PROJECT REPORT COMMITTEE OH FOOD RESEARCH QUARTERMASTER FOOD AND CONTAINER INSTITUTE FOR THE ARMED FORCES CHICAGO ILLINOIS RESEARCH AND DEVELOPMENT BRANCH MILITARY PLANNING DIVISION OFFICE OF THE QUARTERMASTER GENERAL COOPERATING INSTITUTION University of California LOCAL ITY Berkeley, California DIVISION Medical School DPP ARTM PM T Division of Physiology OFFICIAL INVESTIGATOR I. L. Chaikoff COLLABORATORS S. Chernick FILE NO. NTT-iy CONTRACT NO. VJ44-109-qm-1019 REPORT NO. 2 FOR PERIOD COVERING I NI II ATI ON DATE _ ._ 1 Sepxenber 1945 TITLE: PROGRESS REPORT PHASE REPORT | ANNUAL REPORT TERMINATION REPORT Effect of Feeding Various Combat Pations and Effect of Adverse Environment on Pancreatic Digestion SUMMARY A BIHLIOCPaPHv of PESEaPCH on tHE EXTFRUaL SECPPTIL'H OF TTJE PAUCPEAS. I cQMOrFORM6 ,2-12 1 r*.vi..co CONTENTS Page Introduction I. Normal Secretion . 1 II. Effects of Feodstuffs and Food Products on Secretion * 7 a. Protein and Protein Derivatives 7 b. Fats, acids and Soaps 15 c. Vitamins 18 d. Mixed Diets and Comparative Studies.,.. 22 III. Fasting and Environmental Conditions.,,,, 38 rr. Substances other than Food 42 a. Insulin and Blood Sugar 42 b. Acids, Alkali and Secretin 50 c. Bile and Bile Derivatives..... 56 d. Miscellaneous Substances. 58 V. Function Tests 67 a. Analysis of Duodenal Contents 67 b. Analysis of Blood Enzymes 74 c. Other Function Tests 83 VI. Books and Reviews. 86 INTRODUCTION "he purpose of this bibliography is to present in con- r " ' ' * ■ • ‘•4- cibc cise form the experimental work on the effect of various stimuli, particularly food, on the Quality and quantity of external pancreatic secretion and on pancreatic function tests; rnho period covered extends fron 1890 to January, 1946, A great deal of the material was obtained from Chemical Abstracts and Nutritional Abstracts and Reviews. The jour- nals containing the greatest amount of material on the ‘sub- ject are American Journal of Physiology, American Journal of Digestive Diseases, Gastroenterology, and Archiv fur die Gesante Physiologie, Section I contains references which were concerned with the determination of ’normal’ enzyme output. However, practi- cally all the articles in sections II - IV will also be' found to contain data on the normal enzyme output of the pancreas. The numerous studios made on the effects of secretin, histamine and drugs acting through the nervous system on pan- creatic secretion are not included in this report, except when other stimuli were used along with then. For a rather complete picture of the experimental work done up until 1928, Die aussere Sekretion Der Verdauungsdrusen by Pabkin is recommended. His later book, ■ ecreto.ry Mechanisms of the Digestive Glands, gives a comprehensive review of the work done since that tine, Lagerlof's book, 'Pancreatic Func- tion and Pancreatic Disease, gives a complete review of the work done on function tests using duodenal content analysis, but many articles on the sub.ic-ct have apoeared since itrs public- tion (1942)* SECTION I 1 fQPT’AL PaNCTNvAT IC SECRET ION Pancreatic Secretion in ari after Intravenous Administration of Secretin G. Agren and H. Lagerlof. Acta. red. Scand. 30, 1 (1956) On normal subjects there are no ill effects after giving secretin repeatedly. After administration of secre- tin there is a washing out of stored enzymes but afterward the secretion is sustained at an even level. The concen- tration and quality of the enzymes run parallel. Formal values are given. Continuous Pancreatic Secretion in the Babbit S. G. Baxter. Am. J, Physiol. 96, 341 (1931) In the rabbit there is a true "spontaneous" secretion of pancreatic juice, which may be increased by exogenous stimuli, such as acid, bile and peptone, present in the duodenum and small intestine. The External Secretion 'f the Pancreas ".*• Berger, J. Hartmann and H. Lcubncr. Klin. Pochschr. 14, 490 (1935) GA. 30;8S255 The authors claim to be able to follow in the human- subject the course of amylase and trypsin excretion by the pancreas, using a duodenal tube and fractional sampling at 2 to 5 minute intervals. Curves are ,iven for these enzymes. Functional Exploration of tho Pancreas It, Ghanbon, p, Us. Hot-Guy and J, Folliet,. Compt, Rend. Soc. Biol. 127, 632 (1938) CA. 32:41869 Tho determination of the lipolytic activity of human pancreatic juice is described. Normal values arc given. Tho Concentration of Pancreatic Enzymes in the Duodenum of Normal Persons and Persons with Disease of tho Upper Part of the Abdomen H, Comfort, R, L, Parker, A. E, psterberg, Am, J, Dig. Pis, £, 249 (1939) Normal values for trypsin, lipase and amylase are given, A marked contraction of the range of concentrations of these was found in patients with carcinoma of head of pan- 'L *V"\ croas, and of the ampulla of Voter, and chronic atrovhic pancrca.tit.is with steatorrhea. The Lipolytic .analysis of Duodenal Contents B, IT. Graver and B, S, alkcr. Am, J. Dig. Dis, 9, 223 (1942) A simple clinical method of lipolytic analysis is de- scribed which is applicable to duodenal contents. The re- sults of fifty intubations on normal subjects ~re reported to serve as a standard of reference. The Clinical Application of Secretin in the Study of Pan- creatic Function J. S. Diamond and S, A, Siege], N.Y, State J. Med. 41, 869 (1941) The use of the secretin test on 90 patients, both nor- mal and with pathological conditions is described, and the findings discussed. It was found that in pathologic states of the pancreas the enzyme production first became affected; the volume and bicarbonate wore, more stable and less easily disturbed, Study of the Enzyme Activities of Duodenal Contents as a Means of evaluating Pancreatic Function A, H. Free, A, J. Beams and V, C. Ayers. Gastroenterology 1, 183 (1943) Cuantitativc determinations of enzyme activity wore carried out in a group of normal subjects during fasting and after stimulation of the pancreatic secretion with olive oil. On the basis of results obtained in these subjects a system of evaluating pancreatic secretory activity is described. Fractional Analysis of the Duodenal Contents in Normal Individuals J, Friodcnwald and J, Sindlor, J. A. I'. A, 77, 1469 (1921) The findings on ten normal individuals arc given. Hunan Pancreatic Secretion Studied from a Case of Pancreatic Cyst and Fistula. J. Hahn and E. IT. Klein. Am. J. Med. Sci, 184, 503 (1932) The pancreatic fluid was collected postoperatively by a drainage tube inserted into the cyst cavity. It continued flowing fqr 59 days after insertion of tube. No constancy was found in the ratio lipase: trypsin: amylase secreted. The daily output of these enzymes, when compared with their amounts estimated to be present in the gland, was found to represent a large proportion of the lip.me present and a much smaller amount of the amylase and trypsin. The latter v:as found to be free of entcrohinasp, Not; Methods for Estimating Enzvrxitic Activities of Duodenal Contents of Normal lean C. a. McClure, n, 5. ctmore and L, Reynoldsf Arch. Int, Med. 2J7, 706 (1921) Methods of determining proteolytic, lipolytic and am- yl olytic enzymes are discussed, and their shortcomings in using them for analvsis of the enzymes of duodenal contents arc pointed out. The authors’ nethods for the determining of these enzymes in duodenal contents arc given in detail, and their accuracy is discussed. Studios in Old Ago. IV. The Cl inicol Significance of Soli* vary. Gastric and Fanereotic Secretion in the Aged. J. Foyer and H. Nechclos, J. A, K, A, 115, 2050 (1940) i j In old ago there is a decrease in salivary, gastric and pancreatic secretion (except Amylase), both in quantity and enzyme content. The diminution in quantity of secretion apparently docs not affect intestinal digestion. Values for secretions obtained at different ages arc given. Physiologic Observations on Patients with External Pancreatic Fistula J, !i. Filler and T. 5, -dper. Ann, Surg. 120, 852 (1944) Formal pancreatic secretion and the secretion v;ith various nutritional and pharmacological stimuli are given for three patients with pancrcatjc fistulas. Studies on Old .-.go, V. Active Pancreatic Secretion in the Aged. H. Hechelcs, F. Plotkc and J, I'cycr. Am. J, Dig, Bis. 9, 157 (1942) The pancreatic secretion of a group of 30 aged subjects with an average age of 66,5 years 7/ns compared with that of a. group of 30 young persons with an average a,go of 23,4 years. Pancreatic secretion was stimulated by intraduodenal injec- tion of oleic acid. 'Bicarbonate and amylase content was sig- nificantly increased in the- older group; lipase was 214 lower. Volume of fluid wnd trypsin concentration wore not signifi- cantly different in both groups. 5 An analysis of the Duodenal Drainage in the Steathorrhoas F. F. Fhilipsborn, Jr. ct.al. J. Pediatrics 26, 107 (1945) The duodenal contents of normal children, "feeding prob- lems", and children with pancreatic diseases were analyzed for enzymatic activity, and the values obtained are given, "Feed- ing problems" may be due to temporary pancreatic insufficiency, physiology of the Pancreatic Secretion of Man Studied by Means of a Fistula of the Duct of ' irsung I:, Villarot and L. Justin-Bcsancon, nutrition (Paris) 6, 209 (1936) The analysis of the pancreatic juice of a patient is given, both ’normal* and as a result of vrrious stimuli. The findings of other workers as regards the volume of juice se- creted by humans arc listed. Continuous Pancreatic Secretion T. F. Zucker, F, G. Newburger and B. N. Berg. Am, J. Physiol, 102, 193 (1932) In dog with cannulatcd pancreas the secretion is con- tinuous, but food or the injection of secretin temporarily increases the rate of flow, . Anaesthesia may completely in- hibit the flow of pancreatic juice. Ether increases the amylase level of the blood. SUCTION II EFFECTS OF FOODSTUFFS .FID FOOD PRODUCTS ON SFCPUTION OF PFNCPEATIC JUICE a. Protein and Protein Derivatives b, Fats, Fatty cids and Soaps c. Vitamins d, I.lixod Diets and Comparative' Studies o.• Protein and Protein Derivatives The Secretory St.imulc.tivo Effect on the Pr.ncrcc.s of the -jnino-—cid Hydrochlorides M. Aral. Eiochcm. Z. 121, 175 (1921) CA, 15:3687* Injection into the duodenum of dogs with pancreatic fistulas of aqueous solutions of the HC1 salt of glycocoll, d-alanino, d-glutamic acid and glycylglycinc stimulated pan- creatic secretion. The HC1 of histidine and d-glucosaminc did not act as stimulants, adrenaline depressed the stimu- lating action of these compounds. The Influence of Sodium Nitrite, Peptone and Pilocarpine on the External Secretion of the Pancreas , x 6 0, ;, Barlow. an, J, physiol. 81, .189 (1927) Ca. 21:2507 Peptone, histamine and IlaHOg given intravenously in- creased the external pancreatic secretory rate, presumably - . . i by improving nutritional conditions, i.c., blood supply to the splanchnic organs. Action of Amino on the Pancreatic Secretion v ’ 3 A, Frouin, Compt. Rend, See, Biol, 74, 131 (1913) CP, 7^:1374 Final products (glycocoll, leucine, alanine, tyrosine, asparagine., aspartic acid, glytamic acid) of the digestion of proteins had no effect on the secretory activity of the pan- creas when 'introduced in various concentrations by intravenous injection, When introduced directly into the intestine they 7 did increase the secretion somewhat, but this is ascribed to the pH of the substances for it did not occur after neutral- ization, Peptone has no effect on the secretory activity when introduced into the intestine, but inhibits the action of mineral acids in exciting secretion. Influence of Peptono on the Secretory Action of Mineral and Organic Acids on pancreatic Secretion A. Frouin and S. Harbo. Compt. Rond. Soc, Biol. 68, 176 (1910) CA. 4:20175 The addition of peptone hinders the formation of se- cretin by mineral acids, although it increases the quantity of secretin set free by organic acids. Influence of the Products of Digestion of Proteins and Sugars or the Secretory Power of Acids on the Intestine A. Frouin and M, do Medeiros. Compt, Rend. Soc. Biol, 68, 174 (1910) CA. 4;201T6 In animals with pancreatic fistulao peptone decreased the secretory action of EC1, although it increased that of lactic acid. Lactose and saccharose increased the secretory action of organic acids. Lactose increased the action of HC1. Hence, among carnivora pancreatic and enteric secretions are not abundant because the albumoses and peptones formed by stomach digestion dimish the secretory action of the gas- thic juice on pancreatic and intestinal secretion. With the herbivora fed on carbohydrates and organic acids the pancreatic and enteric secretions are more abundant. The secretory power of organic acids is increased by the pro- ducts of digestion of proteins and by sugars. The quantity of intestinal and pancreatic secretions can be controlled by the ingestion of peptones, sugars, or of organic acids. Relationship between Mechanical State of the Feed (Moat) and Pancreatic Secretion W. H. Gantt and P, 3. Kupalow, Z. f. d, ges, Exp. Med, 56, 802 (1927) Experiments were performed on 2 dogs with Pavlov pan- creatic fistulae that were fed pieces of meat or ground meat. The volume and dry weight of the secretion were determined. It was found that the volume was greater and the percent dry weight was less when pieces of meat were fed. However, the total dry solids were 2-3 times greater when pieces of meat were fed than when ground meat was fed. It is concluded that the work of digestion is less when ground foods are fed. 9 ll. Portion of the .Pancreatic Secretory Response to_ a Meal Due to the Absorption of Digested Food Products J. Gray, M. S, Kin and A. C. Ivy. Am. J. Physiol. 