diffuse somatostatin-immunoreactive d-cell hyperplasia in

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GASTROENTEROLOGY Volume 91, July-December 1986 Editor Editorial Board Raj K. Goyal Beth Israel Hospital 330 Brookline Avenue Boston, Massachusetts 02215 Consulting Editor William Silen Beth Israel Hospital Boston, Massachusetts 02215 Associate Editors Jules L. Dienstag Massachusetts General Hospital Boston, Massachusetts 02114 John L. Gollan Brigham and Women's Hospital Boston, Massachusetts 02115 James L. Madara Brigham and Women's Hospital Boston, Massachusetts 02115 Satish Rattan Beth Israel Hospital Boston, Massachusetts 02215 Allan Walker Children's Hospital Boston, Massachusetts 02115 Selected Summaries Editor Robert M. Glickman New York, New York Book Review Editor Howard Spiro New Haven, Connecticut Chairman of Editorial Board Robert M. Donaldson, Jr. New Haven, Connecticut David H. Alpers, St. Louis, Missouri Thomas Brasitus, Chicago, Illinois Raymond F. Burk, San Antonio, Texas Martin Carey, Boston, Massachusetts Donald L. Castell, Winston-Salem, North Carolina Wylie J. Dodds, Milwaukee, Wisconsin Robert M. Donaldson, Jr., New Haven, Connecticut Mark Donowitz, Boston, Massachusetts Charles O. Elson III, Richmond, Virginia Jerry D. Gardner, Bethesda, Maryland Peter B. Gregory, Stanford, California Roberto Groszmann, New Haven, Connecticut W. Gary Hardison, San Diego, California R. Thomas Holzbach, Cleveland, Ohio Albert L. Jones, San Francisco, California Keith A. Kelly, Rochester, Minnesota Mary Jeanne Kreek, New York, New York Nicholas F. LaRusso, Rochester, Minnesota Willis C. Maddrey, Philadelphia, Pennsylvania Robert K. Ockner, San Francisco, California Jay A. Perman, Baltimore, Maryland Charles T. Richardson, Dallas, Texas Jack A. Vennes, Minneapolis, Minnesota Tadataka Yamada, Ann Arbor, Michigan Officers of the American Gastroenterological Association President Douglas B. McGill Rochester, Minnesota President Elect John M. Dietschy Dallas, Texas Vice-President Robert M. Glickman New York, New York Secretary Paul D. Webster III Augusta, Georgia Treasurer Martin Brotman San Francisco, California

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Page 1: Diffuse somatostatin-immunoreactive D-cell hyperplasia in

G A S T R O E N T E R O L O G Y Volume 91, July-December 1986

Editor Editorial Board

Raj K. Goyal Beth Israel Hospital 330 Brookline Avenue Boston, Massachusetts 02215

Consulting Editor

William Silen Beth Israel Hospital Boston, Massachusetts 02215

Associate Editors Jules L. Dienstag Massachusetts General Hospital Boston, Massachusetts 02114

John L. Gollan Brigham and Women's Hospital Boston, Massachusetts 02115

James L. Madara Brigham and Women's Hospital Boston, Massachusetts 02115

Satish Rattan Beth Israel Hospital Boston, Massachusetts 02215

Allan Walker Children's Hospital Boston, Massachusetts 02115

Selected Summaries Editor Robert M. Glickman New York, New York

Book Review Editor Howard Spiro New Haven, Connecticut

Chairman of Editorial Board

Robert M. Donaldson, Jr. New Haven, Connecticut

David H. Alpers, St. Louis, Missouri Thomas Brasitus, Chicago, Illinois Raymond F. Burk, San Antonio, Texas Martin Carey, Boston, Massachusetts Donald L. Castell, Winston-Salem, North Carolina Wylie J. Dodds, Milwaukee, Wisconsin Robert M . Donaldson, Jr., New Haven, Connecticut Mark Donowitz, Boston, Massachusetts Charles O. Elson III , Richmond, Virginia Jerry D. Gardner, Bethesda, Maryland Peter B. Gregory, Stanford, California Roberto Groszmann, New Haven, Connecticut W. Gary Hardison, San Diego, California R. Thomas Holzbach, Cleveland, Ohio Albert L. Jones, San Francisco, California Keith A. Kelly, Rochester, Minnesota Mary Jeanne Kreek, New York, New York Nicholas F. LaRusso, Rochester, Minnesota Willis C. Maddrey, Philadelphia, Pennsylvania Robert K. Ockner, San Francisco, California Jay A. Perman, Baltimore, Maryland Charles T. Richardson, Dallas, Texas Jack A. Vennes, Minneapolis, Minnesota Tadataka Yamada, Ann Arbor, Michigan

