Myelin forms. c. Ciliated epithelium. d. Crystals of
calcium carbonate. ¢, Hiematoidin crystalsand masses. jf, f’, ”. White blood-corpuscles.
g. Red blood-corpuscles. . Squamous epithelium.

still be seen on them. The mere presence of such cells in the sputum
is of little diagnostic import; but where they occur in great numbers
they may be taken as indicating the commencement of acute catarrh,
either in the back part of the nasal fosse or in the trachea and bronchi.
But there is another variety of epithelium whose appearance in the
sputum is a fact of great importance.’ It is known as “alveolar” epi-
thelium, a name which will serve provisionally, although its derivation
from the alveoli of the lungs has lately been called in question (Bizzozero).§
It consists of elliptical cells, each containing one nucleus, which usually
requires acetic acid to make it visible. The body of the cell is of finely-
granular protoplasm, and very often holds irregular pigment particles in
its substance. These particles consist usually of blood colouring-matter,
iron dust or carbon (fig. 49, a’). In the last case they are unaffected
by reagents generally. Iron dust may be known by its turning blackish-

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96 THE SPUTUM.

green with sulphide of ammonium, or blue with yellow prussiate of
potash and hydrochloric acid. These cells often contain one or more
fatty granules, readily recognisable by their high refractive power, and
at times they exhibit extreme fatty degeneration (fig. 49, a, a”), when
their protoplasm is replaced by oily drops of varying size. Sometimes
large bodies like drops of fat, presumably derived from the rupture of
these cells, are to be seen in the sputum (fig. 49, ¥). They were first
observed by Virchow,® who named them myelin droplets, from the
resemblance they bear to similar forms produced in the destruction of
nerve tissue. According to Panizza,!° however, this myelin (which is
only the outward form of a considerable number of different substances)
is probably mucin ; and in his opinion no diagnostic importance attaches
either to myelin or to myelin-holding cells.

Buhi™ thought that the appearance of alveolar epithelium in the
sputum was characteristic of the disease which he has named desqua-
mative pneumonia. It is certainly a fact that such cells are to be
found in great profusion only in quite fresh specimens of caseous infil-
tration of the lung, whether due to bacilli or not; but then they
occur also in pneumonia, in chronic bronchitis, and in chronic pul-
monary tuberculosis ;!2 sometimes, too, in very large numbers. It
follows from their manifestation in processes differing so entirely that
their diagnostic significance is on the whole slight.

[Troup 1® believes that the presence of alveolar epithelium in the
sputum belongs especially to obstinate catarrhs of the apex, when it
will be found associated with columnar and ciliated cells; he observes
that since such catarrhs tend forthe most part to run into phthisis, we
have in this an early and valuable sign of impending danger.] There
is a special form of alveolar epithelium, consisting of large flat cells con-
taining a golden yellow and brown pigment (failing-heart cells, Wagner),
whose presence in the sputum, according to F. A. Hoffmann, only
occurs in valvular heart-disease and adherent pericardium. They are
absent from the sputum in phthisis and pneumonia, and they may
therefore be taken, in doubtful cases, to point to brown induration
of the lung. Whilst agreeing in general with Hofimann’s view, the
author would insist that in the processes just mentioned the sputum
exhibits cells containing black pigment, which chemical examination
has shown to be a derivative of blood colouring-matter. Such cells
were noticed long ago by J. Sommerbrodt, who described them as
brown alveolar epithelium. He is in accord with Hoffmann as to
their meaning. Lenhartz° has observed them most frequently in con-
nection with mitral stenosis, and regards them as metamorphosed blood-
corpuscle-holding round cells (lymph corpuscles). Krénig}’ endorses
Hoffmann’s view.

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ELASTIC FIBRES. 97

To examine the sputum for epithelium, a small quantity should be
treated with acetic acid, to bring the nuclei and nucleoli into view; or
a specimen may be stained with a watery solution of methylene blue.

4. Elastic Fibres.—These fibres occur in the sputum singly or
in bundles, and they have commonly an alveolar arrangement (fig. 50).
They are of varying length and breadth, dark-coloured, slightly curved,
and generally exhibit a double contour.* Their diagnostic value is great,
as a sign of serious mischief, pointing to destruction of lung-tissue.
They occur, consequently, in tuberculosis, bronchiectasis, pulmonary
abseess, and occasionally in pneumonia, while the other signs of
abscess are wanting. The author has repeatedly found elastic fibres in
cases of pneumonia which otherwise ran a favourable course, and he
supposes that in such cases there was destruction of the pulmonary
parenchyma only over a very limited area. It is a notable fact that

 

Fic. 50.—Elastic fibres in the Sputum (eye-piece ILI., objective 8a, Reichert).

these fibres are rarely to be met with in the expectoration of pulmonary
gangrene, and the reason probably is that they are destroyed in site
by the ferments formed in that process. The fact was first noticed
by Traube.

Elastic tissue may be introduced with the food, and so find its way
into the sputum. <A necessary precaution, therefore, is to direct the
patient to wash the mouth carefully after food, and to separate the
sputa discharged at meal-times from those to be examined for lung-
tissue. Even when every care has been taken, however, one is exposed
to fallacy arising in this way, as fibres derived from the food may lie in
the mouth for days before they are expectorated. Jt ts only when the
bundles of elastic fibres display the alveolar arrangement that we can be

* The figure is taken from a case of ‘pulmonary abscess which was for several
months under treatment in Professor Nothnagel’s clinic.

G

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98 THE SPUTUM.

certain of their origin in the pulmonary alveoli, and it is then only that
they possess any sure diagnostic significance.

For their detection, when they occur in considerable quantity, it will
suffice to add some potash solution to a little of the sputum placed
ona slide. A still better plan is that proposed by Fenwick, who boils
the sputum in a solution (8-10 per cent.) of caustic potash, allows the
mixture to stand for twenty-four hours in a conical glass, and examines
the sediment for elastic fibres under the microscope.

[Prolonged boiling in caustic potash will cause the elastic fibres first to swell
up and then to dissolve. Consequently the boiling must not be too long, and Dr.

Troup recommends that when the sputum is placed on a slide the cover-glass
should remain undisturbed. ]

5. Spirals.—Certain spiral bodies were first observed hy Leyden ™
in the sputum of patients suffering from asthmatic paroxysms.

 

Fic. 51.—Spirals from the Sputum, in a case of bronchial Asthma (actual size).

They were afterwards described by Curschmann as pathognomonic of
disease of the finest bronchial tubes; and since then they have been
seen by O. Vierordt, v. Jaksch, Pel, and Sanger,?® in the sputum of
pneumonia. More recently Lewy?! [and Troup] have written on their
occurrence in asthmatic paroxysms.

Kovdez*2 has seen them in pulmonary cedema, and Czermak *3 observed quite
similar bodies in vascular keratitis. He believes that they are produced by a

twisting upon their axis of the ordinary mucous threads, and he succeeded in
forming well-shaped spirals experimentally by twisting them in this way.

The spirals are usually discernible with the naked eye when the
sputum is carefully examined. They appear then as thick white bodies
of a twisted and tubular form, and distinguished by their clear tint and
great tenacity from all other sputum constituents (fig. 51).

Under the microscope they display a remarkable variety of shape. In
the usual arrangement there is a central thread disposed in a more or
less zigzag manner, and around it a thick meshwork of very delicate

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JURSCHMANN’S SPIRALS. 99

fibres commonly looped round in spirals, but occasionally retiform. The
spirals are often overlaid with epithelium, and sometimes also covered
with Charcot-Leyden crystals. They vary greatly both in length and
breadth. When present, they indicate—so it would seem—a desqua-
mative catarrh of the bronchi (Curschmann) and alveoli (Lewy). Thus
they are found in pneumonia as well as in capillary bronchitis. In
connection with asthma they afford a most valuable diagnostic sign,
showing that the disease is of a bronchial character.

As to the connection between these spirals and the Charcot-Leyden
crystals (see p. 30 and Chaps. VI. and-IX.), it is to be noted that in the
earlier attacks of bronchial asthma, or at the beginning of a fresh attack,
spirals are to be found in the sputa, but no crystals. If, however, a
specimen of such a sputum is placed quite fresh on a slide covered to
prevent evaporation, and allowed to stand for 24-48 hours, crystals will
be seen in it. Later in the asthmatic paroxysm, numbers of similar

 

Fic. 52.—Spirals from Sputum (eye-piece ILI., objective 4, Reichert).

crystals occur in the recent sputa, lying amongst the spirals, and not
elsewhere. From this it would appear that the Charcot-Leyden crystals
are in part derived directly from the spirals. As to the chemical con-
stitution of the latter, the author has ascertained that they are formed of
a substance closely resembling mucin. If one of them be removed from
the sputum and touched with a dilute alkali, it dissolves; and when
acetic acid is added, a precipitate forms. If the alkaline solution be
treated with cupric sulphate and boiled, the resulting peroxide of copper
is not reduced ; but with the previous addition of a mineral acid and
boiling, reduction immediately takes place. All these reactions are
common to mucin.

Observations which the author had recently an opportunity of making
in a case of bronchial asthma went to confirm the statements made
above, and showed further that the portion of the spirals constituting
the central thread is chemically distinct from its envelope of mucin.

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100 THE SPUTUM.

This central thread approached rather to the character of fibrin, but its
precise composition was not ascertained with certainty.

Asthmatic sputa contain large numbers of leucocytes containing eosin-
ophil granulations (Fr. Miiller, Gollasch, Schmidt).?* The fact, however,
is of little aid in diagnosis, since Gollasch and Leyden® have observed
similar bodies in the expectoration of acute and chronic bronchitis.

6. Fibrinous Coagula.—Fibrinous casts are found in the sputa of
plastic bronchitis and pneumonia. They are whitish in colour, of vary-
ing consistence, and branched to the form of the terminal bronchial
tubes in which they are deposited. In pneumonia they are usually few
in number and of no great length (fig. 53), and when more numerous
they mark a severe clinical type of the disease. The abundant forma-
tion of such coagula in pneumonia is attended with much coughing and
great dyspnea.

They are found in greatest perfection in the chronic plastic bronchitis

 

Fics. 53 and 54.—Fibrinous Coagula from a case of Pneumonia, with Paroxysms of
severe Dyspneea (4). ;

of adults. They may be said to be pathognomonic of this affection,
which is otherwise so often difficult to diagnose. The author has seen
them several centimetres long (fig. 55), and minutely branched. Mlicro-
scopically these terminal filaments form a fine network, in which epithelial
cells and blood-corpuscles are enclosed. These coagula being formed of
fibrin resist the action of acetic acid. Their chemical investigation may
be conducted in the manner described under Fibrinuria (Chapter VII.).

The author, in view of the similarity in a clinical sense between bronchiolitis

exsudativa and chronic bronchial croup, investigated the sputum in the case as
to the existence of eosinophil cells. The result was negative.

7. Connective Tissue.—Shreds of connective tissue are occasion-
ally, though rarely, found in the sputum. It sometimes happens in
pulmonary abscess and gangrene that scraps of tissue are coughed up,
which may be recognised by their arrangement as belonging to the alveoli
of the lungs. Fragments of cartilage due to ulceration of the larynx

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CORPORA AMYLACEA—FUNGI. IOI

may also be discharged with the expectoration. Their origin can usually
be determined by the microscope. In sarcoma of the lung particles of
tissue are apt to be discharged, and these, by their characteristic appear-
ance, enable a definite diagnosis to be made (Huber).?6

8. Corpora Amylacea.—Vriedreich 2” has described these starch-
like formations as occurring in the sputum. He refers their origin to
hemorrhagic processes in the lungs. They are partly round, partly
angular in shape, and contain within them a core of pigmentary sub-
stance, which also is usually angular. In a solution of iodine and iodide
of potassium, they sometimes give the amyloid reaction, but not always.

 

Fic. 55.—Fibrinous Coagula from a case of Plastic Bronchitis (%).

Often their form shows stratification. In a sputum sent to him for
examination by his colleague, Dr. Neusser, the author found such bodies,
and he has several times met with others like them, but without the
dark central substance in the sputum of pulmonary gangrene. These
did not give the amyloid reaction, but they showed evident stratification.
It must still be regarded as an open question whether these bodies are
of an amyloid nature or not.

9. Parasites.

1. Fungi.—The investigation of the sputum for fungi has in recent
times engaged much of the attention of scientists and physicians. If we
adhere to the usual classification of parasitic fungi into moulds, yeasts,

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102 THE SPUTUM.

and fission-fungi, it will be found that the chief interest attaches to
micro-organisms of the third class. Of the fission-fungi some indeed are
innocuous; but there are others of a distinctly pathogenic character,
and their recognition in the sputum is a point of prime importance in
diagnosis. It will serve a useful purpose, therefore, if we divide, the
micro-organisms in question into two chief classes, the non-pathuyenic
* and the pathogenic.

(a.) Non-Pathogenic Fungi.

1. Moulds.—There is little to be said of these parasites as a con-
stituent of the sputum. The thrush-fungus rarely occurs (see p. 85),

 

Fics. .56, 57.-— Moulds from the Sputum in Pulmonary Abscess (eye-piece I.,
objective 8a, Reichert).

and its presence is usually to be referred to admixture with the saliva.
In all cases where it is found, the mouth and throat should be carefully
examined for aphthe. At the same time it must not be forgotten that
in thrush aphthous patches may extend to the bronchi, especially where
the subjects are children.

Further, in certain pulmonary diseases mould-fungi have been found
in the sputum. The accompanying figures (figs. 56, 57) show such bodies
as seen in the fresh sputa of a patient suffering from traumatic abscess
of the lung. Virchow 8 has published observations bearing upon this
subject, and Lichtheim found Aspergillus fumigatus in human sputa.

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FUNGI—TUBERCLE BACILLUS. 103

This latter organism has been shown by Schzitz®° to be connected with
disease in the lower animals.

Most writers have concurred in the opinion that mould-fungi are only
incidentally present in the sputum; but quite recently the labours of
Schiitz, based upon the result of Lichtheim’s experiments with animals,
have gone far to show that the multiplication of mould-fungi alone may
cause destructive processes in the lungs. The observations of Paltauy
and Lindt *! tend to the same conclusion. To study the nature of these
fungi they should first be found by microscopical examination, and then
cultivated on bread and nutrient gelatine. Their relation to disease may
also be ascertained by experiments upon animals (see Chapter X.).
Whether innocuous or not, it is quite certain that mould-fungi are fre-
quently present in the expectoration.

2. Yeasts.—Little is practically known of yeast-fungi as constituents
of the sputum. The author has discovered scattered yeast-cells in the
pus from a phthisical cavity. ;

3. Fission-Fungi.

1. Sarcina Pulmonis.—Sarcine have been found in the expectoration
of several diseases. They were first described in this connection by
Virchow and #riedreich.** They are usually smaller than S. ven-
triculi.2? Their presence is of little pathological interest (fischer,
Hauser),** but it would seem that they belong especially to extensive
ulceration of the lung. Pansini * describes a new species under the
name Sarcina variegata.

2. Leptothrix.—Leyden and Jaffé* lave repeatedly found lepto-
thrices in the sputum (see p. 86). They may be recognised in the so-
called fungoid plugs of putrid bronchitis by their property of staining
in iodo-potassic-iodide solution. These fungoid plugs have been analysed
by Dittrich, Traube, and others. They contained, besides leptothrices,
crystals of hematoidin, white and red blood-corpuscles, and in many
cases quantities of fat-laden epithelial cells and a mass of fatty
detritus.

3. Bacilli and Micrococci.—Various forms of bacilli and micrococci
occur in every sputum. <A number of these, and among them bacilli
with terminal spores, are shown in fig. 50.

(b.), Pathogenic Fungi.

1. Tubercle Bacillus.—The researches of Robert Koch ** have shown
that the sputum from tubercular lungs contains definite organisms which
behave in a uniform and remarkable manner towards certain staining
fluids ; and this author was further of opinion that the organisms in
question were the vehicles of the tubercular virus. His conclusions
have been most fully borne out by subsequent observations.** Nothing
more need be said just now to show the great importance of his dis-

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104 THE SPUTUM.

covery. We shall return to the subject later when we come to speak of
tubercular sputum.

The tubercle bacillus cannot be seen in the unstained sputum. When
a preparation is made in the manner to be described presently, the bacilli
appear either separately or more usually in groups, as small rod-like
bodies, slightly curved, very delicate, and of variable length (1.5 4-3-5 #).
They are quite motionless, and spore-formation can sometimes be seen in
them. The spores do not stain by the same process as the parent bacilli,
and thus it happens that the tubercle bacillus will seem to be broken
up into several (2-6) clear oval compartments. This appearance has
led some observers ®® to suppose that they had to do with micrococci,
but by appropriate methods and careful examination the clear outline of
the bacillus can be made visible in such cases through its entire length
(fig. 58).

Detection of Tubercle Bacillus.—Since the tubercle bacillus was dis-
covered some years ago very many methods have been suggested for its
recognition, as those of Koch, Gibbes, Baumgarten, Neelsen, Balmer,
Friintzel, Kiihne, Friimhel, and Gabbett. They all alike depend upon the
remarkable property which the bacillus displays of staining with aniline
dyes in alkaline solution, and (unlike the other micro-organisms, patho-
genic and non-pathogenic, which occur in the sputum), of retaining the
dye tn after-treatment with acid and alcohol.*®

The bacillus may be shown by any of the methods enumerated above
when the requisite skill has been attained, but the methods of Koch and
Ehrlich are the best for a beginner to employ.

A. Preparation of the Staining Fluid.—It is important that the
staining fluid should be freshly prepared for use in every case, both
because the aniline dyes are apt to undergo chemical changes when kept
for a time in solution, and also because fungi may develop in the fluid
itself, and so mislead the observer. It may be made thus: In a test-
tube, carefully washed (with distilled water and alcohol) and dried, an
alcoholic solution of gentian- or methyl-violet is made* by dissolving the
solid substance in 4-5 cc. of absolute alcohol, and to such a point of
concentration that an object cannot be discerned through the fluid in the
test-tube.

In another test-tube, which also must be thoroughly cleaned, 6 ce.
of distilled water are measured out; to this are added 10-15 drops. of
aniline oil. The fluid is well mixed by shaking it up, and then passed
through a moist filter. To the clear filtrate are added a few drops of
the alcoholic solution of gentian- or methyl-violet, prepared as above, till

* To simplify the method, a concentrated alcoholic staining solution might be
kept in readiness.

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STAINING PROCESSES. 105

a slight turbidity appears. This should clear in a few minutes. Should
the mixture fail to become perfectly clear, however, that will not inter-
fere with the success of the undertaking. Thus is obtained the aniline-
water-gentian- or methyl-violet solution (Weigert-Elilich fluid). In
addition a watery solution of Bismarck-brown or vesuvin is needed.
To make this, a small quantity of one of these substances (about as much
as could be taken up on the point of a pen-knife) is added to a few cc.
of distilled water in a test-tube, and dissolved until the fluid is barely
transparent ; it is then filtered. The filtrate will be employed in the
manner to be indicated presently.

B. Preparation of the Cover-Glasses.—The cover-glasses to be used
must be scrupulously cleaned by washing first in distilled water and
then in strong alcohol, and afterwards dried in an exsiceator, or at any
rate in a chamber free from dust. A number of such thoroughly
cleansed cover-glasses should be kept ready for use under a glass shade.
One is now taken up with forceps, previously sterilised by raising them
to a white heat, and with similar forceps a particle of the sputum to be
examined is placed on the cover-glass—such portions as appear most

 

purulent being chosen—and spread in a layer as far as possible of
uniform thickness. Another cover-glass is placed upon the first, and
the two are pressed closely together with the forceps so that the inclosed
sputum is spread very thinly. The cover-glasses, still grasped with the
forceps, are then separated, and dried first in the air, and then passed
two or three times through a carbon-free flame from a spirit- or gas-lamp,
the preparation surface being kept upwards.

C. To Stain and Mount the Preparation.—The cover-glasses, prepared
in the manner just described, are now placed in a watch-glass holding
the aniline-water-gentian-violet staining fluid already mentioned. They
should be allowed to float in the fluid preparation-side downwards.
When removed after twenty-four hours they will be found to be coloured
a dark blue. They must now be placed in dilute nitric acid (1 in 4)
until the preparation appears to the naked eye no longer blue, but
at the most a bright green.

The preparation should not be completely decolorised when taken
from the fluid, because there is danger that the bacilli also may be
deprived of the stain if they are submitted to a too prolonged action of
the acid. When removed from the latter, they must be rinsed with
absolute alcohol, then dried in the air, and mounted in oil of cloves or
Canada balsam.

For microscopical examination Hartnack’s objective No. VII., or
Reichert VIII, serves best with a little practice. The beginner may
use an oil-immersion lens and Abbe’s condenser with advantage. If
tubercle-bacilli are present they will appear in the specimen as minute

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106 THE SPUTUM.

rod-like bodies of a blue colour, but if few in number they may easily
be overlooked. It will then promote their detection to stain the sur-
rounding substances by immersion in the solution of Bismarck-brown or
vesuvin. To do this the cover-glass, prepared and stained in the manner
already described, is placed in the brown staining-fluid (made as above),
and left in it until the whole preparation has assumed an evident
brownish yellow tint. It is then washed with distilled water and
mounted for examination. When looked at through the microscope
the bacilli are seen to be coloured a deep blue, while the other bodies
in the field—fungi, mucus, corpuscles, and epithelium—are brown (fig.
58). The length of the individual bacilli as found in the sputum is
very variable. The author has repeatedly met with specimens as large
as those represented in fig. 58, but smaller forms, as shown in fig. 59,
occur still more frequently. The entire process may be accomplished
in a quarter of an hour by heating the staining fluid, which also

 

Fic. 58.—Tubercle Bacilli from Sputum (eye-piece V., objective Zeiss y,, homogeneous
immersion ; open condenser).
should then be a concentrated solution of the aniline-water and gentian-
violet mixture.

The method of staining with carbol-fuchsin (Ziehl-Neelsen fluid)
is well worthy of notice here. Ten cc. of a concentrated alcoholic
solution of fuchsin are added to go cc. of a 5 per cent. solution of
carbolic acid, and the staining-fluid (carbolised fuchsin solution) is used
in the same manner as the Hhrlich-Wetgert fluid. If the staining-fluid
be warmed, the specimen can be prepared in a few minutes. The
surrounding tissues and remaining fungi (non-pathogenic) had best be
stained with a watery solution of methylene-blue. The tubercle bacilli
then appear red, all other fungi and cells blue (fig. 59).

Other methods which have been found useful clinically are those of
Czaplewskt, the Frinkel-Gabbett method (a modification of Ginther’s),
and Biedert’s.*? The first has no advantage which does not belong also
to the Zehl-Neelsen method. The second is rapid and simple but not
entirely satisfactory in its results.

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STAINING PROCESSES—PNEUMONIA MICROBES. 107

[Gabbett * employs two solutions :—(a.) Magenta solution : Carbolic acid (5 per
cent.), 100 cc.; magenta, 1 gramme; spirit, 10 cc. Mix and preserve in a
stoppered bottle. (b.) Methylenc-blue solution: Sulphuric acid (25 per cent.),
100 cc. ; methylene-blue, 2 grammes. The prepared cover-glasses are floated on
a little of the magenta solution in a watch-glass. he latter is heated until the
vapour can be seen rising from the surface. The cover-glasses are then removed,
washed, and placed for one or two minutes in the methylene-blue solution ; after
removal they are again thoroughly washed, dried, and mounted in xylol balsam.
The whole process can be accomplished in a very few minutes,]

Biedert’s method is very serviceable where the sputum contains but
a few bacilli. Ten to twenty cc. of the sputum are boiled in a watch-glass
with a little dilute caustic soda; water is added, and the mixture again
boiled until it is thinly fluid. It is then allowed to stand in a conical
glass for two or three days, after which the sediment is added to a small
quantity of egg albumin, and examined for bacilli in the usual manner.
The addition of an alkali renders the bacilli more difficult to stain, and
the specimen must therefore be left for a longer time than usual in the
fluid. The use of Stenbeck’s sedimentator,* or of the centrifuge, facili-
tates the research.

Kuhne’s** method may be mentioned, but it has been affirmed that it
is unsatisfactory.

[Gibbes’ 4* double stain is much used in England. It dispenses with the neces-
sity of washing the preparation in acid and can be rapidly applied. It is made
thus ; («.) Rosanilin hydrochloride, 3 grammes, and methylene-blue, 2 grammes,
are rubbed up together in a mortar; (.) anilin oil, 5 cc., is dissolved in alcohol,
20 ce. (b.) is slowly added to (a.) in the mortar until all the stain is dissolved ;
distilled water, 20 cc., is then added slowly while the mixture is stirred. The
stain is now ready, and may be kept in a well-stoppered bottle. To use it a thin
layer of the sputum is obtained on a cover-glass in the usual way. A little of the
mixture is warmed in a watch-glass, and the cover-slip—sputum surface down-
wards—is floated on the warm staining-fluid for four or five minutes. It is
removed and washed with spirit by means of a wash-bottle, until the latter
ceases to remove any of the dye. The preparation is allowed to dry, and mounted
in xylol balsam.]

We shall have occasion by-and-by to point out the great diagnostic
significance which attaches to the presence of tubercle bacilli in the
sputum.

2. Micro-organisms of Pneumonia.—Alels,+’ Hberth,*® and Koch *
have described various micro-organisms, presumably of a specific char-
acter, as occurring in the lungs, and to be found in the sputum of pneu-
monic patients.

Friedlinder © has further investigated this subject, and has succeeded
in cultivating and propagating these micro-organisms, but their nature
is not yet fully understood. They occur in stained preparations in
groups of two, three, or four. They vary in size, have usually a distinct

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108 THE SPUTUM.

envelope, and present the form sometimes of short thick rods (Fried-
linder), sometimes of diplococci (A. Frankel).

For the detection of pneumonococci (see upper part of fig. 60),
Friedliinder ®! recommends a method of staining very similar to that of
Giinther for the detection of spirilla in the blood (p. 45). The cover-

   

 

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Fic. 59.—Tubercle-Bacilli, stained by the Ziehl-Neelsen method (eye-piece IIT., objective
Zeiss }x, homogeneous immersion, Able's mirror, open condenser).

glass preparation, made ready as described above, is passed three times
through the flame of a Bunsen’s burner, placed for a minute or so ina
1 per cent. solution of acetic acid, the fluid removed by blowing upon
it through a pointed glass tube, the preparation dried in the air, and
placed for a few seconds in a saturated aniline-water and gentian-violet

 

Fic. 60.—Pneumonococci (eye-piece IIL., objective j Reichert, homogeneous immersion
dv ? 16 ? ,
Abe's condenser, without diaphragm).

solution, finally washed with water, and mounted on a slide for exami-
nation. When this is done a number of capsulated rod-like micrococci
may be seen with the microscope.

From a series of experiments made by Dr. Richter it would seem that this

method also answers remarkably well for the detection of fungi in exudations
or transucdations.

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ACTINOMYCES—-INFUSORIA. 109

Gran’s method (p. 41) will also serve to show the micro-organisms,
which then appear chiefly as small diplococci (fig. 60, round the edges,
and fig. 63), identical in appearance with the bodies supposed by A.
Frinkel ? and Weichselbaum ®* to be characteristic of pneumonia.

We shall refer later to the pathological significance of these micro-
organisms.

3. Actinomyces.—This fungus settles occasionally in the lungs, and
may then be apparent in the sputum. Baumgarten,°* Israel,®> Jekino-
witsch,© Kuschew, and Paltauf,*" [and Lindt] have described such cases.
Paltauf has found the characteristic granular masses in the sputum in
cases of actinomycosis, and their peculiar ray-like arrangement is made
evident by the application of Gram’s method. Jehinowitsch and Kuschew
have shown that in the sputum the characteristic actinomyces occurs.
For a description of the ray fungus see the chapter on Pus.

 

Fic. 61.—Echinococcus Hooklets and Membrane of Hydatid Cyst (eye-piece III.,
objective 84, Reichert).

It should be mentioned here that organised bodies have often been
observed of late years in the sputum of whooping-cough, some of which
may have a causative connection with the disease. Thus Deichler*
has found in such sputa certain amceboid cells (protozoa), but his state-
ment needs confirmation. Burger and Letzerich established the presence
of bacilli, and Afanasstew* found in the sputum of affected children
bacilli to which he attributed an exciting influence; and since his
opinion is supported by Smtschenko °° (who performed careful cultivation
experiments to elucidate the subject), it is probable that the bacillus of
Afanassiew has really a close relation to whooping-cough.

2. Infusoria.—Infusoria were first found by Kannenberg®™ in sputa
derived from pulmonary gangrene. They were of the monad and cerco-
monad varieties. They occurred usually enclosed in small yellow droplets,
which also held margarine crystals, and exhibited sluggish movements.
Such organisms are described at length in the chapter on Fwces,

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IIo THE SPUTUM.

For their detection in the sputum Kannenberg has adopted the follow-
ine method:—A little of the fungoid substance mentioned above 1s
placed beneath a cover-class on a slide, and spread out by pressure in a
very thin layer. A few drops of a 1 per cent. solution of common salt are
then added. The cover-glass, with some of the preparation on its surface,
is next dried, and afterwards put to stain in a watery solution of methyl-
violet, washed in water, and, while still wet, placed in a concentrated
solution of acetate of potash. By this process the protoplasm of the
monads is stained a beautiful blue.

3. Vermes.—It very seldom happens that ascarides are found in the
sputum, and cysts of echinococcus in a perfect state have been but
rarely known to be expectorated. Hichhorst®* and also Hochsinger %*
have described cases in which this happened. Diagnosis in such cases
cannot be attended with difficulty. The cyst, however, is generally
discharged in fragments. These appear to the naked eye as whitish-
yellow shreds, and may be recognised microscopically by their uniformly
striped texture (fig. 61). The discovery of the hooklets of echinococcus
in the sputum is a fact of great importance in diagnosis. They may
be readily recognised by their characteristic form (fig. 61). Charcot-
Leyden crystals in great quantity commonly accompany them.

It would appear, too, that the expectoration may contain the eges of
Distoma hematobium. The author is indebted to Dr. Schiess-Bey of
Alexandria for a specimen which plainly shows that this parasite settles
in the lungs, and it follows that when the pulmonary structure breaks
down, it may be expelled with the sputum. Similar observations had
already been made by Manson.®4

10. Crystals.—Very many forms of crystals have been found in
the sputum, but for the most part their discovery is without great sig-
nificance in diagnosis.

1. Charcot-Leyden Crystals.—We shall consider these bodies first,
for the reason that they seem to possess some pathological interest.

Leyden® often found crystals in the sputum of asthmatic patients.
They abounded chiefly in the semi-solid greyish-yellow pellets dis-
charged during a paroxysm. ‘These crystals were colourless and of
the pointed octahedral form. They were insoluble in cold water, ether,
alcohol, and chloroform, but dissolved readily in acetic and mineral
acids, alkalies, warm water, and ammonia. They are identical with the
crystals to be seen in post-mortem blood, and described at p. 30, and
with those of the semen, and with others that are met with in the
feeces in cases of anchylostomiasis. According to Schreiner ® such
crystals are the phosphate of a new hase, which, according to the
researches of Ladenburg and Abel, is probably identical with ethyl-
eninim, or dizthylendiamin.®

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CRYSTALS—-H ZMATOIDIN—CHOLESTERIN. III

Leyden believed that the crystals were the exciting cause of the
asthmatic paroxysm. Friedreich and Zenker ® found them in expecto-
rated fibrin-coagula, and Bizzozero™ in the sputum of acute bronchitis
from patients who were not subject to asthma. The author can corro-
borate the statements of these observers. [Zroup™ asserts also that
neither spirals nor Charcot-Leyden crystals are pathognomonic of any
one disease, but points out that the former are invariably to be found
in asthmatic sputa, and by their presence cause the paroxysms. A
characteristic feature of the conditions in which both spirals and crys-
tals are found is marked desquamation of the mucous surface of the
bronchioles, and the same author refers the origin of Charcot-Leyden
crystals to the altered cells which are thus stripped off. |

2. Hematoidin Crystals.—Crystals of hematoidin, described by
Virchow, Friedreich, and Schultze, occur in the sputum as ruby-red
rhombic prisms, either solitary or in groups, or as needles or clusters of

 

Fic. 62.—Charcot-Leyden Crystals, from the Sputum of an Asthmatic patient (eye-piece III.,
objective VII., Hartnack).

needles. These crystals, or fragments of them, are often found enclosed
within the substance of white blood-corpuscles (fig. 49 e). Under such
circumstances hematoidin is also seen, either free or in the interior of
the white blood-corpuscles, as a mass of pigment in which no trace of
the crystalline formation can be discovered.

When hematoidin crystals appear in the expectoration, we may
conclude that blood has been effused and suffered to remain for some
time in the air-passages, or that an abscess has perforated the lune.
They occur most abundantly, therefore, in phthisis after hemoptysis,
when pulmonary clots are in process of absorption, very often in pul-
monary abscess, and when an abscess or suppurating hydatid cyst has
discharged into the lung. When the crystals are contained in cells, they
point to a previous hemorrhage ; but when free hematoidin is present in
considerable quantity, the inference is that an abscess has discharged
from some neighbouring organ into the lung.

3. Cholesterin Crystals.—Crystals of cholesterin were found in the
sputum of tuberculosis by Biermer,’ and in pulmonary abscess. by

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112 THE SPUTUM.

Leyden. In connection with the former disease they are often to be
seen there, but in very small quantity. The author has observed them
in great numbers in a girl who had a hydatid abscess in the lung, and
in a man suffering from chronic pulmonary inflammation. According
to Black,” cholesterin erystals are plentifully present in the remains of
old inflammatory exudation.

These crystals are distinguished by their powerful refractive action on
light. They are in the form of large, and often irregular, rhombic tables,
which have a tendency to cohere in groups. They are readily soluble
in ether; insoluble in water, acids, and alkalies (fig. 125). When the
erystals are treated with dilute sulphuric acid and a little tincture of
iodine, a violet colour is formed, which presently changes to blue, green,
and red. With sulphuric acid alone, they become first yellow and then
green, these colours spreading from the edges.

Pathologically, these bodies are of little consequence. They are per-
haps most apt to form when pus from some other organ has burrowed
into the lung, and lodged there for a time before being discharged
through the bronchi.

4. Fatty Crystals (Margarine Needles).—These are seen chiefly in
putrid bronchitis and pulmonary gangrene. They characterise the
discharge of unhealthy pus within the lungs, and belong to bronchi-
ectasis and occasionally to tubercle. They occur either singly or in
clusters as long sharp-pointed needles, and are occasionally vaulted or
saddle-shaped. They dissolve readily in ether and boiling alcohol, and
are insoluble in water and acids. This character facilitates their recog-
nition (fig. 142). Recently the author has found them in plugs, which
evidently originated in the crypts of the tonsils (see p. 89).

It follows from their occurring in so many different diseases that the
discovery of these crystals in the sputum lends but little aid to diagnosis.

As to their chemical constitution, they consist, most probably, of the
sodium, potassium, calcium, and magnesium salts of the higher fatty
acids, as palmitic, stearic, &e.

5. Tyrosin Crystals.—Leyden™ first found tyrosin crystals in the
sputum of a girl with putrid bronchitis, and again in the case of a man
who had an empyema discharging into the lung. They appear micro-
scopically as fine needles scattered separately or in clusters. As a rule,
they occur sparingly in fresh sputum, but form in greater quantity when
the specimen has been allowed to stand for some time.

Leyden and Kannenberg are of opinion that a profusion of tyrosin
crystals implies the existence of a perforating abscess of the lung,

It should be observed, however, that in many instances substances which

have been taken for tyrosin were, in reality, lime and magnesia salts of the higher
fatty acids.

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CHEMICAL EXAMINATION. 113

Tyrosin is usually associated with leucin in the sputum. The latter
occurs in faintly lustrous spherical particles (R. Fischer). It has the
same import as tyrosin.

For the detection of both these substances the method described in
connection with the Urine may be employed.

6. Oxalate of Lime.—fiirbringer "> has reported a case of diabetes in
which the sputum contained large quantities of oxalate of lime. It
occurs either in the form of octahedral (envelope-shaped) crystals (fig.
112), or as an amorphous conglomerate. Unga? found this body in
the expectoration of a knife-grinder, aged twenty-eight, who had suffered
for years from asthma.

The crystals of oxalate of lime are readily known from the fact that
they are soluble in mineral acids, and insoluble in water, alkalies, a
acids, alcohol, and ether.

7. Triple Phosphate.—The characteristic coffin-lid snyatalg have ocea-
sionally been met with (fig. 113). They are soluble in acids of all kinds,
and are, therefore, only to be found in the alkaline sputum. They are
for the most part a product of the decomposition of proteids, attended
with the liberation of ammonia. They are commonly to be seen in
purulent exudation, and consequently are very plentiful in the expectora-
tion from a discharging abscess.

Other crystals are also occasionally observed in the sputum. Fig. 49, ¢/,
represents some that were expectorated in a case of phthisis. They gave
the chemical reactions of carbonates (carbonate of lime), the evolution of
gas on the addition of acids, Xe.

III. CHEMICAL EXAMINATION.—The chemical examination of
the sputum throws little light upon disease.

1. Proteids and Allied Substances.—Of these, serum-albumin
and large quantities of mucin and nuclein (4. Kossel®) are normally
present. Peptone occurs in the expectoration of pneumonia and other
purulent conditions—in general, in all cases where the sputa contain
pus-cells in abundance.*!

The best method for the detection of proteids is that recommended
by Hoppe-Seyler *? as a test for albumin in serous fluids.

The “prune-juice” expectoration of pulmonary cedema is very rich
in serum-albumin. For the detection of this body, the sputum may be
extracted with very dilute acetic acid, and the filtrate tested with ferro-
cyanide of potassium, when its presence will be shown by turbidity or
a precipitate.

2. Volatile Fatty Acids.—Various volatile fatty acids may occur
in the sputum, and, notably in gangrene of the lung, acetic, butyric, and
sometimes caproi¢ acids are met with.** In testing for these bodies,

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114 THE SPUTUM.

the sputum is diluted with water and phosphoric acid added. The
volatile constituents are driven off by distillmg them in a vessel heated
by steam. The distillate is then tested in the manner laid down in the
chapter on Jeces. Some fat can be obtained from all sputa, and those
of tubercular patients contain a large quantity.*+

To separate the fats and non-volatile fatty acids, the sputum is acidu-
lated and extracted with ether, and by repeatedly shaking up the
ethereal extract with a watery solution of sodic carbonate, the acids
are converted into their corresponding salts, which remain dissolved in
the watery solution. The ether is pipetted or siphoned off, and the
fats obtained after evaporation of the ether. The sputum of pulmonary
gangrene contains several members of the aromatic group, as indol, phenol,
and scatol.®

8. Glycogen.—This body has been repeatedly detected in the
sputum by Salomon.®° Its presence may be demonstrated by Briicke’s
method.

4. Ferment.—Flehne, Stolnikow, and Stadelmann® found that the
sputa, especially in pulmonary gangrene and putrid bronchitis, contain a
ferment resembling in its action one of the pancreatic ferments. It is
soluble in glycerine, and may be extracted by that body from the sputum.
Escherich ® has been able to demonstrate its presence in the sputum in
all cases of extensive destruction of lung-tissue.

5. Inorganic Constituents.°°—-These are chiefly—

Chlorides: of sodium and magnesium.
Phosphates: of soda, lime, and magnesia.
Sulphates: of soda and lime.

Carbonates: of soda, lime, and magnesia.
Per-salts of iron (rarely)—phosphate of iron.
Silicates.

AREY DS o

The inorganic matter of the sputum has little bearing on clinical
diagnosis. For its analysis the organic constituents must first be
removed by incineration, when the usual tests may be applied to the
ash. (For further information consult Hoppe-Seyler’s Handbuch der
Physiologisch- und Pathologisch-chem. Analyse, 5th ed., p. 316.)

IV. THE CHARACTER AND CONSTITUTION OF THE SPU-
TUM IN THE PRINCIPAL DISEASES OF THE LUNGS AND
BRONCHI.

1. Diseases of the Bronchi.

1. Acute Bronchitis.—At the outset the expectoration is viscid,
white, and scanty, and occasionally streaked with blood. Microscopi-
cally it exhibits very few cells, and is devoid of specific fungi (tubercle

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THE SPUTUM IN DISEASE. I15

bacillus, §e.). At a later period it becomes more abundant, assumes a
pale-green tint, and under the microscope is seen to consist chiefly or
entirely of pus-cells. Elastic fibres are never present.

2. Chronic Bronchitis and Bronchiectasis.—The expectoration, which
is copious, green in colour, and without any characteristic odour, is
formed microscopically almost entirely of pus-cells, with which are
mixed a considerable number of fat-holding epithelial cells and myelin
particles, and a host of non-pathogenic micro-organisms. When ulcera-
tion of the bronchi takes place in the course of chronic bronchitis, lead-
ing to bronchiectasis, a very abundant expectoration is discharged in the
morning. The fluid, which is usually thin, tends to arrange itself in
three layers when allowed to settle. Of these, the topmost is frothy,
the next consists of watery fluid, and the third, which is of greater
consistence, 1s formed almost exclusively of cells.

In chronic bronchitis complicated with asthma, the sputum during
the paroxysms, and immediately afterwards, exhibits spirals (see p. 98),
and Charcot-Leyden (pp. 30, 99) and other crystals.

3. Putrid Bronchitis——The expectoration of this disease is thick,
greenish-brown, and has a very disagreeable sweetish odour. Micro-
scopically it contains a profusion of micro-organisms of various kinds,
and very often exhibits large tufts of fungi, which colour blue with
iodine and iodide of potassium solution, epithelium—usually in the pro-
cess of fatty degeneration—and fungoid plugs (p. 102), but no elastic
fibres, no shreds of alveolar tissue, and no specific fungi.

Lumniczer ° has separated by means of Koch’s plate cultivations (see
Chapter X.) a number of micro-organisms from the sputum, amongst
them Staphylococcus pyogenes citreus and albus, cereus flavus and
albus, and Diplococci; and also a fungus, the colonies of which, when
developed in nutrient agar-agar, emitted the odour belonging to the
expectoration of putrid bronchitis. It is a spore-forming bacillus,
1.5-2 » in length, thickest in the middle, and rounded off at the ends.
It was also seen ready formed in the sputum. When introduced within
the lungs and bronchi of rabbits it excited inflammation there.

Lebisch and Rohkitansky,®! by means of Baumann and Udranshky’s
benzol test, have detected cadaverin (pentamethylenediamin) and. an-
other diamin in these sputa.

4. Plastic Bronchitis.— The sputum contains fragments of the
croupous membrane and coagula of fibrin, with which are entangled a
profusion of epithelial cells and fungi (fig. 55). From these appear-
ances, and in the absence of pneumonic symptoms, the condition is
readily diagnosed. Occasionally it has to be distinguished from
chronic fibrinous bronchitis. The distinction will be made on clinical
grounds.

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116 THE SPUTUM.

2. Diseases of the Lung’ Tissue.

1. Pulmonary Tuberculosis.

(a.) Miliary Tuberculosis of the Lung.—The sputum in this condition
is merely that of acute catarrh, Tubercle bacilli are never to be found
ain it.

(b.) Acute Tubercular Infiltration of the Lung.—An early diagnosis
of the condition is of the utmost consequence, and happily it has been
rendered possible by Koch’s epoch-making discovery of the tubercle
bacillus. Two forms of the disease may be distinguished, according as
the symptoms partake of the typhoid or of the pneumonic character.

(a.) The Typhoid Type.—The symptoms are rigors at the outset, per-
sistent high temperature, enlarged spleen, extensive roseolar rash, which
at times suggests that of typhus exanthematicus, and commonly profuse
diarrhoea. The physical signs are those of severe catarrh in both apices.
There is no dyspnea. The pulse is frequent, respiration is but slightly
accelerated, and lividity is not marked, The sputum is viscid and
scanty. It contains but little tissue-débris, and only a few bacilli, which,
moreover, are always provided with spores.

After the lapse of a few days, dulness on percussion and bronchial
breathing may be obtained over the apices. The sputum becomes puru-
lent, and when again examined is found to contain swarms of tubercle
bacilli, There are also to be seen elastic fibres, showing an alveolar
arrangement, and a large quantity of epithelium. The physical signs
now give evidence of one or more large cavities, and the fever assumes
a remittent character. Death generally ensues in three or four weeks,
the mode of dying being that of chronic tuberculosis.

(8.) The Pneumonic Type begins with sustained high temperature,
marked lividity, and accelerated breathing. The physical signs point
to catarrh of both apices, and the sputum contains a few bacilli. Later,
the characteristic symptoms of infiltration of the lungs set in; the
expectoration becomes more profuse, and the contained bacilli more
numerous, The disease runs a very rapid course, often lasting only
for some days. Anatomically, the condition is one of acute tubercular
infiltration of both lungs.

(c.) Chronic Pulmonary Tuberculosis.—The diagnosis of this disease
has been greatly facilitated by Koch’s discovery of the bacillus of
tubercle. As a result of his experience of many hundred cases in the
clinic of Professor Nothnagel, the author has no hesitation in affirming
the principle so often laid down by other authorities, that the presence
of the tubercle bacillus in the sputum invariably implies the existence of
tuberculosis. Let this fact be granted, and no more is needed at once
to emphasise the importance of that recent contribution to our know-
ledge, and to impress upon the physician the necessity of rendering

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THE SPUTUM IN TUBERCULOSIS. 117

himself familiar with the very simple methods by which the bacillus
may he identified (p. 104). Experience has already accumulated cer-
tain data. In the first place, it must be mentioned that in most,
though not in all cases, the abundance of the bacilli is in proportion to
the severity of the disease; and again, the proliferation of bacilli is
apt to run parallel to the intensity of the febrile symptoms. The
supervention of hemoptysis is attended with an apparent (H. v
Frisch ®*) diminution in their number, but this may well be owing to
the fact that the sputa are in such a case diluted by the profuse admix-
ture of blood.

It is only when the tubercular process runs the very rapid course
described above that the bacilli, then usually carrying spores, are so
abundant as to fill the entire field.

It was held at one time that the appearance of elastic fibres in the
sputum was a sure token of incipient tuberculosis, but more recent
research has shown that they may be found equally in the course of
pulmonary ulceration of whatever kind; and so with other manifesta-
tions to which great importance was formerly attached. The signifi-
cance of all or any of them is very slight in comparison with that
belonging to the specific micro-organism, upon the detection of which
alone a positive diagnosis can be formed. [By the method of examining
the sputum in sections already referred to (p. 94), Gabritschewshy °° has
observed giant-cells in three out of four cases of pulmonary tuber-
culosis. |

It does not necessarily folow from the presence of the bacillus in
the sputum that a fatal termination is impending. The author has
met with such cases in which the patient eventually recovered, but they
are very rare. And doubtless an atmosphere crowded with the bacilli
of tubercle (as that of the consumptive ward of a hospital) must neces-
sarily give but little chance of cure. Possibly this is the reason why
the hospital physician has so seldom an opportunity of observing it.®+

Allusion may be made here to Koch’s process®® for the detection
during life of tubercular proliferation in inaccessible parts. The diag-
nostic value of the discovery is not yet finally settled. Numerous
clinical observations have shown that persons infected with tubercle
bacilli do in fact exhibit a reaction when injection has been made upon
them, while the healthy and those subject to other diseases generally
fail to do so. The process, however, zs neither entirely trustworthy nor
altogether free from danger. The initial dose should in all cases be less
than o.or ce.%

2. Chronic (Non-Tubercular) Inflammation of the Lung.—Under
this heading may be grouped all those conditions which would formerly
have been thought to present the typical character of tuberculosis—

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118 THE SPUTUM.

fever, night-sweats, &c.—but in which repeated search will fail to detect
the bacillus in the sputum. In one such case the autopsy showed caseat-
ing masses of considerable extent, but these, even to the naked eye,
were sufficiently discernible from tubercular deposit.

As regards the sputum, its essential characteristic is the absence of
tubercle bacilli. It further contains a large quantity of elastic tissue
and a profusion of epithelium cells, and especially of their myeloid
derivatives. If we may infer from the very slender data which have
as yet accumulated, the disease is attended throughout with slight
fever, and death by asthenia occurs sooner or later.°’ The author is
convinced that, with a little more care, we should learn to recognise
the non-bacillary form of phthisis in many instances where at present
it is not thought of.

3. Croupous Pneumonia.—<At the outset of this disease the expec-
toration is very scanty, of a white colour, and here and there streaked
with blood. Microscopically, it exhibits only a small number of red
and white blood-corpuscles ; it usually, though not always, contains the
specific micrococci which will presently be described.

Later, and in some cases only a few hours after the initial rigor, the
sputum has a rusty tinge. It is usually also at this period remarkably
tenacious, and adheres firmly to the spit-box. When placed under the
microscope, it is seen to contain but a small number of much-shrivelled
blood-corpuscles, the red ones arranged for the most part in rows.
They are too few to account for the colour of the sputum, which is due
rather, as Traube surmised, to the presence of dissolved hemoglobin.
In addition to these there are some leucocytes, and the alveolar epi-
thelium which has been noticed in another place (p. 95). In rare cases
the spiral bodies already described and shreds of fibrinous coagula may
also be observed.

The colour of the sputum at this stage, and even later, may be grass-
green, even though there be no jaundice. Professor Nothnagel 8 is of
opinion that under such circumstances the colouring matter of the
blood is changed into bile pigment. At his desire the author has
examined some of these grass-green sputa. They were dissolved in a
mixture of alcohol with a little chloroform, which was then filtered
and the filtrate evaporated, when a substance remained behind which
presented all the characters of biliverdin. We may assume, therefore,
that the green colour of the sputum in such cases is due to the conver-
sion of hemoglobin or hematin into bilirubin, a change which is the less
remarkable if we consider the very close chemical relations which these
two bodies bear to one another. The bilirubin formed would then be
oxidised to biliverdin in the lungs.

Traube maintains that the grass-green sputa belong especially to

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THE SPUTUM IN PNEUMONIA. 119

subacute pneumonia, and that they also occur when a pulmonary abscess
forms in the course of pneumonia.

It would appear from the researches of Rosenbach ® in Nothnagel’s
clinic at Jena, that the sputa may be tinged green by certain micro-
organisms, most probably the Micrococcus chlorinus,! altogether inde-
pendently of pneumonia. This happens under many circumstances ;
and the fact has in itself no clinical significance.

Later in the course of pneumonia the expectoration becomes more
abundant and watery. Its colour changes from brownish-red to a
saffron- or citron-yellow, the alteration in most cases depending upon a
change in the character of the blood pigment. Fibrinous coagula, and
occasionally also spirals, become now more numerous.

It must be noted, however, here, that such saffron- or citron-yellow
sputa do not belong exclusively to pneumonia. Renz}! has recorded
a case of tuberculosis, in which microscopical examination showed a
profusion of hematoidin crystals in the expectoration, which was of a
yellow-ochre tint. Ldéwer!2 also has called attention to a form of
sputum essentially distinct from that of pneumonia, though, like it,
characterised by a yellow colour, which generally first appears after
the sputum has been voided. It occurs, according to Traube, almost
exclusively during the summer months in connection with tuberculosis,
pleurisy, and pleuritic exudation. The colour in this case is due to the
presence of micro-organisms, and no special importance attaches to the
condition apart from its liability to be taken as a sign of pneumonia.

In the later stages of pneumonia, the fibrinous coagula disappear largely
from the sputum, and the red corpuscles and leucocytes are greatly
lessened in number and show fatty degeneration. There may still be
a few spirals, and elastic fibres are to be met with where ulceration is
in progress. Finally, alveolar epithelium, either very fatty or hyaline (?)
[ Feuerstock 1°], and commonly, too, exhibiting the myelin forms, is pre-
sent in great abundance.

Lastly, if the disease tend towards recovery, the colour begins to dis-
appear from the sputum, which also under the microscope exhibits a
constantly diminishing proportion of epithelium (still, however, fatty),
until at last a time arrives when it is indistinguishable from that of an
ordinary bronchitis. :

The subject under consideration would not be complete without some
notice of the position which may be accorded to the pneumonia-coccus
of Friedlinder, when studied as an adjunct to diagnosis. We are not
here concerned with the discussion of its effects as an agent of disease,
and shall confine ourselves strictly to its significance as a symptom.
Upon this point the author has collected the records of a large number
of cases.

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120 THE SPUTUM.

It should be stated in the first place that, in every case of pneumonia
to which they have been applied, the methods of Friedldnder and Gram,
already described, have disclosed the presence in the sputum of bodies
resembling the microbe of pneumonia. Since this is true also of cases
of central pneumonia, which are always so difficult to diagnose at the
outset, it becomes in the highest degree desirable to assign to these
forms their proper significance. Pure cultivations of pneumonia-cocci
are sometimes to be seen in the sputa of the disease (see fig. 63). It
may, perhaps, be assumed that in doubtful cases their presence will
confirm the suspicion of pneumonia; but inasmuch as Friedlander’s
microbes (or rather, it should be said, certain forms which closely
resemble these) have been found in the expectoration of other conditions,
such as chronic bronchitis and bronchiectasis, and in the buccal fluids

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Fic. 63.—Microbe of Pneumonia from the Sputum, coloured after Gram’s method (compensation
eye-piece IV., apochromatic immersion-objective jy, Zeiss).
and sputum of health, we are never warranted in basing a diagnosis on
such manifestations alone. It may well be that the micro-organisms in
question are not in all cases identical, and that by improved methods of
cultivation we shall be in a position to discriminate them ; but at pre-
sent we are unable to do so. The researches of Pansini 104 have shown
that cultivation-results are not decisive, since fungi resembling the
Frdnkel-Weichselbaum coceus may be derived from sputa which are
not pneumonic. Moreover, it would appear from the observations of
Frenkel and Weichselbaum \ that there are several distinct microbes,
which are capable of giving rise to the symptoms of pneumonia. The
researches of Newmann 1 have still further extended the limits of the
variety which may be observed. It should, however, be mentioned that
the researches of Frdnkel} and Weichselbaum 1 leave no doubt that
amongst the numerous micro-organisms which are present in croupous

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PNEUMONIA MICROBE—GANGRENE. 121

pneumonia, a Diplococeus is most commonly to be found (Micrococcus
of pneumonia, A. Frdnkel ; Diplococcus pneumonie, Weichselbaum).
Frénkel, Poa, Bordoni-Ufreduzzi,™ and Weichsclbaum have observed the same
Diplococcus in the purulent exudation of cerebro-spinal meningitis ; but it would
appear from the researches of Weichselbaum and Goldschmidt! that there are

also other forms which appear to be associated in a closer manner with this
disease.

To sum up our knowledge, it must be admitted that the subject of
the pneumonia microbe needs further elucidation. It is likely that
there are several fungi which may excite the disease. The sputum of
pneumonia occasionally exhibits pure cultivations of these fungi (fig. 63) ;
but their presence must not be made the basis of a too confident infer-
ence. It is only under special circumstances that diagnostic interest
attaches to any of them.1!4

The subject of influenza, which of late years has attracted so much attention,
is purposely avoided here, since in spite of the many efforts that have been made

to elucidate it no distinctive microscopical or bacteriological characters have yet
been assigned to it.

4. Pulmonary Abscess.—The sputum of this condition generally
looks like pure pus when seen with the microscope. It emits a faint
and slightly fetid odour; and it tends on standing to stratify in two
layers, of which the lower consists of pus-cells, whilst the upper is
watery and topped with froth. Microscopically the sputum is subject
to variety, but in general it exhibits shreds of lung tissue, and very
commonly elastic fibres with the alveolar disposition (fig. 50), fatty and
disintegrated pus-cells, hematoidin—partly in the form of well-shaped
erystals, partly as brown or reddish pigment-particles of varying size—
often also cholesterin crystals; these are especially abundant in cases
where the pus has been of long accumulation. Tyrosin and balls of

 

leucin are occasionally present; fatty crystals are more commonly
found ; and finally, a profusion of fungi of various forms, but these are
never specific.

5. Gangrene of the Lung.—The sputum has a penetrating and ex-
tremely unpleasant smell ; is abundant, thin, and of a dull-green colour.
It separates on standing into three well-marked layers. Of these, the
upper is frothy, very turbid, and of a greenish-brown tint; the middle
thin, and of a watery or serous character ; whilst the lowest is opaque,
viscid, and ranges in colour between brown and green. The last occa-
sionally contains brown shreds of lung-tissue of varying size.

Microscopical examination shows that the upper layers contain but
few formed elements. In the lowest layer, however, there is a large
proportion of detritus, fatty globules of irregular size, rarely crystals,
but most commonly hematoidin crystals and amorphous masses; an

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122 THE SPUTUM.

enormous quantity of fungi, notably fission-fungi; often large tufts of
fungi, which stain blue with the iodo-potassic-iodide, solution (Lepto-
thrix), together with other forms, which resemble starch granules and
stain similarly with the same reagent; and sometimes also monads
(Kannenberq).45 It is important to notice the absence of elastic fibres.
Stadelmann,6 however, says they often occur in this kind of sputum.
The sputum contains a ferment which acts like pancreatic juice, and it
is this which probably causes the solution of elastic tissue (see p. 97).*
Bonome™" has constantly found in such cases the Staphylococcus albus
and aureus, which on this account he regards as the cause of this disease.

The researches of Hirschler and Terray™8 have disclosed a great
variety of micro-organisms in this disease. They include a number of
Staphylococci—in addition to those already mentioned, Staphylococcus
pyogenes citreus, and cereus albus—Bacillus pyocyaneus, and a micro-
coccus which thrives on gelatine, agar-agar, and blood-serum at 20°—24",
and on gelatine produces cultivations resembling four-leaved clover or a
flower of six petals. It liquefies gelatine slowly, and on all nutrient sub-
stances develops a smell closely resembling that of gangrenous sputum.
This fungus causes disease when inoculated upon animals. It assimi-
lates aniline colouring-matters of all kinds. It is stained with difficulty
by Gram’s method. It remains to learn whether it has any relation to
pulmonary gangrene, and of what nature this may be.

6. Pulmonary Gidema.—In this condition the sputum is abundant,
thin, and watery, and according to the nature of the underlying pro-
cess is either white and frothy (like soapy water), or of a rusty brown
colour (like prune-juice) Microscopically it holds comparatively few
cellular elements. The leucocytes and the few epithelial cells to he
seen, especially in cases of acute oedema, are free from fatty changes.
The red blood-corpuscles are few, and their number is inadequate to
account for the deep colour of the expectoration. In one case the
author believes that by digestion with: water and subsequent. filtra-
tion of the sputum he obtained the characteristic absorption-bands of
methemoglobin with the spectroscope. The presence of abundance of
albumin may be shown by chemical means.!!9

7. Hemoptysis.—In cases of profuse hemorrhage from the lung, the
sputum consists entirely of bright-red frothy blood, with scarcely any
trace of other tissues. When the hemorrhage has diminished in inten-
sity, the expectoration for several days continues to exhibit a reddish
or reddish-brown colour. During this period leucocytes and epithelium
are plentifully met with, the cells usually enclosing crystals and amor-
phous particles of hematoidin. The formation of small cavities in the

' * [This view is opposed by Troup (“The Sputum,” p. 48), who adduces important
facts in support of his positioi.]

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HEMORRHAGIC INFARCTION—PNEUMOCONIOSIS. 123

course of tubercle is the commonest cause of pulmonary hemorrhage.
In addition to this we shall here notice only the rupture of an aneurysm
into the bronchi, and remind the reader that a persistent hyperemia of
the lung may also give rise to this condition.

8. Hemorrhagic Infarction.—In cases of recent hemorrhagic infare-
tion of the lung, single coin-shaped masses of blood, of a bright-red
colour, and intimately mixed with froth, are expectorated. After the
lapse of several days the sputa assume a brownish tint, and answer the
description detailed in the last paragraph. Further, as a rule, they
contain a number of epithelial cells and leucocytes undergoing fatty
degeneration. The cause of this condition is generally to be sought in
functional or organic debility of the heart.

9. Pneumoconiosis.!*°

(a.) Anthracosis of the Lung.—The sputum of tobacco-smokers and
those who habitually breathe an atmosphere laden with soot always
contains some proportion of carbon particles. In such cases the expec-
toration in the early morning is of a pearl-grey colour, and is brought
up in pellets of viscid and remarkably tenacious substance. In a typi-
cal case of anthracosis the sputum ranges in colour from dark-brown to
black, and is somewhat abundant. Microscopically it exhibits particles
of free carbon, readily discernible by their resistancee to the action of
acids and alkalies ; and generally a quantity of leucocytes and alveolar
epithelium, in each case choked with pigment particles.

(6.) Siderosis Pulmonum.—The sputum is usually brownish-black in
colour, and has all the characters of that of chronic bronchitis. Under
the microscope the contained leucocytes and alveolar epithelium are seen
to be laden with a reddish pigment, which by its reaction with sulphide
of ammonium (black colouration from formation of sulphide of iron), or
with hydrochloric acid and ferrocyanide of potassium (prussian blue), may
be known to consist of iron.

(c.) Mason’s Lung.—Here, too, the sputum has generally the appear-
ance of that of chronic bronchitis ; but in addition it contains particles
of dust, either free or enclosed within cells. Lime and gypsum dust
are readily recognised by their chemical properties (see the chapters on
Feces and Urine) and ultramarine by its colour. In other cases evi-
dence will be forthcoming from independent sources as to the nature of
the substance in question.

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CHAPTER V.
THE GASTRIC JUICE AND VOMIT.

I. EXAMINATION OF THE GASTRIC JUICE.—Like the saliva,
the gastric juice is the product not of one but of several distinct sets
of glands. It is composed of the fluid secreted by the pyloric glands
of the stomach and that of the cardiac glands, these forming its active
digestive ingredients ; and it includes also a portion of the buccal secre-
tion which has been swallowed and is already partly changed in the
process of digestion.?

1. Naked-Eye Characters.—The gastric juice of man is a colour-
less fluid, generally clear, but it is occasionally turbid. Its reaction
is acid.

2. Formed Elements.—Microscopical examination of the gastric
juice at a time when the stomach contains little or no residue of undi-
gested food shows single squamous epithelial cells derived from the
upper part of the alimentary canal; columnar epithelium very rarely
and only in special instances ; fungi of various kinds, especially bacilli
and micrococci ; and usually also yeast cells. Adelous ? has distinguished
sixteen different micro-organisms. Amongst these are Sarcina ventriculi,
Bacillus pyocyaneus, Bacterium lactis aérogenes, Bacillus subtilis, and
others, all of which effect changes in the food—albumin, milk, or carbo-
hydrates. From this fact it would appear probable that in the stomach,
as in the intestines, certain of the fission-fungi are concerned in physio-
logieal functions. On the other hand, there can be no doubt that the
gastric juice is the means, under appropriate conditions, by which a host
of the most dangerous germs of disease are rendered harmless and
destroyed. This property is derived from the free hydrochloric acid
which hinders the development of such fungi.? According to Jaworski,*
the microscopical characters of the fluid differ according as it has an
acid reaction or otherwise.

If the examination be made while digestion is going on, the character
of the gastric juice will approach that of which we shall have occasion

124

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TO OBTAIN GASTRIC JUICE. 125

to speak later when dealing with the vomit, ze, it will contain the
remains of the food.

3. To Obtain the Gastric Juice.—Leule® and Kiilz® were the
first to employ the gastric sound for this purpose in man. Its use is
unattended with danger provided the tubes are elastic and too energetic
aspiration be avoided. To procure the gastric juice for the purpose of
chemical analysis, whether in health or disease, the following procedure
has been recommended by E. Schiitz.7

A time is chosen when the stomach is empty, so as to prevent, as far
as possible, the admixture of impurities derived from the food, and to
this end the morning is generally the best. A pliable gum-elastic
sound, perforated at the end with a number of apertures not larger than
a pin’s head, and furnished with a lacquered handle, is introduced into
the stomach, and pushed on until a slight resistance is encountered. A
collar of horn is then slipped over its upper part, and grasped between
the teeth of the person experimented upon, so as to keep the sound in
position. After the lapse of about half a minute the handle is removed
and the sound connected with a stomach-pump. The piston is now
drawn out, and the projecting extremity of the tube being grasped with
the fingers, the sound is withdrawn, and its contents discharged by the
movement of the piston into a glass vessel. As already said, the danger
of the operation is very slight when performed in this way ; but it may
be entirely obviated by introducing a mercurial manometer between the
sound and the pump, and estimating beforehand the amount of pressure
(as indicated by the position of the mercury) which may be employed
without applying any considerable suction force to the mucous membrane
of the stomach.

It is advisable in many cases, and especially where children are con-
cerned, to adopt the simpler method of Boas and Hwald,§ which consists
in applying pressure over the abdomen after the introduction of the
elastic tube. By this means the fluid is forced into the latter, and
may be drawn off as by a syphon.®

As a substitute for these methods, Edinger! causes the patient to swallow
pieces of sponge compressed and coated with gelatine, and retained by a thread
which is held in the hand. Spéth" similarly uses scraps of elder pith, stained
with appropriate reagents, or grains of shot having attached to them threads
soaked in the reagent. Bocci}" has devised a little instrument by means of which
0.1 grm. of gastric juice may be withdrawn, Sahli and Giinsburg employ tablets
containing potassium iodide in a thin coating of gum, and connected by threads

of fibrin. These are given to the patient, and the appearance of iodide in the
saliva is taken to indicate the rapidity with which fibrin is absorbed.

4. Chemical Constituents of the Gastric Juice.—Of these,
the most important are—(z.) Pepsin; (2.) Rennet, or milk-curdling
ferment ; (3.) Inorganic and organic acids. Each of these is liable to

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126 THE GASTRIC JUICE.

undergo pathological change, both as to quantity and to quality. Those
which affect the pepsin and acid constituents are of chief consequence in
clisease.

1. Pepsin.

(a.) Detection of Pepsin in the Gastric Juice.—As a test for pepsin,
its property of changing proteids, e¢.g., fibrin, into peptone is turned to
account. The best method of procedure is as follows :—10-20 cc. of
the acid fluid, obtained as above, is taken, diluted with water, and
filtered. To the clear filtrate a small quantity of well-washed blood
fibrin is added, and the whole kept at a temperature of 4o° C. If
pepsin be present, the fibrin will be dissolved after a few hours. If,
after the lapse of 10-12 hours, no change is apparent, or if an odour
of putridity be given off by the fluid, it may be assumed that the latter
is free from pepsin. Should it happen also that the secretion obtained
from the stomach has an alkaline or but feebly acid reaction, it will be
necessary, before applying digestion tests, to add to it its own volume
of a dilute solution of hydrochloric acid (8 ce. of the funiing acid in
992 cc. of water).

(b.) Quantitative Estumation of Pepsin.—Schiit? method may be em-
ployed for the quantitative estimation of pepsin. It is founded upon
a principle first enunciated by Huppert and Schiitz,+ one of fundamental
importance for the theory of digestion—namely, that under certain
conditions at the disposal of the observer, the quantity of peptone formed
is exactly proportional to the square root of the quantity of pepsin used.
Schiitz has taken as the pepsin-unit that quantity of the ferment which
will yield 1 grm. of peptone under the conditions of his experiment,
and expresses his results in terms of this unit. For further details the
reader is referred to the original communication.

2. Milk-Curdling Ferment.—This ferment was first investigated by
Hammarsten. It may be detected by the following process :—2-r1o ce.
of cow’s-milk, of neutral reaction, is well boiled, and to it is added
an equal quantity of gastric juice which has been carefully neutralised
and filtered. The mixture is placed in a warm chamber, or on a water-
bath heated to 30°-40° C. If the milk-curdling ferment be present,
the casein of the milk will be precipitated in flakes after the lapse of
20-30 minutes. The ferment was found by Schumburg and Boas 16 to
be invariably present in health, and absent in serious disorders of the
stomach, as cancer and atrophy of the mucous lining. It is wanting
in infants of from one to two days old; but Raudnitz1" established its
presence in older children who were reared on cow’s-milk. It was
regularly found in a series of investigations conducted on such subjects
(v. Jaksch).

The researches of Johnson,!® Boas, Klemperer,2° C. Rosenthal?!

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MILK-CURDLING FERMENT—ACIDITY. 127

A, Johannessen, and O. Sandberg, have thrown much light on the
subject of the rennet constituent of the gastric juice. These tend to the
conclusion that the ferment is elaborated by the glands, not as such, but
as a zymogen, which is then transformed into a milk-curdling ferment
by the action of hydrochloric acid. For the detection of this antecedent
substance (zymogen), Klemperer’s method may be employed :—To 2 cc.
of filtered gastric juice are added ro cc. of milk containing 2 cc. of a
3 per cent. solution of chloride of calcium, and an excess of a 1 per cent.
solution of carbonate of soda. The mixture is then placed in an incu-
hator, and if the zymogen be present, coagulation gradually ensues.
The amount of the ferment formed varies chiefly with the quantity of
hydrochloric acid generated in the process.

Experience has shown that the milk-curdling ferment is in excess in
conditions of hyper-secretion and undue acidity of the stomach. When
hydrochloric acid is wanting or but scantily present, the ferment is also
absent or reduced in quantity ; but according to Klemperer, the ferment
may also result from its zymogen in presence of organic acids.

3. Acids.—The gastric juice contains hydrochloric acid, and also
butyric, acetic, and lactic acids.*4

(a.) ACIDITY.—In very rare instances an increased quantity of acid
has been found in the stomach,”® and with this is sometimes coupled an
excessive secretion of gastric juice.

Riegel ° made the important discovery that, in cases of round ulcer
of the stomach, the acid constituent of the gastric juice is greatly in excess ;
and the fact has been further established by the observations of Mor-
czynskt, Jaworski," and many others (see p. 147).

According to Reichmann, Riegel, Sticher,?> and others, a distinction
is to be made between hyper-acidity and excessive secretion of the gas-
tric juice. By attending to this point it should be possible better to
discriminate between certain affections of the stomach, and especially
amongst those conditions which are still classed under the general
heading of gastric catarrh, dyspepsia, and the like (see p. 149).?°

A diminished acidity of the gastric juice occurs temporarily when a
large quantity of alkaline substances has been swallowed, and as a
persistent condition apparently in all febrile diseases.

The. acidity of the gastric juice may be measured in this way :—A
certain quantity—increased, if necessary, by the addition of water—is
filtered, and its reaction tested. If this be acid, a known quantity of
the filtrate is taken and coloured with a little neutral tincture of litmus.
Solution of soda of definite strength (the 1/10 normal or deci-normal
soda solution may be used with advantage) is now added slowly from
a graduated burette, until the point is reached finally at which the
onion-red colour of the fluid gives place to a violet hue. From the

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128 THE GASTRIC JUICE.

quantity of soda used, that of the acid present may be known, I ce.
of the normal soda solution employed in this way corresponding to
0.0365 grm. hydrochloric acid.°9 Instead of litmus an alcoholic solution
of phenolphthalein may be used. A few drops of this should be added
to the fluid before titration, and the alkali slowly supplied until a red
colour begins to develop.

The conclusions arrived at by this method are correct only when the
gastric juice contains hydrochloric acid alone, and not, as is generally
the case, several other acids as well (see below). On this account
Ewald* points out the fallacy of directly deducing the total acidity
from the amount of a deci-normal solution of soda required to neut-
ralise it. The expression 50 per cent. acidity implies that 50 cc. of the
deci-normal solution of soda will neutralise roo ce. of the gastric juice
experimented upon.

To determine whether the acidity is due to the presence of free acid
or to acid salts resort may be had to the methods of Ugelmann and Leo,
by which only free acid is detected. Leo*? uses calcium carbonate,
which in presence of acid is decomposed without heat, carbonic acid
being given off and the fluid acquiring a neutral reaction. If no free
acid, but only acid salts, be present, the fluid remains acid and reacts
to litmus paper as before. To carry out the test a quantity of the
gastric juice under examination is rubbed up with chemically pure
calcium carbonate, and the reaction obtained before and after the addi-
tion of the salt is compared. If in the second case this be neutral, the
original acidity was due to free acid; if, on the other hand, it be still
acid, but less so than formerly, the fluid contained both acid salts and
free acids. By an application of the same process it is possible to
estimate the quantity of free acid—hydrochloric and organic acids—in
a particular specimen. By Leo ** this is done as follows :—1o ce. of the
gastric juice is filtered, and 5 cc. of a concentrated solution of chloride
of calcium, and a few drops of an alcoholic solution of phenolphtha-
lein are added. The mixture is titrated with decimormal alkaline
solution. Next, to 15 cc. of the filtered juice is added 1 grm. of dry
powdered calcium carbonate, and the mixture is treated in the way
described above. It is then passed through an ash-free filter—asbestos
serves well—and the aspirator may be used to expedite filtration. Ten
ce. of the filtrate are measured out and placed in a small flask. The
stopper of this flask is perforated by two openings. Through one of these
a glass tube passes to the bottom of the flask; the other transmits one
end of a short right-angled glass tube, which reaches only just within
the flask, while the other end tapers a little and is connected by a
caoutchouc binder with a Bohm’s air-pump. By means of the latter the
carbonic acid which forms is drawn off. The fluid in the flask is then

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HYDROCHLORIC ACID. 129

treated with 5 cc. of calcium chloride solution and a few drops of
phenolphthalein, and titrated. The difference between the results of
this and of the former titration expresses the amount of acidity which
is due to the presence of free acid. Should it be ascertained, in the
way which will be described presently, that there were no organic
acids in the fluid, the difference depends upon the hydrochloric acid
alone, and its amount may be determined by the formula already given,
namely, that 1 ce. of the deci-normal solution of soda corresponds to
0.00365 grm. of hydrochloric acid. This method is sound in principle
and will be justified by its results. It must, however, be mentioned
that exception is taken to it by A. Hoffmann and A. Wagner ** on
theoretical grounds. According to MWossler,*> the process of filtration
may be omitted, and the conclusions both as to acidity and to the pro-
portion of free acid (see below) will be accurate.

(b.) HYDROCHLORIC ACID.—The gastric juice secreted during the
later stages of digestion appears normally to contain only free hydro-
chlorie acid. At an earlier period lactic acid is also present.

A. Detection of Free Hydrochloric Acid.The examination of the
gastric juice for free hydrochloric acid is attended with much difficulty,
since the chlorine salts yield nearly all the same reactions as the free
acid. To obviate this, many expedients °° have been suggested ; but
we shall notice here only those methods which will serve for clinical
purposes.

1. Mohr’s Tests.?’—(a.) ‘l'o the gastric juice to be tested is added first a solution
of iodide of potassium and starch-paste, and then a few drops of a very dilute
solution of ferric acetate. If free hydrochloric acid be present, a blue colora-
tion (starch iodide) appears. This very simple test is not altogether to be relied
upon, inasmuch as it will yield a negative result in presence of phosphoric acid
and its salts, even though free hydrochloric acid be present also.

(b.) The following test, also discovered by Mohr, answers its purpose admir-
ably :—It depends upon the fact that a very dilute solution of ferric acetate,
free from alkaline acetates, is unchanged by the addition of a few drops of
sulphocyanide of potassium solution, and retains its yellow hue, while, if a
mineral acid be present, it colours a deep red.

Ewald *8 has obtained good results by applying the test in the following
manner :—T wo cc. of a Io per cent. solution of sulphocyanide of potassium and
0.5 ce. of a neutral solution of ferric acetate are made up to 10 cc. (with water),
A few drops of the solution, which is of a ruby-red colour, are placed in a small
porcelain dish, and one or two drops of the fluid to be tested are allowed to
trickle slowly on to it. If hydrochloric acid be present, a light violet colour
forms at the point of contact of the two fluids, which gives place to a deep
mahogany-brown when they mix. This test, according to Hwald, has an advan-
tage over the aniline-dye tests in that its result is not materially affected by salts
or peptone ; but it is certainly less sensitive than the methyl-aniline-violet and
tropeolin tests.

2. The Aniline Dye-Tests.—(a.) Methyl-Aniline- Violet Reaction.—
This reagent was first used by Witz and Hilger *® for the detection of

I

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130 THE GASTRIC JUICE.

free mineral and organic acids. Maly has employed it for physiological,
Van der Velden for clinical purposes.4° To obtain the reaction, the
fluid to be tested is mixed with a violet-coloured watery solution of
methyl-aniline-violet. If very much free hydrochloric acid be present
(as is never the case in the gastric juice), the fluid will be bleached. If
a moderate quantity, it becomes green; and if very little, of a blue
colour. The direct examination of the gastric juice never shows more
than the transition from violet to blue. For the detection of a very
small proportion of acid, Maly recommends that the mixture should be
evaporated to the bulk of one or two drops on the water-bath. So
little as $ mgrm. of hydrochloric acid will then cause the change from
violet to blue.

Kost + recommends the addition of a 10 per cent. solution of tannin
before testing with methyl-violet, in order to precipitate peptones, which
would otherwise hinder the reaction.

(b.) Tropzolin (00) in alcoholic or watery solution yields a ruby-red
or dark-brown red colour in presence of free acids. Hwald # maintains
that this reaction constitutes the most sensitive test for free lactic as
well as hydrochloric acid. Boas,** who takes the same view, employs a
tropeolin test-paper for the purpose.

(c.) Fuchsin.—The test with fuchsin is far from sensitive, and on
that account of little utility.

(d.) Emerald-Green.*—The so-called “crystallised” emerald-green
affords a sensitive test for free hydrochloric acid. Concentrated solu-
tions of hydrochloric acid give reddish brown, and very dilute solutions
a grass- or a yellowish-green colour, with this reagent.

A brilliant-green, obtained from the same laboratory, has proved a
very efficient test. Five mgrms. of this reagent will serve to detect 0.48
mgrm. of hydrochloric acid dissolved in 6 cc. of water, giving to the
solution a bright green tint. It is to be noted, however, that a similar
effect is obtained where acetic, formic, or lactic acid is present in a higher
degree of concentration. Bourget # also uses a brilliant-green.

The other emerald-greens produced by Bayer, and distinguished as emerald-
green (extra crystallised) and emerald-green ii. and iii., proved useful, but less
sensitive. Of the other reagents tested, Kaiser blue (Guster, Berlin) was but little
sensitive. Its solutions turned a brown-green with concentrated hydrochloric

acid, and an azure-blue with dilute acid. A number of green pigments prepared
by Poirier of Paris were ineffective as tests for the acid.

Koster has recently employed malachite-green with good results as

a test for hydrochloric acid.

* This substance is made at B. Bayer’s laboratory, Elberfeld, and, with other
reagents, has been made the subject of experiment at the author’s request by Dr.
Voigt, on whose authority the statement in the text is made.

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CONGO-RED—BENZO-PURPURIN. 131

(e.) Congo-Red.—This is an aniline dye, which was first used as a test
for free acid by Herzberg. It may be employed most conveniently in
the form of filter-paper saturated with the reagent, as recommended by
Hosselin, Riegel, and his pupils,*° for the detection of free hydrochloric
acid.47 ‘This, when immersed in a fluid containing free hydrochloric
acid, turns blackish-blue or blue, according as much or little acid is
present. This effect is not obtained with organic acids or acid salts in
dilute solutions, and the intensity of the reaction is lessened in presence
of proteids and of salts in large proportion. The efficiency of the test
is undoubted, and notwithstanding that its use is subject to certain
fallacies,4#8 the Congo-red test-papers must be classed with benzo-
purpurin and the aniline-violet reagent as most suited to the purposes
of the practitioner.

(f.) Phloro-Glucin and Vanillin.—The reagent recommended by (iinz-
burg contains 2 grms. of phloro-glucin and 1 grm. of vanillin dissolved
in too parts of alcohol. When hydrochloric acid is added to this, it
deposits beautiful red crystals. For the detection of the acid in the
gastric juice it is employed thus :—To the fluid to be tested for acid an
equal quantity of the reagent is added, and the mixture evaporated on
the water-bath. The presence of hydrochloric acid is shown by a deli-
cate rose-red tinge on the surface of the porcelain dish. In this way so
little as 0.06 per cent. of the acid is discernible, and the reaction is not
impeded by organic acids, albumin, or peptone. By its means the
author ®° has often detected o.oo1 mgrm. of acid in ro cc. of gastric
juice. It is further commended by Haas.*! This observer has similarly
employed other colour substances, as eosin and methyl-orange, but
experience does not justify their use.°? Boas and Puriz®* have recom-
mended resorcin for the purpose, but it is less sensitive than Giinzburg’s
reagent.

(g.) Benzo-Purpurin.—A still more sensitive colour-test is that fur-
nished by benzo-purpurin 6 B. Five mgrms. will serve to show 0.39
merm. of acid dissolved in 6 cc. of water (Hellstrim), causing the dark-
red colour of the solution to give place to a light violet. A similar
change is effected with acetic, formic, and lactic acids ; but the colour
obtained with organic acids is rather a brownish-violet, and requires a
ereater quantity of the latter for its production ; in the case of acetic
acid, not less than 0.84 mgrm. Test-papers may be prepared by soaking
strips of filter-paper in a saturated watery solution of benzo-purpurin
6 B, and subsequently allowing them to dry. If one of these be placed
in the gastric juice, it will immediately stain a dark blue, provided
hydrochloric acid be present in a proportion not less than o.4 germ. to
100 cc. A brownish-black tint may be due to the presence of organic
(lactic or butyric) acids, or to admixture of these with the hydro-

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132 THE GASTRIC JUICE.

chloric acid. The ambiguity in this case may he dispelled by placing
the paper so stained in a test-tube and shaking it up with sulphuric
ther, when so much of the colour as is due to the presence of organic
acids will speedily disappear, leaving a lighter stain, or restoring the
paper to its original tint. If hydrochloric acid alone be present, no
change will be effected in this way, and even after the lapse of twenty-
four hours the blue stain will be only slightly displaced. It is important,
of course, that the ether used should itself be free from acid. To ascer-
tain this its reaction may be tested with blue litmus paper.

The action of the benzo-purpurin test is not seriously interfered with
by peptone and serum-albumin, even when these bodies are present in
large quantity, and acid salts have no effect upon it.

The following experiments are of interest, as showing the various effects
obtained from benzo-purpurin with hydrochloric and organic acids :—

Two solutions were made, one of 4 grms. hydrochloric acid in 100 cc. of water,
and another of 0.1 grm. benzo-purpurin 6 B in 600 cc. of water. On mixing to-
gether 3 cc. of each, a beautiful blue colour inclining to violet developed, and a
coloured flocculent precipitate formed on standing. The addition of hydrochloric
acid caused this precipitate to dissolve, and it reformed on the further addition
of the dye.

The same effect was produced whether the solution contained 0.4 or 0.04 grm.
hydrochloric acid in 100 cc., 3 cc. being taken in each case, Three cc. of a solu-
tion holding 0.004 grm. hydrochloric acid, when added to 3 cc. of a solution of
0.1 grm. benzo-purpurin in 600 cc, of water, gave an evident violet coloration
with slight turbidity.

With formic or butyric acid, to obtain the reaction rather less than 0.04 grm.
in 100 cc. of water was required; with acetic acid, something more than 0.04
grm.; with lactic acid, over 0.004 grm. in 100 cc. In all cases alike 3 cc. were
taken of each solution.

A comparison of the Congo-red and benzo-purpurin 6 B test-papers
shows that the latter are the more sensitive, and they deserve the pre-
ference for practical purposes. Hyper-acidity and the preponderance
of organic acids in the gastric juice can be shown by this simple pro-
cedure in the space of a few minutes.

None of these coloration processes give entirely satisfactory conclusions.
In cases where the reaction is positively obtained, free hydrochloric acid
is undoubtedly present ; but we may fail to obtain the result when the
gastric juice contains albumin, peptone, or salts in considerable quantity,
even when free hydrochloric acid is present also.64 The reactions with
methyl-aniline-violet, Congo-red, and benzo-purpurin are the most to be
depended upon. They will not serve for scientific purposes, but in view
of their simplicity they are of the utmost value in bedside observation.55

3. Uffelmann’s Tests.—U/felmann *® has employed the colouring-matter of claret
in testing for free acids in the gastric contents, and quite recently, as a still

more sensitive reagent, the amylic alcohol extract of bilberries, which he applies
by means of blotting-paper soaked in it.” The reaction depends upon the fact

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ULTRAMARINE AND ZINC SULPHIDE. ae

that the colour of such a test-paper changes in presence of hydrochloric acid
even when peptone, albuminates, and salts are present, from greyish-blue to a
rose tint, which persists after the paper has been washed with ether.

Lactic, acetic, and butyric acids give similar reactions, but only when in such
a degree of concentration as is never found in the gastric juice ; and, moreover,
the reaction obtained with them is destroyed by the addition of zether.

[Dreschfeld ® employs Uffelmann’s test in a modified form. The test solution
consists of 0.5 cc. of claret (unadulterated), 3 cc. of 90 per cent. alcohol, and 3 cc.
of zther; the solution is almost colourless, and is rendered a rose colour by
the presence of a minute quantity of hydrochloric acid. This test is said by
Dreschfeld not to be interfered with by the presence of peptone or albumin.
Lactic acid gives a similar reaction only when occurring in a more concentrated
form. The mixture does not keep long, and has to be freshly prepared.]

4. Ultramarine and Zinc Sulphide.—These substances were suggested by Maly,
and employed by Kahler® as a test for free hydrochloric acid in the contents
of the stomach. Ultramarine, according to Kraus," is a test for free acids
in general. It is decomposed by them even in dilute solutions, sulphuretted
hydrogen being given off, while silicic acid and sulphur are precipitated, Zinc
sulphide, again, is dissolved in dilute acids with the evolution of sulphuretted
hydrogen. It is, however, insoluble in acetic acid.

In testing for hydrochloric acid the process is as follows:—About 20 cc. of
the fluid under examination is placed in a crystallising crucible, and so much
ultramarine is added as will suffice to give it immediately a blue tinge. The
crucible is then covered with a watch-glass, from which depends a strip of filter-
paper soaked in solution of sugar of lead, and the mixture is gently heated in the
water-bath. After the lapse of a quarter of an hour, if hydrochloric acid be
present, the blue colour of the fluid will have given place to a brown tint, while
the-lead-paper will be stained brown or black. Sulphide of zinc (as much as
will fit on the point of a knife) is then added to another specimen, and the same
process repeated, when the brown or black stain upon the lead-paper will again
show the presence of hydrochloric acid. The reactions are rendered more feeble
by the presence of salts and of phosphates in particular. They can be obtained
also with organic acids (lactic and acetic) in more concentrated solutions.

These circumstances, and the comparative complexity of the process,
render its application at the bedside a matter of difficulty. Whereas, on
the other hand, we possess in the methyl-aniline-violet, benzo-purpurin,
and brilliant-green reactions a series of tests which are at once ready
and accurate.

B. Quantitative Estimation of Free Hydrochloric Acid.—This can be accurately
effected by the very complicated process of Bidder and Schmidt.*! All the acids
and bases in the gastric juice are quantitatively estimated, the proportion of
each in 100 cc. of fluid ascertained, and their equivalents computed. The
remaining hydrochloric acid is that which is free in the secretion.

Another method for the determination of this body depends upon the fact
that the acid is insoluble in ether, whilst organic acids are soluble in that
medium. To utilise this property for the purpose in hand, Richet® shakes up
the gastric juice with zther, and determines by titration the quantity of acid
which is taken up by the latter together with what is retained in the watery
solution.

Recently, v. Meriny and Cahn ® have adopted the expedient of collecting the
volatile acids by distillation, lactic acid by extraction with zther, and combining

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134 THE GASTRIC JUICE.

the hydrochloric acid separated from the organic acids with cinchonine, shaking
up the newly-formed hydrochlorate of cinchonine with chloroform, changing
the acid into its silver salt, and finally weighing the chloride of silver obtained.
Koster (see p. 130) has endeavoured to determine the quantity of hydrochloric
acid in the gastric juice by a process of titration with alkalies after the addition
of methyl-aniline-violet.

Giinaburg’s reagent, according to Zwald,*4 will also furnish a means of approxi-
mately estimating the quantity of hydrochloric acid present.

1. Leo’s Method.—This has been already described (p. 128). If fatty
acids and lactic acid be present, their proportion must be determined
(see p. 139), and deducted from the total acidity. The difference. will
express the quantity of HCl. According to Kossler,® the method
is accurate. Both it and that which follows serve well enough for the
estimation of physiologically active hydrochloric acid.

2. Sjéqvist’s Method.—Sjoqvist % has recently introduced a process
for the estimation of free hydrochloric acid in the gastric juice founded
upon the following facts :—The acids of the secretion may be changed
into their barium salts by the action of barium carbonate, and when
these are incinerated, the baryta salts of the organic acids leave barium
carbonate, whilst the chloride of barium resulting from the combina-
tion with hydrochloric acid remains unchanged. The latter may then
be separated from the insoluble carbonate by extracting the ash with
warm water, and its quantity estimated by titration with chromate
solution. The details of Sjoqvist’s method are these :—Ten cc. of the
gastric juice are filtered and placed in a platinum or silver crucible,
and barium carbonate free from chlorides added in excess. The fluid
is then evaporated to dryness at a gentle heat, and the residue charred
and strongly heated for some minutes. After cooling, the residue
is treated with 10 cc. of water, the mixture rubbed up, extracted
repeatedly with boiling water, and filtered until the filtrate has a bulk
of 50 cc. The quantity of chloride of barium in solution is best esti-
mated by titration with bichromate of potash. This body gives with
salts of barium a precipitate of barium chromate, which is insoluble
in water and acetic acid, and soluble in hydrochloric acid. A solution
of bichromate of potash of known strength is added from a_ burette,
until all the barium present is precipitated in the form of chromate.
A subsequent excess of bichromate of potash would give to the fluid
a deep red colour, which would tend to mask the result. This may be
prevented by the use of tetra-paper (tetramethylparaphenyl-diamine),
which has the property of staining blue with oxidising substances.
In the process of titration, therefore, the filtrate is mixed with one-
fourth or one-third its volume of alcohol and 3-4 ce. of a solution
holding ro per cent. acetic acid and ro per cent. acetate of soda, and
titrated with a solution of bichromate of potash (8.5 grms. to the litre)

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ESTIMATION OF HYDROCHLORIC ACID. 135

until a faint trace of blue appears upon the test-paper. The addition of
acetic acid and acetate of soda has for its object to promote the precipita-
tion of chromate of barium, and at the same time to prevent the forma-
tion of chromate of lime from the small quantity of lime salts and free
hydrochloric acid that may be present. From the quantity of bichro-
mate of potash used, that of the barium salt formed, and also of
sulphuric acid present, results directly.97

This process is attended with difficulty, and it is open to the objection
that it depends too much on the judgment of the observer. The follow-
ing modification of it is more accurate.

3. V. Jaksch’ Modification of Sjéqvist’s Method.—It is the author’s
practice to convert the chloride into barium sulphate, and by weighing
the sulphate to calculate the amount of hydrochloric acid in 10 ce. of
gastric juice. To that end the unfiltered gastric juice (10 ce.) is treated
with chlorine-free carbonate of barium in excess, and placed on a furnace
in a thin porcelain crucible, where it is evaporated to dryness, then
gently fused in a muffle; the residue cooled, extracted with boiling
water, and filtered ; the filtrate evaporated on the water-bath to a volume
of roo cc., and dilute sulphuric acid added. The precipitate (sulphate
of barium) is placed on a thick ash-free filter, washed with water, fused
in a platinum capsule, thence removed with the usual precautions.®
The result is calculated thus :—233 parts by weight of barium sulphate
(BaSO,) correspond to 73 parts of hydrochloric acid (HCl). And the
quantity of the latter contained in 1o cc. of the gastric juice may be
calculated from the formula

eee LS. M=0.3132 x M
233

where M = thequantity of barium sulphate obtained from ro cc. gastric juice

x =the quantity of hydrochloric acid sought in ro ce.

This method enables the examination to be effected within a compara-
tively short time. Its accuracy is attested by Leo, Lenbuscher, Pfungen.®
The objections made to it on the ground of its being too complicated are
ill-founded.” It serves for the estimation of HCl equally when free,
and when combined with organic digestive products (proteids). It is
doubtless true that there are proteids which enter into combination with
HCl in such a way that the acid is no longer perceptible by this process,”
but the author’s investigations have satisfied him that such combinations
do not in fact oceur in digestion. Quite lately Leo"? has contended
against the principle of Sjéqvist’s method, adducing considerations which
gravely affect the pretensions to accuracy both of that method and of the
modification of it just described ; the result of Kossler’s'? researches, how-
ever, has greatly diminished the force of Zev’s objections. It would

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136 THE GASTRIC JUICE.

appear, indeed, that the method is inapplicable where phosphates are
present, and its utility is much curtailed by this fact. In any case it
is only the absolute values as determined by the method which are
affected. The conclusions based upon them remain good. Finally, the
observations of Rosenheim™ show that the fallacies which Leo has
pointed out do not apply to a bedside examination. The modifications
of Salkowshkt and Fawitzky™® and of Boas" offer no special advantages.
Of Bourget’s process’? the author has no experience. That of Winter
and Wagner, according to Kossler,’$ yields an estimate of HCl, free and
combined with proteids, which is somewhat too high.

4. A. Braun’s Method.”—A certain quantity—5 cc.—of the filtered
gastric juice is taken and its acidity determined by titration with 35
normal soda solution in the manner described at p. 127. To another
5 ce. of gastric juice is added soda solution a little in excess of
what was needed to neutralise it. The fluid is now incinerated (see
p. 134), and to the ash is added as many ce. of 7'5 normal sulphuric
acid solution as were needed of 4, normal soda solution to neutralise the
specimen taken, z.e., 5 cc. of the filtered juice. The ash is thus dis-
solved ; the fluid is warmed, and carbonic acid driven off, after which
a solution of phenolphthalein is added to it, and it is titrated with
iy normal alkali solution. The number of cc. of 7'5 normal soda solution
employed, multiplied by 0.00365 (see p. 129), gives the quantity of HCl
in 5 ce. of gastric juice. This method is founded on the same principle
as Sjéqvist’s, but, according to Kossler,®° it is not accurate, since the
acidity which is due to acid phosphates is not allowed for.

5. A. Hoffmann’s Method.*! —In testing the proportion of HCl in the
gastric juice, Hoffmann has availed himself of the property which HCl pos-
sesses of inverting cane-sugar, ze. of breaking it up into dextrose and lvu-
lose, so that the polarisation-phenomena of its solutions are altered. ‘The
following preparations are required :—z. A fluid containing known quan-
tities of cane-sugar and HC]. 2. Equal quantities of cane-sugar and gastric
juice. 3. Gastric juice alone. 4. Gastric juice with cane-sugar and sodium
acetate in equal quantities. The rotatory power of each of the four fluids is
ascertained by means of the polarimeter, and they are then allowed to stand
in a warm place for some hours, and their rotatory power again investigated.
The calculation is then made by the formula, log A—log (A-«x)=C, where
A=the quantity of sugar originally present, «=the quantity which has been
converted at the termination of the process. This method is undoubtedly
ingenious, but it is subject to the drawback that it requires a very accurate
polarimeter, eight polarimetric examinations, and a highly-complicated calcula-
tion. Recently it has been much simplified by substituting titration with
methyl acetate for inspection with the polarimeter.® The researches of Kossler ®%
have shown, however, that it serves only for the estimation of free HCl, to the
exclusion of that which is combined with proteids.

In addition to those described here, many other methods have been brought
forward for the estimation of HCl, but they possess no superior advantages, such
of them as are easier of application being proportionately wanting in accuracy.

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HYDROCHLORIC AND ORGANIC ACIDS. 137

Amongst them are those of C. Th. Morner, Mintz, Jolles, Kronfeld, and Czyr-
nianski.5* Of the method recently suggested by Liittke® the author has no
personal experience. The principle upon which it depends—namely, estimation
of the total quantity of chlorine and chlorides—is not new.

(c.) THE QUANTITY OF HYDROCHLORIC ACID PHYSIOLOGI-
CALLY ACTIVE IN THE GASTRIC JUICE, AND ITS DIAGNOS-
TIC IMPORT.—Concerning the quantity of hydrochloric acid which is
secreted normally during digestion the recorded observations are very
few. Moritz, Wohlmann, and v. Jaksch 6 have investigated this subject.
According to the latter, the quantity formed during digestion in healthy
children varies greatly with the nature of the food, and generally attains
its maximum within one to three hours aftera meal. With milk, which
combines very readily with acids, the increase is slow; it is more rapid
with nitrogenous, slowest, but with greatest initial rapidity, with fari-
naceous food. The greatest quantity of effective HCl was obtained
with a diet of milk alone, a smaller quantity with a meat diet, and the
least with carbohydrates. The quantities were respectively :—o.1615
gim. (mean of fourteen observations), 0.1563 grm. (mean of eleven
observations), and 0.1102 grm. (mean of ten observations), in 100 cc.
of the gastric contents. The facts are the same in healthy adults.
Thus with the method described at p. 135, the author has found that
when 200 grms. of ham have been taken, there are in roo ce. of the
gastric contents 0.0643 grm. of HCl in thirty minutes, 0.1529 grm. in
forty-five minutes, and 0.0992 grm. in an hour. From this it follows
that, as a preliminary to basing any inference upon the quantity
of HCl secreted, it is necessary to consider what food the subject
of the inquiry has taken, and at what time he has taken it. The
absence of free HCl, or its presence only in very small quantity, fifteen
to thirty minutes after a meal, has no pathological significance. But
should there be little or no free HCl present one to three hours after
taking milk or nitrogenous food, the fact is evidence of a grave defect of
function. A large quantity of HCl, even so much as 0.33 per cent. three
hours after food, does not necessarily imply functional disorder (hyper-
secretion). Such considerations must always be weighed in forming an
inference for diagnostic purposes. Again, for practical purposes, those
tests alone are satisfactory which yield information concerning the
physiologically-effective acid. From this point of view the colour-tests
are insufficient, but they have the advantage of being easily applied, and
where approximate results are desired they serve well enough. For
scientific purposes the requirements are :—1. The application of such
methods as dispense with the necessity of filtering the gastric juice,
since this process is attended with much waste of the acid (v. Jaksch).®
2. That the method chosen should be one which takes account of that

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138 THE GASTRIC JUICE.

part of the acid which is physiologically effective. These requirements,
as Kossler has shown, are fulfilled only by Leo’s method, when applied
to artificial digestion. Whether this is true of the natural gastric juice
also remains to be proved. Approximately accurate results, however,
may be obtained by the author’s modification of Sjdqvist’s process. One
of these methods may be used with advantage to control the other.
We shall return to this point presently in treating of the contents of
the stomach in different gastric disorders.

It may be suggested here that for the terms “free” and “ combined ”
hydrochloric acid, “ physiologically active” and ‘physiologically in-
active” should be substituted. By the first would then be meant
either that portion of the acid which has already discharged its function
and has entered into combination with proteids, or that which is still
available, and therefore in the literal sense free.’8

The investigation of the functions of the stomach in disease of all
kinds, and especially with reference to the secretion of hydrochloric acid,
has of late years been pursued with the utmost energy. The contri-
butions to the subject which possess the chief diagnostic interest may be
briefly mentioned. Jmmermann and Schetty*®® found that in tubercu-
losis there was no change in the secretion of HCl. Their conclusions
are supported by Chelmonshi, Klemperer, O. Brieger, Hildebrand, and
Schwalbe.©  Grusdew,® on the other hand, observed a diminished pro-
duction of the acid. vile? states that in heart-disease the acid is
deficient, but this is not in accordance with the observations of Hinhorn,
Adler, and Stern.%

Biernackt®* and the author have noticed a considerable deficiency of
the acid in renal disease in many cases.°° Lenhartz®° has collected much
information upon this subject. In acute and chronic dyspepsia there
was a remarkable deficiency of free acid ; in chlorosis a similar deficiency
was observed in 45.6 per cent. of the cases investigated, whereas in
gastric ulcer the condition was inconstant.

From these facts it results that the presence or absence of free hydro-
chlorie acid is a symptom of doubtful import, and that it must be
weighed in conjunction with the other circumstances of the case. It is
much to be desired that measures should be taken for the acquirement
of accurate data concerning the production of hydrochloric acid in
diseases of the stomach and other parts, and this may be done by the
use of the more scientific methods indicated here, and especially by
observance of the precautions mentioned on p. 137. It is sufficient here
to point out that a failure of the secretion on the one hand, and its pro-
duction in excess on the other, are alike evidence of Gisease.97 Their
precise significance will be dealt with later (pp. 146, 148).

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ESTIMATION OF ORGANIC ACIDS. 139

(d.) ORGANIC ACIDS OF THE GASTRIC JUICH.—In this con-
nection we have to deal with lactic, acetic, and butyric acids.

1. Lactic Acid.—A. Qualitative Tests.—In the detection of this
hody in the gastric juice the carbolo-chloride of iron test is to be recom-
mended (Ujelmann, see ref., p. 132), (Kredel).8 To a mixture of to ce.
of a 4 per cent. solution of carbolic acid with 20 cc. of water, a few drops
of perchloride of iron solution are added, and the resulting amethyst-
blue colour changes to yellow in presence of a few drops of lactic acid.
Alcohol, sugar, and phosphates, however, yield a similar reaction (Ewald).

A further test for this body is derived from a very dilute solution of
perchloride of iron—two to five drops of a watery solution of perchloride
in 50 cc. of water. The faint yellow colour of the fluid, whilst not
affected by the addition of hydrochloric, butyric, or acetic acid, is inten-
sified in presence of dilute lactic acid. To separate lactic acid from the
gastric juice, the distillation residue (see below) of the gastric juice, in
which the acid is dissolved, may be extracted with ether, and submitted
to the tests described elsewhere (see chapter on Urine).

B. Quantitative Estimation.—This may be effected by Cahn and
v. Mering’s method (see p. 133), or by that of Leo.°! 10 ce, of gastric
juice are taken, and when the fatty acids have been removed (see below),
extracted six times with reo cc. of ether in a separator-funnel, the
resulting ethereal extracts collected, the ether driven off by exposure to
the air by heat from a water-bath—(a flame must not be used)—and the
residue dissolved in water. The acidity of the solution is then deter-
mined by a 35 normal soda solution. Since 1 ce. of the soda solution
corresponds to 0.090 grm. of lactic acid, the quantity of the latter con-
tained in 1o cc. of gastric juice may be obtained by multiplying the
number of ce. of alkali used by 0.090.

2. Butyric and Acetic Acids.—(a.) Qualitative Tests.—If the gastric
contents be extracted with ether, butyric and acetic acids may b2 recog-
nised by their smell (Ufelmann). To separate these acids, the gastric
juice is distilled and the distillate tested in the manner laid down for
the examination of the urine.

Hammarsten'? prefers not to distil the gastric juice directly, but to
neutralise it first with caustic soda, and then to extract with alcohol,
proceeding afterwards in the manner to be described for the detection
of fatty acids in the urine. The object is to avoid the error of including
fatty acids derived from proteids.

Uffelmann (ref., p. 132) directs attention to the importance of a syste-
matic analysis of the gastric juice for the detection of free acids. To
do this the contents of the stomach are filtered and their reaction tested.
Should this be acid, they are submitted to the following process :—The
total acidity is determined by titration with a decinormal solution of

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140 THE GASTRIC JUICE.

caustic soda, and a portion is tested with dilute solution of perchloride
of iron for the presence of lactic acid. Another portion is then tested
for free hydrochloric acid with bilberry-dye test-papers. A rose colour
obtained when the degree of acidity is slight, and persisting after the
addition of ether, indicates the presence of hydrochloric acid. If, on the
other hand, the colour is entirely destroyed by treatment with ether, it is
evidence of considerable quantities of lactic, butyric, and acetic acids.

Riegel! and Koster (ante, p. 134) have employed similar methods
with success; and attention may also be directed to the process de--
scribed at p. 135.

(b.) Quantitative Estimation.—Leo’s 1* method is the following : 10 ce.
of the gastric juice are taken, and the total acidity determined in the
manner described at p. 128. Another ro ec. are filtered and boiled until
the fumes no longer present an acid reaction. The residue is allowed to
cool, and is then titrated with deci-normal solution of soda. The differ-
ence between the acidity of this and the former specimen is that due to
the fatty acids. The method is not absolutely accurate, since HCl may
be driven off by boiling.

4. Proteids.—Proteids occur in the gastric contents during digestion,
being partly formed in that process, and in part derived from the food.
Their recognition affords valuable evidence as to the functional condition
of the stomach ; and to make its import clearer, it will not be out of
place to refer to certain facts in physiology. The period of digestion
may be divided into two stages. (1.) The first of these, which lasts
but a short time (15-20 min.), is occupied chiefly with the digestion of
starchy matter, and is characterised by the presence of the resulting
products, and especially lactic acid. (2.) The second stage commences
with the secretion of pepsin and an active gastric juice, by means of
which the albumin of the food is changed. The two stages pass gradu-
ally into one another, and authorities are not agreed as to whether lactic
acid occurs only during the first (Hwald, Boas, and others) or in the
second stage of healthy digestion also, when it is said by some (Cahn
and v. Mering, Ritter and Hirsch) to be present together with the more
abundant hydrochloric acid.

For the purpose of an examination, whether in a healthy individual
or otherwise, a test-meal should be administered on an empty stomach.
This, according to Hwald, should consist of a dry, well-baked roll and
water or weak tea; whilst Leube and Riegel recommend a meal of
water-broth,* semolina and flour-gruel,t and meat. Ewald’s regimen

* Wassersuppe, translated here as water-broth, is made of boiling water with
small squares of dry rolls, some salt and fresh butter.

+ Griessuppe, semolina soup, consists of semolina boiled in water and seasoned
with salt and butter or extract of meat.

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PROTEIDS—-UREA—-AMMONIA. 141

has the advantage that digestion is at its height within an hour after
the food has been taken, whereas in the other case it is necessary to
wait for four to six hours before the examination can be begun The
contents of the stomach are obtained in the manner described at p. 125.
A test-meal of this kind is very useful for many purposes. Klemperer
and the author! administer milk in the same way. It is probably
advisable that the test-meal should be of the simplest possible character,
a single proteid, as, for example, ego-albumin, or a carbohydrate being
given, and the choice will be made in accordance with the subject under
investigation. The proteids in question are albumin, hemialbumose,
peptone, and syntonin.

Albumin and hemialbumose may be detected by the process detailed in
the chapter on Urine. Should these bodies and syntonin be absent, the
biuret reaction (red coloration) will serve directly to show the presence
of peptone. If, on the other hand, following the method referred to,
other proteids (and especially those which are coagulable by heat) are
found to be present, these must first be removed in the usual manner
(see chapter on Urine), provided a sufficiency of material remains to
work upon. The filtrate may then be submitted at once to the biuret
test, the previous precipitation with phosphotungstic acid not being
necessary.

Syntonin may be known by its being precipitated by neutralisation
from its acid solutions.

About 30-40 cc. of gastric juice will suffice for an examination of
this kind when a little skill has been attained in conducting it. The
pathological specimens which come to hand rarely exhibit other nitro-
genous bodies than peptone, as is the case also when the contents of
the stomach are examined several hours after the test-meal has been
taken.

5. Urea.—For the detection of urea, one of the methods adopted for
the same purpose in connection with the blood (p. 69) may be employed.
Considerable quantities of this body are found in the stomach in cases
of ureemia.

6. Ammonia.—Salts of ammonia are abundantly present in the
stomach in rare instances. Where a considerable bulk of the gastric
contents can be obtained (as by vomiting), the quantity of ammonia
present may be estimated, after the removal of the proteids, by Sai-
kowski’s method. For this purpose, 50 cc. of the vomited matter are
taken, 20 grms. of pure powdered chloride of sodium first added, and then

 

too cc. of a mixture holding seven parts by volume of a saturated solu-
tion of chloride of sodium and one part of acetic acid (1.040 sp. gr.).
The whole is then mixed together, allowed to stand for fifteen to twenty
minutes, when it is measured and filtered. .Of the proteid-free filtrate

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142 THE GASTRIC JUICE.

50 to 100 ce. are measured off, treated with milk of lime, and placed
under a bell-glass containing a known quantity of 1/100 normal solu-
tion of an acid. After the lapse of from three to five days, the latter
is removed and titrated with 1/100 normal alkali solution coloured
with rosolic acid. In this way the quantity of ammonia absorbed may
be determined.1°7

The same process is applicable to the determination of ammonia salts in the
blood and other fluids.

7. Carbohydrates.—Grape-sugar may sometimes be found in the
stomach, having either been introduced with the food, or formed
there by the action upon starch of saliva which has been swallowed.
This latter mode of origin belongs especially to conditions of hyper-
secretion of HCl (Riegel, see p. 127, Hwald).°S The mode of testing for
sugar is the same here as in the blood (p. 72), the proteids being first
removed.

The phenomena of the digestion of starch, and the formation of its
intermediate products, involve some points of interest. An hour after
food has been taken, under ordinary circumstances, neither starch
(blue colour with iodine and iodide of potassium solution) nor erythro-
dextrin (red with the same reagent) can be discovered in the filtered
gastric juice. Should it happen otherwise, some cause tending to delay
the amylolytic process may be inferred, and this may be sought either
in the fact that the saliva is deficient in diastase, or that there is an
excessive secretion of free acid by the stomach at the outset of digestion
(Ewald, Boas, Rosenheim"). In health, also, when amylaceous food
has been taken in quantity, starchy particles may be found, and their
nature determined chemically (see p. 145).

5. Estimation of the Rate of Absorption of the Gastric
Contents.—The rapidity with which the gastric contents are absorbed,
and consequently the functional activity of the stomach in this respect,
may be determined thus, after Penzoldt and Faber..! A capsule con-
taining o.1 grm. of iodide of potassium is given to the patient to
swallow. The saliva is then tested for iodine every two or three
minutes, by placing a little of it upon filter-paper saturated with
starch-paste, and adding a drop of fuming nitric acid. The presence
of iodine is shown by a blue colour, which usually appears in 8-15
minutes. According to Zierfel,!!? this period is prolonged—-thus indi-
cating a deferred absorption—in various affections of the stomach, as
dilatation, cancer, and gastric ulcer.

6. To Determine the Contractile Activity of the Stomach.—
For this purpose various expedients have been adopted. Amongst them
may be mentioned those of Lewbe, Klemperer, Stevers, and Ewald.
Leube assumes that the motor function of the gastric walls is impaired

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THE INTESTINAL JUICE. 143

when the use of the sound shows the presence of food seven hours after
it has been taken. Klemperer’s method is objectionable on the score of
discomfort. Ewald introduces within the stomach a gelatine-capsule
containing 1 grm. of salol. This decomposes into phenol and salicylic
acid as soon as it reaches the small intestine, and rapidly appears in the
urine, where it may be detected by solution of ferric chloride (see chapter
on Urine). The interval which elapses before the drug appears in the
urine may be taken to indicate the length of time required for the
stomach to discharge its contents. In health this is from 4o to 60
minutes, but a much longer time in gastric atony and dilatation. The
results obtained in this way have no utility in diagnosis.!4

7. A Summary of the Chemical Examination of the Gastric
Contents.—It is seldom that sufficient material can be obtained for
the systematic examination suggested here, and it will be necessary to
make the investigation by successive evacuations of the stomach, the
administration of test-meals, &c., before the different processes can be
applied.

1. The reaction is to be tested.

2. A known quantity of the fluid, say 10 cc., is taken for the deter-
mination of acidity.

3. Another quantity of 10 ec. is examined to show the presence of
pepsin and milk-curdling ferment.

4. The benzo-purpurin, Congo-red, and brilliant-green tests for free
hydrochloric acid are applied, and the latter estimated quantitatively by
Sjoqvist’s method.

5. A rough estimate is made of lactic, butyric, and acetic acid in the
manner described at p. 139.

6. Examination for proteids, this being confined to serum-albumin
and peptone where sufficient material cannot be had.

7. Test for starch and its digestive products.

8. The remainder of the fluid is distilled, and the residue shaken up
with ether, to determine accurately the quantity of lactic acid which it
contains (p. 139). The distillate is tested for fatty acids in the manner
described in the chapter on Urine.

II. THE INTESTINAL JUICE.—In the present state of our know-
ledge the investigation of the intestinal juice lends but little aid to
clinical study. Notwithstanding this, the subject is worthy of attention,
and it is probable that before long it will be brought within the scope
of a practical inquiry.

1. Naked-Eye Characters.—The intestinal juice is 2 mixed secre-
tion derived from several glands, and its character varies with the part
of the tract from which it is taken. In the small intestine it is the

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144 THE GASTRIC JUICE.

product of Brunner’s and Lieberkiihn’s glands, the liver, and the pancreas.
It is only this fluid, which is a compound of bile, pancreatic fluid, and
the secretion of the intestinal glands, that will be noticed here. It
is a clear yellow thin fluid of a strongly alkaline reaction, and sp. gy.
1.009—1.011. On standing exposed to the air it turns to a grass-green
colour.1%

2. Formed Elements.—Concerning these nothing is accurately
known.

8. To Obtain the Intestinal Juice.—According to Boas," it is
first ascertained whether the stomach is empty. Should it be so, the
patient is made to lie down, and the abdomen over the region of the
gall-bladder is massaged ; then the patient is made to stand upright, and
the sound is again introduced, when he once more assumes the horizontal
position, and the fluid is pressed out.

4. Chemical Constitution of the Intestinal Juice.—The
intestinal juice contains bile-acids and hile-pigments, syntonin, peptone,
a small quantity of leucin and tyrosin (comp. Chapter VII.), and a
number of ferments, of which the chief are the tryptic, fat-splitting, and
emulsifying * (pancreatic), diastatic, and inverting ferments.

Concerning the changes which the secretion undergoes in disease
nothing is yet known. Boas was the first to introduce the subject of
digestion in the small intestine. Physiological research has yet to pave
the way before our knowledge in the matter can be applied to the pur-
poses of diagnosis. Nevertheless, the few facts which have been brought
to light by Boas and Noorden™" afford ample prospect of a rich harvest
both of physiological and clinical results from further study in this
direction. "8

III. EXAMINATION OF THE VOMIT.—The vomit includes the
secretions of the mouth and nasal passages which have been swallowed,
and are, for the most part, already undergoing digestion, the gastric juice
and ingested substances, in part altered by the action of the stomach,
and partly unchanged. Further, it sometimes contains bile.

The naked-eye and microscopical appearances vary with its constitu-
tion, and chiefly with the abundance and character of the food. Apart
from such constituents as are derived from the mucous membrane of the
mouth and nasal passages, and which have been already described, the
vomit almost invariably presents—(1) Columnar and squamous epithe-
lium, both usually much altered in form; (2) isolated white blood-cor-
puscles, generally so transformed by the action of the gastric juice that
little more than the nuclei remains ; (3) isolated red blood-corpuscles,

* [It is, however, doubtful if there is an emulsifying ferment.]

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CONSTITUENTS OF THE VOMIT. 145

usually seen as colourless rings, and very seldom in a quite perfect state ;
(4) the following derived from the food :—

1. Muscle fibres, readily recognisable by their transverse striation.

2. Fatty globules and fat-needles, which are sufficiently characterised
by their refracting property and their solubility in ether.

3. Elastic fibres and connective tissue.

4. Starch granules, to be recognised by their concentric arrangement
and by their property of staining blue with iodo-potassic-iodide solution.
These bodies are frequently disintegrated and more or less dissolved hy
the process of digestion.

5. Vegetable cells of various forms.

 

Fic. 64.—Collective View of Vomited Matter (eye-piece III., objective 8a, Reichert).

a. Muscle fibres. e. Fat globules. i. Various micro-organisms, such
b. White blood-corpuscles. jf. Sarcina ventriculi. as bacilli and micrococci.
c, c’. Squamous epithelium. g. Yeast-fungi. k, Fat-needles; between them
ce’. Columnar epithelium. h. Forms resembling the com- connective tissue derived
d. Starch grains, mostly al- ma-bacillus, found by the from the food.

ready changed by the author once in the vomit|/. Vegetable cells.

action of the digestive of intestinal obstruction.

juices.

In addition, the vomit in disease displays a great variety of fungoid
growths (W. de Bary"), depending upon the nature of the underlying
process. Amongst these :—

1. Mould-Fungi and scattered conidia have occasionally been found.
These are, so far as we know, devoid of pathological significance.

2. Yeasts.—(a.) Saccharomyces cerevisiz. These are about the size
of leucocytes, and refract light powerfully. They cohere in groups of
three or more, and stain deeply a brownish-yellow with iodine and iodide
of potassium. Very often there are also to he seen elliptical bodies
resembling Saccharomyces ellipsoideus (Zees).1°°

K
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146 THE GASTRIC JUICE.

(b.) Very small yeast-like fungi in thick clusters (fig. 64, 9).

(c.) More seldom highly-refracting rod-like bodies, of considerable
length and thickness, which generally exhibit a single nucleus. They
are rounded off at the ends, and are sometimes separate, sometimes
strung together in strands. It would seem that these are the agents
in lactic acid fermentation of sugar.

3. Fission-Fungi—The forms belonging to this class are many and
various.!21 They include rod-like bodies, which stain blue with iodo-
potassic-iodide solution, bacilli and micrococci of every description, and
in particular a bacillus which possesses the property of changing glyce-
rine into alcohol by fermentation (fig. 64, 7).

Sarcinz ventriculi 122 may easily be known by their shape, resembling
that of wool-packs, their dark silver-grey tint, and their property of
staining a deep mahogany-brown to reddish-brown with the iodo-potassic-
iodide solution (fig. 64, /).

After this general view of its microscopical appearances, we shall
advert to the physical, chemical, and microscopical characters of the
vomit in certain diseases.

4. Acute Gastritis.—In this condition the vomit consists partly of
mucus which has been swallowed, and partly of half-digested food
residues. Microscopically it displays the appearances already detailed,
which, however, are here subject to much variety, and notably a few
red blood-corpuscles are generally to be seen.

Its chemical character varies greatly (wald).!°3 At the outset of the
affection, hydrochloric, and commonly lactic, acid in the free state are
wanting. The addition of the former will establish a slow digestive
process. Ewald 14 has been unable to determine the presence of fatty
acids in notable quantity, and the proportion of pepsin would appear
to be considerably diminished.

The vomit usually is coloured green from the admixture of bile pig-
ment (biliverdin). It often also contains biliary acids. The first may
be recognised by Gmelin’s test (see chapter on Urine), and the latter by
Pettenkofer’s (see p. 76), or by means of the furfurol and sulphuric
acid reaction (see Urine). Much remains to be learnt as to the chemical
peculiarity of the gastric contents in this condition.

2. Chronic Gastritis.—The vomit is a thin mucous fluid (vomitus
matutinus), of alkaline, or it may be weakly acid, reaction. Van der
Velden has shown that it always contains pepsin and hydrochloric acid,
also organic acids, especially acetic and butyric acids. It is commonly
rich in proteids, and notably peptones, which may be easily distinguished
by the tests which will be subsequently described in connection with
the examination of the urine. Bile pigment is also generally present.