116, 210 (1936) ( The pancreatic secretion of anaesthetized dogs with cannulated pancreatic dubts was measured after intravenous injections of various substances. Untreated liver extract containing some vaso-depressor substances caused a two-fold increase in the continuous secretion; liver extract freed of vaso-depressor activity was inert. Liver extract plus secretin didn't act synergistically. Witte peptone caused very slight increase of flow. Dextrose and emulsified fats caused no increase in flow. Concludes that secretin is probably the only humoral agent concerned in the secretory response of the pancreas to a meal. The Action of the Nitrogenous Bases of the Gastric Juice on Blood Pressure, Pancreatic Secretion and Flow of Bile S, A, Komarov. Am, J. Physiol. 115, 604 (1936) Dogs with cannulated pancreatic and bile ducts were in- jected intravenously with the test solutions. The histidine fraction isolated from canine gastric juice produced no ef- fect on blood pressure, pancreatic secretion or flow of bile. The arginine fraction exhibited a histamine-like action on the blood pressure and the secretion of pancreatic juice. It had no definite effect on the secretion of bile. The lysine fraction possessed a marked pressure activity and stimulated the secretion of pancreatic juice and bile. None of those effects wore influenced by preliminary sec- tion of the vagi or by atropinization. The Effect of Certain Fractions of Meat Extract on the Secretion of Pancreatic Juice and Bile R, Krimberg and S, A, Komarov. Biochem. Z. 184, 442 (1927) CA. Zl^SOQ1 . The largest part of the phosphotungstic acid ppt, of meat extract which stimulates secretion of pancreatic juice is in the carnosine-methylguanidine fraction. Authors state that camosine isn’t stimulant, but methyl guanidine plays a role. Restoration of the Pancreatic Secretion by Peptone and Histamine M, E, McKay and S, 0. Baxter. Am. J. physiol. 9£, 42 (1931) In anaesthetized dogs and cats with cannulated pan- creas the pancreatic response may be restored by injecting into the duodenum 0,2% HC1 plus 10 - 30 gms, histamine when it has become exhausted by repeated injection of 0*2% HC1. Witte’s peptone may bo substituted for histamine and get same result. The previous feeding of the animals is an important factor in these experiments, (Usual commercial preparations of peptone contain con- siderable quantities of histamine (¥, and E, Schilf, Histamine, Berlin, (1930), pg. 40)) Effect of Albumin and Casein Choose on the Activity of the Gastrointestinal Tract M. T. Olovskii, L, Zelenko and S. Kuz’menko, Med, Exptl, (Ukraine) 12, 64 (1935) CA. 31-.14763 On dogs with chronic fistulas casein cheese produced somewhat smaller quantities of pancreatic juice than albumin cheese• The Pancreatic Secretagogue Action of Products of Protein Digestion J. E# 'Thomas and J, 0, Crider, Am. J, Physiol, 134, 656 (1941) pancreatic juice was collected from dogs by moans of a cumulated duodenal fistula. Effective drainage of stomach was maintained during experimental periods. Products of pro- tein digestion acted in the intestine as stimuli for tho ex- ternal secretory fyinction of the pancreas. Their effective- noss is not dependent on the coincident flow of bile into the intestine nor on the socretagoguc action of water or acid* The secretion produced by peptone stimulation has a higher specific 'gravity and contains many times more than that produced by water, acid, or secretin. Among com- mercial peptones the more effective are those having the higher percentage of proteose. The secretion could not bo produced by secretin alone. The secretion elicited by pep- tones resembles that caused by pilocarpine and other stimuli acting through or on the secretory nerves. Conclusion is / drawn that peptones act through a nervous mechanism. Changes in the Acinar Cells of the Pancreas in Response to the Presence of Peptone in the Small Intestine A, J, Ramsay, J, D. Thomas and J. 0, Crider, Anat. p c, 86, 87 (1S43) Peptone was introduced into the duodenum of unanacsthe- tized dogs with partially exteriorized pancreas by means of an injection tube. During peptone stimulation the acinar cells become depleted of zymogen granules and secretion accu- mulates in the ducts. Acinar cells in the vicinity of the islets retain their granules, some forming halos, changes are similar to those described as occurring during stimulation of the vagus and differ from those said to result from pre- sence of Hcl in intestine. They did not occur in vagotomized animals. Influence of Certain Foods and of Emotion oh Pancreas Secretion , v 9 Togami. Z. Physik,-Ddat. Ther. 12, 453 (1909) CA.3^;2312 When dogs with Pavlov pancreatic fistulas arc fed with asparagus, spinach, carrots, or cauliflower, little stimulation of pancreatic juice was observed, Meat broth produced a marked stimulation, Angor or other psychic disturbances inhibit the flow. Contributions to the Physiology and Pharmacology of the Pancreas B. N, Vailiev, Arch, d. Sc, Biol, 2, 219 (1893) (From the Work of the Digestive Glands, it p, Pavlov, 1910) P, 44 If a dog is fed for weeks on milk and bread, and then given an exclusively meat diet, containing more proteid but scarcely any carbohydrate, a continuous in- crease in the proteid foment of the juice is observed. The ability to digest proteid increases from day to day, while the amylolytic power of the juice decreases. 14 b. Fats, Fatty Acids and Soaps The- Mo-chanism of the Action of Fat as a Secretory Excitant of the Pancreatic Glands B. P. Babkin and H. Ishikawa. Arch, Ges. Physiol. 147, i " 288 (1912) CA. 7_:122Z2 After subcutaneous injection of 0,005 g, atropine the usual slight secretion of pancreatic juice was not in- hibited, Vvhen the injection occurs at the height of the pancreatic activity induced by fat in the intestine there is no effect produced on the volume of the secretion but its content of solid matter and ferments is greatly re- duced. If the atropine is first injected, the introduc- tion of neutral fat or oleic acid fails to induce increased secretion. Atropine likewise inhibits the secretion al- ready induced by oleic acid, but only slightly affects the secretion induced by 2% Na oleate. The continuation of pancreatic activity induced by neutral fat even after at- ropine injection is to be attributed to the soaps produced during cleavage. Influence of Neutral Fat and Its Components on the Gastro- intestinal and Pancreatic Secretions A. Z. Belina, Russky Vartch 11, 296 (1912), 11, 337 (1912) CA. TjilQdQ1 Neutral fats are the most specific stimulants of the secretion of pancreatic juice. After administration of fat the pancreatic juice contains its largest proportions of li- pase. Patty acids and soaps produce similar effects, Gly- cerol does not affect intestinal secretion. The Effect of Margarine on the External Secretions of tho Digestive Organs S. Ryss and G, W, Borisov/, Arch, Verdauungskrankh. 57, 184 (1935), Nutr, Abs, and Rov, 5, 104 (1936) On dogs with various types of gastro-intestinal fis- tula©, the action of margarine on the pancreatic secretion was similar to that of other fats and oils. The Physiology of Pancreatic Secretion A. I, Smirnov. Arch, Ges. Physiol, 147, 234 (1912) CA. 7j12221 In a dog the secretion of pancreatic juice occurs first 20-25 minutes after the introduction of fat into the duodenum where the contents of the duodenum are apparently noutral or alkaline. Simultaneously with the cleavage of the fat the secretion increases considerably. Such secre- tion is characterized by high N, solids, and ferments. A subcutaneous injection of 0,005 g. atropine at the time of greatest fat cleavage does not reduce the quantity of se- cretion but leads within 15 minutes to a reduction of the N and solids which then further continues. 16 Influence of Fats and Soaps on the Secretory Function of the Pancreas V. Studzinsky. Intern* Boitr, Path, Therap. 3, 287 (1912) 2 CA. :1175 With dogs having duodenal and pancreatic fistulas, pure neutral fat causes no secretion of pancreatic juice, whereas commercial fats can cause secretion because of their-ooirtant — of free fatty acid. Pure fatty acids, such as oleic acid, are energetic stimulants of the pancreas, which explains why rancid fats irritate the mucous membrane of the intestine causing inf lamination. Soaps in 1 - 10% solution act as sti- mulants, Atropine, previously injected, docs not prevent se- cretion produced by the action of fatty acids or soaps, The secretion influenced by the fatty acid is identical with that influenced by soaps. Physiology of tho Pancreas A, Tonkich. arch, Ges, Physiol, (Pflugers) 206, 525 (1924) CA, 19_:1156? Fat and milk stimulate the pancreas more than meat, % Atropine inhibits the trophic action of fats on the pancreas, Oloic acid stimulates the secretion of pancreatic juice with a high N content, but after atropinization the N content is reduced. When oloic acid is introduced into the duodenum after separation from tho stomach, tho pancreatic juice has a low N content. The N content of tho juice differs with different preparations of oloinato. 17 c. Vitamins The Effect of Irradiated Ergosterol on the Composition of Gastric and Pancreatic Juicos W. Bauer, A. Marble, S, J, Maddock and J, E, «ood. Am. J. Mod, Sc. 181, 399 (1931) Following administration of irradiated ergosterol to 4 adults, pancreatic enzyme activity was depressed in 1 in- dividual. The latter, however, may have been due to in- creased number of bowel movements of this subject. It had no effect on fixed base content of pancreatic juice. It did causo a fall in the chloride ion and a rise in the carbonate ion. The Effect of Vitamin A on the External Secretion o£ the Pancreas K. Hcrfort, Acta. Mod, Scand, 96, 425 (1938), Nutr. Abs, and Rev, £, 171 (1939) Vitamin A was introduced into the duodenum of humans by means of a sound. The secretion of pancreatic juice elicited was greater than that obtained by similar adminis- tration of secretin or the solvent oil alone. The same action resulted when Vitamin A was given orally or parenterally. Digestive Juice Secretion on Diets Containing Rico _of Varying Degrees of Refinement, II, Pancreatic Secretion on Diets Containing Rico of Various Degrees of Refinement. R. Masuko. Auchi Igakkai Zasshi 4£, 1721 (1935), Nagoya J. Lied. Sci. 10, 85 (1936). CA. 31_;74841 On dogs with pancreatic fistula the addition of vitamin B to polished rice accelerated secretion, lengthened its dura- tion and caused a marked increase in volume and enzymic con- centration, With half polished rice and germ containing rico vitamin B promoted secretion somewhat, but not with unpolished rice, III, The Accelerating Action of Vitamin B on the Secretion of the Digestive Juices’, When vitamins and arc separated the accelerating action on digestive secretion, present in unfractionatod B, is no longer exhibited by either fraction, / Modification of the Eepato-Pancrcatic Secretion by Adminis- tration of Vitamins A f h> and C P. Nicolesco ot.ali Bull, Acad, Med, Rouiranio 5, 121 (1940), Nutr. Abs, and Rev, 12, 117 (1942) On individuals with various liver diseases, administra- tion of Vitamin -a by way of the duodenum increased the total output of pancreatic enzymes. Vitamin increased only the output of lipase and had no effect on trypsin output, and Vi- tamin C had no effect cn the enzyme output. Effects of Massive Doses of Vitamin D on the Histological Structure of the Glands of Internal Secretion I. Nitzescu and S. Braliano* Compt. Rend, Soc. Biol. 121, 1535 (1936), CA. 30:56239 Changes in the pancreas arc described. Pancreatic and Intestinal Enzymes in Experimental Scurvy G, Sunzori, Problcmi Nutriz, 3, 28 (1926), fieri'GeSi Physiol, Expt, pharmakal* 38, 682 (1926). CA. 21:1834 Guinea pigs fed on a Vitamin-C (Randoin) diet were killed shortly before death and their pancreas and intestinal mucosa, were extracted with 0,1% NaGli The only anomalies observed were: dedrease of intestinal amylase by 2/3 and slight decrease in crcptase content. The Influence of avitaminoses on heights of Endocrine Glands 3 B. Sure. Endocrinology 23* 575 (1933). CA. 33:399 In Vitamino **■ deficiency there is a 40/ hypo^try;hy of the pancreas. Enzymic Efficiency in avitaminosis. II. Influence of Vitamin Deficiency on Efficiency of Pancroatic Lipase and Esterase. Barnett Sure, M. C, Kik and Kathryn Sue Buchana, J, Biol. Chenu 108, 27-33 (1935). CA. 29:146s1 In uncomplicated vitamin B and in vitamin B complex deficiency there is a pronounced decrease in pancroatic lipase activity which is due to specific vitamin deficiency. A deficiency of the vitamin E complex a.Iso reduces pancreatic esterase efficiency. The Influence of Secretin and Antincuritic Vjtamine on Pancreatic Secretion and Bile Flew 0, Vocgtlin and C, M* Myers. J* Pharmacol. 