Officers of the American Gastroenterological Association

President Douglas B. McGill Rochester, Minnesota

President Elect John M. Dietschy Dallas, Texas

Vice-President Robert M . Glickman New York, New York

Secretary Paul D. Webster III Augusta, Georgia

Treasurer Martin Brotman San Francisco, California

Page 2: Diffuse somatostatin-immunoreactive D-cell hyperplasia in

C O N T E N T S O F V O L U M E 91

NO. 1 , JULY 1986

A L I M E N T A R Y TRACT

Use of 23-Selena-25-Homocholyltaurine to Detect Bile A c i d Malabsorption i n Patients W i t h Ileal Dysfunction or Diarrhea Carnitine Transport i n Human Intestinal Biopsy Specimens. Demonstration of an Act ive Transport System

Reversibility of Exocrine Pancreatic Failure i n Chronic Pancreatitis

Patients W i t h a High Jejunostomy Do Not Need a Special Diet

Preparation of Subcellular Membranes From Rat Intestinal Scrapings or Isolated Cells. Different C a 2 + B inding , Nonesterified Fatty A c i d Levels, and L ipo ly t i c A c t i v i t y Effects of Decreasing Intra luminal Amylase A c t i v i ­ty on Starch Digestion and Postprandial Gastroin­testinal Funct ion i n Humans

Nonspecific Adaptat ion of Jejunal A m i n o A c i d Uptake i n the Rat

Healing of Benign Gastric Ulcer W i t h Low-Dose Antacids and Fiber Diet Chronic Intestinal Pseudoobstruction i n Young Chi ldren

Lack of Specific B inding of Prostaglandin E 2 , Pros­taglandin F 2 a , and 6-Keto Prostaglandin F l a to Se­r u m i n Patients W i t h Peptic Ulcer Disease and i n Healthy Subjects

Estimated Versus Measured Basal Energy Require­ments i n Patients W i t h Crohn's Disease

Comparison of an Intravenous Selective Mesenteric Vasodilator W i t h Intraarterial Papaverine i n Ex­perimental Nonocclusive Mesenteric Ischemia Interaction of Tripotassium Dicitrato Bismuthate W i t h Macrophages i n the Rat and I n Vitro Relationship Between Impaired Gastric Emptying and Abnormal Gastrointestinal M o t i l i t y Decreased F l u i d Tolerance, Accelerated Transit, and Abnormal M o t i l i t y of the Human Colon I n ­duced by Oleic A c i d

Trophic Effects of Pentagastrin on Gastrointestinal Tract i n Fed and Fasted Rats

Mechanical Characteristics of Phase I I and Phase I I I of the Interdigestive Migrat ing Motor Complex i n Dogs

Evidence for Abnormal Cholinergic Neuromuscular Transmission i n Diabetic Rat Small Intestine