Recent observations seem to show that it is possible to distinguish

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CHRONIC ULCER OF THE STOMACH. 147

the different forms of gastric catarrh by the results of the chemical
methods described above. Following the conclusions of Hwald, we may
discriminate (1) Simple gastritis, (2) acid gastritis, (3) mucous catarrh,
(4) atrophy.

1. In the first form, simple gastritis, the test-breakfast is never
followed by increased acidity ; the proportion of hydrochloric acid is
diminished; the secretion contains little pepsin and milk-curdling
ferment, and generally, though not always, includes lactic and fatty
acids. On the addition of acid the secretion shows digestive activity.

2. In acid gastritis acidity is increased, especially that due to hydro-
chloric acid. In other respects the condition is that of simple gastritis.

3. In the third form, mucous catarrh, acidity is always slight and
hydrochloric acid absent ; there is abundance of propeptone, but no pep-
tone. Milk-curdling ferment is absent, or it may develop only after a
prolonged interval. Artificial digestion requires the addition of hydro-
chlorie acid.

4. In atrophic gastritis the fasting stomach is usually empty, and its
contents, after the administration of the test-meal, is free from mucus,
and altogether wanting in pepsin, hydrochloric acid, and the milk-
curdling ferment. !?°

The observation of Mathieu °° that mucus is indigestible has an im-
portant bearing on the study of these conditions. The fact noticed by
John 12" that excessive acidity of the gastric juice impedes salivary
digestion, and that acids, organic and inorganic, promote the secretion of
saliva, is equally instructive. In the case of a gastro-duodenal catarrh
complicating gastritis, the gastric juice exhibits the same variety in
respect of the presence or absence of appreciable quantities of physio-
logically effective hydrochloric acid. The author has investigated three
cases of this kind. In one the acid was altogether wanting, while in
the other two it occurred in diminished proportion.

8. Chronic Ulcer of the Stomach.—The microscopical appear-
ances of the vomit in this disease are those detailed under (2) in the
last section. Otherwise it exhibits nothing distinctive. There can be
no doubt that we have in the hyper-acidity which Riegel’s 128 observa-
tions have connected with this condition in a large number of instances,
a fact of the highest clinical significance. It may be estimated accu-
rately by the method detailed at p. 135, or by titration. The proportion
of hydrochloric acid in the stomach in a case of chronic gastric ulcer is,
according to Riegel, o.4—0.6 per cent., as against O.1-0.2 per cent. in
health.129 It must be mentioned, however, that the researches of Ewald,
Ritter and Hirsch, and Jaworski'®° go. to show that the increased
acidity in connection with round ulcer of the stomach may undergo
diminution with the further progress of the disease.

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148 THE GASTRIC JUICE.

According to Lenhartz! acid may be deficient in gastric ulcer. The
digestion of carbohydrates is accomplished slowly. There is still need
to verify these assertions by the application of trustworthy methods,
such as those described at pp. 133, 136, and especially with reference to
the precautions enjoined in a previous paragraph (p. 137). The conflict-
ing statements quoted here must be in part referred to the want of
such accurate observation.

The presence of blood, and its character, are facts of great significance.

1. When the hemorrhage is considerable, clots of blood are found,
which are not at all, or but slightly changed.

2. More commonly the effused blood remains for a longer time in
contact with the gastric juice, and is thereby altered in such a way that
the oxyhemoglobin is converted into hematin, and the vomit has the
appearance of coffee-grounds.

When examined under the microscope in such a case, no blood-cor-
puscles whatever are to be seen in it, but in their place larger or smaller
pigment masses. The blood may best be identified as such by Tezch-
manns hemin test and by the spectroscopic appearances of hematin.
To obtain the latter, a portion of the vomit should be treated with
caustic potash, filtered, and then examined with the spectroscope for the
spectrum of hematin in alkaline solution (fig. 39).

It should be borne in mind that the exhibition of preparations of iron
will impart to the vomit the same appearance as that due to blood; so
also will the abundant partaking of red wine ; and finally, the presence
of bile-pigment may cause it to assume a brownish-black colour.

Large quantities of blood (blood-pigments) may be found in the vomit
in cases of duodenal ulcer with hemorrhage into the intestine.

4. Carcinoma of the Stomach.—The physical and microscopical
character of the vomit in cases of cancer of the stomach are, in general,
those of gastric ulcer. Sarcine in large quantities are a remarkably
frequent manifestation. The blood is very seldom discharged unaltered,
and it is usually represented only by colouring-matter.

The chemical constitution of the gastric juice in cases of cancer has
been made the subject of research by many observers, van der Velden
(p. 130), Uffelmann (p. 132), Hwald,? and Kredel ;!3 also by v. Mering
and Cahn (p. 133); and more especially by Riegel (p. 131), Korczynsk,
and Jaworski.84 Absence or diminution in quantity of hydrochloric
acid is a point of special interest, and has been recently studied by
many investigators. 18°

The author has analysed the contents of the stomach in a great
number of cases of cancer, and he has found that in many no trace of
free hydrochloric acid could be shown by the colour-tests employed for
the purpose. He has had seventeen cases of cancer under observation

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DILATATION OF THE STOMACH. 149

during the last two years. Either the vomit or the gastric juice with-
drawn after the administration of a test meal—usually of milk or ham—
was repeatedly examined. In fourteen out of the seventeen cases the
reaction with Congo-paper, benzo-purpurin, and Gunzburg’s test, was
either absent or very feebly evinced. The total acidity was also very
low, ranging from 48-4, and the higher figure was obtained in only one
instance. In one case, where the gastric juice was examined an hour
after the administration of half a litre of milk, no result was obtained
by the method described on p. 135, while the same method applied to
the gastric juice of a healthy person under like conditions showed
0.0301 grm. HCl in roo ce. In three cases of cancer the acidity was
remarkably high, viz., 90, 100, 126, and all the tests for free HCl gave
decided results. The experiences of O. Iosenbach and Waetzhold 1%
have been similar to these. The absence of hydrochloric acid, however,
is by no means so constant as to warrant an absolute diagnosis on this
ground alone. Moreover, in other conditions, such as amyloid degenera-
tion of the gastric mucous membrane,!*” in stagnation of the contents of
the stomach, in diabetes,!*8 and in the febrile state, even without demon-
strable disease of the stomach,!? the hydrochloric acid reactions may
also fail.

Aceording to Wolfram, the gastric juice is devoid of HCl in the
course of the infectious fevers, whereas in chronic febrile disorders it is
of quite normal character. Taken, however, in conjunction with the
other clinical symptoms of cancer, we have in this circumstance impor-
tant evidence of the disease. Riegel points out the important fact that the
gastric juice in this affection has entirely lost the digestive property.
Concerning the secretion of pepsin in carcinoma, it would appear that
this, as well as the milk-curdling ferment, are secreted to the end. The
tests for pepsin are described at p. 126, and its quantitative estimation
may be effected by #. Schiitz’s method.

5. Dilatation of the Stomach.—The character of the gastric
contents in this condition is subject to variety, according to the cause
of the dilatation. Nevertheless, there are certain general features which
belong to all cases, and these will be considered first. The remnants of
undigested food are visible many hours after a meal. Microscopically
there is a profusion of micro-organisms of all kinds, and yeast-forms are
rarely absent. Chemical analysis usually discloses an excessive proportion
of volatile fatty acids.

In dilatation from chronic gastritis the contents partake of the
character of the latter disease.

When the primary condition is pyloric stenosis, with gastric ulcer
physiologically active HCl is present in great excess. In one case the
author found that the unfiltered gastric juice withdrawn in the morning

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150 THE GASTRIC JUICE.

before food had been taken contained 0.4629 grm. HCl to roo ce. ; and
when the stomach had been thoroughly washed out, and milk admini-
stered, the gastric juice examined half-an-hour afterwards contained
0.1374 grm.

In dilatation from cancer of the pylorus free HCl is either absent or
diminished in quantity. This is true also of dilatation with atrophy of
the stomach, but the rule is not without exceptions.

6. Parasitic Affections of the Stomach.—(a.) In but one
instance as yet—a case of favus—have the characteristic appearances
of this condition been detected in the stomach (Kundrat).

(b.) Extensive patches of thrush are sometimes formed in the stomach,
and in such cases the vomit contains masses of the thrush fungus
(p. 85).

7. Croup and Diphtheria.—It very rarely happens that a croup-
ous or diphtheritic condition of the mucous membrane extends from the
upper part of the alimentary canal as far as the stomach. When it is
so, the vomit exhibits the appearances described at p. 88.

8. Fecal Substances in the Vomit.—Formed masses of faces
are never discharged by the mouth, but in cases of occlusion or partial

 

paralysis of the intestine, its contents may become mingled with those
of the stomach, and brought up with the vomit, which then has an
intensely feeculent odour, a yellowish-green colour, and a feebly acid or
alkaline reaction. When derived chiefly from the small intestines the
vomited matter will contain bile acids and pigment, and abundance of
fat. These may be detected by chemical examination. Microscopically
it shows nothing distinctive ; but on one occasion the author found in
such a discharge a quantity of large fungi which closely resembled the
comma-bacillus (fig. 70).

9. Pus.—In rare cases pus occurs in the vomit. It indicates sup-
puration in the walls of the stomach, or the rupture into it of an abscess
from some neighbouring viscus.

10. Animal Parasites.—Amongst the Entozoa, Ascaris lumbri-
coides, Oxyuris vermicularis, and Anchylostoma duodenale have been
obtained from the stomach. Other worms, such as Trichina, are excep-
tional manifestations, and the hooklets of Echinococcus and hydatid
cysts are occasionally present. Gerhardt has found dipteral larve
in the secretion, where they give rise to the symptoms of gastritis.
Similar observations have been made by Senator,? Hildebrandt,'** and
Iinlayson.

11. Constitution of the Vomit in Poisoning.**

1.. Poisoning with Acids.—In all cases of poisoning with strong
mineral or organic acids, the vomit acquires a powerfully acid reaction.
It displays a blackened mass of altered blood and charred tissues in

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CONSTITUTION OF THE VOMIT IN POISONING. 15.

cases where the quantity of the poison has been sufficient to cause these
effects. The appearance presented in all cases of poisoning with strong
acids is the same. To distinguish one from the other in the contents of
the stomach, the sense of smell will serve in some instances, as, @.g.,
for acetic acid, while in others resort must be had to the methods of
analytical chemistry. It is important in certain cases to remember that
the vomit may contain an abnormal proportion of organic and inorganic
(hydrochloric and lactic) acids, altogether independently of poisoning.

(a.) Detection of Sulphuric Acid.—The presence of sulphuric acid may
be ascertained thus :—The vomit is mixed with a large bulk of distilled
water, and put aside for several hours, during which it is frequently
stirred. It is then filtered, and the precipitate repeatedly washed with
water on the filter. The filtrate is then collected, and evaporated on the
water-bath until the fluid begins to blacken. It is then allowed to cool,
mixed with twice its bulk of alcohol, and, after standing for some hours,
again filtered. The filtrate, diluted with water, is once more evaporated
on the water-bath until the alcohol is entirely driven off. The fluid
remaining may then be tested for sulphuric acid. The addition of
chloride of barium solution or of lead nitrate should give a white pre-
cipitate, showing the presence of sulphuric acid or its salts.

(b.) Detection of Nitric Acid.—The vomit, which is generally stained
somewhat of a yellow hue from the formation of xanthoproteic acid,
is mixed with water, boiled, and filtered. The reaction of the filtrate is
tested, and if found to be acid, it is neutralised with caustic potash, and
evaporated to a small bulk. When allowed to cool, it should deposit
erystals of nitrate of potash, which will give the following reactions :—

1. To asolution of the crystals concentrated sulphuric acid is added,
and when the mixture is quite cool, a little sulphate of iron solution is
poured upon its surface. At the point of contact of the two fluids, a
deep brown zone shows the presence of nitric acid. The test is appli-
cable only where the brown coloration is not obtained with sulphuric
acid alone.

2. A solution of brucin in sulphuric acid is placed in a test-tube,
and a little of the fluid supposed to contain nitric acid is poured on its
surface. At the point of contact of the two, a red coloration takes
place if nitric acid is present.

The modes of testing for hydrochloric acid have already been given
(p. 129).

(c.) Oxalic Acid.—The contents of the stomach are partially evapo-
rated and extracted with alcohol, the alcohol evaporated, and the residue,
dissolved in water, is treated with acetic acid and solution of chloride of
calcium. A precipitate of oxalate of calcium forms, and the character-
istic crystals may be distinguished by the microscope.

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152 THE GASTRIC JUICE.

2. Poisoning with Alkalies.—The vomit in such cases is a viscid,
glistening, and strongly alkaline fluid. Where a concentrated solution
of a caustic alkali has been taken, the ejected tissues are charred and
brown, as in the case of acids. The determination chemically of the
character of the poison is often attended with great difficulty, and in
other instances, again, it is very easy.

Where ammonia has been taken, the vomit, if examined immediately
after the poisoning, will emit the characteristic odour of that body, and
further evidence of its presence may be obtained by holding over the
fluid a glass rod moistened with hydrochloric acid, when fumes of sal-
ammoniac will be given off. The detection of caustic potash and of
caustic soda, on the other hand, involves much difficulty on account of
the readiness with which they are converted into their carbonates.

The process for the detection of chlorate of potash in the vomit de-
mands a special notice. £. Ludwig’s!4* method is as follows :—The
vomit, if not already acid, is rendered slightly so by the addition of
acetic acid, heated and maintained for one minute at the boiling-point,
filtered, the filtrate evaporated to a small bulk on the water-bath, and
allowed to settle undisturbed. The salt then separates in the form of
crystals, which are dried between folds of blotting-paper and tested in
the following manner :—

1. They are treated with dilute hydrochloric acid and warmed ; the
fluid assumes a greenish-yellow colour, and chlorine gas is evolved. The
reaction may be obtained at ordinary temperatures by the addition of
strong hydrochloric acid.

2. The crystals are dissolved in water, or, where none have been
deposited, the liquid is evaporated and a solution of indigo and dilute
sulphuric acid is added. If chlorate of potash be present, on the further
addition of a watery solution of sulphurous acid or hyposulphite of soda,
the fluid changes from blue to yellow, or altogether loses its colour.

8. Poisoning with Metals and Metalloids.—(a.) Poisoning with
Salts of Lead.—After the lapse of a few hours, a quantity of grey or
blackish-grey substance is vomited. For the detection in this of com-
pounds of lead, it should be partially evaporated on the water-bath, and
organic matter decomposed by treatment with reagents.

For this purpose 4. Ludwig !45 recommends the process of Fresenius
and Babo :—The vomit is placed in a large porcelain dish, mixed with
about its own weight of a 20 per cent. solution of hydrochloric acid, and
3 to 5 grms. of chlorate of potash added, when the vessel is covered
and allowed to stand for about twelve hours. The mixture is then
heated to 60° in the water-bath. When the evolution of gas has ceased,
more chlorate of potash is added to the brown mass, and this process
is continued until the fluid ceases to form a brown colour. Should

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POISONING WITH METALS AND METALLOIDS. 153

the fluid become unduly concentrated, it should be further diluted with
water. If in this way the organic material is not entirely decomposed,
hydrochloric acid must be again added, and the requisite quantity of
chlorate of potash supplied as before. The mixture is then evaporated
on the water-bath until the odour of chlorine is no longer perceived,
when it is diluted with twice its bulk of water, passed through a filter
which has been moistened with water, washed with a large quantity of
water, and the washings finally collected and added to the filtrate. To
the fluid so obtained sulphuretted hydrogen is added to saturation. The
resulting dark precipitate is then filtered off, washed with sulphuretted
hydrogen water, dried, and dissolved in nitric acid in the following
manner :—It is placed in a porcelain dish, and pure (chlorine free)
nitric acid is added in drops until the whole has the consistence of a
thin fluid, when it is evaporated to dryness on the water-bath, and the
residue dissolved in boiling water and filtered. A white insoluble
residue of sulphate of lead may remain. This may be reduced to
metallic lead by the addition of soda and combustion on charcoal in
the reducing zone of a blow-pipe flame.

The addition of sulphuric acid will cause the formation of a azhzte
precipitate of sulphate of lead, and chromate of potash will give a
yellow precipitate if lead be present.

The quantitative estimation may be effected in the same way.

Salts of lead in the vomit may be detected by another very simple
process :—A strip of magnesium, free from lead, is placed in the fluid,
when metallic lead will be deposited upon it, and can then be dissolved
in nitric acid, and subsequently proceeded with as above.

(b.) Poisoning with Salts of Mercury.—Poisoning with compounds
of mercury is very often attended with vomiting. The vomit in such
cases differs greatly according to the strength of the poison. When
large quantities of corrosive sublimate have been taken, pain is expe-
rienced in the region of the stomach, and shreds of tissue stained brown
with hematin are apt to be discharged in the vomit.

The salts of mereury may be detected in the vomit in the same manner
as the compounds of lead. Sulphide of mercury is formed in the pro-
cess, and from this the metal is obtained thus:—To the precipitate
carbonate of soda and cyanide of potassium are added, the mixture dried,
placed in a test-tube and heated, when the metal is sublimed in the
upper part of the tube.

The presence of mercury in the vomit may be shown directly as
follows :—Granulated zine (£. Ludwig) 4° or brass wire (Mirbringer) 16°
is placed in the substances to be examined, which have been previously
acidulated with hydrochloric acid; the mixture heated for an hour in
the water-bath, and exhausted first with water and then with alcohol,

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154 THE GASTRIC JUICE.

and finally washed with ether and allowed to dry in the air. The brass
wire is then placed in a test-tube and heated, when the metal is de-
posited on the sides of the tube. If now, while the test-tube and it’
contents are still hot, a small piece of iodine be introduced, the vapour
of iodine given off will change metallic mercury into mercuric iodide
with the development of a beautiful red colour (Schneider)! In a
similar manner, mercury obtained by other methods may be converted
into mercuric iodide. If, at the same time, the vomited matter contains
an abundance of organic substances, it will be necessary to remove the
latter by Fresenius and Babo’s method before introducing the granulated
zinc or brass-foil.

It should be mentioned that in the distillation of the suspected vomit,
metallic mercury may pass over with the watery vapour (Lecco 1°), and
it may also form from the reduction of corrosive sublimate in the process
of distillation.

(c.) Poisoning with Salts of Copper.— When sulphate of copper has
been taken, it imparts a greenish-blue tint to the vomit. In poisoning
with the copper salts of acetic acid (verdieris, the commonest form), the
green colour may be present, or there may be nothing distinctive in
the appearance of the gastric contents. The recognition of the poison
may be effected by the process described under (a.) Poisoning with Lead
Salts. The sulphide of copper so obtained is dissolved in nitric acid,
when the presence of the metal will be shown by the blue colour of the
solution, which becomes deeper on the addition of ammonia. If the
latter reagent causes a precipitate to fall, the fluid is filtered and the
filtrate acidulated with hydrochloric acid. A portion of the filtrate is
treated with yellow prussiate of potash, when a reddish-brown precipi-
tate forms. In another portion a piece of iron-foil is placed, and after
a little while the metallic copper present is deposited on its surface as a
red coating.

It must not be forgotten that traces of copper occur in every organ.

(d.) Arsenic Poisoning.—The administration of large doses of arseni-
ous acid, Fowler’s solution, or of certain mineral waters abounding in
arsenic (such as those of Roncegno and Levico), is followed after a
short interval by the vomiting of a copious fluid deeply stained with
bile. Where arsenious acid (white arsenic) is the poison in question,
a careful naked-eye and microscopical examination of the vomit will
often afford accurate information as to its nature. In such a case, larger
or smaller particles of this substance are usually to be seen. When
these white. particles are removed with forceps, freed from other impu-
rities by repeated cleansing, washed with cold water, and dissolved in
a test-tube containing a small quantity of boiling water and then

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ARSENIC AND PHOSPHORUS POISONING. 155

allowed to cool, crystals of arsenious acid separate and may be recog-
nised microscopically as small octahedral forms. When the crystals
are heated with soda on a piece of carbon in the reducing zone of the
blow-pipe flame, the characteristic odour of garlic is evolved, and if a
specimen be heated with carbon in a test-tube, a metallic deposit forms
in the upper cool part of the tube.

A more accurate method is to remove organic substances with chlo-
rate of potash and hydrochloric acid, then to heat the remaining fluid
for a long time at 60° with sulphuretted hydrogen. A yellow preci-
pitate of sulphide of arsenic forms. This is dissolved in sulphide of
ammonium, filtered, the filtrate evaporated to dryness, allowed to cool,
some drops of concentrated nitric acid added, heated with more nitric
acid until the evolution of gas has ceased and reddish-brown fumes are
no longer given off. The fluid is then concentrated to a small bulk in
the water-bath, diluted with a little water, and treated with sodium car-
bonate until its reaction is distinctly alkaline. It is then evaporated to
dryness on the water-bath ; the dried residue is fused with a quantity of
carbonate and nitrate of sodium, allowed to cool, several times exhausted
with water, and filtered. The filtrate is repeatedly treated with small
quantities of dilute sulphuric acid until effervescence has ceased, when
more sulphuric acid is added, and the fluid evaporated first on the
water-bath and afterwards over a flame until white fumes are given off.
The residue is then allowed to cool and is dissolved in cold water. Zinc
and sulphuric acid, both free from arsenic, are placed in an apparatus
for generating hydrogen.¥? The hydrogen set free is purified and dried
by being passed through a tube which is fitted to the apparatus, and
contains solid caustic potash and granular chloride of calcium. To the
first tube is adapted, by an air-tight connection, another tube con-
stricted in two or three places and terminating in a point. When all
the air has been driven out, the hydrogen escaping from the point of
the terminal tube is ignited, and then the fluid to be tested is poured
into the apparatus. The tube is next heated in front of the place
where its calibre begins to diminish, and if arseniuretted hydrogen is
mixed with the hydrogen gas evolved, metallic arsenic is deposited in
the constricted portion.

A further test is as follows:—The flame is extinguished and the gas
conducted into a solution of nitrate of silver. A blackish-grey precipi-
tate of metallic silver separates, and the filtrate, on the careful addition
of ammonia, will give a further yellow deposit of arsenite of silver.

(e.) Phosphorus Poisoning.—Poisoning with phosphorus is always
attended with persistent and severe vomiting, which may last for
whole days. The discharged substances are free from blood, shreds
of tissue, and the other signs of a formidable organic lesion. When

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156 THE GASTRIC JUICE.

solid phosphorus in large quantity has been taken, the gastric contents
emit the characteristic odour of phosphorus and are luminous in the
dark, It should be noted, however, that these properties are lost in
presence of alcohol, oil of turpentine, and chloroform.

For the detection of phosphorus, the vomit is distilled with sulphuric
acid in the dark, and the retort connected with a glass condenser
(Mitscherlich). The presence of the poison is shown by the appearance
of luminous rings where the phosphorus fumes come in contact with the
cold water.

Scherer has also devised an admirable method for this purpose. The
vomit is enclosed in a flask provided with an air-tight stopper, and two
test-papers—one saturated with nitrate of silver and the other with
acetate of lead—are placed in it. Jf phosphorus be present, the first of
these will be blackened, whilst the other remains unchanged.!4

4. Poisoning with Alkaloids.*—(a.) Morphia Poisoning.—The
earlier stages of poisoning with morphia are generally attended with
vomiting, and in all cases where it has been taken by the mouth, the
alkaloid can be detected in the ejected contents of the stomach. Alt 1°
has shown that, even when it has been injected subcutaneously, the
drug will be found in the stomach about an hour afterwards. In such
a case, therefore, the stomach should be washed out, and the washings
tested for morphia. The Stas-Otto method °° for its separation may be
employed. In this, the vomit is placed in a flask, and digested with
alcohol and tartaric acid on the water-bath, allowed to cool, and filtered ;
the alcoholic extract is heated on the water-bath at a moderate temperature
(60°) until the spirit is entirely driven off, when the remaining watery
solution is filtered. The new filtrate is evaporated to a syrupy consis-
tence on the water-bath, and the residue extracted with alcohol. In
doing this, the latter should be cautiously added, little by little, until
a flocculent precipitate forms, and then in greater quantities until no
further turbidity occurs. The alcoholic solution is then filtered, and the
filtrate evaporated on the water-bath and dissolved in a little water.
The still acid watery solution is next shaken up with ether, in order
to eliminate other alkaloids and resinous substances, after which it is
rendered alkaline with caustic potash, and again shaken up with ether.
Any nicotin and atropin present (see below) are dissolved in this way.
The residue is treated with sal-ammoniac and repeatedly extracted with
warm amylic alcohol, which takes up morphia. The amylic alcohol
extract is next collected, filtered, and evaporated to dryness on the water-

* In this connection we shall consider only such alkaloids as are most frequently
the subject of investigation by the physician. For more detailed information on the
entire subject, the text-books of F. C. Schneider, J. Otto, Kobert, and E. Ludwig may
be consulted.

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POISONING WITH ALKALOIDS. 157

bath. The residue is dissolved in acidulated water, which is repeatedly
added for the purpose. It is then filtered, extracted with amylic alcohol,
neutralised with ammonia, and again extracted with warm amylic alcohol,
which is driven off by evaporation. Finally, the residue may be tested
thus :—

1. To one portion a freshly prepared solution of molybdate of soda
and concentrated sulphuric acid (1 cc. sulphurie acid and 5-10 grms. of
molybdate of soda—Fdhde’s reagent) is added. If morphia be present,
the fluid turns first violet, and, changing through blue and green, becomes
finally a pale red.

2. Another portion is dissolved in water acidulated with hydrochloric
acid, evaporated on the water-bath to dryness, and treated with a few
drops of a very dilute solution of perchloride of iron, which should be

Sree from hydrochloric acid. A blue colour shows the presence of
morphia.

An acid-free solution of perchloride of iron may be best pre,ared by dissolving
the sublimated silt in water (Ludwig).

(b.) Poisoning with Nicotin.—Vomitine frequently occurs in this
condition, and the poison may be separated from the gastric contents by
the Stas-Otto method. The alkaloid is extracted with ether from the
alkaline solution of the evaporation residue (vide supra), and when the
ether is driven off at a low temperature (30° C.) on the water-bath,
nicotin remains as a brown or yellow mass. If this be dissolved in
zther and an ethereal solution of iodine added, an oily substance forms,
from which ruby-red needles (2ouwssin’s crystals) slowly separate.

(c.) Poisoning with Atropin.—In atropin-poisoning with the pure
alkaloid, whether taken by the mouth or administered subcutaneously,
vomiting rarely occurs; but it is a frequent event in poisoning with the
berries of the deadly nightshade. Under sucli circumstances, the con-
dition is usually rendered evident by the discovery of the berries in the
ejected substances, together with the clinical symptoms (mydriasis, &c.).
If there should be any doubt as to the character of the toxic agent,
recourse may be had to the Stas-Otto method, when the alkaloid will be
taken up by ether from an alkaline solution of the residue, and may be
recognised by the following tests. The ether being driven off :—

1. A portion of the residue dissolved in water, to which a trace of
acid has been added, is dropped upon the conjunctiva of an animal (cat
or rabbit). After the lapse of from 6-20 minutes paralysis of the
sphincter fibres of the iris ensues, and the pupils are widely dilated :
0.01 merm. of atropin suffices to produce this effect.

2. A specimen of the residue is dissolved in a few drops of fuming
nitric acid, and the solution evaporated on the water-bath : a colourless

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158 THE GASTRIC JUICE.

substance remains, and this, when allowed to cool, and subsequently
treated with alcoholic solution of caustic potash, turns first violet, and
afterwards a cherry-red colour.

(d.) Poisoning with Ptomaines and Toxalbumins.'°*—The ingestion
of putrid flesh is occasionally attended with severe symptoms of poison-
ing, and there can be no doubt that in many cases of so-called acute
gastritis, where the use of certain articles of diet—such as liver, kid-
neys, and oysters—has been followed by nausea, vomiting, and profuse
diarrhoea and a retarded pulse, the true cause is to be found in the toxic
effects of ptomaines and toxalbumins. To the same category may be
referred the conditions known as ammoniemia (retention-toxicosis,
v. Jaksch,° see Urine), and the cerebral symptoms (coma carcinoma-
tosum, v. Jaksch °°), which sometimes develop in the course of cancer.!®1
The poisonous substances are probably diamines and toxalbumins, which
are known to be formed in these processes. Further research is needed
for the elucidation of this subject, and in questionable cases the vomit
should be tested for ptomaines. In doing this, the observer should be
euarded in his conclusions, since peptone (which is normally a con-
stituent of the gastric contents) is known to yield toxic substances of an
alkaloid nature.

In view of the great importance which the study of these bodies has
acquired of late years, and also because it enters into the pathology of
other secretions besides that now under consideration, the subject is
dealt with here at some length. The references, which are omitted, will
be found in Brieger and the other authorities quoted.

The Stas-Otto method may be employed for the separation of
ptomaines from the vomit. Such of these bodies, however, as have
yet been distinguished exhibit a very remarkable variety in respect of
their chemical character. Some may be derived by extraction with
ether from an acid, others from an alkaline medium, whilst a third class
is distinguished by the fact that its members are soluble only in amylic
alcohol, chloroform, or benzol. Others again are insoluble in amylic
alcohol. It will be seen from this that the application of the Stas-Otto
process must be supplemented by extracting the derived substances with
various media, and even then it will sometimes happen that the effort
is attended with failure.

For such cases Brieger’s method? may be employed. This is briefly
as follows :—If the material to be examined contains solid substances,
these are first reduced to small particles; sufficient hydrochloric acid is
then added to render the whole feebly acid, and the mixture boiled for
a few minutes and filtered. The filtrate is evaporated, at first over a
flame, and subsequently on the water-hath, until it has attained a syrupy
consistence. It may be noted, however, that in view of the instability

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ANIMAL ALKALOIDS. 159

- of the bodies sought, it is advisable to evaporate in vacuum, and at the
lowest possible temperature (v. Jaksch)—a precaution which, as Brieger 1°
suggests, should also be taken where foul-smelling substances are the
subject of manipulation. The thick fluid is mixed with 96 per cent. of
alcohol (filtered), and the filtrate treated with warm alcoholic solution
of acetate of lead. The lead precipitate which forms is now filtered off,
and the filtrate concentrated—here again preferably in vacuum—to the
same consistence as before, when it is again taken up in 96 per cent. of
alcohol. The alcohol is driven off by evaporation, and the residue, dis-
solved in water, is freed from lead by the addition of sulphuretted
hydrogen and filtering. The filtrate is acidulated with a little dilute
hydrochloric acid, and concentrated (in vacuum) to the consistence of
syrup. It is then diluted with alcohol, and alcoholic solution of mer-
curic chloride added. The resulting precipitate is boiled in water, and
certain ptomaines may separate at this stage in consequence of the
different solubilities of the double salts of mercury. The better to
secure this, the precipitate may be treated successively with water at
various temperatures. Should it be thought that the lead precipitate
may have retained some of the ptomaines, it may be suspended in water,
the lead converted into its sulphide, and the fluid treated in the manner
just described.

The solution obtained as above is filtered, and the filtrate, already
freed from alcohol and mercury, is evaporated, the hydrochloric acid
all but completely neutralised with sodium carbonate, and the residue
again extracted with alcohol, after which it is dissolved in water,
neutralised with soda, again acidulated with nitric acid, and precipitated
with phosphomolybdic acid. The double phosphomolyhdate is filtered
off and decomposed by neutral acetate of lead—an object attained more
readily by the application of heat on the water-bath. The lead is then
removed by means of sulphuretted hydrogen, and the fluid concentrated
and treated with alcohol. Several ptomaines are thus separated as
hydrochlorates, and may be obtained in the form of double salts of gold
or platinic chloride and of picric acid. From these the hydrochlorates
are again derived by precipitation with sulphuretted hydrogen; and in
the case of the picric acid compounds, extracting with water, acidulating
with hydrochloric acid, and finally removing the picrie acid by shaking
it up with ether.

The next step is to ascertain if any ptomaines remain in the phos-
phomolybdic acid filtrate after the precipitation of phosphomolybdic
acid.

The above is a mere sketch of the process, which, moreover, needs to
be modified in many instances.

For the detection of the basic compounds which occur in the secre- -

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160 THE GASTRIC JUICE.

tions as diamines, the best method is that of Bawmann and v. Udransky,
in which these bodies are converted into their benzoic compounds by the
action of benzoyl chloride and caustic potash. By this means these
observers discovered cadaverin (pentamethylendiamine) in the urine,
and established the identity of Brieger’s putrescin with tetramethyl-
endiamine 164 (see chapter on the Urine).

Ptomaines (animal alkaloids) yield the characteristic reactions of
alkaloids ; but otherwise they are not known to possess any distinctive
chemical or physiological properties. :

The characteristic reactions which are common to all the alkaloids are the
following (Otto, £. Ludwig).6 With—

1. Iodine and iodide of potassium solution, a brown flocculent precipitate ; most
readily obtained from the solution of the alkaloid which has been acidulated with
sulphuric acid.

2. Mercuric and potassium iodide, a white or yellow precipitate, insoluble in
water and dilute acid.

3. The iodide of bismuth and potash, an orange precipitate in a solution acidu-
lated with dilute sulphuric acid.

4. Phosphomolybdic acid, a bright or brownish yellow precipitate, insoluble in
water and dilute mineral acids.

5. Metatungstic and phosphotungstic acids, a white flocculent precipitate, with
difficulty soluble in water and diluteacid. (This, according to LZ. Ludwig, affords
a particularly sensitive test.)

6. Tannin, in neutral or feebly acid solutions, a yellow or white precipitate.

7. Platinic chloride, a whitish-yellow or citron precipitate, which is sometimes
readily soluble in water, and but slightly so in alcohol.

8. Chloride of gold, a yellow or whitish-yellow precipitate, which may be amor-
phous or crystalline.

The animal alkaloids already distinguished as occurring in the human
system are sufficiently numerous. They have been detected in the
feeces, the urine, and the milk, and they will find appropriate notice
under the separate headings in this work. They are known by their
effects both in health and disease, and, in many instances, have been
separated as definite bodies from the secretions. Such products result
from the decomposition of articles of food. Thus Vaughan 1 obtained
one of these bodies (tyrotoxin) from rotten cheese and bad milk, and he
supposes that the substance in question is diazobenzol. Ehrenberg 168
found a similar body in putrid sausages. Special mention should be
made also of ptomato-atropin, a basic compound, which has been dis-
covered in the latter food. In all cases where the clinical symptoms are
those of poisoning, and include severe vomiting, the methods described
above may serve to elucidate the matter ; but it should not be forgotten,
meanwhile, that the presence of peptone may be a source of ambiguity,
since it may yield similar poisons. If the vomit or secretion is to be
tested for toxalbumins, Brieger and Frankel’s process 1 may be used.

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ETHYLIC ALCOHOL—CHLOROFORM. 161

5. Poisoning with Ethylic Alcohol.—In acute poisoning with
alcohol (ethylic aleohol), the vomit emits the characteristic odour of that
substance. For its more accurate recognition, the gastric contents are
first diluted with water, and, if very acid, carefully neutralised with
caustic potash, and then distilled by steam.

The distillate may then be submitted to the following tests :—

1. Toa portion a few drops of benzoyl chloride and a little caustic
potash are added. When the mixture is heated and again allowed to
cool, the presence of alcohol is shown by the characteristic odour of
benzoylethylic ether (Berthelot)!

2. With a small portion an equal volume of concentrated sulphuric
acid is cautiously mixed, a little powdered sodium acetate added, and
the mixture heated. The characteristic odour of acetic ether shows the
presence of alcohol (Otto, Z. Ludwig).™

6. Poisoning with Chloroform.—Chloroform may he detected
either directly in the vomit or in the fluid obtained from its distillation.
In either case, the following reactions will disclose its presence :—

1. A little thymol dissolved in caustic potash is added to the fluid to
be tested, and the latter is then heated. If chloroform be present, the
preparation assumes a dark violet tint (Vital/ 1"), and if B-mnaphthol be
used instead of thymol, a blue colour results (Lustyarten).1°

2. A few drops of alcoholic solution of caustic potash and a little
aniline are heated with the distillate of the gastric contents. If chloro-
form be present, isocyanphenyl] is formed, and may readily be recognised
by its unpleasant odour (Hofmann).

In a case of poisoning with chloroform, where the drug was taken by
the mouth, the author was unable to find any trace of it in the sub-
stances vomited three hours afterwards, although the toxie symptoms
were well marked.

7, Poisoning with Carbolic Acid.—When a poisonous dose of
carbolic acid has been administered by the mouth, the vomit usually
emits the characteristic odour of that substance. The presence of
carbolic acid in the ejected substances may be ascertained directly by
the following tests :—

1. Bromine water yields with a fluid containing carbolic acid a yellow
crystalline precipitate of tribromophenol.

2. A solution of perchloride of iron colours dark violet in presence
of carbolic acid.

In testing for these reactions, it is well previously to filter the vomit,
if necessary washing it upon the filter with water. If the reactions
are not obtained in this way, the filtrate is distilled with a little sul-
phuric acid, and both tests are again applied to the distillate.1”*

It is to be borne in mind that carbolic acid may form in considerable

L
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162 THE GASTRIC JUICE.

quantity in the intestine in certain morbid states, and may then, as in
intestinal obstruction, find its way into the vomit. (See chapter on the
Urine.)

8. Poisoning with Nitro-Benzol and Aniline. —(a.) Nitro-
Benzol.—The presence of nitro-benzol in the vomit may be detected
frequently by the characteristic odour, which resembles that of the oil
of bitter almonds. To separate this substance from the gastric contents,
the latter is distilled with a little sulphuric acid. The distillate will
contain oily drops, which are soluble in ether. Aniline may be derived
from nitro-benzol by the addition of granular zine and dilute hydro-
chloric acid. When reduction is effected in this way, the fluid is ren-
dered alkaline with caustic potash, and the aniline formed is extracted
with ether. The oily residue after the expulsion of the ether will yield
the following reactions :—

1. If the aniline solution be treated with hydrochloric acid, and a
shaving of pine-wood be placed in it, the latter assumes a deep yellow
colour.

2. A drop of the oil is suspended in water, and a few drops of dilute
solution of chloride of lime or of a very dilute solution of sulphide of
ammonium added: the fluid assumes a rosy-red colour (Jacquemin).1

3. A very sensitive test is that of H. Ludwig :17°—A watery solution
of aniline colours a dark blue on the addition of a watery solution of
carbolic acid and hypochlorite of soda; and this colour changes to red
on the further addition of hydrochloric acid.

4. The isocyanphenyl test serves well for the detection of aniline
formed in the decomposition of nitro-benzol. It was introduced by
A, Flickiger *” as a test for acetanilide (antifebrin). To the fluid under
examination a few drops of caustic potash and chloroform are added.
It is then shaken up and heated, and when again allowed to cool, should
emit the disagreeable odour of isocyanphenyl.

(0.) Aniline.—Poisoning with aniline also is often attended with
vomiting. The vomit is diluted with water, and distilled with a little
sulphuric acid. The distillate is extracted with ether, and when the
latter has been driven off by evaporation an oily substance remains,
to which the above tests (1 to 4) for nitro-benzol may be applied.

9. Poisoning with Prussie Acid.—This condition may usually be
recognised by the characteristic odour of oil of bitter almonds. For the
detection of the poison the vomit is treated with a small quantity of
tartaric acid, and distilled. Hydrocyanic acid passes over with the
distillate. From its presence, however, poisoning with the drug is to
be inferred only when it can be ascertained that the vomit is free from
innocuous double salts of cyanogen, as, for instance, the yellow or red
prussiate of potash.

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PRUSSIC ACID. 163

The best test is to add solution of ferric chloride and sulphate of iron
to a little of the filtered fluid. With this last reagent yellow ferro
cyanide of potassium gives a white precipitate, which soon changes to
a bright blue, while with the perchloride of iron it forms a Prussian-
blue precipitate. Red ferricyanide of potassium gives a dark blue preci-
pitate with sulphate of iron, and a deep brown coloration with the
perchloride. Should both the above-mentioned substances be present,
the following process may be applied :!’’—The fluid is acidulated with
sulphuric acid, and treated with an excess of carbonate of lime. The
corresponding lime-salts take the place of ferro- or ferri-cyanide of
potassium, and only so much hydrocyanie acid as is not combined in
the double salts of cyanogen passes over with the distillate. The latter
is then tested for hydrocyanic acid in the following manner :—

1. To a few cc. rendered alkaline with caustic potash, a few drops of
a freshly-prepared solution of cupric sulphate are added ; the mixture is
heated, maintained for the space of one minute at boiling-point (Ludwig),
and allowed to cool. It is then rendered strongly acid with hydrochloric
acid. A blue coloration of the fluid results, and when allowed to stand
for some time, a flocculent Prussian-blue precipitate settles in it.

2. To a few drops of the distillate a yellow (holding poly-sulphide of
ammonium) solution of sulphide of ammonium is added, and the mix-
ture boiled until the yellow colour entirely disappears. It is then
allowed to cool and perchloride of iron and hydrochloric acid added.
If hydrocyanic acid be present, the preparation assumes a red colour
(sulphocyanide of iron). #. Ludwig' applies this test in a different
manner :—The fluid is treated with yellow solution of sulphide of ammo-
nium in excess, a few drops of caustic potash added, and the mixture
evaporated to dryness. The residue is exhausted with water, treated
with hydrochloric acid, and filtered. The filtrate is then tested with
solution of perchloride of iron, when a blood-red colour should develop.

3. Another very admirable test has lately been suggested by Vort-
mann.189 To the fluid to be tested a few drops of nitrite of potash are
added, and then two to four drops of the solution of perchloride of iron,
and finally dilute sulphuric acid, until the yellowish-brown colour of
the basic ferric salt formed in the beginning of the reaction has changed
into a light yellow. The solution is then heated to boiling, allowed to
cool, treated with ammonia and filtered, and to the filtrate a small
quantity of a colourless solution of sulphide of ammonium is added.
The presence of a minute quantity of hydrocyanic acid will be shown
by a bluish-green, of large quantities by a beautiful violet-red colour.
Vortmann has named this the ‘“nitro-prusside test.”

The vomit induced by a number of other poisons, as carbonic oxide gas, sul-
phuretted hydrogen, &c., exhibits no distinctive properties.

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CaLIVAGE Waliriaeey ale
THE FACES.

Unper the term feces! are comprised all those substances which,
being formed from the food in the process of digestion, and mixed
with the residues of the secretions of the alimentary canal, are finally
expelled from the body by the rectum.

I. NAKED-EYE CHARACTERS OF THE FACES.—The char-
acter of the faeces varies considerably in health, depending chiefly as it
does on the nature of the food ingested. The labours of Nothnagel,
however, have obtained for us a knowledge of some points which are
more or less characteristic of healthy stools. Such a stool is moulded,
and of a certain consistency. Its reaction is sometimes alkaline,
sometimes acid. It is alkaline in certain morbid states, as, eg.,
typhoid ; but in others, as the acute enteritis of children (and, in the
author’s experience, of adults as well), the reaction is acid. The
so-called “clayey” stools of dyspepsia in children, however, are nearly
always strongly alkaline,—a fact which is due to the presence in them
of carbonate of ammonia. Nothnagel concludes that there is little to
be learned from the reaction of the feces.

The colour, too, is very inconstant. It depends upon the food taken,
and is greatly modified by drugs supplied to the system. When, eg.,
bilberries are eaten freely, the faeces are coloured black. So, too,
they are rendered black by preparations of iron, manganese, or bismuth,
the colour in these cases being due to the formation of the sulphides
of those metals. After a meal of cocoa-nibs or chocolate, the stools are
apt to be coloured grey (Widerhofer).2 The exhibition of calomel will
turn them green, an appearance which was formerly attributed to the
formation of sulphide of mercury, but which is now thought to be
caused by the presence of biliverdin (Betz, A. Vogel, Monti, Zawadshi).8
Researches which the author has made with the green stools passed
after the administration of calomel have shown that these contain
abundance of urobilin, but no biliverdin. Hence it would appear that

the colour is not due to the latter substance. Lesage distinguishes
164

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CHARACTERS OF THE FACES. 165

two varieties of the green stool of children. The colour in the first is
due to biliverdin, but in the second it is caused by a definite bacillus
which produces a green colour-substance. This bacillus can be culti-
vated outside the body, and inoculated upon animals. Its presence in
great abundance in the feces is associated with a
severe form of cholerainfantum. Santonin, rhubarb,
and senna will stain the feces yellow.

The presence of unaltered bile pigment in the
feces is always pathological (Pettenkofer).5 Healthy
excrement contains a pigment which has been
named stercobilin (Vanlair, Masius®), and which
Maly asserts to be hydrobilirubin (urobilin). This
latter body can be prepared artificially from bile
pigment, and it is probable, @ priori, that a simi-
lar change is effected in the process of intestinal
digestion, when we would expect to find urobilin
in the feces. For a further description of this
body and the tests by which it may be recognised,
see the chapter on Urine.

The quantity of feces passed by a healthy man
in twenty-four hours averages 120-200 grms. The
remains of undigested food are often to be found
in the excrement, as berries, fragments of potatoes
and apples, and shreds of fibrous tissue. Virchow"
relates a case in which orange-skins voided with
the feeces were taken for a parasite, and Hichhorst §
one in which great coils of hard, woody asparagus
were passed unaltered by digestion.

Amongst the occasional constituents of the faces
visible to the naked eye, must be mentioned the
cylindrical shreds of mucous membrane, of larger
or smaller size, which are passed in the affection

 

known as tubular intestinal catarrh (Colica mucosa, 46y
Enteritis membranacea or tubulosa), (Mothnagel).®
; P F FIu. 65.—Mucous Cylin-
The cases in which such mucous formations are Heuinemiiheikecest

found are not very rare. Their discharge is attended

with violent tenesmus, and unaccompanied by the passage of feces. They
are ribbon-like or reticular in form, and consist chemically of mucin and
fibrin (Litten).1° They are often of great length. In one instance they
had the appearance of coiled brownish-yellow strings, 0.5 cm. thick, with
here and there shreds of transparent membrane. The material under
description was readily compressible beneath the cover-glass, and when
looked at through the microscope, exhibited a profusion of transformed

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166 THE FACES.

intestinal epithelium involved amongst long, spirally-wound, and twisted
threads. These bore some resemblance to the Curschmann-Leyden
spirals (p. 98), but had no central thread, nor did they exhibit crystals.

The specimen represented in fig. 65 was derived from a child of two years,"
It consisted of mucin and fibrin concentrically arranged, and enclosed bubbles
of gas.

In all probability the presence of these bodies implies chronic catarrh
of the large intestine, usually associated with obstipation and copious
secretion of mucus.?2

A patient, suffering apparently from chololithiasis, whilst under the
author’s observation, passed with the feces a shred of tissue 5 cm. long
and 3 cm. broad, which proved to be intestinal mucous membrane. No
cause could be assigned for its detachment.

Virchow and Nothnagel '* describe the occurrence of bodies resembling
frog-spawn or cooked sago-grains in the stools, and some observers
have supposed that they were derived from ulcerating intestinal fol-
licles. Verchow thinks they come from an excess of farinaceous food.
Nothnagel has also met with particles about the size of a poppy-seed,
which chemically had the constitution of mucus. It must, however,
be mentioned that this author has never found mucin in any quantity
as a constituent of healthy excrement. Avtagawa' found that these
bodies in many cases consist of vegetable débris, but that others, which
‘are distinguished by being more viscous and of softer consistency than
the rest, are formed of mucus.

Foreign bodies of all kinds are occasionally to be seen in the feces of
lunatics and children.

Finally, tumours or parts of tumours originating in the alimentary
canal, and stones or concretions formed in the gall-bladder or intestine,
may be passed with the stools.

The presence of gall-stones is a fact of great clinical interest. They
may in all cases be detected by a careful examination with the naked eye.

The feces of a woman suffering from various symptoms of dyspepsia
were found to contain a number of soft, white and yellowish particles
about the size of a pin’s-head. These proved to contain cholesterin and
carbonate of lime, and it is probable that they were multiple small
biliary concretions.

II. MICROSCOPICAL CHARACTERS OF THE FHCES.—To study
the microscopical appearances of the faces, a small particle should be
pressed between a cover-glass and slide. If the stools are fluid, a drop
may be placed upon a slide, and so examined. Much, of course, depends
upon the character of the food, and the following description applies to
the feeces of an adult living chiefly upon animal diet.

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CHARACTERS OF THE FZCES. : 167

1. Constituents Derived from the Food.

(a.) Vegetable Cells.—These are of very variable form, and occur
separately or in organic connection with one another. They sometimes
exhibit starch granules or remnants of chlorophyll (fig. 66, e-7, 1).

(d.) Muscle Fibres are almost invariably found in the feces. Their
quantity depends upon the supply of flesh-meat. They are relatively
fewer after a mixed diet (Wothnagel).1® They are usually much altered,
stained yellow by the bile, and swollen; but with a high power of the
microscope, their transverse striation can usually be made out.

(c.) Elastic Fibres are readily to be distinguished by their double
contour and curved form. They are always derived from the food, and
occur both in health and disease.

 

Fic. 66.—Collective View of the Feeces (eye-piece III., objective 8a, Reichert).

a. Muscle-fibres; 6. Connective tissue; c. Epithelium; d. White blood-corpuscles ; ¢. Spiral
cells ; f.-i. Various vegetable cells; &. Triple phosphate crystals in a mass of various micro-
organisms; J. Diatoms.

(d.) Connective Tissue is found occasionally in the excrement of
persons who eat much animal food, and is then of no pathological con-
sequence. But if areolar fibres occur plentifully where flesh is sparingly
eaten, they afford an indication of digestive disturbance.

(e.) Fat.—Fatty globules are occasionally seen, but fat occurs more
commonly in needles, arranged separately or in clusters (Nothnagel).
Such needles are found in greater quantity when much fat has been
taken with the food. The stools in alcoholic poisoning are always rich
in fat, so also with the fatty diarrhcea of children (see p. 203).

(f) Starch Granules.—These particles may be easily detected by
their reaction with a solution of iodine and iodide of potassium. They
are commonly to be found, but sparingly and of small size, in healthy
stools. They are also found in the interior of vegetable cells. Moth-

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168 THE FACES.

nagel asserts that an excess of such substances in the excrement points
to a derangement of the intestine.

(g.) Coagulated Proteids.—Undigested milk occurs in the stools,
especially in children and in persons suffering from diarrhea. Noth-
nagel has described a substance resembling coagulated albumin which
is occasionally to be seen in cases of intestinal trouble. It occurs in
round yellow particles, varying from the size of a bean to that of a
millet-seed. Their substance is readily soluble in a 5 per cent. solution
of HCl, is precipitated from alcoholic solution by acetic acid, and redis-
solves in excess of the acid, from which it may be again precipitated
by ferrocyanide of potassium. They resemble the mucous particles of
Nothnagel, to which reference has already been made. That author
thinks that the substance in question is casein.1°

The discharges of infants at the breast are of a very different character
from those of adults. Here muscle-fibres, areolar, and elastic tissue are

 

Fic. 67.—Degenerated Intestinal Epithelium (eye-piece IL., objective 8a, Reichert).

absent, coagulated proteids taking their place. Microscopically they
abound in fat and crystals of the fatty acid salts.

2. Formed Elements Derived from the Intestinal Tract.

1. Red Blood-Cells.—Red blood-corpuscles are rarely to be found in
the feces. Mothnayel has examined the freshly-voided excrement of
typhoid, when it was deeply stained with blood, but could find none of
these cells. In such hemorrhagic stools, however, are seen larger or
smaller masses of reddish-brown pigment (hematoidin), and the rhombic
crystals of hematoidin are also occasionally present. In cases where
the blood is derived from the upper part of the alimentary canal or has
remained for a long time in the intestine, the feces are no longer red
like blood, but are stained a dark brown or black. We have already
seen that a similar effect may be produced by certain drugs (see p. 164),
and consequently it is not possible to infer a hemorrhage from this
appearance alone; neither will red blood-cells be visible under the
microscope. In such cases the presence of blood may be determined

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BLOOD-CORPUSCLES AND~ EPITHELIUM. 169

with absolute certainty by the application of Teichmann’s test to a dried
particle of the faeces (see p. 61).

2. Leucocytes.—In healthy stools leucocytes are rarely to be met
with. They are always loaded with fatty particles. As a pathological
condition, the appearance of leucocytes in great quantity in the excre-
ment is far from common. Nothnagel found absolutely no increase
in the number of these bodies in simple intestinal catarrh. When a
considerable increase does occur, it affords a presumption of ulceration
of the gut.

Pure pus is found when an abscess has discharged into the intestine
and in dysentery. (See p. 208.)

3. Epithelium.—Epithelium is always found in the feces in health.
Squamous epithelium comes from the region of the anus. Columnar
epithelium is more rarely met with (fig. 66, c). The latter is usually
uncoloured, but occasionally stained yellow. The cells occur either
separately or in masses. Their boundaries, as a rule, are not easily to
be recognised, but well-formed goblet-cells are sometimes seen (Woth-
nagel). Sometimes, too, they contain fat, and are then very large.
Altered epithelial cells are often found in the feces. In their typical
manifestation they constitute what Nothnagel has termed “fusiform
degeneration.” They are, for the most part, small, non-nucleated,
homogeneous, and somewhat glossy bodies, tending towards the spindle
shape (fig. 66), but exhibiting every variety of form between this and
the ordinary epithelial structure. Mothnagel’s opinion is that these
bodies are epithelial cells altered by abstraction of fluid, and he remarks
that he has found them most typically shown in the mucous coating of
scybalous masses. The mere presence of epithelium in the stools is a
fact of no clinical consequence. When in disproportionate quantity, it
points to intestinal catarrh.

4. Detritus.—There are certain indeterminate substances always to
be found in the feces, which are usually either derived from the food
or belong to the waste products of digestion. They occur separately or
in masses, and are little affected by reagents, although sometimes they
are soluble in alcohol. Their constitution is very various.

3. Parasites.—There is no part of the body so apt to be infested
by parasites as the intestine. Such parasites belong both to the animal
and the vegetable kingdom, and it is not unreasonable to conclude, from
the vast numbers in which some of them are always to be found, that
they exercise an important function in the final processes of digestion.
This may be said especially of certain vegetable forms, and among them
the fission-fungi, presently to be mentioned, hold a prominent place.’
[Researches by MacFadyean** point to a physiological distinction be-
tween the bacteria inhabiting the small and those of the large intestine.

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170 THE FACES.

The former are stated to act only, or almost only, on carbo-hydrates,
producing ethylic alcohol, which is constantly present in the small intes-
tine ; while the bacteria of the large intestine aid in the disintegration
of proteids. |

A. Vegetable Parasites.—It will be useful to divide these para-
sites, as before, into two classes,—the pathogenic and the non-patho-
genic ; but in doing this, it must be premised that some of the organisms
classed as non-pathogenic may also at times be closely associated with
morbid states. As an instance may be mentioned, the Bacterium coli
commune, which under certain circumstances acquires noxious properties
(Wyss), The non-pathogenic parasites will first engage our attention,
and we shall adopt the usual classification into moulds, yeasts, and
fission-fungi.

1. Non-Pathogenic.

1. Moulds.—The only specimen of this class which has yet been found
in the intestine is the thrush-fungus. It occurs in children suffering
from thrush, and its presence in the stools is clinically of no significance.

2. Yeasts.—Yeast-cells (Saccharomycetes) are the commonest form
of parasite in the intestinal discharges, whether of health or disease
(Nothnagel), (fig. 66, between } and c). Uffelmann *° asserts that yellow
yeast-fungi are often also to be seen in the fresh stools of infants at the
breast. Micro-organisms of this kind are most abundant in the acid
stools of children. They are round or oval ; lie together in groups of three
or four; and commonly exhibit their characteristic sprouting arrange-
ment. Well-formed yeast-fungi, however, such as are seen in fermenting
saccharine solutions, are very rarely to be met with. Nothnagel saw
such once in a case of typhoid in a child. In the bile-stained and acid
discharges of acute catarrh of the small intestine in adults the author
has not infrequently found fungi which closely resembled the form
described by Rees! as the Saccharomyces ellipsoideus, except that they
were somewhat smaller (p. 145).

The yeast-fungi of feces stain a mahogany-brown with the iodo-
potassic-iodide solution. This property depends upon the fact that they
hold glycogen in their substance.

There are other forms to be met with morphologically resembling
yeast-cells, but distinguished from them by giving a blue colour with
the iodo-potassic-iodide solution mentioned above (see p. 171).

3. Fission-Fungi.—These organisms exist in swarms in the intestine,
and they are to be found in greater profusion in the feces than in any
other of the excretions (Vothnagel, Brieger, Uffelmann, Escherich, Bien-
stock, Stahl, Kuisl, Miller, Suchksdorf?*); indeed, it is not incorrect to
say that they always constitute the bulk of these discharges. Bacilli
and micrococci of the most varied kinds are the commonest forms.

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FUNGI FROM THE INTESTINAL TRACT. 171

They occur separately or in colonies, and often exhibit lively movements.
It may be said, as a rule, that micrococci predominate in the solid, and
bacilli in the fluid motions. The former are sometimes found in shapes
resembling torule and sarcine. The organism which occurs most com-
monly and in greatest abundance is the Bacterium termo (Bacterium coli
commune), and there can be little doubt that this body is intimately
associated with putrefactive processes in the intestine ; although it must
be stated at the same time that we are ignorant of its functions in
health, where also it exists abundantly, and that the host of other
micro-organisms which make their appearance when putrefaction is
going on throws a great deal of doubt over this question.

Bacillus subtilis is found in the discharges both of health and disease.
It was first discovered by Nothnagel, and may be seen as long threads
with spores attached, or as separate spore-bearing rods, and elsewhere
the spores alone occur in clusters. Its relatively thick edges and the
remarkably glossy appearance of the spores facilitate its detection. Its
presence has no clinical significance.

The various micro-organisms above alluded to stain brown or brownish-
yellow in solution of iodine and iodide of potassium or of ammonium
iodo-iodide ; and this property belongs especially to the groups of micro-
cocci, which are coloured very deeply a brownish-yellow by contact with
this reagent.

In addition to such forms, the feces exhibit other micro-organisms,
which stain blue or violet in the iodo-potassic-iodide solution. Mothnagel
has described many of these, and one especially which he holds to be
identical with the Clostridium butyricum of Prazmowski.8

The author has investigated this subject with great care, and he is in
a position to confirm Vothnagel’s statements in every particular, and
would venture to add something to his description of the fungi which
stain blue with the iodo-potassic-iodide solution.

To begin with the minutest forms. There is a micrococcus which
occurs in swarms of uniformly and finely granular zoogleaform bodies,
which colour a reddish-violet with the solution.

Next in order is a micro-organism in the form of short delicate and
somewhat pointed rods, which recall the baczllus of septicemia in the
mouse, and which stain in a similar manner with the reagent mentioned.
These rods occasionally contain one or two spherical granules, which do
not stain in the solution.

There are other rods, of varying length, which resemble the Leptothrix
bucealis in the manner of their reaction with the iodine fluid; and a
further variety, which differs from the Bacillus subtilis only in that the
fungus threads stain blue, while the bodies referred to above as the
spores remain uncoloured (fig. 68).

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172 THE FACES.

The author has often had an opportunity of observing the Clostridium
butyricum of Nothnagel. It takes the form of large round cells, usually
visible in uncoloured preparations by reason of their somewhat lustrous
appearance, and in other respects resembling yeast-fungi. In some
cases they adhered to one another like a string of beads, and in others
were simply disposed in groups (fig. 69). These bodies, as Lictheim
and others have observed, stain with the Ziehl-Neelsen fluid in the same

@ > f
Keay Yoo
SS et
~ eS Ee La
iS Z a erliaee

Fic. 68.—Bacilli from the Feeces, staining Blue with the Iodo-Potassic-Iodide Solution
(eye-piece III., objective 84, Reichert).

manner as tubercle bacilli, but they are not likely to be mistaken for
these, since they are sufficiently distinguished by their size, shape, and
peculiarity, of arrangement.

A micro-organism of oblong and somewhat pointed form also occurs
in the feces, and cultivations of this have been made by H. Fischer.

It must be mentioned that although these bodies all stain some shade

ex (a eo
_ 6%, “a”
9 “w 99 ®le

ee “Re eo ~

Fic. 69.—Nothnagel’s Clostridia and Stunted Bacilli from the Feces, staining Blue with the
Iodo-Potassic-Iodide Solution (eye-piece III., objective 8a, Reichert).

of blue with the solution of iodine and iodide of potassium, the tints
which they derive from that reagent exhibit notable differences; for
whilst, on the one hand, the micrococci are but slightly coloured, and
of a purple tint which tends towards red, the rod-like micro-organisms
stain very deeply, and of a dark-blue colour. The stain is in all cases
transitory, fading in from twenty-four to forty-eight hours, and disap-
pearing altogether within a few days.

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PATHOGENIC FUNGI. 173

Those fungi whose characteristic it is to stain blue in iodo-potassic-
iodide solution occur probably in all stools, but in relatively small
numbers in those of health. They are in profusion only in certain
morbid states, and especially in intestinal catarrh. They do not seem
to bear any relation to the reaction of the discharges, having been found
alike when this was alkaline and when it was acid. To conclude, they
are constantly present in health and in disease, and in the discharges
of infants at the breast, as well as of older children nourished on a
meat-diet.

Hence it follows that no definite clinical significance attaches to any
of the parasitic forms hitherto described. It is a matter of observation
that in certain pathological conditions of intestinal derangement one
form or the other is apt to preponderate, but we have no evidence that
they are in any case the cause of disease, or that the multiplication of
a particular micro-organism is not rather the consequence of the dis-
turbance which it is found to accompany.

The intestine is apt to be infested with microbes of a pathogenic
character, which in form closely resemble those innocuous parasites
which have just been described. Much light has been thrown upon
their nature by the researches of recent years, and for their detection
we have to make use of a number of special methods. But these alone
will not suffice. Without an accurate knowledge of the commoner, at
least, of the non-pathogenic organisms which normally inhabit the
intestine, the discrimination of the others is impossible. It is for this
reason that we have dwelt at some length—though still in a far from
exhaustive manner—on the description of the innocuous micro-organisms
which are most frequently to be found in the feces.

2. Pathogenic Fungi.—We pass now to a consideration of the
pathogenic parasites, the bacilli of cholera, typhoid, and tubercle.

1. Cholera-Bacillus (Comma-Bacillus).—To Robert Koch,?* the
pioneer of the modern science of bacteriology, belongs the honour of
having first discovered the micro-organism which causes that most
terrible of the epidemic diseases of our time—cholera.

We shall not attempt to give an account of all that has been written
upon this subject, but shall content ourselves with making here and
there a reference to the leading authorities for the information of the
reader ; and we shall avoid the discussion of controverted points of
which we have no personal knowledge. Nevertheless, there can be no
doubt whatever of the fact that a definite and morphologically distinctive
parasite occurs in the discharges of cholera patients ; and it is a task at
once difficult and of the utmost importance to define the form of this
organism, and to devise methods for its recognition.

Koch described the cholera-bacillus as a short rod-like form, curved

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174 THE FACES.

or semicircular, and somewhat thicker than the bacillus of tubercle.
Such bodies often lie two together, with the concavity of their curves
turned in opposite directions and their extremities in contact, so as to
from an S-shaped figure. Neuhauss?° describes flagella upon them.
Lofler 26 has demonstrated their existence by the method described in
Chap. X. They produce by division peculiar screw-like spirals, which
remind one of the spirillum of relapsing fever, only that these are
thicker (fig. 24). Koch did not find any separate spores belonging to
these organisms, but it would seem that Hweppe?’ has succeeded in
doing so. Such bacilli were discovered by Koch in the intestine and
discharges, rarely in the vomit, of Asiatic cholera, and never in the
blood, saliva, tears, urine, or breath of patients suffering from this
disease. The discharges, according to this authority, sometimes contain
almost unmixed colonies of bacilli. Koch’s statements have been borne

 

FiG. 70.—Koch’s Comma-Bacillus (pure cultivation ; eye-piece III., objective Zeiss y,,
homogeneous immersion ; Abbe's mirror and open condenser).

out by the subsequent investigations of Babes, Vandyke-Carter, Nicati,
Rietsch, van Ermengen, and others.?8

It follows from what has been said of the enormous profusion in
which micro-organisms of various kinds infest the intestine, that the
cholera-bacillus, when not very plentiful, may easily escape detection ;
and therefore it will not suffice to submit discharges which are supposed
to contain it to a simple microscopical examination. To meet the exi-
gencies of the case, Koch has studied the mode of growth of the bacillus,
and he has devised for its cultivation certain special processes, on the
application of which the diagnosis of Asiatic cholera may very safely
rest. The first requisite is to separate some of the bacilli or their germs
from the mass which contains them, and this may readily be done in
the manner to be described in another part of this volume (vide chapter
on Methods of Bacteriological Research).

A complete and exhaustive search for the cholera-bacillus may be
performed as follows :—

1. A particle of the discharge is placed upon a slide, and examined

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BACILLUS OF CHOLERA. 175

microscopically for the bacillus. In doing this, the expedient of
Schottelius®® may be adopted with advantage. He puts a little of
the stool in an open glass, together with an equal quantity of alka-
line meat-broth, and allows the mixture to stand at a temperature of
30-40° C. for twelve hours. At the expiration of that period, the
bacilli will be found in swarms on the surface of the glass, and a
specimen may be obtained which will consist almost entirely of them.

2. A particle of the discharges or a drop of the infected broth
(Schottelius) is next spread out in a very thin layer between two cover-
glasses, dried, passed three times through the flame of a Bunsen burner,
stained with one of the basic aniline dyes (fuchsin, methylene blue) and
examined under the microscope.

3. Plate-cultivations are made from the suspected stools with nutrient
gelatine and agar-agar, as described in Chapter X.

4. If comma-bacilli develop in these, cultivations are to be made by
inoculation in the depth of nutrient substances.

5. The bacillus is to be cultivated in hanging drops (vide Chapter
X.)—(it is well to apply this test at once, in the event of comma-bacilli
being found in Schottelius’ preparation)—and the micro-organisms
developed in the medium are to be compared with those derived by
plate-cultivation.

When the discharges examined belong really to Asiatic cholera, the
processes 1 and 2 will generally show the comma-bacillus of Koch. The
inference to be drawn from the third process depends upon the fact
that the cholera-bacillus, cultivated on a nutrient gelatine plate at
22° C., forms after twenty-four hours white colonies, with irregular,
jagged, or sinuous outlines. These exhibit a light-yellow or rosy tint,
and present an appearance like that of a layer of powdered glass over-
lying the gelatine plate. The colonies grow gradually darker towards
their centre, and presently begin to liquefy.

Plate-cultivations in nutrient agar-agar form a greyish-yellow, fur-
rowed, slimy surface, and do not cause the underlying nutrient medium
to liquefy.

When cultivated by inoculation in the depth of the nutrient sub-
stance contained in a test-tube (v. supra), after the lapse of twenty-
four hours the nature of the bacillus is shown by a white coloration,
which extends along the track of the needle, and the formation of a
funnel-shaped cavity, which increases gradually from the circumference,
and acquires the appearance of an air-bubble. It is only at its super-
ficial part that this liquefaction occurs, the lower layer of the inoculated
substance remaining unaltered for days.

In hanging-drop cultivations, the comma-bacillus exhibits the follow-
ing peculiarities (v. swpra):—When examined on the day following

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176 THE FACES.

the inoculation, or, it may be, after the lapse of a few hours, and with
an oil-immersion lens and a constricted diaphragm, mobile swarms are
seen in the centre of the mass, while at its circumference appear the
spirocheete-like bodies, which sometimes exhibit as many as twenty
spiral twists. Suppose that a specimen, which Schottelius’ method had
previously shown to contain micro-organisms when cultivated in this
manner, displayed some forms which resembled the comma-bacillus, it
will then be necessary to transfer some of these drop-cultivations in the
manner described in Chapter X. for cultivation by the plate and deep-
inoculation methods.

Bujwid has recently recommended his chemical process (see below), in
combination with that of Schottelius for the purpose of disclosing the
cholera microbes, even without the aid of the microscope.

It should be mentioned that the cholera-bacillus will thrive at a tem-
perature of 37°, and even on boiled potatoes. Its cultivations resemble
those of the bacillus of glanders to the naked eye, but their growth is
slower and needs artificial heat. The bacilli are very sensitive to drying
and to exposure to a 5 per cent. solution of carbolic acid.

Bitter and Rietsch®° have shown that the cholera microbes elaborate a peptonis-
ing ferment.

Poehl and Bujwid* found that the addition of a 5 to 10 per cent.
solution of hydrochloric acid will, in a few minutes, impart to cholera
cultivations, and to no others, a violet-rose colour; and Brieger®? has
been able to separate from them a colour-substance, to which he gives
the name of “ cholera-red,” but which Salkowski *° identifies with indol.
Bujwid’s cholera reaction does not seem to merit the commendations
bestowed on it. Other fungi, pathogenic and innocuous, behave in a
similar manner with mineral acids.

The foregoing observations were confirmed by Kitasato.34

Cantani*° notices, as a result of his experiments upon animals, that
cholera-bacilli elaborate a poison ; and Brieger *° has actually separated
from its cultivations specific toxic substances, which occur together with
cadaverin and putrescin, and result from the agency of cholera microbes.
The method he employed is that detailed at page 158. It remains for
the clinical observer to detect these substances ready-formed in the
discharges of cholera patients ; and some progress has already been made
in this direction (Pouwchet).*” Recent research has made it doubtful
whether it is these toxines which play so important a part in the morbid
process, and not rather the toxalbumins from which they are known to
originate.

There are two other micro-organisms which bear a considerable resemblance

to the comma-bacillus. One of these, the bacillus of cholera nostras, is a
pathogenic micro-organism ; the other is Deneke’s spirillum of cheese.

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DETECTION OF CHOLERA BACILLUS. 7:

2. The Bacillus of Cholera nostras.—Finkler and Prior *8 have observed a
micro-organism resembling the comma bacillus in the discharges of cholera
nostras. It is distinguished from the bacillus of Asiatic cholera chiefly by its
size (fig. 71), being both longer and broader than the latter. In addition to
this, the two exhibit notable differences in life-history, When a colony of the
Finkler-Prior bacillus is cultivated on a plate in nutrient gelatine, it is seen to
be of a uniformly round figure with well-defined edges ; and when examined with
a low or medium power, it has a granular appearance, and is usually of a brown
colour. Moreover, the gelatine rapidly liquefies, and emits a very foul and
penetrating odour.

The comma-bacillus of Koch, on the other hand, develops less rapidly. The
colonies are never coloured brown, but of a tint ranging from light-yellow to
rose-colour ; and the figure which they form, as already mentioned, is bounded
with a ragged contour (see p. 175).

Again, when cultivated by inoculation in the depth of nutrient substances,
this bacillus develops in a very characteristic way ; for whilst the comma bacillus
swarms in the funnel-shaped manner already described, the cultivation in this
case assumes a saccular shape, somewhat comparable to that of a stocking. V.
Hovorka and Winkler * employ plover’s egg-albumin as the food medium. This is

 

Fic. 71.—Finkler-Prior Bacillus of Cholera nostras (pure cultivation ; eye-piece III., objective
Zeiss Yo, homogeneous immersion ; Abbe's mirror ; open condenser).

rapidly liquefied by the Finkler-Prior bacillus, while the comma bacillus is pro-
pagated only along the track of the needle and does not decompose it.

The pathological import of the Finkler-Prior bacillus is still a matter of dispute,
but it is plainly of the utmost consequence to be able to distinguish this com-
paratively harmless organism from the very fatal microbe of Asiatic cholera.

Spirillum of Cheese.—Deneke ” found a micro-organism in ripe cheese which
bears a close resemblance to the comma-bacillus of Aoch. But this, like the
Finkler-Prior bacillus, can be distinguished by certain peculiarities in its life-
history. The nutrient gelatine medium is rendered fluid sooner than by Koch’s
bacillus, but more slowly than by that of Finkler and Prior. This micro-
organism, moreover, will not develop in potato, while the other two will thrive
upon this food. The crucial test, however, is the result of inoculation upon
animals. Deneke’s bacillus has no morbid influence on the intestine.

3. Bacillus of Typhoid Fever.—A characteristic parasite was dis-
covered in 1880 by Kberth*! in the implicated viscera in typhoid.
Similar observations were afterwards made by Klebs and Eppinger,*?
and these have been confirmed by the researches of R. Koch, Meyer,
and Friedidnder, and more recently by Gaffiy and very many others.4

M
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178 THE FASCES.

Gafky describes the funeus as consisting of rods, in length equal to
one-third the diameter of a red blood-corpuscle, and occasionally forming
threads of greater length by the aggregation of several segments. They
are about three times as long as they are broad, and rounded off at the
extremities. Spores are sometimes to be seen within the rods. They
stain best in a concentrated watery solution of methylene blue, and
Lofler’s process (p. 43) is the most appropriate to the purpose. They
are not stained by Gram’s method. Friinkel and Pfeifer,4* using
Léjfler’s process for staining flagella, have observed these processes on
the bacilli of typhoid and of malignant cedema.

Gaffky* has ascertained certain facts connected with the life-history
of the typhoid-bacillus. It develops readily in a medium of nutrient
gelatine. In a preparation of this kind the cultivations make their
appearance after the lapse of twenty-four hours. When examined with
a medium power of the microscope, they seem to be yellowish, and they

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Vic, 72.—Bacilli of Typhoid (pure cultivation ; eye-piece ILI., homogeneous immersion, objective
Zeiss pz). From a preparation by Dr.'Paltauf. 4

do not render the gelatine fluid. Rods and threads appear, and they
are endowed with an evident and peculiar motion. The parasite
develops on prepared potato. The colonies can be distinguished with
difficulty by the naked eye. When cultivated in a medium of prepared
potato at a temperature of 37° C., spores begin to form after three or
four days. According to Birch-Hirschfeld,*® solitary and segmented
spores are to be seen, the first in hanging-drop cultivations, and the
latter when cultivated in an incubator. This observer recommends that
the nutrient medium be stained with phloxin-red or benzo-purpurin, by
means of which the spores are deeply coloured. There is much doubt
as to the true character of these so-called spores (Buchner, Pfuhl).¥
The fungi are easily cultivated in hanging drops in sterilised broth.

The bacillus occurs also in the stools of typhoid patients; but on
account of the vast number of micro-organisms constantly to be found
in the dejections, it is impossible to recognise it with the aid of the

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BACILLUS OF TYPHOID. 179

microscope alone. Neither does it possess, like the bacillus of tubercle,
any characteristic staining properties. For its complete recognition,
therefore, we must resort to Koch’s methods for obtaining pure cultiva-
tions, and separate it from the fecal substances. Pferfer 48 was the first
to do this, and he made use of the nutrient agar-agar plate. A useful
adjunct is the employment of a 0.25 per cent. solution of carbol-gelatine,
after the manner of Chantemesse and Widal.49 According to Holtz,°°
however, this is impracticable, since he found that the development of
the bacilli was suspended in presence of 0.1 per cent. of carbolie acid.
The best medium is neutral potato-gelatine containing 0.05 per cent. of
carbolic acid. For the recognition of this micro-organism, Holtz, follow-
ing Grancher and Deschamps,®*! recommends weakly-acid bouillon or
similarly-prepared milk stained by Noeggerath’s*? process. Kitasato >
relies upon the absence of the indol-reaction from such a cultivation as
evidence of the typhoid-bacillus.°4 The researches of Babes and Cas-
sedebat®® have shown that the investigation is attended with much
difficulty, since there are a great many distinct fungi which, when culti-
vated, present appearances quite similar to those of the typhoid-bacillus.

It is difficult to effect the separate cultivation of typhoid-bacillus derived from
the faces in nutrient gelatine, because the discharges contain other micro-
organisms (hay bacillus), which liquefy that medium before the colonies of
typhoid-bacilli appear in it.

When the micro-organism under discussion has been experimentally
communicated to animals, it causes them to manifest the symptoms of
typhoid ; and the researches of L. Frankel, M. Simmonds, and C. Seitz,°°
seem to leave no doubt as to its pathogenic character. Bewmer and
Peiper,®" on the other hand, have come to a different conclusion. Bear-
ing in mind Brieger’s discovery of animal alkaloids (ptomaznes) as a
product of bacillary life, it seems probable that such play an important
part in connection with typhoid, and this may well explain the contro-
verted results obtained in the experiments upon animals reported by
Friinkel, Simmonds, and others.

Finally, it may be noticed that many recent investigations tend to prove the

possibility of typhoid-bacilli being disseminated by means of drinking-water and
by milk.*8

4. Bacillus of Tubercle.—Lichtheim®® and other observers have
found tubercle-bacillus in the stools in cases of tubercular ulceration
of the intestine. For its recognition there, the methods are employed
which have already been described in connection with the sputum
(vide p. 104).

The detection of this bacillus in the feces invariably implies the
existence of tubercle, but not necessarily tubercle of the intestines, since

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180 THE FACES.

it may be derived from sputa which have been swallowed. Still, in
cases where it has been repeatedly found in the stools, and where it
occurs in great profusion, so as to resemble pure cultivations (vide fig. 108),
and especially where the other symptoms of tubercular ulceration of the
intestine (purulent discharges, &c.) are present, the diagnosis is estab-
lished on the firmest basis.

B. ANIMAL PARASITES.

1. Protozoa.—Adopting the classification of Leuchart, these in-
clude Rhizopoda, Sporozoa, and Infusoria.

1. Rhizopoda.

(a.) Monadines.—NVothnagel | found these organisms repeatedly in
the stools of consumptive and typhoid patients, and of persons suffering

 

6. Cercomonas intestinalis (Davaine). e. Monadines, living.
c. Ameeba coli. J. Monadines, dead.

a, Trichomonas intestinalis. | d, Paramecium coli.
from heart-disease. They were always dead unless the stools were
examined directly upon being passed, and then appeared as more or
less circular bodies of various sizes (fig. 73, /).

The still living monadines are pear-shaped, and usually possess a
long pointed process, which moves about rapidly (fig. 73, e). According
to Wothnagel, they have no pathological significance. Grassi 6? found
similar bodies in the stools of a patient suffering from entero-colitis.
Bodies altogether resembling these, but not as yet identified with them,
occur in the discharges of infants and children (see v. Jaksch).®

(b.) Ameeba coli. Ldsch % has described certain cellular bodies of
large size which he found in the feces in a case of intestinal ulcer of a
quasi-tubercular character. These bodies were contractile, and some of
them, of circular form, had a diameter of 20-35 ~. They consisted of
hyaline and coarsely granular protoplasm, with a round nucleus and
hyaline vesicle, but no distinct cell-wall (fig. 73, ¢).

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ANIMAL PARASITES—PROTOZOA. 181

Similar organisms have been found in the intestine by Lambl,® and
Kartulis, Massuitin, Osler, and Dock have seen amceba-like organisms
in the stools of patients suffering from dysentery and chronic enteritis.

2. Sporozoa.—Again reverting to Leuckart’s classification, the sporozoa
which chiefly concern us here are the oval psorospermia, the group to
which belong the coccidia which infest the intestinal tract of man
(Dressler, Gubler, Kjellberg, Eimer) ®™ and the liver (Podwyssoki).®
They appear in the feces as elliptical forms, 0.022 mm. long, furnished
with a thin membrane, and enclosing within their substance a number
of granular nuclei, arranged for the most part in groups. They are to
be found in great numbers. Their favourite seat is the intestinal mucous
membrane, where they burrow, doing much damage to its structure.
For this reason Leuchart appropriately names the parasite Coccidium
perforans.

3. Infusoria.—1. Cercomonas intestinalis.—This protozoon was first

 

Fic. 74.—Cercomonads from the Stools.

a. Megastoma entericum (Grassi).
b, b'. Encysted forms of Cercomonas intestinalis.
c. Cercomonas intestinalis after loss of its tentacles (Lamb/).

found by Lambi° in the jelly-hke mucous discharges of children, and
it was afterwards observed by Davaine, Marchand, and Zunker. It is
of piriform shape, clearly nucleated, and furnished with eight tentacles
of varying length (see fig. 74, @). Davaine discovered it in cholera,
Marchand in typhoid, and Zunker in nine cases of diarrhoea. It would
appear from these facts that the Cercomonas intestinalis is apt to thrive
in a gut which is already diseased, and when present tends to cause
severe diarrhcea. The observations of Zunker especially strengthen this
conclusion. According to Grassi and Schewiakof'™ the parasite causes
anemia and diarrhoea in human beings, and by the changes which it
effects in the mucous membrane interferes with absorption from the
intestine. The Cercomonas was observed by Miller 7 in the jejunum
of a healthy man.

The Megastoma entericum, lately described by G'vassz, is almost cer-

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182 THE FACES.

tainly identical with Lambl’s Cercomonas.” Per roncito ™ has observed
the encysted forms of the parasite in the intestine (fig. 74, 6)—observa-
tions confirmed by the author in the case of children.”

Other Cercomonads have been seen in the same situation (Davaine),
(see fig. 73, 0).

2. Trichomonas intestinalis.—This is a pear-shaped organism, some-
what larger than Cercomonas intestinalis, and distinguished from it by
bearing a ciliated dise at one extremity (fig. 73, a). It has been obtained
from the intestine by Marchand and Zunker.

3. Paramecium coli (Balantidium col/).—An entozoon first found
by Malmsten™ in the discharges of diarrhcea, and afterwards observed
by Stieda, Graziadet, Perroncito, and K. Ortmann."8 It is oval, o.1
mm. long, and covered with cilia, which are planted more thickly around
the buccal (2) orifice. The anterior extremity is smaller than the posterior,
and the opening (anal) in this situation is but sparingly provided with
cilia. The abdominal surface is less arched than the dorsal. Internally
it is furnished with a nucleus and two contractile vesicles, and frequently
contains amylum particles and fatty granules. Its presence appears to
be associated with diarrhcea, but it has no other clinical significance.

In addition to the varieties mentioned here, other infusoria are occa-
sionally present in the intestine (V. Jalsch).7

2. Vermes.—The investigation of the feces for intestinal worms
has become of late years a matter of special interest to physicians,
because experience daily teaches us that, even in temperate climates,
the alimentary canal is apt to be beset with certain parasites of this
class, which must be reckoned amongst the most formidable pests of
mankind ; and it often happens that an accurate diagnosis of their
nature can alone enable the physician to adopt intelligent methods for
their removal, and so, it may be, to save his patient’s life.

Class I.—Platodes.

(a.) Cestodes.—The following tapeworms concern us here :—

1. Tenia saginata (mediocanellata).

Tenia solium.

N

Tenia nana.

Tenia flavopunctata.

Tenia cucumerina (elliptica).

Bothriocephalus latus.

Tenia saginata (mediocanellata).°—This parasite is longer than
the Tznia solium, attaining to four or five metres, and its segments
are also longer. The head is surrounded with four large and usually
black-pigmented suckers, but is not provided with a rostellum, and is
without a circle of hooklets. The segments increase in length more

ec

gradually than in Tenia solium, and are commonly pigmented.

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TAPEWORMS. 183

The uterus is very much branched, and the genital pore is situated
at the side of the proglottis. The eggs resemble those of Tzenia solium,
but are more oblong, and exhibit the primordial yolk membrane.
Hooklets are not discernible in the embryo (fig. 75).

  

Fic, 75.—Tenia saginata: Head ; Proglottis; Egg. (Reichert’s eyepiece III., objective IV.)

2. Tenia solium.*'—The Tenia solium may measure upwards of
two or three metres. Its head is quadrilateral, about as large as a
pin’s-head (;; to =; of an inch), and dark in colour. This is succeeded
by a delicate, thread-like neck, about an inch in length, and unjointed.
The segments, or proglottides, which form the rest of the body, are

   

Fic. 76.—Tznia solium, Head (magnified), Proglottis (actual size), and Egg (maguitied).

short and relatively broad near the neck; but as they increase in size
this relation ceases, and still growing in both dimensions, their quadri-
lateral form becomes evident about three feet from the head. Their
average length is from 9 to ro mm., and their breadth 6 or 7 mm.
Under the microscope the head is seen to present four. prominent
suctorial discs, usually pigmented, and between them a rounded elevation

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184 THE FACES.

or rostellum, which is surrounded with about twenty-six hooklets of
different sizes.

The sexual apparatus first becomes visible about a foot from the head
(Bristowe). The uterus is but little branched, and the genital pores are
situated somewhat behind the middle of each segment.

The eggs are oval in shape, about 0.03 mm. in diameter and 0.036
mm. long, and surrounded with a thick shell, which is radially striated.
When the eggs are mature, they may be seen to contain embryos fur-
nished with hooklets (fig. 76).

3. Tenia nana.S2—This parasite averages from ro to 15 mm. in
length, and its greatest breadth is about o.5 mm. It has a globular
head 0.3 mm. in diameter, furnished with four circular suckers, and a
rostellum o.06 mm. long, carrying twenty-two to twenty-four hooklets
at its anterior extremity, which is rounded off. The rostellum can be
protruded to a considerable distance from the head or entirely withdrawn

 

Fic. 77.—Teenia nana: Head (with Rostellum drawn in ; Proglottis Egg.

within it. Jn the latter position it has the form of an hour-glass. The
body is attenuated in its anterior third, but proceeding backwards grows
quickly in bulk. The segments are short, and towards the end of the
body are scarcely one-fourth so long as they are broad. The uterus is
oblong and loaded with eggs of 0.03 to 0.04 mm. in diameter. The
shell does not exhibit the rod-like structure, but consists of a double
membrane, within which are a spiral thread and amorphous matter, in
which granules are embedded. Jn the interior of the ege may be seen
the embryo, already provided with five or six hooklets (fig. 77). The
parasite may be present in great numbers in the intestine, and is apt to
produce severe nervous symptoms, such as epileptic seizures, insensi-
bility and mental derangement, and melancholia (Grass¢, Comint).8*
Recent observations go to prove that the Tenia nana is very widely
distributed. It especially attacks children and young persons. It was
first discovered by Bilharz in Egypt, and since then has been recognised

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THENIA FLAVOPUNCTATA—CUCUMERINA. 185

as of common occurrence in Italy and Sicily.8! It is probable that it
exists elsewhere more frequently than is supposed. tanson has pub-
lished an account which goes to prove that it-was observed in England
so long ago as 1856.8 According to Grassi, Tenia nana is in Sicily the
commonest parasite. The number present in a single individual may
reach 4000-5000.

; 4. Tenia flavopunctata.—This bears a close resemblance to Tenia nana, but it
is of greater length (12 to 20 mm.), has no rostellum, and only two suckers. The
eggs are like those of Tenia solium (Parona), and larger than those of Tzenia
nana. The occurrence of the parasite in man rests upon the testimony of Leidy
and Parona,® but is disputed by others; and Grassi‘? identifies it with Tzenia
leptocephala, which has hitherto been found only in certain species of mice and
rats (Mus decwmanus and Mus rattus).

5. Tenia cucumerina (elliptica).—This is a worm which averages
18-25 cm. in length. The head is situated at the thinner end, and has

 

Fic. 78.—Tenia cucnmerina: Head ; Proglottis (magnified).

some sixty hooklets irregularly disposed around the rostellum, which is
a coarse club-like process when projected. The first forty proglottides
are of small size, but increasing as they proceed backwards both in length
and breadth, and especially in the former dimension, measure at the
extremity 6 to 8 mm. by 2 mm. in breadth. The mature segments are
of a reddish colour, and readily separate from those nearer to the head.
The eggs, when shed, have a diameter of 0.05 mm., and contain an
embyro furnished with hooklets.

The parasite is not at all rare amongst human beings;** it especially
infests children, and is acquired by them from dogs.

It is sufficient merely to mention here the rarer forms of tape-worm known to
be present in the human intestine. These are Tzenia, madagascariensis (Grenet) *
and Tenia leptocephala (Grassi), which possibly is the same as Tenia nana.°°

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186 THE FACES.

6. Bothriocephalus latus.°1—This worm attains a length of 5-8
metres. The head is ovoid, and 2 mm. long by 1 mm. broad. It is
cleft, and provided with two lateral suckers, placed on either side of the
middle line. It has no hooklets. The proglottides are at first short
and small. They increase in breadth as they proceed, and towards the
end of the parasite approach the square form. ;

The uterus of mature proglottides containing eggs exhibits a reti-
form arrangement, and appears superficially as a small rosette. This
uterine rosette is characteristic of Bothriocephalus latus.

The eggs are oval, and measure 0.07 mm. by 0.045 mm. They are
covered with a brown shell, and open by a small lid at one end. They
contain centrally-transparent masses of protoplasm of uniform size.
Bothriocephalus latus has recently acquired an increased clinical signi-
ficance, inasmuch as it has been found frequently by different observers
in conjunction with the symptoms of pernicious anemia.?2

Other varieties of this parasite have been observed, as the B. cordatus in
Greenland,® and the B. liguloides in Japan and China. The latter infests the
sub-peritoneal tissue, and especially that of the lumbar region in man.

The presence of one of the tape-worms here described is made evident
—apart from clinical symptoms, which do not concern us here—by the
discovery of proglottides in the stools.

 

lic. 79.—Head of Bothriocephalus latus (eye-piece IL1., objective 1V., Reichert).
a. Seen on edge; b. Seen on the flat; ¢. Proglottides; d. Eggs.

A careful microscopical examination with a medium power (Hart-
nack objective IV., Zeiss objective C., Reichert objective IV.) may
show the eggs in the feces. When it is supposed that a patient is
suffering from tape-worm, whilst yet no evidence of the parasite can
be derived from a careful inspection of the stools, it is well to mix
these with water, which is constantly poured off and renewed until the
greater part of the fecal mass has been dissolved. An examination of
the sediment will then inevitably reveal the eggs, if the suspicion be
well founded. To determine to what form of tape-worm a particular
proglottis belongs, the best proceeding is to examine the specimen,

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. DISTOMA. ; 187

mounted in glycerine, with a low magnifying power; and the same
thing may be done if a head be obtained.%

Cysts of echinococcus and hooklets may be found in the feces when a hydatid
cyst has burst into the intestine. Heller °° was able by the discovery of such a
cyst to diagnose a doubtful liver complaint as one of hydatids.

(0.) Trematodes.*’—The varieties of distomata, D. hepaticum and D.
lanceolatum, have been found in rare instances in the intestine or
biliary passages of man.

_ 1. Distoma hepaticum.—This is a leaf-shaped worm, measuring
28 mm. by 12 mm. The head is short, and furnished with a sucker.
There is another sucker on the ventral aspect, and between the two the

 

Fic. 80.—Distoma hepaticum.

genital pore is situated. The latter leads to a uterus, which is convo-
luted like a ball of wool.

The eggs are oval, 0.13 mm. long and 0.08 mm. broad, brown in
colour, and covered with a shell consisting of two layers; one end is
broader than the other, and opens by a small lid. Bvermer, Bostroem,
and Baelz,°® have described these parasites as occurring in human beings.

2. Distoma lanceolatum.—This entozoon is from 8 to 9 mm. long
and 2-3.5 mm. broad. It is lance-shaped, as its name implies, and
pointed at either extremity, but more so in front than behind. In
other respects its form resembles that of Distoma hepaticum.

The eggs are 0.04 mm. long and 0.03 mm. broad, and they contain

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188 THE FACES.

the mature embryo. Bizzozero® maintains that when the worm is
present in the intestine, its eggs are to be found in the stools. The
observations of Baelz,!° corroborate this view. Perroncito 1! found the
eggs of this fluke in the case of persons infested by anchylostoma.

The last two forms of parasites but rarely occur in man, and con-
sequently neither they nor their ova are often to be seen in the feces.
Moreover, they very seldom cause serious symptoms.

3. Distoma rathonisi.'°°—This distoma was described by Rathonis, who observed
the first specimen in a Chinese woman, thirty-seven years of age. The host
suffered from severe pains, referred to the liver. The parasite resembles D. hepa-
ticum, but is larger (25 mm.); the ramifications of the alimentary canal are less
complex, especially towards the hinder end.

 

Fic. 81.—Distoma lanceolatum (eight times actual size) and Egg:.

CLASS II.—ANNELIDES.

1. Order Nematodes (Round Worms).

a. Family Ascarides.10

1. Ascaris lumbricoides (common round worm).—This is a cylindrical
worm, of some size, with a body that tapers from before backwards.
The male is 250 mm. and the female 4oo mm. long. The head, which
is distinct from the body, consists of three conical prominences (lips)
furnished with tactile papille and minute teeth. The caudal process of
the male is folded hook-like on the abdominal surface, and is provided
with papille. In the female, the vulva lies deeply behind the anterior
third of the body. The eggs are nearly round, and brownish yellow in
colour. Their diameter is 0.06-o.07 mm. In the fresh state they are
covered externally with an albuminous layer, and beneath this is a tough
shell, which in turn encloses the very granular contents.

The Ascaris lumbricoides infests the small intestine in man, and it
appears to be common to all climates. It occurs also in cattle and in
sheep. It has no special medical interest ; but it is thought by Lutz 1

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ASCARIDES. 189

to cause spasm and tympanitis, and to impede nutrition in children.
Kartulis!© records a case of death in a man following directly upon an
invasion of the liver by ascarides. Severe nervous symptoms also, as

 

Fic. 82.—Ascaris lumbricoides. a. The Worm; b. Head; c. Egg.
a, half natural size; 6, slightly magnified ; c (eye-piece I., objective 84, Reichert).

amaurosis, strabismus, and evidence of meningitis,}°° have been found
to accompany their presence in great abundance. They have caused
death by invading the liver.’

 

Fic. 83.—Ascaris mystax.
a. Male; b. Female; c. Head; d. Egg.

2. Ascaris mystax (round worm of the cat).—This worm closely
resembles the preceding, but is smaller, and is readily distinguished

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190 THE FACES.

from it by the shape of its head, which is pointed, and bears two lateral
wing-shaped processes. The male is 45-60 mm. long, and the female
110-120 mm. The eggs are globular, larger than those of A. lum-
bricoides, and covered with a dimpled shell (fig. 83).

3. Oxyuris vermicularis (common thread-worm or teat-worm).—The
female is ro mm. in length, and exhibits two fully-developed uteri,
which extend symmetrically backwards from the vaginal orifice. The
male is rather less than half the length of the female, and its tail is
provided with six pairs of papilla. The head of both sexes is similar.
It displays a remarkable cuticular enlargement and small prominent
lips.

The eggs are irregularly oval, and measure 745 (0.05 mm.) by 7755
(0.02-0.03 mm.) inch. The shell is membranous, and consists of two

 

Fic. 84.—Oxyuris vermicularis.

a. Head; b. Male; c. Female; d. Eggs.

or three lamin. Its contents are coarsely granular. The eges often
contain an embryo with an indistinct alimentary canal and a tail equal
to half the entire length. The presence of the parasite is attended with
uncomfortable sensations, among which itching in the situation of the
anus is prominent. 105

B. Family Strongylides (Leuckart).!°°—To this family belongs one of
the most important and formidable of the parasites which infest the
human intestine. This is—

Anchylostoma duodenale (Dochmius duodenalis, Strongylus duo-
denalis).—It was formerly believed that this worm occurred only in
the tropics and in certain districts of Italy.4° Of late years, numerous

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ANCHYLOSTOMA DUODENALE. I9QI

observations in Italy (Perroncito and others"), Germany, Switzerland
(Menche and others 112), and Belgium 13 have made it clear, together with
the older researches, that the inhabitants of temperate regions are not
free from its attacks.115

The Anchylostoma is cylindrical in form. The male measures 8 to
12 mm. in length, the female 10 to 18 mm. The anterior extremity
is pointed, and reflected towards the dorsal surface. The oral orifice
is armed with four claw-like teeth. The caudal extremity of the male
expands into a pouch with three flaps; that of the female is pointed
and conical ; the vulva is situated behind the middle third of the body.

The eggs are smooth and oval, measure 0.05 to 0.06 mm., and usually
contain two or three large daughter-cells. The embryos develop rapidly

 

Fia. 85.—Anchylostoma duodenale.

d. Female (magnified).
e. Head (eyepiece II., objective C, Zeiss).
i. Eggs.

a. Male (natural size).
6, Female (natural size).
c. Male (magnified).

 

outside the human body. In stools which contain eggs, the embryo:
may be seen and observed after the lapse of twenty-four to forty-eight
hours.

Except when anthelmintics have been administered, the eggs are the
only signs of the parasite to be found in the discharges, and it is con-
sequently of the utmost importance to be familiar with their appearance.
The accompanying figure shows this at various stages of their develop-
ment (fig. 85, /).*

The presence of Anchylostoma is to be suspected in all cases where
a severe form of anemia occurs in labourers (and especially in brick-
burners, miners, and tunnel-borers), without any obvious and sufficient

* [An instructive case of this disease is reported in the Lancet, February 1, 1890.],

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192 THE FACES.

cause. It is, however, necessary to bear in mind that Bothriocephalus
latus produces similar symptoms (p. 186). Examination of the stools
will then afford the means of diagnosis. If the intestines contain
Anchylostoma, the characteristic eggs with their large blastomeres will
be seen. If any uncertainty as to their nature should persist, the fecal
substances containing them should be allowed to remain for some days
in a warm place, and again examined microscopically. The process of
segmentation of the egg will then be seen to have advanced, and fully
developed embryos will be visible here and there. The administration
of anthelmintics, and especially of the ethereal extract of male-fern,
will cause the expulsion of the mature worm, and an inspection of the
resulting discharges cannot fail to establish the diagnosis.

The character of the stools in this affection varies greatly. Diarrhcea

 

Fig. 86.—Trichocephalus dispar.

a. Male; b. Female; c. Eggs; a, 6. Slightly magnified ; c. (eye-piece 11., objective 8a,
Reichert).

is usually present, and blood is frequently passed. But it may happen
that the discharges are altogether normal. They have been known to con-
tain great quantities of Charcot-Leyden crystals (Levchtenstern, see ante).
[In the report of the Ceylon Commission, 1887,"6 anchylostomiasis
was stated to be a cause of beri-beri. The-association is probably
accidental (Sonsino). | 11"

y. Family Trichotrachelides (Leuchart)..8

1. Trichocephalus dispar (whip-worm).—This worm has a whip-like
form, consisting of a short, stout hinder-part, and a long, spiral, filiform
process anteriorly. The male is 40 mm., and the female 50 mm. long.
The short hinder part measures 1 mm. in thickness (fig. 86, a, b).

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TRICHOCEPHALUS DISPAR—TRICHINA. 193

The eggs, which are occasionally to be found in the feces, are brown
in colour, 0.05-0.06 mm. long and 0.02 mm. broad. The shell consists
of two layers and is flattened at either end, where it is furnished with
a small lid, formed of a glossy substance. The yolk is very granular
(fig. 86, ¢). According to Erni" and others, this parasite, together
with Anchylostoma and an insect-larva, produces the beri-heri disease
which is endemic in Sumatra. This view is, however, opposed by other
writers (Scheube, Scheffer).

2. Trichina spiralis.!2°—Trichina occurs in two different forms in
the human body, according as its habitat is the muscular tissue or the

 

Fic. 87.—Trichine.

a. Male, and ), Female Intestinal Trichine, slightly magnified; ce. Trichina of muscle
(eye-piece III., objective IV., Reichert).

intestine. It is with the trichina of the intestine that we have to do
here, since this form alone is found, though rarely, in the feces. The
male is 1.5 mm. in length, and the female 3 mm. The former has four
prominent papille situated between the conical protuberances at the
extremity. The sexual organs of the female consist of a tubular ovary,
which is placed at the hinder part of the body, and a tubular uterus,
with which the ovary communicates in front (fig. $7). Impregnation
takes place in the intestine. The eggs develop into embryos while still
within the uterus, and the newly-born parasite almost immediately per-
forates the gut, and becomes imbedded in the muscles of its host.
N
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194 THE FACES.

Of their own accord these worms rarely pass with the stools. But
in any case where there is reason to believe that trichinous meat has
been eaten and trichinosis is apprehended, an anthelmintic may be given,
and the detection of intestinal trichina in the feces will establish the
diagnosis in a very early stage of the affection.

8. Rhabdonema Strongyloides (Leuckart).—Certain nematode worms
have been discovered in the stools in cases of Cochin-China diarrhcea
(Normann, Bavay, Seifert). They occur commonly in conjunction
with Anchylostoma (Grassi, Parrona, Perroncito).!22 It was formerly
thought that there were two distinct parasites of this kind, viz., Anguil-
lula intestinalis and Anguillula stercoralis; but more recent observa-
tions by Leuekart and Grassi "3 have shown that the latter is only an

 

Fic. 88.—Anguillula stercoralis.

a. Female; b. Male; c. Head (eye-piece II., objective 8a, Reichert).

intermediate form in the development of A. intestinalis. A complete
knowledge of the subject, however, implies an acquaintance with this
form, as it may be confounded with other Helminthide. The life-
history, according to Grassi, is as follows :—

The Anguillula which infests the human intestine deposits eggs, from
which the young are produced as embryos or larve. These are dis-
charged with the stools. As found there, they already exhibit sexual
maturity (Anguillula stercoralis) and produce embryos, which undergo
no further change in the human system. The body of this worm is
round, and shows faint traces of transverse striation. The head is in
the form of a blunted cone (fig. 88) and sessile upon the body. It is
furnished with two lateral jaws, each bearing a pair of teeth. The

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ANGUILLULA STERCORALIS—INSECTS. 195

male is 0.88 and the female 1.22 mm. long. Anguillula intestinalis
measures 2.25 mm. in leneth and 0.04 mm. in thickness at its middle.
It has a triangular mouth closed by three small lips. The vulva lies
at the junction of the middle with the posterior third. Its habitat is
the small intestine. The egos resemble those of Anchylostoma duode-
nale, but are longer, more elliptical, and pointed at the poles. In recent
stools the larve alone are to be seen. It is doubtful whether the para-
site 1s directly mischievous ; but its constant association with Anchylos-
toma, and the readiness with which the two may be confounded, render
its recognition a matter of consequence.

3. Insects.—It requires to be noticed that insect larve infest the
stools. Joseph !*4 has reported a number of species, which are for the
most part taken into the intestine with food (cheese, meat), and give
rise to a variety of morbid symptoms, as colicky pains, vomiting, Xe.
(see p. 158). Special mention may be made of the immature cheese-
maggot (Piophila casei) and Drosophila melanogastra, which are derived
from curdled milk, and may attain the chrysalis form in the intestine
before they are discharged per rectum. Of other species are the larvee
of three varieties of Homalomyia, of Hydrothza meteorica, Cyrtoneura
stabulans, Calliphora erythrocephala, Pollenia rudis, Lucilia caesar and
regina, Sarcophaga hemorrhoidalis and hematodes, and Eristalis arbus-
torum, all of which are apt to occur. Rembold, Lampa, and Kohn 1°
have also observed in the stools certain lancet-shaped bodies, 8 mm,
long, which are covered with hair and indented on the surface, and
these have been identified by V. Graff as the larve of Anthomyie.
[ Finlayson °° records a case in which swarms of larve were passed alive
from the bowel of a man. He identified the insect as Anthomyia
canicularis or scalaris. |

4. CRYSTALS.—Crystalline bodies are a common constituent of the
feeces, and in some cases are to be found in great quantities. They may
be organic or inorganic.

1. Charcot-Leyden Crystals.—These bodies, of which an adequate
description has already been given in connection with the Blood (p. 30)
and the Sputum (p. 110 and fig. 62), are comparatively rarely to be seen
in the feces. Nothnagel has met with them in typhoid fever, and
Leichtenstern 2" in phthisis and anchylostomiasis. Their presence, how-
ever, has no pathological significance.

2. Hematoidin Crystals.—It is surprising that so little attention has
been paid to this subject. Ufelmann,!* indeed, remarks that crystals
of hematoidin are sometimes present in the discharges of infants at
the breast ; but apart from this notice the matter has been passed by in
silence. The author has found these crystals often enough in the feces,
especially in chronic intestinal catarrh from over-eating, and in many

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196 THE FAECES.

instances in which blood had been discharged into the intestine some
time (several days) before the stools were passed. They usually exhibit
an ill-marked crystalline structure. Particularly good specimens were
seen in the stools of a patient suffering from nephritis. The crystals
are sometimes free, and sometimes enclosed in masses of a shining

 

Fic. 89.—Hematoidin Crystals from Acl olic Stools (eye-piece III., objective 8a, Reichert).

substance which resembles mucin (fig. 89). Similar crystals were found
in the liquid motions of a man who suffered from pernicious anemia
(v. Jaksch).

8. Cholesterin.—This substance enters normally into the constitution
of the feces, and can always be obtained from them.

It seldom appears in its crystalline form (fig. 125), according to Noth-
nagel, and the statement is undoubtedly correct. (For the microscopical
and chemical character of cholesterin, vide infra and chapters on Sputum
and Urine.)

4. Fat Crystals.—Nothnagel, in his well-known monograph,! states
that fatty substances occur in the feces in the form of needles.

 

Fic. 90.—Acholic Stools (eye-piece 11I., objective j;, oil immersion, Reichert >
Abbe’s mirror, narrow diaphragm),

Gerhardt 1° found quite an enormous quantity of organic crystals in the

stools of jaundice (fig. 90). He was himself of opinion that such bodies ©
consisted of tyrosin; but one of his pupils, named Oéesterlein,31 who

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CRYSTALS—INORGANIC SALTS. 197

ed the investigation farther under Gerhardt’s auspices, came to the
clusion that chemically they were lime and magnesia salts of the
her fatty acids, and that, therefore, soaps of lime and magnesia hases
form a part of such discharges. According to Stadelmann,!? they are
sodium soaps. The author, however, can add his own testimony to
Gerhardt’s statement, for he has repeatedly seen great quantities of
crystals arranged in clusters in acholic stools; and is disposed, on the
grounds of separate investigation, and especially of the ascertained
character of similar bodies occurring in other excretions (see chapter on
Urine), to believe that such crystals do not consist of tyrosin, but rather
of a combination of the alkaline earths with the higher fatty acids.

Uffelmann, 8° who had already observed these crystals in the discharges
of infants, arrived independently at the conclusion that they could not
consist of tyrosin. According to #r. Jfiller,!** their presence indicates
an impediment to the absorption of fat from the intestines,

In cases of jaundice, so frequent among children, such crystals are
profusely present in the stools, and they are normally found in those
of infants during lactation (v. Jahsch).

5. Oxalate and other Organic Salts of Lime.—Ovxalate of lime is a
sufficiently common constituent of the feeces, and appears on micro-
scopical examination (see fig. 112). According to Nothnagel, it is always
derived from the food. It is most abundant after a vegetable diet, and
when manifested in considerable quantity the discharges also contain
abundant débris of plant-tissues.

Uffelmann'® asserts that crystals of lactate of lime occur in the
discharges of children as sheaves of radiating needles. Other organic
salts of lime, as the acetic and butyric acid salts, have been observed in
the discharges of persons suffering from acute gastric and intestinal
catarrh (v. Jahsch) 1%

6. Carbonate of Lime occurs rarely in the stools as amorphous par-
ticles and dumb-bell figures (fig. 124).

7. Sulphate of Calcium.—This salt is very seldom present in the
stools. It can be obtained, however, by the action of sulphuric acid
on the feces, which shows that other lime salts are present. Its form
presents the same variety here as in the urine (fig. 116).

8. Phosphate of Lime.—This substance crystallises in stout or elon-
cated wedges, grouped together so as to form larger or smaller gland-
like masses (fig.115). The presence of such crystals in the feeces is without
pathological significance.

Other salts of lime are occasionally met with. They are impregnated
with bile-colouring matters, and deeply stained a yellow colour.

9. Triple Phosphate-—The phosphate of ammonia and magnesia
occurs sometimes as well-formed coffin-lid crystals (fig. 66, 7), some-

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198 THE FECES.

times in ill-defined crystalline masses, and very rarely in the elder-leaf
arrangement (fig. 121).

Perfect crystals are most commonly to be found in fluid motions,
and in the mucus which adheres sometimes to the feces, whether liquid
or solid. Fragments of coffin-lid crystals alone may be visible, and
these often exhibit fissures and flaws, or there may only be mere
splinters (Nothnagel). It is notable that these crystals seldom take
up bile pigment. By their chemical constitution they may he readily
recognised ; and they dissolve easily, as has been already mentioned, in
acetic acid (p. 113).

10. Sulphide of Bismuth Crystals —When preparations of bismuth
have been taken internally, the stools may be found to contain crystals
which bear a remarkable resemblance to those of chloride of hematin

 

Fic. 91.—Sulphide of Bismuth Crystals from the Stools (eye-piece III., objective 84, Reichert).

(hemin). They consist of sulphide of bismuth, as may readily be shown
by a comparison with the bodies formed when nitrate of bismuth is
added to ammonium sulphide.

IiIl. CHEMICAL EXAMINATION OF THE FACES.—In striking
contrast with the valuable information to be derived from the naked-eye
and microscopic investigation of the feeces is the very slight assistance
which the chemical examination of those discharges lends to the purposes
of diagnosis.

A. Organic Substances.

1. Mucin.—Mucin, as Hoppe-Seyler 1°" has said, may be looked upon
as the basis of the fecal substances, a statement which can be confirmed
by the author. #7. Miller, on the other hand, asserts that mucin is
not so abundantly present in the stools. For the detection of mucin

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ORGANIC SUBSTANCES. 199

in the stools the following process may be recommended :—The feces
are stirred up with water, their own bulk of lime-water added, and the
mixture allowed to stand for some hours. It is then filtered, and the
filtrate tested with acetic acid for mucin (see chapter on Urine).

2. Albumin.—The presence of albumin may be shown as follows :—-
The feces are mixed with a large quantity of water, to which a trace
of acetic acid has been added, and a watery extract is thus made. This
is repeatedly filtered, and the filtrate may be submitted to the tests for
albumin mentioned in the chapter on Urine (q. v.). Under ordinary
circumstances no proteid reactions can be obtained, but albumin occurs
in considerable quantity in the stools of typhoid and diarrhcea. In one
instance, much serum-albumin was found in the discharges of a chlorotic
woman, who passed pale stools almost devoid of bile; and once again in
the case of a patient whose stools were deficient in bile, but who was
not jaundiced (v. Jaksch).

3. Peptone.—For the detection of peptone, the feces should be
mixed with water so as to form a thin pulpy fluid, then boiled, and
filtered while still hot. The filtrate will be clear or slightly tinged with
red. When it has cooled, it may he tested for albumin with acetic
acid and ferrocyanide of potassium. It usually happens that the liquid
becomes a little turbid when the acetic acid is added (mucin), but the
turbidity does not extend on the addition of ferrocyanide of potassium.
When this is so, the mucin may be precipitated with acetate of lead,
the filtrate tested in the manner afterwards to be described (chapter on
Urine) with phosphotungstic acid, and the fluid which finally remains
may be submitted to the biuret test. Should it happen that the fluid
after boiling contains albumin as shown by the acetic acid and ferro-
cyanide of potassium test, this substance must be removed by combina-
tion with ferric acetate (see chapter on Urine), and the remainder of the
process conducted as above.

The author has never found peptone in healthy feces, but has met
with it repeatedly in disease. He has collected the records of some fifty
or sixty cases bearing upon this matter, and the results which were
obtained depend upon seventy or eighty separate analyses.

Out of seven cases of typhoid, peptone occurred in the liquid stools
in large quantities in five. Its presence remained doubtful in one, and
it was absent from the discharges of the seventh.

It was present in all cases where the stools contained pus, as in dys-
entery (two cases), tubercular ulceration of the intestine (three cases),
and suppurative peritonitis discharging pus into the intestine (one case).

In hepatic affections, the character of the feces in this respect was
very inconstant. In a series of cases of catarrhal jaundice with more
or less acholic stools, no peptone was to be found; whilst, on the other

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hand, the thin non-purulent discharges from a patient with syphilitic
inflammation of the liver exhibited it in considerable quantity. It
occurred plentifully in certain cases of atrophic cirrhosis and of car-
cinoma of the liver.

Acholie stools without jaundice were generally rich in peptone, but
the results of analysis in these cases show much variety (v. supra).

4. Urea.—The presence of urea may be best ascertained by the
method previously described (p. 69). For the estimation of metabolism,
it is necessary to ascertain the total quantity of nitrogenous substances
contained in the feces. To do this, the stools should be treated with
dilute acid (to prevent the evaporation of ammonia) and dried. The
usual method for the analysis of organic compounds will then serve to
determine the proportion of nitrogenous bodies present (see chapter on
Crine).

5. Carbohydrates.— Various carbohydrates occur in the feces. Of
these starch is the most prominent. It may be recognised at any time
by the aid of the microscope. Hoppe-Seyler 8 asserts that grape-sugar
and certain gummy carbohydrates may be contained in the stools.

To ascertain the presence of these substances, the feeces must be
boiled with water, filtered, and the filtrate partially evaporated on a
water-bath. One part of the fluid may then be tested with Trommer’s
or the phenyl-hydrazin test for sugar. To another part a little of the
iodo-potassic iodide solution may be added, to show the presence of
starch. The remainder of the fluid may now be distilled, and the
residue extracted with alcohol and ether (see chapter on Urine); the
extract boiled with water and filtered ; the filtrate partially evaporated ;
treated with dilute sulphuric acid, and boiled; saturated with caustic
soda; treated again with cupric sulphate, and boiled. The reduction
phenomenon will show the presence of dextrin and gums (Hoppe-
Seyler).

The property of benzoyl chloride to form insoluble compounds with
carbohydrates in alkaline solutions may also be utilised as a test.

6. Acids.

(«.) Bile Acids.—For the detection of bile acids, the distillation
residue of the feces may be tested in the manner already described in
connection with the blood (p. 75). If biliary acids be present in great
quantity, the application of Pettenkofer’s test directly to a watery
extract of the feces (p. 76) will suffice for their recognition. They
may also be detected by the addition of a watery solution of furfurol
and sulphuric acid (p. 76, and chapter on Urine).

(8.) The Volatile Fatty Acids.—To obtain these bodies from the
feeces, the following plan may be adopted :—Dilute the fecal mass with
water, add phosphoric acid, and distil. The distillate contains these

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ORGANIC ACIDS. 201

acids together with indol, phenol, and scatol. If this distillate be
neutralised with carbonate of soda and again distilled, the indol, phenol,
and scatol will pass over, and the sodium salts of the fatty acids remain
behind. Let these now be evaporated to dryness on the water-hath,
the residue extracted with alcohol, and after the evaporation of the
latter dissolved in water. The solution may then he tested for fatty acids.

The separation of the different fatty acids may be accomplished by
fractional distillation when they are present in abundance. Moreover,
they may be partially isolated by precipitation of the sodium salts with
ether in alcoholic solutions of varying degrees of concentration (v.
Jaksch).4° When there is sufficient material at hand, it is a good
plan to convert the acids into their silver or barium salts, and to effect
their separation on the principle of their different degrees of solubility
in water,

The estimation of the silver, barium, or sodium constituent in the
corresponding salts may be effected in the reactions given below, and
the proportion of the respective acids determined accordingly. Of the
volatile fatty acids, butyrie and acetic acids are those most readily to
be found in the feces.!4! Formic and propionic acids do not appear to
have been recognised with absolute certainty, but we shall take account
of them here, since it is certain, at any rate, that they occur in another
secretion (urine).1#

(a.) Formic Acid.—This is a colourless liquid, of a pungent pene-
trating odour, which freezes at o° C., boils at 100° C., and is miscible
with alcohol and water.

1. Free formic acid is not precipitated by nitrate of silver, but. this
reagent will precipitate the alkaline salts of the acid from concentrated
solutions. The silver compound blackens quickly in the cold,, and
when heated reduction takes place.

2. If a solution of perchloride of iron be added to a solution of a
neutral salt of formic acid, a blood-red colour appears. This hue disap-
pears on boiling, and a rust-coloured sediment remains.

3. If formic acid or an alkaline salt of the acid be heated with
mercuric chloride to 60° or 70° C., a precipitate of subchloride of
mercury forms. This reaction is impeded by the presence of free
hydrochloric acid or of excess of an alkaline chloride.

(b.) Acetic Acid is a fluid with an acrid, pungent odour. Its boiling-
point is 119°, and it crystallises at o° C. Heated with ferric chloride,
its salts behave like those of formic acid. Nitrate of silver yields a
precipitate in neutral solutions of a salt of acetic acid, and this preci-
pitate dissolves in boiling water without being reduced.

When a salt of this acid is heated with sulphuric acid and alcohol,
the characteristic odour of acetic ether is obtained.

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202 THE FACES.

(c.) Propionic Acid.—This is an oily fluid. It boils at 117°C. Pro-
pionic salts exhibit the same reactions with nitrate of silver as those of
formic acid. With ferric chloride they do not yield a red colour.

(d.) Butyric Acid.—In the pure state butyric acid is an oily fluid,
with a goat-like odour, which boils at 137° C. It is miscible in all
proportions with alcohol and ether. Its salts, when treated with
mineral acids, develop the characteristic goaty smell. Ferric chloride
solution does not give a red colour in solutions of such salts, while
nitrate of silver forms a crystalline sediment which is insoluble in cold

water.

To isolate butyric acid from the isobutyric acid in the feces, the portion which
distils at 158° C. should be treated with carbonate of guanidin (Brieger 4%), and
the guanidin salt obtained converted by heating into the corresponding guanamin.
The base examined under the microscope will then exhibit the characteristic
pointed rhomboids of the guanamin of isobutyric acid.

Valerianic, caproic, and others of the higher fatty acids are also present in the
feces. Wegscheider 4 asserts that oleic, palmitic, stearic, capric, and caproic
acids occur in the discharges of infants.

7. Phenol.—This substance is always a constituent of feces. When
the fatty acids have been converted'‘into their sodium salts in the
process described above for the separation of the volatile fatty acids,
phenol passes over in the distillate. To isolate it from indol and
scatol, the distillate must be rendered alkaline with caustic potash and
again distilled. The phenol remains behind, and may be purified by
distillation with sulphuric acid.

(1.) If a portion of the distillate now be treated with a solution of
ferric chloride, a violet colour will show the presence of phenol.

(2.) The addition of bromine-water to another portion will cause the
deposition of a crystalline sediment of tribromophenol.

(3.) Millon’s reagent gives a red colour.

8. Indol and Scatol.—Both these bodies occur in the feces, the
latter having been detected there by Brieger.14° To separate them
from the phenol present, the distillate in the above process (see ante,
Volatile fatty acids) should be treated with an alkali and again distilled,
when indol and scatol will pass over. Indol forms in small colourless
scales like those of benzoic acid. It dissolves in boiling water and
very readily in alcohol, and is decomposed by strong alkalies.

Scatol, which also crystallises in colourless scales, is much less readily
soluble in water, and possesses a disagreeable pungent smell. It is not
decomposed by fairly strong alkalies.