13, 301 (1919) CA. 14-.11564 Antincuritic vitamino from brewers ’ yeast on injection into dogs stimulated pancroatic and biliary secretions. d, llixcd Diets r.nd Comparative Studies The Effect of Different Ferns of Diet on the External Secretion of the Pancreas I. Abramson. .'.eta, Med, Scand. 86, 4-78 (1935), Nutr. .Ads, and Rev. _5, 982 (1936) Normal human subjects lived on (Group ,1) the usual I mixed diet of Sweden, and (Group B) a diet practically de- void of meat, fish and eggs but rich in milk and carbohy- drate, On an empty stomach ether was injected into the duodenum by a tube to stimulate the pancreas, and the juice \ was collected. In Group B the diastase content was higher but thw trypsin and lipase 1 ower than in Group The dif- ferences were not statistically significant, although they are in keeping with previous work showing that Group B had hypochlorhydria. The Action of Acid Solutions of Cano Sugar on the Secretion of Trypsinngen E, P, Babkin and V, V, Savich, Russ, J, physiol, 3, 143 CA. 1/7:21 468 The pancreatic juice secreted on introduction of acid into the stomach is poorer in trypsinogen than that secreted on giving meat or carbohydrate. Addition of cane sugar to / the acid increases the concentration of trypsinogen in the pancreatic juice. The increase does not depend on the act of feeding, since the acid sugar* solution was injected di- s. rcctly through a gastric fistula* The Content of Solids C mtained in Pancreatic Juice Produced by Various Secretory Stimulants B. F. Babkin and W, W. Sawits’ch. Z„ Physiol. Chem. 56, 321 (1908). CA. £:1414? The character of tho secretion vras not dependent on . I the volume, but on the type of stimulation. The secretion set up by soaps is brought about by nervous influences* Experiments v;ith milk, bread and meat indicated that secre- tion occasioned by milk is the result of the formation of soaps in tho intestine. Heat and breat stimulate the pan- creas by virtue of the high acidity of the gastric juice passing into the intestine, independent of nervous action.- Kliniske Studier over den Digestive Duodenalsaftschkrotion. Samt et bidrag fil Sporgsmallet om den Exokrine pancreas- Funktion ved Achylia Gastrica Christiansen, Copenhagen, Levin & Hunksgaards (1933) (From McClure: Observations on the Physiology and Patholo- gic Physiology of External Pancreatic . Rev. Gas- troenterology 3, 1 (1936)) P, 5 & 6. No ono kind of pure foodstuff stimulates the greatest concentration of its specific enzyme; however, the degrees of concentration of all types of pancreatic enzymes arc related to the foodstuff fed. External Pancreatic Fistula: Report of a Case with Physio- logic Observations H. W, Comfort, A. J, Osterberg and J, T, Priestley, Am, J. Dig. Dis. 10, 7 (1943) The fasting secretion was low in volume, total bicar- bonate and enzyme content, with gastric juice excluded pan- creatic juice was stimulated very slightly by casein, glucose, and olive oil introduced through a duodenal tube. Given oral- ly glucose and casein promoted vigorous secretions. Lipase was not stimulated to flow by olive oil given orally, but there was a slight increase in amylase. The typo of secretory response did not appear to depend as much on the effect that food exerts directly on pancreatic secretion as on the effects of food on gastric secretion. Gastric contents (gastric secre- tion plus' food) wore a much more potent stimulant of pancreatic secretion than were foods alone. Meals low in fat and high in carbohydrate and protein stimulated a greater flow of all com- ponents of the pancreatic juice than did meals high in fat, physiology of the pancreas 0, Cohnhcim and ph, Klee. Z, Physiol, Chcm. 78', 463 (1912) CA. 7jl227 Various liquids were injected into the duodenum and the quantity of pancreatic juice obtained was compared with the nor- mal, IIC1 is the strongest stimulant. The free acid is more effective than when combined with protein. Oil caused but a slight flow of pancreatic juice. The Influonco of Combinations of Basic Foodstuffs (containing chiefly proteins and carbohydrates) upon Gastric and Pan- creatic Secretion M, Li Eidlinova* Arch. sci, biol. (U.S.SoR.) 54, 113 (1934) CA. 28t58697 Dogs were fed combinations of bread, potatoes, starch, moat and soy-meal and the pancreatic secretion collected by r means of a Pavlov fistula. Equal weights of moat and pota- toes or starch resulted in greater secretion than each of thes-r alone, TThen the starch content was increased secre- tion was decreasedj an increase in the potato content in- creased secretion. Soy-meal was loss effective as a pan- creatic stimulant then meat. Starch alone stimulates pan- creatic secretion. The changes in acidity of the juice pa- rallolod the volume changes while enzyme concentration did not. The Action of Physiological Stimulants on Pancreatic Secretion B, Goldstein, Arch, Verdauungs-Krank, 40, 56 (1927) CA. 21:29356 After a high fat diet for about two weeks, 5 normal subjects showed an increase in lipase concentration, and an increase in concentration of protease when a high protein diet was given under the same conditions. Diastase did not show this adaptation to diet. On the I'ochanism of the Adaptation of Pancroatic Enzymes to Dietary Composition M, J; Grossman., H, Greengard and A. C, Ivy. Am, J. Ihysiol. 141, 38 (1944) The young white rats used as experimental animals were sacrificed and the enzymes determined by analyzing the pan- creatic tissue. Substitution of dextrose for corn starch an a balanced diet results in increased amylase content of the pancreatic tissue« Administration o.‘ zinc insulin to rats fed a balanced diet causes a dopro.sion of amylase content, Substitution of casc?.n hydrolysar;o for casein, in a balanced diet produces a depression ti yp:- in content The Effect of Dietary Composition on Pancreatic Enzymes ti. J. Grossman, i. Greengard and A., 0. Ivy Am, J. "hyoid, » 136. 676 U943) Rats were fed various diets for 21 days and their pan- creas was then removed and analyzed for enremes . On a high carbohydrate di< t there 'as prenounced anc.vaso an amylase with \ decrease ..a trypsin. High protein diet resulted in increased trypsin and slight increase in lipase. High fat diet showed no alterations in trypsin or amylase, A diet high in fat and low in protein causes a repression of all pancreatic enzyme formation. The addition of 1% choline to such a diet increases uniformly the content of all enzymes. The Control of the eternal Secretion of the Pancreas in Cats A. A, Harper and C. C, N. Vass. J. Physiol. 99, 415 (1941) The Juice was collected by means of a cannula in the pancreatic duct after .normal saline, distilled water, 5% inu- lin solution, 5- 8'% starch solutions or 5% casein solution were either injected into the stomach through a catheter passed down the esophagus or directly into the duodenum. In the latter instance the gastric juice was prevented from en- tering the duodenum. The presence of foodstuffs in the stomach did not in- crease the enzyme output of the pancreas. As soon as the meal began to pass through the pylorus there was a sharp in- crease in enzyme output and of total Juice, The passage of a casein or starch meal brought about in each case a paral- lel increase in the amount of trypsinogen and amylase. All the substances caused an increase in enzyme output v/hen in- jected into the duodenum. The fact that water and a non- utilizable substance like inulin caused an increase in en- zyme output was thought possibly due to the distension of the duodenum. But experiments using a balloon in the duo- denum showed that it was the substances that exerted the stimulatory effect. The above effects occurred v/hen all the extrinsic nerves to the small intestin had been cut. The Buffer Capacity of Pancreatic Juice M. T, Hoomor, Am. J. Dig, Dis. SOO (1935) From dogs with pancreatic fistulas the juice was col- lected every half hour during fasting and after test moals. Protein diets stimulated the flew more than carbohydrates \ or fat, Tho buffering capacity of the juice reached its maximum one to throe hours after ingestion of food and gradually diminished as the acidity in the duodenum de- creased, The secretion was always alkaline and oven pos- sessed slight buffering power while fasting. t Physiology of External Pancreatic Secretion. VI. Further Studios. A. C. Ivy. J. A, M. A. 39, 1030 (1927) A review is given of the mechanisms of pancreatic secretion. The pancreatic secretory response of dogs to moat and olive oil under various conditions is given in volume per 15:..adnutos, over a period 4-5 hours. The amount of juico secreted in response to moat was about 0 three times that elicited by olive oil. Enzyme analysis of the juice is not reported. The Influence of Plot of Milk and Broad upon tho Activity of tho Pancreas U. M. Joblonski. Arch, d, Sci. Biolog. 4, 377 (1894) (From Tho Work of tho Digestive Glands, I* P. Pavlov, 1910) P* 45 The protoolytic power of tho pancreatic juice of a dog fed on meat was very high, but when placed on a milk and bread diet it decreased continuously over a period of tine. "vdion, under tho influence of a given diet, a parti- cular condition of tho pancreatic activity had been estab- lished in our experimental animals, we were able, by alter- ing the feeding, to reverse it several times in one and tho same animal," , w J P» 46 "Although our laboratory dogs live and are fed under the same conditions, nevertheless tho pancreatic juice of the different animals often differs very essentially in tho t > . .amount' of ferment,, A change of diet in tho case of one dog may very soon manifest itself in altered properties of the juice, while, in another, the remoulding of the pancreas takes place in tho slowest manner. In such cases as tho latter, an abrupt transition from one regime to another may often produce serious illness." A Study of External Pancreatic Secretion in Man B, Kogut, M. J. Matzncr and A, E, Sobol, J, Clin, Inv, 15 393 (1936) in a woman with a partial external pancreatic fistula, an increased rate of secretion was observed after the inges- tion of food. Tests were insufficient to make any con- clusions as to the effect of different typos of food on se- cretion, Enzyme analysis was not done, but the various chemical components wore analysed quantitatively. Experimental Criticism of the Doctrine of the Adaptation of the Digestive Enzymes I, Ercpsin of the pancreatic juice collected after varied feeding, U. Lombroso. Intern, Bo3.tr, Path. Therap, 3, 333 (1912) CA. 6_:1174 II, Lipase of the pancreatic juice collected after varied feeding. R. Bompiani. Ibid.347 III, Amylase of the pancreatic juice collected after varied feeding, T. Rinaldini. Ibid. 356 As a result of their work they conclude that there is no special production of specific enzymes in pancreatic juice to meet the immediate needs of different foods. The variations in enzyme output are ascribed to other sources than the ingested food, 4 Tho Dynamics of Internal Secretions, III* Internal and External Secretions, E. S. London. Arch. Gos. Physiol. (pflugors) 228, 531 (1931) CA. 2^7:21918 Tho maximum output of pancreatic juice after the inges- tion of moat is 2 hours, after broad 2 hours, and after milk 3 hours, while tho maximum output of insulin occurs at the 4th, 5th and 6th hours respectively. The External Secretory Function of the Human Pancreas J. M. McCaughan, B, L. Sinner and C, J. Sullivan. Arch. Int. Mod, 61, 73S (195G) Physiologic observations on the external secretory function of the human pancreas wore made on a patient in whom a pancreatic fistula developed after a gastric resec- tion. A rise in tho secretory rate of juice followed tho administration of secretin, a mixed meal, water, hydrochloric acid, beef broth, dextrose, olive oil, peptone, coffee, mech- olyl and physostigmino. A fall occurred after the adminis- tration of sodium bicarbonate, bile salts, magnesium sulfate, atropine, epinephrine and histamine. The total base was ele- vated after tho administration of secretin, sodium bicarbo- nate and coffee, and was depressed after administration of a mixed meal, beef broth, dextrose, bile salts, physostigmino, epinephrine and histamine. There was no significant change after administration of hydrochloric acid, peptone and magnesium sulfate. Effects of Administration of Pure Foodstuffs and Inorganic Substances on External Secretory Activities of the Liver, Pancreas and Stomach C. VI. McClure, M, S, Huntsinger and a. T. Fernald, Ami J. Physiol. 