Twentieth Century History of Findlay and Hancock County, Ohio, and Representative Citizens, Part 112

Author: Jacob Anthony Kimmell
Publication date: 1910
Publisher:
Number of Pages: 1189

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Blakiston's ? Quiz-Compends ! Compend of Gynecology. By William Hughes Wells, M. D. Fourth edition, revised and enlarged with 153 illustrations. 1911. 12º. 290 pages. P. Blakiston's Son & Co., Philadelphia.

Diseases of the Joints and Spine. By Howard Marsh, M. A. M. C. Cantab., F. R. C. S. New and enlarged edition thor- oughly revised by the author and C. Gordon Watson, F. R. C. S. With 4 colored and 8 black-and-white plates, and up- wards of 100 illustrations in the text. 1910. 12º. 632 pages. Chicago Medical Book Company, Chicago.

Atlas of Microscopic Diagnosis in Gynecology. With Preface and Explanatory Text by Dr. Rudolf Jolly, Priv. Doc. Only authorized English translation by P. W. Shedd, M. D. With 52 lithographs in color and 2 textual figures. [1911.] 4to. 192 pages. Rebman Company, New York.

A Manual of Physical Diagnosis. By Brefney Rolph O'Reilly, M. D., C. M. (F. T. M. C., Toronto; M. R. C. S., Eng .; L. R C. P., Lond.). With 6 plates and 49 other illustrations. 1911. 12°. 369 pages. P. Blakiston's Son & Co., Philadelphia.

The Johns Hopkins Hospital Bulletins are issued monthly. They are printed by the LORD BALTIMORE PRESS, Baltimore. Subscriptions, - year (foreign postage, 50 cents), may be addressed to the publishers, THE JOHNS HOPKINS PRESS. BALTIMORE ; single copies will be sal" mail for twenty-five cents each. Single copies may also be procured from the BALTIMORE NEWS CO., Baltimore.

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BULLETIN

THE JOHNS HOPKINS HOSPITAL

Entered as Second-Class Matter at the Baltimore, Maryland, Postoffice.

XXII .- No. 243.]

BALTIMORE, JUNE, 1911.

[Price, 25 Cents

CONTENTS.

PAGE

›hydrate Tolerance and the Posterior Lobe of the Hypophysis Jerebri. An Experimental and Clinical Study. (Illustrated.) By EMIL GOETSCH, HARVEY CUSHING AND CONRAD JACOBSON 165

Distortions of the Visual Fields in Cases of Brain Tumor. Statis- tical Studies. (First Paper.) (Illustrated.)

By HARVEY CUSHING, M. D., and GEORGE J. HEUER, M. D. 190 Notes on New Books . 195

RBOHYDRATE TOLERANCE AND THE POSTERIOR LOBE OF THE HYPOPHYSIS CEREBRI.' AN EXPERIMENTAL AND CLINICAL STUDY. By EMIL GOETSCH, HARVEY CUSHING AND CONRAD JACOBSON.

(From the Johns Hopkins Hospital and the Hunterian Laboratory of Experimental Medicine.)

SUBJECT HEADINGS.

Introduction.

Presupposition of a lowered assimilation limit. Methods followed in the experiments.

Protocols of hypophysectomies, demonstrating:

Early post-operative lowering of carbohydrate tolerance. Ultimate overtolerance for carbohydrates.

The relation of this overtolerance to posterior lobe de- ficiency.

Summary of experimental results.

The assimilation limit in clinical cases of dyspituitarism. Ultimate increase of tolerance in acromegaly and gigan- tism.

An increased tolerance the rule in all cases of primary glandular deficiency.

Effect of posterior lobe extracts in lowering the assimila- tion limit.

Relation of the high assimilation limit to adiposity. Therapeutic dosage.

Influence of ductless glands in general and hypophysis in particular on tolerance for sugars.

Historical summary. Acromegaly and diabetes. Explanation of the discrepancies in past studies. Résumé and conclusions.

I. INTRODUCTION.

the series of 100 experimentally hypophysectomized ls observed in this laboratory in 1908-1909,' certain un-

sented by Dr. Cushing at the meeting of the American logical Society held in New Haven, December, 1910.

J. Crowe, Harvey Cushing and John Homans: Experi- hypophysectomy, THE JOHNS HOPKINS HOSP. BULL., 1910, 27-169.

looked for symptoms were found to occur in a number of the animals surviving for long periods after a partial removal of the gland. They were interpreted as manifestations of pitui- tary insufficiency and laid-erroneously as we now believe- solely at the door of anterior lobe defects. The most note- worthy of these symptoms was a tendency toward adiposity, coupled with genital dystrophy ; the females failed to go into heat and sexual indifference or impotence was apparent in the males, some of whom showed a definite testicular atrophy.