To obtain either of these bodies separately, we avail ourselves of the
lesser solubility of scatol in water, or of its property of resisting the

action of alkalies.

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CHOLESTERIN—FATS. 203

 

(1.) If nitric acid which contains nitrous acid be added to a solution
of indol, a distinct red colour is produced, or a red precipitate if the
solution be concentrated.146

(2.) Pine-shavings steeped in hydrochloric acid are tumed red in an
alcoholic solution of indol. The first test, when applied to scatol, does
not produce a red coloration, but at most a slight turbidity. The second
entirely fails. Jointly they will serve sufficiently for the discrimination
of these two substances. 17

9. Cholesterin, Fats, and Non-Volatile Organie Acids.—
Cholesterin, as we have seen, seldom occurs as crystals in the feces,
but, according to Hoppe-Seyler, is in one form or the other an invari-
able constituent of those discharges. For its detection chemically, the
residue which remains when the volatile fatty acids and phenol group
have passed over in the process of distillation is to be treated with
excess of sulphuric acid, and extracted first with alcohol and then with
ether. (1.) The ethereal extract is filtered, the wether removed by
distillation, and the residue first digested with carbonate of soda on the
water-bath, so as to remove any traces of the volatile fatty acids that
may have failed to pass over with the ether, evaporated to dryness,
and again extracted with ether. (2.) The alcoholic extract is also
filtered, treated with carbonate of soda, the alcohol distilled off, the
residue dissolved in water, and finally, as before, extracted with ether.
In the alkaline watery residue are contained the biliary acids (v. supra),
oleic, palmitic, and stearic acids, which, according to Hoppe, may be
separated by converting them into their barium salts.

Cholesterin and fat are taken up by the ether. The latter is evapo-
rated, the residue treated with alcoholic solution of caustic potash, the
alcohol removed by evaporation on the water-bath,48 and the remain-
ing fluid diluted with water and extracted with ether. The fats remain
as soaps in the watery solution, while the cholesterin is dissolved by
the ether.

Cholesterin may be recognised by the following tests :—

(1.) A little concentrated sulphuric acid applied to the crystals on
a slide will cause them gradually to colour a reddish-yellow round their
borders, and finally to grow smaller and disappear.

(2.) When the crystals are dissolved in chloroform and sulphuric acid
is added, a blood-red colour forms, presently changing to purple-red.
The sulphuric acid at the same time shows a strong green fluorescence.

(3.) A particle of cholesterin to which a little nitric acid has been
added is placed in a small dish and evaporated to dryness in the water-
bath. . It leaves a yellow stain, which turns a yellowish-red on the addi-
tion of ammonia (Schulze).

The soap-solution obtained in the above process is to be rendered

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204 THE FASCES.

acid with dilute sulphuric acid, and the resulting fatty acids removed
by filtration. If the filtrate be neutralised with ammonia, evaporated,
and extracted with alcohol, it will be found to contain glycerine. The
fatty acids may be again dissolved in ether, repeatedly saponified,!°?
collected and dried, and then identified, first by ascertaining their
melting-points, and again by converting them into their barium salts,
and determining in each case the value of the barium constituent
( Hoppe-Seyler).11

Fats, and especially neutral fats (tri-glyceride), soaps, non-volatile
fatty acids, and cholesterin, are present in all feces. Acholic stools
present them in relatively large quantities. According to Miiller,'>?
clinical inferences can be based on a. knowledge of the melting and
solidifying points of the fatty acids.“? Both points are higher in pro-
portion to the efficiency of intestinal absorption. When the fatty acids
of the feces contain a proportion with a melting-point so low as 50° C.,
this function is probably impaired.

For the quantitative estimation of fats in the stools the methods of
Hoppe-Seyler and Benedikt + may be employed. That of Atiller! is
more expeditious and serves well for clinical purposes. To determine
the amount of fats formed with a given diet, as milk or flesh, powdered
animal charcoal is administered with the first meal, which should be
taken on an empty stomach. The earliest resulting feces are thus
stained black. A portion is dried at 100° C., and by extraction with ether
in Soxhlet’s apparatus the neutral fats and free fatty acids are obtained.
These are dissolved in warm alcohol and a little ether, and submitted to
titration with phenol-phthalein solution and alcoholic solution of caustic
potash. The result of titration shows the proportion of fatty acids
present. Another portion of the dried feces is extracted first with acid
alcohol and afterwards with ether to determine the amount of soaps
contained in it. In intestinal disease, especially such as involves the
lymphatics, and where the flow of bile is suspended (M/ziller) °° the feces
contain great quantities of fat, showing that absorption is impeded.

10. Colouring Matters.

1. Urobilin—This is the normal colouring matter of the feces
(p. 164). It can readily be obtained from the stools by treating them
with acid alcohol.

Mehws*’ method for the isolation of urobilin in feces yields
excellent results. A watery extract of the feeces is made, and to this
is added sulphuric acid in the proportion of 2 grms. to the litre, and
solid ammonium sulphate. The fluid is then filtered, and the pre-
cipitate washed with a warm. saturated solution of ammonium. sul-
phate, dried on a water-bath, and extracted with a boiling alcoholic
solution of ammonia. Urobilin may be shown in the extract so formed

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COLOURING MATTER—GASES. 205

by its characteristic spectrum in acid solutions. This exhibits a well-
defined absorption-band between the lines ) and F' (Fraunhofer) of the
solar spectrum (fig. 130).

It should be noted that urobilin may be present even in acholie stools.

2. Blood Colouring-Matter.—Pure blood occurs in the stools only
after very profuse and rapid hemorrhage into the intestine. In all
other cases where its constituents are found they are greatly altered.
Hematoidin crystals are rarely seen. Hematin is the form in which
blood pigment occurs most commonly. This substance may best be
recognised by Teichmann’s test, or with the spectroscope (pp. 61, 66).

3. Bile Pigment.—The feces never contain bile pigment in health,
but it is found abundantly in the discharges in cases of catarrh of the
small intestine. It may be best detected by the application of G'melin’s
test (nitric acid). On the addition of a little impure nitric acid to a
specimen of feces in which bile pigment is present, the mass changes
colour quickly, and the separate drops of the acid are surrounded with
rings of green, red, and violet. The appearance of a green ring is very
characteristic of bile pigment, and is due to the formation of biliverdin.
We have already spoken of the other pigments which may occur in the
stools (see p. 165).

11. Intestinal Gases.—These consist of hydrogen, carbonic acid,
nitrogen and volatile carburetted hydrogen (methan).* It is not yet
definitely determined whether sulphuretted hydrogen is formed in the
intestine or not. Senator and Ottavio Stefano,? however, maintain that
in certain morbid states this gas is generated in such quantity as to
cause symptoms of poisoning. The fact that sulphide of bismuth is
formed in the alimentary canal when nitrate of bismuth has been taken
(v. Jaksch), lends probability to the assumption that sulphuretted hydro-
gen is also produced there. According to Hammarsten,! the latter
occurs in small quantity in normal feces.

12. Ptomaines. — Putrescin and cadaverin are present in the
stools, and may be recognised by the methods already laid down.
Moreover, the ptomaines known to be produced by pure cultivations of
certain pathogenic fungi have recently been obtained directly from the
feeces, as by Powchet1®! in cases of cholera. Bawmann and Udranshy,
Stadthagen and Brieger1® have separated diamines from the stools of
patients with cystinuria (see chapter on Urine). They believe that these
substances are absent from normal feces. See the methods described at
p- 158.

13. Ferments.

Diastase and Invertin are generally present in the stools of healthy
children (v. Jaksch).1°* For the detection of diastase see p. 82.

B. Inorganic Substances.—The consideration of such inorganic

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substances as assume a crystalline form has already engaged our atten-
tion (p. 195). Chloride of sodium may be detected in the feeces thus :—
An extract is made with water, acidulated with nitric acid, filtered, and
the filtrate tested with nitrate of silver. A white precipitate (chloride of
silver), soluble in ammonia, will show the presence of the sodium salt.

In Hoppe-Seylei’s 1+ method for the quantitative analysis of inorganic
matter in the stools, the substances which are soluble in alcohol are
separated from those which are soluble in dilute acetic and hydro-
chloric acids before the process of incineration is commenced. If this
is not done, there is danger that the nuclein, which is nearly always
present in feces, will be decomposed, setting free its phosphoric acid,
which may then either remain uncombined or displace other acids from
their compounds. The analysis, both quantitative and qualitative, of
the incinerated ash is conducted according to methods which are suffi-
ciently familiar.!%°

IV. EXAMINATION OF THE MECONIUM.—The term ‘meco-
nium” is applied to the substance discharged from the rectum of the
child immediately after birth. It is a thick, sticky, viscous fluid, of a
greenish-brown colour. When examined by the microscope, meconium
exhibits some intestinal epithelium cells, fatty particles, both fluid and
solid,!®* numercus cholesterin crystals, a quantity of more or less well-
formed crystals of bilirubin, and some downy hairs. There are imme-
diately after birth no fungi, and (according to Escherich 1%") no spores.
After the lapse of twenty-four hours, however, the discharges exhibit a
very different character. They now contain abundance of micro-organisms,
and Escherich obtained from them by Koch’s plate-cultivation methods
three distinct microbes.

After the child has taken the breast, the bacteria of the stools,
according to the same authority, are represented by two species of micro-
organisms. The first consists of thick, curved, rod-like bodies, measuring
1-5 “in length by o.3-0.4 w in thickness. The other is a micro-organism
which closely resembles the lactic acid bacillus of Hvippe.168

In addition to the above, the meconium contains numerous squamous
epithelium cells, derived from the pharynx and esophagus, or from the
anal orifice (Bizzozero).1

Zweifel and Hoppe-Seyler, who have investigated the chemical con-
stitution of the meconium, found it to contain bilirubin, biliverdin, and
bihary acids, but no hydro-bilirubin (urobilin), Wegscheider 17! found
traces of peptone, fats, and soaps, bilirubin, and traces of hydro-bilirubin
in infantile stools. In a specimen which the author examined, there
was no serum-albumin, peptone, or sugar. There was abundance of
mucin, Pilirubin was the only pigment present.

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ACUTE AND CHRONIC INTESTINAL CATARRH. ZOY

V. CHARACTER OF THE FACES IN CERTAIN INTESTINAL
AFFECTIONS.

1. Acute Intestinal Catarrh.—In this condition the quantity of
the stools is subject to great variety. They are usually fluid, thin, and
slimy, yellowish-brown in colour, and emit a most unpleasant smell.
Their reaction is alkaline, except in the case of acute enteritis of chil-
dren, when it may be acid. Such stools usually contain great quantities
of mucus, and there are often visible to the naked eye food remnants in
great quantity.

Microscopical examination reveals an abundance of fungi of vari-
ous descriptions, large quantities of intestinal epithelium, and isolated
leucocytes.

2. Chronic Intestinal Catarrh.—In this disease the stools
exhibit no very distinctive characters, whether to the naked eye or
microscopically.

Vothnagel 1"? lays down the following rules for the localisation of
chronic idiopathic intestinal catarrh, according to the character of the
feeces :—-

1. When the large intestine is alone involved, a single discharge
takes place within twenty-four hours. Diarrhcea, however, is apt to
recur at certain regular intervals.

2. When the small intestine alone is engaged, the motions are also
likely to be sluggish.

3. When both the large and small intestines are the seat of catarrh,
continuous diarrhea is apt to ensue.

4. Solid or semi-solid stools containing hyaline particles of mucus,
which can be recognised only with the microscope (see p. 166), and
devoid of mucus visible to the naked eye, point to implication of the
upper part of the large intestine.

5. The presence of bile pigment in the stools, as shown by Gmelin’s
test, invariably indicates a catarrh of the ileum and jejunum. In such
cases also the feces are usually found to contain epithelial cells and
mucus, deeply stained yellow by the bile colouring matter.

In certain forms of chronic catarrh, where the large intestine is
especially involved, it sometimes happens that the bodies described at
p. 165 are to be found in the stools. Such an affection is then called
enteritis tubulosa or membranacea; but it is probable that these mani-
festations accompany other sufficiently dissimilar morbid states. Our
present knowledge of the subject is defective.

3. Ulcerative Enteritis. —The diagnosis of this condition is
always attended with difficulty. It is usually (though not always)
accompanied with diarrhea. In a questionable case, the appearance
of blood in the stools makes ulceration probable ; but we cannot derive

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208 THE FACES.

any conclusive evidence from either the physical or the chemical char-
acter of the feces to establish the diagnosis. A diligent examination
of the discharges, however, may in certain specific forms of ulceration
disclose the presence of the pathogenic organisms to whose influence
the process is known to be due. The detection of the tubercle-bacillus
especially is in this way a fact of the utmost clinical significance
(see p. 103).

4. Typhoid Fever. — This disease is usually characterised by
abundant foul-smelling discharges of the colour of pea-soup. They
contain large quantities of bile pigment, a fact which points to a catarrh
of the small intestine, and to which also Nothnagel attributes the
peculiarly offensive character of the smell emitted,

The reaction of typhoid stools is in all cases alkaline.

Microscopical examination shows numbers of bile-stained epithelial
cells, some leucocytes, abundance of triple phosphate crystals, and a
profusion of fungi. Nothnagel’s clostridia are especially prominent
amongst these. The typhoid-bacillus, of course, infests the discharges
of this disease ; but it cannot be distinguished from the other micro-
organisms by a simple microscopical examination. This can be done
only by the bacteriological methods indicated at p. 178.

The stools of typhoid in its later stages may be those of intestinal
ulceration. Thus, when hemorrhage results from the extension of
typhoid ulcers, the feeces will be blackened, and yield the chemical
reactions which denote the presence of a derivative of blood pigment
(hematin).

5. Dysentery.—The discharges of dysentery are subject to a great
variety of character ; but there is one respect in which they are constant,
for they always contain abundance of mucin, and in the author’s experi-
ence also some serum-albumin and much peptone.

Under the microscope there are to be seen great quantities of
leucocytes, intestinal epithelium, and fungi. Tolerably perfect red
blood-corpuscles are occasionally visible. The number of these latter
varies within broad limits, but the other microscopical appearances are
remarkably uniform.

The grosser properties of dysenteric stools, on the other hand,
display notable differences. Founded upon these, Heubner 1”? distin-
guishes :—

1. Mucous and muco-sanguineous discharge.—A pale yellow, viscous,
transparent substance tinged with blood, cohering in masses, with or
without admixture of feces.

2. Sanguineo-purulent discharge.—A reddish or yellow fluid, contain-
ing floceulent or solid particles as large as a pea or a bean. Such stools
may be compared to raw minced meat.

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DYSENTERY—CHOLERA. 209

3. Discharge of pure blood.—This oceurs when a vessel has been
opened by the extension of a dysenteric ulcer.

4. Discharge of pure pus.—This consists almost exclusively of leuco-
cytes, and belongs to the later stages of dysentery.

5. Gangrenous stools.—Such stools are brownish-red or brown-black
in colour, from the presence of altered pigment. They emit a putrid
odour. They indicate extensive gangrene of the intestinal mucous
membrane.

It was in dysentery that the stools were first noticed to contain those
mucous particles which have been compared to frog-spawn (see p. 166),
and which Nothnagel afterwards observed in other intestinal diseases.
They have no special clinical significance in this disease.

On the whole, it may be said that the naked-eye characters of dysen-
teric stools are so remarkable that they will ordinarily suffice to establish
a diagnosis without the aid of the microscope.

Amebe, which have lately been found in such stools, have been
credited with a causal relation to the disease (Hlava and Kartulis)."*
A similar importance is attached by others to a pathogenic fission-fungus
(Klebs, Chantemesse and Widal),° but with less reason.

6. Cholera.—During an epidemic of cholera, there is usually pre-
valent a form of diarrhcea which is distinct from that disease, and it is
of the utmost importance to possess the means of discriminating between
the two. The discharges of the less formidable complaint are not charac-
terised by any special changes ; but, in a doubtful case, the investigation
in the stools for cholera bacillus (as indicated at p. 173) may be needed
to establish the diagnosis.

In a pronounced case of Asiatic cholera, on the other hand, no kind
of ambiguity can exist. The discharges are thin, and devoid of smell
and colour. They have been aptly termed ‘“rice-water” stools. Micro-
scopically they abound in leucocytes and epithelium, and their specific
micro-organism, the comma-bacillus, may be readily detected. It must,
” stools are not by themselves
pathognomonic of cholera. They are seen repeatedly in heat-apoplexy
and arsenical poisoning ; and in such connection, as well as in cholera,
they hold a profusion of intestinal epithelium. It follows that the
diagnosis of Asiatic cholera will rest on an absolutely secure basis only
when the comma-bacillus has been found, separated from the stools,
and cultivated by the methods with which we are already familiar
(p. 174). Chemically, the discharges of cholera contain serum-albumin 17°

however, be borne in mind that “‘vice-water’

and much mucin.

7. Hemorrhagic Stools.—Blood is discharged with the stools in
cases of great venous congestion of the intestine, in typhoid, in tubercular
and dysenteric ulceration of the stomach or intestine, and in round

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210 THE FACES.

ulcer of the stomach or duodenum, ‘These cases are always attended

with symptoms of severe intestinal trouble. The blood is usually '
profoundly altered (p, 205); but when the hemorrhage has taken place

in the lower part of the alimentary canal, as the sigmoid flexure or

rectum, pure bright blood may be passed.

8. Acholic Stools.—The stools may he deficient in bile in cases of
jaundice from obstruction of the biliary ducts, or they may be so in the
absence of this condition.

’ They are characterised by (1) their whitish-grey colour, (2) the abun-
dance. of fat which they contain, and (3) a profusion of fat crystals,
probably soaps of soda, lime, and magnesia (fig. go).

Such stools in. connection with jaundice imply an obstruction to the
flow of bile by blocking of the ducts. When they occur independently
of obstruction, the underlying cause is not yet sufficiently understood.
Many theories have been framed to account for the phenomenon :—(1.)
It may be either that the bile pigment has undergone some change in
the intestine which prevents the formation of its metabolic product
(urobilin) ; or (2.) the secretion of bile may be so scanty that there is
not enough pigment for the elaboration of urobilin ; or (3.) it is possible
in such cases that the latter is replaced by certain colourless metabolites
of bilirubin (v. Nencki’s leucohypobilin). The latter view is supported
by the fact that considerable quantities of urobilin may be obtained
from acholic stools by extraction with acid alcohol (v. Jaksch, Pel,
Le Nobel)."" The stools may be devoid of bile in cases of the most
varied origin—as in tuberculosis of the intestine, chronic nephritis, and
chlorosis—where no trace of jaundice is present. They are commonly
so in the fatty discharges which accompany indigestion in children
(Biedert)."8  Berggriin and Katz" have observed acholic stools in
the chronic tubercular peritonitis of children. In these cases, as usual,
the feeces contained excess of fat. It follows, therefore, that we cannot
infer the character of the stools from the presence or absence of this
symptom. But in all cases where colourless stools concur with jaundice,
the cause is to be found, as has already been said, in obstruction of the
biliary passages.

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CHAPTER VII.
EXAMINATION OF THE URINE.

THE urine is the secretion of the kidneys.!* <A sufficient and exhaus-
tive knowledge of the characters of this secretion is a point of the
utmost consequence to the physician, since the changes which it
undergoes are the expression of numerous morbid processes, and their
intelligent interpretation affords the surest aid to diagnosis.

I. NAKED-EYE INSPECTION OF THE URINE.

1. Quantity. — The quantity of urine secreted in health varies
within broad limits, and depends at any time upon the relation subsist-
ing between the imbibition and abstraction of fluids in the system. It
follows that an error as to excess or deficiency can be considered morbid
only when very marked. In general terms it may be said that a healthy
able-bodied man will pass 1500 to 2000 cc. of urine in twenty-four
hours. The rate of secretion varies at different periods of the day. In
the early hours of the night the urine is abundant and of relatively
low specific gravity ; later it is scantier and more concentrated, while
during the waking hours it again becomes more abundant (Wollheim de
Fonseca).? Secretion is diminished in sleep (G7wm).?

Under pathological conditions the healthy standard may be widely
departed from in either direction.

In order to estimate the quantity of urine secreted, that which is
passed within twenty-four hours should be collected ; and it is well to
date the period from eight o’clock of one morning to eight o’clock of the
next. When only half this interval is taken—and especially when the
estimation of urea is in question—it is important that the bladder
should be previously emptied. The patient should be admonished to
make water before going to stool, and even then a certain allowance
must be made for urine passed in the act of defecation. Should the
patient be the subject of incontinence, it is very difficult to form an

* We shall confine ourselves here to a description of the simpler processes, and

such as are likely to be applied clinically. For more exhaustive information the
reader is referred to the text-books of urinary chemistry (see references I and 4).

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Zile2 THE URINE.

accurate estimate of the quantity of urine secreted ; and this can be done
only by passing the catheter as often as possible—hourly, if it may
be—so as to minimise the escape of fluid. In paralysis of the bladder,
while sensation remains unimpaired, the escape of urine may be pre-
vented by the use of a permanent receptacle. The urine saved should,
in any case, be placed in a vessel of two litres capacity, and provided
with a graduated scale showing its capacity in cubic centimetres. Its
quantity may be most accurately estimated by weighing it.*

A diminution of the quantity of the urine (oliguria) occurs in febrile
conditions, in disturbances of the circulation of all kinds, and especially
of the capillary circulation, in acute, and in some forms of chronic
nephritis. The urine is increased in quantity in diabetes mellitus,
diabetes insipidus, contracted kidney, amyloid degeneration of the
kidney, and usually in convalescence after acute diseases. [To these
causes may be added rare cerebellar disease, hysteria, and nervous con-
ditions.] Under the heading of acute diseases the increase is most
pronounced in the non-febrile period of relapsing fever, at the termina-
tion of an attack of acute nephritis—whether cure be impending or the
acute is passing into the chronic form of the disease—and in the resto-
ration of the balance in the capillary circulation, as where compensatory
changes take place in heart-disease, &c. Finally, the renal secretion
is promoted by certain drugs, as the salts of acetic and salicylic acid,
digitalis, and calomel.

A complete suppression of the urinary secretion (anuria) is an accom-
paniment of uremia and of all diseases that are attended with the
abstraction of water from the system: such are severe acute anemia,
gastric and intestinal catarrh, cholera, and dysentery. [A remarkable
case ® has been recorded in which total anuria lasting for a week was
attributed to the impaction of a calculus in one ureter, causing obstruc-
tion of that, and suppression by reflex influence ; there were slight
symptoms of uremia shortly before recovery.] The transitory suppres-
sion of urine which sometimes occurs in healthy persons after profuse
perspiration, and lasts only a few hours, is altogether physiological. A
simple increase or diminution of urine will not by itself establish the
nature of a disease, but it is always an important factor in diagnosis, and
we shall see by and by that the consideration of this point will enable
us especially to discriminate between certain forms of kidney-affection.

2. Specific Gravity of the Urine.—The density of the urine
varies greatly in health, and is for the most part in inverse ratio to its
quantity. If we assume the latter to be on an average 1500-2000 cc.,
then the sp. gr. of healthy urine may be stated at 1.017 to 1.020. It
may be estimated most accurately by means of the pycnometer (see

* See the text-books referred to, reference 4.

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SPECIFIC GRAVITY. 213

text-books), but for clinical and pvractical purposes an instrument con-
structed on the principle of the hydrometer will serve well. Such
an instrument, when employed for testing urine, is called a urino-
meter. It is well to have two in use, one for taking the specitic gravity
when this lies between 1.000-1.02 5, the other where it is as high as
I.025-1.050.

A serviceable urinometer should be so made that the degrees on the
index-scale shall be separated by a sufficient interval, not less than
t mm. ; and when very accurate results are aimed at, it should be
graduated in tenths. Moreover, it should be furnished with a thermo-
meter, also graduated in tenths of a degree, and recording temperatures
between o° and 30° C.

A new urinometer should be tested in distilled water. If accurate, it will sink
to the mark 1.000, where the scale is graduated so low as this.

The specific gravity is tested in the following manner :—The urine
is poured into a cylindrical glass vessel of suitable width. Should froth
form, it must be removed either with filter-paper or by filling the vessel
to the brim, when it may be blown off. The winometer is then placed
in the urine, and care is taken that it is not anywhere in contact with
the sides of the vessel. When it is quite stationary in the liquid, the
specific gravity is read off, the observer bringing his eye on a level with
the concave surface of the liquid. The mark on the scale which corre-
sponds to the lowest point of this concavity will indicate the specific
gravity of the fluid.

Greater accuracy may be attained by testing the urine at some particular
temperature, for which the urinometer has been constructed.

An abnormal specific gravity of the urine is a fact of great import-
ance in disease. It affords an approximate estimate of the quantity of
solids excreted by the kidneys, and consequently of the energy of the
metabolic processes within the system. It may be stated as a general
rule, that when the quantity of the urine is diminished in disease, its
specific gravity is raised. A considerable departure from this rule im-
plies one of two things :—Either tissue-changes are notably suspended,
and their products, urea, uric acid, &c., formed in smaller quantities ;
or these processes remaining active, such products fail to be removed by
the kidneys. To the first of these causes is to be assigned that rapid
decline in the density of the urine which sometimes precedes a fatal
termination in acute fevers. Of still more serious import is a sudden
fall in the specific gravity in nephritis, unattended with any alteration
in the quantity of urine passed. The phenomenon in this instance
points to the failure of the diseased kidneys to separate the urea and

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214 THE URINE.

salts elaborated within the system. The author has had many oppor-
tunities of observing that such a fall in the specific gravity is apt to
precede—usually by several days—-the oliguria and suppression which
herald an attack of uremia; and it often affords a valuable warning of
what is impending at a time when all other symptoms are wanting.
Moreover, the symptoms of uremia may develop whilst the urine
remains but little diminished in quantity, and in such cases we shall
always find that its specific gravity is greatly lessened.°

8. The Colour of the Urine.—The normal urinary pigments
have not yet been separated. C. Vierordé™ concludes from spectroscopic
appearances that they are several in number. Up to the present, on the
other hand, but two chromogens have been determined in the urine,
viz., indican (sulphate of indoxyl; see Indicanuria), and the chromogen
of urobilin.

[Four pigments are usually distinguished as belonging to the urine
(F, Taylor). These are:—r. Normal urobilin. 2. Febrile or patho-
logical urobilin, which is identical with stercobilin (MacMunn). 3.
Urohematoporphyrin, derived from hematin. 4. Uroerythrin, which
is the pigment of pink urates.

The chromogens of the urine are substances which develop a colour
on the addition to the fluid of some oxidising or other reagent. These
are likewise four, namely :—The chromogens (1.) of indigo (indican) ;
(2.) of pathological urobilin ; (3.) of anemia; (4.) of melanin. MacMunn
believes further that normal urobilin, which is the principal pigment of
healthy urine, exists there in part as a chromogen. |

The colour of healthy urine depends upon its degree of concentration,
being darker as this is more pronounced.

The same statement holds in general for disease, but with notable
exceptions ; for there are some affections in which a high colour and
an abundant flow coincide, and others in which the urine is at once pale
and scanty.

In some diseases, and especially in fever, additional colouring matters
are secreted. The nature of some of these is a mattér of speculation
(uroérythrin, urochrome).

At some period in the course of a disease, the urine may undergo
a change of colour from the admixture of blood. When the latter is
present in small quantity, the secretion may be flesh-water-coloured.
When blood is more plentifully effused, it may be a bright ruby-red
(see Hematuria).

Bile pigment imparts a brownish-yellow or green tint. Its presence
may usually he detected by shaking up the urine, when a yellow foam
will form upon it. It must, however, be borne in mind that urine
which contains much wrobilin will yield a similar foam (Leo Lieber-

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THE COLOUR OF THE URINE. 215

_ mann *); in the latter case the secretion is always of a dark brown-redi
(see Urobilinuria). An excess of indoxyl sulphates will cause the urine
to assume a dark-brown tint, and the yellow foam will not form upon
it’ (see Indicanuria). The brown tint in such cases is due, not to the
indoxyl salts, which are colourless, but to some other substance which
is present with them.

Certain drugs, too, will affect the colour of the urine. Rhubarb and
senna cause it to become brown or blood-red; a black colour is deve-
loped when carbolic’acid is taken into the system, especially if the urine
be allowed to stand for some time, and the same appearance follows
the exhibition of naphthalin, hydrochinon, resorcin, and pyrocatechin.
The blackening of the urine by carbolic acid is ascribed by Baumann
and Preusse® to the formation of the oxidation-products of hydrochinon.
The use of quinine, kairin, antipyrin, and thallin, and sometimes sul-
phonal, also colours the urine more or less deeply.

It may be stated in general that the urine is darkly coloured in fevers,
and in congestion of the kidneys due to heart-disease, emphysema, &c.
It is, on the other hand, deficient in colouring matter in diabetes mellitus
and insipidus, chronic nephritis, urina spastica, and all kinds of anzmia.,
[The urine of pernicious anemia, though of low specific gravity, not
exceeding 1016 (Hunter), is usually of very high colour (Yagge,!° Mott,
Hunter”). The urine of phthisis has'a tendency to become dark on
standing, and sometimes turns quite black (Hale-White).!7] In cancer,
especially when it implicates the intestinal canal, the urine is apt to be
dark and pigmented. In such cases an excess of indican may generally
be determined. -

'

Vogel has endeavoured to construct a standard scale for the estima-
tion of colour in the wine. ! 3
[The following table from Halliburton 4 shows the nature and origin

of the chief variations in tint :—

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216 THE URINE.

 

Cause of Colour.

Colour. | Pathologie: Condition.

 

Nearly colourless. Dilution or diminution of | Various nervous conditions,
normal pigments. hydruria, diabetes  insi-
pidus, granular kidney.

Dark-yellowtobrown- | Increase of normal or occur- | Acute febrile diseases.

red, rence of pathological pig- |
ments. |
Milky. | Fat globules. | Chyluria.
Pus corpuscles. | Purulent disease in urinary
tract.
Orange. Excreted drugs, c.g. -| Santonin, chrysophanic acid.
| '
Red or reddish. Unchanged hemoglobin. Hemorrhage or hemoglobi-
Pigments in food (logwood, |  nuria.
madder, bilberries, apeheiD)|
Brown to  brown- | Heematin. | Small hemorrhages.
black. Methemoglobin. | Methzemoglobinuria.
| Melanin. Melanotic sarcoma.

Hydrochinon and catechol. Carbolic acid poisoning.

|
Greenish - yellow, | Bile pigments. | Jaundice.
greenish - brown, |
approaching, black. |
Dirty green or blue. :| A dark blue scum on surface | Cholera, typhus ; seen espe-
with a blue deposit, due to} cially when the urine is
excess of indigo-forming | putrefying:]
substances. |

| Brown-yellow to red- | Substances introduced into
brown, becomes the organism with senna,
blood-red on addi- rhubarb, and chelidonium,
tion of alkalies.

 

 

 

 

4..The Reaction of the Urine.—Healthy human urine is ordi-
narily acid. The reaction is due not to free acid, but to the acid’ salts
(phosphates and urates) which it contains.

It is, however, subject to considerable variations in this respect.
Quincke has determined that the acidity is in general less in the fore-
noon than at any other time, and the urine of healthy persons may even
exhibit an alkaline reaction then.!®

The reaction of the urine is also modified by diet. It may be alkaline
after an ample meal, or the ingestion of alkalies and of substances such
as the salts of acetic, tartaric, and citric acids, which are converted into
carbonates in the system. The administration of acids, on the other
hand, renders the acidity of the urine more marked.

Healthy urine when allowed to stand for some time becomes [first
more acid from an increase of acid phosphates, as well as lactic and
acetic acids, and then] alkaline in consequence of the action of a micro-

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REACTION

 

MICROSCOPICAL CHARACTERS. 217

organism, the micrococeus ure (see p. 234), which decomposes the
contained urea into carbonate of ammonia. [The urine of’ phthisis
remains acid for a very long time, sometimes even for four months
(Hale-White) .] It occasionally happens that the same urine will turn
red litmus paper blue, and blue litmus red, é.¢., it is amphoteric. This
(lepends upon the presence in it of acid or neutral phosphates (Huppert).18

In different morbid states the freshly passed urine may be either alka-
line or acid; but its reaction in disease is valuable as a symptom only
when the causes which are known to influence it in health can be
excluded. A fact of the greatest consequence in this connection is the
alkalinity due to ammoniacal fermentation, and this can usually be
ascertained directly by the sense of smell. The urine is, as a rule, acid
in febrile conditions, diabetes, and leukemia; in scurvy, too, it is apt
to be intensely acid. On the other hand, it is alkaline in simple and
pernicious anemia and chlorosis.!” According to Bence Jones, the
alkalinity in these cases depends upon the deficient formation of acid
in the stomach. In chlorosis the point is of interest to the physician,
insomuch that whilst the reaction of the urine continues to be alkaline,
it may be inferred that the morbid process on which it depends is still
going on, Ammoniacal urine implies ammoniacal fermentation within
the bladder. This may be due to the use of an unclean catheter, and
commonly arises in the course of cystitis. [Alkalinity due to the pre-
sence of ammonia may be distinguished from that caused by fixed
alkalies from the fact that litmus paper turned blue by it again becomes
red when dried in a gentle heat. ]

The reaction of the urine is best tested with red and blue litmus paper.
The comparative estimation of acidity may be effected by Muppert’s
method.*° [The acidity of the urine during twenty-four hours is equiva-
lent to about 14 gers. of carbonate of sodium or to 30 grs. of oxalic acid
(Taylor).?"|

II. MICROSCOPICAL EXAMINATION OF THE URINE. —
Healthy urine is generally quite clear when first passed. On standing, if
not decomposed by the rapid development of fungi, it deposits a filmy
cloud. Microscopically this deposit is seen to consist of a few crystals
of various kinds, some white blood-corpuscles, and epithelial débris.22
But the appearance of freshly passed urine may differ greatly from this,
even in health. The concentrated urine passed in the morning some-
times deposits an abundant sediment of urates altogether independently
of disease.

The examination of morbid urine affords information of the utmost
consequence in diagnosis. Such urine may either be turbid when passed,
or it may deposit a variable quantity of sediment when allowed to stand

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218 THE URINE.

for some time ; and when this sediment is looked at through the micro-
scope, it is seen to hold certain substances of very variable character.
For convenience of description we shall divide these substances into
two classes, the Organised and the Unorganised urinary deposits.

The microscopical examination of the urinary sediment may be conducted in

the following manner :—'The urine is allowed to settle, the clear supernatant
fluid poured off, and some of the sediment placed in a conical glass, when it is

 

Fic. 92.—Stenbeck’s Sedimentator.

again allowed to stand fora while. A little is then removed with a pipette and
placed on a slide for examination. If the sediment should be scanty and require
a long time—say twenty-four hours—to deposit, it should be set apart in a cool
place, so as to check the excessive development of fungi and fermentative pro-
cesses, which might alter the character of the specimen. It is well also to add
some indifferent antiseptic substance to the urine, as thymol, hydriodic acid, or
oil of turpentine. An admirable admixture is that of Salkowski ; 20 to 30 cc. of
a fluid containing 5 to 7.5 cc. of chloroform in a litre of water. Carbolic acid
should not be employed, because it will cause a precipitate with any albumin
which may be present.

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RED BLOOD-CORPUSCLES. 219

The process may be rendered more certain and expeditious by the use
of Stenbeck’s sedimentator (v. Jaksch, Litten 4), the nature of which is
explained by the accompanying figure (fig. 92). As used by the author,
it is fitted with a treadle-wheel, and worked by the foot instead of the
hand. It is also protected by a wooden case, within which the centri-
fugal apparatus is made to rotate. This is a precaution against accidents.
With this instrument a few minutes is sufficient to produce a deposit
even in urine which contains but little sediment, and where it is avail-
able no other procedure is required. The sediment when deposited is
withdrawn by means of a pipette and submitted to microscopical exami-
nation as already directed.

1. Cellular Constituents (Organised Sediment) of the Urine.

1. Red Blood-Corpuscles.— Red blood-corpuscles occur in variable
quantity as a morbid constituent of the urine. They may be so few
in number as not to affect the colour of the fluid, and to be discernible
only with the microscope ; or they may be present in such abundance
as to form a layer several centimetres deep at the bottom of the vessel,
and when intimately mixed with the wine impart to it a deep red
colour.

The condition in which they are found is not less liable to vary than
their number. They may retain their proper form, or they may appear
as pale yellowish rings (phantom corpuscles of Z7aube). (See fig. 96.)
Important inferences as to their origin are to be drawn from the number
and character of the red blood-cells in the urine. Such cells may be
derived from the urethra, the bladder, the ureters, the renal pelvis, or
the kidneys themselves.

When they are intimately mixed with the urine, in such a way that,
though present in large quantity and deeply tinging the fluid, they do
not form a sediment after many hours’ standing, it may be inferred
that the hemorrhage took place in the substance of the kidney or in
the renal pelvis or ureters. If, under these circumstances, they are
seen with the microscope to be profoundly altered, having lost their
colouring matter and presenting the appearance of pale yellow rings,
the further conclusion results that the blood was effused in the kidney
itself, and the symptom points to acute nephritis or to a fresh exacerba-
tion in the course of chronic nephritis. When the blood-cells appear
as comparatively few, attenuated, and washed-out rings, they may have
originated in congestion of the kidneys or in miliary tuberculosis of
those organs, and the diagnosis of these conditions may be established
on this ground—in conjunction, of course, with other symptoms.

It is more difficult to decide from the character of the blood passed
whether the lesion has taken place in the renal pelvis or the ureters.
To arrive at a just conclusion on. this point, a careful examination

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220 THE URINE.

must be made for the other occasional organic constituents of the urine,
as epithelium, casts, &c., and the diagnosis will rest in a large measure
upon their character (see pp. 221 and 224).

When blood is present in considerable quantity without being inti-
mately blended with the fluid, it is derived in the majority of cases
from the bladder. Intermittent hematuria, attended with severe pain,
is caused by calculi or tumours in that organ. Hemorrhages into the
kidney oceur in hemophilia 2° and leukemia.

2. Leucocytes.—The urine contains isolated leucocytes in health. It
is only when they occur in greatly increased quantity, or in conjunction
with other cellular elements of a pathological character (casts), that
their presence attains any serious import. They are usually unaltered
in form, but sometimes, and especially in alkaline urine, they swell
up, become glossy and homogeneous, and their nuclei disappear, but
can again be made visible with acetic acid. Occasionally they enclose
much fatty matter, and this chiefly when they are derived, not from
the urinary passages themselves, but from the bursting into them of a
slowly-formed abscess of some neighbouring organ, as the rectum or
prostate.

Leucocytes are occasionally seen to present protoplasmic processes.
This happens when the secretion possesses a feebly alkaline reaction.

The leucocytes of the urine may be derived from the substance or
the pelvis of the kidney, the ureters, the bladder, the urethra, or, as
already mentioned, from the rupture of an abscess into some part of the
urinary passages.

These bodies may form a compact layer of sediment several centi-
metres deep in purulent catarrh of the bladder, and a similar deposit of
pus has been found in the urine in cases of acute infectious urethritis
(v. Jaksch). Such pus is thick and viscid, and the constituent leucocytes
are usually much altered in character (vide supra).

Pus cells occur in the urine in considerable quantity in inflammation
of the ureters-and in pyelitis, but in this connection they are never so
abundant as in cystitis, and they are commonly deposited in the form
of a flocculent sediment of a slimy translucent appearance, which, when
looked at through the microscope, is seen to consist of a more or less
dense aggregation of leucocytes. The distinction as to the nature of
the sediment is not, however, altogether characteristic, nor is it in
either case invariable. With this qualification, it may be reeommended
as a point worth attending to in the differential diagnosis of cystitis and
inflammation of the pelvis and ureters.

In renal disease there are but few leucocytes to be found in the
urinary sediment, unless in the rare cases where a renal abscess dis-
charges directly into the large tubules or the pelvis of the kidney.

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LEUCOCYTES—EPITHELIUM. 221

Care must be taken in the case of women to ascertain whether pus
found in the urine may not have been derived from the vaginal secre-
tion. In blennorrheea a considerable quantity of pus may find its way
from this source into the urine.

When pus in great quantity appears suddenly in the urine (pyuria),
it points to the opening of an abscess into the urinary passages, but two
cases are on record (v. Jaksch) where no such causes could be assigned,
and these constitute rare but remarkable exceptions to the principle laid
down. They depended, doubtless, upon unusual conditions favouring
diapedesis.

In these two cases the patients—a boy of six and a girl of thirteen years—both
suffered from pulmonary phthisis, and the accident referred to occurred during
the last week of life. The purulent sediment of the urine contained no bacilli,
and the post-mortem failed to disclose any condition to which the discharge might
be referred.

The fact is of importance, since it shows that a purulent deposit may
appear in the urine apart from the causes mentioned above. Glaser 2%
has shown that the urine of healthy persons may contain great quantities
of leucocytes as a result of alcoholic excess.

Leucocytes can generally be recognised by the microscope ; but should
any doubt arise as to their nature in a particular case, it may be at
once resolved by the addition of a little iodo-potassic-iodide solution.
With this reagent the leucocytes stain a deep mahogany-brown (glyco-
genic reaction), whilst the forms of epithelium, with which they are
occasionally blended, and which may be confounded with them, assume
a light yellow colour.

A, Vitali?” recommends the following test :—The suspected urine, if
alkaline, is acidulated with acetic acid and passed through a thick filter.
The deposit on the filter is then treated with a little euaiacum tincture
which has been kept in the dark. If pus be present, the inner surface
of the filter takes a deep blue tint. Dr. Frank, who has employed this
test in the author’s clinic, reports in very high terms of its efficiency.
The result is obtained even with a small proportion of leucocytes in
the urine.

3. Epithelium.—The slight cloud which ordinarily forms in healthy
urine contains a number of. epithelial cells. These are for the most
part of the squamous variety, but amongst them are also some smaller
forms, which are derived chiefly from the mucous surface of the renal
pelvis and ureters, and very rarely from the substance of the kidneys.

In addition to these, there are to be seen in every specimen of urine
a considerable number of uninuclear polygonal cells, and similar round
cells, which are their earlier form. These belong to the meatus’ and
prepuce, and in women to the vagina. Their presence in compara-

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DOD) THE URINE,

tively small numbers has no special significance ; but when they occur
in excess, they indicate a catarrh or catarrhal irritation of the parts
from which they are derived. A form of epithelium, consisting of
oblong cylindrical cells, diminishing in size towards their attached
extremity, and with well-defined borders, comes from the surface of
the male urethra (Bizzozero).

It is very difficult to distinguish between the epithelial cells which
are derived respectively from the bladder, ureters, and renal pelvis,
Bizzozero*® maintains that the cellular type is the same for all these
parts, and Eichhorst °° agrees with him.

It follows that a particular affection in one of these situations can
hardly be localised by the character of the urinary epithelium. The
cells in each case have this in common, that they, are smaller than
those already described. Those that come from the superficial layers

 

Fic. 93.— Urinary Epithelium (eye-piece II1., objective 8a, Reichert), collected from thirty
different specimens.
ec, c’, c’, c”. Epithelium from the kidneys.

d, d’, Yatty epithelium from the kidneys.
e-h. Epithelium from the bladder.

«a, wv. Squamous epithelium from the urinary
sediment.
», v', b”. Epithelium from the bladder.

 

of the mucous membrane are polygonal or elliptical im shape. They
usually have a single large nucleus, and their protoplasm is apt to be
very granular. The cells which are derived from the middle and deeper
layers are more oval in shape, often irregular and conical, and furnished
with one or two long protoplasmic processes (fig. 93, 0, 0’, b”). They
also have a single nucleus of large size, and their substance is clearly
eranular. Like Bizzozero and Kichhorst, v. Jaksch has been unable to
find any morphological distinction amongst these cells, by which their
origin in the bladder, ureter, or pelvis can be known; nevertheless, he
is of opinion that certain inferences may be drawn from their number.
Given a disease of one of these parts, it may be assumed to involve the
ureter alone when the epithelial forms which we have been considering
are very few. When in greater quantity and superimposed upon one
another like the tiles of a roof, they probably come from the pelvis ;

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URINARY EPITHELIUM. 22

and when in very great abundance they indicate cystitis. These points
should not be strongly insisted upon, but taken in conjunction with other
symptoms, they should carry some weight in a differential diagnosis.

The general pathological condition to which the presence of these
cells in excess is, in any case, to be ascribed, is that of irritation or
inflammation of the mucous surface of the bladder, ureter, or pelvis of
the kidney. If the reader will refer to what has been said of the
leucocytes in the urine in connection with these diseases, he will see
that the character of the sediment in the two particulars taken
together, and read in conjunction with the clinical symptoms, will
suffice very accurately to discriminate cystitis from inflammation of
the pelvis or ureter.

Much importance attaches to the appearance in the urinary sediment
of epithelial cells derived from the mucous lining of the tubules of
the kidney. Under normal conditions they are distinguished by their
smaller size from the forms just considered, or at any rate from such
as belong to the middle and deeper layers of the urinary mucous mem-
brane. They are polyhedral in shape, and finely granular, with com-
paratively large oval nuclei and nucleoli. They occur separately or
cohering in groups (fig. 93, ¢, ¢’, ¢’, ¢””), and in the latter case may
display the cylindrical arrangement (epithelial casts, fig. 95). They
are often to be seen, singly or several together, on the surface of the
casts to be described later (fig. 104, ¢).

The cells of kidney epithelium exhibit remarkable deviations from
the normal type. They are sometimes hard, tough, and glossy, like the
obsolete cells of the intestine described by Nothnagel (p. 169). They
occasionally contain fatty globules in greater or less profusion (fig. 93,
d, d'), and again cells are seen overlying the surface of casts (fig. 103, a),
which may conform in shape to the type described above, but consist
entirely of fatty matter (see also fig. 103, c}.

In the convalescent stage of acute nephritis (of scarlatina and ery-
sipelas), small round cells with an eccentric resting nucleus are frequently
to be seen, and these are doubtless the young kidney-cells formed in the
process of repair within the tubules (v. Jaksch).

The detection and the character of the kidney epithelium in the
urine is a point of the highest import in diagnosis. Its presence is
always a sign of renal disease, and usually of inflammation. In addi-
tion to this, and where the coincident symptoms indicate a nephritis,
the character of the epithelium will enable us to form a probable
opinion as to whether the inflammatory process is accompanied with
degeneration of the kidney substance. Thus where the cells are found
loaded with fat, the autopsy will most likely disclose a fatty condition
of the renal tissues ; and the detection of the obsolete cells described

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224 THE URINE.

above points with some degree of certainty to an amyloid degeneration
of the organ.

It is needless to add that a diagnosis can never be based upon such
appearances alone, but must in all cases be controlled by the clinical ,
symptoms and the other manifestations of the urine.

4, Casts.—The subject of urinary casts, which will now engage our at-
tention, is one of the highest interest. Casts were first seen in the urine
by Vigla, Quevenne, and Rayer,*® in France, and almost simultaneously
in Germany by Simon and Nasse.*1  Henle*? discovered them in the
urine of a dropsical patient, and afterwards in the renal tubules both of
health and disease. Glaser,** working in the author’s clinic, has ascer-
tained that the recent urine of healthy persons, while free from albumin,
often contains casts, and that a slight toxic influence (alcohol) is often
sufficient to determine their presence. ovida*+ has contributed the
most ample information concerning urinary casts. These bodies are
subject to very great variety as to their number when present, their
form, and the import which attends their manifestation. It must be
premised that they have been found in urine which is entirely free from
albumin, and even from every other morbid product. Thus Nothnagel
has seen them in the urine of patients with jaundice, which at the same
time contained no albumin; Burkhart and Fischl*° likewise observed
them, in the absence of albumin, in cases of severe inflammatory affec-
tions of the stomach and intestine. Hence it follows that the presence
of casts in the urine does not by itself imply disease.

Urinary casts may be conveniently divided into two chief classes, viz.,
Unorganised and Organised.

(a.) Unorganised Casts.—These are formed of crystals. They are
pathologically of little consequence. Those that have been described
consisted of urates (fig. 94) and hematoidin ; and as yet they have been
found only in infants, and in cases of gout and renal congestion. If
healthy urine be concentrated in vacuum at a low temperature, 37°—39° C.,
casts may be observed which consist of acid urate of soda (Lezube).°" :

Perhaps we ought to include under this heading some of those bodies
which are at present classed together under the general name of
“detritus” casts.

(b.) Organised Casts consist of cellular elements, or the products of
their transformation.

They may be subdivided into three groups: (1.) Those which consist
of cells (red blood-corpuseles, leucocytes, and epithelial cells). (2.)
Those which consist of the products of cellular change. (3.) Those
so-called hyaline casts, whose origin is still a subject of dispute, but
which are sufficiently distinguished from the others, both clinically and
morphologically.

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CASTS.

Ny
NO
wn

(1.) The first group includes :—

(a.) Casts formed of red blood-corpuscles (fig. 96).
(6.) Casts formed of leucocytes (fig. 97).

(c.) Epithelial casts (figs. 95 a, 6, and 98 a, 0).
(d.) Casts consisting of colonies of bacteria.

(2.) Under the second group we distinguish :—
(a.) Granular, (b.) waxy, and (c.) fatty casts.

(3.) The group of hyaline casts may be subdivided according as its
members are simply hyaline, or, in addition, coated with certain sub-
stances, amongst which kidney epithelium, red and white blood-cor-
puscles, bacteria, and various forms of crystals may be enumerated.

The cylindroids of Thomas should perhaps be included in this group.

The number of casts occurring in a specimen of urine, and the length
and breadth of each, is subject to very great variety. The latter fact is
sufficiently seen in the accompanying figures.

1. Perfectly formed cellular casts appear in the urine only under
such circumstances as cause the renal tubules to become crowded with

 

Fic. 94.—Cast of Urates, from a Case of Emphysema (eye-piece III., objective 8a, Reichert).

red or white blood-corpuscles, or bring about a separation of the renal
epithelium in the entire circumference of a tubule. When this occurs,
the casts formed are forced onward by the flow of the fluid secreted
behind them, and are ultimately discharged from the bladder.

Fig. 98 (a and 0) shows a rare specimen of casts, consisting of renal
epithelium and leucocytes from the urine in a case of nephritis with
oliguria and uremia.

The clinical significance of these casts is very great. They always
imply an affection of the kidney, and their presence alone suffices to
establish the existence of acute nephritis, or the supervention of a fresh
paroxysm in that disease. When found in small numbers, the kidney
is probably but slightly diseased. When, on the other hand, the urine
holds abundance of these casts, the fact is ample evidence of inflamma-

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226 THE URINE.

tory changes in the organ. Figs. 95, 96, and 97 represent specimens
of cellular casts formed in different proportions of the several cellular
elements which enter into the formation of these bodies.

  

Fic. 96.—Cast of Fic. 97.—Cast

shrunken blood-cor- formed of leuco-

= puscles, in part me- oyten trom Acaee

is .—Epitheli ; tamorphosed (acute of acute neph-

nae aaa Hee pelon Aa nephritis), (eye-piece ritis (eye-piece

ritis: a. fully differentiated ; IIl., objective 8a, IIl., oe
b. in part granular (eye-piece Reichert). 8a, Reichert).

III., objective 84, Reichert).

 

Fic. 98.—a. and b. Rare forms of casts composed of leucocytes and epithelium ; from a case of
chronic nephritis which began with oliguria and uremic paroxysms (eye-piece III., objective
8a, Reichert).

Casts are sometimes found which consist almost entirely of masses of
micrococci, but these have quite a different significance. Fig. 107, d,
represents such a one. Morphologically, they bear a close resemblance

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GRANULAR CASTS. 227

to the granular casts presently to be described, but are distinguished
from them by their resistance to powerful reagents, such as caustic
potash and nitric acid. They may also be known by their opacity and
the grey colour which they display, as well as by the remarkable
uniformity of their substance (Martin/).*

Casts of micrococci in the urine are a matter of very grave signifi-
cance. They imply, as a rule, the existence of septic embolism of the
kidney. They may also arise from the extension upwards of a septic
pyelitis (pyelo-nephritis).

The author *® has seen a number of casts formed of minute bacilli in
the urine of a boy after a few days’ illness with acute nephritis. Their
formation was transitory.?

The specimen represented in fig. 107, d, was from fermenting diabetic urine,
and had no connection with the symptoms.

2. The members of the second group, as we have seen, are granular,
waxy, and fatty casts. ;
(a.) Granular Casts vary much in dimensions. They are most fre-

 

a b a b
Fic. 99.—a. and b. Granular cast in Fic. roo.—a. and b, Granular cast in
chronic nephritis (eye-piece III., objective acute nephritis (eye-piece III., objective
8a, Reichert). 8a, Reichert).

quently seen in a fragmentary state, but are occasionally of perfect
form. Their borders, which are usually well defined, are often sinuous
in casts of some length (fig. ro1, a and 0). In the latter case, too, they
are somewhat concave at the extremities; but when very short and
broken, they present a zigzag ending. Their constitution is very
variable. Sometimes they consist of fine particles, which can be dis-
tinguished only by a high power of the microscope (fig. 99, a), as Zeiss’
objective F. In other cases they are coarsely granular, and the
constituent particles can be readily made out with Hartnack IV. (fig.
100, b). In colour, too, they manifest considerable differences. They
may be of all shades, from pale yellow to a reddish-brown. They are

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228 THE URINE.

occasionally coated with leucocytes, fatty globules, and needles of fatty
crystals (figs. 101, b, and 103, a, b). These distinctions of character are
not known to correspond to special derangements of the kidney.

Granular casts sometimes exhibit a transition form of epithelium
(fig. 95, 2), and it is probable that they usually originate in the de-
generation of the blood and epithelial casts already described. This
theory was first stated by Rindjleisch and Langhans.*!

The presence in considerable quantity of granular casts in the urine
indicates an inflammatory condition of the kidneys. They have been

    

a

Fic. ror.—a. and'b, Granular cast in chronic nephritis (eye-piece I1I., objective 8a, Reichert).

found (v. Jaksch) as an exceptional constituent of the secretion in
cyanotic induration of the kidney, and especially when the latter con-
dition was associated with nephritis (secondary nephritis). These bodies
may be regarded almost equally with cellular (epithelial) casts as a certain
indication of nephritis.

(b.) Waxy Casts.—These casts attain a greater length than the others,
and when comparatively perfect they may be seen to be segmented like
a tapeworm. They also occur in shorter fragments of relatively great
breadth. Under the microscope they are homogeneous and refractive,
and often bear upon their surface fatty globules, separately or in con-
fluent masses, white and red blood-corpuscles, fungi, and crystals of ©
various kinds.

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WAXY AND FATTY CASTS. 229

Their constitution has not been definitely ascertained. It would
appear to be very complex, and that such casts result alike from the
breaking down of epithelium and from the exudation of occasional
products (fibrin, amyloid material) into the renal tubules. Their
number also is very inconstant.‘2

They are not characteristic of any special disease. They are found
in acute and chronic nephritis, in contracted granular and in amyloid
kidneys. They frequently exhibit the amyloid reaction with methyl-

 

Fic. 102.—Different Forms of Waxy Casts: a, with a coating of urates ; 6, waxy casts covered
with crystals of oxalate of lime; c, fragments of waxy casts (eye-piece III., objective 8a,
Reichert).

violet and iodo-potassic-iodide solution; and this in the absence of
amyloid degeneration of the kidney. Moreover, the reaction is not
obtained in some cases where this condition exists, and consequently
no inference can be drawn from its manifestation.

(c.) Fatty Casts.—Fatty globules are found upon the surface of
granular casts (fig. 103, @); but they also form by themselves short,
powerfully refracting cylinders, which often are beset all over with
needles of fatty crystals (fig. 103, ¢, d).

These casts and fatty crystals were first pointed out by Knoll. They

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230 THE URINE,

are most commonly associated with subacute and chronic inflammations
of the kidney of protracted course, with a tendency to fatty degenera-
tion of the renal tissues (v. Jaksch). Consequently their detection
affects the prognosis unfavourably.

 

(G

Fic. 103.—a, Granular cast beset with fatty globules and fat crystals; b, granular cast covered
with leucocytes; c and d, fatty casts; from a case of nephritis and large white kidney (eye-
piece III., objective F, Zeiss).

Post-mortem examination has shown that they form most frequently
in cases of large white kidney. In some instances where they were
present, however, the organ was found to be more or less contracted ;
but when this was so, it was invariably far advanced in fatty degenera-
tion. The crystals which beset fatty casts are not formed exclusively
of fat, but probably to some extent of lime and magnesia salts of the

  

a b 5 ¢

Fic. 104.—Hyaline casts : a. hyaline cast; b. hyaline cast coated with leucocytes ; c. hyaline
cast covered with kidney epithelium; from a case of chronic hypertrophic hepatitis with
jaundice (eye-piece III., objective 8a, Reichert).

higher fatty acids and allied compounds, for they are not all soluble in
ether. They have their origin doubtless in fatty degeneration of the
renal epithelium.

3. Hyaline Casts.—Hyaline casts are for the most part pale and
delicate bodies, of varying length and thickness, and more or less

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HYALINE CASTS—CYLINDROIDS. 231

abundant in different specimens. They cannot, as a rule, be detected
without being previously stained. Their pathological significance differs
greatly according as they are coated with certain substances or not.

In some diseases, whilst the urine contains no albumin, very pale
hyaline casts are found in small numbers in the sediment. Nothnagel *°
has met with such in albumin-free urine in cases of jaundice, and
Henle ** in others where the kidneys were quite healthy. Their pre-
sence, therefore, has no necessary connection with renal disease. The
author has repeatedly been able to recognise hyaline casts in the urine
in affections whose subsequent course altogether excluded the possibility
of diseased kidney ; and Huppert* has shown that the urine voided
after an epileptic paroxysm may contain both albumin and hyaline casts
in the absence of any kind of inflammation in that organ. According
to Leube*® hyaline casts are seldom met with in urine free from
albumin.4”7 Nothing more need be said to enforce the precept that the
existence of renal disease, or at all events of nephritis, must not be
hastily concluded from the mere presence of hyaline casts.

But when these casts bear a coating of other substances upon their
surface the case is altogether different. In nephritis we sometimes find
in conjunction with other casts cylinders of hyaline substance which
are covered with epithelium (fig. 104, c), unaltered or loaded with fat,
leucocytes (fig. 104, 6), and red blood-corpuscles.

In severe cases of jaundice depending upon disease of the liver, as in secondary
carcinoma of that organ complicated with nephritis, colourless hyaline casts
are formed in the urine, and overlying their substance are golden-yellow cells of
kidney epithelium, which colour red, changing to blue in presence of nitric acid.

Urates are seen deposited upon such casts in cases of congested
kidney ; and other bodies, as oxalate of lime and bacteria, may simi-
larly occupy their surface.

This is perhaps the place where mention should be made of the
so-called cylindroids (fig. 105). These are long, ribbon-like bodies,
resembling casts, which were first discovered by Thomas * in the urine
of scarlet fever. They occur also in nephritis, cystitis, and renal con-
gestion, and Bizzozero has found them in healthy urine.’ They are
not, therefore, characteristic of kidney-disease. They are observed most
commonly in the urine of children, which may or may not also exhibit
albumin, in the absence of other symptoms. Pollak and Térok®° have
noted these occurring together with abnormal excretion of urates.

With regard to the mode of origin of hyaline casts and cylindroids,
Rovida®! suggests that they are the products of secretion by the epi-
thelium lining the urinary tubules, and his view is borne out by the
experiments of Pollak and Torch. In this way it is possible to account

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232 THE URINF.

for their manifestation in the absence of severe renal affections. At the
same time it must be borne in mind that the experiments which Ribbert
made some years ago upon animals point
to the conclusion that hyaline casts may
result directly from the exudation of albu-
min within the tubules.

Method of Examination for Casts.—The
urine should be treated, when necessary,
with antiseptic agents’ (v. supra). It
should be covered and allowed to stand
for several hours, and some of the sedi-
ment which has then fallen should be
removed with a pipette for examination
on a slide.

The casts belonging to the first two
classes can usually be recognised without
special preparation. Simple hyaline casts
may need to be stained to render them
visible, and this may be done best in their
case by the use of a drop of dilute solution
of iodine and iodide of potassium. Other
staining fluids may be used for colouring
the different varieties of casts. These are
picro-carmine, gentian-violet, eosin, acid
hematoxylin solution, safranin, Bismarck-
brown, and methylene-blue (Knoll). It
should be mentioned, however, that the
staining properties of casts vary greatly,
and that some which are morphologically
similar will behave very differently in solu-
tions of the substances enumerated here.

Fic. 105.0, and b, Cylindroids from For the investigation of these staining
Meco Th cbiestite aa Rehan’ O° properties the sediment should be washed

with the normal saline (75 per cent. NaCl)
solution (Knoll **), and care should be taken that the dyes employed are
sufficiently diluted.

Chemical Constitution of Renal Casts.—Rovida is still the classical
authority upon this subject. According to him, the characteristic pro-
perty of hyaline casts is their solubility in weak mineral acids. This
property they possess in common with cylindroids.

Waxy casts in their behaviour with chemical agents resemble albu-
minates, but they also exhibit reactions which sufficiently distinguish
them from the latter substances. It would appear in general that the

 

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SPERMATOZOA—FUNGI. 233

substance of which casts are formed is not a proteid, but some deriva-
tive of one. In this conclusion Rovida had been long anticipated by
L. Mayer.** Knoll has also satisfied himself that the substance of
which renal casts are composed is not identical with any of the proteids
with which we are familiar, as acid albumin, albumin, albuminate,
albumose, globulin, fibrin, mucin, or peptone.

5. Spermatozoa.—These are pear-shaped bodies, about 50 in
length. Of this, the head occupies 4 to 5 “, and the remainder is a
long tail which tapers towards the extremity (see fig. 144).

Spermatozoa are found in the urine of men after coitus, involuntary
emissions, ¢.g., of epileptic paroxysms (Huppert), and masturbation.
They may also occur in the urine of women when passed directly after
connection (see Chapter IX.).

6. Fragments of Tumours.—It rarely happens that fragments
of a tumour are found in the urine. The author has never yet by
their aid been able to diagnose a growth in the kidney. On the other
hand, a carcinoma of the bladder, or a tumour of some other organ, as
the vagina or rectum, which has burst into the bladder, may betray its
character by imparting its constituents to the urine. Thus a pigmented
tumour may be known by the detection of melanotic particles in the
sediment ; but in other cases, as where cancer-cells are mixed up with
ordinary epithelium, it is more difficult to base a diagnosis upon such
appearances, and this can only be done in conjunction with the other
symptoms.

Tumours of considerable size (polypi, &c.) have been known to pass
with the urine. An observation by Heitzmann °° shows that it is some-
times possible to diagnose renal tumours by a microscopic examination
of the urine.

7. Parasites.

1. Fungi.—Adopting the same classification as before, we shall divide
the fungi of the urine into moulds, yeasts, and fission-fungi, and we
shall also consider them under the two headings of pathogenic and non-
pathogenic organisms.

(a.) Non-Pathogenic Fungi.—Fresh healthy urine is free from fungi
(Leube *") ; but when allowed to stand for some time, it becomes crowded
with these organisms.

All three classes of fungi may be represented in the wine. It must
be mentioned, however, that where ammoniacal fermentation is in
progress, as a rule only fission-fungi, and perhaps a few yeast-cells, are
to be found. Moulds are, under normal circumstances, a very rare
manifestation in decomposing urine ; but in that of diabetes, when the
alcoholic fermentation of sugar has ceased, they make their appearance
in great quantities, floating in a layer of upwards of a millimetre in

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234 THE URINE.

thickness on the surface of the fluid, to which they impart a disagree-
able mouldy smell. The urine is at the same time turbid with yeast-
fungi and bacteria, and its appearance alone may be conclusive as to
the abundant excretion of sugar.

The development of yeast-fungi in large numbers is a sure sign of
sugar in the urine, and their detection will serve to suggest this con-
dition where it has been previously overlooked.

The microscopical character of fermenting healthy urine is subject

 

Fic. 106.—Micrococcus Ure from the surface of a Normal Urine undergoing Ammoniacal
Fermentation (eye-piece III., objective 8a, Reichert).

to great variety. The transformation of urea into carbonate of ammonia
is most likely effected through the agency of several forms of fungi
(Miquel, v. Jaksch, Leube, Billet, C. Fligge, v. Limbeck**), but most
prominent are the micrococci. Of these, the Micrococcus ure (fig. 106)
may be seen in almost pure cultivations upon the surface of the fluid.
This micro-organism forms in long chain-like series, and is of com-
paratively large size. In addition to these, there are rod-shaped
bacteria of all sizes and forms, and as occasional manifestations certain

 

F1G, 107.-- Sediment from Fermenting Diabetic Urine with Casts of Micrococci.

a, b, ¢, various forms of urates; d, micrococci in form of casts; c, moulds; jf, yeast-fungi ;
g, bacilli and micrococci (eye-piece III., objective 84, Reichert).

long spiral bacilli with large spores, and cocci, which group themselves
into globular masses of dark colour and varying size (fig. 107, 9).
Sarcina is also found in the urine. It is smaller than that which forms
in the stomach, being in point of size comparable to the sarcina of the
lung (see p. 103).

(b.) Pathogenic Fungi.When recently-voided urine is found to con-
tain a profusion of fungi, the condition is in every case: serious, because
these fungi—even though not specifically pathogenic—may give rise to

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PATHOGENIC FUNGI, 235

serious trouble by promoting decomposition within the bladder. The
circumstances which influence the development of non-pathogenic fungi
in fresh urine have been made the subject of repeated investigations
(Roberts, Schottelius, Reinhold).°° The matter is still surrounded with
a great deal of uncertainty, and it is convenient provisionally to dis-
tinguish the condition as idiopathic bacteriuria. According to the
researches of Schottelius, it is unattended with any morbid symptoms.
In the case of a patient who had suffered for a year from gonorrhea and
cystitis, and who said that he had never had a catheter passed, the
author found the urine turbid and ammoniacal, and proliferating crowds
of micrococci of every description. This continued long after the cessa-
tion of symptoms, and was attended with pain.

The diagnosis of idiopathic bacteriuria must be made with great caution. ‘The
author had the opportunity of observing another case, apparently analogous to
the one described above, From a communication recently made by the patient,
however, the symptom is sufficiently explained by the appearance in the interim
of a prostatic abscess.

Bacteriuria is very often observed after the use of unclean (non-steri-
lised) catheters. Often (although not always) cystitis supervenes as a
result of this. Very interesting communications on the subject of the
decomposition of urine by bacteria have been made by Crémer and
Albertoni.®

Pathogenic fungi occur in the urine in connection with certain specific
diseases, as erysipelas, relapsing fever, septic processes, typhoid, and
tuberculosis, and it is a matter of great importance to be able to de-
tect them.

In introducing this subject a few general remarks are called for :—

In the first place, there can be no doubt that large numbers of suffi-
ciently characteristic micro-organisms may be present in the freshly-
voided urine of infectious diseases, especially when it also contains
albumin and casts (Kannenberg, Litten, v. Jalsch).°2 In one such
disease, namely, erysipelas, the author’s experience has been that, in
all cases where the typical symptoms of acute nephritis supervened, the
urine contained a profusion of fungi which were indistinguishable in
their form from the Streptococcus pyogenes or erysipelatos (Fehleisen).*
The urine was nearly always turbid, and while still quite fresh exhibited
these bodies in moniliform arrangement. In these cases it always
happened that the bacteriuria and nephritis disappeared with the cessa-
tion of the erysipelas.

That it was a true nephritis which terminated favourably in all these cases was
sufficiently shown by the results of microscopical and chemical examination,

which disclosed the presence of albumin, blood casts (of Groups I. and II.), renal
epithelium, and numerous leucocytes in the urine.

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236 . THE URINE.

It has been already mentioned that in septicemic processes the urine
has repeatedly been seen to hold cylindrical bodies, whose chemical
properties showed them to consist of micrococci (Martini, Litten,
Senetz).64 Weichselbaum © has found specific micrococci in the urine
in ulcerative endocarditis ; Lustgarten and Mannaberg ® cocci in acute
nephritis ; and Letzerich °" bacilli in the “ primary” nephritis of children.
Mircoli ® also determined the existence of pneumonococci-like forms in
the urine of children suffering from this disease. Further, Mewmann ®
has found the typhoid bacillus in the urine in six out of twenty-three
cases investigated, and Karlinski" has obtained cultivations of the
bacillus from typhoid urine in the earliest period of the disease.
Philipowicz™ has recognised the tubercle bacillus and the bacillus of
glanders in urine.

The spirilla of relapsing fever (p. 44) occur very rarely, and only

    
 
 

A A
NeEZ |
~

 

Fic. 108.—Tubercle Bacilli from Urinary Sediment in a Case of Tuberculosis of Urinary Organs
(eye-piece III., objective },, oil immersion, Reichert).

when hemorrhage takes place in the kidney during the period of
exacerbation ; but Kannenberg @ asserts that various forms of microbes
are detached from the kidney in very great numbers in the exacerba-
tions of this disease.

The recognition of tubercle-bacillus in the urine has of recent years
been invested with great pathological interest (Lewbe, Rosenstein, Babes,
Shingleton Smith, Irsai, Benda, Kreske).”’ The method of its detection
is the same as that already described in connection with the sputum
(p. 104). Its presence in general points to tubercular ulceration in some
part of the urinary tract, and most unequivocally when the bacilli
are found to be arranged in S-shaped aggregations (fig. 108), or in
colonies of unmixed constitution (pure cultivations). It should be
stated, however, that Phdlépowicz™* has discovered isolated specimens
of the bacillus in the urine in miliary tuberculosis, where there were
no tubercular ulcers in the genito-urinary passages. The localisation
of ulcerated patches must depend upon the other microscopical consti-

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INFUSORIA—VERMES. 237

tuents of the urine. When these point to an affection of the kidney,
we are warranted in inferring tuberculosis of that organ.

A form of caseation is known to occur in the kidney which, in its gross appear-
ances, closely resembles chronic tuberculosis. And in this condition a careful
examination, whether of the urine or of the caseous masses removed from the
organ after death, will fail to reveal the specific bacillus. It would appear, there-
fore, that chronic non-specific inflammatory changes, such as we are familiar
with in the lungs, may take place also in the kidney, and lead to destruction of
its tissues.

When, in the course of pulmonary tuberculosis, the urine is found to
contain albumin or pus, it will suggest to the physician the possibility
of the renal complications which are known to attend the diathesis ; he
will diligently examine the urine for the tubercle-bacillus, when the
symptoms, after microscopical, chemical, and clinical investigation, do
not find their explanation in the assumption of amyloid degeneration of
the kidneys, of chronic nephritis, or cystitis.

Actinomyces may also appear in the urine in cases where the genito-
urinary tract is infested with it, or when it has discharged thereby
from other parts.”

In searching for pathogenic fungi, it is essential that the parts about
the meatus be carefully cleansed, and the urine passed into a thoroughly
disinfected vessel.76 It should then be allowed to settle, and cover-
glass preparations made from the sediment in the usual manner. In
some cases it will be necessary to resort to Koch’s method of plate-
cultivation to obtain the various micro-organisms in an unmixed con-
dition. Finally, the inoculation of animals will resolve doubt as to the
character of the specific organisms obtained.

2. Infusoria.—The author has frequently observed infusoria in the
urine, but never when it was fresh. They made their appearance in all
cases when it had been allowed to stand for some time, and the fluid
containing them was generally feebly alkaline. Amongst these organ-
isms were bodies which were similar to the cercomonad already described
in the chapter on /eces. Hassall” has given to one of the infusoria of
the urine the name of Bodo urinarius.

The presence of infusoria has no pathological significance. Baédlz 8
observed a great quantity of Amcebe in the turbid urine of a girl
twenty-three years of age who was affected with phthisis. These
were of larger size than the forms already described as occurring in
the stools.

3. Vermes.

1. Distoma Hematobium.—The eggs of this parasite are often found
both in the urinary passages and in the urine of inhabitants of the
tropics (see p. 187). In such cases the latter furnishes other evidence

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238 THE URINE.

of the parasite, as blood, and frequently abundance of fat. The con-
dition is attended with severe burning pains in micturition.” These
are momentary, and are caused by the passage of the eggs (see p. 58)
along the urethra, which they irritate with their sharp angles. With
the last drops of urine a blood-clot is often passed. The fluid is usually
clear, and contains blood-cells and pus, amongst which the eggs repre-
sented in fig. 109 are to be sought.

 

Fic. ro9.--Distoma Heematobium in Sediment (eye-piece II., objective C, Zeiss).

2. Filaria Sanguinis Hominis.—Lewis has detected filaria in the
urine in some cases in which the blood was much infested by it (fig. 36),
and its appearance was generally accompanied with blood and pus. It
is most likely this worm which causes the tropical hematuria of which
Wucherer first sent an account from Brazil.

3. Echinococci.—The hooklets and fragments of the cysts of echino-
coccus occur as a very rare manifestation in the urine (Mosler).8° In
such cases, the cysts may have formed originally in the urinary pas-
sages—and this is very exceptional—or they may have found their way
into them by rupture from a neighbouring organ. When the hooklets
and characteristic membrane (fig. 61) are present, the sediment is likely
also to contain red blood-corpuscles, numerous leucocytes, and a quantity
of cellular débris from that part of the urinary apparatus which has been
injured by the separation of the cyst.

4. Eustrongylus Gigas.—This parasite has been said to exist in the
urine, but the researches of Leuckart®! have thrown doubt upon the
matter. At all events, it must be very rare.

5. Ascarides._-In exceptional instances ascarides make their way
from the intestine into the urinary passages. Their presence in the
urine is usually brought about by an abnormal communication between
the latter and the alimentary canal. Schezber * has recently found in
the urine of a woman worms which he thought had been derived from
the genital organs, and he has named them Rhabditis genitalis. Similar
observations have heen reported hy £. Petper, Westphal, and Baginsky.®*

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UNORGANISED SEDIMENT. 239

Il. CRYSTALLINE AND AMORPHOUS DEPOSIT (UNORGANISED
SEDIMENT).—It will be convenient in treating of the inorganic deposit
of the urine to consider, in conjunction with the microscopical appearance
of its constituents, some of the more characteristic of their chemical and
histochemical properties.

The colour of the sediment and the reaction of the urine will often
afford some indication of the nature of the deposit. Thus, if sedi-
ment of a deep red colour forms when the urine has stood for a short
time, it consists mainly of urates. The colour is then due to the pre-
sence of urinary pigments, carried down by the deposit, uric acid and
its salts being themselves colourless. If the deposit redissolves on the
application of heat without the addition of acid, it is a further proof that
it is composed of urates.

If, on the other hand, the urine is alkaline, and deposits a white
flocculent sediment, the latter probably either consists of pus or contains
a large proportion of phosphates, carbonates, and alkaline urates. Such
a sediment is insoluble by heating, but readily so in presence of acid
(acetic acid).

A third kind of sediment, of a mixed character, may be distinguished.
This consists of urates and phosphates, and it forms in urine which
was acid when passed, but which has become gradually alkaline from
the supervention of ammoniacal fermentation.

An abundant sediment of urates belongs to the urine of fever and
renal congestion, and occurs also in healthy individuals after excessive
perspiration without partaking freely of water (see p. 212). It is
thought by Mygge ®* that the presence of such sediment, when it con-
sists of uric acid, has a certain clinical significance, inasmuch as it is.
generally found in cases of rheumatism or renal disease.

Phosphatic sediment is apt to form in all conditions where the urine
possesses an alkaline reaction when passed. It does not, however,
always indicate disease, because it may be induced by the drinking of
aérated water and by other means. Amongst pathological conditions
dyspepsia often occasions the deposit of phosphates, and in general
it may be said that phosphatic sediment is associated with chronic, as
distinguished from acute, affections.

The characters above referred to will serve to indicate which class
of salts preponderate in the urine. A more accurate estimation of its
inorganic constituents can be formed only from a microscopical and
histochemical investigation of the sediment.

Such constituents may be crystalline or amorphous. Their nature
will further differ according as the precipitate is an acid or an alka-
line urine. We shall, therefore, consider the sediments of acid and of
alkaline urine separately.

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240 THE URINE.

A. Sediments of Acid Urine.

(a.) Crystalline Deposits.

1. Urie Acid.—Uric acid occurs in crystals, which are deeply stained *
a brownish-yellow [or red] colour, and differ much as to their form and
size. [The colour is due to uroerythrin, which has a great affinity for
the crystals.] They are sometimes large and thick, in shape like a whet-

  

Fig. 110.—Pointed Crystals of Uric Acid Fic. 111. — Urie Acid Crystals from the
from the Simple Urine in Congestion from Urine in Congestion of Heart-Disease (eye-
Emphysema (eye-piece III., objective 8a, piece III., objective 8a, Reichert).

Reichert).

stone (figs. 107, a, and 110), and then commonly exhibit a dark nucleated
centre ; sometimes they are longitudinally striated spicules (fig. 111),
and sometimes again rhombic tables (figs. 107, b, and 110) with rounded
angles. They may appear separately or in masses. Their shape and
size vary greatly, their most characteristic property being their colour,
and through it alone they may be readily recognised. They may be seen
under the microscope to dissolve in caustic potash, and can again be

 

Fic. 112. -Oxalate of Lime from Sediment in a Case of Cystitis and Pyelonephritis
(eye-piece III., objective 84, Reichert).

made to crystallise in the rhombic form by neutralisation with hydro-
chloric acid. The murexide test (see p. 71) may be employed in appro-
priate cases for their detection.

2. Oxalate of Lime.— This substance crystallises in transparent,
strongly refracting octahedra (envelope crystals), which are readily
soluble in hydrochloric and insoluble in acetic acid (Fiirbringer).®

The occurrence of isolated crystals of oxalate of lime (fig. 112) has
no clinical significance. ‘They have been found in healthy urine, and
their number may be greatly increased after the ingestion of food
containing a large proportion of oxalic acid, such as tomatoes, fresh

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BILIRUBIN—-H EMATOIDIN. ~ 241

beans, beetroot, asparagus, &c. On the other hand, oxaluria as a morbid
state cannot be measured by the use of the microscope alone, since the
urine may contain a large proportion of oxalic acid, whilst neither it nor
its salts are precipitated as crystals. In such cases, the urine must be
analysed with a view to ascertaining the proportion of oxalic acid which
it contains.

3. Bilirubin and Hematoidin.—Bilirulin is deposited in the urine
either in the amorphous form or in crystals. Crystals of bilirubin
have a twofold character, occurring either as clusters of needles, or
as minute rhombic tablets, and their colour ranges from yellow to
a beautiful ruby-red. They are soluble in caustic:soda, and on the
application of a drop of nitric acid a green rim forms round them.
Kussmaul ®° has discovered these crystals in jaundice, and Hbsteim * in
pyelonephritis.

Hematoidin resembles bilirubin as closely in appearance as in its
chemical properties. The crystalline formations of the two are identical
(see fig. 89) ; but it would appear that hematoidin may be distinguished

 

Fic. 113.—Triple Phosphate Crystals from the Sediment in Chlorosis (eye-piece III,
objective 8a, Reichert).

chemically from the fact that it turns a transitory blue when treated
with nitric acid (Holm **), and is insoluble in caustic potash and ether
(Stddeler).8° According to Hoppe-Seyler,®® hematoidin and bilirubin
are in all respects indistinguishable, and the experience of the author
lends support to the view of this great authority ; for he has repeatedly
had occasion to observe that, in the urine of jaundice, the yellow cellu-
lar elements, and notably the epithelium, are stained red, passing to blue
on the application of nitric acid—a reaction which is assumed to belong
only to hematoidin, and yet in these cases there can be no doubt that
the substance present is bilirubin (see also p. 61).

Leyden®! found these crystals in nephritis gravidarum, Foltanek
and Rosenheim? in acute yellow atrophy of the liver, and Fritz in
various chronic and acute diseases, e.g., in a case of carcinoma of the
liver, in scarlatina and typhoid. They were usually connected with
cellular débris, and in jaundice alone were they also met with in the

Q
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2A THE URINE.

free state. In general it may be said that the presence of such free
crystals in considerable quantity implies an antecedent hemorrhage or
the bursting of an abscess—as a suppurating echinococcus cyst—into the
urinary passages.

4. Triple Phosphates.—Crystals of triple phosphate occur commonly
in weakly acid urine, as in the feces (see p. 197), as bodies of large size
and of the coffin-lid form (fig. 113). They are readily soluble in acetic
acid. Even when found in large numbers, this fact alone will hardly
warrant the diagnosis of phosphaturia.

5. Basic Phosphate of Magnesia.—The crystals of this body have
the form of large strongly refracting plates, usually in the shape of

 

 

Fic. 114.—Basic Phosphate of Magnesia (eye-piece II., objective C, Zeiss).

elongated rhombic tablets (fig. 114). They are readily soluble in acetic
acid, and precipitated again on the addition of carbonate of soda. They
are found in concentrated urine of feebly acid, neutral, or alkaline
reaction (Stein).°*

6. Neutral Phosphate of Lime.—These crystals appear as pointed
wedge-shaped prisms, either singly or in clusters, They are decom-

 

Fic. 115.—Neutral Phosphate of Lime from the Urine of Chronic Nephritis after standing for
twenty-four hours. The urine was feebly acid (eye-piece III., objective 8a, Reichert).

posed by ammonia, and dissolve in acetic acid (fig. 115). They occur
commonly in feebly acid urine which is becoming alkaline.

7. Sulphate of Calcium.—This substance is rarely present in the
urinary sediment. It generally takes the form of long colourless
needles, but occurs also in elongated tables with abrupt extremities.
Amongst such crystals are sometimes to be seen masses of indeter-

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HIPPURIC ACID—CYSTIN. 243

minate crystalline structure (fig. 116). They are insoluble in ammonia
and acids. Clinically their presence is of little consequence ( Valentiner,
Piirbringer).®

 

Fic. 11€.—Calcium Sulphate, Abundant Sediment (eye-piece II., objective C, Zeiss).

8. Hippuric Acid.—Crystals of hippuric acid have the form of four-
sided prisms, and are scattered separately or in groups (figs. 117 and 118)
through the sediment.

They are soluble in ammonia, insoluble in hydrochloric acid. They

 

Fig. 117.—Crystals of Hippuric Acid (eye-piece II., objective C, Zeiss),

occur in considerable quantity after the exhibition of benzoic acid, or
the ingestion of certain fruits, as cranberries and bilberries. Otherwise
they are a rare manifestation, and have little influence on diagnosis.

Pur =
eS a

Fic, 118.—Hippuric Acid from the Urine of a Rheumatic Patient after large doses of Benzoic
Acid had been taken (eye-piece II., objective 8a, Reichert).

9. Cystin.—The crystals of this body are seen as symmetrical hexa-
gonal tables (fig. 119, 0), superimposed upon or contiguous to one
another. They are insoluble in acetic acid, but readily soluble in
ammonia. In this they differ from the crystals of uric acid.

Cystin may also be present in solution in the urine. It may then
be precipitated by acetic acid.

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244 THE URINE.

When crystals are found in the urine which answer to the descrip-
tion’ given here, they should be separated by filtration or decanting,
the sediment washed with a little water, and the substance in question
tested on the platinum foil. Cystin burns with a bluish-green flame,
and without melting.”®

If cystin be boiled in caustic potash holding oxide of lead in solution,
sulphide of lead forms (Liebig).°”

When heated with caustic potash on a silver plate (as a coin), it
leaves a brown or black permanent mark. When dissolved in a boiling
solution of caustic potash, dilution with water and the addition of a
solution of ferrocyanide of sodium give a violet colour (J. Miiller).®

This reaction, according to Krukenberg,®® belongs not to the cystin,
but to sulphide of calcium, which constitutes an impurity of the caustic
potash with which it has been boiled.

 

Fic. 119.—¢. Tyrosin ; b. Cystin; c. Leucin (eye-piece II., objective 84, Reichert).

10. Xanthin.—H. Bence Jones! once found this substance in the
urine of a lad who had three years previously exhibited the symptoms
of renal colic. It was seen in the sediment in the form of whetstone
crystals, which were insoluble in acetic acid and soluble in ammonia
(thus distinguished from uric acid). Such bodies are clinically of import-
ance, inasmuch as they may give rise to the formation of calculi (see
the observations of Bence Jones, 1.c.).

11. Tyrosin and Leucin.—These substances generally occur together
in the urine.

(a.) Tyrosin is seen in the sediment in sheaves of very fine needles
(fig. 119, a), which are insoluble in acetic acid, soluble in ammonia and
hydrochloric acid.

To determine the character of tyrosin chemically, the sediment con-
taining it should be separated by filtration, washed with water, dissolved
in ammonia with the addition of carbonate of ammonia, and the solution
allowed to evaporate. The tests for tyrosin may then be applied :—

t. A milligramme of the substance obtained is’ placed on a watch-
glass and moistened with a drop or two of sulphuric acid. The mixture
is covered and allowed to stand for half-an-hour. It is then diluted
with water, heated, while still hot saturated with calcium carbonate,
and filtered. The filtrate is colourless, and when treated with acid-

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TYROSIN—LEUCIN. 245

free ferric chloride (see p. 157), it assumes a violet tint (Piria,
Stideler).11

2. When the tyrosin is heated with nitric acid on. platinum foil, it
assumes an orange-yellow colour. The residue is dark-yellow, and turns
reddish-yellow on the addition of caustic soda. When the latter is
evaporated, the substance which remains is of a deep brownish-black
colour (Scherer).1

3. Tyrosin crystals are dissolved in hot water, and the still hot solu-
tion is treated with mercuric nitrate and nitrite of potash. The fluid
assumes a dark red colour, and yields an abundant red precipitate (2.
Hoffmann and L. Meyer).10

4. C. Wurster °* recommends the following process :—Tyrosin is dis-
solved in boiling water and a little dried quinone is added. The fluid
quickly assumes a deep ruby-red colour, which changes to brown after
the lapse of twenty-four hours. The quinone-tyrosin reaction can be
depended upon only when tyrosin has been isolated as the free acid
[para-hydro-oxyphenol-amido-propionie acid], and will not serve as a test
unless it appears readily after the application of heat without prolonged
boiling. Quinone alone, or in presence of phenol, gives, when boiled,
a rosy-yellow colour to its solutions.

Tyrosin occurs dissolved in the urine as well as in erystals. To
obtain it from solution, basic acetate of lead should be added, when a
-precipitate will form. The fluid should now be filtered, and the filtrate
freed from lead by the addition of sulphuretted hydrogen, again filtered,
and partially evaporated on the water-bath. The residue is repeatedly
extracted with small quantities of strong alcohol, and the extract
several times boiled with weak alcohol and then allowed to evaporate
spontaneously.

(b.) Leuein.—This body, which is commonly associated with tyrosin,
is for the most part held in solution in the urine, but to some extent
occurs also in the sediment in the form of small spheres (fig. 119, ¢).
The process for its detection is the same as that for tyrosin. It may be
separated from the latter by crystallisation from a watery solution, and
then purified by recrystallisation from a solution of ammonia in boiling
alcohol. When quite pure, leucin ecrystallises in delicate plates ; when
impure, it forms little bulbs of amorphous structure. It may be known
by the following tests :—

r. A solution containing leucin, when heated with proto-nitrate of
mercury, deposits metallic mercury (Hofmeister).1°

2. When consumed with nitric acid on platinum foil, it leaves a
colourless residue. This, when heated with caustic potash, forms drops
of an oily fluid which does not adhere to the platinum (Scherer).1%

Tyrosin has been found in the urine in conjunction with leucin in

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246 THE URINE.

phosphorus poisoning, acute yellow atrophy of the liver, and several of
the infectious diseases (Frerichs, Schultzen, Reiss, Pouchet, A. Frankel,
Blendermann, A. Irsat).107

It is probable, however, that in some instances where these bodies
were supposed to have been in the urine they were not sufficiently
identified ; and it is within the author’s experience that a deposit has
repeatedly been taken as consisting of tyrosin, until subsequent chemical
analysis exposed the error. Prus18 has found abundance of leucin in
the urine in cases of leukemia.

12. Soaps of Lime and Magnesia.—In the urine of various diseases
are often found crystals bearing a very close resemblance in form to
those of tyrosin (v. Jaksch), but possessing distinctive characters of
their own. The accompanying illustration (fig. 120) represents such

 

Fic. 120.— Lime and Magnesia Soaps from the Urinary Sediment of a Woman with Puerperal
Septiczemia (eye-piece II., objective 84, Reichert’.

crystals, which the author had the opportunity of examining once only
in tolerable abundance. They occurred in the sediment from the feebly
acid urine of a woman with severe puerperal septicemia. They are
obviously very similar to those of tyrosin, but yielded none of the
characteristic reactions of that body as given above (1-3). The material
was not sufficient for further analysis; but it appeared from the be-
haviour of the substance in question with regard to solubility, &e. (see
p. 196), that it was probably formed of the lime and magnesia salts of
the higher fatty acids.

(o.) Amorphous Deposits.

1. Urates.—Amorphous urates have the appearance of fine granules,
disposed singly or in masses. They are entirely dissolved by heating
cr the addition of acids, and the sediment when treated in this way
exhibits free uric acid, for the most part in the form of rhombic tablets.

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OXALATE OF LIME—FAT. 247

2. Oxalate of Lime.—The envelope crystals of oxalate of lime have
been already described (see p. 241). This substance appears also as
dumb-bell-shaped figures. They are unaffected by acetic acid, and dis-
solve in concentrated solution of hydrochloric acid.1 [The oxalate of
lime dumb-bell is really a disc with a central depression on either face,
and it presents this appearance when seen sideways (Ff. Taylor).1°
Such formations result from slow precipitation in presence of colloid
matter (Ord). ]

3. Sulphate of Calcium.—In addition to its crystalline form (p. 242
and fig. 116), sulphate of calcium in the urine takes the appearance of
dumb-bell-shaped amorphous masses, which are insoluble in ammonia
and in concentrated solutions of hydrochloric acid.

When the sediment contains this substance in considerable quantity,
it may be separated from the other constituents by decanting, filtering,
and washing in cold water. It is then dissolved in a large bulk of hot
water. If to one portion of this solution a quantity of chloride of
barium be added, a precipitate of barium sulphate forms, and this is
insoluble in nitric and in hydrochloric acid. If another portion be
treated with ammonium oxalate, a precipitate of oxalate of lime falls.
This precipitate is insoluble in acetic and soluble in hydrochloric and
nitric acids.

4. Brown and Yellow Concretions.—The urinary sediment may
contain such concretions either free or associated with cells, and con-
sisting of hematoidin or of bilirubin, which, as we have seen, is perhaps
indistinguishable from haematoidin. According to Holm,4? when a
substance of this sort is found to be soluble in caustic potash, and
exhibits a coloured ring, of which green forms one zone, on the appli-
cation of nitric acid, we are to assume that it consists of bilirubin.
When, on the other hand, it is insoluble in caustic potash, and colours
transitorily blue with nitric acid, he would suppose that it is formed of
hematoidin.

5. Fat.—Fat is deposited in the form of strongly refracting globules
of varying size, which are readily soluble in ether. It may be present
in the urine in small quantities after the fracture of bones, and in chronic
inflammation of the kidney, attended with much fatty degeneration of
that organ. It occurs in greater abundance, however, only in chyluria,
which for the most part depends upon the action of certain worm
parasites (Distoma hematobium and Filaria sanguinis hominis), and in
phosphorus poisoning. We shall have occasion later to revert to the
subject of chyluria and lipuria.

B. Sediments from Alkaline Urine.

(a.) Crystalline Deposits.

1. Triple Phosphate.—The crystals of triple phosphate deposited in

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248 THE URINE.

alkaline urine exhibit a very great diversity of character, especially
when newly formed in the process of ammoniacal fermentation. They
may be seen under such circumstances to resemble snowflakes, or again
as peculiar jagged figures, resembling flags or elder leaves (figs. 113 and
121T). Their most permanent and characteristic form, however, is that
of large colourless and more or less perfect coffin-lids or knife-rest form.

 

Fic. 121.—Triple Phosphate Crystals (rare form) from Urine in Alkaline Fermentation
(eye-piece IT., objective 8a, Reichert).

2. Indigo.—Indigo occurs in the urine as concretions and amorphous
fragments, and also in the form of blue crystals and fine blue needles,
which mostly cohere in clusters. Crystals of indigo are no very rare
manifestation in decomposing and fermenting urine. “They are derived
from the decomposition of sulphate of indoxyl. This substance was
found to be present in remarkable abundance during the process of
ammoniacal fermentation in the urine of jaundice, from a patient with
hypertrophic cirrhosis of the liver. The urinary sediment, in the case

eae EG “9 op
‘ we Wi;

   

Fig, 122.—Indigo Crystals from a Urive rich in Indican, after standing for eight days at
ordinary temperature (eye-piece III., objective F, Z<iss).

of abscess of the liver, was recently examined by the author. It con-
tained numerous indigo erystals, and had an acd reaction (fig. 122)
(v. Jaksch).

[Dr. Ord 43 has observed a deposit of indigo in the alkaline urine of
a patient who had long suffered from enlarged prostate. In this case,
besides pure indigo, there were several bodies stained by that substance.
Among them were crystals of urates and phosphates, epithelium, yeast
cells, and bacteria. In this way, as Ord points out, the form of the
indigo is determined by the form of the bodies on which it is deposited. ]

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4
 

URATE OF AMMONIA—AMORPHOUS DEPOSITS. 249

3. Urate of Ammonia.—Urate of ammonia forms spherical bodies,
dark in colour and of varying size. Their circumference is beset with
radiating spicules of crystalline structure (fig. 123). [Hence they are
known as hedgehog crystals.] They are soluble in hydrochloric and

 

Fic. 123.—Crystals of Urate of Ammonia, Sediment in Alkaline Fermentation (eye-piece II.,
objective 8a, Reichert).

acetic acid, with the formation of uric acid, which is deposited in the
form of rhombic tables.

4. Phosphate of Magnesia.—The crystals of this salt have been
already (fig. 114) sufficiently described.

5. Cholesterin.—Crystals of cholesterin are very rarely to be seen in
the urinary sediment. The author has observed them but once, and
that was in the case of a man who suffered from tabes and cystitis. The
cholesterin took forty-eight hours to deposit in crystals. The urine

 

Fic. 124.—Cholesterin Crystals from a Sediment in a Case of Tabes and Cystitis ; crystallised
from wether and alcohol (eye-piece II., objective 8a, Reichert).

when freshly voided had a slightly acid reaction, was turbid, and when
shaken, a great number of scaly particles could be seen in it with the
naked eye (fig. 124).

(o.) Amorphous Deposits.

1. The large, dark-coloured, spherical bodies represented in fig. 123
consist of wrate of ammonia. They are distinguished by their solubility
in acetic and phosphoric acids, with the simultaneous deposit of rhombic
tables of uric acid.

2. Larger or smaller particles, which dissolve in acetic acid without
the evolution of gas: basic phosphatic earths.

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250 THE URINE.

3. Particles of varying size, which are soluble in acetic acid with the
evolution of gas: carbonates of the alkaline earths.
4. Dumb-bell-shaped masses and coarsely granular concretions, dis-

oS,

 

Fic. 125.—Deposit of Carbonate of Lime, Sediment of Ammoniacal Urine (eye-piece II.,
objective C, Zeiss).

solving in acetic acid with the evolution of gas: carbonate of lime

(fig. 125).
5. Indigo.

III. Urinary Concretions.

Concretions of considerable size are occasionally to be seen with the
naked eye in the urine (urinary sand). They consist for the most part
of urates, or of urates and uric acid together. Their recognition is of
great consequence in the diagnosis of renal colic (nephrolithiasis). These
concretions are usually more or less stained, and their constitution may
be readily determined by the tests already given for the compounds of
uric acid (p. 240).

Phosphatic concretions of larger size occur more rarely. They are
light-coloured and of little consistence.

Other concretions occasionally to be met with in the urine are those
of cystin, xanthin, oxalic acid, and indigo (Ord, H. Chiari)..4 Those
of the last-named substance are easily recognisable by their colour.

In a case which occurred in the author’s clinic, and which proved fatal from
uremia, the right kidney was found to be cystic, and it contained a large
quantity of crystalline concretions. These were ascertained by the author’s
colleague, Hofmeister, to consist of oxalate of lime, an insoluble proteid, and a
derivative of blood pigment.

The constitution of these bodies is dealt with at greater length in
the ordinary text-books on the chemistry of urine (see Huppert, Hoppe-
Seyler, and Leube-Salkowsht).

IV. Foreign Bodies in the Urine.

As occasional impurities of the urine may be enumerated fatty par-
ticles (often introduced with the catheter), fibres of silk, linen, and
wool, particles of feathers and wood, and starch granules, the latter
being employed as starch powder in medication of the urethra.

The appearance in the urine of substances belonging to the faeces is

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FOREIGN BODIES—PROTEIDS. 251

a fact of serious import. In drawing a conclusion from their presence,
care, of course, must be taken to ascertain that they were actually passed
with the urine ; and when this is so, they are evidence of an abnormal
communication between the urinary passages and the gut.

Fragments derived from tumours, as sarcoma and carcinoma, may
find their way into the urine by invasion from neighbouring organs
(see p. 233).

Hairs have been known to be passed with this fluid (pilimictio).
They have generally been derived from dermoid cysts in the urinary
passages. Sometimes they have been conveyed by accident or design
(hysteria) into the recipient vessel. In very rare cases gases are voided
with the urine (pneumaturia) in considerable quantity ; but when this
has occurred, there has, as a rule, been an abnormal communication
between the urinary passages and the intestine (see Hydrothionuria).
It must, however, be borne in mind that gas may be freely generated in
the bladder by spontaneous decomposition of the urine.

Thus J, Miller reports the case of a man of sixty years, suffer-
ing from severe cystitis, where the urine held sugar and a number of
gases—namely, hydrogen, nitrogen, carbonic acid, and probably methan.
Senator 1 has observed a similar condition.

III. CHEMICAL EXAMINATION OF THE URINE.

A. Organic Substances.

1. Proteids.—We shall begin with the consideration of albumin,
which is the commonest of all the morbid constituents of the urine.

It is still an open question whether albumin ever occurs in consider-
able quantity in the urine of health. For whilst, on the one hand, the
older authorities (as Frerichs, Vogel, and Ultzmann 1) have recorded its
occasional presence in healthy urine, and the more recent investiga-
tions of Leube, Firbringer, Senator, and C. Posner 8 would seem to
have established the possibility of a physiological albuminuria, the
researches of v. Noorden | are not less decisive in the opposite direc-
tion; and Leube and Winternitz °° from recent very careful experiments
conclude that not every urine contains albumin. [Grainger Stewart 12!
has found that albumin is occasionally present in very minute quantity
in the urine of persons apparently healthy ; and he believes that in some
cases it is derived from epithelial and other débris after the urine has
been secreted at the kidney. ]

For the purpose of such investigations the following plan may be adopted :—
Normal urine is taken, and it is first ascertained to be free from bacteria and
from albumin, as shown by the ordinary methods. It is next distilled in vacuo
at a low temperature (35° to 37° C.), and the residue, with the included sediment,
is either tested directly, in the manner to be indicated at p. 255, or it is first

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252 THE URINE.

treated with alcohol ; and of the sediment which remains when the spirit has
been driven off, one part is dissolved in water, another in acetic acid, and a
third in caustic potash, and the solutions submitted to the tests described at
p. 235 (Anschiitz). Proceeding in this way, it will be found that Leube’s state-
ment concerning healthy urine is entirely correct, and not a trace of albumin
can be shown in it. In the urine of certain diseases, on the other hand, as in
valvular heart-disease with compensating hypertrophy, where the most sensitive
tests directly applied will fail to evince the presence of albumin, it can readily
be shown in the concentrated fluid obtained as above.

It may at all events be confidently stated that the urine occasionally
holds a variable quantity of albumin as a temporary constituent, whilst
at the same time the kidneys exhibit no alteration of structure, and its
presence in such cases is to be attributed to a sudden disturbance of the
circulation (see Se/reiber’s experimental albuminuria). To the same
category of causes must be ascribed the conditions similarly observed by
Stirling in apparently healthy boys, and by Ringstedt, Heubner, and
Washburn.  [Pavy’s 4 “cyclical albuminuria” occurs during the day
and disappears during the night. It seems to be caused by the erect
posture.  Moxon’s! remittent albuminuria has probably the same
significance. Fagge'® has described a paroxysmal albuminuria which
he believed to be a form of hemoglobinuria, where globulin resulted
from the decomposition of hemoglobin. The condition is occasionally
associated with the deposition of oxalates. Finally, a temporary albu-
minuria may depend upon diet or be induced by exercise (Taylor).!"]
Albuminuria of the like cause and import sometimes occurs, as Falken-
heim 18 has remarked, in connection with morbid states. [The abuse of
morphia is recognised by Huchard!® and by Haiy'° as a cause of
albuminuria, dependent probably on vascular disturbance.] Virchow
originally, and after him many other observers, have shown that the
urine of newly-born infants often contains albumin.!31
Bright 2 in England was the first to determine the connection
between renal disease, dropsy, and albuminous urine, and after him
the labours of such men as Christison and Rayer, Frerichs and Traube,!*?
formulated what was known of albuminuria as a clinical symptom.
For a long time it was thought sufficient merely to determine the
presence of proteid matter in the urine, and the further question was
not raised as to whether it occurred in more forms than one. It is now
established on clinical and physiological grounds that, in addition to
serum-albumin, the urine may contain globulin, peptone, albumose, oxy-
hemoglobin, mucin, and fibrin; and it is obviously important to be
able to distinguish between these bodies. At present, the chief clinical
interest attaches to serum-albumin, peptone, and albumose, for by
methods now well established we can readily separate each of these
from the others. The very simple methods which Kauder and Pohl 1°4

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ALBUMIN. 253

(of Hofmeister’s laboratory) have recently communicated for the detec-
tion of globulin in serous fluids and urine have placed us in the same
favourable position with reference to that body, and by their aid we may
hope soon to learn whether globulinuria also exists as an independent
condition. In view of their importance in this connection, we shall
describe these methods with the others. It follows from what has been
said that albuminuria is of different kinds, and we may distinguish :
(1) Serum-albuminuria, which alone will be understood to be meant
by the term “albuminuria” in the following pages; (2) Peptonuria ;
(3) Albumosuria ; (4) Globulinuria, which as yet is not known to occur
by itself ;1%° (5) Fibrinuria; (6) Hematuria (see p. 270); (7) Hemo-
globinuria ; and (8) Nucleo-albuminuria (Mucinuria).

1. Albuminuria.—Under this heading we shall group those states
in which the urine is found to contain serum-albumin, in combination,
perhaps, with a variable proportion of globulin.

The author has come to the conclusion, as the result of repeated analysis, that
the urine of serum-albuminuria does not invariably contain globulin.
DS

Serum-albumin in notable quantity is never found in healthy wrine.
Its appearance is in all cases a morbid symptom of great importance.

The albumin of urine may be derived from the kidney (renal albu-
minuria), or by admixture from parts in the urinary passages beyond
the kidney (contingent, accidental albuminuria).

(a.) Renal Albuminuria.—This form of albuminuria, which is at
once the commoner and the more serious, depends in all cases upon dis-
turbance of the renal functions, and such disturbance may be due to
various causes. By far the most frequent of these are inflammatory
and degenerative changes in the structure of the kidneys. It should be
mentioned here that where such processes in the kidney are the under-
lying cause of albuminuria, we cannot always infer their extent and
severity from the quantity of albumin eliminated. So far indeed is this
from being the case, that there are certain forms of renal disease of an
especially serious character (granular kidney, red atrophy), in which the
urine contains only traces of albumin. Another cause of albuminuria
is found in disturbances of the circulation of different kinds, provided
only that such disturbance extends to the vessels of the kidney. It
must, however, be borne in mind that errors of the circulation, when
of long continuance, may effect changes in the structure (congestion) of
the kidney.

To disturbances of the circulation should perhaps be referred the
temporary albuminuria of epileptic paroxysms (IZ. Huppert !*), and
that which Schreiber }*" induced experimentally by compression of the
thorax in healthy persons. Possibly, also, that form of albuminuria

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264 THE URINE.

which often sets in in acute enteritis should be mentioned here (Singer,
Kobler).\*5 As a permanent condition referable to renal congestion may
be mentioned the albuminuria of emphysema, heart-disease, weakened
heart, &e.

To a third class of causes is to be ascribed the albuminuria of fever
(Leyden).1*9 The circumstances which promote the elimination of albu-
min in the febrile state are manifold. In the first place, the accom-
panying changes in blood-pressure would be alone sufficient to account
for albuminuria. Then it is known that a long continuance of the
febrile processes is competent to induce structural alterations in the
renal epithelium, which in their turn lead to albuminuria. It is con-
ceivable, again, that the special cause (fungi) in certain fevers exerts
an immediate influence in the matter, since we find that in many
infectious diseases the proliferating micro-organisms are eliminated in
large quantities by the kidneys (see p. 233). The admirable experi-
ments recently undertaken by H. Lorenz! lend great support to the
theory that the albuminuria of fever depends directly upon certain
histological changes in the renal epithelium, especially affecting the
““rodded ” lining cells.

There is a fourth form of albuminuria to be distinguished in respect
of causation from those already mentioned. It occurs in anemic and
enfeebled individuals, independently of kidney-disease, disordered cir-
culation, and the febrile state; and can be accounted for only by
assuming changes in the constitution of the blood, of such a character
that, whilst the structure of the kidneys remains intact, and the blood-
pressure is not appreciably altered, albumin is allowed to exude with
the urine (v. Bamberger’s hematogenic albuminuria).

It still remains to say a few words regarding that variety of albu-
minuria which is intermittent in character. In the author’s experience
it occurs under the most varying circumstances, and may be either
renal or accidental (¢.v.) in its origin. A number of observations of the
kind recently published by Bull, Mareau, Klemperer, Canfield, and G.
Johnson 4 have proved its occurrence in health, where, no doubt, it is
due to the circulatory disturbances already referred to.

In the course of a chronic or of an acute nephritis, it will often
happen that albumin is found to be temporarily present in the urine
(v. Jaksch).8 When this is so, a careful microscopical examination
of the fluid, at a time when it is free from albumin, will usually dis-
close the presence of formed material (casts and renal epithelium) by
which the existence of a nephritis may be known. Such intermittent
albuminuria belongs especially to contracted kidney. In a case of this
dlisease, if the quantity of urine passed in the twenty-four hours be
collected together and examined, it will nearly always be found to con-

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ACCIDENTAL ALBUMINURIA. 255

tain albumin ; but if the same urine be examined in separate portions
at shorter intervals—say of one or two hours—it will be found com-
paratively often that that which is collected in the forenoon is devoid
of albumin. But it is not in connection with kidney-disease that inter-
mittent albuminuria is most apt to occur. It is more often associated
with affections of the ureters and urethra, and especially with chronic
inflammation of the prostatic portion of the latter. In this connection
the urine first passed in the morning is generally turbid, and contains
albumin, derived no doubt from the pus cells in the fluid.44 Falken-
heim 1 has recorded a remarkable case of intermittent albuminuria,
caused by the pressure of a tumour on the left kidney. In Pavy’s
disease, it is probable that a careful microscopical examination would
show evidence of an underlying nephritis (see Merley).4° From what
has been said above of the various forms of renal albuminuria, it will
be seen that this condition is in itself a symptom of very ambiguous
significance. Taken with the other physical and microscopical appear-
ances of the urine—but only in conjunction with these—it will afford
a valuable indication of kidney-disease. It must be borne in mind that
we are never warranted in inferring the existence of a renal affection or
of a nephritis from the mere fact that the urine contains albumin. This
was the error of former times.

(d.) Accidental Albuminuria.—The appearance in the urine of albumin
derived from a source other than the kidneys is a symptom of much
slighter consequence. It may come from the renal pelvis, the ureters,
the bladder, or the urethra, or through an abnormal communication
from neighbouring parts, e.g., the lymphatics or thoracic duct. In
general, a positive judgment as to its source may be formed from the
result of chemical and microscopical investigation. Thus, for instance,
if the urine exhibits but little serum-albumin and a considerable pro-
portion of pus cells, the inference is that the former is obtained from
the migration of leucocytes in some part of the urinary passages just
mentioned. The absence of renal casts and epithelium, moreover, goes
far to exclude the possibility of renal albuminuria.

Determination of Albumin (Serum-Albumin).

(a.) Qualitative Tests.—The tests at our disposal for the recognition
of albumin are very numerous. The reactions which we shall describe
here are all more or less to be depended upon; but there are some
amongst them which will engage a larger share of our attention, and
they are those which years of clinical experience have shown to be espe-
cially reliable. Moreover, when applied in the order in which they are
given, they will afford a tolerably accurate means of discriminating the
various forms in which albumin occurs in the urine.

1. Nitric Acid and Heat Test.—A portion of the urine is boiled,

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256 THE URINE.

and a small quantity (7, to z/5 its volume) of nitric acid (sp. gr. 1.18)
added to it. Should a precipitate form on boiling, this may consist
either of albumin or of phosphates. If it dissolves on the addition of
acid, it is composed of phosphates; if not dissolved in presence of the
acid, and if increased thereby, it is albumin (acéd-albumin).

The application of this test, however, is open to certain fallacies.
In the first place, if there be but little albumin present, the quantity
of acid usually added will be relatively in excess ; and under these cir-
cumstances the albumin may combine with the acid to form a soluble
nitrate when no precipitate remains. Where, on the other hand, both
phosphates and albumin are present, if the acid employed be too little,
a portion only of the basic phosphates may be changed into the corre-
sponding acid salts, while the albumin enters into combination with
the rest, and remains in solution as an albuminate (union of albumin
with a base).

Another occasional source of error is the formation of a precipitate
of uric acid. Such a precipitate, however, can usually be known by
its deep brown colour, and from the fact that it is never flocculent.
Moreover, it does not fall until the specimen begins to cool.

Finally, the test may be misleading in cases where the urine contains
a considerable quantity of resinous acids (pine acids), as happens, for
instance, after the use of copaiba balsam. ‘These acids (pinic and
pimaric acids) are then precipitated by heat, but can be readily dis-
tinguished from albumin by their solubility in alcohol.

The heat and nitric acid test will serve for the detection of serwm-
albumin, globulin, and, where the precipitate falls on cooling, albumose,
but not for that of peptone.

2. Acetic Acid and Ferrocyanide of Potassium Test.—The urine is
filtered, and to the clear filtrate a large quantity of acetic acid (sp. gr.
1.064) and a few drops of a ro per cent. solution of ferrocyanide of
potassium are added. If albumin (serum-albumin) be present in con-
siderable quantity, a flocculent precipitate forms ; when merely a trace,
the fluid becomes turbid or slightly opalescent.

In the latter case, it may be necessary to compare it with the filtered
urine, in order to estimate the change in its appearance. It will also
happen, especially when it contains micro-organisms, that the fluid
cannot be rendered clear even by repeated filtration; and here again
the comparison will he between the simply filtered fluid and that to
which the reagents have been added. In the first instance a minimal
turbidity, in the second an increase, shows the presence of albumin.

This is a most satisfactory test, and by its means very minute quanti-
ties of albumin may be detected. The best and most accurate results,
however, may be obtained from its application in the following manner :—

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TESTS FOR ALBUMIN. 257

A mixture containing a few cubic centimetres of fairly concentrated
solution of acetic acid and a little ferrocyanide of potassium is freshly
made in a test-glass, and carefully poured upon the surface of the clear
filtered urine in a test-tube. If the merest traces of albumin be pre-
sent, a white ring forms at the point where the two fluids are in con-
tact. For ferrocyanide of potassium platinocyanide of potassium may
he substituted. The test is then just as accurate, and the advantage of
this reagent is that its solution is colourless.

By this method the presence of serum-albumin, globulin, and albu-
mose, but not of peptone, can be ascertained.

3. Biuret Test.\—The urine is treated with caustic potash, and a
dilute (10 per cent.) solution of sulphate of copper is added, drop by
drop, with a pipette. If albumin be present, the resulting peroxide of
copper (a green precipitate) is dissolved, and the fluid assumes a reddish-
violet colour.

This test serves for albumin, albumose, globulin, and peptone. The
latter substance, however, strikes red, not violet, in the fluid.

4. Heller’s Test.\45—The urine is poured carefully, so as to form a
layer on the surface of some nitric acid in a test-tube. At the junction
of the fluids a white cloud forms in the shape of a ring if albumin be
present. This test is very accurate ; but it is not to be recommended
for general use, because, in the case of undiluted urine, the deposition
of uric acid is apt to cause a brown discoloration, which may easily be
mistaken by the inexperienced for the clouding of albumin. After the
use of copaiba balsam, too, a similar rmg may form.

This reaction is also the basis of an admirable method for approxi-
mately estimating the proportion of albumin in the urine (see p. 260).

There are a number of other tests for albumin of a more or less accurate and
practicable character, and to some of these allusion must be briefly made.

Heynsius’ V'est.4°—The urine is to be rendered strongly acid with acetic acid ;
a few cubic centimetres of a saturated solution of chloride of sodium are added,
and the mixture boiled. The presence of albumin is shown by the formation of
a flocculent precipitate. Very small quantities can be detected in this way.

[Potassio-Mercurie lodide Test (Tanret’s Reagent).—This was found by a com-
mittee of the Clinical Society® to be the most delicate of a series of reagents
examined by it. Tanret’s reagent has the following constitution :—Mercuric
chloride, 1.35 grms.; potassium iodide, 3.32 grms.; acetic acid, 20 cc. ; water,
64 cc. The reaction may also be obtained by Heller's method. Serum-albumin,
peptone, albumose, alkaloids, and bile acids are precipitated by the reagent. It
may be conveniently employed by means of test-papers.]

Hindenlang’s (Metaphosphoric Acid) Test.'—If to urine which contains albumin
a little solid metaphosphoric acid be added, a precipitate or turbidity forms.
This test is very convenient, but will not suffice where only a trace of albumin
occurs. The author has repeatedly failed to obtain with it any indication of this
substance, while the application of the acetic acid and ferrocyanide of potassium
method exhibited its presence. On the other hand, he can confirm the state-

R

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258 THE URINE.

ments of Penzoldt and v. Noorden,! who maintain that a precipitate can often be
obtained by this reagent with urines with which all other albumin tests yield
negative results.

Fiirbringer’s Method 3 of testing with chloride of mercury and sodium has
been shown to be very convenient, especially when the reagent is used in the
form of capsules (Stiitz’s capsules); but it has no other advantage over those
previously described. ‘The use of test-papers also (as Geissler’s) in examining for
albumin, which has of recent years come into vogue in England and on the
Continent, does not seem warranted by experience.

The Picric Acid Test of Dr. George Johnson 4 is sensitive, but it is not alto-
gether accurate, since this reagent will effect the precipitation of alkaloids and
kreatinin (Jaffé}*) in the urine. It must, however, be studied, for it has become
the basis of a well-known method for the approximate estimation of the quantity
of albumin in that fluid. In this connection it will engage our attention later on
(p. 262).

Colour Reactions.—Finally, the albumin group yields a number of colour re-
actions, many of which are applicable to the purpose of detecting its members
when contained in the urine. Amongst these are the biuret test already men-
tioned, and Millon’s reaction. The xanthoproteic test, and the colour-reactions of
M. Schultze, Adamkiewicz, and Frihde,’ hardly call for special mention here, since
their application chemically for the determination of serum-albumin has no
advantage which does not belong to the methods adopted in the text. For par-
ticulars concerning the use of sulphuric and hydrochloric acid as colour tests for
albumin, the reader may consult Liebermann, C. Wurster, and E. Salkowski.1*7

Millon’s Reaction calls for fuller notice. If to a solution containing albumin
mercuric nitrate be added, and heat applied to boiling, the further addition of
potassium nitrite will cause the precipitate (if any) and the supernatant fluid to
turn red. The reaction is common to all the monohydroxyl-benzol derivatives
(O. Nasse**), As a test for albumin it is somewhat ambiguous, inasmuch as it
can also be obtained from members of the aromatic series. In this connection
we shall have occasion to refer to it again.

Schick} has applied Zouchlos’s}® proteid test to clinical purposes. It has no
advantage which does not belong also to those described at pp. 255-257. A. B.

_ Cohen '®1 advocates the use of potassic iodide and the iodide of bismuth and
potassium in acid solutions, He claims for this test greater accuracy than it
possesses, since alkalis are thrown down by it as well as albumin.

G. Roch and J. A. Macwilliam’” have employed salicyl-sulphonic acid as a
means of discriminating serum-albumin from albumoses and peptone. Salicyl-
sulphonic acid is readily soluble in water, and if a concentrated solution be
added to an acid urine which contains albumin, a turbidity or a precipitate
(according to the proportion of albumin present) will result. Should peptone or
albumoses be also present, this precipitate diminishes on boiling, and recurs
when the mixture cools. An acid reaction is necessary for the application of
this test, and should the urine be alkaline, it must be treated previously with
acetic acid, In the author’s experience, the test is very suitable for distinguish-
ing albumin from albumoses and peptone, as Macwilliam}® has pointed out. V.
Engel, however, contends that it is not in any way to be preferred to the method
given on p. 266.164

(Macwilliam applies the test in the following way :—About 20 drops of the
urine is placed in a very small test-tube, and one or two drops of a saturated
watery solution of the reagent is added, or a little more if the urine is strongly
alkaline. The tube is rapidly shaken and the fluid at once inspected. Opal-
escence or. turbidity recurring immediately, ¢.¢., in one or two seconds, is an
indication of greater delicacy than the cold nitric acid test. If turbidity appears

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TESTS FOR ALBUMIN. 259

after a longer time, as from one-half to two minutes, this implies the presence of
a very minute trace of albumin. The fluid is next boiled. The precipitate, if
due to serum-albumin and globulin, does not disappear, but becomes flocculent,
while a precipitate from the presence of albumoses and peptone clears up before
the boiling-point is reached. For salicyl-sulphonic acid as a test for deutero-
albumose and peptone, see p. 268.]

The first three tests described above (pp. 255, 257), when taken to-
gether, afford a means of discriminating between the different forms of
albumin which are apt to occur in the urine.

(1.) If in a given case the tests 1-3 should all give positive results,
it may be concluded that the proteid present is in the form of serum-
albumin, usually in conjunction with a small proportion of globulin ;
but the presence or absence of peptone or albumose in addition remains
undetermined.

(2.) If the urine contains but a small quantity of serum-albumin
alone, only the first two tests will give any result.

(3.) If the first test fails to disclose the presence of albumin, while
a precipitate is formed on the addition of acetic acid in the second, this
may consist of mucin or resinous acids. In the latter case, it is soluble
in alcohol.

(4.) If, on the application of test 1, no result is at first obtained, but
a precipitate forms on cooling the specimen, this precipitate may be
removed by filtration and tested by test 3 (biuret test), when the charac-
teristic reaction will point to the presence of albumose. In such a case,
the inference is strengthened if the pure or diluted urine responds to
test 2, and if test 3, when applied to the urine directly, produces an
abundant precipitate. Further investigation may then be conducted in
the manner indicated at p. 269.