107, 94 (1934) In normal young men, cottonseed oil, peptone, MgSO^, HCl, and dextrose stimulated the secretion of concentrated pancreatic juice in the order given; Ihe secretion of bile was affected in the same manner, except that and IIC1 were reversed in potency. Studies in Pancreatic Function: Enzyme Concentration of Duodenal Contents after the Ingestion of Pure Foodstuffs and Food Mixtures by Normal Men C, W, McClure and 3, 'Jetmore, Dost, Med, & Surgi J. 187, 882 (1922) The juice collected through a gastroduodenal tube was greater after the ingestion of food than during fasting se- cretion. Lipolytic activity of the juice was greatest after the ingestion of olive oil, less after protein and least af- ter carbohydrate. Duodenal contents obtained after the in- gestion of olive oil showed greater degrees of all types of enzymatic activities .than after protein. After the appearance of food substances in the duodenum there was a latent period before the flow of enzymes and bile began. Physical Characters and Enzymatic Activities of Duodenal Contents C. Wk McClure, A, S. IVctmore and L, Reynolds. J* A* M. A. 77, 1468 (1921) * The findings on 15 normal young men are given after they had ingested test meals* The enzymic activity of the juice secreted after the ingestion of cream, cottage choose and milk meals were considered as standard because of the uniformity of enzyme Response to them. After water meals, during fasting and occasionally after starch and lactose meals the output of enzymes was lower. On the so-called Adaptation the Pancreas V, Michelson. Archiv. f. Verdauungskrqnkhciten 5f, 73 (1932) A review article covering the relationship of different types of food to pancreatic enzyme output. According to Poljak tho administration of diets high in carbohydrate, proteins or fat did not elicit any change in the concentration of enzymes of the pancreatic juice. In dogs, various workers have shown an adaptation of en- zyme output to diet, although some workers showed that fat didn’t elicit a specific response* This latter observation was ascribed to tho fact that dogs usually have little fat in their diet. (This is one of the best reviews that has been found on this particular aspect ol tne work*) Some Observations of the Pancreatic Secretion in a Dog T, Muto. Tohoku J, Exptl. Med, 479 (1937). CA. 32s63115 A dog with a permanent pancreatic fistula was fed a mixture of rice and fish foods with beef, broad and milk in amounts equivalent to l/3 of the calories required for mainte- nance of the normal metabolism. Carbohydrate-rich diets in- creased pancreatic secretion but reduced gastric secretion. The pancreatic juice contained more trypsin after a protoin- rich diot and noro amylase after a carbohydrate-rich diet. Lipase was unaltered. Alkali was reduced during the non- digostivo period. The Relationship of Pancreatic Enzymes to Pood Allergy •*, W, Oclgootz, P. A, Oolgootz and J, W, Witteking, Am, J, Dig, Dis. 1, 730 (1934), Ibid. 2_, 422 (1935), Ibid, 3_, 199 (1936), Med,. Roe. 143, 20 (1956), Ibid. 150, 276 (1939) The foiloiving hypothesis is set forth in all the pa- pers: The amount of enzymes secreted by the normal func- tioning pancreas is in excess of that required for diges- tion in the intestine. The ’surplus * of enzymes is absorbed and enters the blood. Food is absorbed in various degrees of digestion—from protein to amino-acid—and digestion is continued in the blood by virtue of the circulating enzymes. In instances of pancreatic insufficiency the enzyme output may be just enough to take care of intestinal requirements 34 and none, or a very slight amount* enters the blood* There- fore the proteins, motaproteins, etc,, in the blood are not digested and the animal becomes sensitive to foods. Further ingestion of food while in this condition causes an allergic ! reaction to occur. To counteract this the administration of loss food, or of dry pancreatic enzymes is suggested, A test is described to quickly and easily measure blood enzyme levels, starch-iodine mixture is used and the sorum is allowed to act on it. This measures tho amylase, but the blood enzymes always follow a parallel concentration and therefore it is considered an index of the total blood onzymo content. Pancreatic Function, V. The secretory mechanism of tho digostive juices. S. Okada, et al, Arch, Internal Mod, 45, 783 (1930) 3 CA, 24:3816 Sugar shows an inhibitory action on tho secretory center of gastric, pancreatic and biliary secretions. Amino acids and fats stimulate these secretions. The Influence of Physiological Stimuli on Pancreatic Function N. N. Poljak, Dcutsch, Arch, f, Klin, Med, 170, 574 (1931), Nutr, Abs, and Rev, 1_, 118 (1931) Tho effect of tost meals, of cano sugar, starch, egg- white, peptone and oils, introduced into tho duodenum, was tried on the secretion and foment activity of the pancrea- tic juice in 13 persons. None of the meals excited a speci- fic secretion of juice rich in the appropriate ferment. Effects of Feeding Stuffs on the Pancreatic Function of Calves n. Popov, E. Shmakova and V, Kuynetsova. J, Physiol, (USSR) 17, 52 (1S34). CA» 31_:74762 Sunflower silage increases the quantity and alkalinity • of pancreatic juice. Straw foods have the reverse effects. The of the Panbreatic Secretion A, A, Walthor. Arch. d. Sci, Biol. 8, (1899) (From The Work of the digestive I* P* Pavlov, 1910) P, 42 In an experiment using diets of milk, bread and meat, the quantity of juice secreted, the duration of secretion, % dry solids, % ash, $ organic substances, % N, and alkalinity of ash, of the juice wore determined. From those results it is seen that, as regards the total quantity of •juice,, the dura- tion, of its outflow, the percentage of total solids, and, in particular, the percentage of organic solids, there are strik- ing differences manifested in the secretion poured out for the different foods. The quantity of juice corresponds neither to the total weight of the food, the amount of solids which it contains, nor to the quantity of protein in the different va- rieties given. It is related to the physical and chemical properties of the food as a whole. The percentage of or- ganic solids which runs parallel with the quantity of fer- ment is soon in "milk juice" to bo nearly double as high as that in "bread juice" and nearly 3 times as groat that in "meat juice". The percentage of ash and the de- gree of alkalinity are also very different in the 3 cases. If the total quantities of organic solids be calculated for the foregoing diets, it will be soen that milk and flesh receive almost equal amounts, while bread receives double that of cither. SECTION III EFFECT OF FASTING AMD ENVIRONMENT ON PANCREATIC SECRETION The Influence of Complete and Prolonged Fasting on the Se- creting Power of the Pancreas, the Proteolytic Activity of the Pancreatic Juice, and on the Content in Secretin and Enterokinase of the Small Intestine A, G. Barbera. Arch, Fisiol. ■!, 413 (1907), CA. 1:2719^ In dogs which have fasted until they lost 45% of their weight, the pancreatic juice is the same as that in fed animals. A Difference in Effect of Distilled and of Isotonic Solution in Intestine and Pancreatic Secretion J, 0. Crider and J. E, Thomas. Proc. Soc, Exp. Biol. & Wed, 44, 299 (1940) Distilled water in the intestine causes pancreatic secretion; isotonic solutions of inert substances in water do not. The Activity of the Pancr'eatic Function under the Influence of Copius Y/ater Drinking with Meals P, B. Hawk, Am, J. physiol. XXVI (1910) The activity of the pancreatic function as measured by the fecal amylase was found to be greatly facilitated when additional volumes of HgO ranging from 1500-4000 cc, were daily ingested at meals by normal men on a uniform diet. Exhaustion of tho Pancroas during Prolongdd .activity, I. Changes in tho Buffer Constituents of Pancreatic Juice. A» Ct. Kantscr. Hod. Exptl. (Ukraine) No, 6, 85 (1936) CA. 31_:22665 In experiments on dogs prolonged pancreatic activity resulted in a decrease in the pH, titratablc alkalinity, and the buffer capacity of the juice, Tho latter occurred mainly at tho expense of N and P constitutonts. Changes in tho Rate of Secretion and Concentration of tho Pancreatic Juice during Prolonged Activity of the Gland a, G. Kantscr, Med, Exptl, (Ukraine) No. 8, 103 (1936) CA. 3]j22666 During prolonged activity of the pancreas, the rate of secretion gradually decreased while the concentration of tho dry residue increased (mainly the organic constituents, tho inorganic constituents remaining more or loss constant). Effect of Body Temperature on Pancreatic Secretion S, L, Osborne and II, GrOongard, Inn, J, Physiol. 133, P404 (1941) Raising the body temperature resulted in an increased flow' of pancreatic juice up to 7 times tho original rate, and lowering of the temperature operated to complete cessation of secretion. Tho Effect of Dehydration on the Pancreatic and Intestinal En z yme s J. R. Ross and L, Li. Shaw. J. Biol. Chem. 104, 131 (1934) 9 CA. 28:1396 Young rats fed a normal diet but given no water, and placed in an incubator for alternate 12 hour periods for 4 days, showed a decrease in the production of pancreatic and intestinal enzymes, Exocrine Pancreatic Secretion in the Fasting Dog V, B. Scott, J. S. Graham, D, H. McCartney, ,‘n. J. Dig. Dis. 7, 1 (1940) Tho flow of pancreatic juico in fasting dogs showed marked irregularities, being greater in Dragstodt and In- low than in the Elman and IvIcCaughan fistulao. Bilateral intrathoraoic vagotomy did not alter those irregularities. The Relation of Fasting External Pancreatic Secretion to l Hunger V, B, Scott, C, C, Scott, and H, J, Bugcl. Am, J, physiol, 151, 60 (1940) In gastrostomized animals with cannulatcd pancreatic ducts, a temporal correlation exists between the periodic motility of the stomach (hunger) and the external secretion of the pancreas, but this only showed up in of the re- cords, However, when both fasting pancreatic secretion and hunger periods were present the correlation of this activi- ty was 83$, Periodic activity of the stomach and pancreas occurred at irregular intervals} fasting pancreatic secre- tion can occur in complete absconco of hunger contractions and can fail to appear vdth the onset of powerful hunger contractions. SECTION IV THE EFFECT OF -SUBSTANCES OTHER TH. ¥. FOOD ON THE SECRETION OF PAKCR3.-TIC JUICE a. Insulin and Bleed Sugar ’b* Acids, Alkali r.nd Secretin c« Bile and Bile Derivatives d. l-iscollanoous Substances ci. Insulin and Blood Sugar B1ood Sugar Concentration and the External Secretion of the Pancreatic Gland B. P. Babkin. J, A, M, A. 105, 1659 (1935) .ii review of the work done. Hyperglycemia always in- creases the output of enzymes from the acinous cells and in certain cases increases the volume of the secretion. Hypoglycemia produced by the administration of insulin lowers the concentrati n of enzymes in the pancreatic juice. After scctin of the vagus this effect disappears. The con- flicting results obtained with humans arc ascribed to the methods of recovering the juice. The External and Internal Secretion of the Pancreas H. Baer. Klin. ATochschr. 1459 (1923). CL'.. 18;5379 The secretion of pancreatic juice is increased when ether is introduced into the duodenum, and blood sugar is reduced at the same time indicating increase of internal secretin. Glucose given intraven usly leads tc an in- ; crease cf stcapsin raid trypsin, but a decrease of diastase, Blood-Sugar Concentration and Pancreatic Secret! an in the Rabbit S, G, Baxter. Quart, J, Exptl, Physiol. 