Upper Esophageal Sphincter Function During Belching

G. S C I A R R E T T A , G. VICINI , G. F A G I O L I , 1

A. V E R R I , A. G I N E V R A , A N D P. M A L A G U T I

J.W. H A M I L T O N , Β U.K. LI , A . L . S H U G , A N D 10

W.A. O L S E N

A . M . G A R C I A - P U G E S , S. N A V A R R O , 17

E . R O S , M. E L E N A , A. B A L L E S T A ,

R. A U S E D , A N D J. V I L A R - B O N E T

P.B. M c I N T Y R E , M. F I T C H E W , A N D 25

J.E. L E N N A R D - J O N E S

J.R.F. W A L T E R S , P.J. H O R V A T H , A N D 34

M.M. W E I S E R

P. L A Y E R , A.R. Z I N S M E I S T E R , A N D 41

E.P. D i M A G N O

G . M . L E V I N E 49

A. R Y D N I N G , R. W E B E R G , O. L A N G E , A N D 56

A. B E R S T A D

S. A N U R A S , F . A . M I T R O S , R.T. S O P E R , 62

K . C P R I N G L E , B.V. M A V E S , M.K. Y O U N O S Z A I ,

E . A . F R A N K E N , Jr.. A N D P. W H I T I N G T O N

J.S. R E D F E R N A N D M. F E L D M A N 71

Α.Τ.Η. C H A N . C R . F L E M I N G , W.M. O ' F A L L O N , 75

A N D K . A . H U I Z E N G A

K . L . M a c C A N N E L L 79

R . L . S O U T A R A N D S.B. C O G H I L L

T . E . S O L O M O N

M. S C H E M A N N A N D H-J. E H R L E I N

T . V . N O W A K , Β. H A R R I N G T O N ,

J.Η. K A L B F L E I S C H , A N D J.M. A M A T R U D A

P.J. K A H R I L A S , W.J. D O D D S . J. D E N T ,

J . B . W Y M A N . W.J. H O G A N , A N D

R . C A R N D O R F E R

84

94 Μ. C A M I L L E R I , M.L. B R O W N , A N D

J-R. M A L A G E L A D A

R . C . S P I L L E R , M . L . B R O W N , A N D S.F . P H I L L I P S 100

108

117

124

133

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iv C O N T E N T S G A S T R O E N T E R O L O G Y Vol. 91, N>. 6

Gastric M o t i l i t y Is Stimulated but Overall Blood Flow Is Unaffected During Cold Restraint i n the Rat Randomized, Double-Blind, Placebo-Controlled Crossover Tria l of Cimetidine and Pirenzepine i n Nonulcer Dyspepsia

LIVER A N D BILIARY TRACT Factors Associated W i t h Postoperative Complica­tions i n Diabetics After Bi l iary Tract Surgery

Effect of Portacaval Shunt on Drug Disposition i n Patients W i t h Cirrhosis Cl inical Significance of Low Molecular Weight (7-8S) Immunoglobul in Μ Ant ibody to Hepatitis Β Core Antigen i n Chronic Hepatitis Β Virus Infections

Corynebacterium parvum-Elici ted Hepatic Macro­phages Demonstrate Enhanced Respiratory Burst A c t i v i t y Compared W i t h Resident Kupffer Cells i n the Rat

Circadian Rhythm of Hepatic Cytosolic and Nucle­ar Estrogen and Androgen Receptors

Differing Effects of Nor-ursodeoxycholic or Ursode­oxycholic A c i d on Hepatic Histology and Bile A c i d Metabolism i n the Rabbit

CASE REPORTS Emergence of Malignant Lesions W i t h i n an Adeno­matous Hyperplastic Nodule in a Cirrhotic Liver. Observations i n Five Cases

Neurologic Syndrome Associated W i t h Low Levels of V i t a m i n Ε i n Primary Bi l iary Cirrhosis

Rupture of the Stomach After Hemorrhage From a Gastric Ulcer Primary Malignant Melanoma of the Gallbladder, Metastatic to the Common Bile Duct

Transformation of Inferior Vena Caval Thrombosis to Membranous Obstruction i n a Patient W i t h the Lupus Anticoagulant

PROGRESS ARTICLE Countercurrent Mechanisms i n the Mammalian Gastrointestinal Tract

EDITORIALS

Technology Il luminates a Shadowy Syndrome Asymptomatic Gallstones. Does Diabetes Mell i tus Make a Difference?

Selective Mesenteric Vasodilators. A Future Role i n Acute Mesenteric Ischemia?