(5.) Again, if tests 1 and 2 are unattended with any result, if acetic
acid alone will not cause a precipitate, and if test 3 at the same time
discloses the presence of albumin, it may be concluded with certainty
that the urine contains a large proportion of peptone. This condition
is doubtless very rare. The author has met with it several times—
repeatedly in the resolution stage of severe pneumonia, and further in
a case of acute rheumatism, when serious and extensive joint symptoms
were rapidly disappearing under the influence of preparations of sali-
cylic acid. For the more accurate determination of peptone, it will
usually be necessary to resort to the method described at p. 266.

By proceeding in the order indicated, it will be possible to form some
judgment as to the character of the proteids under investigation, and
this, as we shall see presently, is often a point of interest clinically.

(8.) Quantitative Estimation of Albumin.

1. By weight.—A certain quantity of the urine—6o-100 ec., accord-

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260 THE URINE.

ing as it is rich in albumin or otherwise—is placed in a beaker, and
heated on the water-bath. A two per cent. solution of acetic acid is
then added, drop by drop, until‘ the albumin has separated in flocculent
masses, when the fluid is boiled, and passed through an ash-free filter
of known weight. The precipitate on the filter is washed successively
with water, alcohol, and ether, and heated to a constant density at
120-130 C. The filter is again weighed, and the difference in weight
due to the precipitate is that of the albumin in the quantity of urine
taken. Devoto’s!® plan is still better. The albumin is precipitated
with ammonium sulphate, coagulated in the steam-bath, and the pre-
cipitate washed with boiling water until the filtrate no longer becomes
cloudy on standing, or with the addition of sodium chloride. The
precipitate is then washed with alcohol and ether, and the remainder
of the process is conducted as before. To ensure greater accuracy in
the result, it will be necessary to ascertain the amount of ash in the
filter, and to allow for it. This may be accomplished by burning the
filter with the albumin upon it in a platinum crucible of known
weight. For such determinations the use of glass-wool filters is to
be recommended.

2. The Methods of Roberts, Stolnthow, and Brandberg'® for the
approximate estimation of albumin are all based upon the principle of
Heller’s test, and are highly serviceable. The principle referred to
may be expressed by the fact, that the richer the urine is in albumin,
the more quickly turbidity is developed in the use of Heller’s test. If
in roo ce. of urine there is 0.0034 gramme (Roberts), or 0.004 gramme
(Stolnikow) of albumin, the fluid begins to cloud after the lapse of
35-40 seconds, and becomes plainly turbid in 1} minute.

Brandberg’s modification of Roberts’ and Stolnikow’s methods gives
the best and most accurate results. This observer has found that in a
solution of one part albumin in 30,000 of water, and consequently in
urine holding 0.0033 per cent. of albumin, Heller’s reaction will take
place in 24-3 minutes, and upon this fact he has based his method.
It is conducted thus:—The urine to be examined is first submitted
directly to Heller’s test. If a precipitate is obtained, a measured bulk
of the fluid is diluted in a graduated tube with nine times its quantity
of water (1 in ro urine), and Heller’s test is again applied to the mix-
ture in the following manner :—In a test-tube of about 1 cm. diameter,
some pure nitric acid is placed with a pipette, and in such a manner
as not to touch the sides of the tube. The latter is now inclined, and
the diluted (1 in ro) urine is carefully poured from a graduated burette
along its lower surface, so that it may float upon the acid without
blending. Two cc. may be placed in the test-tube in this way. Suppose
now that an obvious clouding of the fluid takes place before the lapse of

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BRANDBERG'S PROCESS. 261

three minutes, the diluted (1 in 10) urine contains more than 0.0033 per
cent., and the pure urine therefore more than 0.033 per cent. of albumin.
If, on the other hand, the albuminous cloudy ring takes longer than
three minutes to develop, it is known that the simple urine holds less
than 0.033 per cent. albumin in solution. In the first case the mixture
is further diluted by Brandberg in this manner :—Five test-tubes are
taken, and in each he places 2 cc. of the diluted urine. To the first he
then adds 4 cc. of water; to the second, 13 cc. ; to the third, 28 cc. ; to
the fourth, 43 cc.; and to the fifth, 58 cc. He then repeats the test
with each of these. If in the case of one of them the reaction occurs
in the space of 24-3 minutes, it follows that the fluid in the particular
test-tube contains 0.0033 per cent. albumin; and from this the propor-
tion of that substance in the undiluted urine may be directly calculated
by the following formula :—
as k-+ a
I.30
Where

p=percentage of albumin in the undiluted urine.
/;=the quantity of 1 in 10 diluted urine in each test-tuhe.
x=the quantity of water used for dilution.

Brandberg has compiled for the use of the practitioner a practical
table by which the percentage of albumin can be readily computed
from these data without the trouble of calculation. It is reproduced
here with slight modification.!° Its conclusions are based upon the
supposition that turbidity ensues three minutes after the application of
Heller’s test :—

I. 2 ce. 1/10 urine, 0.05 0.10 0.15 0.20 0.25 0.30 0.35 0.40 0.45 0.50 % albumin.
II. I 4 7 10 13 416 I9 22 25 28 cc. water.
I. 2 ce, 1/10 urine, 0.55 0.60 0.65 0.70 0.75 0.80 0.85 0.90 G.95 1.00 % albumin.
IL. 31 34 37 49 43 46 49 52 55 58 cc. water.
I. 2 ce, 1/10 urine, 1.05 1.10 1.15 1.20 1.25 1.30 1.35 1.40 1.45 1.50 % albumin.
II. 61 64 67 70 73 76 79 82 85 88 cc. water.

The figures in the horizontal line marked II. indicate the quantity
of water in cc. which must be added to the 2 cc. of the 1 in ro diluted
urine in order that turbidity may occur in three minutes. In line I. are
exhibited the corresponding percentages of albumin in the specimen of
urine taken.

In applying this method, it will be convenient to have a burette filled
with the 1 in ro diluted urine, and another containing distilled water.
In each of one series of test-tubes may then be placed an equal quantity
of nitric acid, with the precautions indicated above; and in those of

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262 THE URINE.

another 2 cc. of the r in ro diluted urine and varying quantities of
distilled water (see Table). A preliminary experiment is first made, and,
according as this experiment shows an excess above or deficiency from
the standard percentage of albumin, more or less diluted mixtures of
2 ce. 1/10 urine + water are prepared. These mixtures of urine and
water in the second series are now tested by placing them with a pipette
on the surface of the nitric acid in the test-tubes of the first series, until
that one is reached in which the albuminous ring takes precisely three
minutes to form, and from this the proportion of albumin in the urine
is caleulated. To take an example :—Suppose it is found in this way
that turbidity occurs after the lapse of three minutes from the addition
to the nitric acid of the fluid in a particular test-tube, and that this
fluid has been formed by the admixture of 13 cc. of water to the 2 cc.
of r in ro diluted urine: reference to the table will show that 0.25
corresponds to this number, 13, and consequently the urine contains 0.25
per cent. of albumin. If, however, the fluid in the test-tube to which
13 cc. of water has been added fails, when tested, to become turbid, or
does so only after a longer interval, a less highly diluted mixture must
be examined in a similar way—as, for instance, the contents of the tube
to which ro cc. water have been added, and so successively with the
others (7 and 4 cc. dilution), until the required result is obtained. If,
on the other hand, the mixture in the test-tube diluted with 13 ce.
exhibits turbidity directly, the test must be repeated with those towards
the other extremity of the scale—namely, those containing 16, 19, 22,
&e., cc. respectively—until, as before, one is found in which the pheno-
menon occurs after the lapse of precisely three minutes. Let this be
the fluid formed by the admixture of 25 cc. from the burette containing
distilled water ; then the table will be found to give 0.45 as the cor-
responding figure, and the urine under examination, therefore, contains
0.45 per cent. albumin.

This method, when carefully conducted, is altogether satisfactory.
Hammarsten 1° has compared its results with those obtained by the pro-
cess of weighing, and has found that the two correspond within 0.206
per cent.

3. Estimation of albumin by precipitation with picric acid and Esbach’s
albuminimeter.17

The advantage of this proceeding is its simplicity. It is open to
certain fallacies, contingent upon the unsatisfactory character of the
reagent used (see p. 258); but it calls for description here as affording
the physician a practical, if only approximate, means of determining the
proportion of albumin in the urine.

Ten grms. of pure picric acid and 20 grms. of pure citric acid are dis-
solved in goo cc, water. When the solution is thoroughly cool, water

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3SBACH'S ALBUMINIMETER. 263

is further added to 1000 ce., and the mixture is employed as a preci-
pitating agent. An instrument called the albuminimeter is further
needed. This is a vessel resembling a test-tube, of stout glass. At its
upper part it bears a mark, R, and lower down another
mark U. The lower third is graduated, and the divi-
sions, which are numbered from 3-7, are so disposed that
the intervals between successive units diminish from
below upwards (fig. 126). For the purpose of the ex-
periment, the albuminimeter is used in the following
manner :—It is filled with urine up to the mark U, and
the reagent is then added until the surface of the fluid
reaches to the mark R. The thumb is then applied to
the mouth of the instrument, and it is reversed several
times, until the fluids are well mixed. It is then covered
with an india-rubber stopper, and allowed to stand
upright for twenty-four hours. After this the height
of the sediment in the tube is read off by the scale upon
its surface. This is constructed so that the numbers
express the proportion of albumin in grammes to the
litre. Should it happen in a particular case that the
upper linut of the sediment overtops the number 7 at
the highest point of the scale, z.e., where the proportion
of albumin exceeds 7 per cent., the experiment must be
repeated with diluted urine. And it will save time if

 

% Fic. 126.
the urine be diluted at the outset, wherever it has been — sbach’s Albu-
minimeter 3.

shown by a qualitative test to be comparatively rich in
albumin. It occasionally happens that the albuminous precipitate will
not cohere, or it may remain floating in the fluid. In such cases the
method is inapplicable.

The quantity of albumin present can be estimated only approximately
by this method. The experiments of Czapek! have shown that its
merit is enhanced if certain precautions be observed in its use. The
urine to be tested should be fresh and acid, and of low specific gravity,
to which end it may be diluted. The fluid should not contain
more than four grms. albumin to the litre, and should be kept for
twenty-four hours in the albuminimeter at a moderate temperature
before the reading is taken. Finally, the figures on Esbach’s instrument
are too low. The best results are obtained where the urine is below
1.010 specific gravity, and does not hold more than o.2 per cent.
albumin. The conclusions set forth here are confirmed by Soko-
low and Th. Geisler”? Christensen’s° albuminimeter is applied on
the same principle, tannic acid being used to throw down albumin.
With the instrument the process may be performed more rapidly, but

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264 THE URINE.

the results are less accurate than with Esbach’s (Geisler,* Wavor,
Federer’).

This method is appropriate to the case of transitory or febrile albu-
minuria, and it is inapplicable where the urine may be supposed to
contain quinine, antipyrin, or thallin.

From comparisons made by Zehter, it appears that Eshach’s method
is far less accurate than Brandberg’s. It is open to very considerable
objections, and can be relied upon only within broad limits.

Noel Paton “> employs the albuminimeter to determine the proportion
of albumin in a urine. From another portion of the same urine he
precipitates globulins with magnesium sulphate, as Hammarsten does,
and again tests the “ globulin-free” urine with Esbach’s albuminimeter.
From the difference in the two results he infers the quantity of
globulins present. This plan is commended by its author, but the
process obviously partakes of the uncertainty which is inseparable from
the use of the albuminimeter.

It may be noticed that Huppert and Zdhor® have endeavoured to found a
quantitative method of estimating albumin upon the comparative specific gravity
of the urine. Its efficiency has not yet been sufficiently tested, but it may prove
to be of service clinically.

2. Peptonuria.—This condition has been invested with very great
interest since the discovery by Hofmeister! of a comparatively simple
chemical test for the detection of peptone.

So far as our present knowledge extends, the causes of peptonuria
are quite different from those to which the other forms of albuminuria
are due. Neither nephritis, circulatory disturbances, nor anemia, will
bring about the appearance of peptone in the urine. Its presence there
associated with such pro-

 

is most commonly—though not invariably
cesses as are characterised by the collection and subsequent destruction of
leucocytes under such circumstances that the products of disintegration,
including the peptone constituent, of these bodies can obtain admission
into the blood-stream, to be subsequently eliminated by the kidneys.

_ To the condition arising in this way the name Pyogenie peptonuria
has been given (Hofmeister, Maixner, v. Jaksch).7 Tt occurs chiefly
in the resolution stage of pneumonia, in purulent pleuritic exudation,
and, in general, in suppuration wherever situated, provided that the
conditions are favourable to the absorption of the constituents (peptone)
of the pus.

Peptone has further been found abundantly in the urine in purulent
meningitis, acute articular rheumatism, the suppuration of phthisis—-
briefly, in nearly all those states which are attended with the formation
and breaking down of pus.

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PEPTONURIA. 265

It follows, therefore, that the detection of peptone in the urine goes
far to warrant the inference that suppurative changes are in progress
in some part of the system, but such an inference must, in all cases, be
strengthened by the exclusion of the other known causes of peptonuria.

Amongst these are severe cases of scurvy, tending towards a fatal
termination (heematogenic peptonuria) (v. Jahisch).

Maixzner ®° has also shown that in ulceration of the intestine, peptone
derived from the food may pass directly into the blood through the
ulcerated parts, and so give rise to this condition (enterogenie peptonuria),
an observation confirmed indirectly by those of Pacanowshi.\8! A
number of cases have also been reported in which peptone found in the
urine was attributed to phosphorus poisoning ; and Jischel 18? has shown
that it is normally a constituent of the urine in the puerperal state
(puerperal peptonuria).

These facts are mentioned chiefly to show that peptonuria does not
always imply suppuration; but these other conditions being excluded,
it is a valuable diagnostic sign of that process. It is, moreover, avail-
able as a means of prognosis and of testing the progress of certain
diseases attended with the resolution of pus. Thus, when peptone is
found in the urine in the course of pneumonia, it indicates that the
stage of softening has begun. Again, in connection with abdominal
tumours or pleuritic \effusion, it shows their purulent character; and
in purulent meningitis its manifestation varies with the severity of the
disease—peptonuria occurring together with a relapse, and so on.

As a means of discriminating between tubercular and epidemic cere-
bro-spinal meningitis, the presence of peptone in the urine is occasion-
ally a fact of crucial significance. It is characteristic of the latter disease,
and its absence in presence of the clinical symptoms of meningitis in all
cases implies a tubercular character. Obviously, however, peptonuria
may arise accidentally in the course of tubercular meningitis ; and in
basing a diagnosis upon this condition, care must be taken to ascertain
that it is not due to ulcerative processes in other organs, and especially
to exclude implication of the lungs.

Again, in the condition which has been called “sepsis occulta,” and
which is commonly so difficult to recognise, peptonuria is an important
symptom. By its aid especially it will be possible to distinguish the
symptoms of septicemia from those of latent disseminated sarcoma,
which present quite a similar clinical character (high fever, rigors).

In acase which came under Prof. Nothnagel’s care, there had been rigors and
a high temperature maintained for a long period, and no other symptoms what-
ever. These were ascribed to the formation of a deep-seated abscess. ‘he urine
was repeatedly examined for peptone without result. The post-mortem showed
disseminated sarcomatous nodules.

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266 THE URINE.

The author has been engaged for many years in investigating the
subject of peptonuria, and he feels warranted in asserting that its
clinical value as a symptom is very great. It may be that further ex-
perience will extend and distribute its import; but there can be little
doubt that the significance attaching at present to the form with which
we are best acquainted—that of pyogenic peptonuria—will not diminish
with the progress of knowledge. Recent investigations tend in the
fullest manner to confirm this view.!%* Peptonuria is frequently met
with in connection with syphilis (PvenZ).15* Modern science furnishes
an adequate explanation in many instances where the condition is found ;
for, granting that micro-organisms have the property of changing albumin
into peptone, it is probable that they can also cause the latter to appear
in the urine (Mya, Belfanti).1*

Detection of Peptone.—The methods of Hofmeister and Devoto 186 will
be described here.

1. Hofmeister’s Method.—The urine should first be tested for albumin
by the three processes described above (pp. 255, 257). If tests 1 and 2
give no result, and no precipitate forms on the addition of acetic acid

 

alone, the presence of peptone may be shown by the biuret test (see p.
257), but. only when this body is in great abundance. If it is not so,
the result in this case will be also negative. A further preliminary test
may be applied by adding first concentrated acetic acid, and then a
muxture of acetic and phospho-tungstic acids. If clouding takes place
either directly or after the lapse of a short interval, it may be concluded
that peptone is present. The inference is rendered still more certain if,
before the application of the test, a little neutral acetate of lead be added
(to precipitate mucin), until a flocculent precipitate appears. If the
test again gives positive results, peptone is present ; if it remains nega-
tive, the urine is peptone-free. This, however, only holds good where
the urine contains a considerable amount of peptone.

Hofmeister’s test is more accurate. Assuming that the previous
methods have failed to disclose albumin, the urine is treated with
neutral acetate of lead and filtered. The clear filtrate, which should
amount to not less than 500 to 600 cc. in volume, is acidulated with
hydrochloric acid, and phospho-tungstic acid is added until a precipitate
ceases to form with it. The fluid is then filtered without delay.

Phospho-tungstic acid may be prepared thus :—Commercial tungstate of soda
is dissolved in boiling water and phosphoric acid added until the mixture exhibits
an acid reaction. _ It is then allowed to cool, rendered strongly acid with hydro-
chloric acid, and filtered after standing for twenty-four hours (Huppert).187

The precipitate consists of peptone combined with phospho-tungstic
acid, and various other substances (ptomaines, &c.). It is now washed

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DETECTION OF PEPTONE. 267

on the filter with five parts concentrated sulphuric acid in 100 of water,
until the fluid which passes through is colourless. In this way the salts
are got rid of. The precipitate, while still wet, is washed from the
filter with as little water as possible, and is received in a watch-glass.
Barium carbonate is added until the mixture is alkaline, and the latter
is then placed on a water-bath at boiling-point, and heated for ten to
fifteen minutes, and the biuret test (p. 257) applied. Peptone is shown
by the formation of a colour ranging from bluish-red to violet, and
varying in intensity according to the quantity present. If this be only
a trace, the resulting colour is of a dirty red or dull violet. The accom-
panying precipitate of baryta need not confuse the experiment; but
should any doubt exist as to its result, the entire preparation may be
placed in a test-tube and allowed to stand for a few minutes. The
precipitate then falls to the bottom, and the fluid displays the charac-
teristic tints—from dull red to violet—if it contains peptone. If that
body be absent, it has a greenish colour.

If either of the first two tests (p. 255) should show the presence of
albumin, whilst the addition of acetic acid and ferrocyanide of potas-
sium after filtration causes only very slight turbidity, the albumin must
be removed by combination with a metallic oxide—and best with
oxide of iron—in the following manner :—A solution, first of acetate of
soda and then of perchloride of iron, is added to the urine. This is
exactly neutralised with caustic potash, boiled, filtered, and allowed to
cool. Tests 1 and 2 are next applied. If neither discloses albumin, and
if also with test 2 no blue colour forms, thus showing that the fluid
is free from iron, the further process is that described above—hydro-
chloric acid is added, and a precipitate obtained by the use of phospho-
tungstic acid, and so on, as before.

If, however, after the precipitation of albumin in the manner indi-
cated, one of the tests alluded to should show that the fluid is not yet
free from that body, the previous tests must be repeated until the
filtrate exhibits no trace either of albumin or of iron. Should the former
substance be present in the urine in great quantity, it may be removed
in large proportion by heat, and what remains may be subsequently got
rid of in the manner described above.

The application of this method in the case of highly coloured albu-
min-free urine has the contingent advantage that it involves the
removal of colouring matters whose presence might be a source of
fallacy. J. A. Schulter 188 recommends that the urine be first saturated
with ammonium sulphate, and the filtrate proceeded with as before.
The quantitative estimation of peptone may be effected by the colori-
metric process of Hofmeister and Maixner.1®°

2. Devoto’s Method.—The difficulties attending the application of

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268 THE URINE.

Hofmeister’s method are a serious impediment to its use. That of
Devoto, which will now be described, is at once simple, expeditious,
and efficient.

The two tests have given identical results when the author has employed
them for the investigation of urine. When, however, they were applied to the
examination of the blood and the viscera, there was less conformity between
them, Hofmeister’s usually indicating peptone where Devoto’s failed to do so.’?!

To 2c0-300 cc. of urine is added pure crystalline ammonium sulphate
in the proportion of 80 grms. to 100 ce., and the fluid is placed in a
beaker in a boiling water-bath for half-an-hour, at the end of which the
greater part of the salt should have dissolved. It is then steamed for
half-an-hour in a Budenberg’s steam-steriliser, the vapour being kept at
100° ©. In this way all the proteids (serum-albumin, globulin, hemo-
globin, deutero-albumose, peptone, nucleo-albumin) are precipitated, but
only serum-albumin, globulin, and nucleo-albumin (mucin) are thoroughly
(and hemoglobin partly) coagulated. The fluid having been heated to
100° C. is at once filtered. The filtrate should be straw-coloured, and
free from albumin, as indicated by tests 1 and 2, p. 255. A slight
cloudiness appearing quickly with test 2 does not necessarily imply the
presence of albumin. A decided turbidity or a precipitate would be due
to a proto-albumose, or more probably hetero-albumose. Should the hot
filtrate be cloudy, or give the proteid reactions (pp. 255, 257), the investi-
gation has miscarried, and must be repeated from the beginning. The
residue on the filter is washed first with hot and then with cold water.
The resulting filtrates have a more or less decided brownish tint. These
are collected, and to one portion of the fluid acetic acid and ferrocyanide
of potassium are added to test for albumin. Should no result be
obtained, the biuret test is performed with a portion to which caustic
soda has been added in excess. Any albumin shown to be present is
certainly peptone. The filtrate from the hot washings may exhibit it,
but it often happens that peptone first becomes recognisable with the
biuret test in the filtrate derived from the cold washings. Several
specimens both of the hot and cold washings may be tested until a
positive result is obtained.

[<. Martin! has found that in many cases of supposed peptonuria—especially
of peptonuria in connection with purulent disease—the morbid constituent of
the urine was deutero-albumose and not peptone. The two are distinguished
by their behaviour in solutions with ammonium sulphate; deutero-albumose is
precipitated by saturation with this salt, while peptone is not.

Macwilliam + recommends salicyl-sulphonic acid as a test for albumoses and
peptone. Primary albwmoses are precipitated by a saturated watery solution of
the acid; the precipitate disappears with heat, and reappears when the liquid

cools. Deutero-albumose is precipitated by the reagent when the fluid examined
is mixed with two to three times its bulk of a saturated solution of ammonium

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ALBUMOSURIA. 269

sulphate. Peptone is readily precipitated by salicyl-sulphonic acid in saturated
ammonium-sulphate solutions, and the precipitate clears up on heating, and
reappears when the liquid cools. The peptone precipitate is dissolved by the
addition of water, glycerine, or excess of the reagent. ]

3. Albumosuria.—The distinctive character of this condition was
formerly thought to be the presence in the urine of a single body, to
which the name of propeptone or hemialbumose had been given. The
researches of modern times, however (Kiihne, Chittenden, Herth1*),
have placed the matter in a new light, and the first two observers have
sought to show that propeptone is really a mixture of four different
proteids. However this may be, these interesting observations cannot
as yet be brought to bear upon our clinical knowledge.

Albumose has been found in the urine in connection with various
diseases—as osteomalacia, dermatitis, intestinal ulcer, &c. (Senator, Ter
Gregoriantz, v. Jaksch).! In severe cases of osteomalacia, which were
recently under treatment by Professor Nothnagel, v. Helly, and Schauta,
the author failed to discover albumosuria ; neither has he detected it in
advanced rickets.

Loeb’ believes that he has discovered propeptone in the urine in
measles and scarlatina (in this he is confirmed by Heller 1%"), and from
the observations of Kahler and Huppert® albumosuria would seem
to be a frequent occurrence in inflammation of the medulla of bones.
Koppner™® has observed albumosuria in mental derangement. The
clinical significance of this state is modified by the fact that Posner
has detected propeptone in the seminal fluid (see Chapter IX.). The
presence of albumose, when it occurs alone, may be determined by the
consideration of results derived from the tests given for the detection
of albumin generally. If, on the application of tests, a precipitate first
forms on cooling the specimen, or when it has been allowed to stand for
a long time (vide supra), and if this precipitate, when separated on the
filter, is shown by the biuret test to consist of albumin, a fresh specimen
of the urine may be submitted to test 2. In doing this, it may be
necessary to add water, since albumose is readily soluble in concentrated
salt solutions, and therefore in concentrated urine. Whether with or
without this precaution, a further precipitate with test 2 suggests the
presence of albumose. Another specimen should now be saturated with
common salt, and further treated with acetic acid. If albumose be
present, a precipitate forms, which, after the addition of a large amount
of acetic acid, dissolves when heated and reappears on cooling. A
nitrogenous body resembling albumose was found by Thormdhlen*° in
the urine in a case of hydatids of the liver, with jaundice and
nephritis.

When the urine holds albumose in conjunction with serum-albumin,

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270 THE URINE.

the latter must be removed by boiling with acetic acid and chloride of
sodium before the tests are applied.?0?

4. Globulinuria.—Globulin probably never, or almost never, occurs
alone in the urine, but generally in conjunction with serum-albumin.
Consequently its import in disease is the same as that of the latter body.
{Serum-albumin is usually present in greater quantity, but in severe
organic renal disease and in diabetes Maguire 2” finds that the proportion
of globulin to albumin is often 2.5: 1. Senator? asserts that more
globulin is present in lardaceous kidney than in other forms of Bright’s
disease. ]

To Kauder?% belongs the credit of discovering a simple method for
the detection of this body in presence of serum-albumin. The urine is
rendered alkaline with ammonia, allowed to stand for an hour, then
filtered, and to the filtrate is added its own volume of a saturated solu-
tion of sulphate of ammonium. If globulin be present in any quantity,
a flocculent precipitate falls.

By an extension of this method the quantitative estimation of globulin
may be effected. With this object the precipitate formed is treated in
the manner described before when speaking of the estimation of albumin
by weight (p. 259), (Pohd).?°

[Halliburton ?°" adopts the following method :—The urine is neutral-
ised and then saturated with magnesium-sulphate. If globulin be pre-
sent, a precipitate forms. This precipitate may be collected on a filter
and dissolved by the addition of water. The solution coagulates at
75°C. When the urine holds a large quantity of globulin, Si William
Roberts’ test will serve for its recognition :—A deep glass vessel is filled
with water and the urine is added, a drop at a time. Each drop leaves
a milky track behind it, and when much urine has been added, the fluid
becomes opalescent, and clears again on the addition of acetic acid. ]

5. Fibrinuria.—Fibrin is found in the urine in cases of hematuria
and chyluria (v. infra). It then usually forms coagula. It is found,
moreover, as a consequence of inflammatory exudation in the urinary
passages. The coagula occur most commonly in croup and diphtheria,
and occasionally in tuberculosis.

To detect fibrin the clots should be separated by filtration, washed
with water, dissolved by boiling in solution (1 per cent.) of soda or
(5 per cent.) hydrochloric acid (Huppert °S), and the fluid tested when
cold by the process described on p. 256.

6. Hematuria.—The blood which occurs in the urine may be derived
from several sources, from the kidney, renal pelvis, ureters, bladder, or
urethra (see p. 218).

In well-marked cases, the presence of blood is directly suggested by
the colour of the urine, which varies from that of an extract of raw

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HAMATURIA—H AMOGLOBINURIA. 271

meat to a ruby-red ; but inasmuch as a similar appearance may be due
to hemoglobin in solution (hemoglobinuria), it is never safe to base
the diagnosis of this condition upon inspection alone. It may be
accurately determined by—

1. Spectroscopic Examination.—The freshly-passed urine, which, if
deeply coloured, should be diluted with water, will exhibit the two
absorption-bands of oxyhemoglobin (p. 60, fig. 37), and these, on the
addition of sulphide of ammonium, give place to the absorption-band
of reduced hemoglobin. Lastly, when blood containing urine has stood
for some time, occasionally even in fresh urine, the spectrum of methe-
moglobin may be looked for (p. 62, fig. 42).

2. Heller's Test.2°°—The urine is treated with caustic potash and
boiled. The (basic) earthy phosphates are then precipitated, and to-
gether with them the hematin derived from the oxyhemoglobin present.
The phosphatic sediment is consequently coloured a bright red. Should
it happen that the urine contains abundance of colouring matter (bile-
pigment, &c.), which renders it difficult to appreciate the colour of the
sediment, the latter should be separated on a filter and dissolved in
acetic acid. The solution then becomes red if blood be present, and its
colour vanishes gradually on exposure to the air.?!°

Rosenthal” applies the test for hemin directly to the dried preci-
pitate (see p. 61). Struve’s 2!" method serves well for the detection of
blood-pigment. The urine is treated with ammonia or caustic potash,
and the fluid then rendered acid with tannic and acetic acids. The
presence of blood is shown by a dark-coloured precipitate, which, when
dried and treated with a little chloride of ammonium and glacial acetic
acid, should yield Teichmann’s crystals. This test is very sensitive, but
less practicable than Heller’s, which, with the spectroscopic examination,
best meets the requirements of the physician.

3. Almén’s Blood Test.?\°—A mixture in equal parts of tincture of
guaiacum and mature oil of turpentine is poured on the surface of about
ro cc. of the urine. The presence of blood is shown by the appearance
at the junction of the fluids of a ring at first white and afterwards
turning blue.

If, in addition, the microscope reveals the presence of red blood-
corpuscles (p. 218), the existence of hematuria may be inferred, and
it only remains to judge of its origin on the principles already laid.
down. For its clinical significance the reader may refer to p. 219.

7. Hemoglobinuria.—Sometimes the colouring-matter of the blood
is also found dissolved in the urine (see p. 65). This condition is
apt to arise in the course of acute infectious diseases, in burns, and in
various forms of poisoning. In the latter class of cases it is always
a serious, and even ominous symptom. It has been observed in poison-

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272 THE URINE.

ing by naphthol? and carbolic acid,?!® and in erysipelas.?4° Hemo-
globinuria is known as an idiopathic affection?!" (paroxysmal hemo-
globinuria), and as such often occurs in connection with severe syphilis,
[and also in malaria and rheumatism, when the attacks appear to be
determined by exposure to cold (Zaylor)].?8

The occurrence of hemoglobinuria may be inferred when it is made
evident by spectroscopic analysis and the application of Heller’s and
Almén’s tests that the urine contains blood colouring-matter, whilst at
the same time the microscope discloses smaller or larger masses of brown
pigment, and either no red corpuscles, or so few as are inadequate to
account for the results obtained. The spectroscopic appearances are
usually those of methemoglobin (p. 62, fig. 42); and Hoppe-Seyler 1
maintains that in this condition the blood-pigment is always in the form
of methemoglobin.”° [In seven cases of paroxysmal hemoglobinuria
investigated by Halliburton,??! methemoglobin was the only pigment
present in three. In the remaining four there was found only methemo-
globin at first, but in a few hours the amount of pigment increased, and
oxyhemoglobin appeared as well. In such a specimen the spectra of
methemoglobin and of oxyhemoglobin occur together. In three of
Halliburton’s cases serum-albumin was present in the beginning of the
attack, and in one its appearance preceded that of the blood-pigment.
Albuminuria has been observed to alternate with hemoglobinuria, and
Fragge has described a paroxysmal albuminuria which he believed to be
a mild form of the latter (see p. 252)].

8. Mucinuria (Nucleo-Albuminuria).—The presence of small quan-
tities of nucleo-albumin (mucin) 7? in the urine is not a pathological
symptom ; when found in greatly increased proportion in women, it is
often derived from the vagina. Such an increase, originating in the
urinary passages, invariably points to catarrh of those parts. The urine
in question is usually turbid when passed, and after a little while it
deposits a bulky cloud. The latter is seen by the microscope to contain
leucocytes and epithelium (p. 218). When a great quantity of mucin
is passed, it forms a viscid gelatinous sediment at the bottom of the
urine-elass, and no further evidence of its character is needed.

For the detection of mucin chemically, the urine is treated with an
excess of acetic acid, when it is rendered turbid if much mucin is
present. It may be necessary to dilute it previously, since concentrated
urine, being rich in salts, will retain mucin in solution even in presence
of acetic acid. In testing for the presence of mucin in albuminous
urine, the great bulk of the albumin should be removed by boiling and
filtering previously, and the filtrate allowed to cool.

The best method for precipitating mucin from urine is by the addition
of acetate of lead (vide supra).

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CARBOHYDRATES—GLYCOSURIA. 273

Fr, Miiller ??5 found mucin very abundantly present in the urine of
leukemia. Obermayer 224 maintains that it is invariably to be met with
in jaundice.

II. Carbohydrates.

1. Glycosuria.—Although various forms of sugar are occasional con-
stituents of the urine, as, ¢.g., sugar of milk after parturition, and inosite
and levulose rarely, the consideration of these will nevertheless hardly
detain us, since their manifestation, from the point of view of frequency
and importance, possesses but little practical interest in comparison with
that of the hexose 2” orape-sugar (glucose, glycose, dextrose). Our re-
marks here will be confined to the occurrence and tests for the latter
body.

(a.) Physiological Glycosuria.—It must be mentioned at the outset
that normal urine contains a trace of sugar. The fact of a physio-
logical glycosuria was long ago laid down by v. Briicke,?”" and has
quite recently derived remarkable confirmation.22° Wedenskv has made
use of Baumann’s discovery that benzoyl chloride forms insoluble
compounds with the carbohydrates ; and applying this to healthy urine,
he succeeded in separating from the precipitate a body which gave all
the reactions of grape-sugar. The proportion to be found in health,
however, is so small, that it may be neglected as a disturbing factor,
even in the most sensitive of the tests to be described. [According to
Dr. G. Johnson 7 normal urine is quite free from sugar; and Mr. G. 8.
Johnson ?8 has shown that when all the uric acid and kreatinin have
been removed from such urine by precipitation with mercuric chloride,
all reducing action disappears and no trace of sugar can be found. ]

(b.) Pathological Glycosuria.

(a.) Transitory Glycosuria.—Grape-sugar may appear temporarily in
the urine in the course of many diseases, as cholera, intermittent fever,?29
[typhus and typhoid], cerebro-spinal meningitis, and scarlatina,™° [after
attacks of whooping-cough, asthma, and epilepsy (Taylor) 2°], in affec-
tions of the brain involving the fourth ventricle, in diseases of the heart,
liver, and lungs, in gout, and in tertiary syphilis (Ord).?°! It has also
been occasionally observed in small quantities in cirrhosis of the liver.
Glycosuria in connection with these diseases is, however, very rare. It

 

 

is commoner as an effect of certain poisons, notably morphia and carbon
monoxide [after the inhalation of chloroform, ether, and amy] nitrite, and
in poisoning with prussic acid, mercury, and curare. In some of these
cases, however (morphia, curare, chloroform, &c.), it has been shown
that the substance which reduces Fehling’s solution in the urine is not
sugar, but glycuronic acid (Halliburton) ?**], The author has found
grape-sugar in the urine in two cases of advanced asphyxia from breath-
ing irrespirable gases (a mixture of carbonic acid and nitrogen).?°*

Ss

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BPA THE URINE.

In certain diseases the function of sugar-assimilation is depressed
(Hofmeister), and when that substance is taken as food, it appears tem-
porarily in the urine. This happens especially in hepatic cirrhosis
(Moritz, Kraus, Ludwig 4), and in brain disease (v. Jaksch).

(8.) Persistent Glycosuria.—The continued excretion of grape-sugar in
appreciable quantities belongs exclusively to diabetes mellitus, and it is
the most certain symptom of that disease. Its great clinical importance
lies in the fact that it ordinarily becomes apparent at a time when all
other symptoms of diabetes are wanting. In such cases, however, one
can be certain that diabetes exists only when, by repeated investigation,
grape-sugar is found, and especially when its quantity is observed to
increase with the administration of other carbohydrates, as cane-sugar,?”
and still better, starch.

Determination of Grape-Sugar.

(«.) Qualitative Tests.—It is very easy to determine the presence
of a considerable proportion of sugar in the urine ; but sometimes, when
that body occurs only in traces or in very small quantity, the tests
hitherto most commonly employed, namely, those of Moore and Trommer,
are hardly sufficient for its detection. We have only recently become
acquainted with a method which is in all cases adequate to the purpose.

1. Moore-Heller Test.?°>—The urine is treated with liquor potasse
and boiled. If sugar be present, it is decomposed. Lactic acid and a
number of volatile compounds are formed,27 and with them certain
coloured substances, which impart an intense deep-brown tint to the
fluid. This test is by no means accurate, and conclusions drawn from
it are open to fallacy, since healthy urine turns brown with caustic
potash from the action of that body upon mucin (nucleo-albumin).
Moreover, the change of colour is proportional to the quantity of mucin
present, independently of sugar.

2. Trommer’s Test.°8—The urine is rendered alkaline with caustic
potash, and a fairly strong solution of cupric sulphate is added, drop
by drop, until the cupric oxide formed ceases to be dissolved. The
mixture is then heated in a test-tube. If sugar be present in greater
quantity than a mere trace, a yellowish or red precipitate of the sub-
oxide of copper falls before the boiling-point is reached, and at the
same time the fluid loses colour somewhat.?8® This test is very sensitive.
Trommer was able with it to detect sugar to the amount of 0.001, or
even o.ooor per cent. Unfortunately it is also ambiguous. The pyro-
perty of reducing cupric oxide in alkaline solutions belongs to a number
of bodies which occur in healthy and morbid urine. Amiongst these are
uric acid, kreatin and kreatinin, allantoin, mucin, milk-sugar, pyroca-

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GLYCOSURIA—TESTS FOR SUGAR. 275

techin, hydrochinon, and bile-pigments. In addition to these, the
ingestion of benzoic and salicylic acids, glycerine, and chloral leads to
the formation in the system of substances which possess a similar
reducing power. Hence it happens that the urine is sometimes thought
to contain sugar on the evidence of Trommer’s test when none can be
found with other methods. The error is especially apt to arise when
the boiling is continued for a long time. The test can be depended on,
therefore, only when reduction takes place at a temperature belov boiling,
which, however, occurs only when the urine contains a relatively large
proportion of sugar.

Lehling’s fluid (p. 281) may be substituted for the copper sulphate
and caustic potash in the process. [ Pavy’s 4° fluid, which is much used
in England, is a modification of Fehling’s. It has the following consti-
tution :—(i.) neutral potassic tartrate 640 grs., potassa fusa 1280 grs.,
water ro 0z.; (ii) cupric sulphate 320 grs., water 10 oz. The two
solutions are kept apart and mixed for use. Of the mixture 40 to 60
minims are boiled in a test-tube, and a drop or two of the suspected
urine is added. If heat be continued, the yellow precipitate shows
itself in the upper part of the test-tube, and by adding more urine the
fluid will be made to lose its blue colour entirely. |

A useful modification of Trommer’s test has been suggested by Worm-
Miller. A mixture is made of 1.5 cc. of a 2.5 per cent. solution of
cupric sulphate, and 2.5 ec. of an alkaline solution of tartrated soda
and potash (prepared by dissolving 100 grms. of Rochelle salts in a
normal solution of caustic soda), and heated to boiling-point ; and in a
separate test-tube 5 cc. of the urine to be tested are boiled. The boil-
ing fluids are added together without shaking them, and if sugar be
present in any quantity, the suboxide is precipitated directly. Should
no such precipitate form, the process is repeated with 2, 3, or 4 ce. of
the cupric sulphate solution. This test is said to be very sensitive.

It should be mentioned that the power of a urine to dissolve cupric
oxide does not necessarily imply the presence of sugar in the urine, since
the property belongs to ammoniacal and albuminous urine, whether it
contains sugar or not.

3. Fermentation Test.—This depends upon the fact that grape-sugar
decomposes in presence of yeast into alcohol, carbonic acid, and a number
of other products (succinic acid, glycerine). It is conducted in the
following manner :—A test-tube is filled for two-thirds of its depth
with mercury, and in the remaining third with the urine, to which a
little tartaric acid has been added. In this is placed some yeast which
has been carefully washed. The mouth of the test-tube is then closed
with the thumb, and it is inverted over a vessel containing mercury.
If sugar be present, fermentation takes place directly, and the carbonic

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276 _ THE URINE.

acid formed collects over the mercury. When yeast is placed in normal
urine a limited fermentation takes place and some gas is disengaged.
It is, therefore, well to compare the result of fermentation in saccharine
urine with a healthy specimen (Moritz?#). There are special fermenta-
tion tubes made for such purposes, and the experiment is greatly facili-
tated by their use.22 This test is sufficiently sensitive. It will serve
to indicate o.1 per cent. of sugar in the urine.”4+ [According to Halli-
burton,2% the fermentation-test is the best for distinguishing sugar from
other substances that reduce Fehling’s solution in the urine. These
substances are uric acid, hippuric acid, kreatinin, pyrocatechin, and
glycuronic acid. ]

4. Phenyl-Hydrazin Test.—In this we have a method for the detec-
tion of sugar which is greatly to be preferred to those already mentioned.

 

Fic. 127.—Phenyl-Glucosazon Crystals, from Diabetic,Urine (eye-piece II., objective 8a, Reichert).

Several years’ experience has convinced the author that it is entirely
accurate, simple in its application, and in every way suited to the needs
of the physician. It depends upon the property of phenyl-hydrazin to
form with grape-sugar a highly-characteristic crystalline compound,™®
called phenyl-glucosazon. This body has the form of yellow needles,
and is but little soluble in water. The test is conducted in the follow-
ing manner (v. Jaksch **"):—Two parts of hydrochlorate of phenyl-
hydrazin * and three of acetate of soda are placed together in a test-
tube containing 6-8 cc. of urine. If the salts do not dissolve when the
fluid is warmed, a little water is added, and the test-tube containing the
mixture is placed for 20-30 minutes in boiling water. After this it is
taken out and put into a vessel containing cold water. If sugar -be

* Twice as much of the phenyi-hydrazin salt as will lie on the point of the blade
of a knife.

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PHENYL-HYDRAZIN—BOTTGER'S TEST. 277

present, even in very moderate quantity, there forms directly a yellow
crystalline deposit, which may appear amorphous to the naked eye, but
which when examined under the microscope is seen to contain yellow
needles detached or arranged in clusters (fig. 127). If the urine holds
but a very small proportion of sugar, the preparation should be placed
in a conical glass, and the sediment examined carefully. In a case
where only a mere trace of sugar exists, detached crystals of phenyl-
glucosazon cannot fail to be seen. The discovery of smaller and larger
yellow scales, or of powerfully refracting brown granules, must not, how-
ever, be mistaken for evidence of sugar. This test gives very good
results with every variety of morbid urine,”4§ and it is equally applicable
whether albumin be present or not. In the former case, however, it is
well to get rid of the excess of albumin previously by boiling. Phenyl-
glucosazon crystals melt at 205°, and their character may be ascertained
beyond doubt by submitting them to that temperature. The efficiency
and utility of this test is amply proved.249 The objections to its use
made by Geyer, Moritz, and Luther*™® seem to be without weight.
Doubtless the test requires much practice, but in expert hands highly
satisfactory results are obtained.”°!

In addition to the foregoing methods, which especially merit atten-
tion, other tests for sugar have been suggested, and some of these call
for description.

5. Bottger’s Test.%’—A quantity of the urine is mixed with its own
bulk of a concentrated solution of carbonate of soda, and a little basic
nitrate of bismuth is added. The preparation is then boiled. If sugar
be present, it turns black from the reduction of oxide of bismuth.
This process has no advantage which does not belong to Trommer’s
test, and it is less sensitive. If the urine contains the principles of
rhubarb taken as food, a black precipitate will fall independently
of sugar.*? In albuminous urine, too, sulphide of bismuth will
form a similar black deposit.%+ These conditions must therefore be
excluded.

The modification of Bdttger’s test by Nylander ?? is more accurate.
The reagent employed (called Almén’s fluid) is prepared by dissolving
4 grms. of Rochelle salts (tartrated soda and potash) in roo grms.
and of an 8 per cent. solution of caustic soda, warming the fluid,
adding as much basic pernitrate of bismuth as will remain in solu-
tion. The mixture so formed is added to the urine to be tested in
the proportion of 1 in 11, and the whole is then heated. The fluid
should blacken in the course of a few minutes. In this way it is
asserted “6 that sugar in the proportion of o.1 per cent. can be
detected. It has, moreover, the advantage of simplicity, but is also
open to certain fallacies. It is inapplicable, as we have seen, to the

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278 THE URINE.

case of albuminous urine, and the reaction occurs in presence of
melanin or melanogen, or where the fluid contains a large proportion
of reducing substances but no sugar.

6. Rubner’s Test.25'—The urine is treated with an excess of acetate of
lead (sugar of lead), filtered, and to the filtrate ammonia is added until
a permanent precipitate forms. The fluid is then heated, but not boiled.
If sugar be present, the precipitate formed on the addition of ammonia
gradually assumes a rose-red colour, which vanishes slowly on standing,
more quickly on the application of heat (60°-70° C.), giving place to a
yellowish-coffee colour.

Rubner believes that the precipitate consists of sugar of lead. Milk-
sugar does not give this reaction when the process is conducted as above,
but when a solution of that body is boiled for 3-4 minutes with acetate
of lead, and ammonia then added, a similar precipitate forms. In the
author’s experience, the best plan in performing the test is to heat the
precipitate gradually at a temperature not exceeding 80° C. By its use
Penzoldt has discovered sugar to the amount of o.o1—o.02 grm. in Io cc.
of urine. That writer employs a very simple and practical modification
of Rubner’s test.2°> He adds to the urine a few drops of basic acetate
of lead (subacetate) and a few of ammonia, and then warms the mixture.
The presence of sugar causes a red precipitate as before. This method
is not less sensitive than the other.

7. Mulder’s Test.—'the urine is treated with carbonate of soda in solution, and
solution of indigo-carmine is added until the whole is freely coloured. If sugar
be present, the colour changes to yellow on heating, and becomes again blue
when the fluid is shaken up with air.

This test may be conveniently applied thus :7°—Two pieces of filter-paper are
taken. One is placed in a concentrated solution of carbonate of soda, and the
other in a solution of indigo-carmine. Both are then dried. When wanted for
use, a small piece of the indigo-carmine paper is placed in about 10 cc. of water,
the urine under examination is added, and finally a large slip of the paper satu-
rated with carbonate of soda is placed in the fluid. ‘The result should be as
above. ‘The convenience of its application in this manner is the only merit of
Mulder’s test. It is neither sensitive nor accurate. [Dr. G. Oliver? recom-
mends the use of indigo-carmine papers alone. The test solution is made from
these with heat, and is again boiled with the urine. The colour obtained ranges
from violet to straw-yellow, according to the quantity of sugar present. This is
not a satisfactory test.]

8. Johnson’s Test (Picric Acid).—Both Johnson and Thiéry*®! have employed
picric acid as a test for sugar. A few drops of a solution of picric acid are added
to the urine, which is then treated with caustic potash. If sugar be present,
the fluid assumes a ceep-red colour ; but a red colour may also be obtained from
caustic potash and picric acid alone, or in presence of kreatinin; and conse-
quently, as a test for sugar, the process is not trustworthy.°* [Dr. G. Johnson
claims for picric acid the advantage that solutions do not change with keeping.
When a drachm of normal urine is boiled with the same quantity of picric acid
and half a drachm of caustic potash, a claret-red colour is produced, which in

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TESTS FOR SUGAR. 279

a test-tube of half-inch diameter will transmit light. This colour is due to
kreatinin. he presence of the smallest quantity of glucose in addition will
render the fluid so intensely dark that no light passes through.]

9. Penzoldt’s Test.?3_In this the reagent is diazobenzol-sulphonic acid dis-
solved in water, 1 : 60, without the aid of heat, but a drop of caustic potash may
be added to facilitate solution. A few cubic centimetres of the urine under
examination is placed in a test-glass, and rendered strongly alkaline with caustic
potash. A like quantity of the reagent, which should be feebly alkaline, is now
added. The process is repeated with healthy urine of the same tint and concen-
tration, and the two specimens compared. Both are at first of a reddish-yellow
colour, but whilst the healthy specimen remains unchanged, or nearly so, that
containing sugar becomes a bright claret-colour after some time. If sugar be
present in abundance, the fluid eventually becomes dark-red and opaque.

Penzoldt asserts that 0.1 per cent. sugar is appreciable in this way; but for
practical purposes the test is not to be recommended, since acetone and diacetic
acid have a similar reaction.**4 Moreover, the substance used is highly explo-
sive,265

10, Molisch’s Reactions.—Molisch -®§ has recently devised two methods, by the
aid of which he believes that sugar can be detected in the urine, whether of
health or disease.

(a.) The first depends upon the reaction of sugar with a-naphthol and sulphuric
acid. To obtain this, he takes 4 to 1 cc. of the fluid containing sugar—urine
should be highly diluted for the purpose—places it in a test-tube, and adds to it
two drops of a 15-20 per cent. alcoholic solution of a-naphthol. The fluid
becomes turbid from the precipitation of some of the a-naphthol. Concentrated
sulphuric acid is now added in excess, and the whole is well mixed. ‘he pre-
sence of sugar is shown by the transitory appearance of a blue colour, and the
formation of a violet-blue precipitate on the subsequent addition of water.

(b.) This reaction is obtained with thymol and sulphuric acid. The urine
which is thought to contain sugar is highly diluted, and to 4-1 ce. in a test-tube
is added first two drops of a 15-20 per cent. alcoholic solution of thymol, and
then sulphuric acid in excess. When the mixture is shaken, the momentary
development of a “cinnabar-ruby-carmine red” discloses the presence of sugar,
this colour giving place to carmine when the fluid is diluted with water.

By this method Molisch maintains that so small a proportion as 0.00001 per
cent. of sugar can be detected. Similar reactions, however, may be obtained
with cane-sugar, fruit-sugar, and maltose. Secgen**’ has further investigated
the subject, and found that chemically-pure solutions of proteids, and especially
of serum-albumin, behave in like manner. The author has repeatedly performed
the test with albuminous urine, with the result that the a-naphthol reaction was
obtained when the fluid was diluted in a much higher degree than that (1 : 100)
recommended by Molisch in the case of sugar. In presence of albumin, the dark-
violet coloration of the fluid was followed by the deposition of a greenish-black
precipitate. The thymol and sulphuric acid reaction with this body was almost
identical with that displayed by sugar.

For these reasons, Molisch’s reactions, which no doubt find a valuable applica-
tion in vegetable physiology, are not to be recommended as a test of glycosuria.
The researches of Mylius and v. Udransky*° have made it clear that Molisch’s
reaction is identical with the furfurol reaction, which takes place not only with
sugar, but with any carbohydrate.

It remains to mention that experiments have been instituted by
several investigators (v. Briicke, Seegen, Abeles, Salkowski®) with the

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280 THE URINE.

object of separating the sugar when it exists in very small quantities in
the urine, and submitting it in the concentrated form to the action of
Trommer’s and other tests.

The separation and detection of grape-sugar, as of the carbohydrates
generally, may he effected by the action of benzoyl chloride, which with
the carbohydrates forms insoluble benzoic acid ethers. For this pur-
pose the urine is treated with benzoyl chloride and caustic potash. If
to a litre of urine there be added 200 ce. of a 10 per cent. soda solution
and ro cc. of benzoyl chloride, the nauseous smell of the latter disappears
on shaking the mixture, and a precipitate results. The addition of
concentrated sulphuric acid and a few drops of an alcoholic solution of
«-naphthol causes an intense red colour if a trace of a benzoyl combi-
nation with the carbohydrate be present, and the coloured fluid will
exhibit a well-defined absorption-band in the green part of the
spectrum. 7?

It is indispensable that both the sulphuric acid and the naphthol
solution should be absolutely pure. To ascertain that they are so, a
ro per cent. solution of «-naphthol in chloroform is prepared, and to a
drop of this in a test-glass is added first 0.5 cc. of water, and then 1 ce.
of pure sulphuric acid. If the reagents are serviceable, the mixture
assumes a yellow tinge. A little is next added to the fluid to be investi-
gated,—.e., to a benzoic acid ether precipitate suspended in water. A
reddish-violet ring is evidence of sugar or a carbohydrate (Luther,
Roos).2 This proceeding, though simple, is open to fallacy, since many
other substances, as albumin, fats, &c., form acid ethers with benzoyl
chloride. In other words, it is a form of the furfurol reaction, and
partakes of its ambiguous character. The necessity of securing abso-
lutely pure reagents is a further disadvantage which detracts from its
value as a clinical test.

(8.) Quantitative Estimation of Grape-Sugar.

1. Titration Method (Fehling).?"°-—The principle upon which this
method is founded depends upon the property which grape-sugar pos-
sesses of reducing cupric oxide to its suboxide in alkaline solutions. It
has been applied in various ways, and most of these are to be found
described in the text-books of urinary chemistry. Fehling’s process has
hitherto been chiefly in vogue, but, in common with most of the others,
it is tedious and difficult, and consequently but little suited to the
requirements of the physician. At once the simplest and most satis-
factory mode of procedure is that adopted by Leube and Salkowski.2°

An opinion is first formed from the density of the urine as to the
quantity of sugar which it probably contains. It is then diluted to
such an extent that this shall not exceed 0.5 per cent. of the entire
fluid—6-1o times its volume of water may be needed for the purpose.2”4

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ESTIMATION OF GRAPE-SUGAR. 281

The diluted urine is placed in a burette. Ten ce. of Fehling’s solution
are measured into a white porcelain capsule, 40 cc. of water added,
and the bluish mixture heated until it begins to boil. The diluted
urine is now slowly added, and a precipitate of suboxide (red) or
its hydrate (yellow) falls, whilst the fluid loses its blue colour. It
is important to ascertain the precise point at which this colour has
disappeared entirely, showing that the fluid no longer contains free
sugar. When this is reached, 1 cc. of the fluid is taken and filtered
through thick filter-paper. The filtrate, which should be quite clear,
is acidified with acetie acid, and a little ferrocyanide of potassium
is added. The presence of copper will be shown by a brown colour,
and 0.5-1 cc. of the diluted urine must then be added until the brown
colouration no longer takes place. On the other hand, should it happen
that the fluid when tested is seen to be free from copper, the whole
process must be repeated with a smaller quantity of urine. Finally,
when, as sometimes happens, suboxide of copper is not precipitated,
and passes through with the filtrate, the experiment is entirely frus-
trated. When these points have been attended to, the process is
repeated, that quantity of urine being taken at the outset which was
found to be requisite. A calculation is then made by multiplying the
number which expresses the dilution (in volumes) of the urine by 5
(10 cc. of Fehling’s fluid correspond to 0.05 grm. sugar), and dividing
the product by the number of cc. of diluted urine employed. The
result is the percentage of sugar in the original urine. Salkowshki 2
has suggested that the cuprous oxide formed should also be weighed.
And Munk.?"6 recommends that a few drops of a 15.8 per cent. solution
of chloride of calcium be added to the mixture of urine and Fehling’s
solution, to promote the precipitation of the copper salt.

Fehling’s fluid is prepared as follows :—(1.) 34.639 grms. of pure crystalline
cuprous sulphate are weighed out and dissolved in water with the aid of a little
heat, water is then added to 500 cc., and the whole placed in a tightly-stoppered
flask. (2.) 175 grms. of Rochelle salts (potassium and sodium tartrate) and 100
cc. of caustic soda of 1.34 sp. gr. are dissolved in 500 cc. of water, and well
mixed, and also placed in a well-stoppered bottle.

When required for use, equal parts of these solutions are measured with a
pipette, and the mixture constitutes Fehling’s fluid.

[Mr. Martindale recommends the following formula :—(1.) Sulphate of copper,
181 grains; distilled water to 6 ounces. Dissolve. (2.) Tartrate of potassium,
neutral, 728 grains; caustic soda, 360 grains; distilled water to 6 ounces,
Dissolve.

Of a mixture of these two solutions (Fehling’s fluid) in equal volumes, 10 cc.
will be decolorised and reduced by 0.05 grm. of glucose or diabetic sugar in
solution.

Titration with Pavys Ammoniated Cupric Solution.—This is a
fluid composed as follows:—Cupric sulphate, 4.158 grms.; potassic

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282 THE URINE.

sodic tartrate, 20.4 grms. ; caustic potash, 20.4 grms. ; strong ammonia
(sp. gr. 0.880), 300 ce. ; water, 1 litre. The object of the ammonia is
to prevent the precipitation of the suboxide, and so to render the de-
coloration of the copper solution more evident. In preparing the fluid,
the caustic potash and the tartrate are dissolved together, the cupric
sulphate by itself; the two solutions are mixed, and when cold the
ammonia is added, and water supplied to the specified bulk. Ten ce. of
this solution are decolorised by 0.005 grm. of sugar. Dr. Pavy recom-
mends for clinical convenience the use of hermetically-sealed tubes of
glass, each containing 10 cc. of the solution.2"7]

2. By Fermentation.—This method of analysis was first suggested by
Roberts,?"> and Worm-Miller 2°. applied it to determine the proportion
of sugar in the urine from the density of that fiuid before and after
fermentation. According to Worm-Miiller, this method, with the aid
of a thermometer and a pycnometer fitted with a graduated index-scale,
gives good results where so little as o.5—1 per cent. of sugar is present.
Roberts concluded from experiments that a difference of 0.001 sp. gr
corresponded to 0.23 per cent. of sugar, and arrived at the following
formula :

 

ae Dx 0.230
0.001
Where

x= the percentage of sugar.

D=the difference in the density of the urine before and after fer-
mentation.

It is possible to obtain good approximate results from the application
of this method clinically. The following apparatus is required : Two
hydrometers accurately graduated to four places of decimals, and each
provided with a thermometer carrying a fractional index, and capable
of registering ;4,° C. These instruments should measure densities
ranging between 1.000-1.025 and 1.025-1.050 respectively up to four
places of decimals.

The first step is to take the sp. gr. of the urine at the iemperatute for
which the hydrometer in use was constructed. This may be done by
placing the test-glass containing it in a vessel of water, which may be
cooled or heated as required. 100-200 cc. of the urine are then placed
in a flask, together with some fresh yeast which has been carefully
washed on an ash-free filter to secure removal of inorganic impurities.
The flask is next closed with the arrangement represented in fig. 128,
by which evaporation is prevented. Fermentation is allowed to go on
for 24-48 hours. After this, the fluid, which should be clear, or nearly
so, is passed rapidly through a filter, and its density again taken at the
appropriate temperature, the latter being secured and ascertained as

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FERMENTATION PROCESS—POLARISATION. 283

before. From the observations made, the percentage of sugar is calcu-
lated by the formula given above.

In twelve cases of diabetes this method proved most valuable. Its
simplicity renders it very suitable for clinical use.

The figures in the following table afford the means of comparing the results
obtained by fermentation and by means of Lippich’s polarimeter in a series
of cases :— P

Percent. Percent. Percent, Percent, Percent. Percent, Per cent, Per ceut.

I, Fermentation: 2.22; 3.55; 4.49; 5.38; 6.06; 6.23; 60; 6.1

2. Polarimetry : 2.253; 3-655 4.67; 5.60; 6.01r3 6.00; 6.1; 5,7 280

3. By Polarisation.—Grape-sugar possesses a dextro-rotatory power
for polarised light, and upon this fact a quantitative test for that body
is based. Such a test must necessarily be open to fallacy, inasmuch as
the urine in diabetes is apt to contain other substances, such as B-oxy-
butyric acid and levulose, which rotate light in the opposite direction..
It is well, therefore, in applying it, to do so both before and after fer-
mentation (Hoppe-Seyler, Kulz, Worm-Miiller, and K. A. H. Morner),
when the difference in the results will be a measure of the quantity of
grape-sugar in solution. The advantage of the method is that it dis-
penses with delay. In recent times it has been invested with great
accuracy by the use of a polarimeter constructed on the principle devised

 

I'ic. 128.—Flask for the Approximate Estimation of Sugar by Fermentation (}).

by Lippich. This instrument is represented in fig. 129.°8! It is em-
ployed thus :—

The graduated disc is turned towards the observer, and the tube
towards the lamp, and the cap which covers the telescope and the
posterior end of the apparatus is removed. The lamp is placed at a
distance (45 cm.) equal to the length of the instrument itself. Car-

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284 THE URINE.

bonate of soda is placed in the cage attached to the lamp, and fused
until the receptacle is full. The latter is then fixed in the lamp in such
a way as to be in contact with the flame at the side only, and a screen
is so placed that the light passes only through the aperture in it.

The following description will sufficiently explain the construction of
the instrument :—At the hinder end of the polarimeter is a rod sup-
porting the arc of a circle, and behind this, in the direction of the lamp,
another rod, with a notch marked upon it. The second rod is fitted
with a screw, by means of which it moves upon the first, and can be
fixed in contact with the latter. When the line upon the upper surface
of the adjustable rod corresponds to the central point (0) of the metallic
are, and this with the o of the vernier, the entire field is dark, and by
rotating the are (which is done with the ivory lever in front) both
halves will be obscured or illuminated equally. In experimenting with
the instrument, the adjustable rod is deflected slightly to the right or
to the left. It is practically a lever attached to the box containing a
Nicol prism (d in the section, which is represented as seen from above),
and rotates the prism on its axis.

In conducting an observation, the tube containing the urine or other
fluid to be examined is placed in the capsule, and the second rod is
moved right or left, say as far as the mark 4. The observer then looks
through the telescope, and adjusts the instrument in such a manner
that the field is illuminated to the utmost in one half at least; after
which he moves the telescopic tube until the vertical line dividing the
field into two equal parts is rendered as narrow and well defined as pos-
sible, and the position of the flame is again looked to. The ivory lever
is now moved forward, and the inner notched vim of the disc is rotated
to the right or the left, until both halves of the field are equally obscure.
The lever is next reversed, and the observer works the micrometer screw
at the lower part of the disc, whilst he looks for a difference in the
degree of illumination of the two halves of the field. If this does not
occur, the latter was.either too bright or too obscure. It may be
rendered brighter by increasing and inverting the angle between the
two rods (c, d) to which the polarisers are connected ; and the less this
angle, the less will be the variation with equal differences of adjustment.
When the proper degree of illumination is obtained, a number of read-
ings are taken with different adjustments.

The number of degrees to the nearest 4°, from the zero-point of the
dise to that of the vernier, are read off; and then, proceeding in the
same direction, the first line on the vernier which exactly corresponds
with a division on the disc is noted. This is easily found by inspecting
the divisions to the right and left of that one which is assumed to be
correct. Both are on the inner side of the corresponding marks on the

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286 THE URINE.

circle. The longer lines on the vernier correspond to 0.01’, the short
ones to 0.005". In practice, the adjustments should not differ by more
than 0.005”.

The way in which the readings are taken may best be shown by an
example :—Supposing the zero-point of the disc stood to the right of
the zero-point of the vernier, and that, between the two, 2° in addition
to twenty long vernier marks and one short one had been counted,
then + 2°, 205 is written down. With further readings, the vernier
marks only are noted, added together, and the average taken. Should
the result again be 205, then

2° =0.75°, 0.75° +0.205 = +0.955.

One long mark =0.01", 20 long marks= 0.200".
One short mark = 0.005”, 1 short mark = 0.005".

Finally, the zero-point is fixed by taking the tube out of the capsule
without otherwise altering the arrangement of the instrument.

The field of vision is unequally illuminated, and the mark no longer
distinct. The telescope is focussed to show the mark, the lever brought
forward, the disc put in with the hand, the lever reversed, and the
micrometer screw carefully adjusted. A number of readings is taken,
and an average struck. Supposing this to be = — 2.045° (z.e., the zero
mark for the present inclination of the polariser rods), the number is
to be deducted from the original reading ; thus, + 0.955 — (— 2.045) =
0.955 + 2.045 = 3.0.

If the urine was examined in a tube two decimetres long, then

2 [a], = 3.0%, and [«], = 1.5.
[«], being the specific rotating power for grape-sugar (C,H,,0,), is
in this case = + 52.5°.
52.5 for 100 grms. in 100 ce.
100

grms. I 100 ee.
2.5

 

1 for

, 100 x 1.5 i
1.5° for ————— orms. in 100 ce.
52-5
The percentage of sugar in the case taken would therefore be
] dS 5 )
100 Xx 1.5
52-5

Care should be taken throughout the observation that the position
of the lamp is not altered, otherwise varying results are obtained.

= 2.85 per cent.

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CARBOHYDRATES —CHOLURIA. 287

During the whole process, therefore, the same position of the lamp and
instrument must be maintained, and all readings should be taken con-
tinuously with one filling of the platinum cage.

By carefully observing these precautions, very accurate results may
be obtained.

The instrument will serve also to show whether a liquid has the power of
rotating light or not. In the latter case, the zero-point of the disc stands in the
same lateral position to the zero-point of the vernier as the second pointer to the
zero-point of the segment connected with the polariser (right or left); the devia-
tion of the zero-point of the disc from that of the vernier being half as great as
the deviation of the two rods.

2. Levulosuria.—Fruit-sugar is found sometimes in conjunction with
grape-sugar in the urine (K. Zimmer, Seegen).82_ The latter will then
yield all the reactions of grape-sugar, including that with phenyl-
hydrazin. It may happen under such circumstances that a specimen
of the urine examined with the polarimeter will fail to rotate polarised
light to the right, or may even rotate it to the left; and from this fact
the presence of levulose may be inferred.

3. Lactosuria.— Milk-sugar occurs in the urine of women who are
nursing.” Its recognition can be effected only by separation from the
fluid (Hofmeister). An effort has been made with the phenyl-hydrazin
method to transform this body in the urine into phenyl-lactosazon
(v. Jaksch *§*), but as a test the expedient has not succeeded.

According to Jischer, the presence of milk-sugar may he inferred if,
while no result is obtained with the phenyl-hydrazin and the fermenta-
tion tests, evidence of sugar.is given by Trommer’s and Nylandeyr’s
tests.

4. Dextrin.—Dextrin has been seen in the urine of diabetes (L.
Reichard *§°), where it seemed to take the place of grape-sugar. In such
cases Reichard found that the urine behaved with Trommer’s test in
all respects like a solution of dextrin, the originally blue fluid becoming
first gradually green, then yellow, and sometimes dark brown.

5. Animal Gum.—Landwehr ?*6 has recently found in the urine a
carbohydrate presenting a close analogy to members of the gum series.
To this he has given the name of “animal gum,” and he believes that
it is a normal constituent of the fluid. The methods for its detection
and isolation will be found in the original contribution on the subject.
The statements there made are confirmed by Wedenski.28"

Amongst other carbohydrates occasionally present in health and disease
are maltose (Le Nobel, v. Ackern?*), and a left-rotatory body observed
by Leo and Kiilz 28° in diabetic urine.

III. Choluria.—Of the bile constituents, the biliary acids and _ pig-
ments chiefly concern us here. <A third constituent of the bile, choles-

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288 THE URINE.

terin, has never yet been found in the urine in jaundice, although it
occurs in considerable quantities in other connections.

Hoppe-Seyler °° has satisfactorily proved that biliary acids occur in
the urine of jaundice; but their presence is of relatively little clinical
interest, since they can be detected only by tedious chemical processes,
but seldom suited to our purpose. None of the methods which have
been suggested for the recognition of these bodies directly in the urine
can be relied upon. That of Mackay, which is founded upon their
physiological properties, is perhaps the most useful with which we are
acquainted. Where the presence of bile acids in considerable propor-
tion is suspected, resort may be had to the method for their detection
in the blood (p. 75). The biliary acids, when isolated, or obtained as
an alcoholic extract from the evaporation residue of the urine, may
also be submitted to the furfurol test. To this end the fluid is treated
with a few drops of a o.1 per cent. watery solution of furfurol and sul-
phurie acid. The presence of biliary acids is shown by a red colora-
tion.2! This reaction, however, is given by so many substances that
its value as a test is slight (see p. 280).

A fact of much greater practical interest is the occurrence of bile-
pigments in the urine. This results from the comparative ease with
which they may be recognised. Their manifestation implies, in the
first place, that there has been obstruction of the bile-ducts in the liver,
in consequence of which substances secreted by that organ have made
their way into the lymphatics and the general circulation, from which
they are subsequently eliminated by the kidneys. This is hepatogenic
jaundice, the commonest form of choluria. The conditions which cause
it are manifold and various. Of these, simple obstruction or narrowing
of the bile-ducts is the most obvious. But when it is remembered that
the pressure under which the bile is secreted is very slight, it will become
apparent that other circumstances—as, for instance, one-sided immobility
of the diaphragm, thrombosis of the portal vein, &e.—will tend to retard
the propulsion of bile, and consequently to induce choluria. Such
causes must be discriminated by physical examination, and on other
grounds.

The bile-pigments of urine are not in all cases necessarily derived
from the liver. It is conceivable that, with a quite normal biliary
function, these bodies may be present, and they then owe their origin
to blood-colouring matter which has undergone certain changes (p. 61) ;
and these changes may take place either in the blood proper (hematogenic
jaundice **) or supervene when the colouring matter has been discharged
in the tissues (Quinche’s inogenie jaundice).2

It follows from what has been said, that the appearance of bile-pig-
ment in the urine is a fact of very extended import, and caution must

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TESTS FOR BILE-PIGMENTS. 289

be observed in inferring from it the existence of hepatic disease. Still
the latter is by far its more common association.

Urine containing bile-pigments is usually clear, deeply stained a
yellow- or greenish-brown, and when shaken shows a yellow froth,
even when these bodies are in very small proportion. The chemical
tests for bile-pigments. are very numerous, but it will suffice here to
describe three, which alone, perhaps, are entirely trustworthy.

It has been claimed for the “ cholecyanin test” of Stokvis?% that it is the most
sensitive of all; but of this the author has no experience. It must be borne in
mind that bilirubin alone, of all the bile-pigments, occurs in fresh urine; the
other pigments, biliverdin, bilifuscin, and biliprasin, being its oxidation-products.

1. Gmelin’s Test.2%°—A small quantity of nitric acid containing
nitrous acid is placed in a test-glass, and a little of the urine under
examination is poured in a separate layer upon its surface. To do this
care will be necessary, and it will be facilitated by slanting the test-
glass so that the urine shall float on the surface of the acid. If bile-
pigment be present, there is a play of colours at the point of contact
between the acid and the urine, and a green ring in particular forms,
indicating the production of }iliverdin. Gmelin’s test will not serve
for urine which has heen treated with alcohol, since that body, when
similarly brought in contact with nitric acid, also yields a beautiful
bluish-green ring (H. Huppert).°°

In Rosenbach’s?" modification of Gmelin’s test, the urine is passed
through a filter, and on the latter a drop of nitric acid is allowed to fall,
when the coloured rings will develop around it. This process affords
a very sensitive test, but its results can be relied upon only when the
filter-paper employed is known to be absolutely free from impurities
(colouring matter) which might account for them.

Dragendortf’s 8 method is to place a little of the urine on a plaster
of Paris disc, and when the greater part has been absorbed, a drop of
nitric acid is applied to the remainder. <A parti-coloured ring forms
around, in which the green tinge is prominent.

2. Ultzmann’s test 2° is very serviceable in cases where the urine con-
tains a considerable proportion of bile-pigment. The urine is mixed
with solution of caustic potash (one part to three of water) in a test-
glass, and hydrochloric acid added. The production of biliverdin by
oxidation is indicated by the fluid assuming an emerald-green tint.

Huppert’s method *°° serves for the detection of the merest traces of
bile-pigments. 8 to 10 cc. of urine are treated with milk of lime, and
the resulting precipitate is removed by filtration, and treated with
sulphuric acid and alcohol in a test-glass. Sulphuric acid is added

until the solution has an acid reaction. It is then boiled, when the
T
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290 ‘THE URINE.

precipitate is decolorised, if bile-pigment is present, and the liquid
assumes a green tint. With similar treatment urine abounding in
indican deposits a bluish-grey precipitate at the outset, but with the
subsequent process not a green, but, if any, a yellow or reddish colour
develops. Urine which contains urobilin, on the other hand, is made
in this way to exhibit a deep-rose colour (p. 292).

Ehrlich®°! has devised the following method for the detection of
bilirubin in the urine. The latter is mixed with its own bulk of dilute
acetic acid, and, drop by drop, is added a mixture consisting of 1 grm.
sulphanilie acid, 15 cc. hydrochloric acid, and o.1 grm. nitrite of sodium
to the litre. A dark discoloration takes place, which on the further
addition of glacial acetic or other acid passes to a characteristic violet
colour (bilirubin).

C. le Nobel? recommends that the urine be mixed with zine chloride and a
few drops of the tincture of iodine; this produces dichroism. It should be
displayed by the urine of jaundice, even if all other reactions fail.

IV. Urobilinuria.—Jafé*” was the first to discover urobilin in the
urine. It seldom exists pre-formed *° in the recently passed healthy
fluid, but the latter holds a chromogen (see p. 214) which yields urobilin
on the addition of acid.

According to MacMunn, the urobilin of febrile urine is different from that of
health.

[Febrile or “pathological” urobilin (MacMunn), like normal urobilin, is a
derivative both of bile- and of blood-pigment. It is identical with or closely
resembles stercobilin. It has a distinct spectrum, and, chemically, is a less
highly oxidised product than normal urobilin (see also p. 61). The spectrum
of pathological urobilin show three bands, one before D, one between D and £,
and one at F.]%°

This body is present in large amount in the urine of certain morbid
states, amongst which may be mentioned fever, and the various affec-
tions which are characterised by the disintegration of red blood-cor-
puscles, as scurvy (Kretschy °°), and in Addison’s disease (Kwmmer).3%

[Mott and W. Hwnter* have observed urobilin in the urine in pernicious
anemia, and Hunter regards this as a point of much weight in diagnosis. It
is also of interest as bearing upon the origin of urobilin. The appearance of
urobilin in the urine is associated with an excessive elimination of bile into the
intestine (Hunter), and with evidence of increased destruction of corpuscles in
the portal vein. At the same time, the liver-cells are found to be overloaded
with iron. From these facts and others Mott concludes that hemoglobin is
acted upon by the liver-cells to form urobilin or an allied pigment, which is then
excreted by the kidney, while iron accumulates in the liver. Hunter assigns
reasons for the view that other organs besides the liver effect this decomposition.
In one of his cases the substance found in the urine was pathological urobilin.]

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UROBILINURIA. 291

It often happens in cases which would be described as slight jaundice,
that a very dark-coloured urine is passed, and this is found on examina-
tion to be free from bile-pigments, but abounding in urobilin (Gubler,
Gerhardt).!9 This so-called “‘urobilin jaundice” occurs in connection
with hepatic disease, most frequently with hepatic cirrhosis and conges-
tion (Hayem).?"1 In twelve cases of atrophic and hypertrophic cirrhosis
the author has never failed to detect urobilin; and it is, doubtless,
valuable evidence of hepatic disease when supported by other symptoms,
and in the absence of causes which are known equally to produce uro-
bilinuria. Rossbach*2 has observed the latter in a case of multiple
neuritis, and it follows inoculation with Koch’s tuberculin. Protracted
chloroform narcosis is also recognised as a cause (Cavallero, Kast, and
Mester).318

It is further a fact of great clinical interest that the excretion of
considerable quantities of urobilin has been observed to attend on intra-
cranial hemorrhages [Bergmann, Kunkel*\4], hemorrhagic infarction,
retro-uterine heematocele, and extra-uterine pregnancy (Dick).? Apart
from its occasional association with liver complaints, the author’s expe-
rience has been that urobilinuria occurs most commonly in the course
of extensive cutaneous hemorrhages due to scurvy, carcinoma, the
hemorrhagic diathesis, &c.; extravasation under such conditions was
constantly followed by the appearance of urobilin in the urine, and this
became more marked as the process fell into abeyance, thus suggesting
the inference that the blood colouring-matter discharged into the cuti-
cular tissues was again absorbed and eliminated by the kidneys in the
form of urobilin. [Cases of this kind which occurred under Dr. Ringer's
care are reported by MacMunn.*1°) The individuals in whom this pro-
cess was going on commonly exhibited a pronounced yellowness of the
skin. In such of these cases as afforded an opportunity for post-mortem
examination, the bile-ducts were invariably found unimpeded, and during
life the urine was free from biliary pigments. In the cases of urobilin-
uria which have come under the author’s notice, the skin was very
commonly tinged yellow (jaundiced ?), but this was not without excep-
tion, and in such cases he has invariably found bile-pigment in the
blood (see p. 76). From these facts it appears probable that the blood
colouring-matter, having been converted into bile-pigment, re-enters the
circulation as such, and is excreted as urobilin. Since there is no uro-
pilin in the blood, a “urobilin jaundice” cannot be assumed; but in
some cases bile-pigments derived from the blood are eliminated as
urobilin, and in others bilirubin formed in the liver for some reason
enters the blood, and is similarly disposed of. [The researches of Mott
and Hunter, noticed above, point to the liver as the place where normal
urobilin is sometimes formed. ]

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292 THE URINE.

Recent investigations by Lewbe*!” have made it probable that under
some circumstances bilirubin is reduced to urobilin in the kidney.

Urine which contains much urobilin is characterised by its very dark
colour; but this does not suffice to distinguish it, inasmuch as other
substances, and notably an abundance of the antecedent of indigo, will
impart the same quality to the water. Moreover, it will sometimes
furnish a beautiful yellow froth like that of jaundice. Such urine has
the property of displaying fluorescence in presence of ammonia and
zine chloride. For the detection of urobilin Gerhardt *!§ suggests that
a chloroform extract of the urine should be treated with solution of
iodine, and caustic potash added, when a beautiful green fluorescence
develops. The author has adopted in about eighteen cases of urobilin-
uria the following method :—The urine is submitted to Huppert’s test

 

 
 
 
    
 

Red. Orange. Yellow. Green, Cyanblue,
———_—““_-_-
AaBa D | Hod FF
40 50 60 70 380 90 | 10
elt

 

 

 

 

 

 

 

 

 

 

 

Fic. 130.—Spectrum of Urobilin in Acid Urine.

 

Red. Orange. Yellow. Green. Cyanblue.
se — ——
4AaBe D Eb F

40 50 60 70 sO 90 100 4110

te

 

itil

 

 

 

 

 

 

 

 

 

Fic. 131.—Spectrum of Urobilin in Alkaline Urine.

for bile-pigments (p. 289). If urobilin be present in considerable pro-
portion, the precipitate is coloured a brownish-red, and becomes decolor-
ised on boiling with sulphuric acid, while the fluid assumes a brownish
or pomegranate-red tint. If, on the other hand, the urine contains but
little urohilin, the fluid immediately above the precipitate takes a reddish
tinge.*!" Occasionally this and all other tests will fail, and resort must
then be had to the spectroscope.

The urine in this condition may be freed from colouring-matter by
ether or amylic alcohol. Its spectroscopic characters are remarkable.
When acid, if rich in urobilin, it displays a distinct absorption-band in
the green and blue between Fraunhofer’s lines 6 and F (fig. 130), and
usually extending with diminished intensity beyond 7. When alkaline,
a less well-marked band is seen midway between 6 and F (fig. 131).

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HMMATOPORPHYRINURIA. 293

The quantitative estimation of urobilin may be effected by means of
Vierordt’s 2° spectrophotometer. For its separation, Jaffé’s 22} method,
or that of Méhu *?2 (see p. 204), may be employed.

V. Hematoporphyrinuria.—The presence of hematoporphyrin
in the urine of diseased states has been noticed by [MacMunn, Le Nobel,
and] £. Salkowski,?> although cases previously reported by others, and
amongst them by Sfolvis,24 would appear to be instances of this con-
dition. [ (Uro)hematoporphyrin, like urobilin, may exist in the urine
partly in the form of a chromogen, which becomes a pigment on oxida-
tion. (Halliburton).*5| Viewed by reflected light, the urine is opaque
and almost black—or in a thin layer, brownish-red. The colour is
unchanged by boiling. It is, or may be, free from albumin, since
hematoporphyrin does not contain albumin. When diluted and treated
with HCl the characteristic spectrum (Hoppe-Seyler*?°) may be seen.
This exhibits four absorption-bands, viz., two, narrow and faint, situated,
one between C and D, the second between D and £ but nearer to £,
and two broad and dark bands, of which one overlaps D to the red
end of the spectrum, while the other lies between / and F. These
* latter may alone be visible, and are alone evidence of hematoporphyrin.
To detect this substance chemically, about 30 cc. of the urine are taken
and treated with alkaline solution of barium chloride; the mixture is
filtered and the precipitate washed first with water and afterwards with
absolute alcohol ; the precipitate while still wet is rubbed up in a mortar
with alcohol and hydrochloric acid, allowed to stand for a while and
then heated in the water-bath. The solution thus obtained, if hemato-
porphyrin be present, should have a reddish colour, and when filtered
and examined with the spectroscope, the filtrate should give the two
absorption-bands of hematoporphyrin (Salkowski). The clinical signifi-
cance of this state is not yet fully known. [MacMunn **" and Le Nobel 2?8
have described it in Addison’s disease, acute rheumatism, pneumonia,
measles, pericarditis, typhoid, meningitis, and other diseases.] In some
people it follows the use of sulphonal.*”?

[Hematoporphyrin derived from the blood by the action of sulphuric
acid and (uro)hematoporphyrin derived from urine differ in their
spectra. MacMunn has recently found a pigment, which he regards as
intermediate between the two, in three specimens of urine. These
urines were of a deep Burgundy-red colour, free from albumin, and on
the addition of H,SO, showed the spectrum of acid hematoporphyrin.**°]

VI. #ther-Sulphurie Acids and their Derivatives (Indigo-
Blue, Indigo-Red, Skatol, Phenol, Parakresol, Pyrocatechin, Hydrochinon)
and the Aromatic Oxy-Acids.

(a.) Indicanuria.—Indigo-blue (indigo, indigotin) as such, is rarely
present in the urine, usually in’decomposed urine, and hardly ever so

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294 THE URINE.

plentifully as to impart its colour to the fluid. It may always, however,
be obtained from urine as a product of the decomposition of salts of
indoxyl-sulphuric acid (potassium indoxyl-sulphate).*1

Indol, a regular product of bacterial putrefaction of albumin (see
p. 202), is the basis of indican (indoxyl-sulphuric acid).**? It is oxidised
to indoxyl within the system, and by combination with the sulphuric
acid present forms indoxyl-sulphuric acid. The decomposition of in-
doxyl-sulphuric acid yields, besides indigo-blue, other substances of
similar character, such as indirubin ; but to these no practical interest
attaches in the present state of our knowledge.***

With reference to the clinical import of indicanuria, it must be borne
in mind that the quantity of indoxyl-sulphuric acid formed varies
in health with the food ingested, and it is increased especially by
animal diet. ¢

Apart from this, an undue proportion of indican in the urine is a fact
of pathological interest, and there are certain diseases in which indoxyl-
sulphuric acid is regularly produced in excess.

It was formerly believed that starvation and wasting diseases were
attended with the separation of indican (Senator **+) ; but more recent
observation #85 has shown that this is dependent on the fact that in
such diseases albuminous putrefaction takes place in the alimentary
canal, and in consequence there is an increased production of indol, the
antecedent of indican. The presence of indican in the urine is very
often a sign of intestinal putrefaction, and its quantity in certain cases
varies with the activity of that process.**° It may also accompany the
decomposition of albumin in other cavities. Thus, in a case of pleurisy
with abundant unhealthy exudation, the author has found a profusion
of indican in the urine, and when this manifestation arises in the course
of peritonitis, it may be taken as an evidence of the character of the
disease and of the formation of putrid pus. [Hochsinger *3” has recently
studied this subject in connection with infants. He found that the
urine of new-born children was free from indican, and in healthy infants
it occurs only in traces. It becomes more abundant in intestinal dis-
orders and is always most so when these are attended by acute
diarrhcea.*88 Tuberculosis, whether affecting the intestinal tract or
not, was always accompanied by profuse indicanuria. Hochsinger
attributes the condition to decomposition of milk-albumin in the in-
testinal tract. |

Large doses of thymol were followed by an increased production of indican
(Bohland).**9

In general, therefore, the appearance in the urine of larye quantities of
indican implies that abundant albuminous putrefaction is progressing

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ESTIMATION OF INDICAN. 295

actively in some part of the system. Caution must be observed in further
narrowing the inference as to diagnose a gangrenous suppuration, for
instance, since in simple constipation a notable indicanuria will very
often arise.

It may be remarked here that the deep brown colour which usually
belongs to urine rich in indican is not due directly to the presence of
indoxyl-sulphuric acid, but depends upon the higher oxidation products
of indol which accompany it. These bodies bear to indoxyl-sulphuric
acid the same relation that the brown, green, or black colouring matters
of carbolic urine do to phenol-sulphuric acid.

Detection of Indican.—The methods employed for this purpose pro-
ceed upon the principle of splitting up the indoxyl-sulphates of the
urine, and obtaining from them a coloured product—indigo-blue.

Jafés Test.*°—A few cc. of the urine are treated with an equal
quantity of hydrochloric acid, and, drop by drop, a solution of some
hypochlorite is added by means of a glass pipette, and shaken up with
the fluid. The chromogen formed by decomposition of indoxy]-sulphuric
acid is oxidised into indigo-blue. Care must be taken that hypochlorites
are not in excess, since this would alter and bleach the indigo-blue.
Stokvis **1 recommends the admixture of a little chloroform in the
process, with the object of dissolving the indigo-blue as it forms. The
chloroform solution then takes a blue colour [and the colouring-matter
is obtained as a deposit after evaporation. Albumin if present should
be removed before performing this test, since it forms a blue colour
with hydrochloric acid (Ha/liburton).*4”]

Obermayer *° has suggested a useful modification of Jafé's test. The
urine is treated with 1 in 5 solution of sugar of lead, which, however,
must not be in great excess, filtered through dry paper, the filtrate mixed
with an equal bulk of fuming HCl containing 1 to 2 parts in 500 of ferric
chloride solution, and then’ thoroughly shaken for.one to two minutes.
The indigo-blue formed is then taken up with chloroform.

Weber's Test.°44—Thirty ce. of urine are mixed with an equal quantity
of hydrochloric acid, 1-3 drops of dilute nitric acid added, and the
mixture boiled. The fluid assumes a dark colour. If allowed to cool
and then shaken up with ether, the presence of indigo-blue is shown by
the formation of a blue froth on the surface, while the ether exhibits
a rose or violet tint. [MacMunn uses chloroform instead of ether,
and examines the violet fluid with the spectroscope, which shows
an absorption-band before D (indigo-blue), and another after D (indigo-
red), This method is preferable to Jaffé’s for the detection of small
quantities of indigo, which are destroyed by the hypochlorite (Hadld-
burton).*# |

Quantitative Estimation.—The methods of Jaffé and Salkowshki are

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296 THE URINE.

the most useful. Their principle is the same as that of the tests for
the presence of indican.

Salkowshi’s 4 Colorimetric Process is perhaps the best. A rough
analysis is first effected by determining the quantity of chlorinated lime
solution with which indigo forms in greatest abundance. If in this way
it is found that the urine contains much indican, 2.5—5 cc. are diluted
with water to 10 cc., while, if there be but little indican present, 10 ce.
of undiluted urine are taken as the basis of the experiment. In either
case an equal quantity of hydrochloric acid is added, and that propor-
tion of chlorinated lime solution which was found in the preliminary
reaction to be required. The mixture is then neutralised with caustic
soda, and carbonate of soda added to make it alkaline. The indigo-blue
which forms is collected in a filter, and then washed with water until it
no longer exhibits an alkaline reaction, when it is dried and repeatedly
extracted by heating with chloroform until the latter ceases to colour
with it. The chloroform extract is then, by the addition of chloroform,
made up to a quantity expressed by a round number of ec. placed in a
glass vessel with parallel sides, and the intensity of its colour compared
with that of a freshly prepared chloroform solution of indigo-blue of
known strength.*4* To one or other of these, as required, more chloro-
form is added, until their tint is adjudged equal. From the known
constitution of the standard the quantity of indigo-blue derived from
the urine (2.5-5 or 10 cc.) taken may be also known, and its percentage
may be readily calculated.

From the urine passed in twenty-four hours under ordinary conditions
of diet 5-20 merms. of indigo-blue can be obtained on an average.

Indigo-Red.—There is now no doubt (Rosin *$) that indigo-red (indi-
rubin) as well as indigo-blue occurs in the urine. It is formed together
with indigo-blue when a urine rich in indican is boiled with nitric acid
(O. Rosenbach’s test). For its detection Rosin renders the urine alkaline
with sodium carbonate, and then extracts the indigo with ether. The
inferences which Ros?n has drawn from the presence of this body in the
urine are questioned by other observers, and Rosenbach’s *#9 test cannot
be taken as evidence of anything except that the urine contains abun-
dance of the indigo antecedent.

There are certain other aromatic derivatives of the urine which will
engage our attention here, both because they are chemically allied to
indoxyl-sulphuric acid, and also because pathologically their production
is apt to coincide with the manifestation of that substance.

().) Skatoxyl-Sulphuric Acid.—This body results from the skatol of
the feces (Brieger).°° It is assumed that skatol, by a process analogous
to that undergone by indol, is oxidised to skatoxyl within the body,
appearing in the urine as skatoxyl-sulphuric acid. It is probable that

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ESTIMATION OF ATHER-SULPHURIC ACID. 297

the red colour which develops in the urine in the presence of acids is to
some extent due to decomposition products of this substance.**!

(c.) Parakresol- and Phenol-A:ther-Sulphuric Acid.—The other mem-
bers of the aromatic group which occur in human urine in combina-
tion with sulphuric acid are phenol (carbolic acid), parakresol, pyro-
catechin, and hydrochinon. To the latter we shall have need to refer
again. The methods by which these bodies may be detected are highly
interesting and clinically instructive.

Salkowski*°? has shown that the urine of patients suffering from
ileus and peritonitis, in addition to a large percentage of indican, con-
tains also a considerable proportion of phenol-forming substance, and
Brieger’s *°° experiments have proved that the elimination of the ante-
cedent of indigo (indoxyl-sulphurie acid) on the one hand, and that
of the phenol-producing substances (phenol, parakresol-ether-sulphuric
acid) with the aromatic oxy-acids on the other, bear to one another no
constant relation as to activity ; and that author found that in diphtheria,
searlatina, and facial erysipelas phenol was formed in greatly increased
quantity, whilst in typhoid, relapsing and intermittent fevers, small-
pox, and meningitis it could be obtained but very sparingly from the
urine. These statements are borne out by others.*°4

Again, in all cases where albuminous putrefaction is actively pro-
gressing in the intestine or other organs, in addition to the salts of
indoxyl-sulphuric acid phenol is increased in the urine, and in general,
together with phenol, the other members of the aromatic group become
evident in connection with pulmonary gangrene, putrid bronchitis, foetid
pleuritic exudation, and decomposition generally throughout the body.

Detection of Ather-Sulphurie Acids.—For this purpose the urine is
first treated with barium chloride in excess to precipitate simple sul-
phuric acid and then boiled with hydrochloric acid. If zther-sulphuric
acid be present, it is decomposed with the formation of the uncombined
acid. This combines with the barium present to form sulphate of
barium, and a white precipitate is deposited.

The quantitative estimation of the phenols (phenol, parakresol) is
conducted in the manner to be described at p. 299, and their presence
may be determined by the tests given at p. 161 and p. 202. It must be
mentioned, however, that the investigations of Rumpf*®° have shown
that an accurate quantitative analysis cannot be made by any of the
methods hitherto in use. For the comparative investigation of these
substances the original work of Brieger *°° may be consulted.

Quantitative Estimation of Asther-Sulphuric Acid.—The percentage
of this body in the urine may be best determined by Bauwmann’s 7
method as modified by Salkowshi.?°§

To 200 cc, of urine is added a like quantity of alkaline barium

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298 THE URINE.

chloride solution (two parts saturated solution of baryta, and one part
of solution of chloride of barium saturated in the cold). The mixture
is allowed to stand for some minutes and then passed through a thick
filter which has been carefully dried. Of the filtrate, which must be
perfectly clear, 100 cc. ave taken and rendered strongly acid with ro ce.
of hydrochloric acid (sp. gr. 1.12), then boiled and heated on the water-
bath until all the precipitate which forms has settled. The beaker may
be heated on an iron plate coated with asbestos, and allowed to remain
till its contents are cold. The precipitate is next collected and placed
on a filter of Swedish paper which has previously been washed with
dilute hydrochloric acid, and care must be taken that the filter is not
allowed to empty itself entirely during the process. With the aid of a
glass rod protected with a ring of india-rubber, and rinsing with boiling
water, the entire precipitate is placed on the filter, and is there washed
with boiling water until the filtrate which passes through fails to give
a precipitate with dilute sulphuric acid, thus showing the absence
of free chloride of barium. Should it happen that the fluid passing
through the filter is turbid, this may be due to the presence of soluble
substances, as phenols-produced. by the decomposition of the compound
acids. To ascertain their character in this case, the cloudy filtrate
is placed in a beaker on the water-bath heated to boiling-point, when,
if the turbidity be due to phenols, these pass off in vapour and leave
the fluid clear. Where, on the other hand, the appearance is caused
by the barium precipitate having passed through the filter, the turbidity
will not be removed in this way, and the experiment is spoiled. The
precipitate is next washed with boiling alcohol, and finally with ether,
and together with the filter-paper placed upon a platinum crucible of
known weight and heated for a long time. After this the platinum
crucible is raised to a white heat, allowed to cool, and then weighed
again. The calculation is made as follows :—233 parts by weight of
sulphate of barium correspond to 98 parts by weight of sulphuric acid
(H,SO,), and consequently the quantity of sulphuric acid in 100 ce. of
the urine may be computed by the formula—

ce 98 x M = 0.4206 x M

233
Where
w = the quantity of sulphuric acid required.
M = the quantity of barium sulplate found.

ll

If the object be to determine the total quantity of the sulphuric acids
(simple and compound), so as to find out their respective proportions in
the urine, the latter is filtered. Another too ce. are taken and treated
with 10 ce. of hydrochloric acid (sp. gr. 1.12), then boiled for fifteen

C
c

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ESTIMATION OF PHENOLS—PYROCATECHIN. 299

minutes and chloride of barium solution added in excess. The remain-
der of the process is that described above. The difference between the
total quantity and that of ether-sulphuric acids obtained expresses the
proportion of simple sulphuric acid in the urine.

For the methods of estimating sulphur when present in the urine in
other forms see pp. 323, 327.

Quantitative Estimation of Phenols.—The phenols (phenol and para-
kresol) which have passed over in the distillation of a known quantity
of urine previously acidulated are estimated in the form of tribromo-
phenol by Landolt’s method, with the precautions suggested by Bawmann
and Brieger.*°9

One-fourth of the urine passed in twenty-four hours is mixed with
one-fifth its bulk of hydrochloric acid and distilled. Distillation is
continued until the distillate ceases to colour with bromine water, after
which it is filtered. All the fluid which has passed through—including
that tested during the process—is now treated with bromine water
until a permanent yellow colour is attained. The precipitate is allowed
to settle for two or three days, when it is separated on a filter which
has been weighed and carefully dried over sulphuric acid; it is then
washed with bromine water and dried over sulphuric acid in the dark
until it has acquired an approximately constant density. It is then
weighed on the filter, and the difference between the result and the
weight of the filter recorded expresses that of the tribromo-phenol
formed. From this the quantity of carbol in the urine may be esti-
mated thus :—331 parts by weight of tribromo-phenol correspond to
94 parts by weight of carbol, and the following formula results :—

— 94 =

e==* x M=0,2839 x M

331 59

Where

the quantity of carbol required.

the quantity of tribromo-phenol found.

I

av

M

This method may also be employed for the analysis of vomited matters in cases
of carbolic acid poisoning (compare p. 161).

J. Munk has computed that the quantity of phenols excreted with
the urine averages 0.017 to 0.051 grm. in the twenty-four hours. For
purposes of more accurate analysis it is important to determine the
quantity of indoxyl-sulphuric acid and ether-sulphuric acids eliminated
in the manner already indicated (p. 295), and to remove the analogous
substances generated in intestinal decomposition by means of a calomel
purge. °6°

(d.) Pyrocatechin —This body, like the others, occurs in the urine
only in combination with sulphuric acid ; and it is if not an invariable,

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300 THE URINE.

at all events a very frequent constituent of that fluid.**! The urine
containing it is characterised by the fact that it is colourless when
passed, but becomes dark after exposure to the air; and the change
is expedited by the addition of caustic potash. When boiled with
hydrochloric acid, it becomes a powerful reducing agent. An ammo-
niacal solution of silver exposed to it will quickly deposit metallic silver
in the cold.

These properties, however, are not sufficient to determine the presence
of pyrocatechin. To do this it must be isolated, and the following
method is the best for the purpose.*°? The urine is evaporated to one-
fourth its volume on the water-bath, filtered, and the filtrate boiled
with excess of sulphuric acid. It is then allowed to cool and repeatedly
shaken up with ether, the ethereal extracts collected, the ether dis-
tilled off, the residue neutralised with carbonate of baryta, and again
extracted with ether. Pyrocatechin passes over in the ethereal extract,
and when the ether is distilled off, it remains as a more or less pure
crystalline substance. If the character of the latter is not sufficiently
apparent, it may be re-crystallised from benzol in the form of prisms
belonging to the tetragonal system. If some of these be dissolved in
water in a watch-glass and a few drops of a very dilute solution of per-
chloride of iron be added, an emerald-green colour develops, and this
changes to violet on the addition of a little ammonia.?®

(e.) Hydrochinon.—It has been ascertained by Bawmann and Preusse °*4
that hydrochinon appears in the urine after carbolic acid poisoning,
and these authors believe that to its presence the dark colour of that
fluid after the exhibition of carbolic acid is due. It is always in the
form of ether-sulphuric acid in the urine, and the process for its detec-
tion is the same as that for pyrocatechin.*

The crystals of hydrochinon belong to the rhombic system, and they
crystallise readily from their solution in toluol.

According to Baumann and Preusse,?6> when rapidly heated in an
open test-tube, hydrochinon forms violet fumes, which condense as an
indigo-blue sublimate, and in the application of this property we possess
a very sufficient test for its presence.

(f.) The Aromatic Oxy-Acids.—The aromatic oxy-acids which have
been proved to exist in the urine are paroxyphenyl-acetic acid, paroxy-
propionic (hydroparacumaric) acid,*6” paroxyphenyl-elycolic acid,3% and
oxyamygdalic acid,*°° to which must he added uroleucic (trioxyphenyl:
propionic) acid (Kirk, Wolkow, and Baumann *) and homogentisic
(dioxyphenyl-acetic) acid. In view of the significance which the re-
searches of Wolkow and Baumann have conferred upon these . latter
substances, there will be need to refer to them separately undér the
head of Alkaptonuria. i

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AROMATIC OXY-ACIDS—ALKAPTONURIA. 301

Detection of the Aromatic Oxy-Acids.—Twenty cc. of urine are treated
with hydrochloric acid, and heated for some time on the water-bath to
expel the volatile phenols. It is then allowed to cool, and repeatedly
extracted with ether. The ethereal extract is: shaken up with a weak
solution of carbonate of soda. The oxy-acids are taken up by the
latter, whilst the phenols present are retained by the ether. The
alkaline solution is now acidulated with sulphuric acid and extracted
with ether. The latter is allowed to evaporate, and the residue dis-
solved in water is submitted to Millon’s test (p. 258). A red. colora-
tion shows the presence of aromatic oxy-acids.

In a similar manner an approximate quantitative estimation of these
bodies may be effected.271

VII. Alkaptonuria.—Although the substances with which we have
to deal under this heading belong properly to the aromatic series, and
are oxy-acids, the special clinical importance which attaches to them
makes it convenient to adopt Baumann’s classification, and treat them
apart. By the term alkaptonuria is meant the condition in which the
uroleucic acid of A7zrk and the homogentisic acid of Wolkow and Bau-
mann occur in the urine. There is no doubt that the urine in certain
cases (see p. 300) contains these acids in addition to pyrocatechin.
Bedeker * gave to a substance resembling these, which he dis-
covered in the urine; the name of alkapton. A similar substance
was discovered by Hbstein and J. Miiller*"? very abundantly present
in a child’s urine, and Fiirbringer and Fleischer *"? have obtained
evidence of such in cases of phthisis. The urine has characters very
similar to those conferred upon it by the presence of pyrocatechin (see
p- 299). Baumann and Wolkow believe that the production of the
acids in question is due to an anomalous metabolic process of life-long
continuance, by which the tyrosin (paroxyphenylamidopropionic acid) of
the system is perverted, probably by the action of some definite micro-
organism. For the method of recognising homogentisic acid the reader
is referred to the very interesting treatise of Bawmann and Wolkow.?™
The condition of the urine known as alkaptonuria may be said to exist
when the urine answers the description given at p. 300, thus showing
that it contains a large amount of pyrocatechin.

VIII. Inosituria.—Inosite occurs in small quantity in the urine in
cases of diabetes insipidus and in albuminuria. For its detection it
must be separated from the urine. To this end Cooper-Lane’s ?"* method
is the best. According to Magneune,™ inosite is obtained as hexa-
hydrobenzol.

IX. Melanuria.—The urine of persons suffering from pigmented
tumours sometimes contains a substance to which the name of melanin
has been given, but of which the chemical constitution is not yet sufti-

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302 THE URINE.

ciently established. It is sometimes held in solution, and more rarely
suspended in the form of small granules. It very seldom happens that
the fluid has a dark colour when passed, but it generally blackens in-
tensely when submitted to oxidising agents (sulphuric and hydrochloric
acids and ferric chloride). This fact would point to the conclusion
that the body in question is not melanin, but a chromogen—melanogen
—analogous to that which precedes the formation of urobilin. Such
urine turns dark on exposure to air. The pigment can be partially
separated from the urine by means of acetate of lead or perchloride of
iron. It is insoluble in cold alcohol, ether, and acetic and dilute mineral
acids. It is soluble in boiling concentrated mineral acids, in boiling
lactic and acetic acids, in concentrated solutions of caustic potash and
soda, and in ammonia. It contains iron, sulphur, and nitrogen. The
most sensitive test for the presence of melanin is the addition of bromine
water (Zeller),°° which causes the urine to deposit a yellow precipitate,
which gradually blackens.

More recent experience has shown that a fairly concentrated solution
of perchloride of iron serves well to detect its presence (v. Jaksch,
Pollak)?" A few drops of this reagent will cause the fluid to turn
grey ; and if more be added, a precipitate of phosphates falls, carrying
the colouring-matter with it, and again dissolves with an excess of the
solution.

Sodium nitro-prusside with caustic potash and acetic acid gives a deep
blue colour (Thormdhlen),?"8 which depends probably on the formation
of soluble and insoluble Berlin-blues (v. Jassch).

In connection with this subject the reader may refer to the opinion of Kruken-
berg 7 and Salkowski*®° (see p. 316), that in Weyl’s test for kreatinin boiling with
acetic acid similarly produces Berlin-blue.

The latter, however, cannot always be obtained by the action of the
nitro-prusside salt on melanin isolated from the urine, and the reaction
must ot be regarded as a test for melanuria, or only when other tests
(and especially that with perchloride of iron) have shown the presence
of melanin or melanogen. Moreover, the Berlin-blue reaction can be
obtained in urine which is free from melanin. Thus, in the case of
children suffering from prolonged constipation, it has been had at the
same time that the fluid was rich in acetone or diacetic acid and
indoxyl-sulphuric acid (v. Jaksch), and in a case of diabetes by Dresch-
feld,**! when its nature and the presence of the substances just named
were probably established. It would appear, therefore, that in these
conditions also a body is present which gives Berlin-blue with nitro-
prusside compounds. Possibly this is indol. Investigations with that
body derived from a preparation of picrate of indol gave the same result

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MELANURIA—ACETONURIA. 303

(v. Jaksch), The practical significance of this condition is greatly
limited by the fact that the urine may contain a large quantity of
melanin in wasting diseases, whilst that derived from individuals
suffering from melanotic cancer or sarcoma may be entirely free from
it. Senator **? has recently confirmed this view by a series of clinical
observations. Nevertheless, as an adjunct in diagnosis, the tests given
are of undoubted utility.?8

X. Acetonuria.—Normal urine contains traces of acetone (phy-
stological acetonuria, v. Jaksch **+), but this body occurs in excessive
proportion under certain morbid conditions (pathological acetonuria).
In association with diseases we may distinguish (1) febrile acetonuria ;
(2) diabetic acetonuria; (3) acetonuria accompanying certain forms of
cancer independently of inanition; (4) acetonuria of starvation; (5)
the production of acetone in psychoses; (6) acetonuria as an expres-
sion of auto-intoxication ; (7) acetonuria in derangements of digestion.**°
The commonest of these forms is febrile acetonuria. It does not belong
especially to any~particular fever.**° In connection with diabetes the
appearance of acetone in the urine indicates an advanced stage of the
disease, but does not otherwise affect the prognosis. Of greater con-
sequence 38’ are those cases in which much acetone is found in connection
with grave symptoms of cerebral irritation, less often of depression.
Acetonuria existing alone (auto-intoxication with acetone) tends to a
favourable termination (v. Jaksch).°88 Finally, it should be noticed that
recent researches have shown that an abundance of nitrogenous food
tends to the production of acetonuria.

Detection of Acetone.—A rough test for acetone is that of Legal. A
quantity of the urine (several cc.) is treated with a few drops of a
freshly-made and somewhat concentrated solution of sodium nitro-
prusside, and with a moderately strong solution of caustic soda or
potash. The fluid develops a red colour, which rapidly disappears, and
if acetone be present, gives place to purple or violet-red on the addition
of a little acetic acid. In the absence of acetone the purple-red tint
does not form on the addition of acetic acid.

For purposes of greater accuracy it is necessary to distil the urine, and
to apply to the distillate the tests presently to be described. To do this,
one-half to one litre of the urine may be taken, and a little phosphoric
acid may be placed with it in the retort to prevent the evolution of
gases. Of the distillate 10-30 cc. may be taken and tested with—

(1.) Lieben’s Test.—To several cc. a few drops of iodo-potassic iodide
solution and caustic potash are added. Jf more than a trace of acetone
be present, an abundant precipitate of iodoform crystals is deposited.
This test is very reliable, and will serve even for the detection of traces
of acetone.

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304 THE URINE.

(2.) Reynolds’ Test.—This depends on the property which acetone
possesses of promoting the solution of recently-formed mercuric oxide.
It is conducted as follows :—The yellow precipitate (mercuric oxide)
obtained by the reaction of mercuric chloride with an alcoholic solution
of caustic potash is added to the distillate from the urine, which is then
filtered, and to the clear filtrate sulphide of ammonium is cautiously
added. If acetone be present, some of the mercuric oxide will have dis-
solved and a black ring (sulphide of mercury) forms at the plane of
contact with the ammonium sulphide.

Legal’s Test, already described, may be applied also to the urinary
distillate, but it is less to be relied upon than the others, since parakresol,
which also passes over in distillation, exhibits a similar reaction.**?

Quantitative Estimation of Acetone.—This may be effected by v.
Jaksch’s method as modified by Nenchi.3°° Very good results are
obtained by the process first devised for scientific purposes by Mes-
singer,**! applied to the investigation of urine by Huppert,**? and rendered
available for clinical use by v. Engel and Devoto.**? It is conducted
thus: The urine is first examined by Legal’s test, and, according to the
result, 20-50, or at most roo cc., are placed in a flask and made up to
100 ce. with distilled water and 2 cc. of a 50 per cent. acetic acid solu-
tion. This flask is connected by a long glass tube with the cooler, in
front of which is a distillation flask, and in front of that a bullet
apparatus filled with urine. Distillation is carried on until 7;ths of the
original volume of the fluid have passed over. A portion of the residue is
submitted to Lieben’s test, and if this shows the presence of acetone, the
result must be rejected and the process commenced over again after the
addition of more distilled water. To the distillate 1 cc. of dilute (1 in 8)
sulphuric acid is added and the mixture distilled. The second distillate is
poured into a flask of 1 litre capacity fitted with a polished glass stopper,
and, also, for distillation purposes, with a doubly perforated cork, and
having a bullet apparatus full of water in front of it. When distilla-
tion is completed, the flask is closed with its glass stopper and the fluid
carefully titrated according to Huppert’s directions with {5th normal
iodide solution and ‘5th normal hyposulphite solution. These solutions
being used, 1 cc. of the iodo-solution corresponds to 0.967 mgrm. of
acetone. The researches which v. Engel has pursued by this method
have greatly extended our previous knowledge concerning the secretion
of acetone, and they have also established the facts on a secure basis.

XI. Diaceturia.—By the term diaceturia is meant the condition
in which diacetic acid appears in the urine. It is always pathological,?%
and occurs in diabetes (Gerhardt) and fevers (v. Jaksch, Deichnuiller,
Sedfert), and also idiopathically as a form of auto-intoxication. It is
most common in children as a concomitant of fever,**> and is then gene-

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DIACETURIA—LIPACIDURIA. 305

rally devoid of serious significance, but in adults it is a symptom of
grave import. In febrile and diabetic states the development of diacet-
uria commonly forebodes the advent of coma.

Urine holding diacetic acid is always rich in acetone, and in presence
of perchloride of iron develops a Bordeaux-red. This property, how-
ever, does not serve to distinguish the presence of the former body,
since it belongs equally to a number of substances which are apt to
exist in the urine.#% For its detection the following process may be
adopted.

To the urine a fairly-concentrated solution of perchloride of iron is
cautiously added, and if a phosphatic precipitate forms, this is removed
by filtration and more of the perchloride of iron solution supplied. If
the Bordeaux-red colour appears, one portion of the urine is boiled,
whilst another is treated with sulphuric acid and extracted with ether.
If now the urine which has been boiled shows little or no change, whilst
the perchloride of iron reaction in the ethereal extract is no longer
evident after 24-48 hours; and if at the same time (on testing the
urine directly and its distillate) it is found to be rich in acetone, the
condition may be inferred to be that of diaceturia.

XII. Lipaciduria.—By this term is meant the condition in which
volatile fatty acids are found in the urine (v. Jaksch,?" v. Rokitanshy °°).
These bodies: occur there in traces normally, especially formic, acetic,
and butyric acids ; and they may be derived from healthy urine in con-
siderable quantity by the use of oxidising agents.?"® They are also a
product of alkaline fermentation.

As a manifestation of disease, on the other hand, they are often
present in quantity in the simple urine. Thus, in the urine of fevers,
of hepatic diseases affecting the proper structure of the liver, and in
diabetes, formic, acetic, butyric, and recently also propionic acid have
been detected.

There is no special diagnostic significance attaching to this condi-
tion; in general, it is determined by the same causes which produce
febrile acetonuria.

For the detection of fatty acids the urine is distilled with phosphoric
acid, and the distillate carefully neutralised with carbonate of soda,
evaporated to dryness on the water-bath, the residue extracted with
boiling alcohol, filtered, again evaporated, dissolved in water, and the
solution submitted to the tests mentioned at p. 201. The principal
reactions are shortly recapitulated here.

1. A little of the urine is treated with sulphuric acid and alcohol. An odour of
acetic zether indicates the presence of acetic acid.
2. To another portion perchloride of iron is added. The specimen assumes a
red tint, which disappears on boiling, and a rusty precipitate remains.
U
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306 THE URINE.

3. The addition of nitrate of silver causes a white precipitate, which rapidly
blackens if formic acid be present.
With reference to the appearance in the urine of other organic acids, see

PP. 336, 337:

XIII. Lipuria.—Small quantities of fat are often seen in the urine of
chronic nephritis with a very fatty state of the kidney (see pp. 229, 247),
in phosphorus-poisoning,*! and diabetes mellitus. Fat in large propor-
tion was found by Hbstein 4°? in a remarkable case of pyonephrosis.

Fat is also a common manifestatation in chyluria, and it is a physio-
logical constituent of the urine of pregnant women.

Its presence is sufficiently apparent. The urine containing it is
usually very turbid, and clears when shaken up with ether. The fatty
particles may be separated by means of Stenbeck’s sedimentator (see p. 218).
It is apt also to hold globules of fat, which are easily recognisable by their
powerful refracting properties ; and it is not uncommon for this substance
to occur in the form of needles, as it does in the feces (p. 196), especially
in connection with chronic nephritis and septiceemia.?™

XIV. Chyluria.—By this term is meant the simultaneous appearance
at intervals of fat and albumin in the urine, apart from the manifesta-
tion of other morbid constituents, such as casts, renal epithelium, We.
The sediment, however, usually contains red and white blood-corpuscles
in small numbers. ;

The urine under these circumstances tends to form coagula of fibrin
on standing, and occasionally it gelatinises throughout. Hitherto
chyluria has been met with almost exclusively in the tropics, and in
persons who have lived there for a long time, and it has been shown
by Waucherer and Lewis (p. 58) to depend upon the invasion of the
urinary tract by Filaria sanguinis hominis. The embryo of this parasite
is generally to be found in the urine; and the chemical investigations
of Grim 44 make it appear that in the majority of cases the abnormal
condition of the urine is due to unnatural communications between the
lymphatics and urinary passages affected by filaria. The subject, how-
ever, needs further elucidation, inasmuch as chyluria is occasionally
observed in persons who have never lived in the tropics.4%

Langgaard *° has detected large quantities of cholesterin in the urine
in a ease of chyluria.

XV. Oxaluria.—It has been stated already that oxalic acid occurs
in healthy urine, but it is subject to very great increase in certain
morbid states, and the condition is then called oxaluria.

Oxalates may remain in solution in the urine, and it is important to
be able to determine absolutely the quantity of oxalic acid present as
such. This can be done by a modification of Neubauer’s method (Fiir-
bringer and Czapek).4

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OXALURIA—ESTIMATION OF OXALIC ACID. 307

Quantitative Estimation of Oxalic Acid, Neubauer’s Method.**—The
urine passed within twenty-four hours is accurately measured, and treated
first with calcium chloride and ammonia, then with acetic acid until it
has a slightly acid reaction, and afterwards a little alcoholic solution of
thymol is added to restrain the development of micro-organisms. The
mixture is allowed to stand for some time, when the white precipitate
which forms is separated on a filter, and (together with the latter) is
placed in hydrochloric acid, gently heated, the fluid filtered off, and the
filter washed with water until it has no longer an acid reaction. The
collected filtrate is evaporated to a small bulk in a capsule on the
water-bath, then placed in a strong glass cylinder, and the capsule in
which it was evaporated is washed with dilute hydrochloric acid and
water, the washings being added to the fluid in the cylinder. Ammonia
solution is then poured upon the surface of the latter, and the whole is
tinted with a few drops of tincture of litmus. The mixture is allowed
to stand for a considerable time. The precipitate which has formed
is obtained on a so-called ash-free filter, the ash constituent of which
has previously been accurately ascertained, and the oxalate (of lime)
which adheres to the walls of the cylinder is removed on a glass rod
guarded with an india-rubber ring, and added to the precipitate on the
filter. The latter is next freed from chlorine by washing with water,
and rinsed with acetic acid. The filter is then dried, and ignited
on a platinum crucible, which is heated to a constant weight in the
blow-pipe flame. By this means oxalate of lime is changed into lime.
Now as 56 parts of lime correspond to go parts of oxalic acid, the
quantity of the former obtained when multiplied by 1.6071 shows the
quantity of oxalic acid in the urine taken.*”°

In healthy urine the amount of oxalic acid passed in twenty-four
hours is 0.02 grm. (Liirbringer).

An excess of oxalic acid is occasionally found in diabetes, and espe-
cially when the proportion of sugar diminishes (vicarious oxaluria).*!

Oxaluria is also known as an affection swt generis (oxalic acid diathesis,
idiopathic oxaluria), (Cantand).4™

It must be admitted that our knowledge of this condition as a clini-
cal symptom is very defective, but the author’s experience induces him
to adopt the conclusion of J. Beybie*? and Cantani, that there are
certain complaints, characterised by pains in the back and loins and
attended with rapid emaciation, in which the only objective symptom
besides is an excessive elimination of oxalic acid with the urine.
Neidert *? observed in a complaint with nervous symptoms more than
0.5 grm. of oxalic acid per litre of wine; and Kisch ‘+ found in nine
cases of extreme lipomatosis only one in which there was an increase of
0.040 grm. in the litre.

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308 THE URINE.

XVI. Cystinuria.—This is a condition of rare occurrence, and
clinically of little importance, since it is only accidentally by the forma-
tion of calculi that it gives rise to trouble. It is usually chronic in its
course. It should be mentioned that Hbstein #9 has found cystin con-
currently with albumin in the urine of acute articular rheumatism
(comp. p. 243).

The researches of Stadthagen, Brieger, v. Udransky, and Baumann #6
have shown that such urines also contain diamines, and in particular
putrescin, cadaverin, and a diamin which is isomeric with the latter.
These bodies occur at the same time in the feces of such patients
(p. 205), while both urine and feces of healthy persons are free from
them. It is possible that they originate in a special form of intestinal
infection, are absorbed from the alimentary canal, and eliminated to-
gether with cystin in the urine.

XVII. The Urie Acid Diathesis.—Although the deposition of a
very abundant sediment of urates in the urine does not warrant the
inference that uric acid is excreted in excess, there is no doubt that there
are certain processes in the system, the chief evidence of which is such
an increase in the elimination of uric acid, and it is important to possess
the means of estimating this condition.

Many methods have been devised for this purpose, as those of Fokker
and Salkowski, and in recent years by Haycraft,#" Czapek, and JW.
Camerer.18 That of Fokker,“ as modified by Salkowshi,?° depends
upon the comparative insolubility of urate of ammonia. Those of £.
Salhowshi *?! and of E. Ludwig #2 are based on the estimation of the
almost insoluble double silver salt of uric acid.

Ludwig's process has the advantage that it can be carried out con-
pletely in twelve to fourteen hours, and it is further serviceable as a
qualitative test for uric acid in the other secretions, and in the blood
as well as in the urine.

For its application the following solutions are needed :—

1. An Ammoniacal Silver Solution.—This is prepared by dissolving
26 grms. nitrate of silver in distilled water, and adding ammonia until
the brown precipitate thrown down at first is again dissolved. The
fluid is made up to a litre, placed in a well-stoppered flask, and pro-
tected from the light.

u. A Magnesia Mixture.—A hundred grms. of crystallised magnesium
chloride are dissolved in water, and a large excess of ammonia added,
and then ammonium chloride until the precipitate (magnesium hydrate)
is entirely dissolved. The fluid so derived should be tolerably clear.
It is made up to a litre and placed in a stoppered bottle till required.

il. Solution of Sodium or Potassium Sulphide.—Fifteen grms. of
caustic potash or ro erms. of caustic soda are dissolved in.a litre of

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ESTIMATION OF URIC ACID. 309

water, and one-half of the fluid is saturated with sulphuretted hydro-
gen, after which the other half is added to it. The potash or soda
used must be entirely free from nitrates and nitrites, and to this end
it is well to use caustic soda prepared from metallic sodium.