21, 355 (1932) CA. 26;35508 Insulin hypogluccmia caused a diminished output of en- zymes 'by the pancreatic gland in a rabbit having vagi intact r.nd spontaneously secreting pancreatic juice. This pheno- menon was not observed if the vr.gi had boon cut, -.hen the secretion has been arrested by hypoglucemia it may be re- stored by intravenous injecti n of hypertonic glucose solution. Relati nship between the Internal and External Secretion of the j: ancreas G, Deusch and E. Drest. Klin, 'Vochschr, 6, 2130 (1927) CA. 22:6254 Impairment f the internal secretory function of the pancreas as this occurs in the diabetic, has no effect upon the sccroti n or c -mpositi n cf the digestive fluid. The -cti .n of H rm nics on the Secretion of the Digestive Enzymes, V. Influence of Insulin cn the Secretion of Pan- creatic Enzymes. R. Ferrari. Arch. Fisiol, 35, 145 (1935). Cl*. 30:4907^ Dogs wore treated with insulin and the pancreatic se- cret! was investigated during hypoglucemia. The amyloly- tic power was decreased 10-20 times; the lipolytic and pro- teolytic powers increased 2-6 times. The action is supposed- ly not due to hyp:lycomia, as artificial hyporglucomia has no influence on the enzyme cintent. Concludes that insulin acts directly on the pancreatic tissue. Action cf Insulin on the External Secretion of the Pancreas in the Case of Pancreatic Fistula F. Fonseca and C, Trincac. Compt. Rend. See. Biol. 99, 5 1532 (1928). CA. £3:144l" Experiments with human subjects showed that insulin increased quantitatively the external secretion of the pan- creas when given with a mixed diet, but docs not affect the external pancreatic secretion fasting conditions. .lotion cf Certain Drugs on the External Secretion of the Human Pancreas Ibid 1533 Tests with a patient having a pancreatic fistula proved that odor or sight of food, pituitrin, atropine, pilocarpine and orgotamino increased the flow from the fistula, Pituitrin, atropine and ergotamine decreased the quantity of enzymes in the juice, while pilocarpine increased the enzymes. Adrenalin decreased both the flow and the enzymes, while ephodrino and ephetonine diminished the secretion without changing the enzymes. Effect of Intra-Du ■ dcnal Injection of ..cid :;n tho Internal Secretion of the Pancreas J. and Saadi-Nazim. Cempt. Pend. S c. Bi d. 95, 571 (1926). C-l. 2£:4584 Inject! n of 0.5;a HC1 into the duodenum of dogs anaes- thetized v:ith chloral or into the stomach of n n-anaustho- tized dogs causes a diminution of the blood sugar nhich be- gins 15-50 minutes after the injection and lasts for 1-2 hours,, indicating that substance bringing about the secre- tion cf the pancreatic juice also cause producti n of insulin. % External Pancreatic Socroti n and the Discharge of Bilo Dur- ing Hypogluccmia Follov;ing Intravenous administration of Insulin h, R, Frisk and 0, 'Telin. Mod. Scand, 91, 170 (1937) G„, 30:22918 There v/as a small increase in duodenal contents, a slight increase in the bicarbonate conccntrati n, and a marked increase in diastase. The flotr of bile r/as also » stimulc.tud. Relati n Betaaen the Bl *d-Sugar Conccntrati :n and the Exocrine Function rf the Pancreas C, 0, Hebb, Arch. Intern. Pharmacodynamic 52, 33 (1955) Cl.. 30;64485 The conccntrati n of blood sugar affects the amount of enzyme secreted by the pancreas. Intravenous injection of glucose causes increased enzyme secrcti n but NaCl or docs not. Atropine inhibits the effect so the in- creased lipase activity is probably due to the effect of the bl *'od sugar on the parasympathetic nerves. The direct addition f glucose to the pancreatic juice docs not in- crease its lipolytic activity. Variations in x Gocretion during Hypcrglucemia Resulting from Intravenous Injection of Glucose J, LaBarre and ?. Dcctrec. Compt. Rend, Sc, Biol. 105, 35 (1930). CA. £6:38314 ' Hypcrglucemia stimulates the higher nerv us system, leading to vig reus pancreatic secrcti n. i Insulin and the External Secretion of the Pancreas J. LaBarre and A. Dcstree. Compt. Rend, See. Biol. £8, 1237 (1928). CA. £2;27904 The injection of insulin co.uscs a diminution in the output of pa.ncrcatic juice especially marked at the moment of tho greatest lowering of the glucemia, Lipase, trypsin and amylase arc diminished at the some time. Stimulating Action of Intravenous Injections of Dextrose on the External accretion of tho Pancreas J. LaBarre and p. Dcstrec, Compt, Rend, Soc, Biol. 96, 1240 (1928). CA. 22;27905 Injection of hypertonic glucose solutions causes an increase in the pancreatic secretion and tho enzyme content f of the secretion. The Effect of Insulin Therapy on Pancreatic Enzymes in lialnutriti n C. Luodors and la. E, Watson, Int, Lied. 49_, 330 (1932) Inject!-ns of insulin twice daily in a group of pa- tients with malnutriti n, produced measurable increase in the concentration of pancreatic enzymes recovered from the duodenum during fasting. Studies of the st°ol before and following insulin therapy showed a direct parallel between the more complete digest!.n and assimilation of fo~d ele- ments and the increased concentration of pancreatic enzymes. Pancreatic Function Okada, et. al. „rch. Int. Med. 43, 446 (1929) T/ylth human subjects insulin stimulates gastric, bili- ary and pancreatic secretion; epinephrine and ephedrine in- hibits it. .;hen dextrose is introduced into the duodenum it brings about an initial increase of pancreatic juice; the hyperglycemia resulting after it is absorbed, through, stops the flow of juice almost entirely. Pancreatic Activity in Diabetes Ilellitus S. Okada, ot.al, Proc. Imp. Mead, (Japan) _4, 134 (1928) Cl,. 22_:46383 The disturbance of pancreatic function manifests it- self in the dccroaso of enzymic activity or of the amount of juice, or of both, the greatest alteration in enzymic efficiency end activity being in the proteolytic and lipo- lytic enzymes. There may be disturbances cither in the internal or of the external secretion, or of both, the se- verity of the diabetes not necessarily running parallel to the degree cf distrubance in the external secretion. The External Secretion of the Pancreas and Diabetes Mcllitus H. H, Pollard, L, Miller and 17. Brewer, Mm. J. Dig. Dis, 1£, 20 (1943) In a clinical study using the secretin test there were diminutions in volume of secretion, total secretion of bicar- bonato, and tho enzymes amylase and trypsin. These findings arc correlated only with the duration of the disease and not with the ago of the patient, the severity of the disease, the presence or absconcc of acidosis, the amount of insulin required or the diet. The Relation of External Pancreatic Secretion to Variations in Blood Sugar V. B, Scott, N, J. II, J, Bugol and G. C, Johnson. Am, J, physiol, 134, 208 (1941) Insulin hypoglucomia increases the volume of pancrea- tic juice secreted by unanacsthotizcd dogs with permanent pancreatic fistulas. Intravenous glucose temporarily in- hibits the pancreatic secretion which appears spontaneously or in response to insulin. Exclusion of the gastric juice 1 from tho duodenum abolishes the rapid pancreatic secretion of insulin hypoglucomia. Spontaneous variations in the volume of tho fasting pancreatic secretion and gastric mo- tility arc unrelated to tho fluctuations in blood sugar. Diabetes and External Secretion of the Pancreas ?, B. van Stconis. Nederland, Tijdschr. Gcncoskundc 78, II, 1529-36 (1934). CA, 2£;2121 Records are given shelving that the external secretion of the pancreas is often disturbed in diabetes. b, .acids, Alkali and Sccrobin The Effect of Changes in the Reaction of the Blood on Pancreatic Secretion J. A, Archawskyv Arch. Ges, Physiol, (pflugers) 224, 128 (1930). CA. 24;45439 The pH and CO content of the blood are related to Lj the pancreatic secretion. i The Composition of Pancreatic Juice and Blood Serum as Influenced by the Injection of Acid and Base E. G, Ball. J. Biol. Chem. 86, 453 (1930). CA. 24J38191 The pH of pancreatic juice varies with its rate of flow, the juice being more alkaline when secreted rapidly. The sum of (HCO -) and (C1-) is nearly constant regardless of the rate of flow. Intravenously injected HC1 does not affect the pH greatly. Intravenously injected Na CO in- 2 3 creases the (HCO -) and (N -) of the juice but does not 3 a affect its pH. f A Disturbance of Pancreatic Secretion in Connection with the £linical Observation of a Case of Continued Pancreatic Super-Secretion Bickel. Deut, ivied, 'lochschr, 34, 2111 (1908), CA. The amount of secretion at various times are tabu- lated, The flow was reduced on giving or opium. The Juices of Pancreatic Hypersecretion g C. Fleig, Compt, Rend. Soc, Biol. 70, 16 (1911), CA.5:1293 Hypersecretion from the pancreas obtained by fistulas and injection of HC1 showed a lipolytic power below normal. This is due to changed viscosity and alkalinity rather than to any change in lipase content, Acid-Base Composition of Pancreatic Juice and Bile J, L. Gamble and M. A. Mclver. Jr Exp, Mod, 48, 849 (1928) The juice was obtained from a human with a pancreatic fistula and from dogs with duodenal fistulas. Pancreatic juice contains fixed base at approximately the concentra- tion found in the blood plasma. Chloride ion is present in concentration varying from one-fourth to one-half the fixed base value and the remainder of the acid equivalence is com- posed of bicarbonate ion. Fixed base being a nearly sta- tionary factor, variation of bicarbonate and thereby of al- kalinity is referable to change in the concentration of chloride ion. The Effect of Hydrogen Ions of Carbonated Water on Pancreatic Secretion F, Kmiotowicz, Compt, Rend, Soc. Biol, 89, 493 (1923) CA. 18-.8551 Pancreatic juice is increased following the introduc- tion of carbonated mineral water. The secretory principle 51 in mineral -water containing CO is the H ion of the carbo- Cj nic acid. After boiling such water loses its effectiveness. Pancreatic Secretion in Distrubed Gastric Secretion S, Okada, et.al, Proc, Imp, Acad, Tokyo £, 423 (1928) CA. 2j5:4306 The pancreatic secretion is not necessarily disturbed by disturbed gastric secretion. In some cases it is increased. The presence of HCl is not necessary to stimulate normal pancreatic secretory activity. The Secretory Activity of the Pancreas as Influenced by Hy- drochloric Acid and Intestinal Extracts (so-called "Secretin”) L, Popiolski; Arch, Ges, Physiol, (Pflugcrs) 120, 451 (1907) CA. 2_:20993 The Characters of the Secretory Activity of the Pancreas Under the Influence of the Hydrochloric Acid and of the Intestinal Extracts 3 ibid, 121, 239 (1908). CA, £:3000 Two extensive articles, the main purpose of which is to criticize Bayliss and Starlings’ secretin hypothesis. Contains the results of experiments dealing with the effect of many typos of substances on pancreatic secretion. The Dependence of the Secretory Products of the Digestive Glands on the nature of the Stimulus Inciting Them. The Effect of the Acidity of Fluids Introduced into the Duo- denum on the pH o£ the Pancreatic Secretion N, A. Popov and A* A. Kudryashov. Arch. Ges. physiol. (Pflugers) 224, 66 (1930). CA. 24:45457 The introduction of 0,1% HC1 into the duodenum of a decerebrate dog resulted in the production of pancreatic secretion of greater acidity than that which followed the . « r introduction of a 0,5 to 1,0% HCl solution, A Quantitative Study of Acid in the Intestine as a Stimulus for the Pancreas J. E, Thomas and J, 0, Crider, Am, J, Physiol, 131, 349 (1940) From dogs with gastric and duodenal fistulas pancrea- tic Juice was collected after adding various buffer solutions to the intestine. The pH threshold for the stimulation of . / pancreatic secretion was near pH 5,0, The practical acid threshold for causing a significant amount of secretion in the dog digesting raw moat was estimated to bo near pH 4,0, Specific Gravity and Total Nitrogen of pancreatic Juice Secreted in Response to Various Stimuli J, E. Thomas and J, 0. Crider, Am, J, Physiol. 140, 574 (1933) Various stimuli were injected into the intestines of unanacsthctized dogs provided with gastric and duodenal fistulas. The spocifio gravity and total nitrogen of the juice was noted. Poptono causes the most concentrated sc- 1 crotion, soap a loss concentrated one, and HC1 the most dilute. The latter secretion was similar to that caused by intravenous administration of secretin. Influence * of Alkali on tho Function of the Pancreatic Glands g V, N, Vorobyev. Zontr. physiol, 28, 617 (1914), CA,9:104 Intravenous injection of alkaline salts of Na, K. Li, Ca, and Mg in dogs caused an increase in flow of pan- creatic juico, tho more soluble ones causing a rapid flow of short duration and vice versa. Alkaline solutions cause an increased alkalinity of tho juice and a lowered foment content. Changes in tho Duodenal Juicos Effected by the Introduction- 6f Various Substances M, Wichert and W, Divorjotz, Arch. Vordauungs-Krankh, 34, 158 (1925), CA. 19:1732 The introduction of HC1 into tho duodenum calls forth I increased trypsin secretion; oil effects an increase in tho lipase and other causes marked secretion of tho pancreatic juice. Tho Influence of Sodium Hydrogen Carbonate on the Pancrea- tic Secretion E, Wilbrand. Munch. Mod, Wochschr, 61, 1437 (1914) 7 CA. 223 On dogs with duodenal fistula per os dimin- ishes the pancreatic secretion, more so when given in solution than in substance. Heat Production in the Pancreas. III. Tho inhibitory ef- fect of saline on the HCl-pancreatic secretion. N. Yoshii, Japan J, Mod, Sci. Ill Biophys. 