T. G A R R I C K , F.W. L E U N G , S. B U A C K , 141

K. H I R A B A Y A S H I , A N D P.H. G U T H

N.J. T A L L E Y . D. M c N E I L . A. H A Y D E N . A N D 149

D.W. PIPER

R.S. S A N D L E R . W.F. M A U L E . A N D M.E. B A L T U S 157

G. P O M I E R - L A Y R A R G U E S , P-M. H U E T , 163

J-P. V I L L E N E U V E , AND D. M A R L E A U

M.H. SJOGREN, W . H . B A N C R O F T , 168

J.H. H O O F N A G L E , J.L. S O S E B E E . A N D

S.M. L E M O N

M.J.P. A R T H U R , P. K O W A L S K I - S A U N D E R S . 174

AND R. W R I G H T

A. F R A N C A V I L L A . P.K. E A G O N . A. D i L E O , 182

D.H. V A N T H I E L . C P A N E L L A , L. P O L I M E N O .

C. A M O R U S O . M. I N G R O S S O . A . M . A Q U I L I N O .

A N D T . E . S T A R Z L

B. I. C O H E N . A . F . H O F M A N N . E . H . M O S B A C H , 189

R.J. S T E N G E R . M.A. R O T H S C H I L D . L.R. H A G E Y .

A N D Y.B. Y O O N

M. A R A K A W A , M. K A G E , S. S U G I H A R A , 198

T. N A K A S H I M A . M. S U E N A G A . A N D K. O K U D A

R.E. K N I G H T . A.J. B O U R N E . M. N E W T O N . 209

A. B L A C K . P. W I L S O N . AND M.J. L A W S O N

D.P. O ' D O H E R T Y , A.R. B A K E R , AND 212

W.W. B A R R I E

J.J. V E R B A N C K , L.J. R U T G E E R T S . 214

F.J. V A N A E L S T , J.H. T Y T G A T . J.M. D E C O S T E R .

D.N. N O Y E Z . P.J. T H E U N Y N C K , A N D

K.J. G E B O E S

Η. T E R A B A Y A S H I . Κ. O K U D A . 219

F. N O M U R A . Κ. OHNISHI. A N D P. W O N G

M. JODAL A N D O. L U N D G R E N 225

W.G.M. H A R D I S O N 242

C A . P E L L E G R I N I 245

S.J. B O L E Y A N D L.J. B R A N D T 247

SELECTED SUMMARIES

A Hormonal Basis for Cachexia?

Gut Mucosa, Adaptive Growth, and Enteroglucagon 250

251

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December 1986 C O N T E N T S ν

Determinants of Bi l iary Cholesterol Secretion 252 The Influence of Chronic Ethanol Adminis trat ion 253 on the F l u i d i t y of Liver Plasma Membranes Colon Cancer, Colon Polyps, and Cholesterol 254 What to Do W i t h the Adenoma-Carcinoma 256 Intermezzo

BOOK REVIEWS 258 CORRESPONDENCE 265 NOTICES 270 CORRECTION 272

N O . 2, AUGUST 1986

AMERICAN GASTROENTEROLOGICAL ASSOCIATION Our New President—Douglas B. M c G i l l , M.D.

LIVER A N D BILIARY TRACT Ontogenic and Phylogenic Studies of Intestinal, Hepatic, and Placental Alkal ine Phosphatases. Evi­dence That Intestinal Alkal ine Phosphatase Is a Late Evolutionary Development

Regulation of B i l i r u b i n Glucuronide Synthesis i n Primate [Macaca fascicularis) Liver. Kinetic Analy­sis of Microsomal B i l i r u b i n U r i d i n e Diphosphate Glucuronyltransferase Effect of Dietary Cholesterol on Bi l iary Cholesterol Content and Bile Flow i n the Hypothyro id Rat

Short-Term Adminis t ra t ion of Parenteral Glucose-L i p i d Mixtures Improves Protein Kinetics i n Porta­caval Shunted Rats

Ultrasonographic Study of Gallbladder M o t i l i t y During Total Parenteral N u t r i t i o n

A L I M E N T A R Y TRACT

Development of Gastric Mucosal Protection Against A c i d i n the Rat. Role of Corticosteroids and Prostaglandins

Isolation and Characterization of Crohn's Disease Tissue-Specific Glycoproteins

Influence of the St imulation State of the Parietal Cells on the Inhibi tory Effect of Omeprazole on Gastric A c i d Secretion i n Dogs

Linear Gastric Erosion. A Lesion Associated W i t h Large Diaphragmatic Hernia and Chronic Blood Loss Anemia