A histological study of the ductless glands of this series of animals demonstrated the occurrence of alterations in all of them as a consequence of the primary hypophyseal lesion. The conjecture was a natural one that possibly some of the clinical symptoms which had been observed were due to these secondary changes in other members of the ductless gland series, rather than that they were a primary outcome of the pituitary deficiency itself-an indirect rather than a direct effect, in other words. For example, it was conjectured that the adiposity might be due to defective testicular or ovarian secretion and thus be akin to the adiposity following castra- tion; that the transient glycosuria which was observed in a few instances might be due to a hyperplasia of the thyroid or adrenals, or to a state of lowered activity of the islets of Lan- gerhans, or even perhaps of the pancreatic acini themselves.

With this suggestion in mind it was proposed among other objects to devote our 1909-1910 series to a more careful his- tological scrutiny of the changes in these other glands. We di- rected our attention particularly to the alterations which occur in the pancreas and its islets, with results which will appear in

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JOHNS HOPKINS HOSPITAL BULLETIN.

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a subsequent paper. These studies naturally led us into an in- vestigation of the carbohydrate tolerance of the hypophysecto- mized animals, and our observations in this direction form the basis of this present communication, in which reference will also be made to certain clinical applications of our findings.

In the earlier series (1908-1909) as recorded by Crowe, Cushing and Homans, though polyuria was commonly ob- served, the immediate post-operative presence of a reducing substance in the urine had been noted in a few instances only. It was naturally ascribed to the anasthetic. The animals in our present series (1909-1910) were observed with greater care in this respect, and it was learned that an early and spon- taneous glycosuria might be anticipated in the majority of the animals. This was particularly true of those subjected to the operation for total removal, whether or not the gland proved subsequently to have been extracted in its entirety ; for it is in this procedure that the hypophyseal stalk is manip- ulated and crushed in a particular way.

As this post-operative glycosuria proves to be transient, it is a natural supposition that many cases which would have shown a reducing substance were overlooked in the series of the previous year, since the routine of examining the first voided specimen was not followed. Furthermore, in view of the marked polyuria which usually occurs, if the first speci- men, with its definite reducing properties, is allowed to be- come diluted with the total day's amount the early and transient appearance of a reducing substance may readily escape notice on a casual examination of the mixed 24-hour specimen-another possible source of error.

It must be said, however, that in a number of the animals in our present series a trace of the reducing substance often persisted for a day or two, the early typical reduction of Fehling's solution gradually fading to a mere greenish-yellow discoloration-referred to as an "atypical reduction " and probably not due to dextrose. The reducing body of the earlier specimens, it may be added, gives a positive yeast fermenta- tion test and is dextro-rotatory.

After a fragmentary hypophysectomy this spontaneous post- operative glycosuria was found to occur with less regularity, though as our charts will show, a temporarily lowered assimi- lation limit may be expected even under these circumstances. This fact suggested that the character of the glandular manip- ulations was the essential element in the production of the glycosuria, rather than the operative method of approaching the gland or the administration of the anesthetic: for the surgical procedure and the duration of the performance are practically the same whether the object be a partial or a total removal. The chief difference between the two operations lies in the manner of treating the stalk, for in the partial removals this structure need not, and should not, be damaged by the glandular manipulations. On the other hand, in the extirpa- tion destined to be total, after freeing the vascular dural attachment of the posterior lobe, the infundibular attachment of the dangling gland is pinched off in the forceps as high up as possible, so that as little as may be of the pars intermedia is left adhering to the infundibular stalk and tuber cinerium.

If the manipulations have been successful the isolated gas! is then lifted out intact.

Needless to say, in all of the animals the urine was erar. ined previous to the operation, and it may be noted that i: the large number of dogs subjected to hypophysectomy in «: present series no instance of pre-existing glycosuria has les observed. In order to test the relation of the anesthetic ; the problem, a number of animals of the average size and employed in this series were anæsthetized with ether for (.2. responding periods without the subsequent appearance of a: ducing body in the urine. For further control, a few typix operations were carried to the point of free exposure of fo gland, but without subjecting the structure itself to !! manipulation. These animals also showed no reducing st .: stance in the urine.