4, 409 (1937) CA. 32_:92624 With anaesthetized dogs the intravenous or intraduo- donal injection of physiological saline or of a 15$ salt solution decreased tho secretion of pancreatic juice in response to the introduction cf HCl into the duodenum. There was no effect on the blood pressure or on the temperature of the pancreas. Continuous Pancreatic Secretion T. F. Zucker, p, G, Nowburgor and B. II, Berg, Am, J. Physiol. 102, 193 (1932) % In a dog with cannulatcd pancreas tho secretion is con- tinuous, but food or the injection of secretin temporarily increases the rate of flow. Anaesthesia may completely in- hibit the flow of pancreatic juice. Ether increases the amylase level of the blood. c. Bile and Bile Derivatives The Relation of Bile to the Secretion of Pancreatic Juice L. R, Dragstedt and R, A, Woodbury. Am. J. Physiol* 107, 584 (1934) Concludes that in the dog the presence of bile in the i duodenum cannot be considered essential for the secretion of pancreatic juice. Bile Salts and Secretin as Cholagogs J, Mellanby, J, physiol..64, 5ol (1928), CA. 22;32Q6^ Bile, placed in the duoden an, stimulated the secre- tion of both pancreatic juice aid cile; placed in the il- eum it stimulated the liver and ion the pancreas; injected into the blood bile salts stimuli bile flow and had no effect on pancreatic secretion. The Secretion of Pancreatic Juice J. Mellanby. J. Physiol. 61, 419 (19£c) Cholic acid is the active substance in bile stimula- ting the flow of pancreatic juice, but its activity is mo- dified by its association with taurine and glycine, and the presence of mucin in the bile. The Effect of Bile in the Intestine on the Secretion of Pancreatic Juice J. E. Thomas and J. 0. Crider, Am., J. Physiol. 138, 548 (1943) In normal unanaethetized dogs provided with gastric and duodenal fistulas the injection of ox bile or dog bile into the intestine does not increase the rate of secretion of pancreatic juice. The amount of pancreatic juice se- creted in response to the presence of peptone, soap or HC1 in the intestine is less when bile is also present than when it is absent from the intestine. Experimental Study on the Mutual Relation Between the Pan- creatic and Hepatic Functions T, Yuasa. Japan. J, Gastroenterol, 8, 187 (1936) CA. 31:1484 In hepatic disturbance the pancreatic juice in- creases while the quantity of enzymes remains quite constant. Bilirubin, cholesterol and bile acid salts can be injected into the blood without affecting the secretion of the pancreas. d. Miscellaneous Substances The Parallel Concentration of Enzymes in the Pancreatic Juice S, G, Baxter, Am, J, Dig-, Dis-, 108 (1935) The pancreatic duct of anesthetized rabbits was can- nulated and the juice collected. After stimulating the flow with pilorcarpin the enzymes of the juice showed a parallel increase with the increased flow of juice. The Effect of Magnesium Chloride of Mineral Waters on the Secretion of Glands Emptying into the Intestine P. Carnot and H, Gaehlinger, Compt, Rend. Sec, Biol, 88, 1129 (1923). CA, 1_8;1238 Experiments with dogs and humans shows that isotonic solutions of MgClg either per rectum, subcutaneously or through the duodenum stimulate the activity of the liver, pancreas and intestinal glands, the secretion also posses- sing increased enzymic activity. Similar results were ob- tained with but much thick bile results, produces the same effect when introduced into the duodenum, but no'effect subcutaneously. 58 The Histological Change in the Endocrine and Other Organs after the Administration of Cayenne by Mouth to Rabbits C. Y. Choi and Y. C. Lee,. Korean Med. J. 7_, 77 (1937) CA. 32S42271 Hyperfunction of the pancreas was shown in histological picture at the initial stage of administration, but by con- tinuous feeding hypofunction was gradually exhibited, i The Effect of Barbiturates on Digestive Secretion R. J. Coffey and R, Koppanyi. Am, J, Dig, Dis, 7, 21 (1940) Barbiturates in largo hypnotic and anaesthetic doses produce a reduction of the gastric and pancreatic secre- tions, with a prompt return to normal flow after hypnotic doses, and a delayed return after anesthetic doses. Pancreatic Secretion in Man After Administration of Differ- ent Stimulants: A Comparative Study M, W, Comfort and A, E, Osterberg, Am. J. Dig. Dis. 8, 1 (1941) , Administration of vitamine A and starch did not pro- duce a measurable stimulation of the fractions of the duo- denal contents, I.Iecholyl stimulated various fractions of duodenal contents more uniformly and potently than casein, fat and prostigmine methylsulfate. Secretin is stimulant of choice for study of secretion of fluid and bics.rbonate; secretin plus mecholyl chloride effected greatest secre- tion of all fractions of duodenal contents. The Effect of Ephedrine on Pancreatic Secretion C. B. Craft. Surgery 4, 64 (1938). CA. 32_;7571? Ephedrine produced a definite decrease of secretion of pancreatic juice in dogs. Action of Formaldehyde Injected into the Intestine on Pancreatic Secretion C. Delezenne and E* Pozerski, Compt. Rond. Soc. Biol. 78, 1 23 (1915). CA. 10:2374 In dilute concentrations formaldehyde stimulated the flow of pancreatic juice. The Effect of Phlorhizin upon Pancreatic Secretion L. Dunner and H, Blume. Klin, “ochschr, 10, 445 (1931) CA. 25_:40542 The intramuscular injection of phlorhizin .into nor- mal human subjects usually causes a 1-|- - 2 fold increase in duodenal secretion. The enzyme content of the fluid is markedly increased, particularly with respect to tryp- sin and diastase. With certain pathological conditions the effect was not observed. The Influence of Ilagnesiuqi Sulfate on the Secretory Activity of the Digestive Glands W, H. Gantt and G, V, Volborth, Am, J, Med,.Sci, 179, 375 (1930), CA. 25_;1472 There was a slight increase in pancreatic juice I after giving MgSO through a stomach tube. The Enzymp Content of Pancreatic Secretion .Following Various Stimulants H. Greengard, M, J, Grossman, R, A, Roback and A, C, Ivy, Am, J, Physiol. 141, 509 (1944) Pancreatic juice was collected from anaesthetized dogs after giving the stimulants. Sodium nitrate and pro- stigminc were found to produce an enzyme rich secretion; epinino and SI (secretin plus pancreozymin) and enzyme poor one. All enzymes determined (amylase, lipase and trypsin) wore equally affected by the various stimuli. The Influence of a 5% Extract of Shottsuru (a_ Kind of Animal Seasoning) on the Intestinal Movements, the Score- tion of Bile and the Pancreatic Secretion Y. Hirawa. Mitt, Mod, Akad. Kyoto 29,- 635 (1940) CA. 35_: 37126 Shottsuru accelerated the pancreatic secretion but had no effect on the bile secretion. 61 Tho Action of P- Hydroxyphenylethyl amine, II* Effect on the secretion of Pancreatic juice. M, Kageyana. Acta -Scholao Med, Kyoto 1_, 229 (1916) CA. 11_:3338° Injection of tyramine inhibits tho flow of pancreatic juice, . Hypnotics and Their Action on the Thalamic Centers. IV. The Action of on the Pancreas, J, LaBarro and 0, Vcsselovsky, Arch. Intern, Pharmacodynamie 67, 267 (1942), CA. 38:4329? The intravenous injection of causes a diminution of the response of the pancreas in dogs, and the lipase con- tent of the collected juice is low. Action of Quaternary Amines on Pancreatic Secretion L. Launoy, Compt, Rond, Soc, Biol, 73, 374 (1312) CA. 7_: 517° Ethyltrimethylammonium chloride, bromo ethyl- trimethyl ammonium bromide, and choline - HC1 stimulate pancreatic secretion. The first two are toxic and me- thods of reducing the toxicity are discussed. The Action Quarternary Amines on Pancreatic Secretion III. Ibid ISi CA. 1:8421 Further work with other quartornary amines is discussed. Action of some Amines,. Especially Tetnamethylammonium Chloride and Hydroxide, on Pancreatic Secretion Ibid 7?, 1068 (1912). CA. 7_;29714 The effect of various amines are discussed. The activity of tetramethylammonium hydroxide or chloride is practically identical with that of choline. The Influence of Eserine on the External Secretion of the Pancreas L. Liaci, Biochem, Torap, Spor. 25, 445 (1938), CA. 33:2219''* In dogs small doses of eserine stimulated and larger doses inhibited pancreatic secretion. Biliary, Pancreatic and Duodenal Studies, I. The H-ion concentration of Successive Portions of Duodenal Contents Following Stimulation with HgSQ^ L, Martin,- Arch. Internal lied, 39y 275 (1927). CA,21: Installation of LlgSO by duodenal tube is followed by a slightly acid reaction of the secretion, the acidity increasing the longer the tube is retained. Active pan- creatic enzymes are found in the alkaline fraction before the change of reaction. The Extemal Secretory Function of the Hur.ian Pancreas J. M, McCaughan, B, L, Sinner and C* J, Sullivan. Arch. Int. lied* 31, 739 (1938) Physiologic observations on the function of the human pancreas were made on a patient in whom a pancreatic fistula developed after a gastric re- section, A rise in the secretory rate of juice followed the administration of secretin, a mixed meal, water, hy- drochloric acid, beef broth, dextrose, olive oil, peptone, coffee, meoholyl and physostigmine, A fall occurred after the administration of sodium bicarbonate, bile salts, mag- nesium sulfate, stropine, epinephrine and histamine. The total base was-elevated after the administration of secre- tin, sodium bicarbonate and coffee, and was depressed af- ter administration of a mixed meal, beef broth, dextrose, bile salts, physostigmine, epinephrine and histamine. There was no significant change after administration of hydrochloric acid, peptone and magnesium sulfate. « Effect of Geneserine on Salivary and Pancreatic Secretion M. Polonovski and P* Combemale, Compt, Rend, Soc, Biol. 88, 881 (1923), CA. 17:23268 The alkaloid geneserine increases the salivary and pancreatic secretions. The Ef f ects of the Subcutaneous Injection of Organ Extracts upon the Flow of Pancreatic Secretion J. Rogers, J, M, Rahe, G, G. Fawcett and G. S, Kackett, Am, ■ J, Physiol. 40, 12 (1916) The effect of the subcutaneous injection in dogs of the residue, or non-cogulable portion, of an aqueous ex- tract of the liver is the immediate and vigorous stimula- tion of the external secretion of the pancreas. The resi- dues of the thyroid and thymus produce a somewhat less vigorous and later response,'.- The residues of the pitui- tary, parathyroid, spleen and pancreas are inert, - The residue of the adrenal gland is inhibitory. Only the re- sidues or non-coagulable portion show any appreciable effect.- The Action of Thyroxine on the Amylase,'Lypase, and Trypsin of the Pancreas G.-Scoz, Boll, -Soc,.Ital, Biol. 971-3 (1934) CA. 29^:18426 In dogs treated with thyroxine, the amylase of the pancreas decreased about Q0%; the lipase,.an average of the trypsin,-an average of There was no re- lation between variations in weight and variations in the enzymic activity of the treated dogs. 65 Th<3 Action of Karlsbad, Glauber and Epsom Salt on the External Secretion of the Liver and Pancreas 4 H* Simon. Deut. lied# Wochschr* 50, 1012 (1924). CA. 18:3085 The intraduodenal administration of these salts increases the secretion of liver and pancreas. Effects of Sodium Evipan on Certain Functions of the Digestive Tract. Salivary and Pancreatic Secretion and Intestinal Movements, A, Tournado and E. Joltrain. Conpt, Rond. Soc. Biol, 121, 5 908 (1936). CA. 50:4216 Evipan anaesthesia does not affect the flow of pan- creatic juice after the injection of secretin. 66 SECTION V FUNCTION TESTS a. Analysis of Duodenal Contents b* Analysis of Blood Enzymes c. Other Function Tests a. Analysis of Duodenal Contents The Secretin Test of Pancreatic Function in the Diagnosis of Pancreatic Disease G. Agren, H. Lagerlof and H. Berglund, Acta Med. Scand. 