Intestinal Hydrolysis of Pyridoxal 5'-Phosphate I n Vi tro and I n Vivo i n the Rat. Effect of Protein B inding and p H

Effects of A s p i r i n on Tight Junction Structure of the Canine Gastric Mucosa I n h i b i t i o n of Gastrointestinal Transit Due to Surgi­cal Trauma or Peritoneal Irr i tat ion Is Reduced i n Capsaicin-Treated Rats

Esophageal Motor Abnormalities i n Gastroesopha­geal Reflux and the Effects of Fun duplicat ion

H.N. H O F F M A N 273

T . K O M O D A . I. K O Y A M A , Α. Ν A G A T A . 277

Y . S A K A G I S H I , K. D e S C H R Y V E R - K E C S K E M E T I ,

A N D D.H. A L P E R S

S . C H A U S E R , J.C. Z I U R Y S , A N D J.L. G O L L A N 287

F.J. F I E L D , E . A L B R I G H T . A N D S.N. M A T H U R 297

J.J. P O M P O S E L L I . L . L . M O L D A W E R , 305

J.D. P A L O M B O . V . K . B A B A Y A N , B.R. B I S T R I A N ,

A N D G.L. B L A C K B U R N

N. C A N O , F. C I C E R O , F. RANIERI , J. M A R T I N , 313

A N D J. di C O S T A N Z O

E.J. D I A L A N D L . M . L I C H T E N B E R G E R

S. B A G C H I , B. B A R A L , A N D K . M . D A S

318

326

J. D E G R A E F A N D M-C. W O U S S E N - C O L L E 333

A.J. C A M E R O N A N D J.A. HIGGINS

H . M . M I D D L E T O N , III

338

343

R.A. M E Y E R , D. M c G I N L E Y , A N D Z. P O S A L A K Y 351

P. H O L Z E R , l .Th. LIPPE, A N D 360

U . H O L Z E R - P E T S C H E

R . C . G I L L . K . L . B O W E S . P.D. M U R P H Y , A N D 364

Y.J . K I N G M A

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vi C O N T E N T S G A S T R O E N T E R O L O G Y Vol . 91, No. 6

Human Duodenal Mucosal Bicarbonate Secretion. Evidence for Basal Secretion and Stimulation by Hydrochloric A c i d and a Synthetic Prostaglandin Ei Analogue Altered Patterns of Secretion of Monomeric IgA and IgA Subclass 1 by Intestinal Mononuclear Cells i n Inflammatory Bowel Disease

Human Interdigestive M o t i l i t y : Variations i n Pat­terns From Esophagus to Colon

Sulfapyridine Appearance i n Plasma After Sali-cylazosulfapyridine. Another Simple Measure of Intestinal Transit

Endoscopic Ultrasonography of Non-Hodgkin L y m ­phoma of the Stomach Endoscopic Measurement of Papillary Sphincter Zone and Pancreatic M a i n Ductal Pressure i n Pa­tients W i t h Chronic Pancreatitis When Is Endoscopic Polypectomy Adequate Thera­py for Colonic Polyps Containing Invasive Carcinoma? Dermatoglyphic (Fingerprint) Evidence for a Con­genital Syndrome of Early-Onset Constipation and Abdomina l Pain

Bacterial Contamination of Pancreatic Necrosis. A Prospective Clinical Study Effect of Ethanol on A c i d Secretion by Isolated Gastric Glands From Rabbit

Use of a 3T3 Cell Growth Factor Assay for the Delineation and Characterization of Humoral Tro­phic Factors Involved i n Intestinal Adaptation i n the Rat

CASE REPORTS

Resolution of Diffuse Granulomatous Fibrosis of the Liver W i t h Antituberculous Chemotherapy

Tularemic Hepatitis Presenting as Obstructive Jaundice Primary Sclerosing Cholangitis Associated W i t h Hyper immunoglobul in Μ Immunodeficiency (Dys-gammaglobulinemia)