A hundred or 200 ce. of urine are measured off in a dry glass cylinder
and carefully poured into a beaker of 200-300 cc.
capacity. Ten or 20 ce. (according as 100 or 200 ce. 2
of urine has been taken) each of solutions i. and ii.
are mixed together in a measure-glass, and ammonia a)
is slowly added until the precipitate is dissolved. The
clear fluid is then poured from the cylinder in which
the urine was measured and added to the latter in the
beaker-glass, and the mixture stirred for some time.
The precipitate which forms is allowed to stand for
half an hour or an hour, after which it is placed with
the fluid on a filter, and two or three, times the quan-
tity of water, to which a little ammonia has been added,
is supplied. For this purpose Ludwig employs an aspi-
rator, but it is not necessary, since filtration proceeds
rapidly enough without it.

The precipitate and the filter together are placed in
the beaker, and ro or 20 ec. (according to the quantity
of urine taken) of solution iii., diluted with an equal
quantity of water, is heated to boiling in a flask, added to
the precipitate in the beaker, and the mixture frequently
stirred, 40 ec. of boiling water supplied, and the mix-
ture heated over a flame until it begins to boil. It is
repeatedly stirred while allowed to cool, and passed
through a filter, which is afterwards washed two or
three times with boiling water and collected in a large
capsule. The filtrate is treated with hydrochloric acid
until it has a feebly acid reaction, and is then concen-
trated on the water-bath to a volume of 10-15 ce.
Uric acid begins to separate at this point in crystals,
which are often of a beautiful white colour.

 

 

The best plan is to continue evaporating, without regard to
the quantity of fluid remaining, until the point is reached
when uric acid begins to separate from the hot solution.

 

The fluid is now allowed to cool for an hour, when F!. 132.—Ludwig’s
f 7 . Filter (actual size).

the separation of uric acid will be completed. The
precipitate is brought upon a Ludwig's filter arranged with glass-wool.

This instrument consists of a glass tube about 14 em. long and 2 em.

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310 THE URINE.

in diameter in its upper point, growing rapidly narrower below, and
constricted to little more than capillary calibre at a point 4 cm. from
its lower end (fig. 132). The lower end is cut off obliquely. The tube
is packed from the point of constriction upwards as far as the beginning
of the broad part with glass-wool, which is best introduced by means of
a slender glass rod, and in such a manner that the obstruction is densest
below, and less compact as it proceeds upwards.

To facilitate this, the glass-wool with which the funnel is to be blocked may be
previously moistened with a little ether.

The author prefers asbestos to glass-wool. It answers the purpose well
and does not irritate the skin.

The upper end of the instrument is closed with a ground-glass
stopper.

When arranged with glass-wool as described, the whole is dried at 110°
C., allowed to cool, and weighed.

The filter is fixed in a suitable support, and the fluid with the uric
acid precipitate is placed upon it. The filtrate is used to wash out
the uric acid from the capsule in which it was formed, and this is
repeated until no trace of the uric acid is left in the latter, the whole
having been placed on the filter. Finally, the latter is washed repeatedly
with a little water, and best by means of an aspirator, after which the
filter. and precipitate together are dried at 100° C. They are then
allowed to cool, and small quantities of bisulphide of carbon added in
three portions of about 2 or 3 cc., the bisulphide of carbon removed by
the addition of ether, and the filter dried at 110° C. until it attains
a constant weight. The difference between this weight and that of the
filter as previously ascertained expresses the amount of uric acid in the
quantity of urine taken. The dried filter containing the uric acid may
be conveniently weighed by placing it in the scale upon a little triangular
glass support of known weight and hollowed into a suitable angle, in
which the thin end of the filter rests. The disturbing oscillation of the
latter in the scale-pan may be prevented in this way.

It may be remarked that Ludwig’s process has the advantage over the
other methods referred to that by its means several observations can be
made in one day.

A healthy adult excretes o.2-1.0 grm. of uric acid with the urine in
twenty-four hours. The quantity is increased in health by an abundant
animal diet, and pathologically in fever, leukemia (Fleischer and Penzoldt,
Rohland and Schurz), pernicious anemia, and in diseases of the heart
and lungs with obstructed respiration.4#4 A series of observations which
the author has made with the Salhowshi-Ludwig method in a case of
diabetes gave the quantity of uric acid excreted as between 0.9400 and

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URIC ACID—UREA. 311

1.4814 grm., and this quantity was not diminished by the administration
of alkalis.

The excretion of uric acid is diminished in a number of chronic
affections, such as nephritis, gout (after the acute paroxysm), diabetes,
and chronic arthritis. A diminution was also found by v. Bamberger #
in a case of progressive muscular atrophy. Salkowski and Spilker °°
have observed that taking alkali internally is followed by a fall in the
amount of uric acid in the urine ; and in sick children the use of alcohol
has a similar effect (v. Jaksch).427

Finally, we sometimes meet with a condition in which, with emacia-
tion and certain subjective symptoms, as hypochondriasis, &c., is asso-
ciated an enormous increase in the elimination of uric acid as the only
objective manifestation, and such cases undoubtedly constitute what is
called the uric acid diathesis. 48

XVIII. Urea.—By far the greater part of the nitrogen taken in with
the food is eliminated as urea. It must not, however, be forgotten that
there are in the urine other nitrogenous compounds, such as uric and
hippuric acids, amido- and other acids, and ammonia salts, but the great
bulk of nitrogenous waste is removed in the form of urea. Of this
body 32-40 grms. are daily excreted by a healthy man, but its quantity
varies considerably under physiological, and still more under morbid
conditions.

Amongst diseases, fever and diabetes are attended with increased
elimination of urea. [Prout has described a morbid condition which
he calls azoturta, and which he ascribes to an excessive formation of
urea. | On the other hand, this is diminished in chronic affections
accompanied by malnutrition and in diseases involving the proper struc-
ture of the liver, where it is elaborated (Schréder).

The quantity of urea excreted is lessened by taking alcohol in the case of
children (v. Jaksch).“° On the other hand, there is an increased excretion of
urea in children during the febrile period of lobar pneumonia (v. Jaksch).4}

Bernabei #3" has observed a diminished excretion (hypoazoturia) as a constant
occurrence in chronic alcoholism.

Variations in the output of urea are an expression of changes in nitro-
genous metabolism generally, and as such possess the highest clinical
interest. It would be well if we could measure the quantity of that
body in the urine at any given time, but the processes by which this
can be done are not available for clinical purposes.

An approximate estimate of the quantity of urea excreted in the
course of twenty-four hours may, however, be effected by Hiifner’s #°
method. In this the urea is decomposed by means of alkaline hypo-
bromites, and the nitrogen given off as a gas is collected, whilst the
carbonic acid combines with caustic soda present. The apparatus

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312 THE URINE.

required is represented in the accompanying figure. It consists of a
cylinder of stout glass of 100 cc. contents (B), expanding at its middle,
and connected below by means of a binder and tight-fitting tap with a
smaller tube (A), also of glass, which holds about 5 cc. It is important
that the capacity of the latter, which serves to receive the urine,
together with that of the perforation in the tap, shall be accurately

 

 

Fic. 133.—Hiifner’s Apparatus for Estimation of Urea.

known. To this end the apparatus is carefully washed with water,
rinsed out with alcohol, and dried. The tap is opened, and mercury
poured into the lower vessel so as to overflow into the upper one. ‘The
tap is now closed, the overflow of mercury above it poured off, and the
contents of a removed and weighed in a vessel whose own weight is
known. The result divided by the sp. gr. of mercury (13.59) gives the

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ESTIMATION OF UREA. 313

cubie contents of the tube a. This must be verified by repeating the
process, and if the capacity ascertained should vary each time, the mean
must be taken. It should be calculated to three places of decimals.

In cases where the method of weighing cannot be conveniently carried out,
the capacity of the vessel destined to hold the urine may be ascertained with
great accuracy thus :—This portion of the apparatus is filled with a watery solu-
tion of some aniline dye which is not taken up by chloroform, the apparatus
washed out with chloroform and the tinted water together with the chloroform,
in which little or none of the dye dissolves, is placed in an accurately graduated
burette. The chloroform is allowed to settle and the quantity of the aniline
fluid in the burette is read off. This process should be gone through at least
three times, and the mean is taken of the ascertained results, which, however,
usually agree well.

The remaining parts of the apparatus are a glass bowl (c¢) fitting by a
caoutchoue stopper in its bottom upon the upper extremity of B, and a
glass tube 30-40 cm. in length, 2 cm. wide, and accurately graduated in
0.2 em. units of capacity.

A rough estimate of the proportion of urea is formed either by previous
analysis, or, better, by inference from the sp. gr. of the urine, and the
‘latter diluted in such a way that a specimen shall contain not more than
1 per cent. urea. The vessel a, whose capacity is accurately known, is
filled by means of a long funnel with urine, the well-greased tap closed,
and the bulbous vessel B washed well with water, so as to remove all
trace of urine from its surface. Another tube, about half a metre long,
may be interposed between the upper end of B and the bowl (c), with
the object of prolonging the contact between the column of urine and
the hypobromite, and so securing its complete decomposition.

A fresh solution of hypobromite is then made in the following man-
ner :—1o0o germs. of caustic soda are dissolved in 250 cc. of water, the
mixture allowed to cool, and 25 cc. of bromine added. The solution
must be freshly prepared for use, withheld from the light, and kept in
a cool place. The concentrated fluid so prepared gives better results
than the more diluted reagent formerly in use (Pfliiger and Schench).434
With the vessel c in position, B is entirely filled with the above solution,
and a concentrated solution of common salt is poured into c to a depth
of rem. The graduated tube p is likewise filled with the common salt
solution, care being taken to exclude air-bubbles, and inverted in c over
the tapering extremity of B, which projects into the solution of common
salt contained in that vessel. It is fixed by a clamp in this position.
Distilled water may be substituted for the salt solution.

The tap is now opened. The relatively heavier hypobromite solution
sinks, and as it does so a rapid evolution of gas takes place and lasts
for 15-20 minutes. The nitrogen formed collects in the graduated tube,
and when it has ceased to be given off, the latter is closed with the

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314 THE URINE.

thumb and, still inverted, placed in a cylinder of pure water. It is
there held with a clamp, and is depressed as much as possible for a
space of fifteen minutes. After that it is raised with wooden forceps
until the fluid in the tube and that in the cylinder stand at the same
level. The volume of contained gas is then read off, and the barometric
pressure and temperature are noted at the same time. i
From the volume of nitrogen obtained in this manner the weight in
‘orammes of the urea taken may be deduced by the following formula :—

v(b-')

ae 354-3. 760 (1 + 0.00363t)

Where
G = weight of urea in grammes.
as
t
) = barometric record.

volume of gas generated (in cc.).

temperature.

}’ = tension of water-vapour at temperature ¢.

The percentage of urea is expressed by the product of G x 100
divided by the volume of urine analysed. The number 354.3 is sub-
stituted in the equation for 372.7, since it has been found that from
t grm. of urea the total quantity of nitrogen, namely, 372.7 cc., is
never obtained in this way, and that the number chosen more aptly
represents the fact.

The value of 0’ will be found in Bunsen’s tables, from which the

following figures are extracted.“° They express in millimetres the
tension of water-vapour at the corresponding temperatures, which are
those most commonly existent :—

oC. . . 9.165\14°C. . . 11.908) 18°C. . . 15.357] 22°C. . . 19.659
u°C. . . 9792/15°C. . . 12.699 | 19°C. . . 16.346] 23°C. . . 20.888
WAP. 5 Mowat GSP Ch 5 5 eESAS || or, 5 6 Were ian, . . aaa
1 Cm eal LOZ 177 Chee 4 a2 aoe Caen lS: 405) 0251 Canes 550

To carry on-such investigations uninterruptedly at least two sets of
apparatus should be available. The researches of Pfiiger®° and his
pupils have shown that the results obtained are not entirely accurate,
but sufficiently approximate. The method has the advantage over
others presently to be described, that it can be carried out quickly.
Moreover, the object of a clinical investigation is less often to ascer-
tain the precise quantity of urea than to determine its variations at
different times, and this purpose the method admirably fulfils.
Huppert ®" has shown that by this process one can ascertain approxi-
mately the total amount of nitrogen excreted in the urine, provided
that the uncorrected number representing the amount of nitrogen, as
obtained by Hiifner’s method, be multiplied by 1.136. In the case of

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ESTIMATION OF UREA—KREATININ. 315

a febrile urine the factor is 1.18. Recently a number of other apparatus
of the same kind have been employed.#28 That of Lange seems specially
serviceable,*9

The quantitative estimation of urea may also be effected by Liebig’s
titration method, as modified by Pfitiger. It will be found described
at length in the systematic works of Huppert, Hoppe-Seyler, and Leube-
Salkowsht.° The method of Morner and Sjoqvist*“ is also a good one,
but the figures derived by it are a little too high.

To estimate exactly the total quantity of nitrogen obtainable from the
urinary products other methods are needed, as those of Will-Varrentrapp
and J. Kjedahl.“2 It is often desirable to determine the amount of
urea with reference to the total excretion of nitrogen, and this may be
done by the application separately of Morner’s and Kjedahl’s methods.

The qualitative tests for urea are described in the chapter on Blood
(p. 69). In connection with urine they possess but little practical
interest.

XIX. Kreatinin. —-In addition to the substances mentioned at
p- 321, human uwrine contains certain other-nitrogenous organie com-
pounds, by means of which nitrogen is also eliminated from the system.
Amonest these are betain, hypoxanthin (sarkin), xanthin, xanthokrea-
tinin, kreatin, and kreatinin. The occurrence of these substances is,
with the exception of the last, without clinical significance at present.
The interest attaching to the separation of kreatinin is of a very sub-
ordinate kind, and it will suffice to state a few facts concerning its
production, detection, and clinical import. For information about the
other substances named the reader may consult the books of reference
already mentioned.

The formation of kreatinin has been shown to be intimately associated
with the decomposition of ruscle-substance, and the quantity produced
is in direct relation to the amount of flesh-meat consumed as food,
and, under certain circumstances, to the muscle-waste within the body.
Under these circumstances muscle contains kreatin, which is changed
into kreatinin as it passes through the body.

This is to be borne in mind when a clinical inference is drawn from
the observation of an increase or diminution of the quantity of kreatinin
secreted. Hitherto such inferences as were possible have had but a
limited application to the purposes of diagnosis. They are insufficiently
based, and rest for the most part on the experience of individual cases.
According to Neubauer,#* the quantity excreted by a healthy man is
about 1 grm. According to Pouwchet,** it is 1 grm. in the case of the
male, 0.75 grm. in that of the female, while kreatinin is altogether
absent from the urine of sucklings. This point, however, is contested
by Gocco.”

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316 THE URINE.

An increase in the output of kreatinin has been observed in acute
diseases of all kinds while attended with fever, and in diabetes (Senator),
and a diminution in chronic nephritis and diabetes insipidus, in convales-
cence after acute diseases, in chlorosis, aneemia, tuberculosis, and maras-
mus,*" and as a consequence of insufficient feeding.45

Kreatinin is a base which forms highly characteristic compounds with
acids, such as phosphotungstic and phosphomolybdic, hydrochloric and
sulphuric, and with salts of the heavy metals.

Qualitative Vests—Kreatinin may be detected directly in the urine
by the methods of Weyl # and Jafé.#°

Weyl’s Test.—For the application of this test the urine should be
freed from acetone by distillation (p. 303). A freshly prepared and
very dilute solution of nitroprusside of soda and caustic potash is
added. If kreatinin be present, the fluid will take a beautiful red
colour (like that produced in Legal’s test for acetone), which soon dis-
appears, and does not return with the further addition of acetic acid.

Jagés Test.—A fairly concentrated solution of picric acid and a little
caustic potash are added to the urine. If the fluid be heated, the
presence of kreatinin will be shown by the appearance of a beautiful
red coloration. Acetone and grape-sugar yield a similar reaction.
Picrie acid with caustic potash alone gives a slight red colour.

Quantitative Estimation.—Kreatinin forms with zine chloride a double
salt of slight solubility, and this property is made the basis of the
quantitative method, which was first devised by Mewbauer #! and modi-
fied by Salkowshi.4°?

Two hundred ce. of urine are mixed with a little milk of lime until
the fluid has an alkaline reaction. This is to precipitate phosphoric
acid. A solution of calcium chloride is added until a precipitate ceases
to form. The fluid is allowed to stand for half an hour, after which
the precipitate is filtered off and repeatedly washed with water, and
the filtrate and washings (a¢idulated with a little sulphuric acid) are
evaporated on the water-bath to a syrupy consistence. To the residue
is added 50-100 cc. of 78 per cent. alcohol; the mixture is well stirred
and allowed to stand in the cold for several (6-8) hours; then it is
filtered, and to the filtrate (which, if alkaline, must be rendered acid
with acetie acid) 10-15 drops of an alcoholic solution of zinc chloride
are added. The latter is prepared by adding alcohol to a concentrated
solution of zine chloride until a density of 1.2 is attained. After the
lapse of two or three days the precipitate is brought upon a filter of
known weight, and the filtrate as it passes through is constantly
returned to wash the vessel which contained the precipitate. When
all the precipitate has been brought upon the filter in this way, it is
washed with go per cent. alcohol until the filtrate shows but slight

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ESTIMATION OF KREATININ—PTOMAINES. 317

opalescence with silver nitrate; after which it is dried to a constant
weight at roo° C. One grm. kreatinin-zinc-chloride corresponds to
0.6242 grim. kreatinin. The amount of kreatinin in the quantity of
urine taken may therefore be known by multiplying the quantity of
kreatinin-zine-chloride obtained by 0.6242.4%

Kreatin, which is closely related to kreatinin, does not occur as such in the
urine, but it is readily formed from kreatinin in alkaline fluids. Hence it follows

that alkaline urine should not be employed clinically for the quantitative estima-
tion of kreatinin.

In addition to kreatinin a number of basic substances have recently
been isolated from urine by precipitation with phosphotungstic acid
(Thudichum **), such as urochrome, urotheobromin, omichol, and reducin.
The physiological action of these substances is not yet known.

Salomon * has proved that hypoxanthin is a normal constituent of
urine. Future researches will show in what relation it stands to cer-
tain diseases, or to the putrefaction bases presently to be described.4°6

XX. Ptomaines (Putrefaction Bases) in the Urine.—It would
appear from the investigations of Powchet 1°" that healthy urine contains
traces of certain toxic substances of an alkaloid character, and according
to the researches of Bouchard,#® Lépine, and Guerin,®® these bodies
are more abundant under morbid conditions. They were found by
A, Villiers *° as an invariable manifestation in measles, diphtheria, and
pneumonia ; and in the urine of cholera A. G. Pouchet #1 discovered an
alkaloid which was not identical with that observed by him in the feces
of the same disease (see p. 205). Feltz *°? found similar bodies in the
urine of cancer patients, and Lépine +? in that of pneumonia. Roges and
Gaume ** observed that the toxic property of the urine was lessened in
the febrile period of pneumonia (retention of potash salts ?). Bouchard *
discovered that human urine acted as a poison when injected within the
veins of animals (rabbits), and he referred the effects to various sub-
stances, among which were animal alkaloids. For the detection of the
urinary alkaloids the following method has been adopted by Tanret,
Bouchardat, and Cardier #8 ;—

To the urine which has been acidulated with acetic acid a solution of
the iodide of mercury and potassium is added. The precipitate, which
contains the alkaloids, is readily distinguished from those of other
substances, as albumin, mucin, and uric acid, obtained with the same
reagent, by its solubility in alcohol at a warm heat.

Ch. Bouchard rendered the urine alkaline with caustic soda, and
derived a poisonous body as an ethereal extract.

Pouchet fixed the alkaloid by combination with tannic acid, and
subsequently precipitated it with oxide of lead from alcoholic solution.

The methods adopted by the other observers mentioned above differed

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318 THE URINE.

much as to details. They will be found described at length in the
original communications. That of Brieger (p. 158) serves best for the
detection of animal alkaloids in the urine. In some cases, however, it
is important that the urine be previously concentrated in vacuo. Should
no result be obtained with this, Gautier’s 467 method may next be tried.
Finally, the Stas-Otto method may be applied to the same purpose.
(See p. 158.)

The diamines of the urine may be precipitated as benzoyl compounds,
and best by the action of benzoyl chloride and caustic potash. Bav-
mann and Udransky 8 succeeded in separating several basic derivatives,
amongst them cadaverin (pentamethylendiamine), putrescin (tetramethyl
diamine), and a small quantity of a third diamine, from the urine of a
patient with cystinuria and vesical catarrh (see p. 308). Normal urine
was found to be free from these bodies. The author has been for some
time engaged in observing the occurrence of similar poisonous bases in
the urine of health and disease, and he has found that normal urine and
that of some diseases, notably typhoid, pneumonia, leukemia, cystic
pancreas, and Weil’s disease,#°? hold such only in very small quantity.
He would venture to make some suggestions for the benefit of those who
are engaged with similar researches. In the first place, it would be well
to follow the example of Brieger, Baumann, and v. Udransky, and with-
hold the name of alkaloids from the bodies (diamines) alluded to, which
are derived from the system under morbid conditions, because all that
have been recognised as yet are simply diamines, and because none yet
examined exhibit the characteristic property of alkaloids, namely, the
pyridin radicle. Next, it would be desirable to discriminate between
the physiological bases of the urine (kreatinin, reducin, &c.), which belong
normally to the fluid, and those which are associated only with certain
diseased states. It is not intended to imply that the physiological bases
cannot under any circumstances give rise to the symptoms of disease
or of poisoning. (See below.) Experience is not wanting to make it
seem in the highest degree probable that the retention, and still more
the increased formation, of such physiological products in certain dis-
eases may induce symptoms of the gravest character, and greatly imperil
the life of the patient.

Again, it would appear that in certain acute affections specific sub-
stances of a toxic character, not observable in normal urine, may be
excreted with that fluid. Undoubtedly the matter is somewhat obscure.
The author’s views may be stated as follows. It is possible to dis-
tinguish :—

(1.) Clinical (morbid) symptoms depending upon the retention of
the physiological bases (and under this heading would come uremia)
and certain of the symptoms of obstruction (retention-toxicosis).

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ANIMAL ALKALOIDS—FERMENTS. 319

(2.) Clinical symptoms, referable to the presence of basic products,
which are formed in the system (blood, &c.) in disease and eliminated
with the urine (noso-toxicosis). [Bruschettini*™ has conveyed tetanus
to animals (rats and rabbits) by injecting the urine of patients suffering
from that disease—a fact which would make it appear that the poison
of tetanus is eliminated by the urine. ]

(3-) Clinical symptoms which are caused by the formation of toxic
basic substances from morbid matter, such as pathological fluids lodged
in certain parts of the system. Such bases are absorbed, and then give
rise to manifestations of severe poisoning. Under this heading would

 

come the collective symptoms of ammoniemia (see p. 77), and others
which follow the absorption of gangrenous pus (auto-toxicosis). The
latter are sometimes characterised by the presence of guanin,*? and it
is probable that the formation of toxalbumins has much to do with
them. These may readily be detected by the methods of Brieger and
Fraenkel.+?

(4.) Clinical symptoms, and consequently morbid types, induced by
the action of toxic bases taken into the system with the food, such as
the poison of sausages and cheese, p. 158 (exogenic toxicosis).

These distinctions are based partly upon clinical observation and
partly upon experiments on animals. They will serve as a scheme for
the further elucidation of this very important subject.

If we have dwelt at some length on the result of observations which
are not yet completed, we have done so because we believe that the
careful investigation of the urine in this direction will throw light
upon the nature of some diseases which are at present not sufficiently
understood,

XXI. The Ferments of the Urine.—The appearance in the
urine of a body resembling pepsin was long ago established by ».
Briicke.** Sahli, Leo, Gehrig, Stadelmann, and Patella + made similar
experiments, and confirmed the presence of pepsin in the urine. It has
been asserted that trypsin is also an occasional constituent of that fluid,
though some observers, Leo, Stadelmann, and Grriitzner,*® have failed to
find it.

With reference to the pepsin ferment of the urine, clinical interest
attaches to it from the fact that it is absent in typhoid and carcinoma
of the stomach,*”" and according to some observers (Mya, Belfanti #78) in
nephritis.

For the detection of pepsin Sahl’s method (adapted from those of
y. Wittich and Griitzner) may be employed. It is founded upon the
property which, as v. Wittich originally observed, blood fibrin possesses
of readily absorbing that body from solutions. To this end a little
pure fibrin is placed in the urine and allowed to rest there several

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320 THE URINE.

hours. It is then removed, placed in dilute hydrochloric acid (.2 per
cent.), and the mixture kept at a temperature of 30-4o° C. Any
pepsin present is precipitated on the fibrin, and the latter is slowly
digested in the acid fluid.

Diastatic ferment also is said by Hovoltschiner and Rosenberg to occur
in urine.479 The researches of Breusing *° and observations made by
the author tend to show that the ferment in question is in many cases
not diastase, but an amylolytic substance. At the same time it must be
stated that the author has frequently determined the presence of diastase
by the usual.methods, both in health and disease. So, too, Leo #8! has
found diastase both in healthy and in morbid urine.

Milk-curdling ferment is occasionally present in the urine (Hovolt-
schiner,*®? Boas,*83 Helwes).

As to whether the urine contains a ferment capable of decomposing
urea into carbonic acid and ammonia, opinions differ. On the one
hand, Musculus+8+ believes that he has isolated such a ferment, but
Leube*® has sought for it in vain in urine which was actually under-
going ammoniacal fermentation. 4°

B. Inorganic Substances.—The inorganic constituents of the
urine are for the most part salts of hydrochloric, sulphuric, and phos-
phoric acids, to which must be added carbonates, silicates, nitrates and
nitrites, and sulphuretted hydrogen.

1. Chlorides.—The chlorides of sodium, potassium, ammonium, and
magnesium are found in the urine, and of these we are chiefly con-
cerned with chloride of sodium. Of this salt 10-15 grms. are voided
by a healthy man in twenty-four hours; but its quantity is greatly
influenced, even in disease, by the supply of salt taken as food.

It is increased by an abundant diet and as a consequence of condi-’'
tions which determine the retention of chlorides within the system ;
and diminished in fevers, and notably in croupous pneumonia.487 The
elimination of chloride of sodium has also been observed to be less in
cases of chronic nephritis, and sometimes in certain diseases of the
stomach (Gluzinsh?).4§

Detection of Chlorides.—The urine is treated with nitric acid, and a
solution of nitrate of silver added. A caseous precipitate soluble in
ammonia, insoluble in nitric acid, shows the presence of chlorides.

Quantitative Estimation of Chlorides.—Mohr’s method is to treat the
urine with chromate of potash, and gradually add nitrate of silver,
when all the chlorine combines with the silver to form silver chloride,
and the occurrence of a-red precipitate (chromate of silver) marks
the end of the reaction. The details of the process will be found in
works on urinary chemistry. Saliowshi’s ° modification of Volhard’s 49
method is to be preferred.

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ESTIMATION OF CHLORIDES. 321

When to a solution of nitrate of silver acidulated with nitric acid is
added some of a solution of sulpho-cyanide of ammonium, a curdy
white precipitate forms, and this, like chloride of silver, is insoluble in
nitric acid, soluble in ammonia. If the fluid also contains a ferric salt,
a blood-red colour (ferrocyanide) forms at the moment when the last
of the silver is precipitated. If now the sulpho-cyanide of ammonium
solution is of a known degree of concentration, it is possible to deter-
mine the quantity of silver present by noting the point at which the
red coloration takes place. To apply this principle for gauging chlorides
in solution to the fluid containing them, a silver solution of a definite
degree of concentration is added in excess, and that portion of it which
is not precipitated as chloride of silver is measured in the manner indi-
cated above.

The following solutions are needed in the process :—

1. Pure nitric acid of 1.2 sp. gy.

u. Concentrated solution of double sulphate of ‘ron and ammonia free
From chlorine. It is necessary that this be free from chlorine, and if
not already so, it must be purified by crystallisation.

ili. Nitrate of silver solution of definite strength. The chemically pure
crystalline salt is dissolved in water in the proportion of 29.075 grms.
to the litre. <A cc. of this solution corresponds to o.o1r grm. of chloride
of sodium. {

iv. Sulpho-cyanide of ammonium solution. This should be of such a
constitution 4° that 25 cc. shall correspond to 10 ce. of the silver solu-
tion. For this purpose 6.5—7 grms. of sulpho-cyanide of ammonium may
be dissolved in water, and more water added to 4oo ce. <A burette is
filled with the solution so prepared.

Titration with the sulpho-cyanide of ammonium solution is effected
thus:—Ten ce. of the silver solution (ii.) is placed in a flask and
diluted with water to roo cc. ; 4 ec. of nitric acid (i.) are next added,
and after that 5 cc. of the double sulphate of iron and ammonia (ii.).
The mixture is well shaken up, and sulpho-cyanide of ammoniun: solu-
tion from the burette is carefully added until a slight but permanent red
coloration appears. The process is repeated several times, the quantity
of the reagent employed in each case being noted and the mean taken.

Tn accordance with the result obtained, the sulpho-cyanide of ammo-
nium solution is diluted to such a point that 25 cc. shall correspond to
ro ce. of the silver solution., Thus, if the terminal reaction (red colour)
occurs after the addition of 22 cc., the following formula may be ap-
plied to determine the volume to which a litre of the solution must be
diluted :—22 :25=1000:a, and x=1136.3. To the litre of sulpho-
eyanide of ammonium, therefore, 136.3 cc. of water must be added in
order that 25 cc. shall correspond to ro ce. of the silver solution (iii.).

x
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322 THE URINE.

The remainder of the process is as follows:—Ten cc. of urine are
measured out with a pipette and placed in a graduated flask of 100 cc.
capacity ; 50 cc. of water are added, and then successively 4 cc. of the
nitric acid (i.) and 15 cc. of the silver solution (i1.). The flask is closed
with a glass stopper and well shaken up until a precipitate ceases to
form and the fluid tends to clear; the flask is then filled to the mark
too ; its contents passed through a dry paper filter and received into a
dried measure cylinder or a flask holding 80 cc. The 80 ce. of fluid
thus obtained are poured into a larger flask of some 250 cc. capacity ;
5 cc. of the double sulphate of iron and ammonia (ii.) are added, and
the sulpho-cyanide of ammonium solution (iv.), prepared in the manner
already indicated, is gradually supplied from a burette, until the terminal
reaction is shown on shaking the fluid by a faint but abiding red colora-
tion. The quantity of the sulpho-cyanide of ammonium used to effect
this is now read off. Experience has shown that 15 cc. of the silver
solution is more than sufficient to precipitate all the chlorine from urine
strongly acidulated with nitric acid, and that an excess of silver nitrate
remains in solution. The excess of silver may be measured volumetri-
cally by means of the sulpho-cyanide of ammonium solution, and the
quantity of chlorine in the urine calculated from the difference.

The quantity of chloride of sodium in grammes in one litre of the
urine may be ascertained by the following formula :—

« = (37.5-¢R] x
Where

x =the quantity of NaCl in a litre of urine in grms.

=the quantity of sulpho-cyanide solution used in ce.

The formula is derived thus :

 

Ten cc. of the silver solution correspond to 25 ce. of the sulpho-
cyanide of ammonium, and consequently 15 cc. of the former to 37.5 cc.
of the latter. For 100 ce. of the fluid examined, therefore, are needed
37-5 cc. of the sulpho-cyanide solution less by five-fourths of the total
quantity of the latter employed. Since 80 cc. of the titration fluid,
i.e.. sulpho-cyanide, was used, consequently too ce., being the volume’
of the original fluid, will require five-fourths of the quantity read off
(on the burette).

Now 25 cc. of the sulpho-cyanide correspond to ro ce. of the silver
solution, and therefore 1 cc. of the former to 0.4 cc. of the latter.

One cc. silver solution corresponds to 0.01 grm. sodium chloride ;
0.4 ce. silver solution corresponds to 0.004 grm. sodium chloride.

Therefore, to obtain the quantity of chloride in the volume (10 cc.)
of urine tested, the expression [37.5 — ¢ R] must be multiplied by 0.004,
or by 0.4 = 745 for 1000 ce. (litre) of the urine.

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SULPHATES— PHOSPHATES. 323

2. Sulphates.—Sulphuric acid is present in the wine both as
simple (preformed) sulphuric acid and as ether-sulphuric (compound
sulphuric) acid (see p. 294). The combinations of the latter acid have
been already spoken of. Further, the urine contains sulphur as sulpho-
eyanides,#! hypo-sulphites (thio-sulphates 4°), and sulphuretted hydrogen
(see also p. 327).

The total quantity of sulphuric acid excreted in twenty-four hours by
a healthy adult under ordinary conditions of diet is about 2 grms., of
which 0.1 grm. is in the form of ether-sulphuric acid compounds.

Sodium, potassium, magnesium, and calcium sulphates are found in
the urine (see pp. 240, 249). But little clinical significance attaches
to a general increase or diminution in the output of sulphuric acid in
disease. Of far greater import are changes of the relative quantities
of simple and of ether-sulphuric acids (see p. 294).

Thus a urine rich in indigo compounds contains little of the pre-
formed sulphuric acid, and in carbolic acid poisoning this may entirely
disappear,

Detection of Simple Sulphurie Acid.—The urine is filtered if turbid,
acidified with acetic acid, and solution of chloride of barium added.
A fine precipitate, barium sulphate, forms. This reaction never fails
with the nortial fluid.

Estimation of Simple Sulphuric Acid.—This may be effected by
determining first the total quantity of sulphuric acid present, and then
that of ether-sulphuric acid, according to the methods indicated at
p- 297. The difference will be the quantity of free sulphuric acid
sought.

Estimation of the Total Quantity of Sulphur.—Where it is of conse-
quence to ascertain the total quantity of sulphur in the urine, the best
plan is to evaporate the alkaline urine, either the whole or a known
proportion of it, on the water-bath, then to fuse the incinerated residue
with saltpetre and soda (Heffter**) to extract the fused mass with
boiling water, and to proceed further as directed in the process for
determining the total quantity of sulphuric acid on p. 298. The extract
is treated with barium chloride, and the sulphur estimated as barium
sulphate.

3. Phosphates.—The phosphoric acid of the urine is combined
partly with sodium, potassium, and ammonium, and partly with hme
and magnesia. Being a tribasic acid, it forms three classes of salts—
acid, neutral, and basic. Of these, the acid phosphates of alkalis and
alkaline earths and the neutral and basic phosphates of the alkalis are
soluble in the urinary fluid. The neutral phosphates of the alkaline
earths are but little soluble therein, and their basic phosphates still

less so.

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324 THE URINE.

Upon this fact depends the deposition of phosphatic sediment when the urine
is boiled. The acid and neutral phosphates of the alkaline earths are changed in
the process into the insoluble basic salts. The phosphorus salts occur partly in
solution and partly as a crystalline deposit (see pp. 242, 247).

Two to three grms. of phosphoric acid is excreted in twenty-four hours.

According to Lennmaim,* the amount is the same, in proportion. to
the body weight, in children as in adults.

It appears, especially from the researches of French authors,* that
in certain morbid states the phosphatic constituent undergoes notable
increase, and that consequently a condition of phosphaturia, analogous
to that of oxaluria, may properly be spoken of; and further, that this
condition may take the place of glycosuria in diabetes. The subject,
however, is still under discussion. A diminished elimination of phos-
phates was observed by Stokvis4 in arthritis, and v. Jahsch, unlike
other observers, has: found that in some, though not all cases of lobar
pheumonia amongst children, the quantity of phosphoric acid eliminated
during the continuance of fever was increased as compared with the non-
febrile period.497 Lennmalm 8 has studied this subject in connection
with children.

A phosphatic sediment does not imply phosphaturia.*”” The diagnosis
of this condition can be safely based only upon the quantitative estima-
tion of phosphoric acid, and this is effected best by Newbauer’s °” method
of titration with a solution of uranium oxide (see below).

Detection of Phosphates.—The urine is treated with caustic potash
and cheated. The phosphates are precipitated as earthy phosphates.
By the addition of ammonia they may be precipitated without heat.

To detect the presence of phosphoric acid in combination. with alkalis,
the urine is treated with ammonia and filtered, and to the filtrate an
ammoniacal solution of magnesia (a mixture of sulphates of magnesia
and ammonia) is added, whereby the phosphates. are precipitated as
triple phosphate.

Another method is to treat the filtrate (vide supra) with acetic acid,
when the further addition of uranium solution yields a’ yellowish-white
precipitate.

The same filtrate with perchloride of iron solution gives a white
precipitate, which becomes yellow on the addition of more of the per-
chloride.

Estimation of Phosphoric Acid.—-To urine which contains the phos-
phates as acid phosphates, uranium acetate or nitrate is added in solution
until an excess of the reagent first becomes appreciable. If the nitrate
be used, free nitric acid forms, and causes a part of the precipitated
uranium phosphates to redissolve. To prevent this, in practice a little
sodium acetate is added to the urine before titration with uranium

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ESTIMATION OF PHOSPHATES. 325

nitrate. As an indicator a little tincture of cochineal is employed.
This yields a green precipitate in presence of a uranium salt in excess.
[Instead of the cochineal fluid a solution of potassium ferrocyanide (1 in
10) may be used. This reagent deposits a deep brown precipitate with
a mere trace of a uranium salt. |

This test, however, is less sensitive in presence of acetate of soda than
in simple watery solutions. Hence it is necessary to use a definite
quantity of the salt, and to take care that the proportion is maintained
in preparing the titration fluid.

The solutions required for the process are :—

1. Solution of Acetate of Soda.—A hundred grms. of acetate of soda
are dissolved in 800 cc. of water, 100 cc. of a 30 per cent. solution of
acetic acid added, and the mixture made up to a litre. Five ce. are
employed with 50 cc. of urine.

ii. Cochineal Tincture. A cold infusion is made of a few grms. of
cochineal in a quarter of a litre of,a.fluid composed of 3-4 parts of water
with 1 of alcohol, and the solution filtered for use.

il. Solution of Uranium Oxide.—Ahout 20.3 grms. of commercial
uranium oxide purified and well dried is dissolved in pure acetic acid,
or in the smallest possible quantity of nitric acid, and the preparation
made up to a litre. Of the mixture 1 cc. indicates 5 mgrms. of P,O,.

iv. A Solution containing a Definite Quantity of Phosphoric Actd.—
Fifty ce. should contain precisely 0.1 grm. P,O;. The preparation is
made by dissolving 10.085 grms. of neutral phosphate of soda in a litre
of water. The commercial salt should be crystallised from solution to
obtain it free from chlorine, so that no precipitate forms with nitrate
of silver and nitric acid. The crystals are then placed on paper in a
funnel, the neck of which is stopped with glass wool and allowed to
dry there until the mother liquid is no longer found to adhere to them.
A known weight is then taken and rubbed up in a mortar and a portion
of the powder submitted to a gentle heat in a platinum crucible, and
finally incinerated. 266 grms. of sodium-pyrophosphate (Na,P,O-) corre-
spond to 716 grms. Na,HPO, + 12H,O. Consequently that quantity
of the dried erystals which, when incinerated, yields 266 grms. corre-
sponds to 716 grms. of pure phosphate of soda.

Titration Process.—Fifty cc. of the phosphoric acid solution (iv.) are
measured into a flask, 5 cc. of the solution of acetate of soda (i.) and a
few drops of the cochineal tincture are added, the mixture boiled, and
the uranium solution (ii1.) gradually supplied until the mixture becomes
slightly but permanently green on shaking. In the process a high
temperature should be maintained, to promote the formation of uranium
phosphates. [When ferrocyanide of potassium is used as the indicator,
the addition of the uranium solution is suspended when a precipitate

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326 THE URINE.

ceases to form. The fluid is again heated and a drop is tested by adding
to it a drop of ferrocyanide in a porcelain capsule. The further supply
of uranium solution is regulated by the earliest appearance of a brown
colour in the specimens successively tested. ]

The uranium solution is now diluted, according to the quantity found
to be necessary, as above, in such proportion that 20 ce, shall just
suffice for the titration of 50 cc. of the phosphoric acid solution.

Now, 50 ce. of the phosphoric acid solution represent o.1 grm. P,O,,
and consequently 20 cc. of the diluted uranium solution also correspond
to o.1 grm. P,O,.

The titration process is repeated with the urine in precisely the same
manner as before: 50 cc. are taken, 5 cc. acetate of soda and a little
cochineal added, and the mixture heated and the terminal reaction
sought.

Every cubic centimetre of the uranium oxide solution employed in
titration represents 5 mgrms. P,O,;. Hence the phosphoric acid con-
tained in 50 ce. of urine may be calculated by multiplying the number
of cubic centimetres of uranium oxide solution used by 0.005. The
result is the quantity of phosphoric acid in grammes contained in 50 cc.
of urine. It is advisable in each case to make two such investigations
and to take the mean of their results. i

4. Carbonates.—The carbonates of lime, magnesia, and ammonia
are sometimes present in the urine. The latter salt, however, is found
in large quantity only as a result of alkaline decomposition. Heintz
has proved that ammonium salts may be detected in every specimen of
urine, whether decomposed or not. They may be shown best by the
addition of milk of lime in a test-tube, when ammonia is given off, and
if a piece of red litmus paper be moistened and held over the mouth of
the test-tube, it becomes blue. Ammonium carbonate in considerable
quantity occurs only in decomposing alkaline urine (see p. 216). The
method described on p. 141 will serve for the quantitative estimation
of ammonia.

Test.—The presence of carbonates in the urine is shown by the evolu-
tion of a colourless gas on the addition of acid, and this gas will render
haryta water turbid.°0?

5. Nitrates and Nitrites.— Nitrates and nitrites occur in the urine
(Schénbein).°°% Nitric acid is thought to be derived from the water and
food ingested (Rohmann).5%

Nitrites occur only in decomposing urine, and are derived from the
reduction of nitrates in urinary fermentation.

Tests for Nitiites -—

(a.) Solution of iodide of starch paste in presence of dilute sulphuric
acid (see p. 83).

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SULPHURETTED HYDROGEN. Bey,

(v.) Metadiamido-benzol is coloured a deep yellow by nitrites.

Amongst the inorganic constituents of the urine there remain to be
mentioned silicic acid and salts of iron, which are sparingly repre-
sented.

Striimpell °° found hyposulphurous acid in a case of typhoid. The
urine became turbid from the separation of sulphur on the addition of
hydrochloric acid. The plan adopted by Salkowshi and Presch °° is to
distil the urine with hydrochloric acid, when a deposit of sulphur takes
place in the upper part of the condensing tube. If sulphur be present
in small quantity, this has the appearance of a faint blue exhalation. It
should be mentioned further that urine contains traces of silicic-acid
(Pfeiffer °°") and iron salts.

6. Sulphuretted Hydrogen (Hydrothionuria).—Sulphuretted
hydrogen is rarely present in the urine, but it can always be obtained
from it by heating with mineral acids.°% It has been ascertained
(Betz, Senator, Ottavio Stefano) that when retained in the system
in considerable quantity it may produce toxic effects (auto-intoxication).
In the great majority of cases, according to Miiller*!° and others,
hydrothionuria is due to a sulphuretted hydrogen fermentation of the
urine, caused by the action of certain micro-organisms.

This gas is sometimes derived from the alimentary canal, and its
presence depends upon an abnormal communication between the urinary
passages and the gut. etz further maintains that it may pass by
endosmosis from the intestine into the urine; and it would appear also
that the gas may be absorbed from the intestine by the blood, and so
find its way into the urine. This, according to Miiller, is a rare event,
and happens only when the quantity of sulphuretted hydrogen is so
great as to give rise to symptoms of general poisoning.

Tests.—The urine, which should be ‘acid, is placed in a flask, which
is closed by a tight-fitting cork. From the latter depends a strip of
blotting-paper ‘soaked in sugar of lead and caustic soda. If sulphuretted
hydrogen be present, the paper turns black.

Fy. Miiller recommends the following plan :—A current of air is passed
through the urine, and directed by means of a fine-pointed glass tube
upon a strip of blotting-paper soaked in alkaline sugar of lead solu-
tion. If sulphuretted hydrogen be present, the paper is blackened.
Emil Fischer's *"! test is also applicable to the urine. Some particles of
p-amido-dimethylanilin are added to a few ce. of water, and a little con-
centrated sulphuric acid and one or two drops of a yellow solution of
perchloride of iron supplied. The reagent is poured on the surface of
the urine to be tested, when, if sulphuretted hydrogen be present, a blue
ring (methylene-blue) forms at the place of contact of the two fluids.
This ring often takes some minutes to develop.

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328 THE URINE.

7. Peroxide of Hydrogen.—This body was first observed in the
urine by Schdnbein.*!2 Its presence there has no pathological import.

Test.
in presence of sulphate of iron solution.°! Tetra-paper (see p. 134)
immersed in the fluid will show the presence of ozone by taking a blue
colour.

8. Gases of the Urine.—The urine contains a small proportion of
gases, which may be withdrawn from it by the air-pump. They are
chiefly carbonic acid, oxygen, and nitrogen.*!4

 

Dilute solution of indigo is bleached by peroxide of hydrogen

IV. CHARACTERS OF THE URINE IN DISEASE.

I. The Urine in Febrile States.—In fever the urine is diminished
in quantity, acid, deeply coloured, and of high sp. gr. On standing, it
often deposits an abundant sediment of urates. Microscopically it
exhibits a profusion of crystals of uric acid and urates, and a few
hyaline casts, with scattered leucocytes, renal epithelium, or fungi on
their surface. It commonly contains a small quantity of albumin
(febrile albuminuria) or acetone in variable proportion. Diacetic acid
may. be present when the disease is of an acute infectious character, or
when its subject is a child. In the first case it betokens great danger ;
not so in the latter.

The presence of peptone (p. 264), with or without serum-albumin and in con-
junction with the clinical symptoms of a puerperal or hematogenic origin,
indicates the formation and absorption of pus within the system.

According to Ehrlich,” it is characteristic of the urine in typhoid,
measles, and acute tuberculosis to yield a deep-red colour with diazo-
benzol-sulphonic acid. Authorities differ much as to the diagnostic value
of this reaction, On the one hand, the opinion of Eiilich is supported
by #. B. Goldschmidt,>'© while Penzoldt®™ and Petri *'8 dissent from it.
Ehrlich obtains the reaction, not with dia-benzol-sulphonic acid itself,
but with sulphanilic acid. Fifty cc. hydrochloric acid are made up to
1ooo ce. with water and sulphanilice acid added to saturation. To 200
ce. of the mixture 5 cc. of a 4 per cent. solution of sodium nitrite are
added, and the resulting fluid is added to the urine in equal parts.
Ehilich*®™ has recently recommended that five to six times the volume
of absolute alcohol should be added to the fluid to be tested, and the
reagent, prepared as above, then added drop by drop to the filtrate.
Normal urine gives a yellow colour, while the urine of fever patients,
&e., turns scarlet.°° The author’s experience would induce him fo dis-
claim for this test any clinical importance whatever, and he would especially
enjoin the necessity of avoiding inferences based upon the appearance of

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THE URINE IN DISEASE. 329

the reaction indicated. He believes that the colour when obtained is
always due to the presence of acetone, and he prefers to regard the pro-
cess rather as an uncertain indication of that body than as a test for
anything else.°21

It will be seen from this brief statement that a careful analysis of the
urine will serve to make evident the details of acute processes earlier
and more readily than the methods formerly at our disposal. Other
lines of investigation are appropriate to certain acute affections ; thus,
for instance, in pneumonia the presence of chlorides will be sought.

II. The Urine in Disorders of the Circulation (Congestion).
—Under such conditions the urine in its physical characters closely
resembles that of fever. It is diminished in quantity, of acid reaction,
and high sp. gr. (1.025-1.035). It commonly deposits urates.

Chemically it may be distinguished from fever urine hy—

(1.) The absence of acetone and diacetic acid.

(2.) The presence of albumin in greater quantity.

Microscopically, and especially when the congestion is chronic, the
urine exhibits some leucocytes and altered red blood-corpuscles, often
also hyaline casts and cylindrical aggregations of urates (see p. 224,
fig. 94), waxy and a few granular casts and renal epithelium. Such
constituents indicate secondary changes in the kidney of a chronic
inflammatory character.

[The Urine of Phthisis.—Hale-White**? has pointed out that the urine of
phthisis exhibits two peculiarities. Such urine remains acid for a very long
time, occasionally for several months, and contains few bacilli, but a large pro-
portion of yeast-like organisms. The persistence of acidity is probably due to
a form of acid fermentation. ‘The urine, when kept for a long time, turns very
dark in colour, some specimens becoming quite black. The cause of this change
is not known.]

III. The Urine in Diseases of the Urinary Organs.

1. Renal Affections. .

(a.) Acute Nephritis.—In this disease the urine is at first diminished
in quantity—s5o0o0-800 ce. or less being passed in twenty-four hours—
of acid reaction, and high sp. gr. (1.015-1.025). The sp. gr. rarely
attains to so great a height as in the urine of congestion. It ranges in
colour from blood-red to that of a watery extract of meat, and the
presence of blood-pigment in considerable quantity may be determined
by Heller’s test or by spectroscopic examination. In the latter case, if
the urine be. fresh, the characteristic bands of methemoglobin may be
visible.

Chemical analysis shows large quantities of albumin.

Microscopical investigation of the sediment affords the clue to the con-
dition. It exhibits—

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339 THE URINE.

(1.) Red blood-corpuscles in variable proportion. These are for the
most part altered, and present the appearance of washed-out discs
(phantom corpuscles).

(2.) Some leucocytes. These are always less numerous than the
phantom cells just mentioned.

(3.) Epithelium. Chiefly small polyhedral uninuclear cells from the
urinary tubules, with a few others derived from the renal pelves and
bladder.

(4.) Casts. These are (a) formed of blood-corpuscles ; (4) formed of
leucocytes ; (¢) formed of renal epithelium; (@) hyaline, more or less
thickly beset with epithelial cells and red or white blood-corpuscles.

Such. are the microscopical constituents of the sediment at the
outset of an acute nephritis, as in the first and second days of the
nephritis of scarlatina and erysipelas. They alter their character as
the disease progresses, and after the lapse of a few days, and side by
side with those described, appear the metamorphosed casts, granular and
waxy, We.

When in the course of chronic nephritis an acute exacerbation takes
place, the urine possesses a similar character to that described above.
But, as before, the description applies with full force only to the earlier
period of the attack. If death from uremia or cedema of the lungs
does not ensue, the physical characters of the urine tend gradually to
return to those of health. It is more abundant, the contained blood
grows less, and then a light flesh-water tint alone declares the existence
of acute nephritis. Albuminuria becomes less marked, and finally ceases
with the approach of health. The other signs, recognisable only by
means of the microscope, disappear with, or shortly after, the cessation
of the albuminuria. It must be borne in mind that to justify the
diagnosis of nephritis the formed material of the urine must be present
in considerable quantity.

The occurrence of micro-organisms has been noticed at p. 235.

(v.) Chronic Nephritis.—The urine is normal in quantity, or some-
what lessened (1200-1500 ee. daily), acid, and of normal sp. gr. It
usually contains a very considerable proportion of albumin. Micro-
scopically the sediment is very variable in character, but renal epithelium
is never absent, and the cells are often fatty. There are metamorphosed
casts of different kinds, especially granular casts, and hyaline casts
covered with blood-corpuscles or renal epithelium (p. 226). These are
of special importance in diagnosis.

The occurrence of casts composed of fatty matter or pyeriendl with
fat-erystals indicates advanced fatty degeneration of the renal. tissue

(p. 229).

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CONTRACTED AND AMYLOID KIDNEY. 331

It occasionally happens that, with all the symptoms of chronic nephritis
present, no trace of casts or epithelium can be found in the urine. This occurs
most often in long-standing and very chronic cases. Schrwald**3 has called
attention to the occasional absence of casts from the urine of nephritis, and
believes that this is to be accounted for by their solution by pepsin (see p. 319) in
acid urine. To guard against this, he suggests that the urine should be allowed
to stand only for a short time and at a low temperature. To obtain the deposit
by means of the sedimentator would undoubtedly add an element. of certainty.
Glaser °** has shown that, as the result of moderate indulgence in alcohol, the
non-albuminous urine of healthy persons may contain abundance of leucocytes
and casts of all kinds. These he ascribes to irritation of the kidney by alcohol.
In conclusion, it may be stated that in rare cases of chronic nephritis the urine
is altogether normal.

(c.) Contracted Kidney.—The quantity of urine is very greatly in-
creased—4oo0o to 5000 ce. being passed in the twenty-four hours. Its
reaction is acid and sp. gr. low (1.008-1.012 and less). In this respect,
however, exceptions are not uncommon. The author has met with
cases in which the quantity of the excretion was diminished and the sp.
gr. proportionally increased. It is pale in colour, and contains but little
albumin, sometimes only a mere trace. The sediment is usually scanty,
and, when examined with the microscope, exhibits generally but a few
hyaline and some granular casts

It is to be observed that even those cases in which only a trace of albumin is
to be found (small red kidney of &ibbert) often run a particularly unfavourable
course.

(¢.) Amyloid Kidney.—In this condition the urine presents charac-
ters which are for the most part similar to those of contracted kidney,
that is to say, it is increased (though sometimes normal) in quantity, of
acid reaction, and low sp. gr. As a rule, however, it contains more
albumin.

Microscopical examination of the sediment shows hyaline casts in
comparative abundance and some epithelium. The microscopical ap-
pearances, however, are subject to much variety, and the author has
observed cases which were hardly to be distinguished from those of
chronic nephritis. The amyloid reaction (iodo-potassic-iodide and sul-
phuric acid, &c.) with the casts cannot be depended upon, since, on the
one hand, it is often obtained when the post-mortem appearances show
no amyloid degeneration of the kidneys, and, on the other, it is absent
in many cases where the symptoms (enlarged spleen and liver, &c.) point
to this condition.

(e.) Ureemia.—The urine in cases where the symptoms of uremia
supervene is always rich in albumin, and microscopically resembles
that of nephritis. It is scanty in a degree that sometimes amounts to
anuria, and even when greatly reduced in quantity, we often find that

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332 THE URINE.

its sp. gr. is still below the healthy standard. Again, the quantity
excreted may remain unaltered, but the sp. gr. in such cases is always
greatly reduced.

When the urine is of this character, it would seem to hold poisonous
bases in smaller quantity than ordinarily.52°

What has been said here applies only to typical forms of renal disease. The
appearances are modified according to the various anatomical perversions of the
kidney structure upon which they depend.

Investigations which the author has made as to the character of the
urine of children suffering from nephritis show that the important con-
stituents of the excretion, urea, uric acid, sulphuric and phosphoric
acid, are constantly diminished in quantity. In adults, according to
Miinzer, the urea is less, and the total elimination of nitrogen is always
reduced.5*6

2. Pyelitis Caleulosa.—The urine passed during the paroxysms
of this affection is diminished in quantity, contains mucin in abundance,
blood and pus in variable proportions, and concrete masses of uric acid
or urates. After the paroxysms the urine is passed in great abundance.
It is then pale in colour and of low sp. gr., and exhibits probably a
flocculent precipitate of mucin. Persistent polyuria is common. When,
as commonly happens, the condition is complicated with catarrh of the
ureter and bladder, a more or less abundant purulent sediment forms
independently of the attack.

According to J. Fischi,°*" the urine at the commencement of this
disease always contains casts, both hyaline and granular, and this
authority regards their presence as of great importance in the differ-
ential diagnosis of pyelitis and cystitis. In addition, there occur plugs
of cylindrical form composed of conglomerated white blood-corpuseles.
These are probably derived from the renal pelves, and indicate an exten-
sion of the processes to the kidney proper, or pyelonephritis. When
the latter. condition is established by the appearances of pyelitis, then
the presence of nephritis, and granular casts, renal epithelium, &c., may
be observed.

In a case which was under the author's care, investigation of the urine dis-
closed a remarkable appearance. ‘The patient was a woman with renal calculus
causing pain, The urine held abundance of carbonate and sulphate of calcium
and triple-phosphate, and in it were long spiral bodies of large size, which
macroscopically, microscopically, and chemically exactly resembled Curschmann’s
spirals. There was no pus. ‘he condition was probably an affection of the
ureter analogous to enteritis membranacea, and it might be appropriately called
ureteritis membranacea. These membranous bodies continued to be discharged
for some days.

8. Cystitis.—In uncomplicated cystitis the urine is generally pale,

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CYSTITIS—TUBERCULOSIS. 333

of normal sp. gr., and has an acid reaction, unless when alkaline fermen-
tation takes place within the bladder. In the latter case it is turbid,
and deposits on standing a more or less abundant deposit of fat-laden
and swollen leucocytes and triple-phosphate crystals. Microscopically,
moreover, pus cells and epithelium of various forms are to be seen.
Amongst the latter, certain cells from the deeper layers of the mucous
lining, provided with one or two finger-shaped processes, are especially
noticeable (see p. 219). In connection with ichorous or hemorrhagic
cystitis, red blood-corpuscles and pigment masses appear in the urine.
The complication of cystitis with an affection of the ureter cannot be
determined by chemical and microscopical investigation, but its presence
must be diagnosed from the existence of the other clinical symptoms.

Schnitder 8 has observed that the urine in cases of cystitis often
contains a bacillus, pure cultivations of which, when transferred to the
bladder of animals (rabbits), give rise to symptoms of the disease.°?

Similar indications may be produced by a purulent urethritis, and
confusion in this respect is to be guarded against.

The condition which has been designated as ammonizmia, and which depends
upon the absorption of ptomaines from the bladder, is often, but not always,
accompanied with cystitis. In this connection the urine, when freshly voided, is
undergoing alkaline fermentation (see p. 217).

4, Tuberculosis of the Urinary Organs.

(a.) Tubercular Ulceration. — Chemically and microscopically the
urine in this condition resembles that of cystitis or pyelitis. It is
pale, of normal sp. gr. and quantity, contains a variable proportion of
albumin, and an abundant sediment, which consists principally of
swollen and fat-laden ‘pus-cells. The diagnosis must rest chiefly upon
the recognition of tubercle-bacillus by the methods described in con-
nection. with the examination of the sputum (p. 104). In chronic
tubercular affections the micro-organism is to be seen in great abund-
ance in the urine, as in the specimen represented in fig. 108, and, as
in this case, it tends to cohere in groups shaped like the letter S (comp.
p- 236). The precise localisation of the affection must rest upon other
grounds.

(b.) Miliary Tuberculosis.—In this affection the urine is often un-
changed. It is apt, however, to contain blood at intervals, and may
be distinguished from nephritis by the absence of casts and renal epi-
thelium. Tubercle-bacilli are never to be found in considerable quantity
in the sediment.*

5. Calculus and Tumours of the Bladder.—These are to be
suspected when copious intermittent hemorrhages take place, and
when the blood which is passed with the urine separates from it and

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334 THE URINE.

is deposited in a thick layer at the bottom of the receiving vessel. The
subjective symptoms, pain, &c., are usually sufficiently distinctive (see
p- 250).

6. Catarrhal Urethritis.—The urine in catarrhal urethritis is
altogether unchanged, except that. the first flow contains pus. The
affection is rarely met with. Bockhart**! ascribes it to infection with
non-specific vaginal secretion.

7. Gonorrhzal Urethritis.—The appearances are the same as in
simple urethritis, but pus is usually very copious. It would appear
that in all cases, while the infection is recent, specific micro-organisms,
gonococci, are to be found. These were discovered by Weisser. They
are diminutive roll-shaped cocci, aggregated in large groups, which often
closely pack the exfoliated epithelium cells of the urethra and cover

 

Fic. 134.—Gonococci of Urethritis (eye-piece I1I., objective, oil-immersion y;, Zezss).

their surface (Weisser, Bumm, Bockhart).°*2 More recent experience
tended at first to lessen the clinical significance of these forms (v. Zeissi,
Hartdegen, Wendt),®*? since bodies altogether resembling gonococci
have been found to be present in the genital tract under the most dis-
similar conditions. The researches of Wertheim 4 in Schauta’s clinic,
however, have quite lately established their specific character beyond
any doubt. Aceording to Rous,°* the supposed gonorrheal microbe
may be distinguished from other forms by the fact that it does not stain
with Gram’s method. C. Schiitz’s®6 process is as follows :—The pre-
pared cover-glasses are placed in a semi-saturated solution of methylene-
blue holding 5 per cent. carbolic acid, and left in it for 5-10 minutes.
They are then removed and washed in distilled water, to which acetic acid
has been added in the proportion of five drops of the dilute acid to 20 ce.
of water. After this they are given the contrast-stain in a very dilute
solution of safranin. This method furnishes good specimens, but there

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URETHRITIS— HEPATIC DISEASE. 335

is no reason to prefer it to staining with carbol-fuchsin, by which the
specimens figured here were obtained. Fig. 134 represents gonorrheal
pus from a case of old infection ; fig. 135 shows gonococci from a pre-
paration of Dr. Kolisko, made with the pus two days after the infecting
coitus.®°7 The occurrence of gonococci threads and hyaline epithelium
occurring in the urinary sediment of this condition is worthy of notice.®**

IV. The Urine in Diseases of the Alimentary Canal.—
Diseases of the alimentary canal, for the most part, do not specially
affect the urine pathologically ; but in general it may be stated, that
where they are attended with increased albuminous decomposition
within the intestine, that fluid is apt to contain a large amount of indi-
can. Carcinoma of the stomach with ulceration is occasionally attested
by the appearance of peptone in considerable quantities (Matxner). In

@.” o©&

y ea?

 

No G oh ZX 5
@ w & @
— SO i
mm >

CO ; ag
So" @@ e

Fic, 135.—Gonococei (two days after infection).

chronic catarrh of the stomach, and especially in dyspepsia, the acidity
of the urine is apt to be much lessened.

V. The Urine in Hepatic Affections.—It may be stated in
general that in all diseases which seriously involve the proper struc-
ture of the liver, the excretion of urea is diminished, and even in certain
severe forms (acute yellow atrophy) entirely suppressed (Schultzen
and Riess).°°9 It is then to some extent represented by other nitro-
genous metabolites which appear in the urine as leucin and tyrosin *4°
(comp. p. 244), and together with these certain non-nitrogenous sub-
stances. Oxyamygdalic acid (Schultzen and Riess, Réhmann**), lactic
acid, and the volatile fatty acids are often eliminated, as in cancer and
syphilis affecting the liver (v. Jaksch).>#

Diseases which cause an obstruction to the flow of bile are attended
with the presence of bile-pigments in the urine (see p. 288).

In atrophic cirrhosis the latter is scanty, rich in urates, and almost

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336 THE URINE.

or entirely devoid of biliary colouring-matters, but often contains a
high percentage of urobilin. In hypertrophic cirrhosis it is often quite
normal in quantity, sometimes increased, and exhibits abundance of
bile-pigment.

The appearance of sugar and albumin in connection with disease of
the liver is too uncertain to be of service in diagnosis. According to
Kraus and Ludwig,°* the ingestion of carbohydrates (grape-sugar) when
the liver is diseased is attended by glycosuria. The knowledge of this
fact, however, is of little use since glycosuria belongs equally to other
conditions, as diabetes insipidus, cystic pancreas, &c. Indeed, the
chemical constitution of the urine in hepatic disease generally exhibits
much variety.°+#

VI. The Urine in Diabetes Mellitus. —In this disease the urine
is pale and clear, and in colour often inclines to green. Its quantity
is enormously increased, as much as 12-15 litres being passed in twenty-
four hours, sp. gr. high, ranging from 1.030-1.050. It is usually rich
in the indigo-forming substance, and invariably contains a greater or
less proportion of grape-sugar (p. 273). Towards the close of the
disease albumin in considerable quantity is apt to make its appearance
(Stokvis).°4° Exceptional cases of diabetes are met with in which the
quantity of urine is not increased, and its sp. gr. is even lowered. When
diabetes is complicated by acute disease, the excretion of sugar may
entirely cease, as has been pointed out by &. v. Engel in a contribution
from the author’s clinic.

The author has met with one case of diabetes mellitus, in the practice of
Professor Nothnagel, in which the urine contained much acetone, and showed a
sp. gr. of 1.003. It.was also found to hold more than 0.3 per cent. sugar in
solution.

Other substances that are occasionally to be found in the urine of
diabetes are acetone in large quantity, diacetic acid, and a number of
other organic acids, such as f-oxy-butyric acid,°#” fatty acids,48 We.
[The urea of diabetic urine is in excess of the normal—uric acid is un-
affected or diminished (Zaylor). Ammonia, according to Stadelmann,
is present in large quantity, but it is neutralised and the urine remains
acid in consequence of the $-oxy-butyric acid which it contains. ]

In view of the fact that B-oxy-butyrie acid occurs in the. urine of
diabetes, and of other conditions, as febrile states, some notice of the
method of detecting that body is called for. The following method by
Kiilz is the best.o4? The grape-sugar in the urine is fermented with
yeast, the fluid filtered, and the filtrate concentrated to a syrupy con-
sistence. The latter is mixed with its own bulk of concentrated
sulphuric acid, the mixture distilled, and the distillate collected in a

 

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DIABETES—AN MIA. Bae

test-glass. If 8-oxy-butyric acid be present, crystals of a-crotonic acid
separate on cooling from the contents of the test-glass, and may be
recognised by determination of their melting-point (72° C.). Should
no such crystals form in the process, the distillate is shaken up with
zther, and the crystals which deposit on evaporation of the ether are
tested to ascertain their melting-point.

[The researches of Stadelmann and others point to B-oxybutyric acid as the
toxic agent in diabetes. It yields diacetic acid on oxidation, and this breaks
up into CO, and acetone.]

Diabetic urine contains other carbo-hydrates, fruit-sugar,°®? dextrin,
&c. According to Kiilz,°°! casts occur at the commencement of diabetic
coma.

VII. The Urine in Diabetes Insipidus.—Marked polyuria is the
characteristic symptom. Sixteen to twenty litres may be passed in the
day. The urine is clear and almost colourless, of greatly reduced sp. gr.
(1.0001~-1.004). It contains neither albumin nor sugar, although it
sometimes yields a small proportion of indican and inosite.

VIII. The Urine in Anemia.—The fluid is pale, of low sp. gr., and
neutral or alkaline in reaction. [Though pale when passed it sometimes
turns a deep red colour on the addition of nitric acid (Zaylor). This
depends on the presence of a chromogen (see p. 214).] In the later
stages of a severe anemia albumin may be found, whilst at the same
time, except for a few hyaline casts, tissue elements are entirely absent
from the sediment (Bamberger’s hematogenic albuminuria).

[The urine of pernicious anemia is of low sp. gr. and very highly
coloured. It contains (1) pathological urobilin ; (2) granules of blood
pigment, microscopically ; (3) excess of iron. These characters are of

549

much importance in diagnosis (Hunter).5°2

According to Hunter, the elimination of iron by the urine, while diminished in
chlorosis, is greatly increased in pernicious anzemia. He estimates the daily out-
put as follows: In health, 5.6 mgrms. ; in chlorosis, 1.7 mgrm.; in pernicious
anemia, 32.2 mgrms. The same observer has found diamines in the urine of
this disease.>°3]

B55

In leukemia the elimination of uric acid is increased.*54 Pyrus 555 has
observed leucin, and lactic acid is also found in the urine.*5* The
urine is rich in nucleo-albumin,°*” but never contains peptone.

It will be convenient here to describe the method by which the lactic
acid may be detected.

Detection of Lactic Acid.The urine is evaporated on the water-bath
to the consistence of a syrup and extracted with alcohol. After the
alcohol is distilled off or evaporated, the residue is extracted with ether,
the ether distilled off, and the residue dissolved in water. To the

Y
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338 THE URINE.

solution a little basic acetate of lead is added. It is then filtered, the
filtrate treated with sulphuretted hydrogen, again filtered, and finally
digested on the water-hath. Lactic acid remains behind in the form of
a syrup. From this the zine salt may be obtained by the addition of
carbonate of zinc. It may be recognised by its microscopical appearance
(small prisms), or chemically by the proportion of water and of zine
respectively which result from its decomposition.

Colasanti and Moscatelli®® assert that sarcolactic acid appears in the urine
normally after great bodily exertion. AHcuss*° failed to detect lactic acid in the
urine either of health or in osteomalacia.

IX. The Urine of Toxie States.

1. Poisoning with Acids.—Poisoning with strong mineral acids—
nitric, sulphuric, and hydrochloric—is generally followed by the appear-
ance of blood and albumin in the urine. The symptoms, however, are
often very transient. Toxic nephritis may ensue, and this especially
when sulphuric acid was the poison. The urine is then scanty, of high
sp. gr. and acid reaction. Chemically and microscopically, it presents
the characters of that of acute nephritis (see p. 329). In every case of
poisoning with acids which the author has had an opportunity of observ-
ing, the urine possessed the property of dissolving cupric sulphate in
alkaline solution, and reducing it when subsequently boiled, whilst at the
same time the most sensitive tests besides gave no indication of sugar.

2. Poisoning with Alkalies.— After poisoning with caustic potash,
which may be taken as the type of this condition, the urine passed
during the first few hours contains albumin, invariably in severe cases,
but very often also when the symptoms are slight. Its chemical and
microscopical characters at the same time are not otherwise those of
nephritis. Its reaction is feebly acid, seldom neutral, very rarely
alkaline. It possesses the reducing property in a marked degree; while
no evidence of sugar can be obtained with the phenylhydrazin reaction
and other tests. Where the toxic agent has heen chlorate of potash,
acute nephritis is apt to follow. ‘The detection of this salt in the urine
may be effected by the method described at p. 152.

3. Poisoning with Metals and Metalloids.

(a.) Lead Salts.—In acute lead-poisoning, especially when attended
with colic, large quantities of albumin are often transitorily present in
the urine ; more frequently still a true renal albuminuria, due to secondary
nephritis, occurs. The presence of lead may be determined directly by
the method described in connection with the vomit (see p. 152).

(v.) Salts of Mercury.—The urine in mercurial poisoning, after the
lapse of a few hours, contains a large proportion of albumin, and very

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POISONING WITH METALS. 339

often blood. The symptoms of nephritis are usually sooner or later
developed. This is especially true of poisoning with corrosive sub-
‘imate.

Mercury may be detected in the same manner as in the vomit (p. 153),
or in the urine Firbringer’s process may be employed,* or, better still,
Ludwigs method.

Five hundred ce. of urine are acidified with hydrochloric acid (1-2 cc.) in a
beaker and heated to 50-60° C. Three grms. of granular zine or finely-divided
copper are then placed in the fluid, which is shaken up for half a minute. The
metal is then allowed to settle, the supernatant fluid poured off, and the sedi-
ment obtained upon a filter, where it is well washed with boiling water, and dried
at 60° C. The powdered metal is then placed in a tube of hard glass, of 8-10
mm. diameter, closed at one end, covered with a plug of asbestos, upon which
again is put a layer some 5-6 cc. deep of granular oxide of copper ; then another
asbestos plug, and, finally, another layer of granular zinc, which has been pre-
viously dried and well heated. When the tube is filled in this way, it is drawn
out to capillary calibre at a point some millimetres behind the last asbestos plug,
and a bulbous expansion is made at the end. ‘The cupric oxide is first heated to
a dull red, the layer of zinc to a lesser degree, and, finally, the powdered metal
containing mercury.

The mercury is deposited as a metallic powder in the capillary tube. The
latter is then broken off above the last of the asbestos rings by letting water drop
on it; a few particles of metallic iodine are placed in the first part of the
tube while still hot, and the other expanded end of the capillary is connected
with an aspirator (Béhm’s air-pump serves best). ‘The iodine vapour impinges
on the mercury, and mercuric iodide forms, and is easily distinguished by its
colour.*#4

Wolf and Nega*® have employed a modification of this process. Organic
matter is first removed by hydrochloric acid and chlorate of potash, and copper
as a thin foil is introduced to receive the metal (mercury) instead of granular
zinc or powdered copper. The method is said to be very satisfactory. That of
Al¢*66 is still more simple. Winternitz**? has devised a method for the quanti-
tative estimation of mercury in the urine.

Almén’s*®3 method is the following :—About 300 cc. of the urine to be tested
are taken, a little caustic soda and some sugar added, and the mixture boiled.
The phosphatic sediment which falls carries the mercury with it. When it has
entirely settled, the fluid is decanted off, the sediment dissolved in hydrochloric
acid, and a piece of fine copper or brass wire placed in the fluid, which is then
maintained at a moderate heat for an hour and a half. After this the wire is
removed, boiled in alkaline water, and dried with blotting-paper. It is then
placed in a glass tube of small calibre, which is broken a few millimetres in front
of the wire, fused at the end, and heated over a small flame. The mercury sub-
limes, and is deposited in small globules, which can be readily recognised with
the microscope. The reagents employed in the process should be previously
tested for such mercury as they may themselves contain (see p. 153).

(c.) Salts of Copper.—In poisoning with copper salts, the urine is
always reduced in quantity. It usually contains albumin, and very often
also blood. As to whether acute nephritis can originate in this way,
some doubt exists. Experiments on animals would seem to favour the

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340 THE URINE.

assumption. To detect the poison in the urine, the method described at
p- 154 will serve.

(d.) Arsenic.—In acute arsenical poisoning albumin and sometimes
blood in considerable quantities appear in the urine. In one case the
author has observed all the signs of acute nephritis. The urine pos-
sesses the reducing property, but sugar cannot otherwise be made evi-
dent. The effect on the urine of chronic arsenic-poisoning is but little
understood. Albuminuria would seem occasionally to occur in this
connection.

For the detection of arsenic, see chapter on the vomit (p. 154).

(e.) Phosphorus.—At the outset of a case of phosphorus-poisoning the
urine is not notably changed as to quantity or sp. gr. Later it contains
albumin, but not usually in considerable quantity, occasionally blood,
and very commonly casts of different kinds. The presence of peptone
has repeatedly been recorded (Gerhardt, Maixner, v. Jaksch). Biliary
acids and colouring-matters are also met with, and Schultzen and Riess
have detected sarcolactic acid. In a case which recently came under
his notice, the author obtained an appreciable quantity of fatty acids
from 300 ce. of the fluid. Tyrosin and leucin are rarely present, as is
the case in acute yellow atrophy ofthe liver. Fat has been found in
large quantities in the urine of phosphorus-poisoning.°® The elimina-
tion of urea has been reported as exceeding or falling short of the healthy
standard in different cases.

In a case of severe phosphorus-poisoning under the author’s care the output of
urea estimated as nitrogen was, on the first day (of twenty-four hours) after the
poisoning 5.6028 grms., on the second day 7.9946 grms., on the third day 16.0406
grms., and on the fourth day 10.2458 grms. The patient was at once submitted
to rigorous treatment, and ultimately recovered. It will be observed that the
accident was followed immediately by a diminished elimination of urea, which
again exhibited a notable increase. Observations by Dr. Miinzer, the author's
assistant, which will shortly be published, furnish valuable information on the
subject of metabolism in connection with phosphorus-poisoning. With his per-
mission, it may be stated here that the urine contains an enormous increase of
ammonia, side by side with a falling off in the quantity of urea and of the nitro-

genous excretion. Uric acid was normal. These results were obtained by the
investigation of two fatal cases.

4. Poisoning with Alkaloids.

(a.) Morphia.—In acute poisoning with morphia the urine is com-
monly found to contain sugar. In chronic morphinism, again, it has a
powerful reducing action, and sugar may sometimes be found with other
tests (see p. 273). [The reducing property depends upon the presence of
glycuronic acid (Halliburton.] For the detection of morphia in the urine
the method described at p. 156 may be adopted. It must be borne in
mind, however, that morphia does not appear in the urine in all cases of

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POISONING WITH ALKALOIDS—WITH CARBOLIC ACID. 341

morphia poisoning or morphinism, and its absence does not prove that the
alkaloid has not been taken. The researches of Donath®” have shown
that it may disappear entirely within the system.

(b.) Nicotin.—The toxic effects of nicotin are not associated with any
special changes in the character of the urine. For the detection of the
alkaloid see p. 157.

(c.) Atropin.—Little that is definite is known of this condition.

Atropin may be isolated from the urine in the same manner as that
described in connection with the vomit (p. 157). As a test for its
presence a little of the urine may be placed in an animal’s eye, and the
mydriatic effect watched for. This will be obtained, according to de
Ruitter and Donders,*™! when the urine contains the alkaloid in the
proportion of one part to 130,000 of water. In cases of poisoning with
deadly nightshade berries (Atropa belladonna), the urine has a peculiar
fluorescence (A. Paltauwf*"?), due to the presence of scopoletin. This
does not occur in poisoning with the pure alkaloid, and in certain cir-
cumstances it affords an indication as to the source of the poison.

(d.) Ptomaines (Exogenic Toxicosis).—The phenomena of poisoning
with ptomaines need further investigation. In a case (of sausage-
poisoning) which was recently under the care of Professor Nothnagel;
albuminuria and the signs of nephritis supervened. Subsequent experi-
ence has convinced the author that kidney trouble regularly occurs in
the later stages of ptomaine-poisoning.

5. Poisoning with Ethylic Aleohol.—Chronic alcohol-poisoning
appears to produce nephritis and arterio-sclerosis.°"? In the acute condi-

 

 

tion the poison can be found only as the merest trace in the urine.°4
To recognise its presence the urine must be distilled by means of a
steam-bath, and the distillate treated in the manner described at p. 161.

6. Chloroform-Poisoning.—In this condition the wrine is gene-
rally of high sp. gr. It often contains a trace of albumin and some
sugar [or glycuronie acid (Halliburton).| According to Kast and Mester,°”
the urine after the prolonged administration of chloroform contains an
organic sulphur compound and urobilin, and is highly toxic.* For the
detection of chloroform the urine is distilled by means of a steam-bath
to prevent frothing, and the first drops of the distillate are submitted to
Hoffmann’s or Vitali’s test (see p. 161). The results obtained in this way
are equally useful with those of Maréchal’s method.?™

7. Carbolic Acid-Poisoning.— When large quantities of carbolic
acid have been administered through the mouth or absorbed from a
wound, the voided urine assumes a dark-green colour, which changes
to black on standing. This colour is due to the presence of hydro-
chinon, a derivative of phenol, which, while still within the system, is
in part transformed into coloured oxidation products (Baumann and

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342 THE URINE.

Preusse).*"* Pure phenol is never present, but even in the severest
cases is found only in combination with sulphuric acid (p. 297). Hence
a violet coloration with

 

the characteristic reaction of carbolic acid
solution of perchloride of iron—cannot be obtained with the urine.
The latter contains a small quantity of albumin, and commonly also
hemoglobin (p. 271). A further evidence of the condition depends
upon the diminished proportion of simple sulphuric acid which it con-
tains. When chloride of barium is added to healthy urine acidulated
with acetic acid, an abundant precipitate of barium sulphate falls; but
when from any cause the quantity of sulphuric acid in the uncombined
form is lessened, this precipitate fails, or is represented by a mere tur-
bidity. If now in this case the urine be filtered and boiled with hydro-
chloric acid, so as to decompose the phenol-sulphurie acid (see p. 297),
with the reproduction of simple sulphuric acid a copious precipitate of
barium sulphate forms.

Inasmuch as phenol-sulphuric acid is normally a constituent of the
urine, it serves but little purpose in cases of carbolic acid-poisoning to
attempt an estimate of the phenol which passes over as tribromo-phenol
(see p. 299) in the process of distillation. A better plan is to determine
the relative proportion of simple and compound sulphuric acid present
(see p. 323). If it be found that the latter is increased while the first
is diminished, and if at the same time such affections as promote the
elimination of vther-sulphuric acids (active albuminous decomposition)
can be excluded, this is strong presumptive evidence of carbolic acid
poisoning.

The same method will serve for the detection of all the aromatic
substances which appear in the urine as ether-sulphuric acids in cases
of poisoning or after the administration of drugs.

8. Poisoning with Nitro-Benzol and Aniline.

(a.) Nitro-Benzol.—In cases of poisoning with this substance, the
urine has the odour of nitro-benzol, and generally contains a substance
which has the property of rotating polarised light to the left, and of
reducing cupric sulphate in alkaline solution.*”

().) Aniline.—The recorded observations of cases of poisoning with
aniline show that the character of the urine varies considerably. It is
usually dark in colour and highly concentrated (Grandhomme).®° In
one instance (Fr. Miller 1) it was free from sugar, albumin, and blood,
and exhibited the reduction phenomenon in a marked degree. A®ther-
sulphuric acids were notably increased. An ethereal extract was found
to contain aniline by its yielding a violet colour in presence of solution
of chloride of lime (see p. 162). Muller is of opinion that this substance
is in part eliminated as paraamido-phenol-sulphuric acid.

9. Poisoning with Carbonic Oxide Gas.—The urine passed in

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DETECTION OF DRUGS. 343

this condition invariably contains grape-sugar**? (see p. 273), and an
uncertain proportion of albumin. The quantity of sugar varies directly
with the intensity of the poisoning.

V. THE DETECTION OF CERTAIN DRUGS IN THE URINE.

1. Iodoform and Salts of Iodine and Bromine.—After the
exhibition of iodoform, whether internally or by outward application
iodides and iodates may be detected in the urine. So too with iodine
when applied externally as the tincture, or taken by the mouth as iodide
of potassium, it may be readily recognised in that fluid.

To test for iodine. the urine is treated with a little fuming nitric
acid or chlorine water, and shaken up with chloroform. If a salt of
iodine be present, the metal is set free, and dissolves in the chloroform,
with the formation of a red colour.

The quantitative estimation may he effected best by Harnach’s>*
method, in which all the iodine is converted into palladium iodide.
Iodine appears in the urine very shortly after it has been taken into the
system. A quarter of an hour will suffice for its manifestation there.

Bromine salts, when very abundant, may be detected thus :—The
urine is treated with chlorine water, and shaken up with chloroform,
when bromine dissolves in the latter, with the production of a yellow
colour. It will usually be found necessary, however, to evaporate the
urine previously, then to incinerate it carefully, and to test the colour
less watery extract from the ash in the manner described above.°*+

2. Salicylates—Salol and Betol.—Salicylates also very quickly
pass into the urine. The latter then exhibits a remarkable reducing

 

power, and yields a violet colour in presence of solution of perchloride
of iron. This reaction depends partly upon the presence of salicylic
acid and partly upon that of salicylurie acid, into which the latter is
changed within the system. This reaction is not readily prevented by
boiling. The body on which it depends is taken up by ether from
acidified urine, and can be detected in the ethereal extract by means
of solution of perchloride of iron. The reaction, unlike that of diacetic
acid (see Diaceturia), does not disappear on standing. It is well in
testing for it to precipitate the phosphates with solution of perchloride
of iron and filter, and then test the filtrate with more of the reagent.

The exhibition of salol (phenyl-ether of salicylic acid) imparts a
similar character to the urine, which also on standing acquires a tint
varying from dark-green to black, like that following the use of car-
bolic acid.

The use of betol (naphthalol, salicylate of B-naphthol-ether) does not
impart any special colour to the urine, which, however, yields the per-

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344 THE URINE.

chloride of iron reaction. Both salol and betol appear in the urine as
sulphuric acid combinations (v. Jaksch).>*

3. Quinine, Kairin, Antipyrin, Thallin, Antifebrin, and
Phenacetin.

(a.) Quinine.—This alkaloid is said by Kerner *%* to be eliminated as
dioxyquinin. It renders the urine dark. For its detection a large
quantity of the fluid is taken, treated with ammonia, and shaken up
with ether. The latter is then distilled off or evaporated, and quinine
remains in the residue. It is dissolved in acidulated water, and the
addition of chlorine water and ammonia causes an emerald-green tint to
develop.

(b.) Kairin.—Under the influence of this drug the urine acquires a
brown colour, which becomes brownish-red with solution of perchloride
of iron. The substance upon which this reaction depends may be
extracted with ether from acidified urine. The reaction in the ethereal
extract remains even after the lapse of weeks. The addition of strong
acids to the urine destroys the reaction, and it is, moreover, impaired
by prolonged boiling. According to v. Mering,°* kairin is eliminated
as kairin-potassium sulphate.

(c.) Antipyrin imparts a darker tint to the urine, which gradually
becomes a purple-red when treated with perchloride of iron. If the
urine be acidulated and extracted with ether, a substance is obtained
which colours brown with perchloride of iron. This reaction is gradually
lost after the lapse of a few days. It is impaired, but not destroyed,
by boiling the urine. It is destroyed by the addition of acids. Esti-
mation of the quantities of simple and of ether-sulphuric acids in
appropriate instances has shown that antipyrin is eliminated as a sul-
phuric acid combination (v. Jaksch).

(d.) Thallin.—The urine after the administration of thallin is usually
a brownish-green when viewed in bulk, greenish in a thin layer.
Treated with perchloride of iron, it presently exhibits a purple-red tint,
which, after the lapse of four or five hours, if undisturbed, passes into
a brownish-red. If a little mineral acid be added and the fluid be
shaken up with ether, the latter takes up a substance which colours
brown-red with perchloride of iron. The coloration does not vanish
when the specimen is allowed to stand, but rather becomes more
marked, When the pure thallin urine is shaken up with ether, the
ethereal extract contains a body which colours green with perchloride
of iron (thallin).°% The tint in this case disappears on prolonged
standing. The red colour obtained with perchloride is lost by boiling
for a few seconds. It is likewise destroyed by mineral acids. Thallin
is partly eliminated in the form of chinanisol.

(e.) Antifebrin.—-The physical character of the urine is unaffected

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CHRYSOPHANIC ACID. 345

even by large doses of antifebrin. Chemically it has been ascertained
by F. Miiller that it contains more than the normal proportion of
ther-sulphuric acids; and this is accounted for by the supposition that
antifebrin is changed within the system to paraamido-phenol-sulphuric
acid. Where the drug has been exhibited in large quantities, it may
be recognised in the urine (F. Miiller 8°) thus :—The fluid is boiled with
one-fourth its bulk of strong hydrochloric acid, and when it has cooled,
a few ce. of a 3 percent. solution of carbolic acid is added, and then a
few drops of a solution of chromic acid. If paraamidophenol be present,
the specimen develops a red colour, which gives place to blue on the
addition of ammonia.

For the detection of antifebrin Yvon” recommends the following
method :—The urine is shaken up with chloroform, and the residue from
the extract is heated with a little mercurous nitrate. If antifebrin be
present an intense green coloration takes place. When antifebrin has
been separated from the urine, as by shaking it up with ether and
acid, it can also be recognised by the addition of chloroform and caustic
potash. Antifebrin also is excreted for the most part in combination
with sulphurie acid (fr, Miiller, Morner, v. Jaksch). According to
Morner,°*! this body is in part oxidised to acetylparaamidophenol within
the system, and eliminated as ether-sulphurie acid.

(f.) Phenacetin (acetphenetidin).—The colour of the urine is un-
affected by this body, even in large doses. It rotates polarised light
to the left (glyeuronic acid combination, Fr. Miller”), and exhibits
the paraamidophenol reaction described above. It contains no free

 

phenacetin, but the presence of phenetidine may be shown by changing
it into its diazo compound, which then yields a purple coloration with
naphthol or yellow with phenol (Jfiller). The process is as follows :—
To a specimen of the urine two drops each of hydrochloric acid and of
sodium nitrite solution (1 per cent.) are added. The further addition
of an alkaline watery solution of a-naphthol and a little caustie soda
causes a beautiful red colour to develop, and this passes into violet if
hydrochloric acid be supplied. Under the same conditions phenol gives
a citron-yellow in alkaline and a rose colour in acid solution. When
large doses of the drug have been taken, the urine gradually takes a
brown-red tint in presence of perchloride of iron solutions and oxidising
substances, changing slowly to black on standing for a long time. Ac-
cording to Ubaldi,°°? the ingestion of phenacetin is attended by an
increase in the amount of combined sulphuric acid in the urine.

4. Chrysophanie Acid.—The administration of infusion of senna
or of preparations of rhubarb imparts a reddish-brown colour to the
urine, which may be present in the freshly-voided fluid or develop on
standing. This gives place to red on the addition of alkalies at ordinary

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340 THE URINE. Y

temperatures. When boiled with alkalies the resulting phosphatic sedi-
ment is not red, but yellow; and if dissolved in acetic acid the solution
also colours yellow, changing to violet on exposure to the air; in this
respect differing from the precipitate of blood-pigments, which is also
soluble in acetic acid, but gradually bleaches when exposed.

5. Santonin.—Santonin taken internally colours the urine yellow,
which again gives place to red on the addition of alkalies. Its presence
may be discriminated from that of rhubarb (Afunh:) °*+ from the fact that
the red colour developed by the latter in presence of alkalies, though
permanent, is rapidly destroyed by reducing agents (granular zinc,
sodium amalgam), whilst that due to santonin persists under like cir-
cumstances. Chrysophanic acid is precipitated with baryta water. The
precipitate is red and leaves a colourless filtrate. The latter is yellow
if santonin be present. The addition of alkaline carbonates turns the
urine red, rapidly if it contain rhubarb, very slowly and gradually in the
case of santonin.

G. Hoppe-Seyler®” has suggested the following method for the dis-
crimination of chrysophanic acid and santonin :—The urine is treated
with caustic soda and extracted with amylie alcohol. If the colouring
matter of santonin be present, it passes over with the alcohol, and the
specimen is decolorised. The colouring matter of chrysophanic acid
derived from the exhibition of rhubarb or of senna is little or not at all
taken up by amylic alcohol in presence of the alkali.

6. Tannin.—When tannin has been taken medicinally in large
doses, the urine turns dark-green with solution of perchloride of iron.

7. Naphthalin.—Naphthalin in large doses causes the urine to
assume, especially on standing for a long time, a dark tint, like that
due to carbolic acid.

According to Penzoldt,°"’ a dark-green colour develops rapidly in
presence of concentrated sulphuric acid.

8. Copaiba Balsam.—Copaiba balsam in the urine yields a red
colour with hydrochloric acid, changing to violet when heated. If
ammonia or caustic soda be added to the urine, a light-brown colour
with a blue fluorescence develops (Ei/lefsen).5°7

When boiled with an acid the urine gives a precipitate which is
soluble in alcohol.

It may be mentioned here that after the use of oil of turpentine the
urine sometimes gives a precipitate with acids. It has also a charac-
teristic odour of violets.

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CHAPTER VIII.

INVESTIGATION OF EXUDATIONS, TRANSUDATIONS,
AND CYSTIC FLUIDS.

Fiuip may be effused into any of the cavities of the body as a conse-
quence of inflammation or of disturbances in the circulatory system.

Under appropriate circumstances a portion of such fluid may be
drawn off by puncture or in some other way, or a spontaneous opening
may occur, and in either case the fluids so obtained may be submitted
to examination. In this way much useful information may be secured
for the purposes of diagnosis. A question arises at the outset as to
whether the fluid is an inflammatory product (exudation), or the result
of impediment to the circulation, or derived from the degeneration of
certain organs. (transudation).

A.—EXUDATIONS.

An exudation may be purulent, sero-purulent, putrid, hemorrhagic,
or serous, All such fluids, with the exception of the last two, imply,
of course, an inflammatory origin. Upon its other characters, and
especially upon the nature of the tissue elements which it contains,
more precise inferences may be based in the case of any one of them.

1. Purutent Exupations.

I. NAKED-EYE APPEARANCES.—Pus (bonum et laudabile) is
a turbid fluid of varying consistence and high sp. gr., with an alkaline
reaction, and ranging in colour from grey to a greenish-yellow. It
may accumulate in natural cavities (exudations), or be effused amongst
the tissues (phlegmon), or, finally, it may be secreted from the surface
of a wound. On standing in a cool place, it separates into two layers,
the upper of which is of a light-yellow colour and tolerably transparent,
and the lower opaque from the deposit of pus-cells. It is often brown
or brownish-red from admixture with blood. Putrid pus can always
be discriminated by its naked-eye properties. It is thin, green, or
brownish-red, and emits an extremely penetrating odour of indol and

skatol.

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348 EXUDATIONS

II. MICROSCOPICAL CHARACTERS.

1. White and Red Blood-Corpuscles and Epithelium.— When
pus is submitted to microscopical examination, it discloses a multitude
of cells which entirely resemble white blood-corpuscles. When derived
from a perfectly fresh specimen, these cells exhibit the contractile pro-
perty, and the mahogany coloration obtained with solution of iodine
and iodide of potassium or ammonium attests the presence of glyco-
gen. This reaction is obtained best with fresh pus from the surface
of a wound. The dead cells are shrunken and very granular, or may
appear as decomposed or decomposing particles of protoplasm.

In addition to this, giant pus-corpuscles and fat-laden cells are occa-
sionally observed. No special significance attaches to their presence.
They have been seen in the pus from an abscess of the gum (Boettcher 1),
in hypopyon (Bizzozero?), and in the contents of suppurating ovarian
cysts (v. Jaksch).

Some red blood-corpuscles are nearly always present in freshly-secreted
pus, and when blood in considerable quantity has been effused and after-
wards its elements disintegrated, the discharge may be more or less
amply tinged by admixture with blood-pigment or hematoidin crystals.

Fatty particles and globules are seldom wanting, either free or com-
bined with the protoplasm of the cells. The epithelium elements are
comparatively few. In cancerous exudation from the pleural cavity
vacuolated epithelial and fatty endothelial cells are commonly to be
met with.

2. Fungi.—Modern research® has established the fact that the
formation of pus in animal organisms is effected almost entirely through
the agency of micro-organisms, and that such bodies can nearly always
be detected in the discharge with the aid of the staining methods (p. 377)
which the recent advances of science have placed within our reach, where
the microscope alone fails to disclose their presence.

Important experiments upon animals+ have shown also that suppura-
tion may be caused by certain chemical substances, as cadaverin, croton
oil, &c., independently of micro-organisms ; and it is possible that the
human system may be similarly affected by them.

1. Micrococci.—Micrococci of varying form and size are very often
to be seen in fresh pus.° Fig. 136, which represents the appearance of
a specimen taken from a pleural exudation and stained by Gram’s
method, affords an appropriate illustration, They are usually arranged
in chains (Streptococci), occasionally in pairs (Diplococci).

Passet,® proceeding on Koch’s method, has cultivated no less than
eight different forms of fungi from pus. When suppuration has con-
tinued for a long time in a cavity excluded from the air, micro-organisms
are sometimes wanting in the pus. Bréeger™ has observed Staphylo-

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FUNGI—BACILLUS OF TUBERCLE. 349

coccus pyogenes aureus and Streptococcus pyogenes in pus from a
woman with puerperal fever. The presence of micro-organisms hitherto
mentioned is evidence of suppuration in the course of septic processes
(comp. p. 47). Bujwid® lately made the interesting discovery that the
effect of grape-sugar upon the tissues is to promote the development of
Staphylococcus aureus by diminishing their resistance, and so to favour
the formation of pus. The tendency of diabetics to undergo suppurative
processes, so long a matter of clinical observation, is explained in this
way.

A blue colour has occasionally been observed on the surface of suppurating
wounds. This is produced by colonies of Bacillus pyocyanogenus or of a fungus
resembling it. The colouring-matter has been isolated from such pus in combina-
tion with hydrochloric acid.1°

  
           

7
a if

0%
*

Nery
Rg

O sO ‘s

Fic. 136.—Cocci from an Empyema, prepared by Giam’s method (eye-piece III., objective
Zeiss oil immersion ,!;; Abbe's mirror and open condenser).

The detection of pathogenic fungi in pus is a point of great im-
portance.

2. Tubercle - Bacillus.—The tubercle-bacillus has often been dis-
covered in tubercular pus,!! but the author has sometimes failed to find
it even in the fresh discharge. Its presence, of course, is conclusive as
to the nature of the disease, but its absence does not imply that no
tubercle is present. It would appear that under certain conditions the
bacillus rapidly disappears from fresh discharges (Metschnihof}).

8. Bacillus of Syphilis.—The bacillus discovered by Lustgarten ! in
the pus of syphilis affords a valuable indication of this disease ; but
caution must be observed in identifying it, since Alvarez and Tavel 4
have shown that certain secretions, as the smegma preputiale and

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350 EXUDATIONS.

vulvare, are apt to contain forms which closely resemble the venereal
microbe. Such forms are to be discriminated by the behaviour of
stained preparations in presence of alcohol. In the case of the bacillus
of syphilis, these are with difficulty and very slowly bleached by alcohol,
whilst the microbe of smegma readily loses its colour under the action
of that substance.

An important addition to our knowledge of the bacillus of syphilis
was recently made by Kamen, who found the micro-organism in the
sputum of a child of nine years. The character of Lustgarten’s bacillus
hag been much questioned of late, and others have regarded certain
cocci as the specific excitants of syphilis (Kassowitz, Hochsinger, Disse,
Taguchi).

For the detection of the bacillus of syphilis Lustgarten 1 proceeds as

 

Fic. 137.—Actinomyces Granules in Glycerine from Actinomycosis of Pleural Cavity
37 y' y
(eye-piece II., objective IV., Hartnack).

follows :—The cover-glass preparation is immersed in an Ehrlich-Weigert
gentian-violet fluid for 12-24 hours at the ordinary temperature. It
is then removed, rinsed for some minutes with absolute alcohol, and
placed for ten seconds in a 14 per cent. solution of permanganate of
potash, after which it is treated with a watery solution of pure
sulphurous acid, and finally washed with water. Should it happen
after this that the preparation still shows colour, it is again placed in
permanganate of potash for three or four seconds, and afterwards in
sulphurous acid until all colour has disappeared, the remainder of the
process also being repeated. It is to be noted that other microbes,
both pathogenic and innocuous, are stained by Lustgarten’s process as
well as that of syphilis.

De .Giacomi}® has suggested a method which is very serviceable for

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ACTINOMYCES. Sw

the detection of the bacillus of syphilis. In this the dried cover-glass
preparation is warmed for some minutes in an aniline-water fuchsin
fluid, then washed with water to which a few drops of perchloride of
iron solution have been added, and finally decolorised in a concentrated
solution of that salt. The bacillus then remains of a red colour, while
all other micro-organisms are bleached.

 

Fic. 138.—Actinomyces from a Case of Actinomycosis of Pieural Cavity (eye-piece III.,
objective, oil immersion j};, Reichert ; compressed).

4. Actinomyces.—This parasite was first discovered by Bollinger!” in
cattle, and afterwards in man by Ponfick 8 and Israel." In the former
it gives rise to tumours of considerable size, but in man its proliferation is
usually associated with chronic inflammation and the production of pus.

It would appear from numerous communications that have been made
in recent years that actinomycosis is a disease of very wide distribution,

 

Fic. 139.--Actinomyces from Peritoneum (eye-piece III., objective, oil immersion 5, Reichei't,
unstained preparation).

and that amongst its symptoms is a severe form of angina, till lately
obscure, to which the name of angina Ludovici has been given.2°

[It usually affects the intestinal?! tract, but primary actinomycosis of the

apices of the lung has been met with,” and six cases °3 have been recorded in
which the disease had its seat in the brain. One of these by Dr. Orlow™ is of

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352 EXUDATIONS.

exceptional interest. Anderson” of Nottingham has lately recorded a case
of actinomycosis of the face and neck, which was successfully treated by
operation. ]

The pus of this disease is thin, viscous, and somewhat tenacious, and
discloses to the naked eye small nodules of a grey or yellow colour, and
about the size of a poppy-seed. Under a low power of the microscope
these particles appear as a dense bunch-like aggregation of spherules,
which under a higher magnifying power are seen to consist of pear-
shaped, and radially arranged masses, which have a considerable refrac-
tive power (figs. 138, 139). Towards the centre of such masses the
individual elements diminish in size and fade into a fine network of
ramifying fibres. If one of the nodules be bruised, it shows in the first
place numerous detached club-shaped forms, having a radiating disposi-
tion toward the periphery (fig. 138), and passing gradually at the centre
into a sort of detritus ; and in addition to these are a variety of other
objects, club-shaped and of indeterminate appearance (degeneration types
of the fungus), lying apart.

There was for a long time much doubt as to the botanical character
of Actinomyces. Recently, however, it has been established 7° that it
belongs to the class of fission-fungi, being a fission-alga (Cladothrix).
The characteristic club-shaped bodies must be regarded as degeneration
forms of the fungus. In unstained microscopical preparations they
may be seen sometimes to fade into the central fine network, and even
occasionally to be enclosed in its meshes (fig. 139). [C@rookshank**
believes that actinomyces is a fungus intermediate between the fission-
and the higher fungi ; and Dr. W. Hill °$ refers it to the Basidiomycetes. |

With the aid of staining methods (Gram’s is the best) the individual
threads of the network are readily distinguishable. They present a
jagged or undulating contour, and result from the cohesion of a series
of minute spherical organisms, connected together by a remarkably
delicate envelope. The centre, to which all the constituent threads of
a group converge, is occupied only by a very dense network of this
formation (fig. 140).

The pear-shaped bodies above alluded to may be more clearly defined
by staining with Wezgert’s*® process. For this purpose a solution is
made by adding together zo cc. absolute alcohol, 5 cc. concentrated
acetic acid, and 40 ce. of distilled water, and to the mixture so much of
the so-called French extract of litmus as will give the fluid a dark-red
colour, remaining ruby-red after repeated filtering (Wedl’s®° litmus
solution). In this solution the cover-glass preparations are allowed to
remain for an hour or so, then lightly rinsed with alcohol, and placed
for two or three minutes in a 2 per cent. gentian-violet fluid, which
should be boiled before use, and filtered after cooling.

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BACILLUS OF GLANDERS. 353

If the specimen be now examined, it will be found that whilst the
central’mass of Actinomyces is colourless, the fungus threads are
stained a ruby-red. Baranski*! advocates staining with picro-carmine.
In most cases, however, the character of this fungus can be determined
by a simple microscopical examination. The physical qualities of the
pus, and the discovery in it of groups of Actinomyces or the club-
shaped degeneration forms of the parasite, are points which will aid the
diagnosis. In particular cases it may be necessary to resort to Gram’s
staining method, and to observe the minute structure of the ultimate
threads of the fungus, as noticed above (comp. p. 352). Bujwid *? has
obtained pure cultivations of actinomyces by means of Buchner’s** method
(p. 388). Seen with the naked eye, these bear a close resemblance to
cultivations of tubercle-hacillus.

 

Fic. 140.—Preparation from same case as last, stained by Gram's method (eye-piece IV.,

objective, oil immersion j,, Zeiss ; Abbe's mirror and open condenser).

5. Bacillus of Glanders.—The specific micro-organism may be found
in the pus from the ulcerated nasal passages in glanders. The method
deseribed in connection with the examination of the blood (p. 46) will
serve for its recognition here.

Another method has recently been suggested (Loffler).°4 An aniline-
-water-gentian-violet fluid or a concentrated alcoholic solution of methylene-
blue may be employed, and immediately before use it is added to its
own bulk of a (1: 10,000) solution of potash. In the fluid which results
the cover-glass preparation is immersed for five minutes. It is then
removed and placed for a second in a 1 per cent. solution of acetic acid,
tinged slightly yellow with oo-tropeolin. By means of another mix-
ture, containing two drops of concentrated sulphurous acid and one of a
5 per cent. solution of oxalic acid in ro ce. of water, the alkaline stain-
ing fluid may be decomposed and the preparation freed from colour. In
this way the micro-organisms are very beautifully stained.

The bacillus of glanders may also infest the pus from an abscess.
In any case, its character may usually be sufficiently determined in
stained specimens by means of the microscope. When necessary, how-
ever, all doubt may be removed by observing the result of inoculating

Z
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354 EXUDATIONS.

animals with the microbe. In the intermediate process of cultivation
certain characteristic properties are disclosed. When the various other
micro-organisms which are nearly always present in the pus have been
eliminated by Koch’s method (p. 385), the pure plate-cultivation crop
made in nutrient agar-agar at 37° C. has the appearance of a greyish-
white drop. The pure cultivation-product, when inoculated upon
animals, as the mouse or guinea-pig, induces glanders. When engrafted
on the potato and kept at a temperature of 35° C. the bacillus forms,
in two or three days, a thin greasy coating of a brown colour. In
coagulated blood-serum at a low temperature it develops after two or
three days in the form of small scattered transparent drops which have
a colour very much the same as that of the serum. ‘The fungus is
readily cultivated in glycerine agar-agar *° and in nutrient milk-peptone.*¢
When allowed to rest for some time longer, the cultivations are said to
develop spores, but this point is not established (Bawmgarten).37

6. Bacillus of Anthrax.—Opportunity occasionally offers of exa-
mining the pus derived from a carbuncle in anthrax. The specific
micro-organism is that described at p. 42. <A certain familiarity with
its life-habits will often facilitate its recognition, especially where it
can be obtained only in very small numbers. The process by which
these have been studied is in general the same as that employed for
other pathogenic microbes. Thus the elimination of other forms is
effected by Koch’s plate (nutrient agar-agar and nutrient gelatine)
and inoculation methods (see p. 385). When cultivated in a nutrient
gelatine medium, the bacillus of anthrax develops in twenty-four to
thirty-six hours, and forms minute points which are scarcely visible to
the naked eye. With a lens the colonies are seen to be dark figures
with an irregular undulating outline. Their peculiar shape becomes
more evident after the lapse of forty-eight hours, and later the culti-
vation liquefies, and from the dark central point it stretches in wavy
strings over the entire surface of the plate.

The fungus does not liquefy agar-agar. When cultivated on steri-
lised potato, it forms a whitish-grey slimy patch of uneven surface, and
extending but a few millimetres from the site of inoculation. Blood-
serum cultivations form a superficial coating of white colour. Nutrient
gelatine test-tube cultivations take the form of delicate white threads
much interwoven, and gradually liquefy the gelatine ; drop-cultivations
of anthrax-bacillus in nutrient broth take the shape of long threads, in
which, after a time, lustrous spots (spores) develop at regular intervals
(comp. p. 43).

If the bacillus be imparted by inoculation to such animals as the
mouse or guinea-pig, the animals exhibit the symptoms of splenic fever,
and the micro-organism may be obtained from their blood.?8

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BACILLUS OF LEPROSY. 355

7. Bacillus of Leprosy.—The nodes which are apt to form on various
parts of the skin and mucous membrane in leprosy occasionally break
down and ulcerate, with the formation of an abundant thin pus. In
this, as indeed in the growths of leprosy generally, large numbers of
bacilli may be found (A. Hansen, Neisser).*® They have the form of
minute rods 4-6 » long and 1 m in breadth, and have a close resem-
blance to the bacillus of tubercle (see p. 106). Like the latter, they
stain in alkaline fluids, and are not bleached by subsequent exposure
to acids. They are distinguished by the comparative readiness with
which they stain, and by more easily taking up the colouring-matter
from a simple watery solution of aniline dye.4” For their detection in
the pus a suitable dry cover-glass preparation must be made (see p. 105),
stained with Ziehl-Neelsen’s carbol-fuchsin fluid, and again decolorised
m acid (best with nitric acid) aleohol. [Ehrlich’s, Weigert’s, and Gibbes’
methods also serve. ]

Melcher and Ortmann*! claim to have produced leprosy in animals
(rabbits) by inoculation with diseased tissue; and Bordoni-Uffreduzzt ®
to have cultivated the fungus from the spinal cord of lepers by inocula-
tion in glycerine peptone-serum, glycerine blood-serum, and glycerine
agar-agar. According to the latter, when cultivated by surface inocula-
tion of nutrient substances, it forms ribbon-like cultivations with irrecular
borders, and of a light-yellow colour. On glycerine agar-agar it develops
in small round whitish-grey cultivations, somewhat elevated at the
centre, thinned at the edges and having a jagged outline. |

[These statements need further confirmation. The attempt to culti-
vate the bacillus of leprosy has been made without decided success by
many pathologists both in England and abroad. Patrick Manson * was
one of the earliest to investigate the subject, and its literature includes
contributions by Campana,** Kanthack and Barclay, Beavan Rake
and Buckmaster,*® Stallaro* and Byron.8 Dr. P. S. Abraham, the
Secretary of the English Leprosy Commission, to whom the editor is
indebted for a personal communication, has examined specimens of the
cultivations obtained by some of these observers, and he is of opinion
that they are growths of a micro-organism of the skin which has nothing
to do with leprosy. |

8. Bacillus of Tetanus.—In view of the fact that the bacillus is
found in the pus from wounds in cases of tetanus, and that much
importance attaches to its recognition, some description of it is required
here.*® It occurs as delicate slender rods which have often a terminal
spore, and thus present the appearance of bristles (see fig. 141). They
stain with all the aniline dyes, and also with Gram’s fluid. To obtain
pure cultivations from pus, the cultivations first derived, which contain
fungi of different kinds, are heated to 80° C. in a water-bath, for from

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356 EXUDATIONS.

a half to one hour during a few days, after which they are inoculated
on gelatine plates to which 1.5 to 2 per cent. of grape-sugar has been
added, and these are kept in a hydrogen atmosphere (Kitasato %°) at
20-25° C. The resulting colonies are somewhat dense at the centre,
with a more delicate and uniform periphery radiating from it. The
preparation becomes fluid in time, and gas is evolved.

If a pure cultivation be inoculated under the surface of gelatine,
growth begins near the surface of the gelatine, and the resulting
cultivation is marked with faint radiating striz, or sometimes as thorn-
like processes projecting from it. Development is more rapid in agar-
agar. After exposure of the bacilli for thirty hours to a temperature
of 37° C. the spores already mentioned make their appearance.

 

ONS | ey oe ‘
> nN XY o 2e6
' Fic, 141.—Bacilli of Tetanus (pure cultivation). Compensation eye-piece VIII., objective oil-
immersion ,, Zeiss (from Koch).

9. Bacillus of Influenza.—R. Pfeifer has found in the sputum, and
cultivated, a definite micro-organism, which he believes to be charac-
teristic of influenza. By Kitasato*? it was cultivated to the fifth gene-
ration in glycerine-agar, and Canon ** has detected a similar fungus in
the blood of those infected with the disease, and afterwards by means
of cultivation-experiments established its identity with the bacillus of
Pfeifer and Kitasato. Although the micro-organism has not yet been
found in pus, it will be described here, both because its discovery was
announced too late to notice it in its proper place in this book, and
also because it doubtless exists in the pus of those infected with
influenza.

According to Pfeiffer, the bacilli have the form of very minute rods
of about the same thickness as those of mouse-septicemia. They stain

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PROTOZOA—VERMES—CRYSTALS. 357

well in Léffler’s methylene-blue fluid when heated (see p. 41), and also
in dilute Ziehl-Neelsen fluid (p. 106). They do not stain with Gram’s
method. On glycerine-agar solidified obliquely, after twenty-four hours
they develop the appearance of drops of water which require a lens to
make them visible. The colonies remain separate. For the detection
of the bacillus in the blood, according to Canon, the latter is spread on
a cover-glass and dried in the usual way ; the cover-glass preparation is
treated for at least five minutes with absolute alcohol, and is then put
for three to six hours to stain in Chenzinshy’s eosin-methylene-blue fluid
(see p. 57).°+

It is probable that the pathogenic micro-organisms of pus include
others besides those mentioned here. Reference may be made espe-
cially to the interesting observations of Eppinger,®® concerning a new
cladothrix which has been found in abscesses.

3. Protozoa.—Little is known as yet as to the presence of these
parasites in pus. Kiinstler and Pitres®® found numerous large spores
with ten to twenty crescentic corpuscles in the pus from the pleural
cavity of a man. These bodies closely resembled the coccidia which
occur in the bodies of mice (comp. pp. 89, 180). Litten *" observed cerco-
monads in the puncture-fluid, derived probably from the lungs. Masse 8
has reported the presence of amcebe in the pus from a hepatic abscess.

4. Vermes.—Filaria have been observed occasionally as occurring
in the pus of tropical abscess of the liver.*® In temperate climates also
abscesses result from an invasion of hydatids, and in such cases the
pus contains entire echinococcus cysts, or fragments of the membrane
and hooklets. Babesiu® found filaria in the gastro-splenic omentum.
They were probably the same as G'rassi’s®! Filaria inermis. With
these should be mentioned the bodies resembling filaria which Sarcani °?
reports as found by him in the suppurating parotid of a woman.

5. Crystals.

1. Cholesterin.—Crystals of cholesterin are very rarely to be found in
fresh pus—more commonly in that derived from cold abscesses, and most
abundantly in foetid discharges and in suppurating ovarian cysts. For
their character and recognition the reader is referred to pp. 111, 203, 249.

2. Hematoidin.—This body exhibits the same variety of form here
as in the sputum, the urine, and the feces (pp. 111, 195, 241). Its
presence invariably points to a previous hemorrhage. It is specially
abundant in the case of suppurating hydatid cysts.

3. Fatty Needles.—These are of very many shapes and forms, occur-
ring sometimes singly, and sometimes in groups and clusters. They are
the outcome of a degenerative process, and show that the pus in which
they are found has been long formed. Very perfect margarin needles
may be obtained from gangrenous pus (fig. 142).

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358 EXUDATIONS.

4, Triple Phosphate.—Crystals of triple phosphate are a common
constituent of the pus (see p. 248). Crystals of carbonate and of phos-
phate of lime are also met with, and most commonly in foetid pus.

III. CHEMICAL EXAMINATION OF THE PUS.—lIt rarely hap-
pens that much aid accrues to diagnosis from the chemical examination
of the purulent discharges. The albuminous substances which may
commonly be recognised are serum-albumin, globulin, and especially
peptone (Hofmeister) in large quantity. The latter is derived from
the cells, not from serum. For the means of detecting these bodies the
reader is referred to p. 255.

Fresh pus always contains glycogen, and traces of grape-sugar are
seldom wanting. In testing for the latter, the pus should be boiled
with an equal weight of sodium sulphate, to free it from albumin,
filtered, and the filtrate treated in the manner previously described
(p. 274).

In cases of jaundice the pus may contain bile-pigments and biliary acids.

Considerable quantities of nuclein, fats, cholesterin, and a number
of inorganic salts, notably phosphate and chloride of sodium (Miescher,
Naunyn °°), are constantly to be found.

In three specimens of pleuritic exudation which he has investigated
the author found abundance of acetone, and it would appear from a
private communication of Professors Baumann and Batimler that that
body is commonly a constituent of pus. In another specimen sub-
mitted to him by Dr. R. Paltauf, whose attention had been attracted
by the evident odour of acetone, it was found by the author to be plen-
tifully present; and the researches of others have shown that acetone
is frequently present in large proportion in exudation fluid. Feetid
pleural exudation often contains sulphuretted hydrogen. The method
for its detection is described at p. 327. There, as in certain forms of
hydrothionuria, fungi possessing the property of liberating sulphuretted
hydrogen may be isolated from the fluid.

Guttmann > found indigo-producing substances in exudations. The
author has repeatedly established the presence of fatty acids,—acetic,
formic, and butyric acids. Pus contains further a trace of uric acid and
several xanthin bases. Much interest attaches to the occasional presence
of guanin (v. Jaksch).©

2. Sero-Purutent Exupations.

Sero-purulent closely resemble the purulent discharges in their chemi-
cal, physical, and morphological character. They are distinguished
chiefly by the relatively smaller proportion of extractives which they
yield. They invariably point to antecedent inflammation.

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PUTRID, HAZ MORRHAGIC, AND SEROUS EXUDATIONS. 359

3. Purrip Exupations.

Discharges of this character are brown or brownish-green in colour,
and have a penetrating and disagreeable odour. Their reaction is
usually alkaline. Microscopically they exhibit much-shrunken leuco-
cytes and an abundance of crystals, chiefly of fat, and of cholesterin
and hematoidin in lesser proportion. They also contain a profusion of
fission-fungi of different kinds (see fig. 136).

4. H&morrHacic Exupations.

A hemorrhagic exudation contains an abundance of red blood-cor-
puscles, and often also a considerable quantity of dissolved hemoglobin.
Endothelial cells loaded with fat are almost invariably to be found,
and when these occurring in pleuritic fluid exhibit the glycogen re-
action in a marked degree, they favour the assumption of carcinoma

 

Fic. 142.—Pus from Putrid Empyeina (eye-piece III., objective 8a, Reichert).

(Quincke).®8 A positive diagnosis upon this point results from the
further discovery of cancer-cells.

In the absence of determinate (specific) elements, as cancer-cells,
tubercle-bacillus, &c., no very definite conclusion can be drawn from
the hemorrhagic character of the discharge, since many different pro-
cesses may be associated with the effusion of blood. Still, in the case
of pleuritic fluid, where scurvy and cancer of the pleura can be excluded,
the appearances would point to tuberculosis.

5. Serous Exupations.

Fluids of this class are almost quite clear and more or less deeply
tinged yellow; they coagulate on standing (for twenty-four hours),
and yield a clot which is usually rich in fibrin, Microscopically they
exhibit scattered red blood-corpuscles in usually fairly good preserva-
tion, but sometimes much attenuated, a number of leucocytes, some
fatty globules and endothelial cells, separately or in groups. In addi-
tion to these are sometimes cells ranging from 7-30 u in diameter, and

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360 EXUDATIONS.

formed of very small droplets. These may contain two or three large
cavities (Bizzozero).®

There is reason to believe that micro-organisms very frequently
infest the serous exudations, but the subject calls for further elucida-
tion. It would appear, at any rate, that fungi occur oftener in them
than in the transudations which so closely resemble them in their
physical and chemical properties. The fluid obtained from the pleural
cavity in tubercle of the pleura with breaking down of tissue may
contain the specific bacillus of. that disease. In cases, however, where
no discharge of tubercular matter has taken place into the pleural
cavity, the tubercle-bacillus will not be found.

Cholesterin crystals occur in serous discharges of old standing.
Chemically, serous exudation fluid contains serum-albumin and globulin,
but no peptone. Sugar in small quantity is invariably present,’? and
acetone from time to time. A notable fact is the frequent or perhaps
invariable occurrence of uric acid in exudations of this kind.

The density of the fluid is clinically a fact of much consequence.
It may be estimated by means of a pycnometer, or with an accurate
aérometer, regard being had at the same time to conditions of tempe-
rature. The sp. gr. will usually be found to exceed 1.018 (Reuss).™

6. CHyLous ExuDATIONS.

Peritoneal exudation is commonly characterised by the abundance
of fatty matter which it contains. This also is especially true of dis-
charges depending upon obstruction of the thoracic duct.

The appearance of chyle, however, is sometimes misleading, since it
has been shown that this character belongs in general to pathological
fluids of low sp. gr., especially to such as owe their origin to passive
congestion (Ff. A. Hoffmann).’?

Boulengier*? draws a distinction between chylous and chyliform
exudation, limiting the first of these terms to the case in which chyle
is actually discharged into the peritoneal cavity, while the second im-
plies only that the fluid has the properties of chyle. Chylous effusion
is very rich in fat. A specimen of chylous pericardial fluid was found
by Hasebroek “+ to contain 10 per cent. of the latter.