These primary observations, disclosing the frequent (vz rence of glycosuria immediately after a total hypophysectori. led us to conjecture that the assimilation limit in these anina: would subsequently be found to be altered, and it was pi- supposed-erroneously as events proved-that a permanent; lowered carbohydrate tolerance would be demonstrable. Thi- furthermore is the view which has been the basis apparent! of all previous investigations.

With this preconception, a primary test was made upou tx: young dogs of approximately the same size and age, one being hypophysectomized, the other used as a control. A day « two after the spontaneous post-operative glycosuria of the former puppy had disappeared, a diet of white bread in eque. amounts was given to the two animals. The reducing sch- stance promptly reappeared in the urine of the animal soi- jected to operation, whereas the urine of the control had t reducing properties. Contrary to our expectation, however. this lowered assimilation limit shown by the hypophysete- mized animal did not persist, and after a number of dare even forced feeding with white bread failed to produce giver- suria in either animal. It was evident that the carbohydra tolerance, distinctly lowered during the early post-operative period, had again increased after an interval of a few dar: Whether the former assimilation limit had merely been re- gained or whether an actual increase in tolerance had beents established could not, of course, be determined by such 3 crude experiment.

Having in mind, therefore, that the post-operative sponta- neous glycosuria bore a definite relation to the surgical manip- ulations of the gland and that the brief period of carbor- drate intolerance was followed by a re-establishment of to- erance at least to the normal, it was determined to test these points more systematically.

II. CONDUCT OF EXPERIMENTS.

Healthy young dogs, averaging about one year of age and usually of the fox-terrier type, were chosen as subjects. Each animal was confined in a carefully constructed metabolism cagr for a number of days before the operation, on a diet consisting of 125 to 150 gms. of lean ground beef. This was boiled to obviate the intestinal disturbances engendered by the feeding

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is, wang tre preuminary tests to establish their normal ar tolerance, remained in good condition with normally ned stools, and uncontaminated urine could be obtained. n performing the hypophysectomy we have followed the te operative methods practiced in the Hunterian Labora- during the past two or three years and fully described by we, Cushing and Homans. The surgical difficulties asso- ed with this delicate procedure may with experience be so pletely overcome as to enable one to remove, in the average :, the entire structure, the anterior or the posterior lobe, or stically any desired proportion of either lobe. After one learned to free the posterior dural attachment of the id at the point of entry for the vessels to the para nervosa," dislocation and removal of this separate lobule, together 1 its epithelial investment is one of the simplest of the ous forms of glandular mutilation. However, there need ly be any uncertainty at the time of operation as to the ree of success of the attempted measure, whatever it may

In the entire series, nevertheless, not only have the frag- its removed at operation been sectioned, but in every case al sections have been made of the interpeduncular block issue removed post mortem. This block should include the , of the third ventricle, the optic chiasm and the entire tents of the sella turcica, together with its dural lining. y in this way is it possible to establish beyond equivocation only the size but the state of functional activity of the dular fragment which has been left.

n the carbohydrate assimilation tests definite weighed unts of cane sugar dissolved in warm water were admin- red by a stomach tube. In all cases the normal tolerance he individual animals was approximately established by a es of determinations previous to the hypophysectomy, and post-operative tolerance was established by the same hod after varying intervals of time." For a number of ons we have in most cases preferred to work on the basis olerance for carbohydrate ingested rather than given in- enously. It gave us a better estimate of the power of rption, destruction and storage of sugar than could have

acquired had the carbohydrate been thrown in large ints directly into the circulation. Furthermore, the ani- were less inconvenienced and fewer abnormal factors were duced than would have been the case with such frequent .venous injections as the tests would have required. After or two experiences tractable animals accept the stomach without resistance.

ccharose was chosen-despite its being a somewhat more lex body than glucose-partly for the reason that if the als drooled into the cages after the administration of the there would be no danger of contamination of the urine

administered by mouth. Needless to say, the cages were thor- oughly and frequently cleaned, and in case one of the animals acquired diarrhoea during the progress of the experiments sugar feeding was interrupted and all specimens of urine under the suspicion of contamination by converted saccha- rose which had been carried through the intestinal canal and ineffectually screened out, were discarded. However, the chance of error on this score with cane sugar feeding seems very slight; for in a few animals afflicted with diarrhea, causing an obvious contamination of the urine, the dextrose tests were always negative provided the amount of sugar ad- ministered had been below the assimilation limit.