90, 224 (1936) Normal values for pancreatic enzyme output are given. There is very little functional disturbance in acute pan- cretitis, but in disturbances associated with a decrease in diastase and trypsin, the gastric juice is not affected by the secretin injection during the test. V ’ ' r Pancreatic Enzymes in the duodenal Juice in the Celiac Syndrome D. H. Andersen. Am. J. Dis, Child, 63, 643 (1942) .The assay of trypsin in the duodenal juice is a re- liable means of diagnosis of pancreatic deficiency. The assay of amylase is not a reliable means of diagnosis, be- cause of its low concentration during the first months of life in normal infants and in older infants and children with chronic diarrhea. Amylase may occasionally be pre- sent with pancreatic fibrosis because of the failure of salviary amylase to be destroyed in the stomach. Lipase is present in normal infants of all ages. The values of enzyme concentration in normal and diseased infants is given. 67 Diagnostic Value of Pancreatic Function Tests in 4£ Surgical- ly Treated Cases L, Bauman, A. 0. ‘‘hippie* Am. Ji lied* Sci. 207, 281 (1944) The pancreatic enzyme content of patients v.rith vari- ous pathological conditions are listed and the findings discussed. The Measurement of the External Pancreatic Secretion in the Clinic by the Secretin Test M* Chiray and M* Bolgert, Nutrition (Paris) 6, 223 (1956) The results of use of the test in the clinic on patients with various pathological conditions are described* The Diagnosis of Pancreatic Affections by a Test with Purified Secretin M. Chiray and M, Bolgert. Presse Med, 44, 428 (1936) CA. 31:1S372 A technic is described of collecting pancreatic juice after application of secretin, and evaluating the enzyme value of the sample-. Tests of Pancreatic Function M* Tf, Comfort. J, A'* A-, 115, 2044 (1940) The use of purified secretin plus mecholyl cloride as a diagnostic aid is described; both normal and abnormal . I values for the secreted juice (obtained by a double-barreled gastroduodenal tube) are given. The use of stool analysis for undigested and unabsorbed food, blood enzyme determina- tions and urine amylase determination as tests for pancrea- tic dysfunction are discussed. The Concentration of Pancroatic Enzymes in the Duodenum of Normal Persons and Persons with Disease of the Upper Part of the Abdomen M, W, Comfort, R. L, Parker and A, E, Ostorberg, Am, J, Dig, Dis. £, 249 (1939) Normal values for trypsin, lipase and amylase are given-, A marked contraction of the range of concentra- tions of these was found in patients with carcinoma of head of pancreas, and of the ampulla of Vater, and chronic atrophic pancreatitis with steatorrhea. Studios in Pancreatic Disease, I, Duodenal Content An- alyses as an Index of Disease and Functional Activity of the Pancreas. B., B* Crohn, Arch. Int, Mod, 15, 581 (1915) Correlates the quantitative results of enzyme an- alysis of duodenal contents with diseases of the pancreas.. The Clinical Application of Secretin in the Study of Pancreatic Function J. S. Diamond and -S, A, Siegel. .N, .Y• State .J, Med. 41, 869 (1941) 4; The use of the secretin test on 90 patients, both normal and with pathological conditions .is described, and the findings discussed. It was found that in pathologic states of the pancreas the enzyme production first became affected; the volume and bicarbonate were more stable and less easily disturbed. The Secretin Test in the Diagnosis of Pancreatic Diseases with a Report of One Hundred Thirty Tests J, -S, Diamond and S, A, Siegel, Am, .J, Dig, Dis, 7, 435 (1940) The use of the secretin test and the results obtained with it on patients with various pathological conditions are discussed, TThen secretin alone is injected, pancreatic juice of low enzyme content is elaborated, TAien insulin or other vago.l stimuli are used in conjunction with secretin the enzyme concentration is increased 2 or 3 fold. The Use of Secretin as a Clinical Test of Pancreatic Function J.-S, Diamond, S, A, Siegel, jiL -B. Gall and,S, Karlen. Am, - J, Dig, Dis, 6, 366 (1939) The results of studies of pancreatic function in nor- mal and abnormal cases by means of the secretin test are given. The Secretin Test as an hid in the Differential Diagnosis of the Steatorrheas with a Report of Fourteen Cases J. S. Diamond, S. A, Siegel and S, Myerson, Rev. Gastro- enterology 7, 429 (1940) The use of the 6ecrctin test in diagnosing cases of pancreatic dysfunction is described. The results of its use on fourteen patients are given in detail. The Involvement of the Pancreas in Liver Diseases with a New Method of Testing Pancreatic Function P, Bckey. Ztchr.'f, d, ges, Exp, Mod, 94, 726 (1934) Nutr, Abs, and Rev, 4, 791 (1935) A method of estimating pancreatic efficiency is de- scribed which consists in estimating the volume and tryp- tic activity of duodenal juice before and after the intra- duodenal administration of 3 ml, other. Disturbances in secretion wore noted in cases of hepatic cirrhosis,, chole- cystitis,. jaundice and pernicious anemia. Pancreatic Function and Disease in Early Life, I, Pancrea- tic Enzyme Activity and the Celiac Syndrome. S, Farber, H, Schwachman and C, L, Haddock, J, Clin, Invest, 22_, 827 (1943) Over 150 determinations of the activity of trypsin, amylase, and lipase were made. Patients with ’pancreatic fibrosis’ exhibit a reduced enzyme content of duodenal juices. Study cf the Enzyme Activities of Duodenal Contents as a Means of Evaluating Pancreatic Function A* H. Free, A, J, Beams and V* C* Myers, Gastroenterology 1, 188 (1943) Quantitative determinations of enzyme activity were carried out in a group of normal subjects during fasting and after stimulation of the pancreatic secretion with olive oil# On the basis of hesults obtained in those sub- jects a system of evaluating pancreatic secretory activity is described* Pancreatic Function and Disease in Early Life* II# Effect of Secretin on Pancreatic Function of Infants and Children* C. L. Haddock, S, F.arbcr and H, Schwachman* Am* J* Dis* Child. 66, 370 (1943) / By means of intravenous injection of *pancfootest1 secretin pancreatic function tests wore carried out on children (6 wks. to 11 yrs.) with various nutritional and pancreatic disorders. In normals and in all cases except those of pancreatic fibrosis there was a postinjoction in- crease in' volume and pH, Patients with pancreatic fibro- sis and trypsin deficiency both failed to show postinjec- tion increase in tryptic activity, -ill cases except fi- brosis showed increase of lipase after secretin, and there was increased amylase in all except fibrosis and celiac disease, in which there was a decrease* Now Methods for Estimating Enzymatic Activities of duodenal Contents of Normal Man C. W. McClure, A. S, Wetmore and L. Haynolds, Arch. Int, Med. £7, 706 (1921) Methods of determining proteolytic, lipolytic and amylolytic enzymes are discussed, and their shortcomings in using them for analysis of the enzymes of duodenal contents arc pointed out. The authors' methods for the determining of these enzymes in duodenal contents are given in detail, and their accuracy is discussed. An Analysis of the Duodenal Drainage in the Stcathorrheas H. F, Philipsborn, Jr, et.al, J, Pediatrics 26, 107 (1945) The duodenal contents of normal children, 'feeding problems', and children with pancreatic disease were ana- lyzed for enzymatic activity, and the values obtained are given, 'Feeding problems' may be due to temporary pan- creatic insufficiency. The External Secretion of the Pancreas and Diabetes Mellitus H, M, Pollard, L. Miller and W, A, Brewer. Am, J, Dig, Dis, 10, 20 (1943) In a clinical study using the secretin test there were diminutions in volume of secretion, total secretion of bicar- bonate, and the enzymes amylase*and trypsin. These findings are correlated only with the duration of the disease and not with the age of the patient, the severity of the disease, the presence or abscence of acidosis, the amount of insulin required or the diet. 73 b* Analysis of Blood Enzymes Acute Pancreatitis, with Special Reference to Pathogenesis and the Diagnostic Value -of the Blood Amylase Test W# R, Cole, Am*-•. J# Surgery 40, 245 (1938) In acute pancreatitis the level of the blood amylase is high usually only during the first 2 or 3 days of the attack. The amount of serum amylase found in clinical cases is given,, Serum Lipase; Its Diagnostic Value M, W* Comfort, Am, J, Dig. Dis, 817 (1937) A method of determining serum lipase is described. Values obtained with normal subjects and with patients with various diseases are given. Serum Lipase: Its Diagnostic Value M. W. Comfort, Proc, Staff Hayo Clinic 10, 810 (1935) Discusses the values obtained in the clinic with various pathological conditions. An increased activity of the s erum lipase appears to be a very efficient test for pancreatitis, less so for malignant disease of the pancreas. 74 Serum Amylase and Serum Lipase in the Diagnosis of Disease of the pancreas M. W, Comfort and A, E. Osterberg, Lied* Clin, N. A 24, 1137 (194-0) Discusses the determination of serum amylase and li- pase and the use of them in diagnosing diseases of the pan- creas, The authors are of the opinion..that as of the time of writing the article the determination of the value for scrum lipase is the more reliable as a test for pancreatic function. Lipase and Esterase in the Blood Serum. Their Diagnostic Value in pancreatic Disease. M, W, Comfort and A, E, Osterberg, J, Lab, Clin. Med. 20, 271-8 (1934). CA. 2_9:25947 An increased activity of serum lipase was observed in acute and subacute pancreatitis and in cases of obstruc- tion to the outflow of pancreatic juice due to carcinoma of the head of the pancreas. An increase observed in duodeni- tis, cancer of the stomach and other conditions was appar- ently due to associated pancreatic disease. The concentra- tion of esterase, which is normally present in blood scrum, appears to boar no relation to the condition of the pancreas. Lipase and Esterase in the Blood Serum: Their Diagnostic Value in Pancreatic Disease M. V. Comfort and A. E, Osterberg, Proc, Staff May Clinic £, 250 (1934) A discussion of the methods of determining serum lipase and esterase, and the use of them in diagnosis of pancreatic dysfunction. The Variations of Blood Amylase During Acute Transient Disease of the Pancreas R, Elman* Ann, Surg, 105, 379 ('1937) The results of the use of the scrum amylase test with patients suffering from transient attacks of acute abdominal pain and having other symptoms of gastrointestinal distur- bance are discussed. There was a very high concentration of blood amylase at the height of the attach, but returned to normal with a subsidence of the symptoms• Value of Blood Amylase Estimations in the Diagnosis of Pancreatic Disease R, Elman, N. Arnoson and E. A. Graham, Arch. Surg. 19, 943 (1929) A clinical study in which the blood amylase was de- termined in 60 patients. Deviations from the normal range were found in patients with pancreatic disorders. Diagnostic Significance of Determinations of Scrum Lipaso T. A, Johnson and H# L, Bockus. Arch, Int, Hod, 66, 62 (1940) A report of tho study of 371 eases in which the scrum lipase was determined, Tho reports of others showing that diseases of tho pancreas show tho highest incidence of increased values for serum lipaso are confirmed, A Clinical Evaluation of tho Laboratory analysis of tho Function of tho Pancreas, g B. E, Logon. Klin. Hod. (USSR) 17, 57 (1939). CA, 33_j6431 The most satisfactory diagnostic index of chronic pancreatitis is tho increase in diastase in tho blood and urine. Ho cases were observed of an increase in diastase under normal functioning conditions. The Clinical Value of tho Serum Amylase Test E, F, Leva.son. Burg,, Gyn, and Obs, 72, 202 (1941) The serum amylase of 720 patients with various dis- eases wore determined and tho values obtained are given, Tho methods of serum amylase determinations are reviewed. Ago, sox, diet, vitamin deficiency and starvation have no effect on scrum amylase values. Deviations from normal were found in mumps, liver disease and acute pancreatitis. The Dynamics of Blood-Diastase Activity in Different Types of Patients B*,V» Lyntrovkin, Khirurgiya No, 2-3, 62 (1940), CA. The blood diastase was determined in 110 subjects in the fasting condition and after a meat test-meal*. In pa- tients with diseases of the pancreas the diastatic activity is 1ower than the normal in fasting conditions and higher after the ingestion of the test meal. Concludes that the test may serve as a diagnostic aid in diseases of the pancreas. An Evaluation of the Clinical Significance of Serum Amylase and Lipase Determinations IV M0 McCall and J, G, Reinhold, Surg, Gyn, Obs, 80, 435 (1935) The relative diagnostic value of serum amylase and serum lipase in patients with diseases of the pancreas, liver and gall bladder is compared and the methods of determining them are discussed,. Values obtained with normal and diseased subjects are given. Diagnosis of Pancreatic Disease; Limitations of Present Blood Diastase Test, Suggestion for Increasing Its Effectiveness Je IV McCaughan, Proc. Soc. Exp. Bio,. Med,.40,-665 (1939) Experiments are described using a balloon in the duo- denum of a dog to block the pancreatic secretions,. Using this technique in a test for pancreatic function, a nor- mal patient might be expected to show a rise in blood diastase, whereas one with the function impaired might remain unaltered or change but slightly. The Value of Estimations of the Amylase of the Blood in the Diagnosis of Suspected Pancreatic Disease J. M, IlcCaugham, Surg., Gyn, and Obs. 59, 598 (1934) A review of the literature and a discussion of the use of the test. The Clinical Significance of the Serum Amylase Tost in the Diagnosis of Acute Pancreatitis K, McCorkle and L, Goldman, Surg,, Gyn, and Obs, 74, 439 (1942 ) Gives 10 case histories in which the test was used for diagnosis and discusses the use of the test. Study of the Diastase in Blood raid Urine under Definite Dietary Conditions A, Meklcr, Gastrocnterologia 66, 12 (1941) 24 patients under definite diet were examined daily for the diastase secretion in the urine and the diastase content in the blood scrum. Those having no manifest ail- ments of the abdominal organs had normal diastase in urine and blood. Those having higher diastase levels in urine and blood, who didn*t exhibit pancreatic disease, wore af- fected in other abdominal organs. The latter is explained by inferring that in spite of lack of clinical symptoms of pancreatic disease* poncrcatic function may be affected by diseases of neighboring organs—the latter producing a slight disease of the pancreas. The method may bo devel- oped as a clinical test for pancreatic function. The Relationship of Pancreatic Enzymes to Food Allergy A# W, Oclgoctz* P< A, Oclgoctz and Jrv'V» ‘/ittekind* ' Am, Ji Dig. Dis, 3., 730 (1934), Ibid. 2_,.422 (1935), Ibid, 5_, 199 (1936), Mod# Rcc*• 143, 20 (1936), Ibid. 150, 276 (1939). The following hypothesis is sot forth in all the pa- pers: The amount of enzymes secreted by the normal func- tioning pancreas is in excess of that required for diges- tion in the intestine. The ’surplus' of enzymes is absorbed and enters the blood. Food is a.bsorbcd in various degrees of digestion—from protein to amino-acid—and digestion is continued in the blood by virtue of the circulating enzymes. In instances of pancreatic insufficiency the enzyme output may bo just enough to take care of intestinal requirements and none,, or a very slight amount, enters the blood. There- fore the proteins, metaportcins, ete,,in the blood are not digested and the animal becomes sensitive to foods. Further ingestion of food while in this condition causes an allergic reaction to occur*. - To counteract this the administration of loss food,, or of dry pancreatic enzymes is suggested,: A tost is described to quickly and easily measure blood enzyno levels* A starch-iodine mixture is used and the scrum is allowed to act on it* This measures the amy— laso, but the blood enzymes follow a .parallel concentra- tion and therefore it is considered an index of the total blood enzyme content* Blood Amylase D* Polowe. Am, J. Clin. Path. 15, 288 (1943) y The methods of determination and the conditions in which there arc a deviation from the arc discussed, i A New Tost for Pancreatic Function. II, Experimental Observations. H* J, Popper, T'« K, Olson-and H# Nochclcs, Surg,, Gyn, and Ohs* 77_, 471 (1943) A tost is described giving mccholyl plus secretin to the subject and then determining the scrum lipase. In the normal the latter shows an increase. The work to date has boon done with dogs, A New Test for Pancreatic Function: Experimental Observa- tions H. L, Popper and H. iicchclcs. Gastroenterology 1, 490 (1943) The subcutaneous injection of a Combination of acotyl- bota-mothylcholinc hydrochloride plus oserine sulfate results in cm increase of scrum amylase cmd lipase only in the pre- sence of normal pancroaso, but not in tho presence of an atrophic pancreas. Amylase in the Blood in Subacute and in Chronic Pancreatic Diseases E. G* Wakefield, J. M. McCaugham and C. S• UcVicar. Arch. Int. Mod. 45, 473 (1930) The percentage of data is too small to war- rant tho adoption of a routine diagnostic procedure of study of tho amylase of the blood in cases of suspected pancreatic disease. 82 c. Other Function Tosts Tests of Paneroatic Function M. W. Comfort. J. A, M. A. 115, 2044 (1940) Tho uso of purified socrotin plus mocholyX chloride as a diagnostic aid is described; both normal and -abnormal values for tho secreted juice (obtained by a doublc-bar- ralod gastroduodenal tube) are given. Tho use of stool y analysis for undigested and unabsorbod food, blood enzyme determinations and urine amylase determination as tests for pancreatic dysfunction are discussed* IV. Contributions to tho Physiology of tho Pancreas. Tho Elimination of Dyes in tho External Secretion of tho Pancreas L. A. Crandall, E, Oldberg and A, C, Ivy. Am. J, Physiol. 89, 225 (1929) Of 90 dyes tested, none v/oro eliminated in sufficient quantity to be of practical value as a pancreatic function test, Tho Activity of tho Pancreatic Function under tho Influence of Copius Water Drinking vdth Meals P. B. Hawk, Am, J. Physiol. 27, XXVI (1910) The activity of tho pancreatic function as measured by the focal amylase was found to bo greatly facilitated when additional volumes of HgO ranging from 1500-4000 cc, were daily ingested at meals by normal men on a uniform diet. The Dependence of the External Secretion of the Pancreas And Liver on the Amount of Work Required of These Organs If D,, KlimenkOj* Acta* Mod., Scand. 83, 565 (1934), llutr• Abs, and Rev, 4, 791 (1035) *"* i : . if : Both in lower animals and man the presence of oil or *• : J fat in the duodenum loads to closure of the pylorus. This action is chemical., not mechanical; vaseline is without effect. The greater the quantity of oil or fat, the more prolonged is the closure of the pylorus. Since the dis- appearance of the fat or oil depends on. the secretion of the pancreas and liver, the length of time of pyloric clo- sure is an index of pancreatic and liver efficiency, A Study of the Diastatic Activity of the Urine and Feces with Special Reference to Diseases of the Pancreas C, IT, McClure and J, K. Pratt, Arch, Int, Med, 19, 568'(1917) They conclude that the measurement of the diastatic activity of the urine and feces is of little value in diag- nosing pancreatic diseases, A Practical Tost of Pancreas Function with Iodized Oil T, Trcmoliorcs, Rev, Med, 57, 1 (1940), CA, 54» 6513 A test is described in which the patient take cap- sules of iodized oil on an empty stomach and the iodine content of the urine is observed for the next 24 hours. 84 Tho digestion r.nd absorption of oil arc impaired in pan- creatic disturbances and consequently only small amounts of iodine appear in tho urine* Pancreatic Function Tests J* A, Wolfor and L. W. Christian, Arch* Surg, _!?, 899 (1928) Tho literature on pancreatic function tests is re- viewed, An attempt to use the determination of focal amy- lase as a test for pancreatic function was made. Focal amylase values of normal persons vary from day to day, de- pending on the diet. As a tost of function it is only « useful when there is complete lack of pancreatic secretion* With dogs it was shown that increases in pancreatic secre- tion upon tho application of stimulants can be measured by tho focal amylase• 85 SECTION VI BOOKS AND NEVIS’TS Secretory Mechanism of the Digestive Glands B, i. Babkin. New York. Paul Hoeber, Inc. {19 tM) Contains the results of, and discusses the experi- mental work done on pancreatic secretion, both 'normal' and as a result of various stimuli. Blood Sugar Concentration and the External Secretion of the Pancreatic Gland B. I. Babkin. J. A. M. A. 105, 1659 (1935) A review of the wark done. Hyperglycemia always in- t creases the output of enzymes from the acinous cells and in certain cases increases the volume of the secretion. Hypoglycemia produced by the administration of insulin lowers the concent ration of enzymes in the pancreatic juice. After section of the vagus this effect disappears. The con- flicting results obtained with humans are ascribed to the methods of recovering the juice. The External Secretion of the Digestive Glands (Die Aussere Sekretion Per Verdauungsdrusen) B. P. Babkin. Berlin. Julius Springer (1928) Pages 462-543 Contain a very extensive review of the work done on the determination of normal pancreatic secre- tion and of the effect of various stimuli upon it. Quanti- tative results of much of the experimental work cited are included. Tests of Pancreatic Function M. VI. Comfort. J. A. M. A♦►3-15, 2044 (1940) The use of purified secretin plus mecholyl chloride as a diagnostic aid is described; both normal and abnor- mal values for the secreted juice (obtained by a double- barreled gastroduodenal tube) are given. The use of stool analysis for undigested and unabsorbed food, blood enzyme determinations and urine amylase determination as tests for pancreatic dysfunction are discussed. ■1 ’i■ The Origin and Significance of Blood Serum Enzymes L. A. Crandall. Am. J. Dig. Dis. 2, 230 (1935) A review containing a section on the relation of blood enzymes to pancreatic function. The Pancreas: Contributions of Clinical Interest Made In 1943 R. Elman and J. T. Gastroenterology 2, 412 (1944) The Pancreas: Contributions of Clinical Interest Made In 1942 R. Hilman and C. E. Lischer. Gastroenterology 1, 633 (1943) / Contributions in Regard to the Pancreas in 1941 R. Elman and A. M. Large. Am. J. Dig. Dis. 9, 303 (194,2) 1940 Contributions in Regard to the Pancreas H. Elman and'L* Ai Sachar. Am* J* Dig. Dis. 8, 108 (1941) Contributions Made in 1939 to Knowledge in Regard to the Pancreas. R. Elman* Am. J. Dig. Dis. 7, 227 (1940) Contributions Made in 1938 to Knowledge in Regard to the Pancreas R. Elman* Am. J. Dig. Dis. 6, 233 (1939) A series of reviews covering the effects of food and other stimuli on pancreatic secretion, pancreatic insuffi- function tests, and the clinical, surgical and pathological aspects of pancreatic disorders. m Certain Aspects of the Applied I hysiology of the External Pancreatic Secretion A. C. Ivy. Am* J. Dig. Dis. 3, 677 (1937) • 4 » 1 * A review article dealing with the effects of exclu- sion of pancreatic juice from the intestine, blood enzymes and exclusion of pancreatic juice, functional tests of ex- ternal secretory activity of the pancreas, and the effect of foods on the pancreatic secretion. 88 The Role of Hormones in Digestion A. C. Ivy. Physiol. Rev. 10, 282 (1930) A review article containing a section dealing with the effects of various stimuli on pancreatic secretion. Pancreatic Function and Pancreatic Pis ease H. 0. Lagerlof. New York. The Macmillan Co,, (1942) A comprehensive work containing a history of the ex- perimental work done on pancreatic secretion, the methods used in recovering pancreatic juice and in analyzing it for its enzyme content, the use of secretin preparations in functional tests, the responses of the pancreas to various stimuli, and case histories of patients with various pan- creatic diseases. The quantitative results of much of the experimental work are included. The Value of Estimations of the Amylase of the Blood in the Diagnosis of Suspected Pancreatic Disease J. M. McCaugham, Surg,, Gyn. ana Obs. 59, 598 (1934) A review of the literature and a discussion of the use of the test. \ f Blood Amylase in Diseases of the Pancreas V. C. Myers. Gastroenterology 1, 617 (1943) A review. Functional Activities of the Pancreas and Liver - I 1 C. VI. McClure. Medical Authors Pub. Co. (1937) A monograph dealing vdth tests of pancreatic function, and the response of the pancreas to food and various stimuli. Observations on the Physiology and Pathologic Physiology pf External Pancreatic Functions u C. VI, McClure. Rev. Gastroenterology 1 (1936) A review dealing with the effects of food and various stimuli on pancreatic .function and the physiology of pan- creatic secretion. Disturbances of the External Secretion of the Pancreas K. Hissen, Deutsch. Med. Lochnchr, 59, 1464 (1933)> Nutr. Abs, and Rev. 3, 731 (1934) A review of literature on disturbance of pancreatic function. The Fork of the Digestive Glands I, P. Pavlov. London. Charles Griffin and Co. 1910 A series of lectures with the physiology of the diges- tive glands. Experimental work on the relation of the out- put of pancreatic juice to the food intake is reviewed in detail. 90 The Pancreatic Secretion (La Secretion Panereatique) E. F. Terroine. Paris. Liorairie Scientifique A. Hermann and Fils (1913) A monograph containing a review of the literature on the experimental work done on pancreatic secretions to that date. 91