For the discrimination of the different forms of pleuritic effusion, the
bacteriological evidence is of much importance. Thus the absence of
micro-organisms points to a tubercular origin when the exudation is
purulent ; sero-fibrinous exudations are also usually free from fungi, and
cases of empyema occur in which only Staphylococcus pyogenes is found.
Exudations occurring in the course of pneumonia often exhibit Frenkel’s
pneumonia-coccus, and such have generally a favourable termination.

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TRANSUDATIONS. 361

In general it is a difficult task to determine whether a particular
fluid effused into one of the cavities of the body is due to inflamma-
tion (exudation) or to simple obstruction (transudation). In such
cases a probable conclusion may be based upon the specific gravity
of the fluid (Méhu, A. Reuss)."® A further point of interest in this
connection is the fact that inflammatory fluids are relatively rich in
fibrin (for the estimation of this body see p. 270), and in dry residue
products."7

B.—TRANSUDATIONS.

Transudation fluids may be serous, sanious, or, in rare instances,
chylous. Their sp. gr. is in general lower than that of inflammatory
effusion into the same cavity. They are always alkaline,” and for the
most part of a yellow colour.

Microscopically they exhibit but few tissue elements—fewer than, but
in other respects similar to, those of serous exudation. It should be
noted that in serous pleuritic effusion a large quantity of endothelium
is often detached. This must not be taken to imply endothelial pro-
liferation in a new growth (carcinoma), unless blood be also present,
when such an inference acquires additional support." Chemically,
transudation products exhibit much albumin, and generally sugar.5?
For the detection of the latter the process detailed at p. 274 may be
employed. They are always free from peptone.

Such fluids are distinguished from exudations chiefly by their low
sp. gr. and the difficulty with which they coagulate. The distinction,
however, is not easy to make in many instances.*!

The author would observe that in six specimens of transudation fluid and serous
exudation, which were entirely free from blood-corpuscles and dissolved blood-
pigment, he succeeded in separating no small quantity of urobilin. This body
is commonly to be found in transudations and exudations, and uric acid is always
present in them. In the transudation from a case of cirrhosis of the liver Mosca-

telli recently found allantoin.®? For the detection of uric acid the process de-
scribed at p. 71 may be applied.

C.—CONTENTS OF CYSTS.

The physician has often to decide whether a particular specimen of
fluid withdrawn from the body by aspiration or puncture is inflamima-
tory in its origin or due to passive congestion, and finally whether it
is derived from a cyst. Such a question is least apt to arise in explora-
tion of the pleural cavity, but in connection with abdominal symptoms
it is frequently very urgent to be able to give a definite answer. And
this is not always easy ; at times, indeed, it is impossible.

The cysts with which we have to do in this way are hydatid and
ovarian cysts, and, in rare instances, cystic kidney and pancreatic cysts.

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362 CYSTIC FLUIDS.

1. Hydatid Cysts.—The fluid obtained by puncture from a hydatid
cyst is clear, alkaline, and usually of low sp. gr., 1.006-1.010. It con-
tains a small quantity of a reducing substance (grape-sugar), very
little albumin, and abundance of inorganic salts, as sodium chloride.®
Succinic acid and inosite have also been detected. The microscopical
appearances are very characteristic. Amongst these are the hooklets
(see also p. 109) and portions of echinococcus membrane, so readily dis-
tinguished by its transverse striation and uniformly granular inner
surface (p. 109, fig. 61). Scolices may also be seen, and are known by
the two circles of hooklets and four suctorial discs on the anterior aspect
(head) and the sack-like hinder part, which is separated from the head
by an annular constriction. If the cysts have suppurated or be filled
with blood, as sometimes happens, chemical examination will usually
throw but little light upon their character. An absolute diagnosis is
possible only when hooklets or shreds of membrane have been seen in
the fluid. Consequently it is well to receive the latter in a conical glass,
and to carefully examine the sediment for these bodies.

Hydatid cysts often contain hematoidin crystals (see p. 196).

2. Ovarian Cysts.—The fluid obtained from ovarian cysts is re-
markably variable in its character.

It is generally to be distinguished from inflammatory and congestion
fluids by its high sp. gr., which ranges from 1.020 to 1.026. Its
reaction is alkaline, and it has little tendency to coagulate.

It is further marked by the great abundance of tissue débris which
it contains, and, from the nature of the cells which preponderate,
information may be drawn as to the kind of cyst from which it has
been taken.

Instances, however, occur in which the fluid from an ovarian cyst
shows nothing by which it may be known from that of ascites, and,
exceptionally, it has a sp. gr. even lower than that of a transudation
fluid. According to Schatz, Gusserow, and Westphalen,8* a low sp. gr.
with little albumin points to a cyst of the broad ligament.

When hemorrhage has taken place into the cyst, its contents may
vary in colour from red to a chocolate-brown, and be very turbid. The
microscopical examination of ovarian fluid shows a very variable quan-
tity of red and white blood-corpuscles, and many forms of epithelium,
squamous, columnar, and ciliated (fig. 143, a, 0, c). These cells, how-
ever, are rarely well preserved, but are for the most part far advanced in
fatty degeneration, and often with difficulty recognisable. Colloid con-
cretions (fig. 143, 7), in all probability derived from epithelium, are
invariably found in the so-called colloid cysts.

Certain forms of ovarian cysts may be readily differentiated by a
microscopical examination of their contents. Thus in dermoid cysts

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OVARIAN CYSTS. 363

may be seen, besides squamous epithelium, hairs, and crystals—choles-
terin, fatty, and hematoidin. Chemical investigation, too, throws
much light upon the character of an ovarian fluid. It will be found
as a rule to contain albumin, and always metalbumin (paralbumin),
and it is this body principally which renders it turbid and stringy
(Hammarsten).®

To Test for Metaliumin.—The fluid is mixed with three times its
bulk of alcohol and allowed to stand for twenty-four hours, when it is
filtered, the precipitate squeezed out, and suspended in water, which
is again filtered. The filtrate is opalescent and has the following
characters :—(a.) On boiling it becomes turbid, but does not form a
precipitate. (%.) No precipitate forms with acetic acid. (c.) Acetic
acid and ferro-cyanide of potassium render the fluid thick and impart

 

Fic. 143.—Contents of an Ovarian Cyst (eye-piece III., objective 8a, Reichert).

a, Squamous epithelinm cells; b. Ciliated epithelium cells; c. Columnar epithelium celis;
d, Various forms of epithelial cells; ¢. Fatty squamous-epithelinm cells; f. Colloid
bodies ; g. Cholesterin crystals.

to it a yellow tint. (d.) Millon’s reagent, on boiling, yields a bluish-
red;colour. (e.) Concentrated sulphuric and glacial acetic acid yield a
violet colour (Adamkiewicz). (f.) Huppert *®® has pointed out that when
the fluid containing metalbumin is boiled with sulphuric acid it yields
reducing substances, and this he regards as one of its most characteristic
properties. It must be noted that metalbumin is a constituent of other
pathological fluids besides that of an ovarian cyst. These cysts, and
especially dermoid cysts, also hold a considerable quantity of cholesterin
in solution. Cystic fluids have been frequently shown to contain dias-
tatic ferment in appreciable quantity.‘

8. Cystic Kidney.—In all cases where a sufficient specimen can be
obtained, the fluid from a cystic kidney (hydronephrosis) may be at
once identified on the ground of its chemical properties and microscopical

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364 CYSTIC FLUIDS.

appearances. An important point is the presence of renal epithelium,
and this should be carefully sought for. Then the determination of
urea and uric acid in large quantity indicates a connection with the
kidney ; but it must not be forgotten that these bodies occur more or
less plentifully in ovarian cysts, or may be supplied to them when they
communicate with the urinary tract by an abnormal channel.

It has been said that for the purpose of diagnosis the greatest signifi-
cance attaches to the presence of epithelium from the urinary tubules ;
and inasmuch as this usually occurs very sparingly in the fluid from a
cyst, the latter after removal by puncture should be allowed to settle
and the sediment carefully examined. Such of the clinical symptoms
of cystic kidney as call for notice here are very various. P. Wagner *§
observed that the urine is often scanty, Albuminuria and intermittent
hematuria, symptoms of sufficiently vague import, also occur.

4. Pancreatic Cysts.—The fluid from a pancreatic cyst is of low
sp. gr.—tr.oro-1.012 (Karewshi®), 1.022 (Hofmeister), 1.028 (v.
Jaksch )—and usually, though not always, has an admixture of blood.
In the author’s experience the blood-pigment is in the form of methe-
moglobin. There is also present abundance of cholesterin. Of proteids
there is serum-albumin ; rarely mucin is found. Metalbumin is absent.
The fluid also contains diastatic ferment, but the fact has by itself no
weight in diagnosis, since that body is very frequently met with else-
where (see p. 205). It is only when the sugar resulting from its action
is found to be maltose that any significance attaches to its presence
(see p. 287).

Such a fluid has the property of digesting albumin without the addi-
tion of acid, and it is this property which lends itself chiefly to the
purpose of diagnosis. -To test it, according to Boas,” the fluid may be
added to milk, and after precipitation of the casein the biuret test is
applied. If the reaction is obtained, the fluid is shown to have the
peptonising property, and it may be inferred that it is derived from the
pancreas, since no other cystic fluid is known to dissolve albumin in
alkaline solution. Of less moment is the property of such fluids to
emulsify fat and to disengage carbon dioxide gas on the addition of
acids. The importance of the characters here described is in most cases
greatly impaired by the fact that the larger and the older the cyst, the
less do its contents exhibit the physiological peculiarities of the pan-
creatic juice (Wolfler).° It follows that where the clinical symptoms
point to a cyst of the pancreas, it is not admissible to reject the inference
on the ground that the fluid is devoid of the tryptic character, and to
this extent the diagnostic value of these chemico-physiological observa-
tions is necessarily curtailed.

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SECRETIONS FROM FISTULA. 365

D.—THE SECRETIONS FROM FISTULZ.

Where these consist of a purulent, or simply serous fluid, discharging
through an unnatural outlet, their diagnosis may be based upon the
considerations already dealt with under the headings Transudations and
Exudations. A greater, or at least, at present, a more physiological
interest attaches to the appearances in those cases where fluids are dis-
charged by an unnatural opening, which might be assumed to communi-
cate with the intestine, because the fluid closely resembles the intestinal
fluid in its physiological properties, while fuller investigation shows that
it is derived from cavities lined by secreting glandular epithelium.

The author has analysed the secretion from a case of this kind which
Professor Woljfler observed and operated upon. The fluid had an acid
reaction, and contained albumose and peptone in considerable quantity,
pepsin, and a ferment which changed maltose into grape-sugar; no
diastatic ferment.”

The maltose employed in this research gave Trommer’s reaction only very
faintly (see p. 274). When it acted upon the secretion at 40° C., both Trommer’s
and Nylander’s tests gave positive results.

Small quantities of free hydrochloric acid were perhaps also present
—the Congo-red and benzo-purpurin tests gave feeble results—but there
was no sugar, urea, bile-pigment, or urobilin. Of inorganic salts there
were chlorides.

From this statement it appears that the fluid in many of its characters
resembled the mixed secretion of the intestinal tract.

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CHAPTER IX.
THE SECRETIONS OF THE GENITAL ORGANS.

I. THE SEMINAL FLUID.

1. Naked-Eye Appearances of the Semen.—The seminal fluid
is a thick, white, and somewhat opaque fluid, of slightly alkaline reac-
tion. It is tolerably tenacious, and resists the pressure of the cover-
class. It owes this property to the presence in it of a gelatinous
substance, which, under the microscope, appears to be hyaline, and
encloses innumerable cavities of various sizes. The semen has a peculiar
odour, which is derived, according to Fiirbringer,! from the prostatic
fluid, and depends upon the large proportion*of compounds of Schreiner’s
base (zethylenimin) (see p. 110) which it contains.

2. Microscopical Examination of the Semen.—The sperma-
tozoa, which are to be seen in great numbers in the semen, are thread-
like bodies about 50 wu in length, and provided with a head 4.5 » long,
and compressed in one plane, so as to appear club-shaped when seen
from the side. They exhibit very lively movements, but their motility
is rapidly destroyed by the addition of water, drying, &c. They are
present only in semen and in fluids with which the latter is mixed, and
obviously they may possess a great interest in the diagnosis of certain
morbid conditions. It may happen that the physician will have to
examine the semen to settle a question of sterility. A persistent
absence of spermatozoa (azoospermia) will show that the individual is
incapable of procreation, and this may occur whilst the other signs of
sexual power are retained. Of forty cases of sterile marriages, Kehrei?
found that azoospermia was the cause in fourteen. It is very impor-
tant to distinguish the persistent condition from the temporary absence
of spermatozoa, which occurs as a result of excessive and repeated inter-
course. Under such circumstances the fluid ejaculated consists almost
entirely of prostatic secretion (Pirbringer).°

In addition to spermatozoa, the semen exhibits certain cells—large
and small, finely granular testicle-cells, with one or more nuclei—some
columnar and squamous epithelium, a few large round hyaline bodies,
lecithin corpuscles, and stratified masses of amyloid substance, which

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THE SEMEN. 367

are finely granular within, and usually enclose a central kernel—these
are derived from the prostatic secretion ; and, finally, a few leucocytes—
which usually have two nuclei—and spermatic crystals. Some red
blood-corpuscles may also be seen.

Certain pathogenic micro-organisms, and especially tubercle-bacillus, may be
present in the secretion from the genital tract. They are usually discharged with
the urine. The seat of the disease may be determined in such cases by other
signs, as swelling of the testicle and epididymis, &c. (comp. p. 236).

In some pathological conditions the semen may be coloured a chocolate-
brown from the presence of a quantity of amorphous blood-pigment.
This happens especially in old people and in persons who have often
suffered from orchitis.

A very particular interest attaches to the spermatic crystals. In their
appearance and chemical properties they very closely resemble the

 

Fic. 144.—Microscopical appearance of the semen (human) eye-piece III., objective 8a, Reichert.
a. Spermatozoa; b. Columnar epithelium cells; ¢c. Bodies enclosing lecithin granules ; d.
Squamous epithelium cells from the urethra; d’. Testicle cells; e. Amyloid corpuscles ;
J. Spermatic crystals ; g. Hyaline globules.

crystals which have been already described as occurring in the blood,
sputum, and feeces (see p. 110). iirbringer has shown that while the
basic compound is derived from the prostatic fluid, the phosphoric acid
combined with it is furnished by the other component of the semen—
the spermatic or testicular secretion. The crystals form immediately
and in great abundance, when a 1 per cent. solution of ammonium
phosphate ([NH,],HPO,) is added to the pure prostatic fluid, and their
presence in large numbers, therefore, under all circumstances, indicates
prostatorrhcea (see p. 366).

It follows, therefore, that such crystals are not characteristic of the
semen, and the admixture of that secretion with some fluid or in a dried
discharge can be established only on the discovery of spermatozoa.. For
this purpose, when dried, they must be dissolved out in water from the
discharge containing them.

3. Chemical Examination of the Semen.—But little informa-
tion can be derived in this way. According to Mvescher, the funda-

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368 SECRETIONS OF THE GENITAL ORGANS.

mental constituent of spermatozoa is nuclein. Globulin and serum-
albumin have been found in the semen, and it is very rich in inorganic
substances. Posner‘ asserts that albumose is also present.

IIl.—_SECRETIONS OF THE SEXUAL ORGANS OF THE FEMALE.

1. Mammary Secretion (the Milk).—During the entire period of
gestation, and especially from the third month of pregnancy onwards,
a thin, whitish, and more or less turbid fluid may be obtained by pressure
from the breast. This is a fact of great importance, and the existence
of such a secretion is by itself strong evidence of pregnancy.

The fluid in question, when examined microscopically, presents in
the first place a great number of strongly refractive bodies of very
irregular size. These are called colostrum-corpuscles; they are fatty

 

Fic. 145.—Colostrum of a Woman in Sixth Month of Pregnancy (eye-piece III.,
objective 8a, Reichert).

in character, and are usually aggregated in groups. In addition to
these are to be seen a few leucocytes and some epithelial cells from the
inner surface of the ducts.

Immediately after confinement the colostrum-corpuscles disappear
from the milk, and eight or ten days after parturition are no longer
to be found. Cerny® supposes that colostrum-corpuscles are lymphoid
cells whose function it is to take up and alter the unused milk-globules,
which they then transfer from the acini of the gland to the lymphatics.
In their place is seen a profusion of fatty globules of irregular dimen-
sions, and together with these certain particles (Hoppe-Seyler) which
consist of casein and nuclein.

In diseases of the breast, and especially in cases of abscess and
inflammation during suckling, the milk is apt to exhibit an inter-
mixture of leucocytes.

Micro-organisms occur in the secretion in connection with certain morbid
states. Thus Escherich® found fungi in the milk of a woman suffer-
ing from septicemia, and these on cultivation proved to be pathogenic.
Pathogenic Staphylococci have also been isolated by Koch’s cultivation-
process from the milk of a woman with facial erysipelas (Karlinsiz).”
Similarly the author has detected micro-organisms, and especially cocci,

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VAGINAL SECRETION. 369

which stained by Gram’s method, in the milk of a patient with puerperal
septicemia.$ Further observations on the presence of fungi in human
milk have been published by Mf, Kohn and H. Newmann.®

From observations which the author has made, it would seem probable
that tubercle-bacillus also is occasionally present. The matter deserves
further notice.

The milk of some of the lower animals has been known to be infested by non-
pathogenic micro-organisms (Bacillus cyanogenus and Micrococcus prodigiosus),
from which it may derive an abnormal blue or reddish tint (Ncelsen, Hueppe).!”

The chemical constitution of the milk varies under different condi-
tions both of health and disease. The milk of sick women is generally
less rich in fat, and the proportion of lactose is diminished. Neither
bile-pigments nor biliary acid have yet been satisfactorily demonstrated
in the secretion of jaundice (v. Juksch).1! The albuminous constituents
of human milk are serum-albumin, casein, and nuclein. In also contains
milk-sugar and fats. For the detection and estimation of the latter, the
method described for the same purpose in the chapter on urine may be
employed. Special processes for the quantitative analysis of the milk
may be found in Hoppe-Seyler’s work.

The examination of the milk of wet-nurses is a point of practical
interest for the physician. It should be tested carefully as to its naked-
eye and microscopical characters, and in all cases chemically analysed.
In addition to this, information may be derived from the employment
of the bacteriological methods. And it is highly expedient that the
milk, whether of healthy or diseased women, should be submitted,
wherever possible, to Koch’s plate-cultivation processes, so as to ascer-
tain the absence of fungi.

2. Vaginal Secretion.—This, under ordinary circumstances, is a
thin fluid with an acid reaction. It contains a few large leucocytes,
each with a single nucleus, and squamous epithelium cells, which, for
the most part, are covered with microbes. In vaginal catarrh the
number of leucocytes is greatly increased, and some red blood-corpuscles
may be visible.

In cases of ulcerating carcinoma implicating the vagina or the vaginal
portion of the uterus, a copious foetid discharge takes place, and in this
the characteristic large cells of cancer may be found (fig. 146).

Hausmann detected fatty needles in the vaginal mucus.

Among the parasites which have been found in this situation are :—

1. Yeast and Fission-Fungi.— Various fungi belonging to these classes
infest the vagina. Thrush-fungus vegetations also have been seen there.
The vaginal secretion normally (Winter’*) and during confinement
(Déderlein and Samschin }*) contains fission-fungi, as, e.g., Staphylo-

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370 SECRETIONS OF THE GENITAL ORGANS.

coccus pyogenes albus, aureus, and citreus. Finally, it is sometimes
important to examine the secretion for tubercle-bacillus and gonococci
by the prescribed methods.

2. Trichomonas Vaginalis.—This parasite is an infusorium of oval
shape, and about 10 # in length. It has a long caudal appendage, three
flagella, and a lateral row of cilia.

Of the chemical constitution of the vaginal mucus little is known. It
has been said to contain trimethylamin (Hilger).

 

Fic. 146.—Preparation of Vaginal Secretion in a Case of Cancer of the Cervix Uteri
(eye-piece I1I., objective 8a, Reichert).

3. The Uterine Secretion.

1. Menstruation.—At the outset of menstruation there is an increased
discharge of vaginal secretion. Later on there is mixed with this an
abundance of red blood-corpuscles and prismatic epithelial cells laden
with fat from the interior of the uterus. The proportion of blood-cells
begins to diminish after a few days, and leucocytes preponderate towards
the close of the period. At this time also epithelium and a large quan-
tity of fatty detritus are discharged.

2. The Lochia.—The fluid discharged during the first few days after
parturition is thin and of a red colour. In addition to red and white
blood-corpuscles it exhibits uterine and vaginal epithelium. Later,
whilst the red corpuscles diminish in number, the leucocytes and epithe-
lium increase, and the discharge assumes a grey or even white colour.!°
Microbes are always plentifully present, even in the absence of septi-
cemia. According to Déderlein,” healthy lochia are free from fungi,
while in disease he found them without exception to contain Strepto-
coccus pyogenes. These statements are confirmed by Thomen.!8

A point of special importance in diagnosis is the examination of the
uterine secretion for the pathogenic fungi, to which reference has been

already made. ‘The secretion may be removed for the purpose by means
of a tampon.

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CHAPTER X.

METHODS OF BACTERIOLOGICAL ‘RESEARCH.

THE great practical importance which this subject has acquired of late
makes it necessary that the physician should be familiar with the pro-
cesses for ascertaining the presence of micro-organisms.

In all cases where micro-organisms may be the exciting cause of
disease, his first task will be to detect them in the secretions or natural
fluids by means of the appropriate methods for staining them.

When this is done, it remains in many instances to discover the
micro-organisms in particular situations, cells or tissues, so as to exclude
a mere misleading coincidence.

Further, the micro-organisms are to be cultivated outside the system 5
so that, where their morphological character and their behaviour to
staining substances are not sufficiently distinctive, the requisite infer-
ences may be drawn from their mode of growth and development.

Finally, it is possible by experiments upon animals to settle definitely
whether the transmission of a pure cultivation of the micro-organisms
will produce symptoms more or less closely resembling those attributed
to their agency in man.

The staining methods at our disposal and the perfection of our optical
instruments in many cases render the detection of micro-organisms easy,
but their cultivation and the transferring of them to animals is often
very difficult. Thus in the case of many diseases, micro-organisms have
been discovered under such circumstances as to leave no doubt that
they were the exciting cause, while every effort towards their cultiva-
tion and transmission to animals has failed of success. This, however,
has been achieved in the case of a number of pathogenic fungi, as, for
instance, the bacilli of glanders, anthrax, tubercle, cholera, leprosy, and
probably of typhoid fever.

It is no longer necessary for diagnosis to pursue the inquiry in every
instance through its entire course (detection, cultivation, and transmis-
sion to animals); but in some diseases, as tuberculosis, it is sufficient
to note the characteristic effect of staining substances. In others,
again (as relapsing fever and, occasionally, anthrax), a simple micro-
scopical examination will serve, without the application of staining

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372 METHODS OF BACTERIOLOGICAL RESEARCH.

processes. In doubtful cases of anthrax, the diagnosis may be settled
securely by the direct transmission of the blood to animals,

With reference to Asiatic cholera, the mere detection of the fungus
in the stools is never sufficient, but it must be isolated by Koch’s
cultivation methods, when it will be recognised by its mode of growth.
With the progress of science we may learn to know a definite fungus
as the cause of each of the infectious diseases; but even then, when
all the conditions indicated above have been complied with, our labour
will not have ended. It will remain to extend our acquaintance with
the life-history of the parasites, so as to determine the sources of
nitrogen and of carbon and the inorganic salts upon which they depend
for their growth. It is only when this is done that a secure foundation
will be laid for a system of rational therapeutics.1

A short account will be given here of the methods employed in such
researches. It will naturally begin with a description of the apparatus,
and in the first place of the microscope.

I._THE MICROSCOPE.

The shape, size, and adjuncts of the body or stand of the microscope
itself are in general of little moment. Habit will determine, in most
cases, whether the tube used shall be worked by a screw or with the
hand. . For the examination of plate-cultivations, however, the former
will be chosen. Neither is it essential that the stand should be jointed,
but it is absolutely necessary that tt be faultless in its construction. It
must also be capable of adjustment for use with the most powerful objectives,
and with an Abbe’s condenser or equivalent arrangement.

The stage must be sufficiently large and firm, and the opening in it
as large as possible, so that a plate-cultivation, for instance, may be
inspected easily with a low power.

For bacteriological investigations, as has been already observed, an
Abbe’s or other condenser adjusted movably to the microscope-stand
is needed. The principle of such an instrument is this: The rays of
light reflected from the mirror of the microscope are passed through
the principal axis of a lens interposed between the mirror and the
objective in such a direction that they fall upon the object, which thus
receives a cone of light as highly concentrated as possible. If narrow
diaphragms be introduced between the mirror and the collecting lens,
an illumination of the image is obtained similar to, but probably some-
what more intense than, that where narrow cylindrical diaphragms are
used. The edges of the image are in all cases well defined, even in
unstained preparations, and such a condenser may be employed with
advantage for histological work. If the diaphragms be removed and

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THE MICROSCOPE—LENSES. 373

an open-condenser light consequently employed, the outlines disappear
and become entirely undistinguishable (Koch).2 Under these circum-
stances nothing else can be distinctly made out with uncoloured pre-
parationus. With stained preparations, however, it is far otherwise,
and in this lies the valuable application of the open-condenser light as
discovered by Koch. The outlines, in so far as they depend for their
appearance on a distinction in the refractive properties of the object
(corresponding to a structural difference amongst its parts) and those
portions which are but lightly stained, are lost to view, while the
deeply-stained particles, as the coloured nuclei of cells (granulations),
and especially fungi coloured with aniline or other dyes, become more
exquisitely defined. In this way micro-organisms may readily be seen
and recognised, even when very sparsely present in a preparation. he
apparatus 1s indispensable for bacteriological research.*

In addition to a suitable stand and a condenser, good objectives are
needed.

First a weak objective, magnifying about 60 to 80 diameters, for the
inspection of plate-cultivations; and in addition it is very advanta-
geous to have a good powerful dry objective. There are many objects,
as fresh blood, fresh milk, or fresh pus, for the examination of which
immersion-lenses are not suitable. For such purposes Zeiss’s lenses F
or D, or Reichert’s 84, may be recommended. With these, especially
if a condenser be also used, many bacteriological preparations, as those
of tubercle-bacillus from the sputum, may be adequately investigated.
For very delicate preparations, and in particular where minute details
of structure are to be made out, an immersion-system is needed. The
water-immersion systems, formerly much in use, have been superseded
of late by the oil-immersion (homogeneous immersion) lenses made by
Stephenson and Abbe and Zeiss, which are to be preferred on account
of the better definition and clearness of the image which they produce.
Instead of water, there is interposed between the front lens of the
objective and the object (cover-slip), a fluid having the same refractive
index as glass. For this purpose a mixture of fennel- and castor-oils
may be used. Reichert employed with his lenses a mixture of vase-
line and olive-oil, which has the advantage of being odourless, and of
penetrating less readily within the lenses. At present concentrated
cedar-oil is most in use. Such a system has the further advantage
that it does not require correction-collars to be used, as do dry lenses,
and that powerful eye-pieces may be employed with it. It is very

* The best results are obtained with the instruments supplied by Hartnack (Pots-
dam), Seibert and Kraft (Wetzlar), Leitz (Wetzlar), and especially by Zeiss (of Jena).
CO. Reichert of Vienna supplies with his little microscopes IV. and V. a condenser
which is very suitable for clinical purposes.

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374 METHODS OF BACTERIOLOGICAL RESEARCH

advantageous also to place a drop of oil on the under surface of the
slide which carries the object, between this and the collecting lens of
the condenser.

 

Fic. 147. GesLicrchenus Stand No. IL.b., with draw-tube, rack-and-pinion fine adjustment,
and Abbe’s condenser.

Of less moment is the choice of an eye-piece. In general, for every
form of investigation, except bacteriological research, eye-pieces of low
magnifying power should be taken. For the rest, the eye-pieces II.

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THE MICROSCOPE. B75

and V. as supplied by the firms of Reichert and Zeiss will serve for
all cases. The periscopic eye-pieces of Seibert and Krafft are very
excellent.*

An objective of crown- and flint-glass was first adopted by Dv. Schott
of Jena. It is an admirable contrivance, and has become indispensable
for many purposes, as in photographing micro-organisms, where a well-
defined achromatic outline is required. Zeiss has given such the name
of apochromatic objectives. The corresponding compensation eye-pieces

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Fic. 148.—Abbe’s Condenser, as made hy Zeiss. Natural size, side view. Sp. mirror.

should be used with them. Their chief advantage lies in the fact that
they give a clear and well-defined image with eye-pieces of greater
streneth than could formerly be used. Apochromatic objectives of

* The author has for many years employed an instrument made by Reichert, and
he has found it to serve well in every kind of microscopical work, histological and
bacteriological. Its parts are as follows :—Eye-pieces II. and IV., objectives 4, 8a,
and oil-immersion 74, ; a small stand with condenser (Abbe’s) and cylinder-diaphragm.
Its price was 207 florins without the oil-immersion, which cost 107 florins. Very
good and inexpensive systems of lenses are also made by Plossl of Vienna.

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376 METHODS OF BACTERIOLOGICAL RESEARCH.

excellent construction are supplied by Reichert. The images of the
most delicate objects obtained with Reichert’s homogeneous immersion
objective of 2 mm. focal length, and even with the working eye-piece
12, are clear and distinct in their smallest details. There is one dis-
advantage attending the use of these lenses. They need a finer
adjustment than the usual mechanism affords, and the image becomes
indistinct with the slightest movement of the instrument. It has then

 
   
    
      

  
 
 

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Fic. 149.—Abbe’s Condenser as above, showing the collecting system of lenses.
d. Iris diaphragm.

to be focussed anew. ‘This defect is apt to produce misleading appear-
ances, and it must be admitted that the otherwise excellent apochro-
matic objectives supplied by Zeiss are so far in need of improvement.
[For bacteriological work, it is convenient to have a microscope with
a stand to which an Abbe’s condenser can be fixed under the stage.
Fig. 147 shows a convenient form made by Reichert of Vienna. Other
makers furnish somewhat similar stands. Abbe’s condenser is placed
under the stage, and the tube of the microscope is provided with a

 
DETECTION OF MICRO-ORGANISMS. 377

“revolver” or ‘“nose-piece,” to which lenses of different magnifying
powers are fixed.

In an Abbe’s condenser (fig. 148) the illuminating apparatus is a
condenser system of very short focus (the section of the lenses is shown
in fig. 149), which collects the light reflected by the mirror (Sp)—the
plane side of the mirror being used—into a cone of rays of very large
aperture, and projects it on the object. For ordinary work the cone
of light is reduced by means of diaphragms, the most convenient form
being that known as the “iris diaphragm,” which can be adjusted to
any size (fig. 149, d). Oblique illumination can be obtained by placing
the diaphragm eccentrically, which is done by means of the rack-and-
pinion movement (e).

When very exact definition is required, apochromatic lenses are
employed. They are expensive, but the objectives are so constructed
as to secure the union of three different colours of the spectrum in one
point of the axis. The images projected by them are nearly equally
sharp with all the colours of the spectrum. As there is very great
concentration of light by these objectives, they permit of the use of
very powerful eye-pieces, thus giving high magnifying power with rela-
tively long focal length. A series of compensating oculars are used
with these lenses. The eye-pieces of extremely low power are called
“searchers,” while the ordinary or working eye-pieces, beginning with
a magnifying power of 4, are classified as 4, 8, 12, 18, and 27. With
these eye-pieces great magnifying power is obtained, partly by the lens,
but also by the ocular used. ]

II. THE DETECTION OF MICRO-ORGANISMS.

In many cases the object to be examined may be placed under the
microscope without preparation of any sort. The characteristic micro-
organisms will then become visible. This is so with the spirillum of
relapsing fever, anthrax-bacilli in the blood, &c. For the most part,
however, special processes are necessary for the detection of micro-
organisms. The details of some of the processes for the prepara-
tion of specimens have been gone into in the chapters on the Blood,
Sputum, &c., which the reader will consult for information concerning
them.

It will not be out of place if we give here a brief summary of the
methods in use, and point out the particular purposes to which each is
applicable. The principles upon which all of them are based were
worked out by Koch, Hhrlich, and Weigert ; and almost every day some
new process or a modification of the old familiar methods is made
known. It would far exceed the limits of this book to attempt an

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account of all the methods which have been suggested, and the various
modes of applying them. We shall confine ourselves to what has
appeared in the more important and systematic essays dealing with the
subject. Those of Giinther*? and Unna,* especially the latter, com-
prise an accurate and exhaustive account of the methods for staining
fungi. Particularly good results in the staining of micro-organisms in
sections, which, however, lies beyond our province, have been obtained
with Kiihne’s® processes. They have been. tested by Rille, a pupil of
the author, and have been found most valuable for dry cover-glass
preparations as well. The methylene-blue method® and Kiihne’s"
modification of Gram’s method (staining with alcoholic solution of
Victoria-blue) are very serviceable in the examination both of sections
and of the secretions.

In the examination of the blood and secretions for pathogenic micro-
organisms it is in general best to proceed with the use of basic aniline
dyes as described at p. 40. Should it happen that no result is obtained
in this way, greater certainty may be secured with Ldfler’s method
(p. 41), which is especially suitable for detecting the bacilli of typhoid
fever and glanders, and, finally, with Gram’s method (p. 41). All the
fungi hitherto discovered stain with this, except the bacilli of typhoid
and cholera, and gonococct. The bacillus of hen-cholera is also un-
affected by it.

Guinther's method (p. 45), is very serviceable for staining the spirillum
of relapsing fever. The investigation of the blood and secretions for
tubercle-bacillus should be carried out precisely in the manner laid down
by Koch and Lhrlich (p. 105). Staining with basic aniline dyes serves
well for the detection of fungi in the buccal cavity, the nasal secretion,
and the gastric contents ; but for examining the buccal secretion Gram’s
or Giinther’s method may also be adopted with advantage, since they
render visible the very delicate Spirocheete buccalis (p. 81) and capsulo-
cocci.

In searching for the fungi of the alimentary canal, pathogenic and non-
pathogenic, all the processes hitherto mentioned should be employed
where a thorough investigation is aimed at, and the observer should not
forget to add a little iodo-potassic-iodide solution to a drop of the fiuid
under examination (see p. 171).

In examining the urine, the best results are secured with Gram’s or
Friedlander’s method (p. 108). By their aid the author has detected in
various specimens of urine from persons both in health and disease an
unexpected profusion of different forms of fission-fungi.

The micro-organisms which occur in pus stain most readily with Gram’s
method, or its modification already referred to (Victoria-blue). Liffler’s
and Friedlinder’s methods are applicable to the same purpose.

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CULTIVATION OF MICRO-ORGANISMS. 379

To stain the spores of micro-organisms a preparation is made in the
manner indicated at p. 40, but exposed for a longer time to the heat.
It may be passed through the flame about ten times (Hueppe).8 When
this is done the bacilli lose their staining properties, whilst the spherical
objects, if they consist of spores, take up colouring-matter. It is still
better to employ the process of double staining. The preparation is first
stained in a hot Ziehl-Neelsen fuchsin solution, then decolorised with
nitric acid, and again stained with methylene-blue. The spores then
appear red and the bacilli blue.? :

Special processes have been devised for the purpose of defining the
flagella which some bacteria present. These have been worked out by
Lofier, Kiinstler, Newhaus, and Trenkman2® As a mordant Loffler
employs a fluid composed as follows: solution of tannin (tannic acid 20
parts, water 80 parts) ro cc. ; a cold saturated solution of ferric sulphate,
5 ec.; watery or alcoholic solution of fuchsin, methyl-violet or wool-
black, r ce. The staining-fluid is neutral saturated anilin-water-fuchsin
solution. The method of proceeding will be described here. The cover-
glasses are heated with concentrated sulphuric acid, washed with water
and then with a mixture of alcohol and ammonia in equal parts, and
afterwards polished with a cloth which should be free from grease.
They are then brought in contact with a platinum needle carrying a
particle of the pure cultivation, and the latter is spread out finely and
divided upon their surface, after which they are allowed to dry in the
air. They are next grasped between the fore-finger and thumb of the
observer and passed through the flame of a lamp. <A drop of the
mordant is now supplied to the preparation, the cover-glass is again
warmed, and after a minute the preparation is rinsed first with water
and then with alcohol. A drop of the staining fluid is next added, and
the preparation is heated and washed with water as before.

ITI. CULTIVATION OF MICRO-ORGANISMS.

A. Methods of Sterilisation.—When the presence of micro-
organisms has been ascertained with certainty by the processes described
above, the next task is to secure their development outside the system,
in other words, to cultivate them. To this end the first requisite is
the means of sterilisation. Zhe essential condition that. must be secured
in all such cultivation researches is the absolute freedom of the instruments
and vessels employed from fungi and germs capable of development.

In the case of metallic instruments, the necessary cleanliness may be
attained best and most readily by raising them to a red heat in the
flame of a Bunsen’s burner. Glass vessels, such as test-tubes, flasks,
&e., should be purified as far as possible by washing first with distilled

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water, then with corrosive sublimate solution (1: 1000), and rinsing
out with alcohol and ether, after which they may be sterilised in a dry
heat. This can be done best by a sterilising apparatus for temperatures
over 200° C.; but if such an apparatus cannot be had, it may also be
done by heating the vessels cautiously over the flame of a Bunsen’s
burner. In the latter case they should first be carefully dried, in order
to prevent the glass from cracking, and the mouth of each should be
closed with a compact plug of sterilised cotton-wool before heat is
applied.

It is very important to heat the sterilised vessel again immediately
before using it, having previously ascertained that the plug is at once
sufficiently compact and easily extracted.

The plug may be made of fine glass-fibre, or, still better, of asbestos, instead
of cotton-wool.

Test-tubes which are to be held in readiness for use are purified in the
manner described, fitted with a plug, and then placed in wire baskets,
and sterilised in a dry heat.

The sterilisation of the nutrient fluids presently to be mentioned
may be effected by boiling them in glass flasks furnished with a plug
of cotton-wool in those cases where the constitution of the fluid is not
altered by heat. To sterilise nutrient gelatine and agar-agar solution
(see p. 383), these substances are repeatedly boiled in the vapour steri-
lisation apparatus. Too frequent, and especially too continued, boiling
should be avoided in the case of these two substances, lest they should
remain fluid after cooling.

When potatoes are employed as the nutrient substance, they are first
freed from sand with a brush, placed for an hour ina 5 per cent. corrosive
sublimate solution, finally sterilised (boiled) by steam at boiling-point,
and cut into strips with a sterilised knife. Where the vapour steri-
lisation apparatus devised by Aoch cannot be had, a Papin’s digester
with a perforated tray will serve. It is more difficult to sterilise those
nutrient substances that will not bear a heat of 100° C. without their
parts coagulating and so becoming opaque. In their case, Koch recom-
mends that they should be sterilised by intermittent heating. This
plan is especially useful for the purpose of freeing blood-serum from
fungi and germs.

To prepare sterilised blood-serum, Hoch proceeds as follows :—The
part of the animal’s skin through which the blood is to be taken is
shaved, and thoroughly cleansed by washing it with solution of corrosive
sublimate, alcohol, and ether. The underlying blood-vessel is freely
exposed, and opened with sterilised instruments. The blood is then
made to flow directly from the artery into a sterilised glass cylinder,

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STERILISATION—NUTRIENT SUBSTANCES. 381

which is filled to the brim and placed in a refrigerator or upon ice for
twenty-four to forty-eight hours, so as to allow the corpuscles to settle.
The clear amber-coloured serum that has separated after twenty-four
hours is drawn off in sterilised pipettes and placed in test-tubes pre-
viously sterilised in the manner already indicated. These are heated
to 58° C. for two to six hours, and finally the serum is made to
coagulate by heating it to 65°—68° C.

With a view to obtaining the largest possible inoculation surface,
it is desirable to procure the coagulation of the fluid in the test-tube
with its surface inclined very obliquely to the latter. This end may
be attained by using a tin vessel with double walls between which water
may be retained, covered on top with a plate of glass, and having at
its anterior end two movable feet which can be fixed by screws. Or
instead of this the test-tube may be fixed by a clamp at an oblique
angle in a pot filled with water. For many purposes, and especially for
the cultivation of the pathogenic fungi occurring in man, human blood-
serum should be employed. To procure human serum the author has
adopted the following plan :—The skin is first thoroughly cleansed in the
manner already described, and a puncture is made in it with a cupping-
blade previously sterilised by exposure to a heat of 200° C. The blood
is taken in a cupping-glass similarly sterilised, and poured into small
test-tubes also sterilised. The remainder of the process is carried out as
before. Human serum has proved, in the author’s experience, to possess
notable advantages over that of animals. It remains clearer after coagu-
lation, and is firmer. Where human blood-serum cannot be had, transu-
dation fluid or serous exudation may be taken instead. In that case it
is prepared in the same way as the former. A very useful modification
of the process for the preparation of blood-serum and of blood-serum
plates has been devised by Unna.1! To the blood-serum of the calf,
peroxide of hydrogen is added drop by drop, until the mixture, which
was at first a brownish-yellow, becomes clear. For this purpose, a
quantity equal to about half the volume of the serum will be required.
The mixture is neutralised with a 2 per cent. solution of sodium car-
bonate and passed through a wet filter packed to one-fourth of its depth
with well-calcined diatomaceous (Kieselguhr) earth. The fluid which
first passes through is usually turbid, and must be refiltered; and,
finally, the clear filtrate is sterilised in the usual manner. For making
plate-cultivations Unna recommends the admixture of 10 per cent.
gelatine or 6 per cent. agar-agar.

B. Nutrient Substances.—By the methods described at p. 378
we are enabled to detect micro-organisms; and the measures that must
be taken to render the fluids and nutrient substances as well as the instru-
ments employed in research free from fungi have also been indicated.

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382 METHODS OF BACTERIOLOGICAL RESEARCH.

It does not suffice to place a fungus or the germs of fungi at random
in solid or fluid nutrient substance duly sterilised in order to ensure
their successful cultivation; but there is for each of the pathogenic
and non-pathogenic fungi an appropriate soil, which differs widely in
its chemical constitution in different cases. The researches of Pasteur 1?
in connection with yeasts, of Mégeli and Buchner 14 with bacteria and
moulds, of A. Schultz!® with moulds, of the author !¢ with the Micro-
coccus urea, and of Hueppe” with the lactic acid bacillus, have shown
that, in addition to a supply of nitrogen and carbon, each fungus
requires certain inorganic salts for its growth. And further, there is
in each case some particular temperature at which the fungus thrives
best (optimum temperature).

It is only when all these conditions have been secured that cultiva-
tions can be made successfully.

To draw unequivocal conclusions from researches of this sort, it is
above all necessary to apply Koch’s process, presently to be described,
for obtaining pure cultivations of the fungus which is being investigated,
and to implant these upon solid or fluid nutrient substances.

1. Nutrient Fluids.—The use of fluids as nutrient substances
entails uncertainty in the result, since the microscope cannot be em-
ployed to examine them. Still it is not difficult to obtain a pure
cultivation in a fluid if it be sterilised, and if a cultivation known to
be pure be planted in it.

The process is then the same as for the preparation of pure cultiva-
tions by Koch’s method, which will be described presently.

The composition of the nutrient fluid must vary with the nature of
the fungus to be cultivated.

Thus yeasts grow best in a somewhat acid saccharine fluid. Moulds
require a medium holding free acids in considerable quantity. Feebly
alkaline fluids are the best for certain non-pathogenic bacteria. Fluids
of definite constitution for the cultivation of bacteria—as those of
Pasteur, Cohn, and the author—agree in that they all contain nitro-
genous and carbonaceous matter and inorganic salts.

Although it is true that by cultivation in nutrient fluids much useful
information has been obtained concerning the life-history of some of
the fission-fungi, the method is not employed for the investigation of
pathogenic micro-organisms, partly because, as has been said already,
there always remains some doubt as to whether the cultivations obtained
with them are in reality pure cultivations, and partly because it would
seem that pathogenic fungi thrive badly in fluids. The author has en-
deavoured, without success, to obtain pure cultivations of pneumonia-cocci,
Streptococcus pyogenes aureus, and other pathogenic micro-organisms, on
sterilised nutrient fluids of the most varied constitution.

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NUTRIENT SUBSTANCES. 383

Control experiments have proved that non-pathogenic fungi developed readily
in such nutrient fluids, while the same fluids, maintained under like conditions,
when infected with pathogenic fungi remained sterile.*8

2. Solid Nutrient Substances.—As in the case of nutricnt fluids,
the chemical constitution of solid nutrient substances will vary greatly
according to the biological character of the fungus under cultivation.

1. Blood-Serum.—The blood-serum of animals is required for certain
pathogenic fungi, e.g., tubercle-bacillus; gonococci are cultivated in
human serum. The method of preparation has been sufficiently de-
scribed.

2. R. Koch’s Nutrient Gelatine.—This is prepared in the following
manner :—50o0 grms. of good meat, free from fat and freshly minced,
is rubbed up with rooo grms. of distilled water and placed for twenty-
four hours in a refrigerator. It is then strained through linen, the
resulting fluid made up to rooo ce., and 10 grms. of dry peptone, 5
erms. of common salt, and 100 grms. of white edible gelatine are added.
The fluid is heated in a flask until the gelatine is dissolved. It is then
accurately neutralised with sodium carbonate, and boiled for half an
hour to an hour, when a specimen is tested for its reaction ; after this
the fluid is filtered through a hot-water funnel and poured into test-
tubes sterilised in the manner directed (see p. 379), and sterilised for
ten minutes a day for three days.

The test-tubes may now be kept for weeks or months at the ordinary
temperature before they are used; but when this is done, an india-
rubber cap should be placed over each above the plug of cotton-wool,
to prevent evaporation from the gelatine. Keeping the nutrient gelatine
thus for a long time in the test-tubes has this advantage, that when
through an accident in its preparation germs have obtained admission
to the fluid, the resulting cultivations are made evident by clouding in
the gelatine, which will not then be employed for cultivation research.

Koch’s nutrient gelatine, which may be modified at will by the addi-
tion of organic or inorganic substances, will serve for the cultivation of
all pathogenic and non-pathogenic fungi which grow at the ordinary
temperature of a room. It cannot be used at higher temperatures (over
25-30 C.), which cause it to melt, and for micro-organisms which
liquefy gelatine rapidly.

3. Agar-Agar.—In many investigations, especially for fungi which
require a temperature not lower than blood-heat to develop well, or
which liquefy gelatine rapidly, agar-agar may be used with advantage
instead of gelatine as a nutrient substance. It is prepared in the same
way as nutrient gelatine fluid, only that instead of gelatine 1.5-2 per
cent. of finely divided agar-agar is added to the fluid. Unfortunately
it is difficult to prepare a perfectly pure and clear agar-agar solution in

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384 METHODS OF BACTERIOLOGICAL RESEARCH.

this way, and that substance, even when added in small particles, filters
badly through the hot-water funnel. Schottelius!® and Richter,? how-
ever, have modified the process in such a manner that a clear nutrient
agar-agar may be easily obtained.

4, Potato.—Fnough has been said about the sterilisation of potatoes
employed for nutrient material (p. 380). Their use is of great service
in studying pathogenic fungi, many of which develop on potato in a
highly characteristic manner (see pp. 176, 354).

Starch to which suitable nutrient salts have been added forms a solid
nutrient substance, which is very useful and easily sterilised. Together
with gluten and bread it is especially good for the cultivation of moulds.
For the latter also boiled blood clots may be employed with advantage.?#
Both starch and blood may be easily and effectually sterilised by a current
of steam.

Recent investigators have in many instances somewhat modified the
constitution of, and the method of preparing, nutrient substances.
Thus the addition of glycerine to peptone gelatine or agar-agar has been
tried successfully. All the modifications suggested cannot be noticed
here. The use of stained nutrient solids and fluids, however, demands
notice.

According to Birch-Hirschfeld,?? living anthrax-bacilli can be procured
stained by inoculating from a pure cultivation of the fungus upon 15 per
cent. nutrient gelatine which contains in 6 cc. 1 cc. of a watery solution
of fuchsin or methylene-blue. The cultivation should remain for twenty-
eight hours at 35°-40° C.*8

In the cultivation of the bacillus of typhoid fever also, stained (benzo-
purpurin) nutrient substances are useful.

The application of this principle, as by the addition of neutral tincture
of litmus,24 or other substances, to show the formation of free acid or
acid salts, has thrown much light upon the nature of pathogenic and
non-pathogenic fungi. The addition of a little watery solution of
Congo-red or benzo-purpurin to nutrient substances has proved, in the
author’s hands, a valuable expedient in the study of the biological
character of micro-organisms. If the material examined contains acid-
forming fungi, the cultivations upon stained nutrient soil take a colour
ranging from a pale to a blackish blue, and their presence is discernible
with the naked eye. The method is particularly appropriate for the
study of micro-organisms from the intestine under normal and patho-
logical conditions.

C. Preparation of Koch’s Pure Cultivations. — Although
Klebs?® and Brefeld° had already suggested, and themselves adopted,
the use of solid nutrient substances for the investigation of fungi, it
was Koch who grasped the significance of these methods, and, by sub-

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PREPARATION OF PLATE-CULTIVATIONS. 385

mitting the cultivations in fluid and solid media to the control of the
microscope, laid the foundation of modern bacteriology.

To this observer we owe not only the knowledge of many funda-
mental facts in bacteriology, such as result from the discovery of the
bacillus of tubercle and of cholera, but nearly all the cultivation and
staining methods in use are derived from his researches and those of
his pupils.

The methods now to be described have for their object as far as
possible to separate the individual germs from a mass of fungi, and to
promote their development apart from one another in solidifying fluids.
This may be done by Koch’s processes for obtaining plate-cultivations
on glass slides and test-tube cultivations. It is usually expedient to
make plate and test-tube (deep inoculation) cultivations together.

1. Plate-Cultivations.—A test-tube, in which from 5-8 cc. of solidified
nutrient gelatine has been placed as directed above, is put into warm
water, and allowed to remain there until the gelatine is quite fluid.
Care is now taken that the plug in the mouth of the test-tube is freely
movable by rotating it a little if necessary. The test-tube is held
obliquely between the thumb and index-finger of the left hand, the
plug with the upper end between the second and third fingers (Koch’s
“orasp”) A little of the fungoid material is taken with a freshly-
sterilised platinum needle, and placed on the gelatine, so as first to
touch its edge and then to mix with the fluid. In doing this, draughts
of air must be excluded from the room. In the same way one or more
drops of this first dilution are placed in nutrient gelatine in another
test-tube (second dilution), and if a provisional inspection has shown
that the fluid under examination is very rich in fungi, the process is
repeated again (third dilution). It may then be assumed that the
germs in the nutrient gelatine are actually isolated. The infected
gelatine is next poured out on to glass plates about 14 cm. in length
and 12 cm. broad, and caused to solidify quickly. This may be done in
a few minutes by the application of cold. The glass plates are prepared
in the following manner:— They are first thoroughly cleansed with
water, solution of corrosive sublimate, and alcohol, and placed immedi-
ately before use in iron cages in the steriliser, where they are heated
for a long time at 100°-150° C. They are taken out when cool, and
laid upon a large sheet of plate-glass made cold with ice. This should
have a polished, even surface, and must also be accurately level
when used, an end best attained by mounting it on a tripod stand
with a spirit-level visible beneath the glass. Such an accessory, how-
ever, is not essential, and it may be dispensed with if a little care
be taken. :

Recently the use of the glass plate cooled on ice has been supplanted

2B

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386 METHODS OF BACTERIOLOGICAL RESEARCH.

in many laboratories by that of a polished plate of iron about 20 cm. in
diameter and 8 cm. thick, which is carefully sterilised beforehand. This
is placed upon the tripod and adjusted with the spirit-level. An iron
plate was first employed in Lichtheim’s laboratory at Berne, and it is
very suitable to the purpose in hand, because with it nutrient fluids
solidify very quickly. In warm weather, as in the summer, the iron
plate must be previously cooled on ice, but ordinarily this precaution
is unnecessary. The author has employed such a plate exclusively in
his bacteriological work during the last four years, and found it most
serviceable.

The nutrient gelatine is poured upon the plates in the following
manner :—The small glass plates upon which nutrient gelatine is to be
spread are laid upon the glass plate made cold with ice or on the iron
plate, and that edge of the test-tube over which the gelatine is to flow
is heated. When the edge has cooled, the gelatine is poured here and
there over the cold surface of the plates, and spread out upon them as
evenly as possible by means of the sterilised edge of the test-tube, care
being taken that the edges of the plates are left free. The plates are
then covered with a bell-glass. When solidification is complete, they
are placed on sterilised wet blotting-paper in a glass dish of about 30
cm. diameter, which has been previously well purified with corrosive
sublimate, and another bell-glass is put over them.

In order to obtain the sterilised and wet blotting-paper, a jet of super-heated
steam is directed upon the filter-paper in the bottom of the glass dish for from
eight to ten minutes. In this way the bell-jar as well as the filter-paper are
sterilised, and the latter is saturated with sterilised vapour.

In such a vessel six plates, or even more, can be put, with a glass
partition between each pair.

Instead of plates, H. Hsmarch?" has recently employed test-tubes,
which will serve for many of the purposes of plate-cultivations. With
these the process is as follows, Some of the fungoid material is placed
in the fluid nutrient gelatine in the test-tube in the manner already
described, and mixed with it as intimately as possible. The test-tube,
covered with an india-rubber cap above the plug of cotton-wool, is then
held as vertically as possible, and with the sterilised plug and cap
directed somewhat upwards, under a stream of cold water, and in this
position is made to rotate upon its long axis. After a little while the
nutrient gelatine has solidified in the cylindrical form of the test-tube.
This process has considerable advantages. Cultivations so made can be
inspected not only with weak (Reichert IV.), but also with powerful
objectives ; they are less likely to be contaminated ; individual cultiva-
tions may be removed with a little care even under the microscope, and

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PLATE-CULTIVATION. 387

less annoyance is apt to arise from the unpleasant odour which the
cultivations often give rise to than is the case when plates are used.
To these the name of cylinder-cultivations may be appropriately given.
On a plate or in a test-tube so prepared, after a longer or a shorter
interval, there appear little punctiform colonies, which are already
sufficiently distinguishable from one another, and at the same time the
gelatine is often partly liquefied and gives off a disagreeable smell. If
now a minute particle be taken from each of the colonies by means of
a sterilised platinum needle and submitted to the same process over:
again, pure cultivations will be had of all the fungi which develop in
nutrient gelatine.

At the same time, by placing the entire plate under the microscope
and examining it, it will be possible to study the mode of growth of
the fungi, and also to determine whether in any given case the cul-
tivations are pure or contaminated by admixture with other fungi.
Certain distinctions in the shape and colour of the cultivations can
also be recognised with the naked eye, and by removing a particle on
a platinum needle from an individual developing cultivation under the
microscope and transferring it directly to a test-tube (cultivation by
deep inoculation), a definite fungus may be cultivated in a little time
and with little trouble.

Cultivations with nutrient agar-agar are made in the same way as
with nutrient gelatine. The former substance should be used in all
cases of fungi which contain spores and where the growing fungi cause
nutrient gelatine to liquefy quickly; as, for instance, in making culti-
vations from the feces, and in cultivating micro-organisms which require
a high temperature (37° and upwards) for their growth.

The cultivations are placed in an incubator such as Koch and others
(d’Arsonval) have devised. The construction of these is the same in
all cases. The incubator has double walls enclosing a compartment.
for water, with arrangements (thermostats) by which the internal
temperature may be maintained constant to within o.2° C. Experi-
ence, and especially Koch’s researches, have shown that a number of
pathogenic fungi, as, for instance, the bacillus of tubercle, will thrive
only at a definite and continuous temperature. To aid in securing
this, various thermostats have been constructed recently. Of these, the
author uses the thermo-regulator of Z. Meyer. The principle of the
instrument is to regulate the supply of gas for heating the incubator
by conducting it through an ethereal atmosphere confined by a mer-
curial valve, so that more or less gas is conducted to the jet according
to the temperature required in the incubator.

This instrument answers well. Such a thermostat has been in use:
for several months in Professor Nothnagel’s clinic. Notwithstanding

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388 METHODS OF BACTERIOLOGICAL RESEARCH.

the great variation in gas-pressure, the temperature recorded never
varied by more than o.2° C.

2. Cultivation by Deep Inoculation.—A particle of the fungoid mass
is taken on a sterilised platinum needle and implanted on nutrient
gelatine or agar-agar in a test-tube by removing the sterilised plug
with the mouth of the tube downwards and plunging the inoculating
needle into the nutrient substance. After the lapse of a few days the
fungus develops in a very characteristic manner in the gelatine. This
proceeding is adopted only when a pure cultivation has been obtained
with plates, and it is then of service in the further study of the micro-
organism. &, Fischl29 has removed the cylinder of gelatine from
the test-tube with a cork-borer, and Weisser ®° by the action of heat;
and by subsequently hardening it in alcohol or a 1 per cent. solution of
bichromate of potash, these observers were able to observe the develop-
ment of the fungus in microscopical sections.

3. Cultivations on Glass Slides.—A sterilised platinum needle is —
infected with a particle from the fungoid fluid in the manner indicated
on p. 385, and drawn across the surface of nutrient gelatine spread upon
a slide in such a manner that the fungi lodge in the furrow. After a
few days colonies of fungi develop in the line of inoculation.

4. Cultivation in Hanging Drops.—MKoch was the first to adopt this
method of cultivation. With it the growth of the micro-organisms
can be observed directly under the microscope. It is carried out
thus:—A glass slide with a hollow surface is taken, and the edge of
the concavity is smeared with a little vaseline, or a mixture of five
parts of vaseline and one of paraffin may be used instead, as Birch-
Hirschfeld recommends. A drop of sterilised broth is then placed on
a clean cover-glass infected from the bacterial fluid, and covered. with
the slide in such a way that the drop is suspended in the middle of, the
cell. The sterilised broth is prepared in the same manner as nutrient
gelatine, except that the addition of gelatine is omitted. For micro-
scopical examination an oil-immersion lens with an Abbe’s condenser
and narrow diaphragm should be used. And where fungi are studied
in this way, the edges of the drop should be observed with special care,
since it is there that the morphological characteristics of the micro-
organisms are best marked.

5. Cultivation by Exclusion of Air.—A number of micro-organisms
develop only in the absence of air (oxygen), and the processes for their
cultivation have been worked out by Koch, Hesse, Buchner, Gruber,
and others.

Koch seals up the test-tube cultivation with plates of mica, Hesse with
oil. Gruber exhausts the air with an air-pump and fuses the vessel.
Buchner *! employs a solution of pyrogallol and caustic potash to absorb

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TRANSMISSION OF PURE CULTIVATIONS TO ANIMALS. 389

oxygen. When this is to be done, the test-tube cultivation, suitably
prepared, is placed within a second larger test-tube, which contains the
solution, and which is then closed at the top with an air-tight caoutchoue
cap. For cultivations in hanging drops, Buchner’s method is recom-
mended by N2kiforoff.2 The exclusion of air from plate-cultivations is
best effected by Bliicher’s** contrivance.

IV. THE TRANSMISSION OF PURE CULTIVATIONS TO
ANIMALS.

This constitutes a very important part of bacteriological study. It
may be conducted in many ways.

(a.) The animal is placed in a closed chamber, and the atmosphere
is saturated with sterilised water containing the bacteria by means of
a spray producer. Experiments of this kind are very valuable for the
study of infectious diseases and of inhalation remedies.

(b.) The pure cultivation of a definite fungus is given to the animal
with its food. In doing this the chief precaution necessary is to
see that the food itself is innocuous. Koch's plan is to enclose the
cultivation in a small starch capsule provided with a lid, and to
place this on the back of the animal’s tongue. Most of the bacteria
that are devoid of spores appear to be destroyed by the action of the
free acid in the stomach, and on this account it is advisable to neutra-
lise the acid by the administration of alkalies, such as Koch used
in his cholera researches, or to perform laparotomy with strict anti-
septic precautions, and to introduce the cultivation directly within the
duodenum.

(c.) Cutaneous inoculation. The hair having been removed from
some part of the body, as the ear, which the animal cannot easily reach
with its tongue, a superficial wound is made there, and a portion of
the cultivation is lodged within it.

(d.) In mice the inoculation is best made subcutaneously at the root
of the tail. Or the purpose may be effected by infecting subcutaneously,
or within one of the natural cavities, by means of Koch’s modification
of Pravaz’s syringe. In this instrument a dise of cork is substituted
for the india-rubber, which will not bear the great heat necessary to
ensure sterilisation. A part of the cultivations suspended in water is
sucked into the syringe, and the fluid injected beneath the animal’s
skin. A simple glass cannula with a compressible india-rubber bulb

will also serve.

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390 METHODS OF BACTERIOLOGICAL RESEARCH.

V. SCHEME OF A BACTERIOLOGICAL INVESTIGATION.

1. The fluid to be examined is taken from the body with sterilised
instruments and under the requisite precautions, and a drop is inspected
microscopically, either with a powerful dry system or a homogeneous
immersion objective; narrow diaphragms and an Abbe’s condenser
being also used. Dry preparations are made and stained. In doing
this, solutions of the basic aniline dyes are used, or one of the other
methods (p. 378), as those of Gram, Friedlander, &c., according to the
character of the fungi supposed to be present.

2. Another drop of the fluid is added to fluid nutrient gelatine or
agar-agar to obtain plate-cultivations.

The plate-cultivations are examined with the microscope after twelve
to twenty-four hours, and it is seen whether they contain fungi which
are identical with, or resemble in their mode of growth, others already
known or under observation.

Should it appear that no pure cultivations have yet formed, other
plates are made from those already prepared, until one is obtained in
which a single fungus develops.

3. Drop-cultivations are made, and their growth observed directly.
Moreover, these are nourished on various substances, such as potatoes,
gluten, &c., and their behaviour to different nutrient fluids and under
different conditions of temperature is studied.

4. Pure cultivations so obtained are transferred to different animals,
and the morbid symptoms induced are observed. If such symptoms
are analogous to those occurring in the human system in presence of
the same micro-organism, they may be assumed to be due in both cases
to the agency of the latter.

When this is done, however, the resources of bacteriology are not yet
exhausted. The biological characteristics of the fungi remain to be
investigated, as to what sources of nitrogen, what sources of carbon,
and what inorganic salts they require. It is only in this way that
we can arrive at just conclusions concerning the nature of infectious
diseases, and attain to rational methods of anti-bacterial treatment.

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BIBLIOGRAPHY.

CHAPTER I.
THE BLOOD.

Landois and Stirling, Human Physiology, p. i., 4th edit.

~ Inebreich, Berichte der deutschen chem. Gesellschaft, i. 48, 1868.

* Zuntz, Centralblatt fiir die medic. Wissenschaften, v. 531 and Sor, 1867.

4 Lassar, Archiv fiir die gesammte Physiologie, ix. 44, 1874.

® Landois, Real-Encyclop., iii. 161, 2nd edit., 1885.

® V. Jaksch, Zeitschrift fiir klin. Med., xiii. 350, 1887.

* Proceedings of the Royal Society of Edinburgh, 18th June 1888.

8 H. Meyer, Archiv fiir experimentelle Pathologie und Pharmakologie, xiv. 336,
1881, and xvii. 304, 1883, where also other references occur.

® H. Winternitz, Zeitschrift fiir physiologische Chemie, xv. 505, 1891.

0 VY. Jaksch, Zeitschr. fiir klin. Med., xiii. 350, 1887.

1 Canard, Zeitschrift fiir klin, Med., xiii. 351, 1887.

2 Mya and Vassinari, ibid., p. 351.
3B. Griiber, Zur klinischen Diagnostik der Blutkrankheiten. Hzmatologische
Studien, p. 64. Leipzig, 1888.

4 Peiper, Archiv fiir pathologische Anatomie, cxvi. 337, 1889.

 W. H. Rumpf, Centralbl. f. klin. Med., xii. 441, 1891.

16 Kraus, Zeitschrift fiir Heilkunde, x. 106, 1889; Archiv fiir experimentelle
Pathologie und Pharmakologie, xxvi. 181, 1889.

7 Klemperer, Verhandl. d. Congreses f. innere Medicin, ix. 39, 1890; Charité-
Annalen, xv. 151, 1890.

18 Cantani, Centralblatt fiir die medic. Wissenschaften, xxii. 785, 1884.

 Landois, Real-Encyclop., iii. 163, 1885.

*0 FE. Lloyd Jones, Journal of Physiol., viii. 1, 1887.

21 Landois and Stirling, op. cit., p. 2.

2 Roy, Proc. Physiol. Soc., 84.—Devoto, Zeitschr. f. Heilkunde, xi. 175, 1889.—
Siegl, Wiener klin. Wochenschr., iv. 606, 1891.

3 #. Lloyd Jones, Brit. Med. Journ., 1888, ii. p. 1345.

24 Hammerschlag, Wiener klin. Wochenschrift, iii. 1018, 1890.

°5 Schmaltz, Archiv f. klin. Med., xlvii. 145, 1890.

26 Peiper, Centralbl. f. Klin. Med., xii. No. 12, 1891.

27 Roy, Journ. of Physiol., 1884, ix.

23 Monckton Copeman, Brit. Med. Journ., 1891, i. p. 161.

°° Hayem, Legons sur les Modifications du Sang, p. 75. Paris, 1882.

30 For further information, see Bizzozero, Giornale dell’ Accad. di medicina di
Torino, 1882. Centralblatt f. d. medic. Wissenschaften, xx. 353, 1882; Virchow’s
Archiv, xc. 261, 1882.—Zaker, Sitzungsber. der k. Akad., Vienna, Ixxxvi., 1882 ;
xciii., 1886 (sep. pub.).—Schimmelbusch, Fortschritte der Med., iii. 95, 1885.—
391

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392 BIBLIOGRAPHY.

M. Liwit, Yortschritte der Med., iii. 175, 1885, vi. 369, 1888 ; Sitzungsberichte der
k, Akademie, Vienna, lxxxviii. 356, 1884.—Virchow’s Archiv, cxvii. 545, 1889 ;
Beitrage zur pathologischen Anatomie, &c., v. 472, 1889.—Afanassiew, Archiv
fiir klin. Medicin, xxxv. 217, 1884.—Schimmelbusch, Lberth, Die Thrombose nach
Versuchen u. Leichenbefunden, Stuttgart, 1888. Landois and Stirling, op. cit.,
4th edit., p. 20.

31 4. Rollett, Hermann’s Handbuch der Physiologie, iv. 1, p. 5, 1880.—/andois
and Stirling, Text-book of Physiology, § 1, 1891.—D. Schiefferdecker u. A. Kossel,
Gewebslehre, ii. 356, 1891.

* 4, Rollett, op. cit., p. 28.

33 Stierlin, Inaug. Diss., 1889 ; Deutsches Archiv, xlv. 75, 1889.—Oppenheimer,
Deutsche med. Wochenschr., xv. 859, 880, 904, 1889.—Klein, Wien. med. Wochen-
schr., xl. 36-40, 1890.— Wilkens, Schmidt’s Jahrbiicher, cexxviii, 112 (ref.), 1890.—
Reinert, Die Zahlung der Blutkérperchen u.s. w., 72. Leipzig, 1891.—Reincehe,
Fortschritte der Medicin, vii. 408, 1889.

34 Frey, Das Mikroskop und die mikroskopische Technik, p. 127. Leipzig, 1873.

% y, d. Hurst, Centralbl. f. klin. Med., xi. 961, 1890.

35 Abbe, Sitzungsberichte der Gesellschaft fiir Med. und Naturwiss. in Jena,
No. 29, 1878.

37 Daland, Fortschritte der Medicin, ix. 824, 1891.

38 Sadler, ibid., ix., 1891.

39 Lyon and Thoma, Virchow’s Archiv, lxxxiv. 131, 1881; see also A. Halla,
Zeitschrift fiir Heilkunde, iv. 198 and 331, 1883.

40 Thoma, Virchow’s Archiv, lxxxvii. 201, 1882.—Maragliano u. Custcllini, Cen-
tralbl. f. klin. Med., xi. 947 (ref.), 1890.

41 Reinecke, Fortschritte der Medicin, vii. 411, 1889.

#2 Mayct, Académie des Sciences, Wiener med. Presse, xix. $33 (ref.), 1888.

43 Gowers, “On the Numeration of the Blood Corpuscles,” Lancet, Dec. 1877.

#4 Bizzozero, Handbuch der klinischen Mikroskopie, Erlangen, 1887 ; and Wiener
med. Jahrbiicher, p. 252, 1880.—V. Ficisehl, Wiener med. Jahrbiicher, 425, 1885,
and 167, 1886.—Hénoeque, Notice sur ?Hématoscope. Paris, 1886.—Landois and
Stirling, op. cit., p. 23.

45 Hedin, Skandinavischer Archiv fiir Physiologie, ii. 154, 1890.

46 Limbeck, Prager med. Wochenschr, xv. 351, 365, 1890.

4” Laker, Wiener med. Presse, xxxi. 1375, 1890.

48 Bizzozero, Handbuch d.klin. Mikroskop. ‘Translated by Bernheimer. Erlan-
gen, 1887.

9 Bizzozero, Atti della Regia Acc. d. Sc. di Torino, xiv., 1879.

50 Sadler, Prager med. Wochenschr., xvi. 256, 1891.

51 (ottlich, Wiener med. Blatter, ix. 505 and 537, 1886.—Lakcr, Wiener med.
Wochenschrift, xxxvi. 639 and 877, 1886.—Barbacci, Centralbl. f. d. med. W., xxv.
641, 1887.—Aisch, Zeitschrift f. klin. Med., xii. 357, 1887.—Mcyer, Archiv f. Gyna-
kologie, xxxi. 145, 1887.—Hdberlin, Miinch. med. Wochenschrift, xxxv. 364, 1887.
—Widowitz, Jahrbuch fiir Kinderheilkunde, xxvii. 380, 1888.—Stierlin, Deutsches
Archiv f. klin. Medicin, xlv. 75, 1889.—Schiff, Zeitschrift fiir Heilkunde, xi. 17,
1890.— Wilkens, Schmidt’s Jahrbiicher, ccxxviii. 7, 1890.—Meinl, Beitrage zur
Geburtshilfe und Gynakologie (sep. pub.); he combines Glan’s spectrophoto-
meter with v. Fleischl’s apparatus. Consult Benczux und Csatary, Deutsches
Archiv f. klin. Med., xlvi. 478, 1890; the observations were made by Vierordt’s
spectrophotometrical method.—Z. Reinert, Die Zahlung der Blutkérperchen, &c.,
Leipzig, 1891.

52 Hénocque, see (44), and Weiss, Prager medicinische Wochenschrift, xiii. 117,
1888.

53 Loos, Wiener klinisch Wochenschrift, i. 679, 1888.

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CHAPTER I.—-THE BLOOD. 393

Henschen, Upsala likare foren. férh., xxii. 497, 1887.

55 See Hénocque, Gazette hebdomadaire, xliii. 1886.

Hedin, Skandinavischer Archiv fiir Physiologie, ii, 134, 1890.

57 Daland, Fortschritte der Medicin., ix. 823, 867, 1891.

V. Jaksch, Prager med. Wochenschr., xvi. 195, 1891.

Cf. Pohl, Archiv fiir exper. Pathologie u. Pharmakologie. xxv. 87, 1888.
60 Grdber, see (13).

61 Sadler, Fortschritte der Medicin., ix. 1891.

* Reinecke, ibid., vii. 408, 1889 ; Virchow’s Archiv, cxviii. 148, 1889.

R. Miller, Prager med. Wochenschr., xv. 213, 228, 238, 1890.

54 Schiff’, Zeitschrift fiir Heilkunde, xi. 23, 1890.

6 Virchow’s Gesammelte Abhandlungen zur wissenschaftlichen Medicin, iii. ;
“On Colourless Blood Corpuscles and Leukemia,” p. 180; also Nasse, Donné,
Remak, Henle.

66 7'wmas, Deutsches Archiv f. klin. Med., xli. 323, 1887.

87 Y. Jaksch, Festschrift zu E. Henoch’s 70. Geburtstag, 1890: Centralbl. f.
klin. Med., Feb. 6, 1892; V. Limbeck, Zeitschrift f. Heilkunde, x. 392, 1890.—
Pick, Prager med. Wochenschr., xv. 303, 1890.

68 VY. Limbeck, see (67).

69 Sadler, see (61).

70 V. Jaksch, Prager med. Wochenschr., xvi. No. 1, 1891.—Tochitowitsch, Berliner
klin. Wochenschr., xxviii. $35, 1891. Cf. also G. Alexandre, De la Leucocytose,
&c., Paris, 1887, and Sadler, (61).

71 See Sadler, (61); V. Jaksch, 1.c., p. 20; and, from a clinical point of view,
the remarkable observations of Horbaczewski, Sitzungsberichte d. k. Akademie,
c. (3), 78, 1891.

7” Virchow, op. cit.—Ortner, Wien. klin. Wochenschr., ili. 677, 697, 720, 757,
830, 871, 892, 914, 937, 1890.—G. Roux, Centralblatt f. klin. Med., xi. 947 (ref.),
1890.—H. F. Miiller, Deutsches Archiv f. klin. Med., xlviii. 47, 1891.— Wertheim,
Zeitschr. f. Heilkunde, xii. 280, 1891.

73 See Riemer, Schmidt’s Jahrbiicher, clxxxi. 185, 1879.

74 Mosler, Zeitschrift fiir Biologie, viii. 147, 1872.

7 For further statements see Fleischer and Penzoldt, Archiv fiir klin. Medic.,
XXvi. 368, 1880.

76 VY. Jaksch, Wiener klin. Wochenschr., ii. 435, 456, 1880.

7 Bizzozero, op. cit., pp. 13 and 65.

78 Hayem, Du Sang, p. 856, et seqq.

79 Gowers, Art. ‘‘ Leucocythemia,” Quain’s Dict.

80 W. Beatty, Brit. Med. Journ., April 19, 1891.

81 M. Léwit, Sitzungsber. der k. Akad. (Vienna), xcii. (3), 22, 1886; and xcv.
(3), 1887.

8 Hayem, Du Sang, p. 857.

83 Hayem, ibid., p. 857.

84 Gazette médicale, 1853. Gazette hebdomadaire, 1860.

8 Newmann, Archiv fiir mikros. Anatomie, ii. 1866.

86 Ph. Shreiner, Liebig’s Annalen, cxciv. 68, 1878, where also other references
will be found.

8 £, Wagner, Archiv fiir Heilkunde, 1862.

88 Prus, see Westphal, (89).

89 Westphal, Archiv f. klin. Med., xlvii., p. 614, 1891.

9 Fleischer and Penzoldt, Archiv fiir klin. Med., l.c., p. 22.

9 V, Jaksch, Prager med. Wochenschr., xv. 404, 1890.

92 Cf. Sadler, (61); Miiller u. Rieder, Archiv f. klin. Med., xlviii. 100, 1891.

% Bhrlich, Verhandlungen der physiologisch. Gessellchaft zu Berlin, 1879-80,

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394 BIBLIOGRAPHY.

No. 20; Zeitschrift fiir klin. Med., i. 553, 1880; Charité-Annalen, xii. 288, 1887 ;
and Farbenanalytische Untersuchungen zur Histologie und Klinik des Blutes,
Berlin, 1891.

‘4 Huber and Becker, Die pathologisch-histologischen und bacteriologischen
Untersuchungs-Methoden, p. 49. Leipzig, 1886.

% Gabritschewsky, Archiv f. exper. Pathologie u. Pharmakologie, xxviii. 83, 1891.

%6 Aldchof’, Prager med. Wochenschr., xvi. 92, 1891.

%” Dolega, Fortschritte der Medicin, viii. 811, 1890.

8 Miiller u. Rieder, Archiv f. klin. Med., xlviii. 100, 1891.

89 Fink, Inaug. Dissert. Elberfeld, 1890.

100 Miiller, Archiv f. klin. Med., xlviii. 51, 1891; Archiv. f. exper. Pathol. u.
Pharmakol., xxix. 221, 1891.

101 Weiss, Wiener med. Presse, xxxii. 1538, 1578, 1617, 1891 ; Centralbl. f. die
med. Wissensch., xxix. 722, 753, 1891.

12 Ehrlich, Zeits. f. klin. Med., i. 553, 1880.

W3 Ehrlich, ibid., Charité-Annalen, 1884, p. 107.—Zugen Westphal, Ueber Mast-
zellen, Inaug. Diss., Berlin, 1880, pp. 18, 19.—Nordmann, Beitr. ziir Kenntniss v.
namentlich z. Farb. d. Mastzellen. Inaug. Diss., Berlin, 1884.

104 Lauder Brunton, Brit. Med. Journ., 1276, 1889.

10 Westphal, Inaug. Dissert. Schade, 1880.

6 Einhorn, Inaug. Dissert. Berlin, 1884.

107 Rv. Jaksch, (76), (91).

108 Loos, Wiener klin. Wochenschr., iv. 6, 27, 1891.

109 Zuzet, Etude sur les Anémie de la premitre Enfance et sur la Anémie in-
fantile pseudo-leucémique. Paris, 1891.

10 Hayem, Du Sang, p. 858.

Ml Spieteschka, Archiv f. Dermatologie u. Syphilis, xxiii. 265, 1891.

12 Hayem, Du Sang et ses Altérations anatomiques, etc.; Gazette des Hopitaux.
No. 113, 1889.

13 Literature: Mosler, Milzkrankheiten, Ziemssen’s Handbuch, viii. 2, 198,
2nd ed., 1878.—O. Nystréim, Schmidt’s Jahrbiicher, clxiii. 242, 1874.—Meissner,
Schmidt's Jahrbiicher, clxviii. 293, 1875.

14 Vanlair and Masius, De la Microcythémie. Bull. de Acad. Roy. Méd. de
Belgique, ser. iii. tom. 5.

15 Bettclheim, Wiener med. Presse, No. 13, 1868, separate supplement.

U6 Gram, Fortschritte der Medicin, ii. 11, 1884.—Grdiber, see (13).

U7 Quincke, Deutsches Archiv fiir klin. Medic., xx. 1, 1877, and xxv. 577, 1880.
See also Lépine and Germont, Gaz. méd. de Paris, 218, 1877.—Hayem, ibid., 293,
1877.—Lisenlohr, Archiv fiir klin. Medic., xx. 495, 1877.—Litten, Berlin. klin.
Wochenschr., xiv. 1, 1877.—Nothnagel, Archiv fiir klin. Medic., xxiv. 253, 1879.—
Ehrlich, Charité-Annalen, 198, 1878.—Centralbl. f. die med. Wissensch., xxviii.
625, 1890.

8 V. Jaksch, Prager med. Wochenschr., xv. No. 31, 1890.

19 Dolega, Congress fiir innere Medicin, ix. 511, 1890. See also Marigliano and
Castellini, Riforma medica, maggio, 1890; and Browicz, Verhandl. des Congresses
fiir innere Medicin, ix. 424, 1890.

12 Quincke, Mitth. f. d. Verein Schleswig-Holsteiner Aerzte, 1890.

121 (riiber, see (13).

122 See //oppe-Seyler, Handbuch der physiologischen Chemie. Berlin, 1881, p.
478.—Immermann, Von Ziemssen’s Handbuch, xiii. 2nd half, p. 274, 2nd. edit.
Leipzig, 1879.

223 See Immermann, V. Ziemssen’s Handbuch, xiii. 2nd half, p. 350, 2nd. ed.,
1879.—Fichhorst’s Monograph on Pernicious Anemia, Leipzig, 1878.—Quincke, see
(117).—Laache, Die Anzmie, Christiania, 1883.

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14 Copeman, Lancet, i. 1076, 1887.—Rindflcisch, Virchow’s Archiv, cxxi. 176,
1890.— Dowd, Centralbl. f. d. med. Wissensch., xxviii. 954 (ref.), 1890.

25 Hayem, op. cit.-—-Kahler, Prager medic. Wochenschrift, v. 373> 394, 404,
415, 423.—Quincke, see (117).—Laache, see (123).

16 Muir, Journal of Anatomy, xxvi. p. 393.

1 Neubert, St. Petersburger med. Wochenschr., xiv. No. 32, 1889; Dehio, ibid.,
Xvi. 1, 1891.

18 Kraepelin, Neurologisches Centralblatt, No. 3, 1890.

129 F, Miiller, Charité-Annalen, xiv. 253, 1889.—A. Klcin, Wiener klin. Wochen-
schr., iv. 721, 745, 1891.—v. Noorden, Charité-Annalen, xvi. (sep. pub.).

130 Block, Diss. Stettin, 1871.—Grawitz, Virchow’s Archiv, lxxix. 546, 1877, and
Ixxxi. 355, 1880 —Lichtheim, Zeitschr. fiir klin. Medic., vii. 140, 1884.

131 Kitasato, Zeitschr. f. Hygiene, vii. 225, 1889.

132 Koch, Cohn’s Beitriige zur Biologie der Pflanzen, ii. 429, 1877 ; and Mittheilun-
gen aus dem kaiserlichen Gesundheitsamte, i. 1, 1881.—Zhrlich, see (93).— Weigert,
Centralbl. fiir die medic. Wissensch., ix. 609, 1881 ; and Berl. klin. Wochenschr.,
XV. 241 and 261, 1877.

133 See Daland, Fortschr. der Med., ix. 824, 1891.

134 Scheurlen, Centralbl. f. Bakteriol. u. Parasitenkunde, viii. 257, 1890.

13 Ehrlich, Zeitschrift fiir klin. Med., ii. 710, 1881.

136 Lifler, Mittheilungen aus dem kais. Gesundheitsamte, ii. 439, 1884.

137 Gram, Fortschritte der Medicin, ii. 186, 1884.

138 Weigert, Fortschritte d. Medicin, v. 228, 1887.

139 Pollender, Mikroskopische und mikrochemische Untersuchung des Milzbrand-
blutes, sowie tber Wesen und Cur des Milzbrandes. Casper’s Vierteljahrshcrift
fiir gerichtliche und 6ffentliche Medicin, viii. 103, 1855.—Brauel/, Virchow’s
Archiv, xi. 132, 1857, and xiv. 32, 1858.—Davaine, Compt. rend. de l’Académie des
Sciences, lvii. 220, 1863.

140 Bollinger, V. Ziemssen’s Handbuch, iii. 544, 2nd edit. For exhaustive in-
formation, see Wilhelm Koch, Milzbrand und Rauschbrand, 1886. Deutsche
Chirurgie, 9. Lief.—Baumgarten, Jahresbericht iiber die Fortschritte in der Lehre
von den Mikro-organismen, &c., i. 52, 1886; ii. 124, 1877; ili. 101, 1888.—Fliigge,
Die Mikro-organismen, &c., 2nd edit., Leipzig. 1880.

141 2. Koch, Cohn’s Beitriige zur Biologie der Pflanzen, ii. 277 and 429, 1877.—R.
Koch, Wundinfectionskrankheiten, Leipzig, 1878; and Mittheilungen aus dem
kaiserlichen Gesundheitsamte, i. 49, 1881.

12 Eppinger, Wiener med. Wochenschr., xxxviii, Nos. 37, 38, 1888.—R. Paltauf,
Wiener klin. Wochenschr., Nos. 18-26, 1888, where a fullaccount of the literature
on the subject will be found.

18 Obermeyer, Centralbl. fiir die medic. Wissenschaften, xi. 145, 1873; also for
further information consult v. Jaksch, Wiener medic. Wochenschr., xliii. 120, 159,
and 186, 1884.—Fliigge, see (141).

144 Sarnow, Der Riickfallstyphus in Halle a. 8. im Jahre 1879-81. Inaugural
Dissertat. Leipzig, 1882.

145 Karlinski, Fortschritte d. Medicin, viii. 161, 1891.

U6 Sacharof, Baumgarten’s Jahresbericht, iv. 314 (ref.), 1889.

M7 Giinther, Fortschritte der Medic., iii. 755, 1885. :

48 Weichselbaum, Wiener med. Wochenschr., xxxiv. 333 and 365, 1884.

149 Meisels, Wiener med. Wochenschr., xxxiv. 1149 and 1187, 1884.

150 Lustig, Wiener med. Wochenschr., xxxiv. 430, 1884.—Sticker, Centralbl. fiir
klin. Med., vi. 441, 1885.—Doutrelepont, Deutsche medic. Wochenschr., xi. 98, 1885.
—Riitimeyer, Centralbl. fiir klin. Med., vi. 353, 1885.

151 Tiebmann, Lo Sperimentale, xlv. 30, 1891.

132 Ehrlich and Guttmann, Berliner klin. Wochenschr., 124, 1891.

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396 BIBLIOGRAPHY.

153 Hamerle, Prager med. Wochenschr., xvi. 106, 1891.

14 Lofler, Arbeiten aus dem kaiserl. Gesundheitsamte, i. 141, 1836.

155 Lofler and Schiitz, Deutsche medic. Wochenschr., ix. 52, 1882.

156 [srael, Berl. klin. Wochenschr., xx. 155, 1883. For exhaustive information
as to the older and more recent literature on the subject, see Fliigge (140), and
Baumgarten, Jahresb., ii. 181, 1887; iii. 156, 1888; iv. 154, 1889; v. 226, 1890.

17 ~Weichselbaum, Wiener medic. Wochenschr., xxxv. Nos. 21-24, 1885.

8 Meisels, Wiener med. Wochenschr., xxxvi. 759, 1886.

19 Riitimeyer, Centralbl. fiir klin. Med., viii. 145, 1887.—Neuhauss, Berlin. klin.
Wochenschr., xxiii. 89 and 389, 1886.

160 Janowski, Centralbl. f. Bakteriol. u. Parasitenkunde, v. 657, 1889.

161 VY, Noorden, Minch. med. Wochenschr., xxxiv. No. 3, 1887.

162 Orthenberger, Munch. med. Wochenschr., xxxv. Nos. 49 and 50, 1888.

3 Sanger, Deutsche med. Wochenschr., xv. No. 8, 1889.

164 Weichselbaum, Wiener med. Wochenschr., xxxviii. Nos. 35 and 36, 1888.

165 4, x. Liselsberg, Wiener klin. Wochenschr., iii. 731, 1890.—Levy, Centralbl. f.
klin. Med., x. 65, 1890.—Brunner, Wiener klin. Wochenschr., iv. 392, 1891.

166 4. y, Rosthorn (oral communication).

167 Crookshank. An investigation into the so-called “‘ Hendon Cow Disease,” in
its relation to scarlet-fever in man. Trans. Patholog. Society, 1888, printed
separately in pamphlet form.

168 Crookshank, op. cit.

169 The account was published in Reports xv. and xvi. of the Local Government
Board, in the “Transactions of the Epidemiological Society,” New Series, vol. v.,
“Proceedings of the Royal Society,” vol. xlii., and in “ Nature,” No. 919, vol. xxxiv.

170 Bareggi, Gaz. Lomb., viii. p. viii— Babes, Virchow’s Archiv, ex. 562, 1888.

W1 Nikolaier, Deutsche med. Wochenschr., x. 842, 1884. —Rosenbach, Archiv fiir
klin. Chirurgie, xxxiv. 306, 1886.—/Hochsinger, Centralbl. fiir Bacteriol. und Para-
sitenkunde, ii. 145 and 177, 1887.—Beumer, Zeitschr. fiir Hygiene, iii. 242, 1888. —
Peiper, Centralbl. fiir klin. Medic., viii. No. 42, 1887.—V. Hiselsberg, Wiener klin.
Wochenschr., i. 232, 259, 1888, where exhaustive references to the literature on
the subject are given.

i” Brieger, Untersuchungen iiber Ptomaine, pt. iii. p. 89, Berlin, 1886 ; Berlin.
klin. Wochenschr., xxv. 311, 1886 ; and Deutsche med. Wochenschr., xiii. 303,
1887 ; Virchow’s Archiv, exii. 549, 1888.

173 Nissen, Deutsche med. Wochenschr., xvii. 775, 1891.

M4 A, Bruschettini, Riforma Med., April 11, 1892.

7% Kitasato, Archiv f. Hygiene, vii. 225, 1889.

7% Belfanti and Pescarolo, Centralbl. fiir Bacteriologie und Parasitenkunde, iv.
514, 1888 ; Bawmgarten, Jahresbericht, iv. 230, 1889; v. 201, 1890.

17 Klebs, Die allgemeine Pathologie, &c., pt. i. p. 144. Jena, 1887.

v8 Laveran, Comptes rendus, xcv. 87, 1882.

 Marchiafava and Celli, Fortschritte der Medic., i. 573, 1883 ; and iii. 339 and
787, 1885. For further literature—Laveran, Richard, Councilman, and Abbot—see
Baumgarten, i. 153, 1885 ; also Schelling, Centralbl. f. Bacteriol. u. Parasitenkunde,
x. 570 (ref.), 1891.

180 See O. Rosenbach, Berliner klin. Wochenschr., xxviii. 840, 1891.

181 Gerhardt, Zeitschr. fiir klin. Med., vii. 372, 1884.

182 Golgi, Centralbl. f. Bacteriologie und Parasitenkunde, i. 346, 349, 1887;
Fortschritte der Medicin, 82, 1889.—Metschnikoff, Centralbl. f. Bacteriol. u. Para-
sitenkunde, i. 624, 1887.—Chenzinsky, ibid. iii. 457, 1888.—¥For later literature
see Baumgarten’s Jahresbericht, iv. 230; v. 201, 1890.—Osler, British Med.
Journal, xii. 556, 1887.——-Shattuck, Boston Med. and Surg. Journal, cxviii. 450,
1888.—Evans, Brit. Med. Journal, No. 1426, 897, 1888.

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183 Dyer, Proc. Roy. Soc., May 28, 1$91.—Fenton Evans, ibid., February 12,
18y1.

184 Councilman, Centralbl. fiir Bacteriologie und Parasitenkunde, ii. 377. 1887.
Fortschritte der Medicin, vi. 449, 500, 1888.

185 Mosso, Centralbl, fiir Bact. und Parasitenk., ii. 17, 1887.

186 [. Pfeiffer, Zeitschr. fiir Hygiene, ii. 397, 1887.

187 Yommasi-Crudeli, Centralbl. f. Bact. und Parasitenk., i. 349, 1887.

188 Schiavuzzi, ibid., i. 203, 1887.—F. Cohn, ibid., ii. 363, 1887.

189 Danilewsky, Gisuimenal fiir die med. vyecenneneit XXV. 737 and 753, 1886;
Centralbl. f. Bacteriol. u. Parasitenkunde, ix. 397, 1891.

19 Grassi and Feletti, see (191).—Celli and Sanfelice, Fortschritte d. Med., ix.
449, 1891.

19 Laveran, see (178).—Marchiafava and Celli, Riforma Medica (sep. pub.),
April 1890: Berliner klin. Wochenschr., xxvii. 1010, 1890; Fortschritte der
Medicin, ix. 283, 1891.—(olgi, Sulla infezione malarica, Torino, 1886; Beitrage
zur pathologischen Anatomie, &c., vii. 649, 1890; Fortschritte der Medicin, vii.
81, 1889; Zeitschr. f. Hygiene, x. 136, 1891.—Celli and Guarnieri, Fortschritte
der Medicin, vii. 521, 561, 1889.—Grassi and Calandraccio, Centralbl. f. Bacteriol.
u. Parasitenkunde, vii. 396, 430, 1890.—(rassi and Feletti, ibid., ix. 403, 430, 461,
1891; X. 430, 481, 517, 1891.—Canalis, Giornale medico del. R. Esercito e della R.
Marina, Rome, 1889; Fortschritte d. Med., viii. 286, 325, 1890.—R. Paltauf,
Wien. klin. Wochenschr., iii. 24, 47, 1890.—Quincke, Mitth. f.d. Verein Schleswig-
Holsteiner Aerzte, 1890.—Dolega, Fortschritte d. Med., viii. 769, 809, 1890;
Verhandl. d. Congresses f. innere Medicin, ix. 518, 1890.—P. Lehn, Berliner
klin. Wochenschr., 26, 292, 1890; Zeitschr. f. Hygiene, viii. 78, 90, 1890; tio-
logische u. klin. Malariastudien, Berlin, 1890, which has an exhaustive re-
ference to the literature.—Chenz ae see the Russian translation of this book by
Prof. V'schudnowsky, p. 120, St. Petersburg, 1890, which also has an excellent figure
of the Plasmodium malariz.—Rosenbach and Rosen, Deutsche med. Wochenschr.,
xvi. 325, 1890.—V. Jaksch, Prager med. Wochenschr., xv. 40, 1890. See also
Hochsinger, Wiener med. Presse, xxxii. 658, 1891.—Mannaberg, Centralbl. f. klin.
Med., xii. 513, 1891.—Z. Malachowshi, ibid., 601, 1891.—Baumgarten’s Jahresbericht,
iv. 306, 1889 ; v. 425, 1890.—Bein, Charité-Annalen, xvi. 181, 1891.

192 Dock, Fortschritte der Med., ix. 187, 1891 ; Medical News, 1891.—C. Spener,
Centralbl. f. Bacteriol. und Parasitenkunde, x. 554 (ref.), 1891.

193 Hehir, Lancet, May 28, 1892.

194 Golgi, Fortsch. der Med., 7, Pl. I.—Plehn; Celli, and Guarnieri, Fort-
schritte der Med., Pl. III. fig. 15.

195 Golgi, ibid.

196 Golgi, ibid.

197 Golgi, Zeitschr. f. Hygiene, x. 136, 1891.

18 Golgi, l.c.

199 Celli and Marchiafava, Berliner klin. Wochenschr., xxvii. 1010, 1890.

200 Celli and Guarnieri, l.c., Pl. IIIa.

201 Compare the striking observations made by Danilewski, op. cit., p. 398.

2022 See also O. Hertel and C. v. Noorden, Berliner klin. Wochenschr,, xxviii.
(sep. pub.), 1891.

203 V, Jaksch, see (191).

204 Chenzinsky, in Prof. Tschudnowsky’s translation of this book, p. 420, St.
Petersburg, 1890.—Plehn, Atiol. and klin. Malariastudien, Berlin, 1890.—Mala-
chowski, Grassi, and Feletti, see (191).

205 Hochsinger, see (191).—Paltauf (oral communication).

206 Loef, Centralbl. fiir Bacteriologie und Parasitenkunde, ii. 353, 1887,—Pfeiffer,
ibid., ii. 126, 1887.

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398 BIBLIOGRAPHY.

*07 See Leuckart’s classical work : Die menschlichen Parasiten und die von ihnen
herriihrenden Krankheiten, Leipzig, i. 617, 1865; also LZ. K. Schmarda, Lehrbuch
der Zoologie, i., Vienna, 1871; and B. Hatschek, Lehrbuch der Zoologie, Jena,
1888.

708 Bilharz and C. Th. V. Siebold, Zeitschrift fiir wissenschaftliche Zoologie, iv.
59, 72, and 454, 1853; and Bilharz, Wiener medic. Wochenschr., vi. 49, 1856. For
further literature, see Meissner, Schmidt’s Jahrbiicher, clxv. 289, 1875 ; clxxxix.
84, 1881; cxciii. 30, 1882.

£09 Cobbold, Lancet, ii. 1877.

10 Ringer and Patrick Manson, Med. Times and Gazette, July 2, 1881.

"ul Leuckart, 1.c., ii. 628, 1876.—Meissner, Schmidt’s Jahrbiicher, clxv. 289, 1875 ;
clxxxix. 81, 1881 ; cxciii. 29, 1882.

“12 Lewis, Lancet, i. No. 2. 1873; and the same in Centralbl. fiir med. Wissen-
schaft, xi. 335, 1873; xiii. 771, 1874. “On a hematozoon inhabiting human
blood,” Calcutta, 1872; Deutsches Archiv f. klin. Med., xii. 540, 1873; xv. 613,
1874.

213 Bourne, Brit. Med. Journal, No. 1429, p. 1050, 1888.

"14 Meissnér, Schmidt’s Jahrbiicher, clxv. 289, 1875.

215 John Guitéras, Philad. Med. News, April 1886; Fortschritte der Medicin,
iv. 974, 1886.

16 Myers, Wykeham, Centralbl. fiir Bacteriologie und Parasitenkunde, ii. 761,
1887.

217 Stephen Mackenzie, Lancet, ii. 398, 1881.—Patrick Manson, op. cit.—Scheube,
Festschrift fiir E. Wagner, p. 242, Leipzig, 1888.—Lanceraux, Gazette des Hépi-
taux, lxi. 630, 1888.

18 See Hoppe-Seyler, Medic.-chem. Untersuchungen, Tiibingen, 1867-70.—
Schneider, Wiener medic. Wochenschr., xvii. No. 14, 99, 102, 1868.—Preyer, Die
Blutkrystalle, Jena, 1871.—Hoppe-Seyler, Physiol. Chemie, Berlin, 375-399, 1881.—
Rollett, Hermann’s Handb. der Physiol., iv. Bd. i. p. 38, 1880.—Zandois and
Stirling's Text-book of Physiology, p. 22, 4th edit., 1891.

19 Teichmann, Zeitschr. fiir ration. Med., iii. 375, 1853, and viii. 141, 1857; also
Funke, ibid., N. F., i. 185.

220 Hoppe-Seyler, 1.c., Medic.-chem. Untersuchungen, p. 44.

221 Nencki and Sieber, Archiv fur experiment. Pathol. u. Pharmakol., xviii. 401,
1884; xx. 325, 1886; xxiv. 430, 1888.

222 Hoppe-Seyler, Berichte der deutschen chem. Gesellschaft, vii. 1066, 1874.

3 (. le Nobel, Centralbl. fiir die med. Wissensch., xxv. 305, 1887; and Archiv f.
die ges. Phys., xl. 501, 1887.

24 Maly, Centralbl. fiir die medic. Wissensch., ix. 849, 1871; and Liebig’s An-
nalen, clxiii. 77, 1872.

25 Virchow, Virchow’s Archiv, i. 379, 1847.

26 Latschenberger, Sitzungsberichte der k. Akademie (Vienna), xcvii. 2, 1888
(pub. sep.).

27 Hoppe-Scyler, Physiol. Chemie, p. 391. Berlin, 1881.

228 Jaderholm, Zeitschr. fiir Biologie, xiii. 193, 1877.

29 See Bohm, Ziemssen’s Handbuch, xv. 158, 2nd edit., 1880.—Lewin, Lehrbuch
der Toxikologie, p. 23. Wien, 1885.—Hoppe-Scyler, Virchow’s Archiv, xi. 288,
1857.—For additional information, see Husemann’s Handb. der Toxikologie.—4A.
Jéderholm, Die gerichtlich-medicinische Diagnose der Kohlenoxydvergiftung,
1876.

230 Hoppe-Seyler, Virchow's Archiv, xili. 104, 1858.—Otto, Anleitung zur Aus-
mittlung der Gifte, p. 246, 6th edit., 1884.

231 FB, Salkowski, Zeitschrift fiir physiolog. Chemie, xii. 227, 1888.

232 Kuniyost Katayama, Virchow’s Archiv, cxiv. 53, 1888.

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CHAPTER I.—THE BLOOD. 399

3 Kunkel, Sitz. d. phys. med. Gesellschaft zu Wiirzburg, ix., Sitzung vom 28
April 1888.—A. Wetzel, Inaug. Diss., Wiirzburg, 1889.

*44 Rubner, Archiv f. Hygiene, x. 155, 1890.—Dreser, Archiv f. experimentelle
Pathologie u. Pharmakologie, xxix. 119, 1891.

*5 Hoppe-Seyler, Physiolog. Chemie, op. cit., p. 386.

36 Lewin, Virchow’s Archiv, lxxiv. 220, 1878; and Lehrbuch der Toxikologie,
p. 48.

*37 Preyer, Centralbl. fiir die medic. Wissenschaft, v. 259 and 273, 1867.

238 Hoppe-Seyler, Physiolog. Chemie, l.c., p. 385.

*39 Marchand, Virchow’s Archiv, lxxvii. 488, 1879.

*40 Stokvis, Archiv fiir experiment. Pathologie und Pharmakologie, xxi. 169,
1886.—A. Bokai, Deutsche med. Wochenschr., xiii. 42, 1887.

*4l Marchand, Archiv fiir experim. Pathol. und Pharmakol., xxiii. 273, 347, 1887.
—Cahn, ibid., xxiv. 180, 1887.

242 Lenhartz, Deutsch. med. Wochenschr., xiii. 9, 1887.—Hammer, Prager med.
Wochenschr., xiii. 275, 1888.—Dittrich, Archiv f. experiment. Pathol. u. Pharma-
kol., xxix. 247, 1891.

*43 Hoppe-Seyler, Physiolog. Chemie, p. 476.

44 Gf. Hayem, Compt. rend., cii. 698, 1886.—Fr. Miiller, Deutsche med. Wochen-
schr., xiii. 27, 1887.

24 Filehne, Archiv fiir experiment. Pathologie, ix. 329, 1878.—Lewin, Virchow’s
Archiv, lxxvi. 443, 1879. ;

+46 See Ponjfick, Verhandlungen des Congresses fiir innere Medicin, ii. 205, 1883.
—Stadelmann, Archiv. fiir experiment. Patholog. und Pharmakol., xv. 337, 1882;
Xvi. 118, 225, 1884.—Afanassiew, Zeitschr. fiir klin. Med., vi. 281, 1883.

47 Thudichum, Journal fiir prakt. Chemie, civ. 257, 1868.—Maly, Jahresbericht
fiir Thierchemie, xi. 126, 1882.—Ch. A. MacMumnn, Maly’s Jabresbericht fiir Thier-
chemie, xi. 210, 1882.—C. Vierordt, Zeitschrift fiir Biologie, x. 21 and 399, 1874.

248 PR. v. Jaksch, Verhandl. des Congresses f. innere Med., x. 353, Wiesbaden,
1891.

“49 1, Hering, Prager. medic. Wochenschrift, xi. 97, 1886.

250 Maschek, ibid., xi. 185 and 197, 1886.

°51 Hoppe-Seyler, Handb. der physiol. u. patholog.-chem. Analyse, 5th edit.,
421, 1885.

252 Hoppe-Sceyler, ibid., p. 432.

253 F. Ludwig, Wiener medic. Wochenschrift, xxxi. 122, 1881.—V. Jaksch, Zeitschr,
fiir klin. Medic., vi. 413, 1883.

254 Devoto, Rivista clin. archivio italiano de clin. med., xxx, 11 (pub. sep.),
1891.

*55 Picard, Virchow’s Archiv, xi. 189, 1857.

236 H, Schiff, Berichte der deutsch. chem. Gesellschaft, x. 773, 1877.

27 LT. v. Udransky, Zeitschy. f. physiol. Chemie, xii. 355, 377, 1888.

258 Hoppe-Seyler, Handbuch, p. 140.

259 Haycraft, from Gamgee, quoted by Ralfe, Clin. Chem., p. 87.

260 V, Schréder, Archiv f. experiment. Patholog. u. Pharmakol., xv. 375, 1882.

761 4, B. Garrod, Med. and Chirurg. Trans., xxxi. 183, 1848; xxxvii. 49, 1854;
The Nature and Treatment of Gout, Schmidt’s Jahrbiicher, cx. 124, 1861.

262 Abeles, Medicinische Jahrbiicher, ii. 497, 1887.

263 Salomon, Charité-Annalen, v. 137, 1880; Zeitschr. f. physiol. Chemie, ii. 65,
1878.

264 R. v. Jaksch, Zeitschr. f. Heilkunde, xi. 415, 18go.

*65 _Hoppe-Seyler, Handbuch, pp. 142 and 419.

266 R, v, Jaksch, Zeitschr. f. Heilkunde, xi. 438, 1890.

267 R, v, Jaksch, ibid., xi. 424.

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p.
400 BIBLIOGRAPHY.

68 J, Horbaczewski, Sitzb. d. k. Akad. Wien, c., pt. iii., 1891.
69 Claude Bernard, Legons sur le Diabéte. Paris, 1877.
*70 Abeles, Zeitschr. f. physiol. Chemie, xv. 495, 1891.
+1 Y. Jaksch, Zeitschr. fiir. klin. Medic., xi. 20, 1886.
272 Pavy, Ralfe, Clin. Chem., p. 88.
73 Claude Bernard, Beaunis, Nouv. Elements de Physiol., 3rd ed., p. 138, 1888.
74 Seegen, in Pfluger’s Archiv, xxxiv. 1884; xxxvii. 1885 ; xxxix. 1886.
75 Hoppe-Seyler, Physiolog. Chemie, 1.c., p. 430.
76 Freund, Wiener medic. Blatter, viii. 268 and 873, 1885; and Matray, ibid., p.815.
°77 Trinkler, Ceutralbl. f. d. med. Wissenschaft, xxviii. 498, 1890.
278 Salomon, Deutsche med. Wochenschr., iii. 92, 421, 1877.—v. Frerichs, Zeitschr.
klin. Med., vi. 33, 1885; Ueber Diabetes. Berlin, 1884.
79 Gabritschewsky, Archiv f. experiment. Pathol. u. Pharmakol., xxviii. 272, 1891-
80 Freund, Wiener medic. Jahrbiicher, i. 335, 18386.
81 Baumann and v. Udransky, Berichte der deutsch. chem. Zeitschr., xxi. 2744,
1888. Compare Chapter on Urine.

282 V. Jaksch, Zeitschr. fiir. klin. Medic., xi. 307, 1886.

°83 J/oppe-Seyler, Handbuch der physiolog. und patholog. chemischen Analyse,
1.¢., p. 103.—Berlinerblau, Archiv fiir experiment. Patholog. und Pharmakolog., xxiii,
333, 1887. See Chapter on Urine.

284 Hougouneng, Maly’s Jahresbericht, xvii. 430, 1888.

85 Hoppe-Seyler, op. cit., p. 399.

*6 Pettenkoffer, Annalen der Chemie u. Pharmacie, lii. 90, 1844.

*87 Mylius, Zeitschr. fiir physiolog. Chemie, xi. 492, 1887.

"88 L. v. Udransky, see (257).

*89 Mackay, Archiv fiir experimentelle Pathol. u. Pharmakol., xix. 269, 1885.

80 On the subject of cholemia, see Ponfick, v. Ziemssen’s Handb., vol. viii. pt. i.
p. 12, edit. of 1880.

*91 R. v. Jaksch, Verhandl. des Congresses f. innere Med., x. 353, 1891.

292 Silbermann, Archiv fiir Kinderheilkunde, viii. 401, 1887.

°93 Harveian Oration, Royal Coll. Physicians, 1888, British Med. Journal.

54 Ch. Bouchard, Compt. rend., cii. 669, 727, 1127, 1886; and Lecons sur les
Auto-intoxications dans les Maladies. Paris, 1887.

*9 Horbaczewski, Wiener Med. Jahrbiicher, 389, 1883.

296 V. Jaksch, Zeitschr. fiir klin. Med., xiii. 350, 1888.—Peiper, Virchow’s Archiv,
exvi. 337, 1889.

*7 R. v. Jaksch, Zeitschr. f. Heilkunde, xi. 433, 1890.

*“8 VY. Jaksch, Ueber Acetonurie und Diaceturie. Berlin, 1885.

*99 R. Wanach, Inaugural Dissertation. St. Petersburg, 1888.

300 Schenk, Anatom.-physiol. Untersuchungen, p. 10. Vienna, 1872.

3. Freund, Wiener medic. Wochenschr., xxxvii. 10, 40, 1887.

30° _Hoppe-Seyler, Handbuch der physiolog. und pathol. chem. Analyse, l.c., p. 316
and 423.—Rollett, Hermann’s Handb, der Physiol., vol. iv. pt. i, p. 124.—Landois
and Stirling, 4th edit., 1891.

393 VY. Limbeck, Grundriss einer klin. Pathol. des Blutes. Jena, 1892.

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CHAPTER II.
THE BUCCAL SECRETION.

1 Heidenhain, Hermann’s Handbuch, v. 1, 1883; Maly, ibid., v. 2, 1881; as also
Sticker, No. 297 of Volkmann’s Clinical Series, Leipzig, 1887 ; Die Bedeutung des
Mundspeichels in physiologischen und pathologischen Zustiinden. Berlin, 1889.

* W. D. Miller, Die Mikro-organismen der Mundhihle, p. 54, 60. Leipzig, 1889.

* Lewis, Lancet, ii. 513, 1884.—Miller, Deutsche medic. Wochenschr., xi. 138 and
843, 1885.

4 Vignal, Archives de Physiologie, viii. 325, 1886, and x. 285, 1887, where also
abundant references will be found. See also Le 7h. David, Les Mikrobes de la
Bouche. Paris, 1890.

° D. Biondi, Zeitschr. fiir Hygiene, ii. 194, 1887.

° W. D. Miller, Inaug. Diss., Berlin, 1887; Schmidt’s Jahrbuch, cexvii. 122, 1888.

7 Miller, Centralbl. fiir Bacteriologie und Parasitenkunde. i. 47, 1887.

8 Miller, Die Mikro-organismen der Mundhohle, p. 206.

® Lifler, Mittheilungen aus dem Kais. Gesundheitsamte, ii. 480.—Vetter, Cen-
tralbl. f. klin. Med., xi. 11, 321, 1890.—H. Mery and P. Boulloche, Fortschritte der
Medicin, ix. 851, 1891.—Sanarelli, Schmidt’s Jahrbiicher, ccxxxii. 125, 1891.

0 Friinkel, Deutsche med. Wochenschr., xiv. 443, 1888.

1 fiilz, Zeitschr. fiir Biologie, xxiii. 321, 1887.

™ Colosanti, Maly’s Jahresbericht, xix. 72, 1890.

8 H, Schliesinger, Virchow’s Archiv, cxxv. 146, 350, 1891.

4 Griess, Berichte der deutschen chem. Gesellschaft, xi. 624, 1878.

1 [. Weiss, Centralbl. f. klin. Med., xi. 807, 1890.

16 J, Schramm, Berl. klin. Wochenschr., xxiii. 843, 1886.

W Salkowski, Virchow’s Archiv, cix. 358, 1887.

18 Ralfe, Clin. Chem., p. 176.

19 See Maly, Hermann’s Handbuch, l.c., v. 2, 8.

“0 Fleischer, Verhandlungen des Congresses fiir innere Med., ii. 119, 1883.

1 Boucheron, Compt. rend., 1881.
2 Rosenbach, Centralbl. f. klin. Med., xii. 145, 1891.
8 Ralfe, Clin. Chem., p. 177.

2 Samuel Fenwick, The Saliva as a Test for Functional Disorders of the Liver,
London, 1887.

°5 EB. Friinkel, Virchow’s Archiv, cxiii. 484, 1888.

°6 Frithwald, Jahrbuch f. Kinderklinik, xxix. 200, 1889.—Ze Th. David, Les
Mikrobes de Ja Bouche, p. 161, 1890.—H. Ranke, Jahybuch f. Kinderheilkunde,
xxvii. 309, 1888.

*7 See Kehrer, Ueber den Soorpilz, Heidelberg, 1885, where is given a full
account of the literature of the subject.—Baumyarten, Jahresbericht itiber die
Fortschritte in der Lehre von der pathog. Mikro-organismen, i. 145, 1885 ; ii. 330,
1886 ; iii. 318, 1887; iv. 303, 1888; v. 420, 1889.—Fliigge, l.c., p. 119.

°8- A. Freudenberg, Centralbl. fiir klin. Medicin, vii. No. xl., 1886.

*) Rees, A. de Bary, Vergleichende Morphologie und Biologie der Pilze, p. 405.
Leipzig, 1884.

30 Grawitz, Virchow’s Archiv, lxx. 566, 1877, and Ixxiii. 147, 1878.

31 Plaut, Baumgarten’s Jahresbericht, &c., l.c., i. 149, 1886.

32 Baginsky, Deutsche medic. Wochenschr., xi. 866, 1885.

33 Klemperer, Centralbl. fiir klin. Medic., vi. 849, 1885.

31 Fliigge, l.c., p. 119.

ww 19 89

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402 BIBLIOGRAPHY.

3 Plaut, Centralbl. fiir Bacter. und Parasitenkunde, i. 527, 1887 (ref.).

°6 Hauser, Deutsches Archiv fiir klin. Med., xlii. 127, 1887.

“7 Miller, Die Mikro-organismen der Mundhoble, p. 54.

38 Zopf, Die Spaltpilze, p. 103, 1886.

39 Schech, Miinchner med. Wochenschr., xxxiv. 254, 1887.

40 Roth, Wiener med. Presse, xxviii. 897, 1887.

41 Dickinson, Lumleian Lectures, 1888.

2 Roux and Versin, Baumgarten’s Jahresbericht, iv. 234 (ref.), 1889; v. 215
(ref.), 1890.—Zarniko, Centralbl. f. Bacteriol. u. Parasitenkunde, vi. 153, 178, 224,
1889.—Spronck, Wintyens, and van den Brink, Centralbl, f. d. med. Wissensch.,
xXvili. 363 (1890).—Aolisko and Paltawf, Wiener klin. Wochenschr., ii. 147, 1889.
—Escherich, Centralbl. f. Bacteriol u. Parasitenkunde, vii. 8, 1890; Piidiatrische
Arbeiten, p. 302, Berlin, 1890.—A'lein, Centralbl. f. Bacteriol. u. Parasitenkunde,
vii. 489, 521, 1890.— Beck, Zeitschr. f. Hygiene, viii. 434, 1890.

43 Lofler, Mittheilungen aus dem kaiserlichen Gesundheitsamte, ii. 421, 1884;
and Centralbl. fiir Bacteriologie und Parasitenkunde, ii. 105, 1887 (ref.) ; vii. 528,
1890.

4G. v. Hofmann Wellenhof, Wiener med. Wochenschr., xxxviii. Nos. 3 and 4,
1888 (Supplement).

4 Brieger and Fraenkel, Berliner klin. Wochenschr., No. ii. 1890.— Wassermann and
Proskauer, Deutsche med. Wochenschr., xvii. 585, 1891; other references to the
literature are given in Baumgarten’s Jahresbericht, iv. 234, 1889; v. 211, 1890.

46 Baginsky, Archiv f. Kinderheilkunde, xii. 421, 1891.

47 Peters, Berlin. klin. Wochenschr., xxv. 420, 1888.

48 Th. Hering, Zeitschr. fiir klin. Med., vii. 358, 1884.

49 0. Chiari, Revue mens. de Laryngologie, No. 10 (Sup.), 1887.—See also Decker
and Sezfert, Sitz.-ber. der phys.-med. Gesellschaft. Wiirzburg. II. Sitz., Jan. 7,
1888.

CHAPTER IIL
THE NASAL SECRETION.

1 L. Weibel, Centralbl. f. Bacteriologie und Parasitenkunde, ii. 465, 1887.

2 See Reimann, Baumgarten’s Jahresbericht, iii. 417, 1888 (ref.).

3 Notinagel, Wiener med. Blatter, Nos. 6, 7, 8, 1888.

4 FE. Frénkel, Virchow’s Archiv, xciv. 499, 1882.

° Hajek, Baumgarten’s Jahresbericht, iii. 416, 1888 (ref.).

6 Lowenberg, Deutsche medic. Wochenschr., xi. 6, 1885.

7 Tost, Deutsche medic. Wochenschr., xii. 161, 1886.

8 Lowenberg, ibid., xii. 446, 1886.

® H. v. Schritter and Winkler, Beitrag zur Pathologie der Coryza. Vienna, 1890.

0 Schubert, Archiv fiir klin. Medic., xxxvi. 162, 1885 ; Berliner klin. Wochenschr.,
No. 39, 1889.

1 Proskauer, Zeitschr. f. Ohrenheilkunde, xxi. 311, 1891.

2 B. Friinkel, v. Ziemssen’s Handbuch, iv. 1, 189, 2nd edit., 1879.

B Leyden, Deutsche med. Wochenschr., xvii. 1085, 1891.

14 Sticker, Zeitschr. f. klin. Med., xiv. 8, 1888.

1 Levy, Berliner klin, Wochenschr., xxviii. 816, $45, 1891.

16 Q, Chiari, Wiener medic. Wochenschr., xxxv. 1397 and 1461, 1885.—Scifert,
Sitzungsberichte der Wiirzb. phys.-med. Gesellschaft, 1885, 14th session; and
Volkmann’s Sammlung klin, Vortriige, 204.

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CHAPTER IV.
TH SPUTUM.

1 For an exhaustive account of the literature on this subject up to the year 1855,
see A. Biermer, Die Lehre vom Auswurfe, Wiirzburg, 1855; and for later contri-
butions, von Ziemssen’s Handbuch (the chapter on Diseases of the Lungs and
Bronchi), also Troup, The Sputum: its Diagnostic and Prognostic Significations,
1888. Further recent literature will be referred to in the text.

2 H. Kossel, Zeitschr. fiir klin. Medicin, xiii. 152, 1888.

Krinig, Verhandl. des Congresses f. innere Med., x. 407. Wiesbaden, 1891.
Gabritschewsky, Deutsch. med. Woch., Oct. 22, 1891.

See Biermer, p. 50.

Henle and Bihlmann, see Biermer, p. 34.

See Friedlinder, Untersuchung iiber Lungenentziindung, 1873.—Amburger,
Petersburger med. Wochenschr., xii. 13, 1876.—Hcitler, Wiener med. Wochenschr.,
XXvii. 1185 and 1219, 1877.—Hichhorst, Lehrb. der physikal. Untersuchung innerer
Krankh., i. 381, 1886, 2nd edit.—7roup, The Sputum, 1888, pp. 207-211.

8 Bizzozero, l.c., p. 202.

» Virchow, Virchow’s Archiv, vi. 562, 1854.

W Panizza, Archiv fiir klin. Medic., xxviii. 343, 1881.

1 Buhl, Lungenentziindung, Tuberculose, Schwindsucht. Munich, 1872.

12 Guttmann and Smidt, Zeitschr. fiir klin. Medic., iii. 124, 1881.

3 Troup, The Sputum, p. 210.

14 FA, Hoffmann, Archiv f. klin. Med., xlv. 252, 1889.

15 Sommerbrodt, Virchow’s Archiv, lx. 165, 1872; Berliner klin. Wochenschrift,
xxvi. 1025, 1889.

16 Lenhartz, Deutsche med. Wochenschr., xv. 1039, 1889.

7 Kronig, Charité-Annalen, xv. 227, 1890.

18 Leyden, Virchow’s Archiv, liv. 328, 1872.

19 Curschmann, Archiv fiir klin. Medic., xxxii. 1, 1883. Further, Ungar and
Curschmann, Verhandl. d. Congresses f. inn. Med. Wiesbaden, i. 162, 192, 1882.