In some animals in the late post-operative stages, when the assimilation limit became very high, the large amount of carbohydrate would not always be completely retained by the stomach. If any sugar was regurgitated, however under such circumstances the urine would betray this fact by its high specific gravity and content of mucus and food particles and the findings could be disregarded. Scrupulous observance of these precautions should eliminate the possible sources of error associated with this manner of making the tests.

However, for purposes of control, tests were made in cer- tain cases with the intravenous injection of from 20 to 25 per cent glucose solution.ª In a number of instances, further- more, extracts of posterior lobe, of anterior lobe and of thy- roid gland were administered hypodermically, intravenously or by mouth, simultaneously with the sugar feeding, with the re- sults to be recorded below.

III. PROTOCOLS OF EXPERIMENTS.

At the outset of our investigations it was unknown to us whether the obvious disturbances of carbohydrate metabolism were associated with the activity of the pituitary body as a whole or with the function of one or another of its anatomical subdivisions. We were somewhat prejudiced in favor of the anterior lobe, in view of the stress laid on this portion of the gland in the earlier studies from this laboratory. Thus in practically all of the cases of spontaneous post-operative gly- cosuria and in the instance of white bread feeding related above, we were dealing with animals subjected to a complete or to a nearly complete extirpation of the entire gland-ani- mals, in other words, in whom the characteristic symptoms of acute glandular deficiency (cachexia hypophyseopriva) were likely to appear after intervals varying from two to three weeks. As the carbohydrate tolerance was first systematically studied in connection with operations of this type the results may be presented at the outset, for though they are far less striking than in the case of the longer lived animals they nevertheless show points of interest.

Four of our observations (Nos. 60, 63, 57, 66) belong in this group. In two of them the normal tolerance was estab- lished for cane sugar by mouth, and in the other two for glu-

ndy and Goetsch: The blood supply of the pituitary body. : Anat., 1910, XI, p. 137.

d we been cognizant when these studies were undertaken of ore refined methods of quantitative determination of the output in the urine we would have been spared the tedium Be repeated tests to establish the tolerance.

" In order to prevent the introduction of an unnecessarily large amount of fluid into the circulation, the more concentrated solu- tions were used as the assimilation limit increased.

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cose intravenously, before the hypophysectomy. All four ani- mals promptly recovered from the operation, but it was neces- sary to sacrifice them in from two to three weeks owing to the onset of symptoms of cachexia. Nevertheless the post-opera- tive observations made in this interval showed in two cases a transient spontaneous glycosuria, in three cases a temporary lowering of the assimilation limit and in three a slight in- crease in the tolerance before death even in this short period. This restoration of the normal tolerance and a final slight in- crease over the former assimilation limit was shown for the intravenous as well as for the intraoral method of sugar ad- ministration. For the purpose of comparing these two methods both of them were employed in one individual (No. 58) in a subsequent group.

A. Observations on the changes of the assimilation limit for cane sugar by mouth and glucose intravenously in ani- mals deprived of nearly the entire gland.

The first four protocols therefore will record the observa- tions made upon animals subjected to a complete or nearly complete glandular extirpation. Needless to say they have been shorn of practically all data unrelated to the subject in question.

No. 60 .- (Series of 1909-10.) Primary lowering of tolerance for cane sugar by mouth during week after operation. Subsequent rise to normal. Tests interrupted by attack of distemper with onset of cacheria hypophyseopriva on 23d day. (Table I.)

TABLE I .- TESTS OF TOLERANCE FOR CANE SUGAR BY MOUTH IN No. 60.

Date.

Grams of cane sugar given.

Amt.

Sp.Gr.

Fehling.

Nylander.

Fermen- tation.

Polari- scope.

May 17

160 240

1032

80 90

240

1020

150

1029

110

1038

1044

80 (?)

140

1040

150

1060

200

1040

oo+++++otoo 0 0

.8%

A healthy male, 6.6 kilo, adult fox terrier about one year of age. Kept in metabolism cage for four days prior to operation to determine normal assimilation for saccharose by mouth (cf. Chart I). Tolerance established between 70 and 80 gms.

May 28. Operation .- Removal of posterior lobe and practically entire anterior lobe; gland fragmented in removal. Operative estimate a "nearly total " hypophysectomy. A small tag, sup- posedly of anterior lobe, left adherent at infundibular stalk.

May 29 .- No post-operative polyuria or glycosuria.

May 31-June 10 .- Establishment of post-operative tolerance at about 20 gms. below normal on the third and fourth days. Sub- sequent rise to 80 gms., the normal tolerance. Rapid accession of body weight from 6.6 kilos to 7.4 kilos during period of sugar in- gestion.