Gastrointestinal Involvement Complicating Ste­vens-Johnson Syndrome

Treatment of Acute Mesenteric Ischemia by Percu­taneous Transluminal Angioplasty

EDITORIALS Surgical Intervention i n Necrotizing Pancreatitis

You See What You Look For

SELECTED SUMMARIES

What Are Transgenic Mice and How W i l l They Affect Medicine? Man Is What He Eats (Der Mensch ist was er isst)

Neuropeptide Modulat ion of Mucosal Immuni ty

Current Concepts of Pancreas and Liver Trauma Management

J.I. I S E N B E R G . D.L. H O G A N , M.A. K O S S . AND 370

J.A. S E L L I N G

R.P. M a c D E R M O T T . G.S. N A S H . M.J. B E R T O V I C H , 379

R.F. M O H R M A N , I.J. K O D N E R . D.L. D E L A C R O I X .

AND J-P. V A E R M A N

J.E. K E L L O W , T.J. B O R O D Y . S.F. P H I L L I P S .

R.L . T U C K E R , A N D A . C . H A D D A D

J.E. K E L L O W . T.J. B O R O D Y . S.F. P H I L L I P S .

A . C . H A D D A D . A N D M.L. B R O W N

T . L . T I O , F .C .A. den H A R T O G JAGER. A N D

G.N.J. T I J T G A T

Κ. ΟΚΑΖΑΚΙ, Υ. Y A M A M O T O , A N D Κ. I T O

J.P. C R A N L E Y . R.E. P E T R A S , W.D. C A R E Y ,

K. P A R A D I S , A N D M.V. S I V A K

S.H. G O T T L I E B A N D M.M. S C H U S T E R

H.G. B E G E R , R. B I T T N E R . S. B L O C K . A N D

M. BÜCHLER

386

396

401

409

419

428

433

B.J. R E I C H S T E I N . C. O K A M O T O . AND J.G. F O R T E 439

J.A. B I L L E R . R.K. M O N T G O M E R Y . R.J. G R A N D , 448

M. K L A G S B R U N . A N D A. R O S E N T H A L

K. O K U D A . K. K I M U R A . K. T A K A R A , Μ. O H T O . 456

Μ. O M A T A . A N D L. L E S M A N A

T.J. O R T E G O , L . F . H U T C H I N S , J. R I C E , A N D 461

G.R. D A V I S

J.A. D i P A L M A . C T . S T R O B E L , A N D

J.G. F A R R O W

B. Z W E I B A N , H. C O H E N . A N D

P. C H A N D R A S O M A

W.H. V a n D E I N S E . J.K. Z A W A C K I . A N D

D. P H I L L I P S

H.A. R E B E R

J.F. M O R R I S S E Y

464

469

475

479

481

483

484

485

486

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December 1986 C O N T E N T S vii

Salicylates and Reye's Syndrome 487 The B i l i r u b i n Controversy: Settled? 488 Flexible Sigmoidoscopy Training—Is Some 489 Enough?

Reply to Selected Summary: Is Delayed Gastric 490 Emptying a Contributing Factor i n the Failure of Fundoplications for Reflux? (GASTROENTEROL­OGY 1986;90:1299-1300)

BOOK REVIEWS 491

TRAINING A N D EDUCATION I N GASTROENTEROLOGY List of Available Training Programs 495

CORRESPONDENCE 522 NOTICES 528 CLASSIFIED ADS 532

NO. 3, SEPTEMBER 1986

A L I M E N T A R Y TRACT

D A a Receptor Mediates Dopamine-Induced Relax­ation of Opossum Lower Esophageal Sphincter In Vitro

Evidence for a Midgastric Transverse Band i n Humans Comparison of Methodologies for the Measurement of Antroduodenal Motor Act iv i ty i n the Dog Induct ion of Duodenal Ulcers in Rats Under Wa­ter-Immersion Stress Conditions. Influence of Stress on Gastric A c i d and Duodenal Alkal ine Secretion

Experimental Diabetic Diarrhea i n Rats. Intestinal Mucosal Denervation Hypersensitivity and Treat­ment W i t h Clonidine

Substrate Dependence and Oxygen Sensitivity of Tone and of Spontaneous and Evoked Contrac­tions of the Distal Colonic Muscularis Mucosae of Opossum