20 OQ. Vierordt, Berlin. klin. Wochenschr., xx. 473. 1883. V. Jaksch, Centralbl.
fiir klin. Medic., iv. 497, 1883. Pel, Zeitschr. fiir. klin. Medic., ix. 29, 1885. 4.
Sanger, Festschrift zur Eroffnung des neuen allgemein Krankenhauses zu Ham-
burg. Eppendorf, 1889 (sep. pub.).

1 Lewy, Zeitschr. f. klin Med., ix. 522, 1885.

2 T'roup, Edin. Med. Journ., Dec. 1885 ; ‘The Sputum,” 1888.

2 Wovdez, Wiener klin. Wochenschr., iv. 41, 1891.

*3 Ozermak, ibid., iv. 378, 1891.

2t Fr, Miiller and Schmidt, see Leyden, l.c.—Gollasch, Fortschritte der Medicin,
vii. 361, 1889.—Fink, Inaug. Dissert., Bonn, 1890.

“5 Leyden, Deutsche med. Wochenschr., xvii. 1085, 1891.

26 4, Hiiber, Zeitschr. f. klin. Med., xvii. 341, 1890.

27 Friedreich, Virchow’s Archiv, ix. 613, 1856; x. zor and 507, 1856; and xxx.
388, 1864.

:8 Virchow, Virchow’s Archiv, ix. 557, 1856.

2 Lichtheim, Berlin. klin. Wochenschr., xix. 129 and 147, 1882; and Zeitschr.
f, klin. Medic., vii. 140, 1884.

30 Schiitz, Mittheilungen aus dem kaiserlichen Gesundheitsamte, ji. 208, 223
(for full bibliography on the occurrence of moulds in diseased lungs, 1884).—Pan-
sini, Virchow’s Archiv, cxxii. 424, 189o.

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404 BIBLIOGRAPHY.

3! Paltauf, Virchow’s Archiv, x. 543, 1885.—Lindt, Archiv fiir experim. Pathol.,
XX1. 269, 1886.—Zoss, Centralbl. f. Bacteriol. u. Parasitenkunde, ix. 506, 1891.

3° Virchow, Virchow’s Archiv, ci. 401, 1856.—Friedreich, ibid., xxx. 390, 1864.
See Falkenheim, Archiv fiir experiment. Pathologie, xiv. 339, 1885.

Fischer, Deutsches Archiv fiir klin. Medic., xxxvi. 344, 1885 (with further
notices).— Hauser, Deutsches Archiv fiir klin. Medic., xlii. 127, 1888.

*® Pansini, Virchow’s Archiv, cxxii. 424, 1890.

36 Leyden and Jaffé, Deutsches Archiv fiir klin. Medic., ii. 488, 1867.

37 R. Koch, Erster Congress fiir intern. Medicin, Wiesbaden, i. 56, 1882; Ber-
liner klin. Wochenschr., xix. 21, 1882; Mittheilungen aus dem kais. Gesund-
heitsamte, ii. 1, 1884, Berlin.

38 The literature on the tubercle bacillus has increased greatly of late years.
Here it miust suffice to refer the reader to Fliiqge, l.c., p. 15 ; Weichselbaum, Cen-
tralbl. fiir Bacteriologie und Parasitenkunde, iii. 496-750, 1888 ; and Baumgarten,
Jahresbericht, iv. 158, 1889 ; v. 247, 1890.

39 Lutz, Monatshefte fiir prakt. Dermatol. Erganzungsheft, i. 77, 1886.—Amau,
Baumgarten’s Jahresbericht, iii. 170 (reference), 1888; compare also Biedert and
Sigel, Virchow’s Archiv, xcviii. 91, 1884, and Biedert, Berliner klin. Wochenschr.,
Xxill. 713, 1886.

# See Cornil and Babes, 1.c., p. 584.—Hiippe, l.c., p. 54.—LHdgar Crookshank, An
Introduction to Practical Bacteriology, p. 162, London, 1886.—Fliigge, l.c., p. 208.

4. Neelsen, Baumgarten’s Jahresbericht iiber die Fortschritte in der Lehre von
den pathogenen Mikro-organism., i. $5, 1886.

*® Czaplewski, Centralbl. f. Bacteriol. u. Parasitenkunde, viii. 685, 1890.—Fréinkel,
Berliner klin. Wochenschr., xxi. 195, 1884; Deutsche med. Wochenschr., xviii.
552, 1887. See Giinther, Wiener klinische Wochenschr., i. 292, 1888.—Biedert,
Berliner klin. Wochenschr., xxiii. Nos. 42, 43, 1886; xxiv. 30, 1887.

8 Gabbett, Lancet, April 1887.

4 VY. Jaisch, Prager med. Wochenschr., xiv. 210, 1891.—JZitten, Wiener klin.
Wochenschr., iv. 415, 1891.

® Kiihne, Centralbl. f. Bacteriol. u. Parasitenkunde, viii. 293, 1890.

4 Gibbes, Pract. Pathol. and Morbid Histol., p. 118; and Lancet, May 5, 1883.

4” Kiebs, Archiv fiir experimentelle Pathol., iv. 420, 1875.

48 Eberth, Deutsches Archiv fiir klin. Medic., xxviii. 1, 1881.

4% Koch, Mittheilungen aus dem kaiserlichen Gesundheitsamte, i. 46, 1881,
Berlin.

°° Fricdlénder, Fortschritte der Medicin, i. 716, 1883; and Virchow’s Archiv,
Ixxxvii. 319, 1882. See also Cornil and Babes, 1.c., 349.—Crookshank, l.c., p. 133.—
Baumgarten, Jahresbericht, i. 10-17, 1886; ii. 70, 1887; iii. 33, 1888; iv. 42, 1889;
Vv. 52, 1890.—Fliigge, |.c., p. 343-

1 Friedlinder, Fortschritte der Medicin, iii. 757, 1885.

* A. Friinkel, see (108).

3 Weichselbaum, see (109).

*4 Baumgarten, Jahresbericht, i. 142 (reference), 1886; also ibid., ii. 311, 1887;
iii. 309, 1888; iv. 286, 1889; v. 395, 1890.

» J. Isracl, Klinische Beitriige zur Kenntnis der Actinomykose des Menschen.
Berlin, 1885.

8 Jekinowitsch, Centralbl. £. Bacteriol. u. Parasitenkunde, v. 352 (reference), 1889.

7 Kuschew, ibid., v. 353 (reference), 1889.—R. Paltauf, Anzeiger der k.k. Gesell-
schaft der Aerzte in Wien, No. 6, Feb. 15, 1886.

8 Deichler, Zeitschrift fiir wissenschaftl. Zoologie, xliii, Part i., 1886; xlviii.
303, 1889.

® Afanussiew, St. Petersburger Wochenschr., xii. 322, 331, 339, 347, 1887.

0 Smtschenko, ibid., xiii. 193, 203, 1888,

ce

3
Bd

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CHAPTER IV.—THE SPUTUM. 405

5. Kannenberg, Virchow’s Archiv, lxxv. 471, 1879; and Zeitschr. fiir klin. Medic.,
i. 228, 1880.

6 Bichhorst, Lehrbuch der physik. Untersuchungsmethoden, i. 406, 2nd edit.,
1886.

68 Hochsinger, Wiener med. Blatter, x. 20, 21, 1887.

Manson, see Chap. i. (210).

Leyden, Virchow’s Archiv, liv. 324, 1872.

Schreiner, see Chap. i. (86).

Ladenburg and Abel, Berichte der d. chem. Gesellschaft, xxi. 758, 1888.
Compare 4. W. v. Hofmann, ibid., xxiii. 3297, 3723, 1890; W. Majert and
A. Schmidt, ibid., xxiii. 3718, 1890.

6 Friedreich, see (27). — Zenker, Schmidt’s Jahrbiicher, clxxii. 284 (reference),
1876.

0 Bizzozero, l.c., p. 150.

1 Troup, l.c.

7 Virchow, Virchow’s Archiv, i. 395, 1847.—Fricdreich, ibid., xxx. 380, 1864.—
Schultze, ibid., 1xi. 130, 1874.

73 Biermer, ibid., xvi. 545, 1859; and l.c., p. 55.

™ Leyden, Volkmann’s Sammlung klin. Vortrage, 114 and 115.

> Black, Schmidt's Jahrbiicher, cv. 305 (reference), 1860.

Leyden, Virchow’s Archiv, lv. 239, 1872; and Ixxiv. 414, 1878.

7 R. Fischer, Jahresbericht fiir Thierchemie, ix. 361 (reference), 1879.

73 Fiirbringer, Deutsches Archiv fiir klin. Medic., xvi. 499, 1875.

% Ungar, ibid., xxi. 435, 1878.

80 HT. Kossel, see (2).

81 See also Devolo, Rivista clinica, xxviii. (sep. pub.).

2 Hoppe-Seyler, Handb. d. physiol. u. pathol.-chem. Analyse, p. 414, 5th edit.

83 Peters, Prager medic. Wochenschr., iv. 5, 1864; Schmidt’s Jahrbiicher, exxiii-
277 (reference), 1864.—Leyden and Jaffé, Deutsches Archiv fiir klin. Medic., ii.
499, 1867.

4 Biick, Dissert., Wiirzburg, 1888.—Jacobson, Dissert., Berlin, 1889.

8 Hirschler and Terray, Wiener med. Presse, xxxi. 648, 747, 1890.

86 Saiomon, Maly’s Jahresbericht, viii. 55 (reference), 1879.

8 Filchne, Aus den Sitzungsberichten der physikal.-medic. Societit in Erlangen,
Sittings of 11th June and roth Dec. 1877.—Stolnikow, Petersburger medic. Woch-
enschr., No. 8, 1878.—Stadelnunn, Zeitschr. f. klin. Med., xvi. 128, 1889.

88 Escherich, Deutsches Archiv fiir klin. Medic., xxxvii. 196, 1885.

89 V. Bamberger, Wiirzburger medic. Zeitschr., ii. 333, 1861.—Renk, Zeitschr. fur
Biologie, xi. 102, 1875.

90 Lumniczer, Wiener med. Presse, xix. 666, 711, 750, 791, 811, 1888.

% Lobisch and v. Rokitansky, Centralbl. f. klin. Med., xi. 1, 1890.

Hv. Frisch, Wiener medic. Presse, xxiv. 1437, 1469, 1883.

% Gabritschewsky, Deutsch. med. Wochenschr., Oct. 22, 1891.

% Cf. Leyden, Zeitschr. fiir klin. Medic., viii. 375, 1885.—Jichtheim, Fortschritte
der Medic., i. 1, 1883.—Brchmer, Die Aetiologie der chronischen Lungenschwind-
sucht, &c. Berlin, 1885..—G. Sée, Die bacillire Lungen-Phthise, German edit. by
Dr. M. Salomon, Berlin, 1886.

9 Robert Koch, Deutsche med. Wochenschr., xvi. 1029, 1890.

9 V, Jaksch, Verhandl. des Congresses f. in. Med., x. 82. Wiesbaden, 1891.

97 Biedert and Siegel, Virchow's Archiv, xcviii. 91, 1884.

98 Nothnagel, Berl. klin. Wochenschr., i. 273 and 283, 1864.

99 Rosenbach, Berl. klin. Wochenschr., xii. 645, 1875.

10 Zopf, Spaltpilze, p. 59, 3rd edit. Breslau, 1885.

101 Renz, Schmidt’s Jahrbiicher, cxxiii. 278, 1864.

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as
406 BIBLIOGRAPHY.

102 Lower, Berl. klin. Wochenschr., i. 335, 1864.

103 Feuerstock, Fortschritte der Medic., i. 456 (reference), 1883.

104 Pansini, Virchow’s Archiv, cxxii. 424, 1890.

105 A. Frénkel, Zeitschr. fiir klin. Medic., x. 401, and xi. 437, 1886.

106 Weichselbaum, Wien. med. Wochenschrift, xxxix. 1301, 1339, 1367, 1886.

107 Newmann, Zeitschrift fiir klin. Medic., xiii. 73, 1888.

108 Frdnkel, Zeitschrift f. klin. Med., xi. 437, 1886.

109 Weichselbawm, see above (106).

WW Friénkel, Deutsche med. Wochenschr., xii. No. 13, 1886.

M1 Pio Fou and Bordoni-Uffreduzzi, Zeitschrift fiir Hygiene, iv. 67, 1888.

12 Weichselbaum, Fortschritte der Medicin, v. Nos. 18 and 19, 1887; and Wiener
klin. Wochenschr., i. 573, 595, 659. 1888.

13 Goldschmidt, Centralblatt f. Bacteriologie und Parasitenkunde, ii. 649, 1887.

114 Yor further notices of pneumonia cocci :—Seifert, Berichte der Wiirzburger
medic. Gesellschaft, 1884.—Platonow, Mittheilungen aus der med. Klinik zu
Wiirzburg (Gerhardt), p. 221, Wiesbaden, 1885.—Matray, Wiener allgem. medic.
Zeitung, xxxi. 217, 1886.—Fliigge, l.c., p. 204.—Baumgarten, Jahresbericht, i. 9,
1886; ii. 54, 1887; iii. 33, 1888; iv. 53, 1889; v. 52, 18900.—Weichselbaum, Cen-
tralbl. f. Bacteriologie u. Parasitenkunde, i. 553, 587, 1887.—Knauthe, Schmidt’s
Jahrb., ccoxi. 28, 1886 —Dippe, ibid., ccxiii. 35, 1887.—Wolf, Wiener medic.
Blatter, x. 10-14, 1887.—Baumgarten, Lehrbuch der pathologischen Mythologie,
i. 236, Brunswick, 1890.—Levy, Archiv f. experimentelle Pathol. u. Pharmakol.,
xxix. 139, 1891.—Pansini, Virchow’s Archiv, cxxii. 424, 1890.

5 Kannenberg, see (61).

16 Stadelmann, l.c., p. 127.

uu” Bonome, Deutsche med. Wochenschr., xii. 932, 1886.

es Hirschier and Terray, Wien. med. Presse, xxxi. 698, 747, 1890. 1

9 Bouveret, Schmidt’s Jahrbiicher, ccxxvii. 152 (reference), 1890.

120 Merkel, Ziemssen’s Handbuch, i. p. 501, 2nd edit.

CHAPTER V.
GASTRIC JUICE AND VOMIT.

1 On the physiology of this subject, see Maly, Chemie der Verdauungssafte
und Verdauung, Hermann’s Handb. der Physiologie, v. 2, p. 37; Hoppe-Seyler,
Physiolog. Chemie, l.c., p. 47, Verdauung, p. 175.

2 Abelous, Comptes rendus, cviii. 310, 1889.

3 Compare also Wasbutski, Archiv f. experiment. Pathol. u. Pharmakol., xxvi.
133, 1889.—Leubuscher, Zeits. f. klin. Med., xvii. 474, 1890.—Kast, Maly’s Jalires-
bericht, xvii. 271 (reference), 1890.— Strauss and Wurtz, Archiv de Med. experi-
ment., Schmidt’s Jahrbiicher, ccxxv. 119 (reference), 1890; Hamburger Centralbl.
f. klin. Med., xi. 425, 1890.—Kabrhel, Archiv f. Hygiene, x. 382, 1890.

4 Jaworski, Centralblatt fiir klin. Medic., vii. 849, 1886.

5 Leube, Ziemssen’s Handb. der spec. Pathol. und Therapie., vii. 2; also Volk-
mann’s Sammlung klin. Vortriige, No. xii. p. 496 ; Archiv fiir klin. Medic., xxxiii.
I, 1883.

® See Maly, Hermann’s Handbuch, l.c., v. 2, p. 41.

? Schiitz, Zeitschr. fiir Heilkunde, v. 4o1, 1884.

8 Ewald and Boas, Virchow's Archiv, ci. 325, 1886, and civ. 271, 18°8.

® See also Ritter and Hirsch, Zeitschr. fiir klin. Medicin, xiii. 1888.— Jaworski,

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CHAPTER V.—GASTRIC JUICE AND VOMIT. 407
Archiv f. klin. Med., xxxiii. 227, 1883.—Other methods are given in the Russian
translation of this book by Profs. V'schunowsky, Jawein, and Pruriz, p. 426.

10 Edinger, Deutsches Archiv f. klin. Med., xxix. 555, 1881.

1 Spéith, Minch. med. Wochenschrift, xxxiv. 51, 1887.—.J. Czyrmianski, Thera-
peutische Monatshefte, i. 265, 1887.

12 Boeci, Moleschott's Untersuchungen der Naturlehre, xiv. 437, 1891.

18 Sahli, Correspondenzbl. f. Schweizer Aerzte, xxi. (sep. pub.), 1891.—Giinsburg,
Deutsche med. Wochenschr., xv. No. 41, 1889.

4 Huppert and Schiitz, Zeitschr. fiir physiolog. Chemie, ix. 577, 1885; and
Schiitz, see (7).

1 Schumburg, Virchow’s Archiv, xcvii. 260, 1881.

16 Boas, Centralblatt fiir die med. Wissenschaften, xxv. 417, 1887.
W Raudnitz, Prag. med. Wochenschrift, xii. 24, 1887.

18 Johnson, Zeitschrift fiir klinische Medicin, xiv. 240, 1888.

19 Boas, ibid., xiv. 249, 1888.

*Y Klemperer, ibid., xiv. 280, 1888.

“1 @. Rosenthal, Berliner klin. Wochenschr., xxvi. No. 45, 1888.

22 Johannessen, Zeitschr. f. klin. Med., xvii. 304, 1890.

3 Sandberg, Schmidt's Jahrbiicher, ccxxiii. 256 (reference), 1889.
24

See Catrin, Arch. gén., xix. 455, 584, 1887.

> Reichmann, Berl. klin. Wochenschr., xix. 606, 1882 ; xxi. 768, 1884; and xxiv.
12-16, 1887.—Sahli, Corresp.-Blatt der Schweizer Aerzte, xv. 1885, quoted by
Riegel.—L. Schiitz, Prager medic. Wochenschr., x. 173, 1885.—Van der Velden,
Tagebl. der 58. Versamml. deutsch. Naturforscher, 437, 1885, Strassburg.— Riegel,
Deutsches Archiv fiir klin. Medic., xxxvi. 427, 1885 ; and Zeitschr. fiir klin. Medic.,
xi. 1, 1886.

*6 Riegel, Deutsche med. Wochenschrift, xii. 52, 1886 ; and Zeitschrilt fiir klin.
Medicin, xii. 434, 1887.

7 Korezynski and Jaworski, Deutsche med. Wochenschrift, xii. 829, 856, 872,
1886.

*8 Reichmann, l.c., see (25).—Riegel, Deutsche med. Wochenschrift, xiii. 637,
1887.— Sticker, Miinchener, med. Wochenschrift, xxxiii. 32, 33, 1886.

*9 Boas, Deutsche med. Wochenschrift, xiii. 519, 548, 577, 1887.—Honigmann,
Miinch. med. Wochenschrift, xxxiv. 951, 972, 994, 1887.

*0 For the estimation of acid, see £. Ludwig, Medicinische Chemie, p. 118
Wien-Leipzig, 1885.

31 Bwald, Klinik der Verdauungskrankheiten, ii. 18, 1888. Berlin.

32 Teo, Centralbl. f. d. med. Wissenschaft, xxvii. No. 27, 1889; Diagnostik
der Krankheiten der Verdauungsorgane, p. 92. Berlin, 1890.

33 Leo, Diagnostik, p. 114, 1890; Archiv f. d. ges. Physiol., xlviii. 614, 1891.

344A. Loffmann and A. Wagner, Centralbl. f. klin. Med., xi. 713, 1890.—Lco,
ibid., xi. 865, 1890.

35 Kossler, Zeits. f. physiol. Chemie, 1891.

36 See R. Miller, Schmidt’s Jahrbiicher, clxxi. 113. 1876; clxxix. 113, 1878;
and cxcii. 65, 1881.—Muly, Chemie der Verdauungssafte und der Verdauung.
Hermann’s Handb. der Physiol., v. 2, l.c., p. 59.

37 Mohr, Zeitschr. fiir analytische Chemie, xiii. 321 (reference), 1874.

38 Zwald and /oas, see (8).

39 Witz, Zeitschr. fiir analyt. Chemie, xv. 108 (reference from Pharm. Centyral-
halle, p. 94, 1875), 1876.—Hilger, Zeitschr. fiir analyt. Chemie, xvi. 116 (reference
from Pharm. Centralhalle, xvii. 257), 1877.

40. Maly, Zeitschr. fiir physiol. Chemie, i. 174, 1877.—Van der Velden, Zeitschy.
fiir physiol. Chemie. iii. 25, 1879; Deutsches Archiv fiir klin. Medic., xxiii. 369,
1879; xxvii. 186, 1880.

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408 BIBLIOGRAPHY.

41 Kost, Dissertation, Jahresbericht iiber die Leistungen und Fortschritte der
gesammten Medicin, xxviii. 136 (reference), 1888.

2 Hwald, see (31).

43 Boas, Deutsche med. Wochenschr., xiii. 852, 1887.

44 Bourget, Revue médicale de la Suisse romaine (sep. pub.), 1888.

4° Koster, Likare forenings forhandlingar, xx. 355.—Hammersten, Maly’s Jahres-
bericht fiir Thierchemie, xv. 287 (reference), 1886.

46 Héssclin, Miinch. med. Wochenschr., xxxiii. 93, 1886.— Riegel, see Alt, Central-
blatt fiir klin. Medicin, ix. No. 3 and No. 13 (sep. Supplement), 1888.—<Alt, ibid.
—Sticker, Miinch. med. Wochenschrift, xxxiv. 52, 1887.—Auhn, Inaugural Disser-
tation. Giessen, 1887.

47 See also Wurster, Centralbl. fiir Physiologie, i. No. 11 (sep. Supplement),
1887 ; and Schulz, Centralblatt fiir die med. Wissenschaften, xxiv. 449, 1886.

48 Boas, Deutsche med. Wochenschr., xiii. 852, 1887.— Wurster, l.c. (47).—
Ginzburg, Centralblatt fiir klin. Medic., ix. 185, 1887.

49 Ginzburg, Centralblatt fiir klin. Med., viii. No. 40, 1887; ix. 10, 1888; and
xi. 913, 1890.—Germain Sce and Villejeau, Maly’s Jahresbericht, xviii. 163 (re-
ference), 1889.

50 V, Jaksch, Zeitschr. f. klin. Med., xvii. 394, 1£90.

51 Haas, Miinchener med. Wochenschr., xxxv. 76, 96, 111, 1888.

52 See Schaffer, Zeitschr. f. klin. Med., xv. 162, 1888.

53 Boas, Centralbl. f. klin. Med., ix. (sep. pub.), 1888 ; xi. 943, 1890.—Pruriz,
ibid., xi. 452 (reference), 1890.

54 Compare Griacosa, Molinari, Santoni, Maly’s Jahresbericht, xix. 248 (reference),
1890.—Sansoni and Molinari, ibid., xix. 251 (reference), 1891.—Moritz, Archiv f.
klin. Med., xliv. 277, 1889.

55 R, v. Jaksch, Zeitschr. f, klin. Med., xvii. 394, 1890.

56 Uffelmann, Deutsches Archiv fiir klin. Medicin, xxvi. 431, 1880.

57 Ufelmann, Zeitschrift fiir klin. Medicin, viii. 393, 1884.

°8 Dreschfeld, Clinical Diagnosis of Cancer of the Stomach, Medical Chronicle,
May and June 1886.

59 Kahler, Prager med. Wochenschrift, xii. 271, 279, 1887.

60 Kraus, Prager med. Wochensehrift, xiii. 439, 1888.

6 Bidder and C. Schmidt, Die Verdauungssiafte und der Stoffwechsel, p. 44, 1852.

6 Richet, Du Suc gastrique chez | Homme et les Animaux, ses Propriétés chimi-
ques et physiol. Paris, 1878.

63 V, Mering and Cahn, Deutsches Archiv fiir klin. Medic., xxxix. 233, 1886.

64 Ewald, Klinik der Verdauungskrankheiten, ii, 25, 1887. Berlin.

65 Kossler, see (35).

“6 Sjéqvist, Zeitschrift fiir physiologische Chemie, xiii. 1, 1889.

67 Katz, Wiener med. Wochenschr., No. 51 (sep. pub.), 18go.

88 V. Jaksch, Sitz. d. k. Akad. der Wissench., xcix. (sep. pub.), 1889.

8 Leo, Diagnostik der Krankheiten der Verdauungsorgane, p. 111, Berlin,
1890.—Leubuscher, Congress f. in. Medicin, x. 387, 1891.—Pfungen, Zeitschr. f.
klin. Med., xix. (Supplementary part), 224, 1891.

70 See Mayer, Dissert. Schade. Berlin, 1890.

1 VY, Jaksch, Wiener klin. Wochenschr., iv. 205, 1891.

72 Leo, Deutsche med. Wochenschr, xvii. 145, 1891.

73 Kossler, see (35).

74 Rosenheim, Deutsche med. Wochenschr., xvii. 1323, 1891.

7 Salkowski and Fawitzky, Virchow’s Archiv, cxxiii. 307, 1891.—Salkowski, Cen-
tralbl. f. klin. Med., xii. 90, 1891.

76 Boas, Centralbl. f. klin. Med., xii. 34, 1891.

77 Bourget, Schmidt's Jahrbiicher, ccxxix. 146 (reference), 1891.

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CHAPTER V.—GASTRIC JUICE AND VOMIT. 409

73 Wagner, Archives de physiologie (3), lv. July (sep. pub.), 1891.—KXossler,
see (35).

™ See Leube, Specielle Diagnostik, &c., p. 234. Leipzig, 1889.

80 Kossler, see (35).—Compare Dinochowski, Internat. klin. Rundschau, v. 1881,
1891.

‘1 4. Hoffmann, Centralbl. f. klin. Med., x. 793, 1890; xi. 521, 1890.

8 4. Hoffmann, Verhandl. des X. internationalen Congresses, ii. 201. Berlin. —
Compare Heubner, Jahrbuch f, Kinderheilkunde, xxxii. Parts i. and ii., 1889.

83 Kossler, see (35).

84 Morner, Maly’s Jahresbericht, xix. 253 (reference), 1890.—Mintz, Wiener
klin. Wochenschr.,, iii. No. 20, 1:90.—/ollcs, Wiener med. Presse, xxxi. 2008, 1890.—
Kronfeld, Wiener klin. Wochenschr., iv. 46, 1891.—Czyrnianski, Wiener med.
Wochenschr., xl. No. 20, 1890.

85 Luttke, Deutsche med. Wochenschr., xvii. 1325, 1891.

86 Moritz, Archiv f. klin. Med., xliv. 277, 1889.—Wohklmann, Jahrbuch f. Kinder-
heilkunde, xxii. 297, 1881.—V. Jaksch, see (71).

& V. Jaksch, see (71).

8 Compare also #. (eigl, Aus den Sitz. d. Wiirzburger phys. med. Gesellsch.
(sep. pub.), 1891.—N. C. Kjaergaard, Maly’s Jahresbericht, xix. 258 (reference),
1890.—Hayem and Winter, Centralbl. f. klin. Med., xi. 530 (reference), 1890.—
Salkowski and Kwmagawa, Virchow’s Archiv, exxii. 235, 1890.

8 Immermann, Bericht der Congresses f. in. Medicin, viii. 219, 1889.—Schetty,
Deutsches Archiv f. klin. Med., xliv. 219, 1890.

90 Chelmonski, Schmidt’s Jahrbucher, ccxxvi. 134 (reference), 1890.—A lemperer,
Berliner klin. Wochenschr., xxvi. 11, 1889.—P. Bricger, Deutsche med. Wochen-
schr., xv. 14, 1889.—Hildebrand, ibid., xv. 15, 1889.—Schwalbe, Virchow’s Archiv,
cxvii. 316, 1889.

% Grusdew, Centralbl. f. klin. Med., xi. 92 (reference), 1890.

© Hiifler, Miinchener med. Wochenschr., xxxvi. 561, 1889.

%3 Pinhorn, Berliner klin. Wochenschr., xxvi. 1042, 1889.—Adler and Stern,
Berliner klin. Wochenschr., xxvi. 1063, 1889.

94 Biermacki, Centralbl. tf. klin. Med., xi. 265, 1889.

%” R.v. Jaksch, Real Encyclopadie der gesammten Heilkunde, xxii. 90, 1890.

%8 Lenhartz, Schmidt’s Jahrbiicher, cexxv. 277, 1840; Deutsche med. Wochen-
schr., Nos. 6 and 7, 1890.

87 Leo, see (32) and (33).—Boas, Allgemeine Diagnostik und Therapie der
Magenkrankheiten, p. 120. Leipzig, 1890.

% Kredel, Zeitschr. fiir klin. Medic., vii. 592, 1884.

8 Ewald, op. cit., ii. 27.

10 See also Grundzach, Virchow’s Archiv, xi. 605, 1888.

101 Leo, 1.c., p. 114.

1022 Hammarsten, Letrbuch der physiol. Chemie, p. 164. Wiesbaden, 1891.

103 Riegel, Zeitschr. fiir klin. Medic., xi. 167, 1886.

104 Leo, Centralbl. f. d. med. Wissensch., xxvii. No. 26, 1889.

5 Klemperer, Charité-Annalen, xiv. 228, 1889.—V. Jaksch, Zeitschr. f. klin.
Med., xvii. 393, 1890.

106 Salkowsk?, Centralbl. fiir die med. Wissenschaften, xviii. 690, 1880.

107 Wor further particulars about these methods, see Hoppe-Seyler, Handb. der
physiol.- und pathol.-chem. Analyse, l.c., p. 348—//uppert, Neubauer, and Vogel,
Anleitung zur Analyse des Harns, &c., p. 458, 9th edit., 1890.

108° Hwald, Berliner klin. Wochenschr., xxiii. 825, 846, 1886.

09 Hwald and Boas, Centralbl. fiir die med. Wissensch., xxvi. 273, 1888.

WW Rosenheim, ibid., xxv. 865, 1887 ; xxvi. 273, 1888; and Virchow’s Archiv,
exi. 414, 1888.

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410 BIBLIOGRAPHY.

11 Penzoldt and Faber, Berliner klin. Wochenschr., xix. 363, 1882.

12 P. Zweifel, Deutsches Archiv fiir klin. Med., xxxix. 349, 1886.

13 Leube, Deutsches Archiv f. klin. Med., xxxiii. 1, 1883.—XKlempercr, Deutsche
med. Wochenschr., xiv. 962, 1888.—Sievers and Ewald, Therapeutische Monatshefte,
1. 289, 1887.—Kwald, Deutsche med. Wochenschr., xv. 211, 1889; Berliner klin.
Wochenschr., xxvi. 977, 1889.

M4 Wolitzky, Prager med. Wochenschr., xvi. 355, 1891.—Compare Fal, Wiener
med. Wochenschr., ii. 922, 1889.—JZeo, l.c., p. 80.—Huber, Miinchener med.
Wochenschr., xxxvi. No. 19, 1889.—Decker, Berliner klin. Wochenschr., xxvi. 975,
1889.

™ Boas, Zeitschr. f. klin. Med., xvii. 154, 1890.

16 Boas, ibid., 158.—1'schlenoff, Centralbl. f. klin. Med., xi. 60 (reference), 1890.

"7 Boas, see (116) and Berliner klin. Wochenschr., xxvii. 20, 21, 23, 1890.—
Noorden, Zeitschr. f. klin. Med., xvii. 137, 1890.

18 Compare Boas, Deutsche med. Wochenschr., xvii. 869, 1891.—MacFadyean,
Nencki, Sieber, Archiv. f. experiment, Pathol. u. Pharmakol., xxviii. 311, 1891.

19 W. de Bary, Archiv fiir experimentelle Pathologie und Pharmakologie, xxi.
283, 1886.

0 See Mayer's Lehrbuch der Gahrungschemie, p. 93. Heidelberg, 1879.

"See Miller, Deutsche med. Wochenschrift, xii. 117, 1886.

™ Fischer, see Chap. iv. (34).—Fulkenheim, Archiv fiir experimentelle Pathologie
und Pharmakologie, xix. 1, 1885.

8 Ewald, l.c. (64), p. 234.

™ Ewald, ibid., p. 293.

5 Compare Litten, Deutsche med. Wochenschr., xiv. No. 47, 1888.—Litten and
Rosengart, Zeitschr. f. klin. Med., xiv. 573, 1888.—Jaworski, Verhandlungen 4d.
Congresses f. in. Med., vii. 272, 1888.—Rosenheim, Berliner klin. Wochenschr.,
xxv. Nos. 51 and 52, 1888.—G. Meyer, Zeitschr. f. klin. Med., xvi. 366, 1890.

16 Mathieu, Rev. de Méd., ix. 708, 1889.

1% John, Virchow’s Archiv, cxxii. 271, 1890.

"8 Riegel, Zeitschrift fiir klin. Med., xii. 5, 1887; and Deutsche med. Wochen-
schr., xiii. No. 29, 1887. See also S. Rothschild, Maly’s Jahresbericht, xvi. 245
(reference), 1886.— Vogel, Inaug.-Dissertation, Karlsruhe, 1887.

129 See Gerhardt, Deutsche med. Wochenschr., xiv. 18, 1888.

19 Ewald, l.c., p. 202.—Ritter and Hirsch, see (9).—Jaworski, Miinchener med.
Wochenschr., xxxiv. 117, 139, 1887.

131 Lenhartz, Deutsche med. Wochenschr., xvi. Nos. 6 and 7, 1890.

132 Ewald, Zeitschr. fiir klin. Medic., i. 619, 1880.—Hwald and Boas, see (110) ;
and Virchow’s Archiv, civ. 271, 1886.

183° Kredel, Zeitschr. fiir klin. Medic., vii. 592, 1884.

4 Korezynski and Jaworski, Deutsche medic. Wochenschr., xii. 829, 856, 872,
1886.

189° Cahn, Verhandl. des Congresses fiir innere Med., vi. 354, 1887.—Rosenbuch,
Centralblatt fiir klin. Med., viii. 12, 1887. — Honigmann and V. Noorden, Zeitschr.
fiir klin. Med., xiii. 87, 1887.—Sticker, Centralblatt fiir klin. Med., viii. 34, 1887.—
Klemperer, Zeitschrift fiir klin. Med., xiv. 147, 1888.— Haberlin, Deutsches Archiv
f. klin. Med., xlv. 337, 1880. s

136 Q, Rosenbach, Centralbl. f. klin. Med., viii. 585, 1888.—Wactzhold, Charité-
Annalen, xiv. 237, 1889.

7 Edinger, Berliner klin. Wochenschr., xvii. 117, 1880; and Deutsches Archiv
fiir klin. Medic., xxix. 555, 1881.

138° Rosenstein, Berliner klin. Wochenschr., xxvii. 289, 1890.—Gans, Berichte des
Congresses f. in. Med., ix. 286, 1890.—Honigmann, Deutsche med. Wochenschrift,
Xvi. 947, 1890.

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CHAPTER V.—GASTRIC JUICE AND VOMIT. 411

9 Grundzach, Berliner klin. Wochenschr., xxiv. 30, 1887.—Ewald and Wolf,
ibid.
140
141
142

Gluzinzski, Deutsches Archiv. f. klin. Med., xlii. 312, 1887.

Kundrat, Wiener medic. Blitter., vii. 1538, 1884.

Gerhardt, see Ewald, Klinik der Verdauungskrankheiten, ii. 272. Berlin,
1888. Other observations are also given there by Meschede, Lublinski, Fermaud.

M43. Senator, Berliner klin. Wochenschr., xxvii. 141, 1890.—Sehreiber, ibid., xxvii.
408, 1890.

4 Hildebrandt, ibid., xxvii. 434, 1890.

™ See F. C. Schneider, Die gerichtliche Chemie fiir Gerichtsarzte und Juristen.
Vienna, 1852.—Fr. J. Otto, Anleitung zur Ausmittlung der Gifte, 6thedit. Bruns-
wick, 1884.—Z. Ludwig, Med. Chem., in l.c. (30). Aobert, Compendium der prak-
tischen Toxikologie. Stuttgart, 1887.

M6 See EZ. Ludwig, Medic. Chemie, l.c., p. 278.

M7 E. Ludwig, \.c., p. 289.

48 EF. Ludwig, 1.c., p. 239.

M9 E. Ludwig, Medicinische Jahrbiicher, 143, 1877; and 493, 1880,

1 Fiirbringer, Berliner klin. Wochenschr., xv. 332, 1878.

UI F.C. Schneider, Sitaungsberichte der kaiserl. Akademie der Wissenschaften
(Vienna), xliv. 255, 1860.

'® Lecco, Berichte der deutschen chem. Gesellschaft, xix. 1175, 1886.

153 See Ludwig, l.c., p. 252; and Fr. Otto, l.c., p. 167.

14 For further methods, see J. Otto, l.c., p. 14; and Lwdwig, l.c., p. 172.

15 Alt, Berliner klin. Wochenschr., xxvi. 560, 18809.

186 J. Otto, 1.c., p. 103; LE. Ludwiy, 1.c., p. 327 ; and Nobert, l.c., p. 116.

7 FB. Ludwig, 1.c., p. 317.

8 Brieger, Ueber Ptomaine. Berlin, 1883, 1886.—Oefiinger, Die Ptomaine oder
Cadaveralkaloide. Wiesbaden, 1885, where are given other notices.—Hugounengq,
Les Alcaloides d'origine animale. Paris, 1886.—Béchamp, Microcymas et Microbes,
&c. Paris, 1886.—Mobert, l.c., p. 162.—Armand Gautier, Maly’s Jahresbericht,
xvi, 523 (reference), 1887.—Bricyer, Virchow's Archiv, cxv. 483, 1889.

159 R. v. Jaksch, Wiener klin. Wochenschr., iii. ror1, 1890.

160 R. vy. Jaksch, Wiener med. Wochenschr., 1888.

161 Fr, Miiller, Zeitschr. f. klin. Med., xvi. 496, 1889.

162 Brieger, Untersuchungen tiber Ptomaine, Pt. iii. p. 19, 1886.

163 Brieger, Zeitschr. f. klin. Med., xvii. (Supplement), 253, 1890.

164 Baumann and v. Vdransky, Berichte der deutschen chemischen Gesellschaft
Xxi. 2744, 2930, 1888.

165 See for details, Brouardel, Ogier, and Minovici, Bull. de Acad. de Méd., li
26, 1887 ; Schmidt’s Jahrbiicher, ccxvii. 4 (reference), 1888.

166 Otto, l.c., p. 43, EL Ludwig, l.c., p. 55.

167 Vaughan, Zeitschr. f. physiol. Chemie, x. 146, 1886; Maly's Jabresber., xvii.
57 and 483, 1888.

168 Ehrenberg, Zeitschr. f. physiol. Chemie, xi. 239, 1887.

169 Brieger and Friinkel, Berliner klin. Wochenschr., xxvii. 241, 268, 1890.

1” Berthelot, Chem. Centralbl., xi. (3), 584 (reference), 1871.

wl J. Otto, see (145).—E. Ludwig, see (145).

7 Vitali, Rivista di Chimica med. et farm., 1 (sep. Supplement).

173 Lustgarten, Monatshefte fiir Chemie, iii. 715, 1882.

4 For the quantitative estimation, see Chapter on the Urine, and also Ludwig,
l.c., p. 186.

175 Jacquemin, Berichte der deutschen chem. Gesellschaft, ix. 1433 (reference).
1876.

176 PD. Ludwig, 1.c., p. 189.

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412 BIBLIOGRAPHY.

V7 A, Flickiger, Zeitschr. f. analyt. Chemie, xxviii. (reference), 1888.
Jacquemin, see Lewin, l.c., p. 182.

Pf. Ludwig, l.c., p. 182.

180 Vortmann, Monatshefte fiir Chemie, vii. 416, 1886.

CHAPTER VI.
THE FECES.

1 For the literature on the subject see Nothnagel, Beitriige zur Physiol. und
Pathol. des Darmes. Berlin, 1884.

2 Widerhofer, Jahrbuch f. Kinderheilk., iv. 256, 1871.

3 Betz, Schmidt’s Jahrb., cviii. 202 (ref.), 1860.—A. Voyel, ibid.—Monti, see
Widerhofer, |.c., p. 257.—Zawadski, Schmidt’s Jahrb., ccxvi. 29 (ref.), 1887 ; ccxxi.
238 (ref.), 1889.

+ Lesage, Archives de Physiologie normale et pathologique, i., 4. Série, 212, 1888 ;
see also G. Hayem, Centralbl. fiir Bacter. und Parasitenk., ii. 531 (ref.), 1887.

> Pettenkofer, Annal. der Chemie, xxv. 95, 1884.

® Vanlair and Masius, Centralbl. f. die medic. Wissensch., ix. 369, 1871.

7 Virchow, Virchow’s Archiv, lii. 558, 1871.

8 Fichhorst, l.c., p. 240.

® Nothnagel, l.c., p. 185.

1 Litten, Berl. klin. Wochenschr., xxv. 292, 1888.

1 Loos, Prager med. Wochenschr., xiv. 579, 1890.

2 See also Kitagawa, Zeitschr. f. klin. Med., xviii. 9, 1890.

13 Virchow, Virchow’s Archiv, v. 278, 1853.—Nothnagel, l.c., p. 96.

4 Q, Kitagawa, Inaug. Dissert. Wiirzbure, 1889.

1 Nothnagel, l.c., p. 90.

16 Compare also Avtagawa, Inaug. Dissert. Wiirzbure, 1890.

7 Vignal, Diastatic Ferments, 1889.

18 MacFadycan, Internat. Congr. of Hygiene, Lancet, Aug. 15, 1891.

19 Wyss, Verhandl. der 7. Versammlung der Gesellsch. f. Kinderheilkunde, vii.
149, 1888. Compare also Levy, Archiv f, experiment. Patho]. u. Pharmakol.,
xxix. 148, 1891.

20 Uffelmann, Deutsches Archiv fiir klin. Med., xxiv. 437 (447), 1881.

21 See Mayer, Gahrungschemie, p. 93. Heidelberg, 1879.

2 Nothnagil, 1.c., p. 113.—Brieger, Zeitschr. fiir physiol. Chemie, viii. 306,
1884.— Ufielmann, see (20).—Lscherich, Fortschritte der Med., iii. 515, 547, 1885;
and Die Darmbacterien des Siiuglings, &c., Stuttgart, 1886; Centralbl. f. Bacter.
u. Parasitenk., i. 705, 1887.—Bienstock, Zeitschr. fiir klin. Med., viii. 1, 1884.—
Stahl, Verhandl. des Congresses fiir int. Med., iii. 193, 1884.—A isl, Fortschr. der
Med., iv. 144 (ref.), 1886.—Miller, Deutsche med. Wochenschr. xi. 138, 843,
1886.—Sucksdorf, Baumgarten’s Jahresb., iii. 420 (ref.), 1888.

23 Prazmowski, Untersuch. iiber die Entwicklungsgeschichte u. Fermentwirkung
einiger Bacterienarten. Leipzig, 1880.

24 Koch, Ueber den Infectionsorganismus der Cholera. Berliner klin. Wochen-
schr., XXi. 477, 493, 509, 1884; Deutsche medic. Wochenschr., x. 499, 519, 1884;
Baumgarten, Jahresber., i. 109, 1885; ii. 290, 1887 ; iii. 278, 1888; iv. 261, 1889 ;
v. 365, 1891; Cornil and Babes, |.c., p. 467 ; Crookshank, l.c., p. 1373; Fliigge, l.c.,
Pp. 344.

°5 Neuhauss, Centralbl. f. Bacteriol. u. Parasitenkunde, v. 81, 1889.

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CHAPTER VI.—THE FACES. 413

°6 Lofler, Centralbl. f. Bacteriol. u. Parasitenkunde, vi. 224, 1889; vii. 639,
1890. See also Frénkel and Pfeiffer, Mikrophotographischer Atlas, fig. 96.

7 HHueppe, Fortschr. der Med., iii. 619, 1885.

*8 Babes, Virchow’s Archiv, xcix. 148, 1885.—Vandyke Carter, Lancet, ii. 405,
1884.—Wicati and Mietsch, Deutsche med. Wochenschr., ix. 361, 1884; and
Archives de Physiol. normale et pathol., xii. 72, 1885.—Van Ermengen, Recherches
sur le Microbe du Choléra asiatique, Paris, 1885; Deutsche Wochenschr., xi.
499, 1885 ; New Investigations on the Cholera Microbes, trans. by Dr. R. Kukula,
1886 ; see further Pfeiffer for exhaustive references ; Deutsche med. Wochenschr.,
xii. Nos. 5, 6, 7, 8, 9, 13. 14, 1886; Rossbach, v. Ziemssen’s Handb., 3rd edit., vol.
ii. p. 32, 1886; Riedel, Die Cholera, Entstehung, Wesen und Verhiitung dersel-
ben. Berlin, 1887.

*9 Schottelius, Deutsche med. Wochenschr., xi. 213, 1885; see also Di Vestea,
Centralbl. fiir Bacter. und Parasitenk., ii. 320 (ref.), 1888.

30 Bitter, Baumgarten’s Jahresber., ii. 299 (ref.), 1886.—Rietsch, Centralbl. fiir
Bacter. und Parasitenk., ii. 654, 1887.

31 Poehl, Berichte der deutschen chem. Gesellsch., xix. 1161, 1886.—Bujwid,
Zeitschr. f. Hygiene, ii. 52, 1887; and Centralbl. f. Bacter. und Parasitenk., iii.
169, 1888 ; iv. 494, 1888. For further literature see Dunham, Zeitschr. f. Hygiene,
ii. 337, 1887 ; Ali-Cohen, Fortschr. der Med., No. 17, 1807 ; for Zéislein, Jadassohn,
consult Bujwid, l.c., p. 70.

®2 Brieger, Deutsche med. Wochenschr., xiii. 305, 469, 1887.

3 Salkowski, Virchow’s Archiv, cx. 366, 1888.

34 Kitasato, Zeitschr. f. Hygiene, vii. 519, 1889.

35 Oantant, Deutsche med. Wochenschr., xii. 89, 1886.
36 Brieger, Berliner klin. Wochenschr., xxiv. 817, 1887.
7 Powchet, Compt. rend., xcix. 847, 1884.

38 Finkler, Tagblatt der Magdeburger Naturforscherversammlung; Deutsche
med. Wochenschr., x. 36, 1884; Tagblatt der 58 Versamml. deutsche Natur-
forscher und Aerzte zu Strassburg, p. 438, 1885,—Finkler and Prior, Ergiinzungs-
hefte zum Centralbl. fiir allgem. Gesundheitspflege, i., Pts. 5 and 6, 1885.

39 V. Hovorka and Winkler, Baumgarten’s Jahresbericht, v. 367 (reference), 1890.

40° Deneke, Deutsche med. Wochenschr., xi. 33, 1885.

41 Lberth, Virchow’s Archiv, 1xxxiii. 486, 1881.

#2 Klebs, Archiv fiir experiment. Path. und Pharmak., xii. 231, 1880; xiii. 381,
1881.—Eppinger, Klebs’ Handb. der patholog. Anatomie, Pt. vii., edit. by Prof.
Eppinger, 1880.

43 Koch, Mittheil. aus dem kaiserl. Gesundheitsamte, i. 45, 1881.—Meyer, Inaue.
Dissert. Berlin, 1881.—Friedldnder, Verhandl. der Berl. physik. Gesellsch., 1881.
—Gaffky, Mittheil. aus dem kaiserl. Gesundheitsamte, ii. 372, 1884.—Further con-
sult Cornil and Babes, 1.c., p. 419; Crookshank, 1.c., p. 1743 Fliigge, 1.c., p. 198;
Baumgarten’s Jahresber., i. 100, 1886; ii. 150, 1887 ; iii. 233, 1888; iv. 142, 1889;
v. 189, 1890.

4 Friinkel and Pfeiffer, Mikrophotographischer Atlas, pl. 46.

4 Gafky, l.c., p. 384.

46 Birch- Hirschfeld, Schmidt's Jahrb., ccxv. 288, 1887; and Archiv fiir Hygiene,
vii. 342, 1888. :

47 Buchner, Centralbl. fiir Bacter. und Parasitenk., iv. 353, 385, 1888.—P/fwil,
ibid., iv., 769, 1888.

48 Pfeiffer, Deutsche med. Wochenschr., xi. 500, 1885.

49 Chantemesse and Widal, Archives de Physiol. &c., ix. 217, 1887.

50 Holz, Zeitschr. f. Hygiene, viii. 143, 1890.

51 Grancher and Deschamps, cited by Holz.

52 Néggerath, Fortschritte d. Med., vi. 1, 1888.

oo

2

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414 BIBLIOGRAPHY.

°3 Kitasato, Zeitschr. f. Hygiene, vii. 515, 1889.

>4 Compare also Heim, Miinchener med. Wochenschr., xxxvi. 408. 1889.—
Petruschky, Centralbl. f. Bacteriol. u. Parasitenkunde, vi. 660, 1889.—Karlinski,
ibid., vi. 65, 1889.—Janowski, ibid., viii. 167, 193, 230, 262, 417, 449, 1890.

°> Babes, Centralbl. f. klin. Med., xii. 682 (ref.), 1891.—Cassedebat, Centralbl. f.
med. Wissensch., xxviii. 678 (ref.), 1890.—Uffelmann, Berliner klin. Wochenschr.,
xxviii. 858, 1891.

6 F. Frankel and M. Simmonds, Centralbl. fiir klin. Medic., vi. 737, 1885 ; and
Die iitiologische Bedeutung des Typhus-bacillus. Leipzig, 1886.—C. Seitz, Bacteriol.
Studien z. Typhus-atiologie. Munich, 1886.

57 Beumer and Peiper, Zeitschr. fiir Hygiene, i. 489, 1886; and ii. 110, 1887. See
further Strotinin, ibid., i. 465, 1886.—EZ. Frankel and M. Simmonds, ibid., ii. 138,
1887. — Dreyfuss-Brissac, Gaz. hebdomadaire, xxiv. 434 (ref.), 1887.

°8 Beumer, Deutsche med. Wochenschr., xii. No. 28, 1887.—Brouardel and Chante-
messe, Centralbl. f. Bacter. u. Parasitenk., iii. 144 (ref.), 1888. — Kowalski, see Seitz,
ibid., ii. 681, 724, 751, 1887.—Ali-Cohen, Baumgarten’s Jahresb., iii. 149 (ref.), 1888.

' 59 Lichtheim, Fortschr. der Med., ii. 1, 1883.

60 See R, Leuckart, vol. i. Pt. i, 2nd edit., p. 221, 1879-86.

6. Nothnagel, l.c., p. 110, where further references will be found.
Grassi, see Bizzozero, l.c., p. 134.

63 VY. Jaksch, Wiener klin. Wochenschr., i. 511, 1888.—Z. Cohen, Deutsche med.
Wochenschr., xvii. 853, 1891.

64 Lésch, Virchow’s Archiv, Ixy. 196, 1875.

6 Lambl, Prager Vierteljahresschr., xi. 1, 1859; and further see Nothnagel, p. 110.

66 Kartulis, Virchow’s Archiv, xcix. 145, 1885; Centralbl. f. Bacteriol. u. Para-
sitenkunde, ix. 365, 1891. See ref. (174).—J/asswiten, Centralbl. f. Bacteriol. u.
Parasitenkunde, vi. 451 (reference), 1889.—Osler, ibid., vi. 736, 1890.—Dock, Texas
Medical Journal (sep. pub.), 1891.

687 Dressler, see Leuckart, tst edit., p. 740.—Gubler, ibid., 2nd edit., 279. — Kjellberg,
Virchow’s Archiv, xviii. 527, 1860.— Himer, see Leuckart, l.c., p. 278.

88 Podwyssoki, Centralbl. f. Bacteriol. u. Parasitenkunde, vi. 736, 1889.

69 Lambl, l.c., p. 51, and plate 1, fig. 2.

7% Davaine, Traité des Entozoaires, vi. Paris, 1860.—Marchand, Virchow’s
Archiv, lxiv. 293, 1875.—Zunker, Deutsches Archiv f. prakt. Med., i. 1878.

1 Grassi and Schewiakof, Zeitschr. f. wiss. Zoologie, xlvi. 143, 1888.

” Erich Miillcr, Verbandl. des biologischen Vereines zu Stockholm (sep. pub.),
1890.

73 Grassi, see Leuckart, l.c., p. 964 and 968.

74 Perroncito, Centralbl, f. Bacter. u. Parasitenk , ii. 738, 1887; Archives ital. de
Biologie, ix. (sep. pub.); x. (sep. pub.); Giorn. d. R. Acad. di Medicina (sep. pub.),
1887.

7 VY, Jaksch, Wiener klin. Wochenschr., i. 511, 1888.

76 Marchand, see (70).—Zunker, see (70).

77 Malmsten, Virchow’s Archiv, xii. 302, 1857.

78 Stieda, Virchow’s Archiv, xxxvi. 285, 1866.—G@raziadei and Perroncito, see
Bizzozero, l.c., p. 189.—A. Ortmann, Berliner klin. Wochenschr., xxviii. 814, 1891.
See also Mittercr, Inaug. Dissert.

79 VW. Jakseh, 1.c., p. 512.

80 See Leuckart, Le., 2nd edit., p. 513.

81 Tbid., p. 617.

82 Tbid., p. 832.

83 Grassi, Centralbl. f. Bacter. u. Parasitenk., i. 97, 1887; and Grassi-Calandruccio,
ibid., ii. 282, 1887.—Comini, ibid., ii. 27 (ref.), 1887.

% Bilharz, see Leuckart, l.c., p. 833.—Grassi, Comini, Calandruccio, see (83).

62

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CHAPTER VI.—THE F.ZCES. 415

Perroncito and Airoldi, Gazetta degli Ospidali (sep. pub.), 1888.—Ors?, Sei casi di
Tenia nana (sep. pub.) ; Senna, Gazetta med. Lombard (sep. pub), 1889.

8 Ranson, see Crassi, l.c., p. 285.

86 Leidy, Parona, see Leuckart, l.c., p. 998.

87 Grassi, Centralbl. f, Bacter. u. Parasitenk., i. 257, 1887.

88 4. Hoffmann, Jahrb. f. Kinderheilk., xxvi. Pts. iii. and iv. (sep. Sup.), 1887.—
Kriiger, St. Petersburg. med. Wochenschr., xii. 341, 1887.—Brandt, Centralbl. f,
Bacteriol. u. Parasitenk., v. 99 (ref.), 1889.

89 Grenet, see Leuckart, l.c., p. 841.

® Grassi, Centralbl. f. Bacteriol. u. Parasitenk., i. 257, 1888.

1 Leuckart, l.c., p. 864.

® Runeberg, Deutsches Archiv f. klin. Med., xli. 304, 1887.—Rayher, ibid., xxxix.
31, 1886.—Lichtheim, Verhandl. des Congresses fiir innere Med., vi. 85, 1887.—
Schapiro, Zeitschr. f. klin. Med., xiii. 416, 1888.—Fr. Wiiller, Charité-Annalen, xiv.
p. 9 (sep. pub.).

%3 See Leuckart, l.c., p. 930.

EEN Mijen@l, NWGE, oh yin

% Cf. Bérenger Féraud, Lecons cliniques sur les Tenias de l’Homme. Paris, 1888,

% F, Heller, Aerztl. Bericht des Wiener Allgem. Krankenhauses, p. 262, 1857.

% Leuckart, l.c., 2nd edit., vol. i. Pt. iii. pp. 1 and 589.

% Biermer, Schweizer Zeitschr. f. Heilkunde, ii. 381, 1865.—Bostroem, Deutsches
Archiv fiir klin. Med., xxxiii. 557, 1882.—Buaclz, Berliner klin. Wochenschr., xx.
234, 1883.

99 Bizzozero, l.c., p. 182.

100 Baelz, see (98).

101 See Bizzozero, 1.c., p. 182.

102 See Poirier, Centralbl. fiir Bacter. u. Parasitenk., ii. 186 (ref.), 1888.

3 Leuckart, l.c., 1st edit., vol. ii. p. 156.

104 Tutz, Centralbl. f. Bacter. u. Parasitenk., iii. 553, 584, 616, 1888.

105 Kartulis, ibid., i. 65, 1887.

106 Devaux, Progrés médicale, xv. 415, 1887.—Hogg, Brit. Med. Journ., No. 1438,
122, 1888.

107 #nystein, Prager med. Wochenschr., xvi. 498, 1891.

108 See Lutz, Centralbl. f. Bacter. u. Parasitenk., ili. 681, 713, 744, 1888.

109 Leuckart, l.c., vol. ii., 1st edit., p. 351.

10 Thid., p. 411.

11 Perroncito, see Meissner, Schmidt's Jahrb., clxxxix. 85, 18$1.—Calandruccio,
Centralbl. f. Bacter. u. Parasitenk., i. 665 (ref.), 1887.

12 Menche, Zeitschr. fiir klin. Med., vi. 161, 1883.—Mayer, Centralbl. f. klin.
Med, Nos. 9 and 16, 1885 ; and Vélkers, Berliner klin. Wochenschr., xxii. No. 36,
1885.—Sahli, Deutsches Archiv fiir klin. Medic., xxxii. 421, 1883.—Leichtenstern,
Centralbl. fiir klin. Med., vi. 195, 1885 ; and Deutsche med. Wochenschr., xi. Nos.
29 and 30, 1885; xii. Nos. 11, 12, 13, 14, 1886; xiii. 565, 594, 620, 645, 669,
691, 712, 1887 ; and Ernst, ibid., xiv. 291, 1888.—Béumler, Correspondenzbl. d.
Schweizer Aerzte, i. 1885.—Seifert and Fr. Miiller, Centralbl. f. klin. Med., vi.
27, 1885.

Us Firket, Académie royale de Belgique, viii. No. 12, 1884.

4 Seifert, Verhandl. der physik.-med. Gesellsch. Wiirzburg, xxi. (N. F.), No.
6, 1888.

15 See Lutz, R. Volkmann’s Sammlung, Nos. 255, 256, 1885.

16 Lancet, Oct. 21, 1887.

7 Sonsino, Lancet, Feb. 22, 1890.

us Leuckart, l.c., p. 460.

19 /yni, Berliner klin. Wochenschr., xxiii. 614, 1886.

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416 BIBLIOGRAPHY.

120 Leuckart, 1.c., p. 512.

121 See Meissner, l.c., p. 88; also Bizzozero, l.c., p. 185.—Seifert, Verhandl. des
Congresses fiir int. Med., ii. 337. Wiesbaden, 1881.

zero, 1.C., p. 185.

13° Leuckart, 1.c., p. 952.—Grassi, Centralbl. f. Bacter. u. Parasitenk., ii. 413
(ref.), 1887.

M4 Joseph, ibid., ii. 533 (vef.), 1887.

125 Rembold, Wiener med. Presse, xix. 373 (ref.), 1888.—Zampa, Centralbl. f.
Bacter. u. Parasitenk., iv. 371 (ref.), 1888.—Hohn, Prager med. Wochenschr., xvi.
107, 1891.

1°6 Finlayson, Brit. Med. Journ., June 8, 1889.

17 Leichtenstern, Deutsche med. Wochenschr., xii. 175, 1886.—Nothnagel, l.c.,
p. 198.

128 Uffelmann, Deutsches Archiv f. klin. Med., xxiv. p. 452.

129 Nothnagel, 1.c., p. 193.

180 Gerhardt, Zeitschr. fiir klin. Med., vi. 78, 1883.

131 Qesterlein, Mittheil. aus der medic. Klinik in Wiirzburg, i. 1, 1885.

182 Stadelmann, Deutsches Archiv fiir klin. Med., xl. 372, 1887.

133 [/felmann, 1.c., p. 450.

134 By, Miller, Zeitschr. fiir klin. Med., xiii. 45, 1887.

135 Uffelmann, l.c., p. 446.

1386 See also Baginsky, Die Verdauungskrankheiten der Kinder., p. 230. Tiibin-
gen, 1884.

137 Hoppe-Seyler, Handbuch der physiol. und pathol. chem. Analyse, l.c., p. 505.

138 Thid., l.c., p. 339.

139 Thid., l.c., p. 507.

10 VY. Jaksch, Zeitschr. fiir physiol. Chemie, x. 536, 1886.

11 Brieger, Berichte der deutschen chem. Gesellsch., x. 1027, 1877.

12 Thudichum, Journ. of Chem. Soc., viii. p. 400.

13° Brieger, see (141).

14 Wegscheider, Ueber die normale Verdauung der Siuglinge. See Hoppe-Scyler,
l.c., p. 338.

U5 Brieger, see (147).

6 Nencki, Berichte der deutschen chem. Gesellsch., viii. 723, 1875.

14” For further statements regarding these bodies see Kiihne, Ber. der deutschen
chem. Gesellsch., viii. 206, 1875 ; Nencki, ibid., viii. 336, 722, 1517, 1875; Brieger,
ibid., x. 1027, 1877; Nencki, Zeitschr. fiir physiol. Chemie, iv. 371, 1880; Brieger,
ibid., iv. 414, 1880; A. Bayer, Ber. der deutschen chem. Gesellsch., xiii. 2339,
1880; Vappeiner, ibid., xiv. 2382, 1881; EZ. Salkowski, Zeitschr. fiir physiolog.
Chemie, viii. 417, 1884; #. and W. Salkowshi, ibid., ix. 8, 1885.

48 Hoppe-Seyler, Lehrbuch der physiol.- und pathol.-chem. Analyse, p. 114.

U9 Schulze in Benedikt, l.c., p. 25.

10 Miiller, Zeitschr. f. klin. Med., xii. 52, 1887.

D1 Hoppe-Seyler, op. cit., p. 96. Compare R. Benedikt, Analyse der Fett, &c.
Berlin, 1889. This work, which deals with the fecal fats, may also be usefully
consulted on various other special points.

132 Miiller, l.c., p. 113.

13 Compare Benedikt, p. 181 and 212.

4 Benedikt, l.c., p. 72.

5 Miiller, l.c., p. 48.

16 Miiller, l.c., p. 112.—Muzzi, Maly’s Jahresbericht, xix. 285 (reference), 1889.

1” Meéhu, Journ. de Pharm, et de Chim., Aug. 1878 ; Maly’s Jabresbericht, viii.
269 (ref.), 1879; and L’Urine normale et patholog., p. 49. Paris, 1880.

458 Hoppe-Seyler, op. cit., p. 329.

 

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CHAPTER VI.—THE FACES. 417

9 Senator, Berliner klin. Wochenschr., v. 251, 1868.—Stefano, Gazetta degli
Ospedali, 1883.

160, Hammarsten, Lehrbuch der physiol. Chemie, p. 183. Wiesbaden, 1891.

161 Pouchet, see (37).—Rose, Zeitschr. f. physiol. Chemie, xvi. 192, 1892.

1 VY. Udransky and Baumann, Zeitschr. f. physiol. Chemie, xiii. 362, 1889.—
Stadthagen and Brieger, Berliner klin. Wochenschr., xxvi. 344, 1889.

163 V. Jaksch, Zeitschr. f. physiol. Chemie, xiii. 116, 1887.

164 Hoppe-Scyler, op. cit., p. 317.

16 See Hoppe-Scyler’s admirable grouping, op. cit., p. 326.

166 Widerhofer, see (2).

67 Escherich, Fortschritte der Med., iii. 515 and 547, 1885.

168 Baginsky, Zeitschr. fiir physiol. Chemie, xii. 434, 1888.

1689 Bizzozero, 1.c., p. 195.

1 Zweifel, Archiv £. Gynakol., vii. 474, 1875.—Hoppe-Seyler, op. cit., p. 340.

M71 Wegscheider, see (144).

172 Nothnagel, see (1).

"3 Heubner, Ziemssen’s Handb., ii. 508, 2nd edit., 1886.

M4 Hlava, Centralbl. fiir Bacter. und Parasitenk., i. 537, 1887.—Aartulis, ibid.,
iii. 745, 1888.

™5 Klebs, l.c., p. 203.—Chantemesse and Widal, see Cornil, Bull. de Acad. de
Méd., lii. 6, 1888; Schmidt’s Jahrbiicher, ccxix. 239 (ref.), 1888; Baumgarten’s
Jahresbericht, iv. 236 (reference), 1889, where also Michelsohn has some critical
remarks.

76 ©, Schmid, Charakteristik der epidem. Cholera, &c. Leipzig, 1850. See
Hoppe-Seyler, Physiol. Chemie, p. 358.

7 Pel, Centralbl. fiir klin. Med., viii. 297, 1887.—Ze Nobel, Archiv fiir klin.
Med., xliii, 285, 1888.

M8 Vogel-Bicdert, Lehrb. der Kinderkrankheiten, 9th edit., p. 115. Stuttgart,
1887.

19 Berggriin and Katz, Wiener klin. Wochenschr., iv. 858, 1891.

CHAPTER VII.
THE URINE.

1 For the Physiology of the subject, see Heidenhain, Hermann’s Handb. der
Physiologie, v. 1, 279, 1883; also Landois and Stirling, Text-Book of Physiology,
p. 479, 4th ed., 1891.

2 Wollheim de Fonseca, Maly’s Jahresbericht, xix. 187 (reference), 1890.

3 Glum, Diss., Centralbl. f. med. Wissensch., xxviii. 243 (reference), 1890.

4 For the special Chemistry of the subject, see Huppert, Neubauer, and Vogel, Anlei-
tung zur qualitativen und quantitativen Analyse des Harns, 9th edit., Wiesbaden,
1891 ; Leube and Salkowski, Die Lehre vom Harn, Berlin, 1882; Lébisch, Anleitung
zur Analyse des Harns, Wien, 1883; Hoppe-Seyler, Handb. der physiol.- und pathol.-
chemischen Analyse, p. 340, 5th edit., Berlin, 1885; Z. Zaache, Harn Analyse fiir
prakt. Aerzte, Leipzig, 1885; further, consult W. Zuelzer, Lehrb. des Harnanalyse,
Berlin, 1880; C. Fr. W. Krukenberg, Grundriss der medic.-chem. Analyse, Heidel-
berg, 1884; Leo Liebermann, Grundziige der Chemie des Menschen, Stuttgart,
1885 ; Tappeiner, Anleitung zu chemisch-diagnostischen Untersuchungen am Krank-
enbette, 2nd edit., Munich, 1888; Seifert and Miller, Taschenb. der medic.-klini-
schen Diagnostik, 4th edit., Wiesbaden, 1888; Schotten, Kurzes Lehrbuch der

2D

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418 BIBLIOGRAPHY.

Analyse des Harns, Leipzig ; 0. Vierordt, Diagnostik interner Krankheiten, p. 334,
Leipzig, 1888; Roberts, Pract. Treatise on Urinary and Renal Diseases ; Halli-
burton, Text-Book of Chemical Physiology and Pathology, London, 1891 ; MacMunn,
Clinical Chemistry ; Proc. Roy. Soc., No. 208; Journ. of Phys., x., Nos. 1 and 2.

> Lanect, i., 1890, p. 481.

6 Compare Dujardin-Bcaumetz, Schmidt’s Jahrbiicher, ccxxviii. 152 (reference),
1890.

7 (. Vierordt, Zeitschr. fiir Biologie, x. 21 and 399, 1874.—MacMunn, Clin.
Chem., p. 104; id, Maly’s Jahresbericht, xx. 201 (ref.), 1891.

8 Leo Liebermann, Maly’s Jahresber. fiir Thierchemie, xv. 447 (ref.), 1886.

® £, Baumann and C. Preusse, Du Bois-Reymond’s Archiv, 245, Jahrgang 1879-

10 Fagge, Principles and Pract. of Med., ed. 1891, ii., p. 644.

1 Mott, Pathol. Trans., lx. 127; Lancet, March 1889.

2 Hunter, Practitioner, Aug. 1888 ; Lancet, Oct. 1888.

8 Hale-White, Brit. Med. Journ., May 21, 1892.

MM Halliburton, Chemic. Physiol., 1891, p. 712.

 Quincke, Zeitschr. fiir klin. Med., (sup. vol.), vii. 21, 1884.

16 See Sticker and Hiibner, Zeitschr. fiir klin. Med., xii. 114, 1887; v. Noorden,
Archiv fiir experim. Pathol. und Pharmakol., xxii. 325, 1887; and O. 7. Rongstedt,
Maly’s Jahresbericht, xx. 196 (reference), 1891.

W Hale- White, Brit. Med. Journ., May 21, 1802.

18 Huppert, Neubauer, Vogel, l.c., p. 19.

19 F. and L. Sestini, Die landwirthschaftlichen Versuchsstationen, Pts. ii..and
iii., 1890.

© Huppert, Neubauer, Vogel, l.c., p. 433; and Ott, Zeitschr. fiir physiolog.
Chemie, x. 1, 1885.

*1 F, Taylor, Pract. of Med., 2nd edit., p. 705.

2 Compare Glaser, Deutsche med. Wochenschr., xvii. 1193, 1891.

3 #. Salkowski, Deutsche med. Wochenschr., xiii., No. 16 (sep. Supplement), 1888.

4 V. Jaksch, Prager med. Wochenschr., xvi. 210, 1891.—Litten, Wiener klin.
Wochenschr., iv. 416, 1891. Rohrbeck of Berlin and Wrana of Prague have con-
structed similar apparatus.

>> Compare Senator, Berliner klin. Wochenschr., xxviii. (sep. pub.), 1891.

26 (laser, see (22).

7 Vitali, Maly’s Jahresbericht, xviii. 326 (reference), 1890.—Compare also £.
Briicke, Monatshefte fiir Chemie, x. 129, 1889.

8 Bizzozero, l.c., 2nd edit., p. 260.

29 Richhorst, Lehrb. der physikal. Untersuchungs-methoden innerer Krankheiten,
and edit., pt. ii. p. 336. Compare also Lehrbuch der Gewebelehre, by C. Toldt,
pp. 493 and 503, Stuttgart, 1884.

30 Vigla, Quevenne, L’Espérience, No. 12, 1837, and Nos. 13, 26, 27, 1838. See
Nasse, Schmidt's Jahrbiicher, xxxiv. 356 (ref.), 1842. Rayer, Traité des Maladies
des Reins, ii., 1840.

3. Simon, Johannes Miiller’s Archiv fiir Anat., Physiol. und wissenschaftl.
Medicin, p. 28, plate ii. fig. 4, 1843.—-Nasse, Schmidt’s Jabrb., xxxiv. 356 (ref.),
1842.

#2 Henle, see C. Pfeufer, Zeitschr. fiir rationelle Med., i. 61 and 68, 1844.

33 Glaser, see (22).

*4 Rovida, J. Moleschott, Untersuch. zur Naturlehre des Menschen und der
Thiere, xi. 1; xi. 182, 1867. é

* Nothnagel, Deutsches Archiv fiir klin. Med., xii. 326, 1874.

* Burkart, Die Harncylinder, l.c., p. 44.—Vischl, Prager Vierteljahrsschr.,
cxxxix. 27, 1878.

“7 Leube, Zeitschy. fiir klin. Med., xiii. 6, 1887.—For further information see 0.

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CHAPTER VII.—THE URINE. 419

Bayer, Archiv fiir Heilk., ix. 136, 1868.—Scnator, Virchow’s Archiv, lx. 476, 1874
It. Wagner, v. Ziemssen’s Handb., vol. ix. p. 47, 3rd edit., 1882.— Knoll, Zeitschr
fiir Heilk,, iii. 148, 1882.—Fiirbringer, Die Krankheiten der Harn.- und Geschlechts-
organe. Braunschweig, p. 20, 1884.—Burkart, Die Harncylinder, 1884.—Knoll,
Zeitschr. fiir Heilk., v. 289, 1884.

*8 Martini, Archiv fiir klin. Chirurgie, xvi. 157, 1884.

* V. Jaksch, Deutsche med. Wochenschr., xiii., Nos. 40 and 41, 1888.

* Compare Loos, Jahrb. f. Kinderheilkunde, xxx. (sep. pub.), 1890.

4. Rindfleisch, Lehrb. der pathol. Gewebelehre, p. 438. Leipzig, 1875.—Lany-
hans, Virchow’s Archiv, Ixxvi. 85, 1879.

® Rovida, see (34); also Weisgerber and Perls, Archiv fiir experiment. Patho-
logie, vi. 113, 1877.—Posner, Virchow’s Archiv, 1xxix. 361, 1880.—Voorhove, ibid.,
Ixxx 247, 1880.—Singer, Zeitschr. fiir Heilk., vi. 143, 1885.—Kobler, Wiener klin.
Wochenschr., iii. 531, 574, 576, 577, 1890.

#3 Nothnagel, see (35).

44 Henle, see (32).

4 M. Huppert, Virchow’s Archiv, lix. 395, 1874.

46 Leube, Zeitschr. fiir klin. Med., xiii. 7, 1887.

47 Compare R. v. Hoesslin, Miinchener med. Wochenschr., No. 45 (sep. pub.),
1888.

48 ZT. Thomas, Archiv fiir Heilkunde, xi. 130, 1870.

49 Bizzozero, 1.c , p. 225.

” S. Pollak and Térik, Maly’s Jahresber., xvi. 458 (ref.), 1887 ; and Archiv fiir
experim. Pathol. und Pharmakol., xxv. 87, 1888.

5l Rovida, 1.c., p. 8.—Kobler, see (42).

52 Ribbert, Centralbl. fiir die med. Wissensch., xix. 305, 1880.

°3 Knoll, see (37).

“4 EB. L. Mayer, Virchow’s Archiv, v. 199, 1853.

°° ‘Huppert, see (45).

*6 Heitzmann, Wiener med. Bliitter, Nos. 24 and 25, 1890.

7 Leube, Zeitschr. fiir klin. Med., iii. 233, 1881.

°8 Miquel, Bulletin de la Société Chim. de Paris, xxxi. 392, 1879, and xxxii. 126,
1879 (see Huppert, l.c., p. 183).—V. Jaksch, Zeitschr. fiir physiol. Chemie, v. 398,
1881.—Leube, Virchow’s Archiv, c. 540, 1885.—Billet, Comptes rendus, c. 1252,
1885.—C. Fliigge, l.c., p. 169.—V. Limbeck, Prager med. Wochenschr., xii. 189, 198
206, 215, 1887.

59 Roberts, On Bacilluria, Int. Med. Congress, ii. 157-163. London, 1881.—
Schottelius and Reinhold, Centralbl. fiir klin. Med., viii. 635, 1886.

60 Fischer, Berliner klin. Wochenschr., i. 18, 1864.—Teufel, ibid., i. 17, 1864. ~

61 Cramer, Zeitschr, fiir klin. Med., vi. 54, 1883.—Albertoni, Maly’s Jahresbericht,
xix. 466 (reference), 1890.

62 Kannenberg, Zeitschr. fiir klin. Med., i. 506, 1880.—Litten, ibid., iv. 191, 1882.
3 Fehleisen, Die Aetiologie des Erysipels. Berlin, 1883.

64 Martini, see (38).—Litten, Zeitschr. fiir klin. Med., ii. 452, 1881.—Senetz,
Petersburger med. Wochenschr., No. 46, 1883.

65 Weichselbaum, Wiener med. Wochenschr., xxxiv. 241, 1885.

66 Lustgarten and Mannaberg, Vierteljahrschr. fiir Dermatologie und Syphilis,
xiv. 905, 1887; and Mannabery, Centralbl. fiir klin. Med., ix., No. 30, 1888;
Zeitschr. f. klin. Med., xviii. 223, 1890.

67 Letzerich, Zeitschr. fiir klin. Med., xiii. 33, 1888 ; xviii. 528, 1891.

68 Mircoli, Centralbl. fiir Bacteriol. und Parasitenk., iii. 336 (ref.), 1888.

69 Neumann, Berliner klin. Wochenschr., xxv., No. 7-9, 1888. Statements will
be found here also as to the occurrence of tubercle bacilli, the spirilla of relapsing
fever, kc.

 

Eos

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420 BIBLIOGRAPHY.

7” Karlinski, Prager med. Wochenschr., xv. 437, 452, 1890.

71 Philipowicz, Wiener med. Blatter, xxxiv. 673 and 710, 1885.

72 Kannenberg, see (62).

73 Leube, Sitzungsber. der physik.-med. Akad. Erlangen, Dec. 11, 1882.—osen-
stein, Centralbl. fiir med. Wissensch., xxi. 65, 1883.—Babes, ibid., xxi. 129, 1883.
—Shingleton Smith, The Lancet, ii. 942, 1883,—ZJrsai, Wiener med. Presse, 1141
and 1173, 1884.—Benda, Deutsche med. Wochenschr., x. 154, 1884.—Kreske,
Miinchener med. Wochenschr., xxxiv. Nos. 30, 31, 1887.

+ Philipowicz, see (71).

7 Cf. Braatz, Petersburger med. Wochenschr., xiii. 119, 127, 1888.

76 Leube, see (57).

? Hassall, The Lancet, ii. 21, Nov. 1859. Schmidt's Jahrbiicher, cix. 157 (ref.),
1861.

78 Balz, Berliner klin. Wochenschr., xxiii. No. 16, 1883.

7) Hatch, The Lancet, i. 875, 1887.

80 Mosler, Deutsche med. Wochenschr., xiii. 507, 1887.

1 Leuckart 1.c., p. 390.—Cannon, The Lancet, i. 6, 1887.
Scheiber, Virchow’s Archiv, ]xxxii. 161, 1884; see also Oerley, Die Rhabditiden
und ihre medic. Bedeutung. Berlin, 1886.

83 2. Peiper and Westphal, Centralbl. fiir klin. Med., ix. 145, 1888.—Baginsky,

Deutsche med. Wochenschr., xiii. 604, 1888.

a

nt

ie)

82

§ Maly’s Jahresbericht, xvi. 469 (ref.), 1887.

8 Fiirbringer, Archiv fur klin. Med., xviii. 143, 1876.
86 Kussmaul, Wirzburger med. Zeitschr., iv. 64, 1863.
87

Lbstein, Archiv fiir klin. Med., xxiii. 115, 1879.
Holm, Journal fiir prakt. Chemie, c. 142, 1867.
G. Stdédeler, Annalen der Chemie und Pharmacie, cxxxii. 323, 1864.
Hoppe-Seyler, Handb. d. physiol. u. pathol.-chem. Analyse, l.c., p. 245.
" Leyden, Zeitschr. fiir klin. Med., ii. 471, 1881.
* Foltanek, Wiener klin. Wochenschr., ii. 15, 1889.—Rosenheim, Zeitschy. f.
klin. Med., xv. 447, 1889.
® Fritz, Zeitschr. fiir klin. Med., ii. 471, 1881.
Stein, Archiv fiir klin. Med., xviii. 207, 1876.
W. Valentiner, Centralbl. fiir med. Wissensch., i. 913, 1865.—Fiirbringer,
Archiv fiir klin. Med., xx. 321, 1877.

% See Huppert, l.c., p. 167.

” Tiebig, see Huppert, l.c., p. 168.

% J. Miiller, Zeitschr. f. analytische Chemie, xii. 234 (ref.), 1873.

® Krukenberg, Chem, Untersuchungen zur wissensch. Medicin, pt. ii. p. 128.
Jena, 1888.

100 H, Bence Jones, Chem. Centralbl., xiii. 847, 2 (ref.), 1868.

1! Piria, Liebig’s Annalen, Ixxxii. 251, 1852.—Staedeler, ibid., cxvi. 57, 1860.

102 Scherer, Journal fiir prakt. Chemie, Ixx. 406, 1857.

“8 R. Hoffmann, Liebig’s Annalen, 1xxxvii. 124, 1857.—L. Meyer, ibid., cxxxii.
156, 1864.

i! C. Wurster, Centralblatt fiir Physiologie, i., No. 9 (sep. Supplement), 1887.

1 Hoffmeister, Liebig’s Annalen, cxxxix. 6, 1877.

16 Scherer, Journal fiir prakt. Chemie, 1xxix. 410, 1857.

7 Frerichs, Wiener med. Wochenschr., iv. 465, 1854.—Schultzen and Ricss,
Annal. des Charité-Krankenhauses, xv.—Pouchet, Maly’s Jahresber. fiir Thier-
chemie, x. 248 (ref.), 1880. —A. Frénkel, Berliner klin. Wochenschr., xv. 265, 1878.
—Blendermann, Zeitschr. fiir pbysiol. Chemie, vi. 234, 1882.—A. Trsai, Maly’s
Jahresber. fiir Thierchemie, xiv. 451 (ref.), 1885.

18 Prus, ibid., xvii. 435 (ref.), 1888.

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109 See also Feser and Friedberger (whose observations refer to horse’s urine),
Maly’s Jahresb. fiir Thierchemie, iv. 231 (ref.), 1875.

0 F, Taylor, Pract. of Med., 2nd edit., 701.

11 Ord, Colloids and Crystallisation, Lond., 1879.

2 Holm, see (88).

U3 Ord, Proc. Pathol. Soc., Brit. Med. Journ., May 21, 1892.

"4 Ord, Berliner klin. Wochenschr., xv. 365, 1878.—. Chiari, Prager med.
Wochenschr., xiii. 541, 1888.

> Fr, Miiller, Berliner klin. Wochenschr., xxvi. 889, 1889.

U6 Senator, Internationale Beitrige zur wissench. Med., Festschrift, Rudolph
Virchow gewidmet zur Vollendung seines 70 Lebensjahres, iii. (sep. pub.). Berlin,
1891.

7 Frerichs, Die Bright’sche Nierenerkrankung und deren Behandlung. Bruns-
wick, 1851.— Voyel, Virchow’s Handbuch der spec. Pathol. und Therapie, vi. 2,
709. Erlangen, 1865.—U/tzmann, Wien. med. Presse, xi. 82, 1870.

us Leube, Virchow’s Archiv, Ixxii. 145, 1878.—Fiirbringer, Zeitschr. fiir klin.
Med., i. 346, 1889.—Senator, Die Albuminurie. Berlin, 1882.—@C. Posner, Berliner
klin. Wochenschr., xxii. 654, 1885 ; Virchow’s Archiv, civ. 497, 1886; and Archiv
fiir Anat. und Physiol. (physiol. Abtheil.), 1888. Compare Mulfatti, Intern.
Centralbl. f. d. Physiol. u. Pathol. der Harn- und Sexual-organe, i. 266, 1889.

19 VY. Noorden, Deutsches Archiv fiir klin. Med., xxxviii. 3, 205, where will be
found also very exhaustive and exact references to the literature on the subject
of physiological albuminuria.

120 Leube, Zeitschr. fiir klin. Med., xiii. 1, 1887.—H. Winternitz, Zeitschr. f-
physiol. Chemie, xv. 189, 1891.

Ll Grainger Stewart, On Albuminuria, 1888, p. 19.

122 Anschiitz, Die Destillation unter vermindertem Drucke im Laboratorium.
Bonn, 1887.

123 Stirling, The Lancet, ii. 1157, 1887.—Ringstedt, Schmidt’s Jahrbiicher, ccxxv-
141 (ref.), 1889.—Heubner, Festschrift zu Henoch’s 70 Geburtstag, p. 26. Berlin,
1890.— Washburn, Centralbl. f. klin. Med., xi. 786, 1890.

124 Payvy, Lancet, i. 711, 1888.

12 Moxon, Guy’s Hospital Reports, 1878.

126 Fagge, see Taylor, Med., p. 791.

127 Taylor, Pract. of Med., 2nd edit., p. 790.

128° Falkenheim, Deutsches Archiv fiir klin. Med., xxxy. 446, 1884.

129 Huchard, L’?Union Médical, 58.

130 Haig, Brit. Med. Journ., Jan. 11, 1891.

131 Wirchow, Gesammte Abhandl. zur wissensch. Med., 846, 1856. Compare
Clinical Lectures on Important Symptoms. On Albuminuria, by (Grainger
Stewart, Edinburgh, 1888.

132 Bright, Report of Medical Cases, 1827 and 1831.

133 Christison, Ueber die Granular-Entartung der Niere, trans. by J. Mayer,
with remarks by Rokitansky. Vienna, 1841.—Rayer, Traité des Maladies des Reines,
ii., 1840.—Frerichs, Die Bright’sche Nierenerkrankung und deren Behandlung, 1851.
—Traube, Ueber den Zusammenhang von Herz- und Nieren-krankheiten. Berlin,
1856. For exhaustive notices, see £. Wagner, v. Ziemssen’s Handbuch der spe-
ciellen Pathol. und Therapie. Leipzig, 1882.

134 Kauder, Archiv fiir experiment. Pathol. und Pharmakol., xx. 411, 1886.—
Pohl, ibid., xx. 246, 1886.

135 Compare A. Csatdry, Archiv f. klin. Med., xlvii. 159, 1890.

136 Mf. Huppert, Virchow’s Archiv, lix. 305, 1874.

137 Schreiber, Archiv fiir experim. Pathol. und Pharmakol., xix. 237, 1885, and
xx. 85, 1886.

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422 BIBLIOGRAPHY.

138 Singer, Prager med, Wochenschr., xii. 9, 1887.—Kobler, Wiener klin.
Wochenschr., iii. 531, 557, 574, 596, 1890.

139 Leyden, Zeitschr. fiir klin. Med., iii. 161, 1881.

WH, Lorenz, Wiener klin. Wochensch., i. 119, 1888.

141 VY, Bamberger, Wiener med. Wochenschr., xxxi. 145 and 177, 1881.

12 Bull, Berliner klin Wochenschr., xxiii. 717, 1886.—Mareau, Revue de Méd.,
vi. 855, 1886. Schmidt’s Jahrb., ccxiii. 146 (ref.), 1887.—Klemperer, Zeitschr. fiir
klin. Med., xii. 168, 1887.—Caufield, Med. News (sep. issue), 1887.—G. Johnson,
Lancet, i. 7, 1888. :

143 -V, Jaksch, Deutsche med. Wochenschr., xiv., Nos. 40 and 41, 1888. Compare
also Loos, Jabrbiicher f. Kinderheilkunde (sep. pub.), 1890; and &. v. Engel,
Prager med. Wochenschr., xv. 615, 189c.

144 See Kinnicr, Centralbl. fiir klin. Med., vii. 772 (ref.), 1886.

45 Falkenheim, see (128).

16 Merley, De  Albuminurie intermittente cyclique ou Maladie de Pavy. Paris,
1887.

17 See F’. Rose, Annal. der Physik und Chemie, xxviii. (104), 132, 1833.

M8 J. F. Heller, Archiv fiir physiol. und pathol. Chemie und Mikroscopie, v. 161,
1852.

9 Heynsius, Pfliiger’s Archiv, x. 239, 1875.

159 Clin. Soc. Trans., xix. p. 339.

151 Hindenlang, Berliner klin. Wochenschr., xviii. 205, 1881.

152 Penzoldt’s Hltere und neuere Harnproben, 2nd edit. Jena, 1886.—V. Noorden,
see (119).

153 Fiirbringer, Deutsche med. Wochenschr., xi. 467, 1885.

14 G, Johnson On the Various Modes of Testing for Albumin and Sugar, p. 6.
London, 1884.

9 M. Jaffe, Zeitschy. fiir physiol. Chemie, x. 399, 1886.

198 See Huppert, Neubauer, and Vogel, 1.c., p. 121.

197 Liebermann, Centralbl. fiir die med. Wissensch., xxv. 321 and 450, 1887.—
C. Wurster, Centralbl. fiir Physiol., i., No. 9 (sep. issue), 1887.—L. Salkowski,
Zeitschr. f. physiol. Chemie, xii. 215, 1889.

158 See Huppert, Neubauer, and Vogel, l.c., p. 71.

19 Schick, Prager med. Wochenschr., xv. 306, 1890.

160 Zouchlos, Wiener allgem. med. Zeitung, No. 1, 1890.

161 4, B. Cohen, Maly’s Jahresbericht, xviii. 116 (ref.), 1888.

182 G. Roch, Pharmaceutische Centralhalle, 549, 1889.—J. A. Macwilliam, Brit.
Med. Journ., No. 1581, 837, 1891.

163 Macwilliam, l.c., p. 840, 1891.

164 See also Jolles, Wiener med. Presse, xxxi. 825, 1890.

165 Devoto, Zeitschr. f. physiol. Chemie, xv. 474, 1891.

166 See Huppert, l.c., p. 554.

187 Roberts, Lancet, i. 313, 1876.—Stolnikow, Petersburger Wochenschr., xii.,
1876; Maly’s Jahresber. fiir Thierchemie, vi. 148 (ref.), 1887.—J. Brandbery,
Upsala Likare forh., 15.—Hammarsten, Maly’s Jahresber. fiir Thierchemie, x. 265
(ref.), 1881 ; see also Laache, l.c., p. 78.

168 Zaache, l.c., p. 79.

169 Hammarsten, Maly’s Jahresb., x. 265 (ref.), 1881, and xiii. 217 (ref.), 1884.

1 Guttmann, Berliner klin. Wochenschr., xxiii. 117, 1886.

™! COzapek, Prager med. Wochenschr., xiii. 128, 1888.

1” Sokolow, Maly’s Jahresb., xvii. 223 (ref.), 1888.—Th. Geisler, Berlin. klin
Wochenschr., xxvi. 1111, 1889.

3 Christensen, Virchow’s Archiv, cxv. 128, 1889.

4 Th. Geisler, see (172).

Ss

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% Noel Paton, Schmidt’s Jahrbiicher, ccxxii. 4 (ref.), 1889.

% Huppert and Zdhot, Zeitschr. f. physiol. Chemie, xii. 467, 1888.—ZdhoF,
ibid., xii. 484, 1888.

1 Hofmeister, ibid., iv. 253, 1880; v. 66, 127, 1881; vi. 51, 1881; Prager med.
Wochenschr., v. 321, 335, 1880.

"8 Hofmeister, see (177).—Maianer, Prager Vierteljahrschr., cxliv. 75, 1879.—V.
Jaksch, Prager med. Wochenschr., v. 292 and 303, 1880; vi. 61, 74, 86, 133, 143.
1881 ; and Zeitschr. f. klin. Med., vi. 413, 1883.

8 VY. Jaksch, Zeitschr. f. klin. Med., vi. 413, 1883.

189 Maianer, ibid., viii. 234, 1884.

181 Pacanowski, ibid., ix. 429, 1885. See also Kottnitz, Centralbl. f. d. med.
Wissensch., xxix. 513, 1891 ; and Loeb, ibid., xxix. 577, 1891.

1 Fischel, Archiv £. Gynikologie, xxiv. 27, 1884. Compare, however, Thomson,
Deutsche med. Wochenschr., xv. 899, 1889 ; and Kottnitz, ibid., xv. 900, 1889.

183 Grocco, Sulla Peptonuria, di nuovo sulla Peptonuria. Milan, 1883-84.—Secchi,
Maly’s Jahresber., xvii. 444 (ref.), 1888.—0. Brieger, Inaug. Dissert., Breslau,
1888.—Katz, Wiener med. Blitter, xiv., Nos. 45, 46, 48, 50-52 (sep. pub.), 1890.

184 Pochl, Maly’s Jahresber., xvii. 432 (ref.), 1888.

18 Mya and Belfanti, Centralbl. f. klin. Med., vii. 729. 1888.
> Hofmeister, see (177).—Devoto, Zeitschr. f. physiol. Chemie, xv. 465, 1891.

187 HT, Huppert, l.c., p. 189, 8th edit.

18 J, A. Schulter, Maly’s Jahresber., xvi. 228 (ref.), 1887.

18 Maixner, Zeitschy. f. klin. Med., xi. 342, 1886.

199 Devoto, see (186); Rivista clin. Archivo italiano di clin. Med., p. 30 (sep.
pub, ), 1891.

11 VY, Jaksch, Zeitschr. f. physiol. Chemie, xvi. 243, 1892.

12 §. Martin, quoted by Halliburton, p. 787.

18 Macwilliam, British Med. Journ., Jan. 16, 1892.

14 Kiihne and Chittenden, Zeitschr. f. Biologie, xix. 159, 1883; xx. 11, 1884;
and xxii. 409, 1886.—Miihne, Verhandl. des naturhistor. medic. Vereines zu
Heidelberg, Nos. i., iii, p. 286.—Herth, Monatshefte f. Chemie, v. 266, 1884.

1% Senator, Die Albuminurie im gesunden und kranken Zustande, p. 9. . Berlin,
1882.—Ter Gregoriantz, Zeitschr. f. physiolog. Chemie, vi. 537, 1882.—V. Jaksch,
Zeitschr. f. klin. Med., viii. 216, 1884.

196 Loeb, Archiv f. Kinderheilk., ix. 53, 1887 ; x. 212, 1889.

1%” Heller, Berliner klin. Wochenschr., xxvi. 1038, 1889.

8 Kahler and Huppert, Prager med. Wochenschr., xiv. 33, 35, 45, 1889.

199 Képpner, Archiv f. Psychiatrie, xx. 825, 1889.

200 ©, Posner, Berliner klin. Wochenschr., xxv., No. 21, 1888.

*0l_ Thormihlen, Virchow’s Archiv, cviii. 322, 1887.

202 Kiihne and Chittenden, .p. 278.

203 Maguire, Brit. Med. Journ., ii. 1886, p. 543.

204 Senator, quoted by Halliburton, 1.c., p. 783.

205 Kauder, see (134).

206 Pohl, see (134); see also A. Csatdry, (135).

207 Halliburton, l.c., p. 783.

208 Huppert, l.c., p. 277.

209 Heller, Wiener med. Zeitschr., i. 48, 1859; Schmidt’s Jahrbiicher, civ. 39
(ref.), 1859.

210 See Huppert, l.c., p. 302.

ll Rosenthal, Virchow’s Archiv, ciii. 516, 1886.

212 Thid., l.c.

13 Almén, see Hammersten, Lehrbuch d. physiol. Chemie, p. 336. Wiesbaden,
1891.

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A424 BIBLIOGRAPHY.

24 Neisser, Centralbl. f. med. Wissenchaften, xix. 545, 1881.
Zur Nieden, Berliner klin. Wochenschr., xviii. 705, 1881.
216 Langer, Prager med, Wochenschr., xvi. 389, 391.

217 Rosenbach, Berliner klin. Wochenschr., xvii. 132, 151, 1880.—Zhrlich,
Zeitschr., f. klin. Med., iii. 383, 1881.—Boas, Archiv f. klin. Med., xxxii. 355,
1885.—Hénocque, Maly’s Jahresber., xvii. 431 (ref.), 1888.—Kobler and Obermayer,
Zeitschr. f. klin. Med., xiii. 163, 1888.—J. S. Bristowe and S. M. Copemann,
Lancet, vi. 256, 1889.—U. de Rienzi and £. Reale, Rivista clinica e terapeutica,
xi. (sep. pub.), 1889.

28 Taylor, Pract. of Med., p. 787.

219 Hoppe-Seyler, Physiolog. Chemie, l.c., p. 862.

Compare Lewin and Posner, Centralbl. f. die med. Wissensch., xxv. 353,

Halliburton, l.c., p. 777-
22 Compare Huppert, Anleitung zur Analyse des Harns, Lc., p. 279.
3 Fr, Miiller, Mittheilungen aus der med. klinik in Wiirzburg, i. 266, 1885.
Obermayer, Centralbl. f. klin. Med., xiii. 1, 1892.
Ls, Fischer, Berichte d. deutschen chem. Gesellschaft, xxiii. 2114, 1890. I
cannot forbear drawing the reader’s attention to these reports, which are of the
highest medical interest.

25 V. Briicke, Vorles. uber Physiologie, i. 375, 2nd edit. Wien, 1875.

~6 Wedenski, Zeitschr. f. physiol. Chemie, xiii, 112, 1888.—L. v. Udrdnsky,
Berichte d. naturforsch. Gesells. in Freiburg, xi. 183.—Moritz, Archiv f. klin.
Med., xlvi. 252, 1890.—Gaube, Maly’s Jahresbericht, xix. 225 (ref.), 1890.

7 G, Johnson, Brit. Med. Journal, April 9, 1892.

28 G, S. Johnson, Proc. Roy. Soc., xliii. pp. 493, 554.

9 Morse, Schmidt's Jahrbiicher, ccxxii. 22 (ref.), 1889.

230 Méhu, Maly’s Jahresber., viii. 188 (ref.), 1888.

304 Taylor, Pract. of Med., p. 784.

“31 W, M. Ord, Centralbl. f. d. med. Wissensch., xxviii. 94 (ref.), 1890.

22 Halliburton, l.c., p. 793-

33 V, Jaksch, Zeitschr. f. klin. Med., xi. 20, 1886.

#4 Moritz, Miinchener med. Wochenschr., Nos. 1 and 2 (sep. pub.), 1891.—
Kraus and Ludwig, Wiener klin. Wochenschrift, iv. 855, 1891.

285 Worm-Miiller, Pfliiger’s Archiv, xxxvi. 172, 1885.

+86 Moore, Lancet, ii. 1884; and Heller, Archiv f. Mikroskopie und mikroskop.
Chemie, i. 212 and 292, 1844.

87 Hoppe-Scyler, Berichte der deutschen chem. Gesellsch., iv. 346, 1871.

238 T'rommer, Annal. der Chemie und Pharmacie, xxxix. 360, 1841.
Compare Jastrowitz, Deutsche med. Wochenschr., xvii. 253, 292, 1891.
Pavy, see F. Taylor, l.c., p. 776.
Worm-Miiller, Pfliiger’s Archiv, xxvii. 107, 1882.
242 Moritz, Deutsches Archiv f. klin. Med., xlvi. 260, 1890; see also (234).
43° Leube and Salkowski, l.c., p. 223.
24 Finhorn, Virchow’s Archiv, cil. 263, 1885.
“4 Halliburton, 1.c., p. 99, 793-
46, Fischer, Berichte der deutschen chem. Gesellsch., xvii. 579, 1884.
V. Jaksch, see (232).

348 JTirschl, Zeitschr. f. physiol. Chemie, xiv. 383, 1890.—Havelburg, Centralbl. f.
klin. Med., xi. 89, 1891.

249 Geyer, Wiener med. Presse, xxx. 1686, 1889.—Moritz, Archiv f. klin. Med.,
xlvi, 264, 1890.—Luther, Inaug. Dissert., Berlin, 1890.

20 Hirschl, 1.c., p. 387.

21 §. Kobrak, Inaug. Dissert, Breslau, 1887. — Rosenfeld, Deutsche med.

Ss

23
240
241

24

a

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Wochenschr., xiv. 451, 479, 1888.—Pollatschek, ibid., xiv. 354, 1888.—Hirschl,
Zeitschr. f. physiol. Chemie, xiv. 378, 1890.

*2 Bottger, Journal f. prakt. Chemie, lxx. 432, 1857.

23 FB, Salkowski, Centralbl. f. d. med. Wissensch., xxiii. 433, 1885.

*4 See Huppert, Neubauer, and Vogel, 1.c., 8th edit., p. 168.

*» Nylander, Zeitschrift £. physiol. Chemie, viii. 175, 1884.

*8 Penzoldt, l.c., p. 16; see also R. Jahreis, Beitrige zur Untersuchung des
Harns auf Eiweiss und Zucker. Inaug. Dissert, Erlangen, 1886.

*7 M. Rubner, Zeitschr. fiir Biologie, xx. 397, 1884.

28 Penzoldt, see (152).

9 Laache, l.c., p. 111.—Penzoldt, 1.c., p. 16.

°60 G. Oliver, Bedside Urine Testing.

*81 Johnson, 1.¢., p. 367.—Thiéry, Progrés médical, xiv. 633, 1886.

*62 Th. Weyl, Schmidt’s Jahrbiicher, ccxii. (ref.), 1886.

*63 Penzoldt, Berliner klin. Wochenschr., xx. 201, 1883.

“1 VY. Jaksch, Mittheil. des Wiener Docteren-collegiums, x. 1884.

*6 Salkowski, Virchow’s Jahresber., xix. 148, 1884.

66 H. Molisch, Sitzungsber. der kais. Akad. der Wissensch. (Wien), xciii. ii. 912,
1886; and Centralbl. f. die med. Wissensch., xxi. 49, 1887.

*67 Seegen, Centralbl. f. die med. Wissensch., Nos. 44 and 45, 1886.

*8 Mylius, Zeitschr. f. physiol. Chemie, xi. 492, 1887.—I”. Udrdnsky, ibid., xii.
381, 1888.

*69 -V. Briicke, Wiener med. Wochenschr., viii. 337, 1858.—Seegen, Archiv f.
Physiol., v. 375, 1872.—Abeles, Centralbl. f. die med. Wissensch., xvii. 33 and 209,
1879.—Salkowshki, Zeitschr. £. physiol. Chemie, iii. 96, 1874.

270 Baumann and v. Udrinsky, Berichte der deutsch. chem. Gesellschaft, xxi.
2744, 1888.

“71 Luther, l.c., p. 12.—Roos, Inaug. Dissert., Freiburg, 189r.

7 Fehling, Annal. der Chemie und Pharmacie, Ixxii. 106, 1848; cvi. 75,
1858.

73° Teube and Salkowshi, 1.c., p. 231.

*74 See ibid., lc, p. 232.

7 Salkowski, l.c., p. 232.

276 Munk, Virchow’s Archiv, cv. 63, 1888.

+7 F, Taylor, Medicine, p. 777.

*78 Roberts, he Lancet, i. 21, 1862.

*79 Worm-Miiller, Pfliiger’s Archiv, xxxii. 211, 1884, and xxxvii. 479, 1885.

*80 P, Guttmann, Deutsche med. Wochenschr., xvi., No. 1, 1890.— Budge,
Zeitschr. f. physiol. Chemie, xiii. 326, 1889.—&. A. H. Mérner, Maly’s Jahres-
bericht, xix. 224 (ref.), 1890. For other similar apparatus, such as that by
Fleischer, see Penzoldt, Aeltere und neuere Harnproben, &c., p. 38. Jena, 1890.

*81 For details regarding the construction of the Polarimeter, see Hwppert,
Neubauer, Vogel, l.c., p. 403.

282 K, Zimmer, Deutsche med. Wochenschr., ii. 329, 1876.—Secgen, Centralbl. f.
die med. Wissensch., xxii. 753, 1884.

283 De Sinety, Maly’s Jahresber. fiir Thierchemie, iii. 134 (ref.), 1874.—Hempel,
Archiv f. Gynikologie, viii. 312, 1875.— Hofmeister, Zeitschr. f. physiol. Chemie, i.
101, 1877.—Johanovsky, Archiv f. Gyniikologie, xii. 448, 1877.—Kaltenbach, Zeitschr.
f. physiol. Chemie, ii. 360, 1877.—Ney, Archiv f. Gynikologie, xxxv. 239, 1889.

24 V, Jaksch, Zeitschr. f. klin. Med., xi. 25, 1886.

285 F. Reichard, Pharm, Zeitschr. f. Russland, xiv. 45 (see Aiilz, Maly’s Jahresber.,
v. 60, 1876).

286 Tandwehr, Centralbl. f. die med. Wissensch., xxiii. 369, 1885.

7 Wedenski, Zeitschr. f. physiol. Chemie, xiii. 127, 1888.

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426 BIBLIOGRAPHY.

88 Le Nobel, Maly’s Jahresber., xvii. 188 (ref.), 1888.—V. Ackern, Berliner klin.
Wochenschr., xxvi. 293, 1889. ;

89 Leo, Virchow’s Archiv, cvii. 99, 1887.—Kiilz, Zeitschr. f. Biologie, xxvii.
228, 1891.

*9) Hoppe-Seyler, Virchow’s Archiv, xiii. 101, 1885.

“1 See v. Udrinsky, Zeitschr. f. physiol. Chemie, xii. 372, 1888.

*2 See the exhaustive essay of M. Schrader, Schmidt’s Jahrb., ccxvi. 73,
1887. .

*83 (Juincke, Virchow’s Archiv, xcv. 125, 1884.

*94 Stokvis, Maly’s Jahresber., xii. 226 (ref.), 1883. ‘

°% Tiedemann and Gmelin, Die Verdauung nach Versuchen, i. 80. Leipzig
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*96 Huppert, Archiv der Heilkunde, iv. 479, 1863.

*87 Rosenbach, Centralbl. f. die med. Wissensch., xiv. 5, 1876.

“8 Dragendorf, see Deubner’s Comparative Investigations of the Newer Methods
for Demonstrating the Presence of Bile Pigment in the Urine of Jaundice. Inaug.
Dissert., p. 24. Dorpat, 1885,

9 Ultzmann, Wiener med. Presse, xviii. 1033, 1877.

00 Huppert, Archiv der Heilkunde, viii. 351 and 476, 1867.

301 Ehrlich, Centralbl. f£. klin. Med., iv. 721, 1883 ; and Charité-Annalen, xi. 139,
1886.

02 Cle Nobel, Centralbl. f. klin. Med., xi. 18, 1890.

°03 Jaffé, Centralbl. f. med. Wissensch., vi. 241, 1868 ; and Virchow’s Archiv,
xlvii. 405, 18609.

84 Salkowski, Zeitschr. f. physiol. Chemie, iv. 134, 1880.

305 Halliburton, Chem. Physiol. and Pathol., p. 750.
306 _Kretschy, Wiener med. Wochenschr., xxxi. 1449, 1881.

87 Kummer, Correspondenzbl. f. Schweizer Aerzte, xvi. 15,16, 1886. Schmidt’s
Jahrb., cexiil. 149 (ref.), 1887.

#8 Mott, Lancet, March 1889 ; Id., Path. Trans., 1x. 127.

809 Hunter, Practitioner, August 1888 ; Lancet, October 1888.

30 Gubler, see Méhu, L’Urine normale et pathologique, p. 55. Paris, 1880.—
Gerhardt, Wiener med. Wochenschr., xxvii. 576, 1877.

3 Hayem, Centralbl. f. klin. Med., xi. 612 (ref.), 1890.—Katz, Wiener med.
Wochenschr., Nos. 28 to 32, 1891.—G. Hoppe-Seyler, Virchow’s Archiv, cxxiv. 36,
1891.

32 Rossbach, Archiv f. klin. Med., xlvi. 408, 1890.

313 Cavallero, see Katz (311).—Kast and Mester, Zeitschy. f. klin. Med., xviii.
479, 1891.

34 Bergmann, Volkmann’s Samml. klin. Vortrige, exc. 1560, 1881.—Hunkel,
Virchow’s Archiv, Ixxviii. 455, 1880.

* Dick, Archiv f. Gyniak., xxiii. 126, 1884.

316 MacMunn, Journ. of Physiol., x. 83.

37 Leube, Sitzungsber. d. Wiirzburger physik.-med. Gesellsch, 13th Session,
23rd June 1888. Compare Areucr and Engel, Maly’s Jabresbericht, xix. 432 (ref.),
1890.

318 Gerhardt, Wiirzburger physik.-medic. Sitzungsber., 2, 1881.

318 For other reactions, see Nencki and Rotschy, Monatshefte f. Chemie, x. 568,
1889.—Grimbert, Maly’s Jahresbericht, xix. 192 (ref.), 1890.

320 Vierordt, Die Anwendung des Spectralapparates zur Photometrie. Tiibingen,
1875. See Huppert, l.c., p. 411.

821 Jaffé, see (303).

32 Méhu, L’Urine norm. et pathol., &c., p. 49. Paris, 1880.

%3 2. Salkowski, Zeitschr. f. physiol. Chemie, xv. 286, 1891.

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CHAPTER VII.—THE URINE. 427

34 B. Salkowskt, ibid., 302.—Huppert, l.c., p. 310.—Stokvis, Med. Tidschr. voor
Geneeskunde, Pt. ii. 409 (sep. pub.).

%5 Halliburton, l.c., p. 750.

*°6 Hoppe-Scyler, Handbuch der chem. Analyse, 5th edit., p. 298.

“27 MacMunn, cited by Lalliburton, 1.c., p. 750.

*8 Le Nobel, Pfliiger’s Archiv, vol. xl. 1887.

329 Jastrowitz, see Salkowslhi, 1.c., p. 306.—Hammarsten, Skandin. Archiv f. Phy-
siol., iii. 319, 1891.—Jolles, Wiener med. Wochenschr. (sep. pub.), 1891.

80 MacMumnn, Proc. Physiol. Soc., 1890, p. 13.

331 See Huppert. l.c., p. 57; Leube and Salkowski, l.c., p. 148 ; and Loppe-Seyler,
l.c., p. 207.

882 Jaffé, Centralbl. f. d. med. Wissensch., x. 2, 481 and 497, 1872; Virchow’s
Archiv, Ixx. 72, 1887.—F. Salkowski, Ber. der deutschen chem. Gesellsch., ix. 138
and 408, 1876.—Bawmann, Pfliiger’s Archiv, xiii. 285, 1876.—Bawmann and
Brieger, Zeitschr. fiir physiol. Chemie, iii. 254, 1879.

*83 See v. Udrdnsky, ibid., xii. 544, 1888.

*4 Senator, Centralbl. f. die med. Wissensch., xv. 357, 370, 388, 1877.-—Hennige,
Archiv f. klin. Med., xxiii. 271, 1880.

*85 Baumaun, Zeitschr. f. physiol. Chemie, x. 123, 1886.

336 Fr, Miiller, Mittheil. aus der Wiirzburger Klinik, ii. 341, 1886.—Ortweiler,
ibid., p. 153.—C. A. Ewald, Virchow’s Archiv, xxv. 409, 1879.

°87 Hochsinger, Wiener med. Presse, xxxi. 1570, 1618, 1890. Deutsche med.
Wochenschr., No. 12, 1891.

338 Compare also Kast and Boas, Miinchener med. Wochenschr., xxxv. 55, 1888

89 Bohland, Deutsche med. Wochenschr., xvi. 1040, 1890.

340 Jaffé, Pfliiger’s Archiv, iii. 448, 1870.

341 See Senator, Centralbl f. die med. Wissensch., xv. 257, 1877.

32 TTalliburton, 1.c., p. 744.

43° Obermayer, Wiener klin. Wochenschr., iii. 176, 1890.

344 Weber, Zeitschr. f. anal. Chemie, xviii. 634, 1879 (see Archiv. der Pharm.,
cexiii. 340, 1879).

“45 Talliburton, l.c., p. 744.
346 Salkowski, Virchow’s Archiv, ]xviii. 407, 1876.

47 Gand L. Kriiss, Colorimetrie und quantitative Spectral-analyse von Ham-
burg. Leipzig, 1891.

348 Rosin, Centralbl. f. klin. Med., 505, 1889; Virchow’s Archiv, cxxiii. 1891.

349 Rosenbach, Berliner klin. Wochenschr., xxvi. 1490, 1889; xxvii. 581, 1890.—
Boginsky, Archiv f. Kinderheilkunde, xiii. 312, 1891.—#. Salkowski, Berlin. klin.
Wochenschr., xxvii. 202, 1889.—2. A. Ewald, ibid., xxvi. 953, 1889.—Abraham,
ibid., xxvii. 385, 1891.— Rwmpel and Mester, Centralbl. f. klin. Med., xii. 527 (ref.),
18901.

350 Brieger, Zeitschr. f. physiol. Chemie, iv. 414, 1880.

351 Brieger, Zeitschr. f. klin. Med., iii. 468, 1881.—WMester, Zeitschr. f. physiol.
Chemie, xii. 130, 1888.

352 7, Salkowski, Centralbl. f. die med. Wissensch., xiv. 818, 1876.

353 Brieger see (351).

354 Hoppe-Seyler, Zeitschr. f. physiol. Chemie, xii. 1, 1887.—Poehl, Petersburger
med. Wochenschr., xii. 423, 1887.—Kast and Boas, Miinch. med. Wochenschr.,
XXxv. 55, 1888.

35 Rumpf, Zeitschr. £. physiol. Chemie, xvi. 220, 1892.

356 Brieger, see (351).

- 337 Baumann, Zeitschr. f. physiolog. Chemie, i. 71, 1878.

358 7, Salkowski, Virchow’s Archiv, ]xxix. 551, 1880; and Zeitschr. f. physiolog.

Chemie, x. 346, 1886.

    
 

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428 BIBLIOGRAPHY.

89 H, Landolt, Ber. der deutschen chem. Gesellsch., iv. 771, 1871.—Baumann
and Brieger, Zeitschr. fiir physiolog. Chemie, iii 149, 1879 ; and Ber. der deutschen
chem. Gesellsch., xii. 804, 1879.

360 Baumann, Zeitschr. f. physiol. Chemie, x. 129, 1886.

361 Baumann, Pfliiger’s Archiv, xiii. 63, 1875 ; and Zeitschr. f. physiolog. Chemie,
vi. 183, 1882.

62 See Huppert, Vogel, Neubauer, l.c., p. 76.

3683 W. Ebstein and J. Miiller, Virchow’s Archiv, Ixii. 554, 1873; 1xv. 394, 1875.

°64 Baumann and Preusse, Du Bois-Reymond’s Archiv f. Anat. u. Physiol., 245,
1879.

#65 Huppert, l.c., p. 78.

365 Baumann and Preusse, Zeitschr. f. physiol. Chemie, iii. 157, 1879.

#67 Baumann, Berichte d. deutschen chem. Gesellschaft, xii. 1450, 1879; Cxxxiii.
79, 1880; Zeitschr. f. physiol. Chem., iv. 304, 1880.—Z. and ZH. Salkowski, Berichte
d. deutschen chem. Gesellschaft, xii. 1438, 1879.

368 Huppert, l.c., p. 151.

369 Schultzen and Riess, see Huppert, l.c., p. 151.

%70 Kirk, see Huppert, l.c., p. 152.—Wolkow and Baumann, Zeitschr. f. physiol.
Chemie, xv. 228, 1891.

*71 Baumann, Zeitschr. f. physiolog. Chemie, iv. 311, 1880.

“72 Boedeker, Zeitschr. f. rat. Med., vii. 130, 1857. —Zbstein and J. Miiller,
Virchow’s Archiv, 1xii. 554, 1873; lxv. 394, 1875.— Fiirbringer, Berliner klin.
Wochenschr., xii. 313, 1875.—Flei cher, ibid., xii. 529, 547, 1875.

*3° Wolkow and Baumann, l.c., p. 252.—Araske and Baumann, Minchener med.
Wochenschr., xxxviii. 1, 1891.

374 Cooper Lane, Ann. d. Chemie und Pharmacie, cxvii. 118, 1861 (contributions
from Prof. C. Boedecker’s laboratory).

*7 See Huppert, l.c., p. 102.

“6 Zeller, Archiv f. klin. Chirurgie, xxix. 9, 1884.

“7 V, Jaksch, Zeitschr. f. physiol. Chemie, xiii. 385, 1889.— Pollak, Wiener med.
Presse, Xxxix. 1473, 1515, 1556, 1889.

*78 Thormiihlen, Virchow’s Archiv, cviii. 317, 1887.

*79 Krukenberg, Maly’s Jahresber., xiv. 60 (ref.), 1885 ; and Chem. Untersuch.
in wissenschaftl. Med., Pt. ii. p. 128. Jena, 1888.

80 Salkowski, Zeitschr. f. physiol. Chemie, ix. 127, 1884.

#81 Dreschfield, Schmidt’s Jahrb., ccxili. 213 (ref.), 1887.

82 Senator, Charité-Annalen, xv. (sep. pub.), 1890.

*85 See Liselt, Prager Vierteljahrsschr., lix. 190, 1858, and lxx. 87, 1862; A.
Pribram, ibid., lxxxvili. 16, 1865; Dressler, ibid., ci. 68, 1869; Ganghofner and
Ptibram, ibid,, cxxx. 77, 1876; £. Wagner, Berliner klin. Wochenschr., xxvii. 431,
1884 ; Paneth, Archiv f. klin. Chirurgie, xxviii. 179, 1884; K. 4. H. Mirner, Zeit-
schr. f. physiol. Chemie, xi. 66, 1886; Mura, Virchow’s Archiy, cvii. 250, 1887 ;
Brandi and L. Pfeiffer, Zeitschr. f. Biologie, xxvi. 348, 1890.

*4 VY. Jaksch, Ueber Acetonurie und Diaceturie. Berlin, 1885.—De Boeck and
A, Slosse, De la Présence de l’Acetone dans 1’ Urine aliénés, &c., 1891.

885 Lorenz, Zeitschr, f. klin. Med., xix. 19, 1891.

*86 Baginsky, Archiv f. Kinderheilkunde, ix. 1. 1887.

“7 V, Jaksch, Zeitschr. f. klin. Med., x. 362, 1885.—Jujinger, Wiener klin.
Wochenschr., i. 367, 1888.—S. West, Maly’s Jahresbericht, xix. 418 (ref.), 1890.—
Pawinski, Berliner klin. Wochenschr., xxv., No. 50, 1888.—Lorenz, l.c., p. 54.

88 Rosenfeld, Deutsche med. Wochenschr., No. 40, 1885.—Zphraim, Inaug.
Dissert., Breslau, 1885.—Honigmann, Inaug. Dissert., Breslau, 1886.—Jufe, Inaug.
Dissert., Wiirzburg, 1886.

“89 For the other reactions of acetone, see v. Jaksch, Ueber Acetonurie und

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CHAPTER VII.—THE URINE. P20

Diaceturie, lc., p. 21; also Lorenz, l.c., p. 21.—Men Taniguti and L. Salkowski,
Zeitschr. f. physiol. Chemie, xiv. 476, 1890.

*0 V, Jaksch, Zeitschr. £. physiol. Chemie, vi. 541, 1882.—Nencki, see Pawinski
(387).

*. Messinger, Bericht. d. deutsch. chem. Gesellsch., xxi. 3366, 1888.
*2 Huppert, 1.c., p. 470.

*8° R. v. Engel, Prager med. Wochenschr., xvi. 247, 1891.—Devoto, Rivista clinica,
Archivio italiano di clinica Medica, xxx. (sep. pub.), 1891.

“4 V. Jaksch, Ueber Acetonurie und Diaceturie, l.c., p. 101.

*% WV. Jaksch, Zeitschr. f. Heilkunde, iii. 34, 1882.—Schrack, Jahrbuch f. Kinder-
heilkunde, xxix. 411, 1889.

%6 V. Jaksch, ibid., p. 116.

37 VY. Jaksch, 58 Versammlung deutscher Naturforscher und Aerzte in Strass-
burg, Sept. 1886; Zeitschr. f. klin. Med., xi. 307, 1886; Zeitschr. f. physiol.
Chemie, x. 536, 1886.

98 V7. Rokitansky, Wiener med. Jabrb., ii. (No. 1), 205, 1887.

*99 VV. Jaksch, see (397).

4 Salkowski, Centralbl. f. d, med. Wissensch., xxvi. No. 38, 1888 ; and Zeitschr.
f. physiol. Chemie, xiii. 265, 1889.—Ken Taniguti, ibid., xiv. 980, 1890.

41 2, Schiitz, Prager med. Wochenschr., vii. 322, 1882.

402 See (87).

#3 See also Rassmann, Centralbl. f. d. med. Wissensch., xix. 567 (ref.), 1881.