June 13 .- Symptoms of distemper led to a discontinuance of further tests.

June 20 .- Distemper followed by usual manifestations of e: suing cachexia. Animal sacrificed.

Autopsy .- Apparently an almost total removal. A smr granule, which might be glandular substance visible at the base of the stalk. No recognizable posterior or anterior lobe. Nothitz of special note in the gross examination of the other organs. la fundibular block, including contents of sella turcica, preserved se usual for serial sectioning.

Histological .- The two fragments removed at operation proved upon microscopical examination to be the intact posterior lobe sz: a large portion, if not all, of the anterior lobe.

The autopsy specimen showed on serial sections a few cells d the intermediate lobe type adnerent to the infundibular fox No anterior or posterior lobe seen-in short, a more complete extirpation than had been intended.

Comment .- The observation is not a particularly valuati- one. The operative intent had been to leave just enough the anterior lobe to preserve the life of the animal, a total n- moval of this lobe being incompatible with life, as has bes: shown. Attention has been called to the fact that an anima' under these circumstances is particularly susceptible to is- fections or to intestinal derangements, which are apt to pr- cipitate the acute symptoms of excessive glandular deficiens shown by a fall in temperature, tremors, arching of the boxi a slowed respiration and ultimate coma. The distemper which occurred on the 26th day interrupted the tests and provoka! these terminal symptoms.

It will be noted that no spontaneous post-operative glory- suria and polyuria were observed. This is so exceptional a. to make us fear that a first specimen may have been lost " unrecorded. A temporarily lowered assimilation limit, how- ever, was apparent, for on the third day 60 gms. of saccharose produced glycosuria, whereas 80 gms. had been required be fore the operation. By the ninth day the original sugar te. erance was practically regained, 80 gms. again giving a slight reduction. Attention is drawn to the increment in body weight of nearly 12 per cent during the sugar feeding period of 10 days.

No. 63 .- (Series of 1909-10.) An increase of tolerance for sa. charose by mouth seven days after a " nearly total" hypophyse tomy. Attempted reduction of tolerance by the hypodermic in-

TABLE II .- TESTS OF TOLERANCE FOR CANE SUGAR BY MOUTH I No. 63.

Date.

Grams of cane sugar given.

Amt.

Sp.Gr.

Fehling.

Nylander.

Fermen- tation.

scope

May 31 June 1

310

1048

150

1050

840

1080

280

1015

+ slight 0

Nearly complete hypophysectomy; small fragment of anterk: lobe remaining.

400

1020

440

1010

120

1040

140

1022

210

1028

110

1022

150

1034

100

210

1032

110

180

1028

120

830

1020

Nearly complete hypophysectomy ; small fragment of anterior lobe remaining.

120

1028

June 1

240

1000

800

1060-+-

200

1046

.6%

150

1030

180

1040

+ slight.

+ 0

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Urine.

Poisn

260

1020

+ +

1050

10 (?)

Urine.

therew woof of ways. (Table Il.)

A healthy male, 9.1 kilo, fox terrier, about six months of age nd apparently full-grown. Observed for six days previous to peration. Normal tolerance to cane sugar feeding established at mething below 80 gms.

June 7. Operation .- A nearly total removal of the gland. No urgical difficulties. Prompt recovery from the anaesthetic. No ost-operative complications.

June 8-9 .- A moderate polyuria without demonstrable glyco- ria.

June 12 .- Animal in perfect condition. Feeding tests begun th 70 gms .; negative.

June 14 .- Glycosuria first induced by 90 gms., more than 10 ove the established normal.

June 16-19 .- The tolerance increased in this interval (cf. Chart I to something below 120 gms., 40 gms. above the established rmal.

Tune 21 .- One hundred grams of sugar with a coincident hypo- mic injection of posterior lobe (0.5 gm.) caused immediate niting, whereas this amount had been readily taken before. 'une 24 .- A repetition of the experience of June 21: prompt niting of 80 gms. On June 26 a similar experience with 80 gms. une 30 .- Subnormal temperature with onset of symptoms of hexia. Animal sacrificed.

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Twentieth Century History of Findlay and Hancock County, Ohio, and Representative Citizens, Part 112

Author: Jacob Anthony Kimmell Publication date: 1910 Publisher: Number of Pages: 1189

Author: Jacob Anthony Kimmell
Publication date: 1910
Publisher:
Number of Pages: 1189