Immunohistochemical Study of Neuron-Specific Enolase and CA 19-9 i n Pancreatic Disorders. The Value of Neuron-Specific Enolase as a Marker for Islet Cell and Nerve Tissue

Cancer Family Syndrome: Marker Studies

Venti latory Function i n Chronic Peptic Ulcer. A Controlled Study of Ventilatory Function i n Pa­tients W i t h Gastric and Duodenal Ulcer

Effects of Differing Concentrations of Sodium Bu-tyrate on 1,2-Dimethylhydrazine-Induced Rat Intes­t ina l Neoplasia

Role of Mucus i n the Repair of Gastric Epithel ial Damage i n the Rat. Inhib i t ion of Epithel ial Recov­ery by Mucolyt ic Agents

D.M. L O M B A R D I , M. G R O U S , C F . FINE, 533

F .C . B A R O N E , P.}. F O W L E R , W.B. PHY A L L ,

I .A. R U S H . A N D H.S. O R M S B E E , III

J.G. M O O R E , A. D U B O I S , P.E. C H R I S T I A N , 540

D. E L G I N , A N D N. A L A Z R A K I

R.M. V A L O R I , S.M. C O L L I N S , E . E . D A N I E L , 546

S.N. R E D D Y . S . S H A N N O N , A N D J. JURY

K. T A K E U C H I, O. F U R U K A W A , A N D S. O K A B E 554

E.B. C H A N G , R.N. F E D O R A K . A N D M. F I E L D 564

W.H. P E R C Y , R.L. R O B E R T S , J.B. M A S O N . A N D 570

J. C H R I S T E N S E N

Κ. I W A S E , Κ. K A T O , A. N A G A S A K A , K. M I U R A , 576

K. K A W A S E , S. M I Y A K A W A , Τ. T E I , S. O H T A N I ,

M. I N A G A K I , S. S H I N O D A . A. N A K A I ,

Τ. O H Y A M A . Y. H O R I G U C H I , Η. N A K A N O , A N D

Μ. I T O H

J.F. M A R K O W I T Z , H.W. A I G E S , 581

S. C U N N I N G H A M - R U N D L E S , Ε. K A H N ,

S. T E I C H B E R G , S.E. F I S H E R , A N D F. D A U M

J.E. K E L L O W , Ζ. T A O . A N D D.W. PIPER 590

H.J. F R E E M A N 596

J.L. W A L L A C E A N D B.J.R. W H I T T L E 603

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viii C O N T E N T S G A S T R O E N T E R O L O G Y Vol. 91, No. 6

Serotonin Release Into Blood After Food and Pen-tagastrin. Studies i n Healthy Subjects and i n Pa­tients W i t h Metastatic Carcinoid Tumors Impaired Transit of Chyme i n Chronic Intestinal Pseudoobstruction. Correction by Cisapride Release and Characterization of Cholecystokinin From Isolated Canine Jejunal Cells Trypsin Suppression of Pancreatic Enzyme Secre­t ion. Differential Effect on Cholecystokinin Release and the Enteropancreatic Reflex

Intracolonic WR 2721 Protection of the Rat Colon From Acute Radiation Injury

Spectrum of Rectal Biopsy Abnormalities i n Ho­mosexual Men W i t h Intestinal Symptoms

Gastric Protection by Sucralfate. Role of Mucus and Prostaglandins

Ontogeny of Gastric Secretion i n the Rat. Ultra-structural Changes i n Relation to Secretory Changes

Translocation of Indigenous Bacteria From the Gastrointestinal Tract of Mice After Oral Ricinole-ic A c i d Treatment

LIVER A N D BILIARY TRACT

Chronobiological Study of Factors Affecting Plasma Aldosterone Concentration i n Cirrhosis

Levamisole Therapy i n Chronic Type Β Hepatitis. Results of a Double-Blind Randomized Trial

Distr ibution of Bi l iary Cholesterol Between Mixed Micelles and Nonmicelles i n Relation to Fasting and Feeding i n Humans

U t i l i t y of Bi l iary Microscopy for the Prediction of the Chemical Composition of Gallstones and the Outcome of Dissolution Therapy W i t h Ursodeoxy­cholic A c i d