Grim, Langenbeck’s Archiv, xxxii. 511, 1885.
Brieger, Zeitschr. f. physiol. Chemie, iv. 407, 1880.—A. Huber, Virchow’s
Archiv, evi. 126, 1886.—Rossbach-Goctze, Verhandl. des Congresses f. innere Med.,
vi. 212, 1887.—Kisch, Deutsche med. Wochenschr., xii. 39, 1886.—Francotte,
Schmidt’s Jahrb., cexiii. 145 (ref.), 1887.

46 Tanggaard, Virchow’s Archiv, lxxvi. 545, 1879.

47 Fiirbringer, Archiv f. klin. Med., xviii. 154, 1876.—Czapcek, Zeitschr. f. Heil-
kunde, ii. 345, 1881.

48 See Huppert, l.c., p. 494.

409 For other methods for the determination of oxalic acid in the urine, such as
those by Schultzen and Buchheim, see Leube and Salkowski, l.c., p. 118; W. Mills,
Virchow’s Archiv, xcix. 305, 1885; Salkowski, Zeitschr. f. physiol. Chemie, x. 120,
1886; Nickel, ibid., xi. 189, 1887.

10 Fiirbringer, Archiv f. klin. Med., xvi. 516, 1875.

41. Cantani, Oxalurie, Germ. transl. by Hahn. Berlin, 1880.

42 Beybie, Schmidt's Jahrb., lxvii. 52 (ref.), 1850.

Neidert, Miinchener med. Wochenschr., xxxvii. 590, 1890.

Kisch, oral communication.

Ebstein, Deutsches Archiv fiir klin. Med., xxiii. 138, 1878, and xxx. 188, 1882 ;
further see A. Niemann, Deutsches Archiv f. klin. Med., xviii. 223, 1876; Loebisch,
Liebig’s Annalen, clxxxii. 231, 1876; Steffenhagen, Virchow’s Archiv, c. 416, 1885.

416 Stadthagen and Brieger, Berliner klin. Wochenschr., xxvi. 344, 1889.—V.
Udrinsky and E. Bawmann, Zeitschr. f. physiol. Chemie, Ixxv. 77, 1890.

47 See A. Hermann, Zeitschr. f. physiol. Chemie, xii. 496, 1888.

Czapek, ibid., xii. 502, 1888.—Camerer, Zeitschr. f. Biologie, xxvi. $4, 1889.

49 Fokker, Pfliiger’s Archiv, x. 153, 1875; xlv. 389, 1889.

0 2. Salkowski, Virchow’s Archiv, Ixviii. gor, 1876 ; Zeitschr. f. physiol. Chemie,
xiv. 31, 1890.

#1 #. Salkowski, Leube, and Salkowski, 1.c., p. 96.

+2 7. Ludwig, Wiener med. Jahrb., 597, 1884.

423 Fleischer and Penzoldt, Deutsches Archiv f. klin. Med., xxvi. 401, 1880,—
Rohland and Schurz, Pfliiger’s Archiv f. Physiologie, xlvii. 469, 1890.

  

404
405

413
4

4
415

418

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430 BIBLIOGRAPHY.

+4 Cf. Stadthagen, Virchow’s Archiv, cix. 390, 1887.

#5 VY, Bamberger, Oesterr. Zeitschr. f. prakt. Heilkunde, vi. 7, 1860.

#26 Salkowski, Virchow’s Archiv, cxvli. 570.

“27 Y, Jaksch, Der Weingeist als Heilmittel, Wiesbaden, 1890.—See also ZL.
Thomas, Anleitung zur qualitativen und quantitativen Analyse des Harns, 9th edit.,
p. 237. Wiesbaden, 1890.

#28 Compare also A. J/aig’s Harnsiiurestudien, and G. Hofman, Prager med.
Wochenschr., xiv. 329, 1889.

£9 Prout, Taylor's Med., p. 699.

430 VY, Jaksch, l.c., p. 32.

431 V, Jaksch, Zeitschrift zu E. Henoch’s 70 Geburtstag, Berlin, 1890.—JZ. Thomas,
ley) pr 221;

482 Bernabei, Centralbl. f. klin. Med., x. (ref.), 1889.

433 Liifner, Zeitschr. f. physiol. Chemie, i. 350, 1877; and Jacobj, Zeitschr. f.
analyt. Chemie, xxiv. 307, 1885.

434 Pfliiger and Schenck, Pfliiger’s Archiv, xxxviii. 325, 1886; Schenck, ibid.,
xxxviii. 511, 1886; and Z. Salkowski, Zeitschr. f. physiol. Chemie, x. 110, 1886.

485 Bunsen, Gasometrische Methoden, 2nd edit., p. 357, 1877.

436 Pliiger, see (434).

“7 Huppert, l.c., p. 531.

438 Méhu, Urine normale, &c., l.c., p. 136.

439 G, Lange, Pfliiger’s Archiv, xxxvii. 45, 1885.

40° Huppert, l.c., p. 504.—Hoppe-Seyler, l.c., p. 363.—Leube-Salkowski, l.c. p. 58.

4 Morner and J. Sjoqvist, Skandinay. Archiv f. Physiol., ii. 438, 1891.

42 Will-Varrentrapp, see Leube-Salkowshi, l.c., p. 58.—J. Kjedahl, Zeitschr. f.
analyt. Chemie, xxii. 336, 1883.

43° Neubauer, Annal. der Chemie und Pharmacie, cxix. 27, 1861.

444 Pouchet. Maly’s Jahresber., viii. 247 (ref.), 1881.

445 Grocco, La Creatinina in Urine normali et patologiche. Perugia, 1886.

46 Senator, Virchow’s Archiv, lxviii. 422, 1876.

447 See Thomas, Neubauer, and Vogel, Pt. ii. p. 583. Wiesbaden, 1890.

48° Baldi, Maly’s Jahresbericht, xix. 132 (ref.), 1890.

49 Th, Weyl, Ber. der deutschen chem. Gesellsch., xi. 217, 1878.

450 Jafé, Zeitschr. f. physiol. Chemie, x. 399, 1886.—Colasanti, Maly’s Jahres-
bericht, xix. 132 (ref.), 1890.

#1 Neubaucr, Annal. der Chemie und Pharmacie, cxix. 33, 1861.

42 Salkowski, see Leube and Salkowski, Die Lehre vom Harn, p.111. Berlin, 1882.

43 Taniguti and Salkowski, Zeitschr. f. physiol. Chemie, xiv. 471, 1890.

#4 Thudichum, Compt. rend., cvi. 1803, 1888.

45 Salomon, Zeitschr. f. physiol. Chemie, xi. 410, 1887.

46 Wor exhaustive information relative to these and other xanthin bodies, see
Huppert, l.c., p. 200 and 551; G. Bruhns, Zeitschr. f. physiol. Chemie, xiv. 533, 1890.

47 4. G. Pouchet, Comptes rendus, xcvii. 1560, 1883, and c. 361, 1885.

#8 Ch, Bouchard, Comp. rend. Soc. Biolog., 604, 1882; 665, 1884; see Maly’s
Jahresber., xii. 55, 1883, and xiv. 216, 1885.

49 Lépine and Guerin, Revue de Médicine (Sup.), 1885.

460 4, Villiers, Comptes rendus, c. 1246, 1885.

461 4, G. Pouchet, see (457).

462 Feltz, Maly’s Jahresbericht, xvii. 433 (ref.), 1888.

463° Lépine, Centralbl. f. klin. Med., xi. 12 (ref.), 18g90.— Lépine and Aubert, Comptes
rendus (sep. pub.), July 1885.

464 Roges and Gaume, Centralbl. f. klin. Med., xi. 12 (ref.), 1890.

45 Bouchard, Legons sur les Autointoxications dans les Maladies, Paris, 1887 ;
and Comptes rendus, cvi. 1582, 1888.

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we

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466 Tanret, Bouchardat, and Cardier, see Huppert, l.c., p. 220.

467 Gautier, Maly’s Jahresbericht, xvi. 523 (ref.), 1887.

468 VY. Udrdnsky and Baumann, see Chap. v. (164).

469 Kerry and Kobler, Wiener klin. Wochenschr., iv. 525, 1891. — Griffiths,
Fortschritte der Medicin, x. 112 (ref.), 1872.

40 Y. Jaksch, Wiener klin. Wochenschr., iii. 1011, 1890.

Bruschettini, Riforma med., April 11, 1892.
V. Jaksch, Zeitschr. f. Heilkunde, xi. 440, 1890.

43 Brieger and Frénkel, Berliner klin. Wochenschr., No. 11 (sep. pub.), 1890.—
Brieger, Zeitschy. f. klin. Med., Supp. to vol. xvii. 253, 1890.

44 V. Briicke, Sitzungsber. der kais. Akademie, Vienna, xliii. 618, 18Sr.

4 Sahli, Pfliiger’s Archiv, xxxvi. 209, 1885.—Jco, ibid., xxxvii. 223, 1885.—
Gehrig, ibid., xxxviii, 38, 1885.—Stadelmann, Zeitschr. fiir Biologie, xxiv. 226,
1887 ; xxv. 208, 1888.—Schnapauff, Maly’s Jahresbericht, xix. 199 (ref.), 1890.—
Patella, Schmidt’s Jahrbiicher, ccxvii. 117 (ref.), 1888.

46 Griitzner, Miinchener medic. Wochenschr., xxiv. 946, 1887.

47 Teo, Verhanal. d. Congresses f. in. Med., vii. 364, 1888.

478 Mya and Belfanti, Centralbl. fiir klin. Medicin, vii. 729, 1886.

479 Hovoltschiner, Virchow’s Archiv, civ. 42, 1886.— Rosenderg, Dissertation,
Tiibingen, 1890.

480 Breusing, ibid., cvii. 186, 1887.

481 Teo, see (477).

482 Hovoltschiner, see (479).

43° Bous, Zeitschr. fiir klin. Medicin, xiv. 264, 1888.—Helwes, Pfliiger’s Archiv,
xiii, 384, 1888.

484 Musculus, Pfliiger’s Archiv, xii. 214, 1875.—Miquel, Berichte d. deutschen
chem. Gesellschaft, xxiii. 702 (ref.), 1890.

45 Teube, Virchow’s Archiv, c. 540, 1885.

486 Compare Benderky, Virchow’s Archiv, cxxi. 554, 1890.

487 Redtenbacher, Wien. med. Zeitschr., 373, 1850. See L. Thomas, Neubauer, and
Vogel (2), 549, 1885.—WHeller, Heller’s Archiv, i. '23, 1844.—F. Réhmann, Zeitschr.
fiir klin. Med,, i. 513, 1886.

#8 Gluzinski, Berl. klin, Wochenschrift, xxiv. 983, 1887 ; also G@. Sticker, ibid.,
p. 768.

#9 HF, Salkowski, Zeitschr. fiir physiol. Chemie, v. 285, 1882.

499 Volhard, Annalen der Chemie, exc. 24, 1877.—See Leube and Salkowski, l.c.,
p- 168.

491 Bouylants, Maly’s Jahresbericht, xviii. 134 (ref.), 1890.

42 See £. Salkowski, Virchow’s Archiv, lviii. 472, 1873; Pfliiger’s Archiv, xxxix.
201, 1887; Berliner klin. Wochenschr., No. 36, 25, 1888. ‘

493 Hefiter, Archiv fiir die ges. Physiologie, xxxviii. 476, 1886.

494 Zennmalm, Lakare forenings Forhandlingen, xxv. No. 34, 1890.

495 J, Teissier, Lyon médicale, xix. 307, 1875; Maly’s Jahresber, v. 311 (ref.),
1876.

496 Stokvis, Centralbl. fiir d. medic. Wissensch., xiii. $01, 1875; see also Z. A.
Ewald, Berliner klin. Wochenschr., xx. 484, 502, 1883 ; Ziilzer, Virchow’s Archiv,
Ixvi. 223, 1876; Luiyi Vanni and Lnrico Pons, Maly’s Jahresber.,"xvii. 446 (ref.)
1888 ; Mosse and Banal, Centralbl. f. klin. Med., xi. 303 (ref.), 1890.

497 V, Jaksch, Fortschrift zu Henoch, p. 11.

498 Lennmalm in 1.c. (494) gives full references to the literature.

499 See Peycr, Volkmann’s klinische Vortrage, No. 336, 1880.

500 Neubauer, Archiv fiir wissenschaftl. Heilk., iv. 288, 1859, v. 319, 1860; and
Huppert, 1.c., p. 450.

501 See Huppert, l.c., p. 520.

471

472

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432 BIBLIOGRAPHY.

02 OC, Wurster and A. Schmidt, Centralbl. fiir Physiol., i. 421, 1887.

503 Schinbein, Journal fiir prakt Chemie, xcii. 150, 1864.

04 Rihmann, Zeitschr. fiir physiol. Chemie, iv. 248, 1880.

505 Striimpell, Archiv fiir Heilk., xvii. 390, 1876.

506 Salkowski, 1.c., p. 393.-—Presch, Virchow’s Archiv, cxix. 148, 1890.—See also
Virchow’s Archiv, cxxv. 102, 1891.

507 Pfeiffer, Verhandl. d. Congresses f. in. Med., ix. 408, 1890.

508 Sertoli, Gazett. med. ital. lomb., ii. Serie vi. 197, 1869.—Munk, Virchow’s
Archiv, lxix. 354, 1877.

509 Betz, Memorabilien, xxvi., 1874; see LZ. Thomas, Neubauer, and Vogel, l.c.,
p. 498.—Senator, Berliner klin. Wochenschr, v. 251, 1868.—Stefano, Gazetta degli
Ospedali, 1883.

510 Fr, Miller, Berliner klin. Wochenscbhr., xxiv. 405 and 436, 1887.— Rosenheim,
Fortschr. der Med., v. 345, 1887; and Zh. Rosenheim and Gutzmann, Deutsche
med, Wochenschr., xiv., No. 10, 1888.

‘ll Emil Fischer, Ber. der deutschen chem. Gesellsch., xvi. 2234, 1883.

‘2 Schénbein, Journal fiir prakt. Chemie, xcii. 168, 1860.

‘3 See Huppert, Neubauer, and Vogel, l.c., p. 25.—Leube and Salkowski, 1.c.,
p. 202.

4 See Wurster and Schmidt, Centralbl. fiir Physiol., i. 421, 1887.—Miiller, Ber-
liner klin. Wochenschr., xxvi. 889, 1889.

515 Ehrlich, Zeitschr. fiir klin. Med., v. 285, 1882; Charité-Annalen, viii. 28,
1883.

16 1). G. Goldschmidt, Miinchener medic. Wochenschr., xxxiii. 35, 1886.

7” Penzoldt, Berl. klin. Wochenschr., xx. No. 14, 1883.

‘8 Petri, Zeitschr. fiir klin. Med., vii. 500, 1884.

519 Khrlich, Charité-Annalen, xi. 139, 1886.

520 For other notices as to the literature, see Lscherich, Deutsche med.
Wochenschr., No. 4, 1884 ; Piering, Zeitschr. f. Heilkunde, vi. 511, 1885; Onopf,
Inaug. Diss., Niirnberg, 1887; Brechte, Livinson, Georgicwski, D. Fischer, Maly’s
Jahresbericht, xiii. 185 (ref.), 1884; Brehmer, Grundics, ibid., xiv. 449, 1885;
Riitimeyer, Correspondenzbl. f. Schweizer Aerzte, xxvi. (sep. pub.), 1890; Howard
Taylor, Schmidt’s Jahresbericht, 228, 277 (ref.), 1890.

> V. Jaksch, Prager med. Wochenschr., xvi. 94, 1891.

°2 Hale White, Brit. Med. Journ., May 21, 1892.

53 Sehrwald, Deutsche med. Wochenschr., xvi. 520, 1890.

524 Glaser, ibid., xvii. 1193, 1891.

° V, Jaksch, Deutsche med. Wochenschr., xiv., No. 40 and 41, 1888.

6 Compare v. Noorden and A. Ritter, Zeitschr. f. klin. Med., xix. 197, 1891.

57 Fischl, Zeitschr. fiir Heilkunde, vii. 279, 1886.

5°8 Schnitzler, Centralbl. f. Bacteriol. u. Parasitenkunde, viii. 789, 1890. For
further literature, see Levy, Archiv f. experiment. Pathol. u. Pharmak., xxix. 152,
1891.
*29 Compare also Arogius, Maly’s Jahresbericht, xx. 469 (ref.), 1891.

530 Gwyon, Wiener med. Presse, Xxx. II, 55, 95, 1889.

531 Boekhart, Monatshefte fiir prakt. Dermatologie, No. 4, 134, 1886.

582 Neisser, Centralbl. fiir die med. Wissensch., xvii. 497, 1879.—Bumm, Der
Mikro-organismus der gonorrhoischen Schleimhauterkrankungen, ‘‘ Gonococcus
Neisser.” Wiesbaden, 1885.—Bockhart, Monatshefte fiir prakt. Dermatologie,
No. 10, 449, 1886.

533 V7, Zeissl, Wiener Klinik., Pts. xi. and xii. Wien, 1886.—Hartdegen, Centralbl.
fiir Bacteriol. und Parasitenk., i. 70, 105, 1887.— Wendt, ibid., iii. 409 (ref.), 1888.

534 Wertheim, Zur Lehre von der Gonorrhoe, Vortrag gehalten in Bonn,
Gynakologen Congress, 1891.

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CHAPTER VII.—THE URINE. 433.
. 85 Roux, Baumgarten’s Jahresber., ii. go, 1888.

588 C. Schiitz, Miinchener med. Wochenschr., xxxvi. 235, 1889.

87 See also Finger, Die Blennorrhoe der Sexualorgane, p. 14. Wien-Leipzig,
1888,—Baumgarten’s Jahresber., ii. 83, 1887; iii. 56, 1888; v. 67, 1890.—Ober-
lénder, Berliner Klinik, Pt. v, 1888,.—Steinschneider, Berliner klin. Wochenschr.,
XXvii. 533, 1890.

588 Fiirbringer, Archiv fiir klin. Med., xxxiii. 79, 1881.

5389 Schultzen and Riess, Charité-Annalen, xv. 1869.

540 Frerichs, Leberkrankheiten, i. 216, 1861.

54 Schultzen and Riess, Chemisches Centralbl., xiv. (2), 681, 1869.—Rohmann,.
Berliner klin. Wochenschr., xxv. Nos. 43 and 44, 1888.

52 V7. Jaksch, Zeitschr, fiir physiol, Chemie, x. 536, 1886.

* Kraus and Ludwig, see (234).

°4 Compare Fawitzky, Deutsches Archiv f. klin. Med., xlv. 429, 1889.

54° Stokvis, Verhandl. des Congresses fiir innere Med., v. 125, 1886.

546 R. v. Engel, Prager med. Wochenschr., xvi. 323, leon

547 Minkowski, Archiv fiir exper. Pathol. und Pharmak., xviii. 35 and 147,
1884.—Kiilz, Zeitschr. f. Biologie, xx. 165, 1884; and Archiv f, exper. Pathol, und
Pharmak., xviii. 291, 1884.

58 V. Jaksch, Zeitschr. fiir klin, Med., xi. 307, 1886.

549 Kiilz, Zeitschr. fiir Biologie, xxiii, 329, 1886.

550 Leo, Deutsche med. Wochenschr., xii. 869, 1887.

551 Kiilz, Vernhandl. des Congresses f. in, Med., x. 345, 1891.

52 Hunter, Lancet, vol. ii., 1888, p. 654.

5538 Halliburton, l.c., p. 174.

554 Flcischer and Penzoldt, Deutsches Archiv fiir klin. Med., xxvi. 368, 1880.—
Jacubasch, Virchow’s Archiv, xliii, 196, 212, 1868.

555 Prus, see (108).

556 Salkowski, ibid., lii. 58, 1871.—Nencki and Sieber, Journal f. prakt Chemie,
cxxxiv. 241, 1882; compare also Bohlund and Schwarz, Pfliiger’s Archiv, xlvii.,
Pts. ix. and x., 1890.

557 Miiller, see (223).—Obermayer, see (224).

558 VY, Jaksch, Zeitschr. f, physiol. Chemie, xvi. 243, 1892.

559 Colasanti and Moscatelli, Maly’s Jahresber., xvii. 212 (ref.), 1888—Moscatelli,
Archiv f. experiment. Pathol., xxvii. 158, 1891.

560 Heuss, ibid., xxvi. 147, 1890.

561 Keller, Archiv fiir Gyniikologie, xxvi. 107, 1885.

562 Piirbringer, Berliner klin. Wochenschr., xv. 332, 1873.

563 Tudwig, Wiener med. Jahrbiicher, 143, 1877, and 493, 1880.

564 Schneider, see Chap. v. (151).

565 Wolf and Nega, Deutsche med. Wochenschr., xii. 15, 16, 1886; see also F,
Welander, Ann. de Dermat. et de Syphil.; vii. 7-8, 1886 ; Schmidt’s Jahrb., ccxii.
270 (ref.), 1886.

566 Alt, Deutsche med. Wochenschr., xii. 732, 1886.

587 Winternitz, Archiv f. experiment. Pathol., xxv. 225, 1889.

568 Almén, Maly’s Jahresber. fiir Thierchemie, xvi. 221 (ref.), 1887.—See also-
Brugnatelli, ibid., xix. 217 (ref.), 1890.

569 #. Schultz, see (401).

570 Donath, Archiv fiir die gesammte Physiologie, xxxviii. 528, 1886.

57l De Ruitter and Donders, see v. Beck, Ziemssen’s Handbuch, lxxv. 368, 1876,

' 572-4, Paltauf, Wiener klin. Wochenschr., i. 113, 1888.

573 Glaser, see (524).

574 Tieben, Annal. der Chemie und Pharmacie, vii. (sup. vol.), 236, 1870.

575 Kast and Mester, Zeitschr. f. klin. Med., xviii. 469, 1891.

25

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434 BIBLIOGRAPHY.

76 Compare C. Thiem and C. Fischer, Maly’s Jahresbericht, xx. 58 (ref.), 1891.

77 Maréchal, Zeitschr. fiir analyt. Chemie, viii. 99 (ref.), 1869; see also 0. Neu-
bauer, ibid., vii..394, 1868.

578 Baumann and Preusse, see (9) and (364).

579 (. A, Ewald, Berliner klin. Wochenschr., xii. 3, 1875.— V. Mering, Centralbl,
fiir d. med. Wissensch., xiii. 945, 1875.

380 Grandhomme, Vierteljabrsschr. fiir gerichtl. Med., xxxii. 1880 ; see Lewin’s
Toxikologie. :

381 Fr, Miller, Deutsche med. Wochenschr., xii. 27, 1887.

582 See v. Jaksch, Prager med. Wochenschr., vii. 161, 1882; and Zeitschr. f.
klin. Med., xi. 20, 1886.

83 FE. Harnack, Berliner klin. Wochenschr., xxii. 98, 1885.

58 Compare Quaedvlieg, Maly’s Jahresbericht, xvii. 218 (ref.), 1888.

°85 Compare Chopin, Maly’s Jahresbericht, xix. 192 (ref.), 1890.

386 Kerner, Pfliiger’s Archiv, ii. 230, 1869.

87 V. Mering, Zeitschr. fiir klin. Med., vii. 148, 1884.

588 -V, Jaksch, Zeitschr. fiir klin. Med., viii. 551, 1884.

89 Fr, Miiller, see (581).

° Yvon, Journal de Pharmac. et de Chimie, No. 1, 1887; Therapeutische
Monatshefte, i. 80 (ref.), 1887.

*l Mérner, Zeitschr. fiir physiol. Chemie, xiii, 12, 1889; cf. Jaffé and Hilbert,
ibid., xii. 295, 1888.

2 Miiller, Therapeutische Monatshefte, ii. 355, 1888.
°8 Ubaldi, Centralbl. f. klin. Med., xi. 329 (ref.), 1891.
°%4 Munk, Virchow’s Archiv, xxii. 136, 1879.
G. Hoppe-Seyler, Berl. medic. Wochenschr., xxiii. 436, 1886.
Penzoldt, Archiv fiir experim. Pathol. und Pharmakol., xxi. 34, 1886.
Edlefsen, Congress fiir innere Med., vii. 435, 1888.

595
596

597

CHAPTER VIII.
EXUDATIONS, ETC.

1 Boettcher, Virchow’s Archiv, xxxix. 512, 1867.
2 Bizzozero, l.c., p. 108.
* Klemperer, Zeitschr. fiir klin. Med., x. 158, 1886; see further Baumgarten’s

Jahresber., i. 23, 1886 ; ii. 13, 1887 ; iii. 11, 1888.—A. Zuckermann, Centralbl. fiir
‘ Bacteriol. und Parasitenk., i. 497, 1887.

+ Grawitz and W. de Bary, Virchow’s Archiv, cviii. 67, 1887.—Scheuerlen, Archiv
fiir klin. Chirurgie, xxxvi. 925, 1888.—Kreibom and Rosenbach, ibid., xxxvii. 737,
1888.—Grawitz, Virchow’s Archiv, cx. 1, 1887.

° Ogston, Archiv fiir klin. Chirurgie, xxv. 588, 1880.—Rosenbach, Ueber die
Wundinfectionskrankh. des Menschen. Wiesbaden, 1884.

5 Passet, Fortschr. der Med., iii. 33, 68, 1885; and Untersuchungen iiber die
Aetiologie der eiterigen Phlegmone des Menschen. Berlin, 1885.

7 Brieger, Charité-Annalen, xiii, 198, 1888.—A. Fréinkel, ibid., p. 147.

* Levy, Archiv f. experiment. Pathol. u, Therapie, xxvii. 379, 1890; xxix.
135, 18901.

* Bujwid, Centralbl. f. Bacteriol. und Parasitenk., iv. 577, 1888.

0 Tnicke, Archiv fiir klin. Chirurgie, iii. 135, 1862.—Girard, Chirurg. Centralbl.,

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CHAPTER VIII.—EXUDATIONS, ETC. 435

li. 50, 1875.—Lrnst, Zeitschr. fiir Hygiene, ii. 369, 1887.—Ledderhose, Centralbl, fiir
Bacteriol. u. Parasitenk., iii. 581 (ref.), 1888.

1 Habermann, Prager med. Wochenschr., x. 50, 1885.—B. Meyer, Centralbl. f,
klin. Med., xi. 72, 1891.

12 Metschnikoff, Virchow’s Archiv, xcvi. 177, 1884.

13 Lustgarten, Med. Jahrbiicher (Vienna), 89 and 193, 1885.

4 Alvarez and Tavel, Archives de Physiologie norm. et pathol., vi. 303, 1885.

Kamen, Internationale klinische Rundschau, iii. 66, 114, 1889.
De Giacomi, Baumgarten’s Jahresber., i. 96 (ref.), 1886.—Doutrelepont and
Schiitz, Deutsche med. Wochenschr., xi. 320, 812, 1885.—Markuse, Vierteljahrsschr.
fiir Dermatol. und Syphilis, xv. 343, 1888.—Bawmgarten, Jahresber., ii. 263, 1887 ;
lil. 75, 232, 1888 ; iv. 223, 1889; v. 237, 1890; vi. 238, 1891.—Bender, Centralbl.
fiir Bacteriol. und Parasitenk., i. 327, 357, 1887.

7 Bollinger, Centralbl. fur die med. Wissensch., xv. 481, 1877.

18 Ponfick, Die Actinomycose. Berlin, 1882.

19 J. Israel, Virchow’s Archiv, lxxiv. 15, 1878; lxxviii. 421, 1879.

*” Roser, Deutsche med. Wochenschr, xii. 369, 1886. See also Bostrém, Verhandl.
des Congresses fur interne Med. in Wiesbaden, iv. 94, 1885.—Zemann, Wiener
medic. Jahrb., 477, 1883.—J. Israel, Klin. Beitrige zur Diagnostik und Casuistik
der Actinomycose. Berlin, 1885.—0. Zsracl, Virchow’s Archiv, xcv. 140, 1884;
and ibid., xevi. 175, 1884.— Virchow, ibid., xev. 534, 1884.—R. Paltauf, Sitzungsber.
ider k.k. Gesellsch. der Aerzte in Vienna, Jan, 29, 1886.—Bawmgarten, Jahresber.,
1. 137, 1886; ii. 311, 1887; iii. 309, 1888; iv. 288, 1889; v. 395, 1890.—Fliigge, l.c.,
p. 116.—C. Frankel, Grundriss der Bacterienkunde, 361. Berlin, 1887.—Partsch
yv. Volkmann's Sammlung klin. Vortriige, Nos. 306-307, 1888.

“1 Trans. Path. Soc., 1885 ; Trans. Med. Chir. Soc., 1886 and 1889.

~ Lindt, Centralbl. fur klin, Med., 48.

*3 Lancet, May 17, 1890.

Orlow, Deutsch. med. Wochenschr., 16, 1890.

* Anderson, Trans. Med. Chir. Soc., Nov. 10, 1891.

*6 Bostrim, Verhandl. des Congresses fiir interne Med. in Wiesbaden, iv. 94, 1885.
—R., Paltauf, Sitzungsber. der k.k. Gesellsch. der Aerzte in Vienna, Jan. 29, 1886.

7 Crookshank, Brit. Med. Journ., Nov. 14, 1891.

3 Dr. W. Hill; ibid.

* Weigert, Virchow’s Archiv, 1xxxiv. 285, 1881.

30 Wedl, ibid., lxxiv. 142, 1878.

3 Baranski, Deutsche med. Wochenschr., xiii. 1065, 1887.

Bujwid, Centralbl. f. Bacteriol. u. Parasitenkunde, vi. 630, 1889.

Buchner, ibid., iv. 149, 1888.

Lifler, Arbeiten aus dem kaiser]. Gesundheitsamte, i. 171, 1886.

Kranzfeld, Centralbl. fur Bacteriol. und Parasitenk., i. 273, 1887.

Raskin, Petersburger med. Wochenschr., xii. 357, 1887.

Baumgarten, Centralb]. fur Bacteriol. und Parasitenk., ili, 397, 1888. See
further, Bawmgarten, Jahresber., ii, 181, 1887; iii. 156, 1888; iv. 154, 1889; v
226, 1890.

38 See Baumgarten’s Jahresber., ii. 118, 1887 ; and iii. 100, 1888.

39 4, Hansen, Virchow’s Archiv, lxxix. 31, 1880, and xc. 542, 1882.—WNeisser,
ibid., Ixxxiv. 514, 1881.

40 Of, Wesencr, Centralbl. fiir Bacteriol. u. Parasitenk., i. 450, 1887 ; ii. 131, 1887;
and Baumgarten, ibid., i. 573, 1887, and ii. 291, 1887.— Baumgarten’ edabresberiy ht;
ii, 243, 1887; iii. 217, "1888 ; iv. 167, 216, 1889; v. 240, 1890.

41 Melcher and Ortmann, Berliner klin. Wochenschr., xxii. 193, 1885.

42 Bordoni- Uffreduze, Zeitschr. fur Hygiene, iii. 1079, 1887.

48 Manson, Patrick, Jour. Lepr. Investig. Com., i. 40. c Bsmt}

15
16

4

32
33
34
35
36
37

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436 BIBLIOGRAPHY.

44 Campana, Riforma med., xiv. 1891.

4 Kanthack and Barclay, Brit. Med. Journ., 1891 ; Virchow’s Archiv, cxxv. 398,
1801, :

4% Beavanm Rake and Buckmaster, Indian Lepr. Com. Report.

47 Stallaro, Occid. Med. Times, 1890.

4% Byron, New York Dermatol. Soc., 1892.

49 Cf, Baumgarten’s Jahresber., ii. 270, 1887; iii. 236, 1888; iv. 230, 1889; v.
201, 1890.

50 Kitasato, Zeitschr. f. Hygiene, vii. 225, 1889.—Baumgarten’s Jahresbericht,.
iv. 230, 1889; Vv. 201, 1890.

51 R. Pfeiffer, Deutsche med. Wochenschr., xviii. 28, 1892.

52 Kitasato, ibid., xviii. 28, 1892.

53 Canon, ibid., xix. 28, 48, 1892.

54 R. Paltauf, Centralbl. f. Bacteriol., xi. 93, 1892. Compare Baumgarten’s
Jahresbericht, vi. 82, 1891.

55 Eppinger, Wiener klin. Wochenschr., iii. 321, 1890.

56 Kiinstler and Pitres, Compt. rend. Soc. Biolog., 523, 1884. See Leuckart, l.c.,
p. 964. .
57 Titten, Verhandlungen des Congresses fur interne Medicin, v. 417, 1886.
Nasse, Deutsche med. Wochenschr., xvii. 881, 1891.
See M. Leo, Heller’s Archiv fur Chemie und Mikroskopie, i. 236, 1848.
Babesiu, see Grassi (61).
Grassi, Centralbl. fur Bacteriol. und Parasitenk., i. 617, 1887.
Sarcani, Wiener med. Presse, xix. 222, 1888.
Leyden, Deutsche med. Wochenschr., xv. 46, 1889.
Hofmeister, Zeitschr. fur physiol. Chemie, iv. 253, 1880.
Miescher, Hoppe-Seyler, Med.-chem. Untersuchungen, iv, 441, 1871.—Naunyn,
Reichert’s and Du Bois-Reymond’s Archiv fur Anat. und Physiol., 166, 1865.

6 Guttmann, Deutsche med. Wochenschr., xiii. 1097, 1887.

8 VY. Jaksch, Zeitschr. f. Heilkunde, xi. 440, 1890.

8 Qwincke, Deutsches Archiv fur klin. Med., xxx. 569, 580, 1882.

9 Bizzozero, l.c., p. 94.

” Fichhorst, Zeitschr. fur klinische Medicin, iii. 537, 1881.—V. Jaksch, ibid.,
xi. 20, 1886; and (67).

71 A. Reuss, Deutsches Archiv f. klin. Med., xxiv. 601, 1879, and xxviii. 317, 1881.

? F, A, Hoffmann, Virchow’s Archiv, lxxviii. 250, 1878.

73 Boulengier, Schmidt’s Jahrbuch, ccxxvi. 28 (1890).

™ Hasebrock, Zeitschr. f. physiol. Chemie, xii. 289, 1888. Compare also A.
Hirschler and Buday, Maly’s Jahresbericht, xix. .468 (ref.), 1890.

 Frdnkel, Charité-Annalen, xiii. 147, 1888.—Levy, Archiv f. experiment. Pathol.
u. Pharmakol., xxvii, 369, 1890; xxix. 135, 1891; he cites Levy, and gives exhaus-
tive references.

76 Méhu, Archiv gén. de Med., i. and ii., 1872 and 1875.—A. Reuss, Deutsches
Archiv f. klin, Med., l.c., (71).—Hoffmann, ibid., xliv. 313, 1889.—Neuenkirchen,

Petersburger med. Wochenschr., xiv. 13, 1889.—Citron, Deutsches Archiv f, klin.
Med., xlvi. 129, 1890.

65

7 Mya and Viglezio, Rivista clinica, xxvii. 712, 1888.—Moritz, Inaug. Dissert.,
Leipzig, 1886.—Fichtner, Deutsches Archiv f. klin. Med., xliv. 323, 1889.

% Runeberg, ibid., xxxiv. 1, 1884, and xxxv. 266, 1884.—Ranke, Mittheilungen aus
der med. Klinik zu Wiirzburg, ii. 189, 1886.—A. Reuss, see (71).

See Hofmann, Neuenkirchen, and Citron (76).

8° Bock, Du Bois-Reymond’s Archiv fiir Anat. und Physiol., Pt. v., 1873.—
O. Rosenbach, Breslauer irztl. Zeitung, No. 5 (sep. sheet), 1882.—Hichhorst, see
(70).— V. Jaksch, see (70).—Ranson, Centralbl. f, klin, Med., xi. 339 (ref.), 1891.

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CHAPTER IX.—SECRETIONS OF GENITAL ORGANS. 437

81 See Senator, Virchow’s Archiv, cxi. 210, 1888.
& Moscatelli, Zeitschr. fiir physiol. Chemie, xiii. 202, 1889.—V. Jaksch, see (70).
8 J. Munk, Virchow’s Archiv, lxiii. 255, 1875.
84 Schatz, Archiv fiir Gyniikologie, ix. 15, 1$76.—Gusserow, ibid., ix. 478, 1876.
— Westphalen, ibid., viii. 72, 1875.
% Hammarsten, Zeitschr. fiir physiol. Chemie, vi. 194, 1882.
86 Huppert, Prager med. Wochenschr., i. 321, 1876.
8 VY. Jaksch, Zeitschr. fiir physiol. Chemie, xii. 116, 1887.
88 P. Wagner, Deutsche Zeitschr. fiir Chirurgie, xxiv. 505, 1886.
89 Karewski, Deutsche med. Wochenschr., xvi. 1035, 1069, 1890 (full references
are given).
% Hofmeister, see Gassenbaucr, Prager med. Wochenschr., xvi. 365, 377, 1891.
2 V. Jaksch, see Wolfler, Zeitschr. f. Heilkunde, ix. 126, 1888.
Boas, Deutsche med. Wochenschr., xvi. 1095, 1890.
% Wolfler, Zeitschr. f. Heilkunde, ix. 127, 1888.
% See A. v, Rosthorn, Wiener klin. Wochenschr.,, ii. 125, 1889.

CHAPTER IX.
SECRETIONS OF GENITAL ORGANS.

1 Fiirbringer, Zeitschr. f. klin. Med., iii. 310, 1881.

2 Kehrer, Beitr. z. klin. u. experiment. Gyniikologie, ii. 1879. Giessen. See
also Ultzmann, Wiener Klinik, p. 36, 1879.

3 Fiirbringer, see (1).

4 Posner, see Chap. vii. (200).

5 Cerny, Festschrift f. Henoch. p. 194. Berlin, 1890.

6 Lscherich, Fortschritte der Medicin, iii. 231, 1885.

7 Karlinski, Wien. med. Wochenschr., xxxviii. No. 28, 1888.

8 Neelsen, Cohn’s Beitrage zur Biologie der Pflanzen, iii. 187, 1880.

9 M. Kohn and H. Neumann, Archiv f. pathol. Anatomie, cxxvi. 391, 1891.
See also a forthcoming contribution from V. Jaksch’s clinic by Dr. Ernest Otl.

10 Neelsen, see (8).—Hueppe, Mittheil. aus dem kaiserl. Gesundheitsamte, ii.
309, 1884.

1 V, Jaksch, Prager med. Wochenschr., v. 83, 1880.

12 Hausmann, Deutsche med, Wochenschr, i. 206, 1877.

13 Winter, Zeitschr. fiir Geburtskunde und Gynikologie, xiv. 443, 1888.

14 Déderlein, Archiv fiir Gyniikologie, xxxi. 412, 1887.—Samschin, Deutsche
med. Wochenschr., xxi. 332, 1890.

16 Zweifel, ibid., xviii. 359, 1881.

16 Gf, F. Winckel, Lehrbuch der Geburtshilfe, p. 188. Leipzig, 1889.

7 Déderlein, Archiv fiir Gynikologie, xxxi. 412, 1887.

18 Thomen, Centralbl. f. d. med. Wissensch., xxviii. 537, 1890. See also
Artemjew, Prager med, Wochenschr., xiv. 574 (ref.), 1889.

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438 BIBLIOGRAPHY.

CHAPTER X.
BACTERIOLOGICAL RESEARCH.

1 The following list includes the most important works on Bacteriology, with
special reference to those which describe the methods of examination and the
morphology of Bacteria. .We direct attention, as a basis of study, above all, to
the already-mentioned works of.&. Koch and his school.—Crookshank, Chap. iv.
(40).—Fliigge, Chap. i. (140).—Cornil and Babes, Les Bactéries. Paris, 1885.—C.
Frankel, Grundriss der Bacterienkunde. Berlin, 1887.—4. Johne, Ueber die
Koch’schen Reinculturen und die Cholerabacillen. Leipzig, 1885.—W. Zopf, Die
Spaltpilze, 3rd edit. Berlin, 1885.—C. Friedliinder and Lberth, Mikroskopische
Technik, 4th edit., 1890.—Stebenmann, Die Fadenpilze. Wiesbaden, 1883.—A. de
Bary, Vergleichende Morphologie und Biologie der Pilze, Leipzig, 1884; and A.
de Bary, Vorlesungen iiber Bacterien, Leipzig, 1885.—H. Huber and A. Becker,
Die pathologisch-histologischen und bacteriologischen Untersuchungsmethoden.
Leipzig, 1886. — H. Mittenzweig, Die Bacterien-Aetiologie der Infectionskrank-
heiten. Berlin, 1886.—Duclauxz, Le Microbe et la Maladie. Paris, 1886.—
Gottstein, Die Verwerthung der Bacteriologie in der klinischen Diagnostik.
Berlin, 1887.—Bawmgarten, Lehrbuch der pathol. Mykologie. Brunswick, 1886
to 1888.—Léfier, Vorlesungen iiber die geschichtliche Entwicklung der Lehre
von den Bacterien. Leipzig, 1887.—Hueppe, Die Methoden der Bacterienfor-
schung, 5th edit. Wiesbaden, 1891.—Giinther, Hinfiihrung in das Studium der
Bacteriologie, 2nd edit. Leipzig, 1891.—Azel Holst, Uebersicht iiber die Bak-
teriologie fiir Aerzte und Studirende, German translation by Rayher. Basel,
1891.—Zisenbery, Bakteriologische Diagnostik. Hamburg and Leipzig, 1891.—
For exhaustive literary notices see Fliigge, Zopf, and de Bary. Woodhead and
Hare, Pathological Mycology, 1885.

2 R, Koch, Untersuchungen iiber Wundinfectionskrankheiten. Leipzig, 1878.

3 Giinther, Deutsche med. Wochenschr., xiii. 471, 1887.

4 Unna, Centralbl, fiir Bacteriol. und Parasitenk., iii. 22, 61, 93, 120, 153, 189,
218, 254, 285, 312, 345, 1888.

5 Kiihne, Zeitschr. fiir Hygiene, i. 552, 1886 ; and Kiihne, Praktische Anleitungen
zum mikroskopischen Nachweise der Bacterien. Leipzig, 1888.

6 Kithne, l.c., p. 28.

? Kiihne, |.c., p. 34.

8 Hueppe, l.c., 1st edit., p. 59.

® For other methods see Lisenberg, Bakteriologische Diagnostik, App., p. 23.

0 Léfier, Centralbl. f. Bacteriologie und Parasitenkunde, v. 209, 1889; vii. 625,
1890.—Fisenberg, l.c., p. 24.

1 Unna, Deutsche med. Wochenschr., xii. 742, 1886; and Monatshefte fiir
praktische Dermatologie, v., No. 9, 1886.

2 Pasteur, Annal. de Chim. et Phys., lviii. (3), 388, 1860.

183 C. v. Négeli, Untersuchung iiber niedere Pilze. Munich, 1882.

44 Buchner, see v. Néigeli, l.c., p. 11.

A. Schultz, Mayer’s Gihrungschemie, p. 214.

16 V, Jaksch, Zeitschr. fiir physiol. Chemie, v.398, 1881.

WV H. Hueppe, Mittheilungen aus dem kaiserlichen Gesundheitsamte, ii. 337,
1884. ‘

18 Cf. Meade-Polton, Zeitschr. fiir Hygiene, i. 104, 1886.

19 Schottelius, Centralbl. f. Bacteriol. u. Parasitenk., ii. 47, 1888.

20 Richter, Berl. klin. Wochenschr., xxiv. 600, 1837.

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CHAPTER X.—BACTERIOLOGICAL RESEARCH. 439:

*1 A. Pfeiffer, see Eisenberg, l.c.

2 Birch-Hirschfeld, Archiv fiir Hygiene, vi. 314, 1888.

23 See Neisser and Jacobi, Centralbl. fiir Bacteriol. und Parasitenk., iii. 506 and
586, 1888; further Noegerath, Fortschritte der Med., vi. 1, 1888.

4 Marpmann, Centralbl. fiir allg. Gesundheitspflege, Supplement ii. Pt. ii.,
1886.—Cahen, Zeitschr. fiir Hygiene, ii, 386, 1887.

25 Klebs, Archiv fiir experiment. Pathol. u. Pharmak., i. 31, 1873.

6 Brefeld, Methode zur Untersuchung der Pilze, med.-phys. Gesellschaft.
Wiirzburg, 1874.

7 £, Esmarch, Zeitschr, fiir Hygiene, i. 293, 1886.

*8 See H. Rohrbeck, Chemisches Centralbl., xvii. (3), 705, 1886 ; and Deutsche
med. Wochenschr., xiii. 1089, 1887.

*® R, Fischl, Fortschr, der Med., v. 663, 1887.

* Neisser, see (23).

31 Buchner, Centralbl. f. Bacteriol. u. Parasitenkunde, iv. 149, 1888.

2 Nikiforoff, Zeitschr. f. Hygiene, viii. 489, 1890.

33 Bliicher, ibid., viii. 499, 1890.—Hesse, Zeitschr. f. Hygiene, xi, 237, 1891.

Digitized by Microsoft®
Digitized by Microsoft®
INDEX.

ABBE’S condenser, 372, 375

Abbe-Zeiss, counting cell,-9

Abscess, pulmonary, 113, 121

pus from, 348

Absorption bands, 60, 292, 293

Absorption, rate of, in stomach, 142

Accidental albuminuria, 255

Acetic acid, 139, 201, 305

—— acid in feces, 201

— acid in gastric juice, 139

— acid in sputum, 113

acid in urine, 305

— acid reaction in gastric juice, 127

—— acid tests for, 305 }

acid and ferrocyanide of potas-
sium test for albumin, 256

Acetonzmia, 77

Acetone, auto-intoxication with, 303

in blood, 77

— estimation of, 303

— in pus, 358

in urine, 303

— tests for, 303

Acetonuria, 303

Acetphenetidin, 345

Acetylparaamidophenol, 345

Acholic stools, 210

Acid, acetic, 113. 139, 201, 305

a-crotonic, 337

— ether-sulphuric, 297

— albumin, 256

— b-oxybutyric, 75

—- benzoic, 275

—— butyric, 129, 201

— capric, 202

—— caproic, 113, 202

 

 

 

 

 

 

carbolic, tests for, 161
carbolic, estimation of, 299
chrysophanic, 345
diacetic, 305
diazobenzol-sulphonic, 328
— formic, 201, 305

—— hippuric, 243

— homogentisic, 300

—— hydrochloric, 139

—- hydrocyanic, 162

—— hydroparacumaric, 300
-—— hyposulphurous, 327

— indoxyl-sulphuric, 297
— isobutyric, 202

 

 

Acid, lactic, 75, 139, 337
metaphosphoric, 257

— metatungstic, 160

nitric, 151

oleic, 202

—— oxalic, 151, 307

— oxyamygdalic, 335

—— palmitic, 202

—— paraamido-phenol-sulphuric, 342
—— parakresol-zther-sulphuric, 300
—— paroxy-phenyl-acetic, 300
paroxy-phenyl-propionic, 300
—— phenol-ether-sulphuric, 300
— phosphates, 323

—— phosphomolybdic, 160 _

— phosphotungstic, 160, 266

— phosphoric, 324

 

 

propionic, 202

salicylic, 275, 343

salicyl-sulphonic, 258

sarcolactic, 75, 338

skatoxyl-sulphuric, 298

stearic, 202

succinic, 362

sulphanilic, 328

sulphuric, 150, 297, 323

uric, 70, 240

uroleucic, 300

valerianic, 202

Acid-forming fungi, 384

Acidity of gastric juice, 127 ; action on
fungi, 389

— of urine, 217

Acids in feces, 201

organic, in blood, 74

—— organic, in feces, 201

organic, in gastric juice, 139

——— organic, in sputum, 113

— organic, in urine, 305, 337

— poisoning with, 150, 338

— volatile fatty, 74, 112, 139, 203,
305, 358

aera

 

 

 

 

Actinomyces, 351

| —— in buccal secretion, 86
| ——in pus, 351

| ——in sputum, 109

44z

Digitized by Microsoft®
442

Actinomyces in urine, 237

Acute bronchitis, 114

—— enteritis, 207

—— gastritis, 146

—— nephritis, 329

—— yellow atrophy, 335

Addison’s disease, urine in, 291, 293

Aither-sulphuric acids, 297

— tests for, 299

—— estimation of, 297

Aithylinimin, 366

Agar-agar, cultivations in, 354

—— nutrient, 383

Ague, parasites of, 49

Albumin, estimation of, in urine, 259

in cysts, 363

in feces, 199

in gastric juice, 144

in pus, 358

in sputum, 113

—— in transudations, 361

—— in urine, 252

—— tests for, 255; Fiirbringer’s, 258 ;
Hindenlang’s, 257; Heller's, 257;
Heynsius’, 257; Johnson's, 258

Albuminate, 256

Albuminimeter, 263

Albuminous putrefaction, 297

Albuminuria, 251

-— accidental, 255

— Bright on, 252

—— causation of, 253

— cyclical, 252

—— experimental, 252

—— febrile, 254

—— hematogenic, 254

in boys, 252

—— intermittent, 252, 25

-— of anemia, 254

—— paroxysmal, 252

—- pathological, 253

—— physiological, 251

—— remittent, 252

—— renal, 253

—— Stewart on, 251

Albumose in semen, 367

Albumosuria, 268

Alcohol, detection of, 161

Alcoholic poisoning, 161, 341

Alimentary canal, diseases of, feeces in,
207

— canal, diseases of, urine in, 335

—— canal, diseases of, vomit in, 146

Alkalies, poisoning with, 152, 338

Alkaline stools, 164

urine, 247

Alkalinity ‘of the blood, 2, 4

of the blood, changes of, in dis-
ease, 4

— of the blood, estimation of, 2

— of the blood, Hayeraft and William-
son’s test for, 3)

— of the plood, Kraus’ test for, 5

—— of the blood, Liebreich’s test for, 2

LIT

 

ue

 

 

 

INDEX.

Alkalinity of the blood, Zuntz’ test for, 2

— of the urine, 216

Alkaloids, animal, 158, 261

— poisoning with, 156, 340

—- Stas-Otto tests for, 156

Alkapton, 301

Alkaptonuria, 301

Allantoin, 361

Almén’s fluid, 277

—— test, 271, 339

Alt’s test for mercury, 339

Alum-carmine, 89

Alveolar epithelium, 94

Amido-acids, 311

Ammonia, urate of, in sediment, 249 ©

—— in gastric juice, 141

in vomit, 152

Ammoniacal fermentation, 217, 233

—— silver solution, 30S

Ammoniemia, 77

Ammonia-salts, in gastiic juice, 141

—— estimation of, 141

—— in urine, 249

—— in vomit, 152

—— poisoning with, 152

Ammonio-magnesic phosphate, see
Triple phosphate

Ameba coli, 180

Ameebee in urine, 237

Amorphous hemateidin, 61, 241

sediment of urine, 239

Amphoteric urine, 217

Amyloid concretions, 366

—— kidney, 331

Anemia, albuminuria in, 254

blood in, 38

—-— infantum pseudoleukemica, 33

—— pernicious, blood in, 38

—-— secondary, 39

-— urine in, 337

a-naphthol, 280

Anchylostoma duodenale, 190

Anchylostomiasis, 191

Angina, croupous, 88

— diphtheritic, 88

—— follicularis, 89

Ludovici, 351

Anguillula intestinalis, 194

—— stercoralis, 194

Aniline, 104, 162

brown, 40

—— dyes, 48, 378

—— oil, 104

—— poisoning with, 162, 342

—— poisoning, urine in, 342

—— tests for, 162

——- tests for hydrochloric acid, 129

—— -water gentian-violet, 104

Animal alkaloids, 158, 341

alkaloids, tests for, 159, 341

—— gun, 287

—— parasites of blood, 49

Annelides, 188

Anthelmintics, 190

 

 

 

 

 

 

Digitized by Microsoft®
INDEX.

Anthomyia canicularis, 195
Anthomyiz in feces, 195
Anthracosis of lung, 123
Anthrax, bacillus of, 42, 354
—— bacillus of, detection of, 42, 354
— bacillus of, in blood, 42
— bacillus of, in pus, 354
Antifebrin in urine, 344

test for, 345

Antipyrin in urine, 215, 344
Antisepsis of urine, 218
Anuria, 212

Apochromatic lens, 377

Areolar tissue in stools, 167
tissue in vomit, 145
Aromatic oxy-acids, 300
Arsenic, detection of, 154
poisoning with, 154, 340
Arterio-sclerosis, 341

Arthritis, 71, 311

Ascarides in feces, 188

-—— in nose, 91

in sputum, 110

in urine, 238

Ascaris lumbricoides, 188

—— mystax, 189

Ascites, chylous, 360

Asiatic cholera, bacillus of, 173
—— —— feces in, 209
Aspergillus fumigatus, 102
Asphyxia, 63

Asthma, 115

bronchial, 98

Atrophic cirrhosis, urine in, 335
Atrophy, gastric, 147

Atropin, detection of, 157

in urine, 341

poisoning with, 157, 341
Aurantia, 32

Auto-intoxication with acetone, 303
—— with diacetic aeid, 305
— with sulphuretted hydrogen, 327
Automatic pipette, 3
Autotoxicosis, 319
Azoospermia, 366

Azoturia, 311

 

 

 

 

 

 

 

 

BACILLI in blood, 39

in buccal secretion, 80
—— in exudations, 348

—— in feces, 170

in gastric juice and vomit, 145
—— in milk, 368

—— in nasal secretion, 91
— in sputum, 103

—— in urine, 233

—— in vagina, 369

Bacilluria, see Bacteriuria
Bacillus, crassus sputigenus, 81
cyanogenus, 369

— Lustgarten’s, 349

— of anthrax, 42, 354

— of Asiatic cholera, 173
— of cholera infantum, 165

 

 

 

 

443

Bacillus of cholera nostras, 177

of decaying teeth, 81

of diphtheria, 88

of Finkler and Prior, 177

of glanders, 46, 353

of hay, 179

of hen-cholera, 378

of hydrophobia, 48

of influenza, 356

of lactic-acid, 206

of leprosy, 355

of septicemia of the mouse, 171,
356

of smegma, 349

of syphilis, 349

of tetanus, 48, 355

of tubercle, 45, 103, 179, 349

of typhoid, 46, 81, 177

of whooping-cough, 109

pyocyanogenus, 349

salivarius septicus, 81

septicus sputigenus, 81

subtilis, 171

Bacteria, see Fission-fungi

Bacterial colonies or casts, 227

—— decomposition of urine, 234

Bacteriological methods, 371

Bacteriology, 372

Bacterium termo, 171

Bacteriuria, idiopathic, 235

Balantidium coli, 171, 182

Bamberger’s hematogenic albuminuria,
254

Barium salts, 134

Basic aniline dyes, 40, 378

—— phosphate of magnesia, 242

— phosphatic earths, 249

Basidiomycetes, 352

Basophil granules, 33

Baumann and Udransky’s method, 160

Bence Jones on alkaline urine, 217

Benzoic acid in urine, 273

zethers, 280

Benzo-purpurin, 131

test for HCl, 131

test-papers, 132

Eee de test for sugar, 74, 76,
280

—— for diamines, 318

for carbo-hydrates, 280

Beri-beri, 192

Berlin-blue reaction, 302

Betain, 315

Betol, 343

Bettelheim’s granules, 36

Bidder and Schmidt's method for esti-
mating HCl, 133

Biedert’s boiling method, 107

Bilberries,amylic alcoholextract of, 132

Bile acids in blood, 75

— acids in feces, 200

—— acids in pus, 358

-—— acids in urine, 287

—— acids, tests for, 75, 288

LE eee a ae

 

 

 

 

 

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444

Bile pigment in blood, 76
—— pigment in cysts, 363
—— pigment in feces, 164, 204
— in pus, 358

— in semen, 367

pigment in urine, 288
— pigment, tests for, 288
Bilifuscin, 288

Biliprasin, 288

Bilirubin, 62, 76, 118, 241, 288, 363, 367
formula of, 62
Biliverdin in blood, 77

in feces, 165

—— in meconium, 206

— in sputum, 118

in urine, 288

-—— in vomit, 150

Biology of micro-organisms, 390
Bismarck-brown, 105
Biuret, 69

Biuret-test, 69, 257
Bizzozero’s chromo-cytometer, 14
Bladder, calculus of, 333
Bladder, catarrh of, 332
—-— epithelium of, 221

—— foreign bodies in, 250
tumours of, 233, 333
Blennorrhea, 220

Blood, the, 1

acetone in, 77

—— alkalinity of, 2, 5

—— animal parasites of, 49
—— bile substances in, 75
—- cellulose in, 74

— chemical changes in, 59
— colour of, 1

— colouring matter of, 59
-— crystals in, 30
estimation of sugar in, 72
—— fatty acids in, 74

—— fibrin of, 67

——. formed elements of, 6
— fungi of, 39

——— glycogen in, 74

—— hemoglobin of, 320

in anemia, 38

in carcinoma, 70

in chlorosis, 37

in dyspnea, 63

in feces, 168, 208

in fever, 78

in melanzmia, 35

—— in poisoning, 63

—— in pus, 348

—- in sputum, 122

—— in urine, 219

—— in vomit, 148

—— lactic acid i in, 74

——- organic acids of, 74
—— parasites of, 39

—- peptone of, 67

proteids of, 67

— protozoa in, 49

—— reaction of, 2

 

 

 

 

 

 

 

aan

 

 

INDEX.

Blood, sarcolactic acid in, 74

—— specific gravity of, 5

—— urea in, 68

uric acid in, 70

Blood-colouring matter, relation of, to
bile-pigment, 61

Blood-cells, see Blood-corpuscles and
Leucocytes

Blood-corpuscles, red, apparatus for
counting, 8

— changes in, 6

— counting of, 9

—— in buccal secretion, 79

—— in cysts, 362

—— in feces, 168

in pus, 348

in sputum, 94, 122

—— in transudations. 361

in urine, 219, 270

tests for, 271

Blood-pigment, 59

—— detection of changes in, 60

in faeces, 168, 205

—— in gastric juice, 148

Blood-platelets, 6

Blood-serum, lutein in, 59

— spectrum of, 59

—— sterilised, 380

Blue milk, 369

Bodo urinarius, 237

Bothriocephalus cordatus, 186

latus, 186

liguloides, 186

Bittger’s test, 277

B-oxy-butyric acid, 75, 336

tests for, 337

Brandberg’s method, 260

Braun's method for estimation of HCl,
136

maa in the nutrition of fungi, 383

Brieger’s method for separation of
ptomaines, 158

Bright on albuminuria, 252

Brilliant-green tests for HCl, 130

Bromide of potassium, detection of, in
urine, 243

of potassium, detection of, in
saliva, 83

Bromine salts in urine, 343

Bronchial asthma, 98

catarrh, 114

Bronchiectasis, 115

— sputum of, 112

Bronchitis, acute, 114

—— chronic, 115

—— plastic, 115

putrid, 115

Broth, nutrient, 333

Browning’s spectroscope, 59, 66

Buccal secretion, 79

secretion, chemical constitution
of, 81

—— secretion, ferment of, 80

— secretion, fungi of, 80, 85

 

 

 

 

 

 

 

 

 

 

 

 

 

Digitized by Microsoft®
INDEX.

Buccal secretion in disease, 82
— secretion, nitrites of, 82
— secretion, physical characters of,

— secretion, sulphocyanide of, 83
urea in, 83

Bujwid’s staining process, 176
Bumsen’s tables, 314

Butyric acid, detection of, 201

— acid in feces, 201

— acid in gastric juice, 129

— acid in sputum, 113
acid in urine, 305.
acids

 

 

See also Fatty

CADAVERIN, 160, 318

Calcium carbonate, crystals of, 197

— phosphate in fzeces, 197

— phosphate, crystals of, 197, 242

sulphate, crystals of, 197, 247

— sulphate in feces, 197

sulphate in urine, 242, 247

Calculus, 333

Calliphora erythrocephala, 195

Calomel, 212

Canada balsam, 105

Cancer, blood in, 74

of alimentary canal, 215

— of stomach, 148

—— urine of, 215

Capric acid, 202

Caproic acid in faces, 202

acid in sputum, 113

Carbohydrates in blood, 72

Carbol-fuchsin, 106

-gelatine, 179

Carbolic acid, estimation of, 299

— acid in feces, 202

—— acid in urine, 299, 341

—— acid in vomit, 161

—— acid poisoning, 161, 341

—— acid, tests for, 161, 342

— acid in feces, 200

acid in gastric juice, 142

— acid, tests for, 200

Carbolo-chloride of iron test for lactic
acid, 139

Carbonate of lime in faces, 197

of lime in sputum, 113

— of lime in urine, 253, 326

of magnesia in sputum, 113

Carbonates of the alkaline earths, 250

in sputum, 113

— of urine, 326

test for, 326

Carbonic oxide, detection of, 63

oxide hemoglobin, 63

— oxide hemoglobin, spectrum of,
63

 

 

 

 

 

 

 

 

 

 

 

oxide poisoning, 63, 273, 342
Carburetted hydrogen in feces, 205
Caries of teeth, 81

Casein in feces, 168

— in milk, 368

 

 

445

Casts, cellular, 225

— chemistry of, 232

—— classification of, 224

— “detritus,” 224

— examination of, 232

— fatty, 229

— granular, 227

—— hyaline, 230

— metamorphosed, 224

— of micrococci, 226

organised, 224

staining of, 232

unorganised, 224

urinary, 224

waxy, 228

Cat, round worm of, 189

Catarrh, bronchial, 114

—— gastric, 146

—— nasal, 91

vesical, 332

Catarrhal urethritis, 334

Caustic potash, poisoning with, see
Poisoning with alkalies

— soda, poisoning with, sce Poisoning
with alkalies

Cellulose in blood, 74

Cercomonads in feces, 181

—— in pus, 357

— in sputum, 109

in urine, 237

Cercomonas intestinalis, 181

Cerebral hemorrhage, urine in, 291

Cerebro-spinal fluid, 91

meningitis, 273

Certoneura stabulans, 195

Cestodes, 182

Charcot-Leyden crystals, 30, 99, 110,
195

Cheese-maggot, 195

—-— spirillum of, 177

Chemical examination of blood, 59

—— examination of buccal secretion,
81

—— examination of cystic fluids, 363

—— examination of feces, 198

— examination of gastric juice, 143

examination of milk, 369

examination of pus, 358

examination of semen, 367

examination of sputum, 113

examination of transudations, 362

examination of urine, 255

examination of vomit, 150

Chinanisol, 344

Chloral in urine, 273

Chlorate of potash in blood, 65

—— of potash, poisoning with, 65, 152

—— of potash, spectrum of, 65

Chloride of ammonium in urine, 320

—— of barium, 134

—— of gold test, 160

—— of magnesium in sputum, 114

—— of magnesium in urine, 320

—— of platinum test, 160

|

LT

 

 

 

|

LTT TTI

Digitized by Microsoft®
446

Chloride of potassium in urine, 320

— of sodium in blood, 78

— of sodium in feces, 204

—— of sodium in urine, 320

—— of zinc solution, 316

Chlorides, estimation of, 320

—— in feces, 204

—— in sputum, 114

in urine, 320

tests for, 320

‘Chloroform, poisoning with, 161, 341

— tests for, 161

Chlorophyll, 167

Chlorosis, blood changes in, 37

urine in, 217

Cholzemia, 75

Cholecyanin test, 289

Choleglobin, 62

Cholera, Asiatic, 209

—— Asiatic, bacillus of, 173

—— infantum, bacillus of, 165

—— nostras, bacillus of, 177

-red, 176

Cholesterin crystals, detection of, 111

—- crystals in feces, 203

—— crystals in pus, 357

—— crystals in sputum, III

—— crystals in urine, 249

-—— tests for, 203

Chololithiasis, 166

Choluria, 287

Chromocytometer, 14

Chromogens of urine, 214

Chromogens of urobilin, 214

Chromometer, 14

Chronic bronchitis, 115

—— enteritis, 207

—— gastritis, 146

— inflammation (non-tubercular) of
lung, 117

nephritis, 330

Chrysophanic acid, 345

Chyliform exudation, 360

Chyluria, 306

Ciliated epithelium in cysts, 363

—-~— epithelium in sputum, 93

Cladothrix, 352 g

Claret, colouring matter of, 132

Claude Bernard’s method, 73

Clostridium butyricum, 171

Coagulated albumin, 168

Coating of the tongue, 87

Coccidia in pus, 357

Coccidium perforans, 181

—— oviforme, 89

Coccus salivarius septicus, 81

Cochin-China diarrheea, 194

Coffin-lid crystals, see Triple phosphate

Colloid cysts, 362

Colour of blood, 1

— of exudations, 347

—— of feces, 164

—— of sputum, 93

—— of transudations, 361

 

 

 

 

 

 

INDEX.

Colour of urine, 214

— scale for urine, 214

—— tests for albumin, 257

Colouring matter of bile, 61, 204

—— matter of blood, 61

—— matter of faeces, 164

—— matter of urine, 214

Colostrum, 368

Comma-bacillus, 173

Compensation eye-piece, 373

Compound sulphuric acids, 297

Concretions of feeces, 166

—— of nasal secretion, 91

—— of urine, 247, 250

Condenser, Abbe’s, 372

Congo-red test for HCl, 131

— staining micro-organisms with,
384

Connective tissue in sputum, 100

tissue in stools, 167

-—— tissue in vomit, 145

Contracted kidney, 331

Copaiba balsam, 346

Copper, poisoning with salts of, 154,

 

339

Cornil’s marrow cells, 32

Corpora amylacea in sputum, IOI

Correction collars, 373

Cover-glasses, preparation of, 40, 105

Croton oil, 348

Croup, gastric, 150

Crystals, calcium carbonate, 197

—— calcium phosphate, 197, 242

— calcium sulphate, 197

— Charcot-Leyden, 30, 99, 110, 195

— cholesterin, 111, 195, 249, 357

— cystin, 243

-—— fatty, 111, 196, 357

— hippuric acid, 243

— hemin, 61 ;

—— hematoidin, 61, 110, 195, 241, 357

— hemoglobin, 38

—— in blood, 38

—— indigo, 248

—— in blood, 30

—— in feces, 195

—— in pus, 357

—— in sputum, 110

in urine, 240

— leucin and tyrosin, 112, 244

—— magnesium phosphate, 242, 249

—— margarine, 112

—— oxalate of lime, 113, 197

-—— phenyl-glucosazon, 276

—— Roussin’s, 157

—— spermatic, 367

—— sulphide of bismuth, 198

— Teichmann’s, 63

— triple phosphate, 113, 197, 242,
247, 358.

—— tyrosin, 112, 244

—— urate of ammonia, 249

—— uric acid, 240

—— xanthin, 244

 

Digitized by Microsoft®
INDEX.

Crystalline sediment of urine, 239

Cultivation, cylinder-, 387

by exclusion of air, 388

—— drop-, 388

in depth of nutrient substances,

387 :

on glass slides, 388

—— on surface of nutrient substances,
386

plate-, 385

Curschmamn’s spirals, 98

spirals, Zroup on, 98

Cupric oxide, reduction of, 274

Cutaneous inoculation, 389

Cyanotic induration of kidneys, 228

Cylinder-cultivations, 387

Cylindroids, 232

Cystic kidney, 363

Cystin, 243

Cystinuria, 308

Cystitis, 332

Cysts, colloid, 362

— contents of, 361

-—-- dermoid, 362

— hydatid, 362

—— of broad ligament, 363

ovarian, 362

Cytometer, 13

 

 

 

 

 

 

DAHLIA, acid solution of, 33
Dammar varnish, 41

D’ Arsonval's incubator, 387
Deneke’s spirillaum, 177

Deposit on teeth, 86
Dermatitis, urine in, 269
Dermoid cysts, 362

“Detritus ” casts, 244

Detritus in feeces, 169
Deutero-albumose, 268

Dextrin in faeces, 200

in urine, 287

Dextrose, see Grape-sugar
Diabetes, blood in, 74

—— insipidus, 337

-—— mellitus, 336

Diabetic acetonuria, 303
Diacetic acid, tests for, 305
Diaceturia, 304

Diamines in sputum, 115

in urine, 318

—— tests for, 318
Diaphragms, 372

Diastase, 205

in urine, 320

Diastatic ferment of cysts, 363, 364
—— ferment of faeces, 205
—— ferment of saliva, 82
ferment of urine, 320
Diathesis, uric acid, 308
Diazobenzol, 160
Diazobenzol-sulphonic acid, 328
Diazo reaction, Lhilich’s, 328
Dickinson on coating of tongue, 87
Differentiation of proteids in urine, 259

 

 

 

 

 

447

Digestion, stages of, 140

Digitalis, 212

Dilatation of stomach, 149

Dioxyquinin, 344

Diphtheria, bacillus of, 88

—— gastric, 150

Diplococci in ozzna, 91

in pneumonia, 120

—— in pus, 348

Dipteral larvee, 91, 195

Disseminated sarcoma, 265

Distoma eggs in blood, 58

eggs in urine, 237

—— hematobium, 57

— hematobium in blood, 57

— hematobium in sputum, 110

-—-— hematobium in urine, 237

—- hepaticum, 187

— lanceolatum, 187

— Rathonisi, 188

Dochmius duodenalis, 190

Double sulphate of iron and ammonia
solution, 321

Dragendorf’s test for bile-pigment, 289

Dreschfeld’s test for HCl, 133

Drop-cultivations, 388

of cholera-bacillus, 175

Drosophila melanogastra, 195

Drugs, effect of, on the stools, 164

Dry measurement, 38

Duodenal ulcer, 148

Dysentery, 208

Dyspepsia, acid in, 127

urine in, 335

Dyspneea, blood changes in, 63

 

 

 

 

EARTHY phosphates, 323

Echinococcus in sputum, 109

—— in urine, 238

— cysts in feces, 187

—— cysts in sputum, 109

— cysts in urine, 238

— hooklets from cysts, 362

—— hooklets in feces, 187

—— hooklets in gastric juice, 150

hooklets in urine, 238

Ehrlich’s granules, 31

staining method, 41

—— test for bilirubin, 290

test for typhoid urine, 328

Lhrlich-Weigert fluid, 41, 105

Eggs of helminthz in blood, 58

—-- of helminthe in feces, 192

—— of helminthe in sputum, 120

of helminth in urine, 237

Elastic fibres in feces, 163

fibres in gastric juice and vomit,
145

—— fibres in sputum, 94

Embolic lipzemia, 75

—— nephritis, 227

Emerald-green test for HC], 130

Emulsifying ferment, 144

Emphysema, urine in, 215

 

 

 

 

 

Digitized by Microsoft® -
448

Endocarditis, 47, 236
Enteritis, acute, 207

—— chronic, 207

—— membranacea, 165

—— mucosa, 165
Entero-colitis, monadines in, 180
Enterogenic peptonuria, 205
Entozoa in nose, 91

Eosin, 31

Eosinophil granules, 31
Epileptic urine, casts in, 231
urine, spermatozoa in, 233
Epithelium, alveolar, 95

—— ciliated, 95

—— in buccal secretion, 79

in exudations, 348

— in feces, 169

in gastric juice, 124

in nasal secretion, 91

in sputum, 95

in transudations, 361

in urine, 221

in vaginal secretion, 369
obsolete in feeces, 169

of male urethra, 222
renal, 223

vesical, 22

Eristalis arbustorum, 195
Erysipelas, streptococcus of, 47, 235
Erythro-dextrin, test for, 142
Esbach’s albuminimeter, 263
Esmarch’s cylinder-cultivations, 386
Eustrongylus gigas, 238
Ewald’s test for HCl, 129
Exogenic toxicosis, 319
Experimental albuminuria, 252
Exsiccator, 40

Exudations, 347

—— chylous, 349

—— hemorrhagic, 348

—— purulent, 347

—— putrid, 359

—— sero-purulent, 359

—— serous, 347

—— see also Pus

Eye-piece, 374

—— periscopic, 375

 

 

eee

 

FRCES, the, 164

— albumen in, 198

—— blood in, 168, 209

— chemistry of, 198

—— colour of, 164

colouring matters of, 204

— crystals of, 195

-—— detritus of, 169

—— fats in, 167

—- ferments in, 205

—— foreign bodies in, 167

— formed elements of, 168

—— fungi of, 170

—- hydatids in, 186

—— indiseases of the alimentary canal,
207

 

 

INDEX.

Feces, insects in, 195
microscopical characters of, 166
mucin in, 166, 198
naked-eye, characters of, 164
non-pathogenic fungi of, 169
parasites of, 169

pathogenic fungi of, 173
proteids of, 168, 198

—— ptomaines in, 205

—— quantity of, 164

— reaction of, 164

—— worms in, 182

Fat crystals, 112, 196

—— crystals in feces, 196

—— crystals in pus, 357

— crystals in sputum, 112

— crystals in vaginal secretion, 369
—- crystals in urine, 249

— crystals in vomit, 145

—— crystals, separation of, 112
Fat in blood, 75

—— in feces, 196, 203

—— in sputum, 112

— in urine, 247

Fatty acids in pus, 358

acids in urine, 305

— acids, non-volatile, of faeces, 203
——- acids of sputum, 113

— acids, tests for, 305

—— acids, volatile, of blood, 74
—— acids, volatile, of feces, 200
—— casts, 229

—— needles, sce Fat crystals
Favus of stomach, 150

Febrile acetonuria, 303

— albuminuria, 254

states, urine of, 328

urobilin, 290

Fehling’s fluid, 281

titration method, 280
Ferment, diastatic, 82, 144
emulsifying, 144

— of feces, 205

—— inverting, 144

—— milk-curdling, 126

 

LITT

 

 

 

 

 

of saliva, 82

of sputum, 114

of urine, 319

Fermentation test for sugar, 275

Ferments of feces, 205

— of gastric juice, 126

— of urine, 319

pancreatic, 144

Ferric salts in sputum, 114

Ferrocyanide solution, 325

Fibres, elastic, in feces, 167

elastic, in gastric juice and vomit,
145

—— elastic, in sputum, 97

Fibrin, estimation of, in blood, 68

—— estimation of, in exudations, 358

estimation of, in urine, 270

of blood, 68

Fibrinous coagula in sputum, 100

 

 

 

 

 

Digitized by Microsoft®
INDEX.

Fibrinous coagula in urine, 270

Fibrinuria, 270

Filaria inermis, 357

—— sanguinis hominis, 58, 238

Filarie in blood, 58

—— in pus, 356

—— in urine, 238

Finkler-Prior bacillus, 177

Fission-fungi of blood, 39

— of feces, 170

— of sputum, Io1

— of urine, 233

—— of vaginal secretion, 369

of vomit, 146

Fistula, secretions from, 365

Flagella, staining of, 379

Fluke, 57

Foreign bodies in faeces, 251

—— bodies in sputum, 95

bodies in urine, 251

Formic acid, detection of, 201

—— acid in blood, 74

-—— acid in feces, 201

—— acid in gastric juice, 132

—— acid in urine, 305

—— acid reaction in gastric juice, 132

Frinke’s pneumonia-coccus, 107

Fresenius and Babo’s test for lead, 152

Friedlinder’s method for staining fungi,
107

pheumonia-coccus, 108

Frohde’s reagent, 157

Fruit-sugar, 287

Fuchsin for staining micro-organisms,
40

 

 

 

 

test for HCl, 130

Fungi, in ozeena, 92

of blood, 39

—— of buccal secretion, 80

—— of faeces, 170

—— of nasal secretion, 91

—— of pus, 348

—— of serous exudation, 360

—— of sputum, Io1

—— of urine, 233

of vaginal secretion, 369

— of vomit, 146

spores of, 45, 354, 379-
Micro-organisms

Fungoid plugs, 103

Fiirbringer’s test, 258

Furfurol, 74, 76, 200, 280

test for bile acids, 200, 288

—— test for carbohydrates, 74, 280

— test for urea, 69

Fusiform degeneration, 169

 

 

See also

 

 

GABBETT’S staining method, 107
Gangrene of lung, 121
Gangrenous stools, 209

Gases in blood, 63

—— intestinal, 205

—— of urine, 328

Gastric croup, 150

 

449

Gastric diphtheria, 150

Gastric juice, acetic acid in, 139

—— juice, acidity of, 127

—— juice, acids of, 127

—— juice, ammonia salts in, 141

—— juice and vomit, 124

—— juice, butyric acid in, 139

—— juice, carbohydrates in, 142

juice, chemical examination of,
143

—— juice, chemistry of, 125

juice, excessive secretion of, 127

-—— juice, formed elements of, 124

juice, hyperacidity of, 127

—— juice, lactic acid in, 139

juice, method of obtaining, 124

—— juice, milk-curdling ferment of,
126

— juice, naked-eye characters of,
124

—— juice, organic acids of, 139

——- juice, pepsin of, 126

—— juice, proteids of, 140

—— juice, urea in, 141

juice, zymogen of, 127

Gastric sound, 124

ulcer, 147

Gastritis, acute, 146

atrophic, 147

—— chronic, 146

Gelatine, nutrient, 383

Genital organs, secretions of, 366

Gentian-violet, 104

aniline-water solution, 105

Giacomi’s method for staining micro-
organisms, 350

Giant-corpuscles, 348

Gibbes’ staining method, 107

Glanders, bacillus of, 46

bacillus of, in blood, 46

bacillus of, in pus, 353

bacillus of, in urine, 236

Globulin in pus, 358

in semen, 367

—— in urine, 270

—— test for, 270

Globulinuria, 270

Glycerine in urine, 274

Glycogen in blood, 74

in exudations, 367

—— in sputum, 114

— in pus, 358

Glycogenic reaction, 221

Glycosuria, 273

— pathological, 273

—— persistent, 273

—— physiological, 273

—— transitory, 273

Glycuronic acid phenomenon, 344

Gmelin’s test, 289

Goblet-cells in feeces, 169

Gonococci, 334

Gonorrheeal urethritis, 334

Gout, blood in, 70

 

 

 

 

 

 

 

 

 

 

 

 

 

2p

Digitized by Microsoft®
450

Gout, urine in, 311

Gowers’ hemacytometer, 13

Griiber’s solution, 8

Gram and Grdber’s theory of micro-
cytes, 35

Gram’s staining method, 41

Granular casts, 227

Granules in colourless blood-corpuscles,

I

Goape sugar. tests for, see Sugar

Grass-green sputum, 118

Green stools, 164

Guanidin carbonate, 202

Guanimin of isobutyric acid, 202

Guanin in pus, 358

Giinther’s staining method, 45

Gunzburg’s reagent, 131

HMACYTOMETER, 13

Hemameceba malaric, 49

Hematemesis, 148

Hematin, formula of, 62

—— in vomit, 148

—— reduced, 60

spectrum of, 60

Hematogenic albuminuria, 254

—— jaundice, 288

—— peptonuria, 265

Hematoidin, amorphous, 61, 241

—— crystals, 61, 110, 195, 241, 357

Hematomonas malarie stellata, 51

Hematophyllum malariz, 49

Heemato-porphyrin, 61, 293

Hemato-porphyrinuria, 293

Hematoscope, 21

Hematospectroscope, 23

Hematoxylin solution, 232

Heematozoa, 49

Hematuria, 270

-—— intermittent, 220

Heemin-crystals, 61.
crystals

Hemoglobin, amount of, 20

—— changes in, I

proteid of, 60

— reduced, 60

rhombic crystals of, 38

-—— spectrum of, 60

Heemoglobinzemia, 65

Hemoglobinuria, 65, 271

—— paroxysmal, 271

Hemometer, 19

Hemoptysis, 122

Hemorrhagic exudation, 359

— infarction of lung, 123

—— sputum, 122

—- stools, 209

Hairs in urine, 251

Halliburton’s test for globulin, 270

Hay-bacillus, 179

Haycraft’s method of estimating urea, 69

Haycraft and Williamson’s test for alka-
linity of blood, 3

Hayem’s solution, 6

 

See Teichmann’s

 

 

 

INDEX.

Heat-apoplexy, 209

Hedge-hog crystals, 249

Hedin’s heematocrite, 25

Heller's test, 257, 271

Helminthiasis, 182

Hemialbumose, 269

Hen-cholera, bacillus of, 378

Hénocque’s double spectroscope, 23

formula, 24

—— hematoscope, 21

—— hemato-spectroscope, 23

Hepatic diseases, faeces in, 210

diseases, urine in, 335

Hepatogenic jaundice, 283

Hering’s lensless spectroscope, 66

Hexahydro-hematoporphyrin, 61

Heynsius’ test, 257

Hindenlany’s test, 257

Hippuric acid, 243

Hofmann’s method for estimating HCl,
136

Hofmeister’s test for peptone, 266

Homogeneous immersion lens, 373

Homogentisic acid, 300

Homolomyia, 195

Hufner's apparatus, 312

Hunter on pernicious anemia, 290

Huppert’s test for bile-pigments, 76,
289

Hyaline casts, 230

Hydatid cysts, 362

Hydatids in feces, 186

— in sputum, 109

—— in urine, 238

Hydremia, 67

Hydriodic acid, 123

Hydrobilirubin in feces, 165

Hydrochinon, 300

Hydrochloride of phenyl-hydrazin, 72,

 

 

274

Hydrochloric acid, benzo-purpurin test
for, 131

acid, bilberries, test for, 132

—— acid, Congo-red test for, 131

— acid, detection of, 129

— acid, Dreschfeld’s test for, 133

—— acid, emerald-green test for, 130

— acid, estimation of, 133

— acid, Mwald’s test for, 129

— acid, fuchsin test for, 129

— acid, in cancer of stomach, 148

—— acid, in gastric juice, 129

— acid, methy]-aniline-violet test for,
129

— acid, Mohr’s test for, 129

— acid, oo-tropzolin test for, 130

acid, phloro-glucin and vanillin
test for, 131

—— acid, Uffelmann’s tests for, 132

— acid, ultramarine and zinc sul-
phide test for, 133

Hydrocyanic acid poisoning, 64, 162

Hydronephrosis, 363

Hydroparacumaric acid, 300

 

 

Digitized by Microsoft®
INDEX.

Hydrophobia, micro-organism of, 48
Hydrothza meteorica, 195
Hydrothionzemia, 64 :
Hydrothionuria, 327

Hyperacidity of gastric juice, 127
Hypersecretion of gastric juice, 127
Hypoazoturia, 311

Hypopyon, 348

Hyposulphites of urine, 323
Hyposulphurous acid in urine, 327
Hypoxanthin, 315, 317

Hysteria, 255

IDIOPATHIC bacteriuria, 235

oxaluria, 307

Incubator, 388

Indican, 294

estimation of, 295

—— tests for, 295

Indicanuria, 293

Indigo, 248, 293

— -blue, 293

-carmine test-paper, 278

crystals of, 248

Indigotin, 293

Indirubin, 296

Indol in feces, 202

in urine, 302

Indoxyl-sulphate, 248

-sulphuric acid, 293

Indulin, 40

Infarction, heemorrhagic, of lung, 123

Infectious diseases, blood in, 39

diseases, urine in, 328

Inflammation, non-tubercular, of Jung,
117

Influenza, bacillus of, 356

Infusoria in fieces, 181

——- in pus, 357

in sputum, 109

in urine, 237

in vaginal secretion, 370

Inoculation with micro-organisms, 3&9

Inorganic substances in blood, 78

—— substances in feces, 205

substances in semen, 367

substances in sputum, 114

substances in urine, 320

Inosite in cysts, 362

test for, 301

Inosituria, 301

Insects in feeces, 195

Intermittent albuminuria, 252, 255

hematuria, 220

Intestinal catarrh, 207

gases, 205

juice, 143

—— putrefaction, 293

ulcer, 269

Intestines, the, diseases of, 207

tuberculosis of, 208

Invertin, 205

Todates, 343

Iodide of bismuth and potash test, 160

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

451

Iodine in urine, 343

-— test for, 343

Todo-ammonic-iodide, 151

Todoform in urine, 343

— test for, 343

Iodo-potassic-iodide test for micro-
organisms, 171

Iris diaphragm, 377

Tron, salts of, in sputum, 114

Iso-butyric acid, 202

Iso-cyan-phenyl test, 162

JACQUEMIN’S test for nitrobenzol, 162
Jaffe’s test for indican, 295

for kreatin, 316

Jaundice, 77, 210

— casts in, 224

hematogenic, 288

Jaundice, hepatogenic, 288

inogenic, 288

urine of, 214, 231, 335

urobilin, 291

Johnson’s picric acid test for sugar, 278

 

 

 

 

 

KAIRIN in urine, 215, 344

—— potassium sulphate, 344

Kidney, amyloid, 331

—— caseation of, 237

—— contracted, 331

— cyanotic induration of, 228

—— cystic, 363

— epithelium of, 223

—— large white, 230

small red, 331

Klebs and Vommasi-Crudeli’s bacillus of
malaria, 49

Klemperer on thrush fungus, 86

Knife-rest crystals, see Triple phosphate

Koch and Lhrlich’s staining methods,
104

Koch’s pure cultivations, 384

Kreatin, 315

Kreatinin, 315

Kreatinin-zine chloride, 316

Kiihne’s staining methods, 378

 

Lactic acid bacillus, 206

acid, detection of, 337

— acid fermentation, 146

— acid in blood, 75

— acid in gastric juice, 139

— acid reaction in gastric juice, 139
— acid, tests for, 337

Lactosuria, 287

Levulosuria, 287

Landois’ test for reaction of blood, 2
Larve, dipteral, 91, 195

Lassar’s test for reaction of blood, 2
Latent disseminated sarcoma, 265
Laverania malarie, 49

Lead colic, 338

Lead, poisoning with salts of, 152, 338
Lecithin corpuscles, 366

Legal’s test for acetone, 304

 

Digitized by Microsoft®
452

Lensless spectroscope, 66

Leo’s method for estimation of HCl, 134

Leprosy, bacillus of, 355

Leptothrix buccalis, 80, 103

buccalis in sputum, 103

Leube and Salkowski's titration process,
280

Leucin in sputum, 113

—— in urine, 244

tests for, 245

Leucocytes in blood, 28

-—— in exudations, 348

—— in feces, 169

—— in semen, 366

in sputum, 94

—— in urine, 220

in uterine secretion, 370

in vomit, 144

Leucocytosis, 28

Leucohypobilin, 210

Leucomaines, sce Ptomaines

Leucourobilin, 210

Leukemia, 29

crystals, 30

—— lymphatico-splenic, 30

—— myelogenic, 29

—- splenic, 30

Lichtheim’s plate, 385

Lieben’s test for acetone, 303

Lipacidzemia, 74

Lipaciduria, 305

Lipemia, 75

Lippich’s polarimeter, 284

Lipuria, 306

Litmus, extract of, 353

Liver, acute yellow atrophy of, 241

—— diseases of, feeces in, 210

diseases of, urine in, 385

Lochia, the, 370

Lifler’s staining process, 41

Lowenberg’s diplococcus, 91

Lucilia cesar, 195

—— regina, 195

Inudwig’s filter, 309

process, 308

Lumniczer’s bacillus, 115

Lung, sce Pulmonary

Lustgarten’s bacillus, 349

Lutein, spectrum of, 66

Lymphatico-splenic leukemia, 30

 

 

 

 

 

 

 

 

Macxay’s test for bile-acids, 76, 288
Macwilliam’s test for peptone, 268
Magenta solution, 107

Magnesia mixture, 308

soaps of, in feces, 196
Magnesium phosphate, 242
Maguire on globulin in urine, 270
Malaria, micro-organisms in, 49
Maltose in urine, 287

Maly’s test for HCl, 130
Mammary secretion, 368
Margarine needles in sputum, 112
Martin, 8., on peptonuria, 268

 

 

INDEX.

Marrow-cells, 32

Mason’s lung, 123

“ Mastzellen,” 33

Measles, urine test for, 328
Measurement of urine, 211
Meconic acid, 82
Meconium, 206
Megaloblasts, 35
Megastoma entericum, 181
Melanemia, 35

Melanin, 301

—— tests for, 302
Melanogen, 302
Melanuria, 301
Melithemia, 72
Menstruation, 370
Mercury, poisoning with salts of, 153,

 

9
3 tests for, 154, 339
Metadiamidobenzol, 327
Metalbumin in cysts, 363

—— test for, 363
Metallic poisons, 152
Metamorphosed casts, 224
Metaphosphoric acid test for albumin,

257

Metatungstic acid, 160
Methemoglobin in blood, 62

—— in urine, 272
spectrum of, 62
Methan, 251
Methyl-aniline-violet test for HCl, 129
-— for staining fungi, 41
Methylene blue, 41
Methyl-violet, 104
Microbes in pneumonic sputum, 119
Micrococci in buccal secretion, 80
—— in nasal secretion, 91

-— in pus, 348

—~— in urine, 233
see also Fungi

Micrococcus chlorinus, 119

— de la rage, 80

—— erysipelatos, 47

— gonorrhoicus, 334

— of sputum-septicemia, 80

-—— prodigiosus, 369

—— tetragenus, 81

—— uree, 234

Microcytes, 35
Microcythemia, 3

Micro-organisms, cultivation of, 379
detection of, 372

—— examination of blood for, 40
— in hydrophobia,. 48

-— in malaria, 49
—— in scarlatina, 47

—— in small-pox, 48

—— methods of staining, 40, 103
— of feces, 170

 

 

 

 

of milk, 369

of mouth, 80

of nasal secretion, 91
of pus, 348

Digitized by Microsoft®
INDEX.

Micro-organisms of urine, 233

— of vaginal secretion, 369

—— of vomit, 146

—— spores of, 45, 354, 355

—— transmission of, to animals, 389
see also Fungi

Microscope, the, 372

Microscopical examination of the blood,

 

examination of cystic fluids, 361

examination of exudations, 348

examination of the buccal fluids, 79

examination of the feces, 166

examination of the gastric con-
tents, 124

—— examination of the nasal secretion,

LT |

 

— examination of the semen, 366

—- examination of the sputum, 94

— examination of the urine, 217

— examination of the vomit, 144

—— examination of transudations, 361

— examination of vaginal secretion,
369

Miliary tuberculosis of lung, 116

tuberculosis of urinary organs, 333

Milk, the, 368

—— -curdling ferment in gastric juice,
126

—— -curdling ferment in urine, 320

-sugar, 287

Millon’s reagent, 202, 258

Mohr’s estimation of chlorides, 320

tests for HCl, 129

Milisch’s sugar reactions, 279

Molybdate of soda, 156

Monadines in feces, 180

in sputum, 109

Monads in feces, 181

in sputum, 109

Monilia candida, 86

Monohydroxyl-benzol derivatives, 258

Moore’s test for sugar, 274

Mordants in staining micro-organisms,
33, 379. .

Morphia in urine, 340

poisoning, 156, 340

tests for, 156

Mott on pernicious anzemia, 290

Mould fungi of blood, 39

fungi of feces, 170

— fungi of gastric juice ani vomit,
146

— fungi of mouth, 80

fungi of nose, 90

—— fungi of sputum, 102

fungi of urine, 233

—— fungi of vaginal secretion, 370

fungi of vomit, 146

Mucin in feces, 198

in nasal secretion, go

—— in saliva, 81

— in sputum, 118

— in urine, 272

 

 

 

 

 

 

 

 

 

 

 

 

 

453

; Mucin, tests for, 272
Mucinuria, 272

Mulder’s test, 278 S
Murexide test, 71

Muscle fibres in feces, 167

—— fibres in vomit, 145

Myelin droplets, 94, 110

Myelogenic leukemia, 29

NAPHTHALINE in urine, 346

Naphthalol, 343

Naphthol-poisoning, 271

Nasal catarrh, 91

—— secretion, 90

— secretion, cerebro-spinal fluidin, 91

—— secretion, characters of, 90

—— secretion, Charcot- -Leyden guide
in, 91

—— secretion, concretions in, 91

—— secretion in disease, go

—— secretion, micro-organisms of, oe

— secretion, pus in, 91 :

Nematodes, 188

Nephritis, 329

—— acute, 329

— chronic, 330

—— embolic, 227

gravidarum, 241

—— sp. gr. of urine in, 213

—- toxic, 338

Nephrolithiasis, 250

Neubauer’s method, 307, 316

Neuralgia, saliva in, 80

Neutral phosphate of lime in feces,
197

—- phosphate of lime in urine, 242

——- phosphates, 323

Neutrophil granules, 33

Nitrate of silver solution, 321

Nitrates in urine, 326

Nicotin, poisoning with, 157, 341

Nitric acid, poisoning with, 151

acid test for albumin, 255

Nitrites in the blood, 65

in the saliva, 82

——- in the urine, 326

-—— tests for, 326

Nitrobenzol, poisoning with, 65, 162,
342

—— tests for, 162, 342

Nitrogen, estimation of, in urine, 315

Nitro-prusside test, 162

of sodium as a test for acetone,
393

— of sodium as a test for melanuria,
302

Normal acid solution, 3

salt solution, 10

— soda solution, 13

—- urobilin, 290

Non-pathogenic fungi of blood, 39

—— fungi of feces, 170

—— fungi of gastric juice and vomit,
145

 

 

 

 

 

Digitized by Microsoft®
454 INDEX.

Non-pathogenic fungi of pus, 348
—- fungi of sputum, 103

— fungi of urine, 233

—— fungi of vaginal secretion, 370
Nose, secretion from, 90
Nose-piece of microscope, 377 -
Nosotoxicosis, 319

Nuclein, 358

—— in milk, 368

—— in pus, 358

— in semen, 367

—— in sputum, 113
Nucleo-albumin. See Mucin
Nutrient agar-agar, 383

— blood serum, 383

fluids, 382

— fluids, sterilisation of, 380
gelatine, 383

— gluten, 384

— milk peptone, 354

— potato, 384

— starch, 384

— substances, 381

substances, stained, 384
substances, sterilisation of, 380
Nylander’s test for sugar, 277

 

 

 

 

OBERMAYER’S test for indican, 295
Objectives, 373

—— apochromatic, 374
Gidema, pulmonary, 122
Oidium albicans, 84
Oil-immersion lens, 373

Oil of cloves, 41

Oleic acid, 202
Oligochromzmia, 8
Oligocythzemia, 7

Oliguria, 212

Omichol, 317

Optimum temperature, 387
‘Orchitis, 367

Organic acids of blood, 74

— acids of freces, 202

-—— acids of gastric juice, 139
— acids of sputum, 113

—— acids of urine, 305

salts of lime in faces, 198
Organised sediment of urine, 219
casts in, 224
Osteomalacia, 78

Ovarian cysts, 362

Oxalate of lime, amorphous, 247
crystals of, 113, 197, 240
Oxalic acid diathesis, 306

acid, estimation of, 307
— acid in urine, 241, 306
— acid, poisoning with, 151
Oxaluria, 306

—- idiopathic, 307

— vicarious, 307

Oxyacids, aromatic, 300
Oxyamygdalic acid, 300
Oxyhemoglobin, spectrum of, 60
reduction of, 25

 

 

 

 

 

 

Oxyuris vermicularis, 190
Ozena, 91
Ozone, 328

P-AMIDO-dimethyl-aniline, 327
Pacini’s solution, 9

Palmitic acid, 202

Pancreatic cysts, 364
Paraamido-phenol-sulphuric acid, 342
Parakresol, 297
Parakresol-eether-sulphuric acid, 297
Paralbumin, 363

Paramcecium coli, 182

Parasites of blood, 39

— of buccal secretion, 80

— of feces, 169

—— of gastric juice and vomit, 146
— of malaria, 49

—— of milk, 369

—— of nasal secretion, 91

-—— of pus, 343

—- of sputum, 101

—— of urine, 233

-—— of vaginal secretion, 369
Parasite affections of stomach, 150
Paroxyphenyl-acetic acid, 300

— -propionic acid, 300

Paroxysmal albuminuria, 252
hemoglobinuria, 272

Pathogenic fungi of blood, 39 a
fungi of buccal secretion, 80, 84 -
—— fungi of feces. 173

—— fungi of gastric contents, 146
—— fungi of milk, 369

—- fungi of nose, 91

—— fungi of pus, 349

—— fungi of sputum, Io1

—— fungi of urine, 234

—— fungi of uterine secretion, 370
Pathological albuminuria, 253
acetonuria, 303

—— glycosuria, 273

——- urobilin, 290

Pavy’s fluid, 275

Pavy’s method for estimating sugar, 73
Pentamethylene-diamine, 115, 160, 318
Penzoldt’s test, 279

Pepsin, detection of, 126 ar
estimation of, 126

—— in gastric juice, 126

— in urine, 319

—— in vomit, 149

Peptone in blood, 67

—— in feces, 199

—— in gastric juice, 140

—— in pus, 358

-—— in sputum, 113

— in urine, 264

tests for, 266

Peptonuria, 264

——- enterogenic, 265

— hematogenic, 265

—— puerperal, 265

—— pyogenic, 264

 

 

 

 

 

Digitized by Microsoft®
INDEX.

Peptonuria, syphilitic, 266

Periscopic eye-piece, 375

Peritonitis, 200

Pernicious anemia, 38

urine in, 215

Peroxide of hydrogen in urine, 32%

Persistent glycosuria, 274

Pettenkofer’s test, 76

Phantom corpuscles, 219

Pharyngomycosis leptothricia, 89

Phenacetin, 345

Phenol in feces, 202

—— in urine, 297

tests for, 202

—— -ether-sulphuric acid, 297

Phenols, estimation of, 299

Phenyl-glucosazon, 72, 276

—— -hydrazin chloride, 72, 276

-lactosazon, 287

Phlegmon, 347

Phloro-glucin, 131

Phloxin-red, 178

Phosphates, estimation of, 324

in feces, 197

in sputum, 114

in urine, 242, 249, 323

tests for, 324

Phosphatic sediment, 239, 249

Phosphomolybdic acid test, 160

Phosphoric acid, estimation of, 324

Phosphorus poisoning, 155, 340

Phospho-tungstic acid, preparation of,
159

acid test, 160

Phthisis, urine of, 215, 329

Physiological acetonuria, 303

albuminuria, 329

glycosuria, 273

Picrate of indol, 302

Picric acid test for albumin, 258

acid test for sugar, 277

Picro-carmine, 232

Pilimictio, 251

Pilocarpin, 83

Pimaric acid, 256

Pinic acid, 256

Piophila casei, 195

Plasma of blood, 1

Plasmodium malariz, 49

Plastic bronchitis, 115

Plate cultivations, 385

Platinum chloride test, 160

Platodes, 182

Plehn’s solution, 57

Pneumaturia, 251

Pneumoconiosis, 123

Pneumonia, 118

—— fibrinous coagula in, 100

--— micro-organisms of. 107, 118

sputum of, 107, 118

Pneumonia-coccus, detection of, 108

—— of Friinkel, 108, 120

~— of Friedldnder, 107, 120

Poikilocytes, 31, 36

 

 

 

 

 

 

 

 

 

 

 

 

 

455

Poikilocytosis, 31, 36

Poison elaborated by cholera bacillus,
176

Poisoning with acids, 150, 338

with alkalies, 152, 338

— with alkaloids, 156, 340

— with aniline, 342

with carbolic acid, 161, 341

—— with carbonic oxide, 63, 273, 342

— with chlorate of potash, 65, 152

— with chloroform, 161, 341

-—- with ethylic alcohol, 161, 341

— with hydrocyanic acid, 64, 162

—— with metals and metalloids, 152,

a

33

 

 

 

with nitro-benzol, 65, 342

—-— with nitrous oxide, 65

—— with ptomaines, 158

— with sulphuretted hydrogen, 64

Polarimeter, 284

Polarisation, 284

Pollenia rudis, 195

Polymitus malarie, 50

Polyuria, 212

Potato, sterilised, 380, 384

Prava? syringe, 389

Preparation of cover-glasses, 40, 105

Propeptone in gastric juice, 141

—— in semen, 269

—— in urine, 269

tests for, 269

Propionic acid, 202

Prostatic fluid, 366

Proteids formed in gastric digestion,
141

—— of blood, 67

— of buccal secretion, 83

—— of cystic fluids, 363

-— of feces, 168, 198

— of gastric juice, 140

—— of pus, 358

—— of sputum, 113

—— of transudations, 361

—— of urine, 251

—— tests for, 141

Proto-albumose, 268

Protozoa of blood in small-pox, 57

—— in malaria, 49

— of feces, 180

—— of pus, 357

of sputum, 109

Prune-juice sputum, 118

Prussic acid poisoning, 64, 162

acid, tests for, 162

Pseudo-diphtheria bacillus, 89

Psorospermia, 181

Ptomaines, detection of, 159

—— in blood, 77

—— in feces, 205

—— in gastric juice, 158

—— in urine, 317, 341

—— poisoning with, 158, 341.

-— tests for, 159

Ptomato-atropin, 160

 

 

 

Digitized by Microsoft®
456

Ptyalism, 81

Puerperal fever, 47

peptonuria, 265

Pulmonary affections, sputum in, 114

—— abscess, 121

—— gangrene, 121

—- edema, 122

Pure cultivations, preparation of, 384

Purulent exudations, chemical exami-
nation of, 358

—— exudations, crystals in, 358

exudations, fungi of, 348

exudations, naked-eye characters

347

characters of, 347

chemistry of, 358

crystals of, 358

fungi of, 348

in feces, 169

in nasal secretion, 91

in sputum, 94

in stomach, 150

in urine, 221

Vitali’s test for, 221

Putrefaction bases, 317

Putrescin, 160, 318

Putrid bronchitis, 115

-— exudation, 359

Pycnometer, 212

Pyelitis calculosa, 332

Pyelo-nephritis, casts in, 22

Pyogenic peptonuria, 264

Pyrocatechin, 299

separation of, 300

—— tests for, 300

Pyuria, 221

 

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us,

Las)
Fb

 

eae!

 

QUARTAN ague, parasite of, 53
Quincke’s inogenic jaundice, 288
Quinine in urine, 215, 344
Quinone-tyrosin reaction, 245

REACTION of blood, 2

of feces, 164

of gastric juice, 127

of pus, 347

of sputum, 93

of urine, 216
blood-corpuscles, see Blood-cor-
puscles
Reduced hematin, 60
— hemoglobin, 60
— hemoglobin, spectrum of, 60
Reducin, 317
Reichert’s lenses, 373
Relapsing fever, spirillum of, 44
Renal albuminuria, 253
—- casts, 224
—— colic, 247

—— epithelium, 223
Resorcin in urine, 214
Retention-toxicosis, 318
Reynolds’ test for acetone, 304
Rhabditis genitalis, 238

ELE

Red

 

INDEX.

Rhabdonema strongyloides, 194

Rheumatic arthritis, urine in, 311

Rhinoliths, 91

Rhizopoda, 180

Rhubarb in urine, 214

Ribbert’s small red kidney, 331

Rice-water stools, 209

Richet’s method for estimation of HCl,
133

Rickets, 78

Roberts’ fermentation process, 282

method of estimating albumen,
260

—— test for serum-globulin, 270

Rochelle salts, 281

Rosanilin hydrochloride, 107

Rosenbach’s test for bile pigments, 289

Round worms, 188

Roussin’s crystals, 157

Rubner’s test for sugar, 278

 

SACCHAROMYCES cerevisie, 145

—— ellipsoideus, 170

Saccharomycetes, 170

Safranin, 232

Sago-grain forms in feces, 166

Sahli’s test for pepsin, 319

Salicylates in urine, 343

Salicyl-sulphonic acid test, 258

Saliva, chemistry of, 81

fungi of, 80, 85

in disease, 82

microscopical appearances of, 80

naked-eye characters of, 79

sec also Buccal secretion

Salivary corpuscles, 79

Salkowski’s colorimetric process, 296

Salol, 343

Salts of the blood, 77

Santonin, 346

Sarcina of urine, 234

—— pulmonis, 103

—- variegata, 103

—— ventriculi, 146

Sarcolactic acid in blood, 75

acid in urine, 338

Sarcophaga hematodes, 195

——- hemorrhoidalis, 195

Sarkin, 315

Scarlatina, nephritis in, 223

—— streptococcus of, 45

Skatol, 202

Scheme of a bacteriological investiga-
tion, 390

Scherer’s test for phosphorus, 155

Schottelius’ method of cultivation, 175

Schreiner’s base, 366

Scolices, 362

Scurvy, urine in, 217, 290

Searchers, 377

Sediment, urinary, 219

Sedimentator, 218

Seegen’s method for estimating grape-
sugar, 73

 

 

 

Digitized by Microsoft®
INDEX.

Semen, chemistry of, 367

—— physical characters of, 366

Senna in urine, 215

Sepsis occulta, 264

Septicemia of mouse, bacillus of, 171,
356

—— milk in, 368

—— urine in, 236

Seropurulent exudation, 358

Serous exudation, 359

Serum-albumin in pus, 358

-albuminuria, 253

— -globulin in urine, 270

—— -globulin, Roberts’ test for, 271

—- in semen, 367

in sputum, 113

in urine, 253

tests for, 255

Siderosis pulmonum, 123

Silicates in sputum, 114

Simple sulphuric acid, 323

estimation of, 323

Sjoqvist’s method for
HCl, 134

Skatoxyl, 296

sulphuric acid, 296

Small-pox, protozoa in, 57

Smegma bacillus, 334

Soaps of lime and magnesia, 246

Soda solution, normal, 13

Sodium pyrophosphate, 325

Spasmotoxin, 48

Spectra, 59

Specific gravity of the blood, 5

gravity of the blood, estimation
of,

Saeedeape: Browning's, 59, 66

— double, 23, note.

lensless, 66

Spermatic crystals, 367

Spermatozoa, 233, 366

Spirals, 98

Spirillum of cheese, 177

of relapsing fever, 44, 236

of relapsing fever, spores of, 45

Spirochete buccalis, 80

— dentium, 80

Spores, preparation of, 354, 355

staining of, 45, 379

Sporozoa in feces, 181

Sputum, the, 93

— alveolar epithelium in, 94

— bacteria in, 102

— blood in, 94, 122

—— chemical examination of, 113

— colour of, due to micro-organisms,
II

ene rrcctive tissue in, 100

erystals in, 112

diamines in, 115

—— elastic fibres in, 97

— fatty acids in, 113

—— ferment in, 114

—— fibrinous coagula in, 100

 

 

 

 

 

estimation of

 

 

 

 

 

 

 

 

457

Sputum, glycogen in, 114

in disease, 114

inorganic constituents of, 114

microscopical examination of, 94

naked-eye characters of, 93

parasites of, 1or

—— proteids of, 113

quantity of, 93

reaction of, 93

specific gravity of, 93

spirals in, 98

stratification of, 93

Staining fluids, preparation of, 105

of micro-organisms, Biedert’s me-
thod, 107

— Ehrlich’s method, 105

—- Gabbet’?s method, 107

Giacomi’s method, 350

—— Gibbes’ method, 107

— Gram’s method, 41

——— Giinther’s method, 45

—— Friedldnder’s method, 107

— Koch's method, 104

— Liffler’s method, 41

— Lustgarten’s method, 349

 

 

 

 

| —— Toison’s method, 12

— Wedl’s method, 352

—— Weigert’s method, 352

with aniline dyes, 41, 104
Staphylococcus pyogenes albus, 81

 

| —— pyogenes aureus, 81, 348
| —— pyogenes citreus, 81

 

pyogenes in milk, 368
Starch as a nutrient substance, 384
digestion of, 142

granules in feces, 167
——- in feces, 167

—— in gastric juice, 142

-— in urine, 250

Starvation, indican in, 293
Stas-Olto method, 156

Stearic acid, 202

Stenbeck’s sedimentator, 218
Stercobilin, 165

Sterilisation, methods of, 379
Sterilised blood-serum, 380
blotting-paper, 386

— nutrient substances, 380
— test-tubes, 380

Steriliser, 380

steam, 381

Stewart, Grainger, on albuminuria, 251
Stomach, atrophy of, 147

— cancer of, 148

contractile activity of, 142
dilatation of, 149

mucous catarrh of, 147
rate of absorption in, 142
Stomatitis, 84

Stratified sputum, 93
Streptococci, 47, 235
Streptococcus erysipelatos, 47, 235
— of scarlatina, 48

— pyogenes, 47, 235, 349

 

 

 

 

Digitized by Microsoft®
458

Strongylides, 190

Strongylus duodenalis, 1go0

Stutz capsules, 258

Succinic acid, 362

Sugar, fruit, see Levulose

grape, estimation of, 230

grape, estimation of, by fermenta-

tion, 282

grape, estimation of, by polarisa-

tion, 283

grape, estimation of, by titration,

280

grape, estimation of, Claude Ber-

nard’s method, 73

grape, estimation of,

method, 73

grape, in blood, 72

grape, in exudations, 358

-—— grape, in urine, 273

—— grape, tests for, 274

—— milk, 287

Sulphanilic acid test, 328

Sulphates of sputum, 114

of urine, 323 :

Sulphide of bismuth crystals, 198

of sodium solution, 309

Sulphocyanide of ammonium solution,
321

— of saliva, 83

of urine, 322

Sulphur in urine, 323

Sulphuretted hydrogen in blood, 64

— hydrogen in feces, 205

—— hydrogen in urine, 327

—— hydrogen poisoning, 64

hydrogen, tests for, 327

Sulphuric acid, compound, 297

— acid, poisoning with, 150

— acid, simple, 323

Syntonin in gastric juice, 141

Syphilis, bacillus of, 349

— hemoglobinuria in, 271

—— of liver, 334

peptonuria in, 266

 

 

 

 

 

Seegen’s

 

 

 

 

 

 

 

 

TANIA cucumerina, 185
— elliptica, 185

-—— flavopunctata, 185

—— leptocephala, 185

——- madagascariensis, 185
—- mediocanellata, 182
—— nana, 184

saginata, 182

— solium, 183

Tannin in urine, 346

test for ptomaines, 160
Tanret’s reagent, 257
Tartrate of potassium and sodium, 281
Taurocholate of soda, 84
Teat-worm, 190

Teeth, deposit on, 86
Teichmann’s crystals, 61

test, 61 :
Tertian ague, parasites of, 51

 

 

 

 

INDEX. mm

Testicle-cells, 366

Test-meal, 140

Test-tube cultivation, 387

Test-tubes, sterilised, 380

Tetanin, 48

Tetanotoxin, 48

Tetanus, bacillus of, 355

Tetramethylene-diamine, 160, 318

Tetramethyl-paraphenyl-diamine, 134

Tetra-paper, 134

Thallin in urine, 344

Thermostat, 387

Thiosulphates, 323

Thomas’ cylindroids, 232

Thoma-Zeiss’ apparatus, 9

Thoracic-duct, obstruction of, 349

Thread-worms, 190

Thrush fungus, 85

in feeces, 170

—— —— in mouth, 85

—— —— in nose, 91

in stomach, 150

in vagina, 369

Thymol test for chloroform, 161

—— test for sugar, 279

to preserve urine, 218

Titration method for estimating sugar,,
280

Yoison’s staining fluid, 12

Toluol, 300

Tongue, coating of, 87

Tonsillitis, 87

Tonsils, coating of, 87

Toxalbumins, 158

Toxic nephritis, 338

states, urine of, 338

Transitory glycosuria, 273

Transudations, 361

Traube on elastic fibres, 97

Traube’s corpuscles, 219

Trematodes, 187

Tribromophenol, 299

Trichina spiralis, 193

Trichinosis, 194

Trichocephalus dispar, 192

Trichomonas intestinalis, 182

—— vaginalis, 370

Trichotrachelides, 192

Trigeminal neuralgia, 82

Trimethylamin, 370

Triple phosphate crystals, 242

phosphate crystals in feces, 197

—— phosphate crystals in pus, 358

—— phosphate crystals in sputum, 113,

—— phosphate crystals in urine, 242,
247

Trommer’s test, 274

Tropzolin (00) test for HCl, 130

Troup on alveolar epithelium, 96

on spirals, 98

Trypsin, 319

Tubercle, bacillus of, 45, 103

bacillus of, detection of, 103

bacillus of, in blood, 45

 

 

 

 

 

 

 

 

 

 

Digitized by Microsoft®
INDEX.

Tubercle, bacillus of, in fecés, 179, 208

—— bacillus of, in milk, 369

—— bacillus of, in pus, 350

bacillus of, in semen, 366

—— bacillus of, in sputum, 103

bacillus of, in urine, 236

— bacillus of, spores of, 116

Tubercular infiltration of lung, 116

—— infiltration of lung, pneumonic
type of, 116

infiltration of lung, typhoid type
of, 116

Tuberculin, 46

Tuberculosis, chronic, 116

—— miliary, 116

— of lung, 116

— of urinary organs, 237, 333

urine in, 328

Tumours, fragments of, in feces, 167

in urine, 233

Tunnel-borer’s anemia, 191

Turpentine, oil of, 346

Typhoid fever, 208

fever, bacillus of, 46, 81, 177

—— fever, blood in, 46

fever, Lirlich’s urinary test for, 328

—— fever, feces in, 177

fever, urine in, 328

Tyrosin crystals, 244

crystals in faeces, 196

erystals in sputum, 112

— crystals in urine, 244

crystals, tests for, 244

Tyrotoxin, 160

 

 

 

 

 

 

 

 

 

 

 

UFFELMANN’S tests for HCl, 132

Ulcer, chronic gastric, 147

— duodenal, 148

—— tubercular, 91

Ulceration, tubercular, of urinary or-
gans, 333

Ulcerative endocarditis, 236

enteritis, 207

rhinitis, 91

Ultramarine and zinc sulphide test, 133

Ultzmann’s test, 289

Unna’s blood-serum plates, 381

Unorganised casts, 224

sediment, 239

Uremia, 77, 331

casts in, 225

Uranium solution, 325

Urates, casts of, 224

in urinary sediment, 239 246

Urea, estimation of, 311

excretion of, 311

—— in blood, 68

—— in feces, 200

 

 

 

 

 

 

in gastric juice, 141

in saliva, 83

in urine, 311

— tests for, 68

Ureteritis membranacea, 332
Urethra, epithelium of, 222

 

 

459

Urethritis, 334

Uric acid crystals, 240

— acid diathesis, 308

— acid, estimation of, 308
—-- acid in blood, 70

—-— acid in exudations, 360
— acid in urine, 240

— acid, tests for, 70

Urina spastica, 215

Urinary concretions, 247, 250
—— organs, tuberculosis of, 236
—— sand, 250

sediment, 219, 240

Urine, the, 211

actinomyces in, 237

— ether-sulphuric acids in, 297
— albumin in, 251

— amorphous deposit of, 219
—— bile acids in, 287 ,

bile pigments in, 241, 288
— blood in, 219

— carbohydrates in, 273 |
— casts in, 224 ;
--— chemical examination of, 255
—— chlorides in, 320

— chromogens of, 214

—— colour of, 214

—— crystalline deposit of, 239
—— detection of drugs in, 343
-——- diacetic acid in, 305

— diamines of, 318

—— epithelium in, 221

— fat in, 247, 306

— fatty acids in, 305

faecal substances in, 255
—— ferments of, 319

— foreign bodies in, 250

-— fragments of tumours in, 233
—— gases of, 328

—— in anemia, 337

— in congestion, 329

in diabetes, 336

in diseases of alimentary canal,
335

inzfebrile states, 328
infusoria of, 237

in hepatic affections, 335
—— in measles, 328

—— in nephritis, 329

—— inorganic constituents of, 320
--— in, septicemia, 236

—— in tuberculosis, 236

—— in typhoid, 328

—— leucocytes in, 220

-—— microscopical examination of, 217
—— organic acids of, 305

—— naked-eye inspection of, 211
—— organised sediment of, 219
—— oxalic acid in, 307

—— parasites of, 233

—— phosphates in, 323

—— pigments of, 214

proteids of, 251

—— ptomaines in, 317

 

 

 

 

 

 

 

 

Digitized by Microsoft®
460 INDEX.

Urine, pus in, 221
quantity of, 211
—— reaction of, 216

— specific gravity of, 212
—— spermatozoa in, 233
sugar in, 273

urea in, 311

—— urobilin in, 290
vermes in, 237
Urinometer, 213

Urobilin, febrile, 290
blood derived from, 76
—— in feces, 164, 204
—— in urine, 214, 290
—— normal, 214

—— of transudations, 361
separation of, 204
spectrum of, 292
—— tests for, 291
Urobilin-jaundice, 291
Urobilinuria, 250
Urochrome, 214, 317
Uroerythrin, 214, 240
Urohzmatoporphyrin, 293
Uroleucic acid, 300
Urotheobromin, 317
Uterine secretion, 370

 

 

 

 

 

 

 

VAGINAL secretion, 369
Valerianic acid, 202

Vanillin, 131
Vapour-sterilisation apparatus, 380
Vermes in blood, 57

in feeces, 182

—— in pus, 357

in sputum, 110

in urine, 257

Vesical calculus, 333

-— epithelium, 221

—— tumours, 333

Vesuvin, 105

Vibrio buccalis, 80

Vicarious oxaluria, 307
Victoria blue, 377

Vierordt’s spectrophotometer, 297
Vitali’s guaiacum test, 221
Vogel’s colour scale, 215
Volatile fatty acids in blood, 74
——. fatty acids in feces, 200
——— fatty acids in gastric juice, 139
—— fatty acids in sputum, 113
fatty acids in urine, 305
Volhard’s method, 320

Vomit, the, 144

—— acids in, 150

— alcohol in, 161

—— alkalies in, 152

—— alkaloids in, 156

-—— blood in, 144

— carbolic acid in, 161

 

 

 

 

 

Vomit, chloroform in, 161

— contents of, 144

— diamines in, 159

fecal substances in, 150

——- fungi of, 145

— hydrocyanic acid in, 162

— in acute gastritis, 146

-— in cancer of stomach, 148

in chronic gastritis, 146

in gastric ulcer, 147

—— in parasitic affections of stomach,
150

—— in poisoning, 150

— nitric acid in, 151

—— oxalic acid in, 151

—— ptomaines in, 158

—— pus in, 150

—— sulphuric acid in, 151

yeasts in, 145

Vomitus matutinus, 146

Von Fleischl’s hemometer, 19

Von Meringand Cahn’s method for esti-
mation of HCl, 133

Vortmann’stest for hydrocyanicacid, 163

 

 

 

 

WASTING diseases, indican in, 294

Waxy casts, 228

Weber's test for indican, 295

Wedl’s litmus solution, 352

Weigert’s staining process, 352

Weyl’s test for kreatinin, 316

Whetstone crystals, see Triple phos-
phate

Whipworm, 192

White blood-corpuscles, see Leucocytes

Whooping-cough, bacillus of, 109

—— protozoa in, 109

Wool-sorters’ disease, 42

Working eye-piece, 377

Worm-Miiller’s test for sugar, 275

Worms, see Vermes

Wiirster’s test for tyrosin, 244

XANTHIN, 315

bases, 71
Xantho-kreatinin, 315
Xantho-proteic test, 258
Xylol, 45

 

YEAST-FUNGI of buccal secretion, 80
— of feces, 170

— of sputum, 103

— of urine, 233

—— of vaginal secretion, 369

— of vomit, 145

ZUISS’S lenses, 377

Zichl-Neelsen fluid, 106

Zinc sulphide and ultramarine test, 133
Zuntz test for reaction of blood, 2
Zymogen of gastric juice, 127

Printed by BALLANTYNE, Hanson & Co., Edinburgh and London

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