Chemical and Morphologic Characteristics of Cho­lesterol Gallstones That Failed to Dissolve on Chenodiol. The National Cooperative Gallstone Study

CASE REPORTS

Pathological Findings of Lymphangiectasia of the Large Intestine i n a Patient W i t h Protein-Losing Enteropathy

U t i l i t y of Specimen Angiography i n Angiodyspla-sia of the Colon

Bil iary Ascariasis: Ultrasonography, Endoscopic Retrograde Cholangiopancreatography, and Bil iary Drainage

Diffuse Somatostatin-Immunoreactive D-Cell Hyper­plasia i n the Stomach and Duodenum

G. R I C H T E R . F. STÖCKMANN, J.M. C O N L O N , 612

A N D W. C R E U T Z F E L D T

M . C A M I L L E R I , M . L . B R O W N , A N D 619

J-R. M A L A G E L A D A

D.L. B A R B E R , J.H. W A L S H . A N D A . H . S O L L 627

C. O W Y A N G , D. M A Y , A N D D.S. L O U I E 637

H.G. F R A N C E . Jr., R.L. J IRTLE, A N D 644

C M . M A N S B A C H . II

C M . S U R A W I C Z , S.E. G O O D E L L . T . C . Q U I N N . 651

P.L. R O B E R T S , L. C O R E Y , K.K. H O L M E S ,

M.D. S C H U F F L E R . A N D W.E. S T A M M

Τ. S H E A - D O N O H U E , L. S T E E L , E. M O N T C A L M , 660

A N D A. D U B O I S

D . M . J A C O B S , S .H. A C K E R M A N . A N D 667

R.D. S H I N D L E D E C K E R

J.L. M O R E H O U S E . R.D. S P E C I A N . J.J. S T E W A R T , 673

AND R.D. B E R G

M. B E R N A R D I , R. De P A L M A , F. T R E V I S A N I , 683

C. SANTINI , F. C A P A N I , M. B A R A L D I N I , A N D

G. G A S B A R R I N I

G. F A T T O V I C H , L. B R O L L O , P. P O N T I S S O , 692

E. P O R N A R O . M. R U G G E . A. A L B E R T I . A N D

G. R E A L D I

N.R. P A T T I N S O N A N D B.A. C H A P M A N 697

E. R O S . S. N A V A R R O , I. F E R N A N D E Z , 703

M. R E I X A C H , J.M. RIBO, AND J. R O D E S

H.S. F R E I L I C H , P.F. M A L E T , J.S. S C H W A R T Z , 713

R.D. S O L O W A Y , A N D T H E N A T I O N A L

C O O P E R A T I V E G A L L S T O N E S T U D Y G R O U P

H. A S A K U R A , M. T S U C H I Y A , S. K A T O H , 719

K. K O B A Y A S H I , Y. Y O N E I , T . Y O S H I D A ,

Y. H A M A D A , S. M I U R A , A. M O R I T A ,

S. K U R A M O C H I , A N D T. T E R A M O T O

S.M. A L D A B A G H , Y.P. T R U J I L L O , A N D 725

J.B. ΤΑΧΥ

P.S. K A M A T H , D.C. JOSEPH, R. C H A N D R A N , 730

S. R A M A R A O , M.L. SRI P R A K A S H , A N D

A.J. D ' C R U Z

G.E. H O L L E , W. S P A N N , W. E I S E N M E N G E R , 733

J. R I E D E L , A N D L. P R A D A Y R O L

Page 8: Diffuse somatostatin-immunoreactive D-cell hyperplasia in

December 1986 C O N T E N T S ix

Celiac Sprue Complicated by Lymphoma Present­ing W i t h M u l t i p l e Gastric Ulcers

PROGRESS ARTICLE Intestinal I m m u n i t y and Inflammation: Recent Progress

EDITORIALS

a 2 -Adrenergic Agonists: A Newer Class of A n t i -diarrheal Drug Role of Biopsy i n Diagnosis of Rectal Infections Changing Concepts of Cholesterol Solubil i ty i n Bile

SELECTED SUMMARIES Cryptosporidium: A Growing Clinical Spectrum Malignant Histiocytosis or T-Cell Lymphoma? Direct Visualization of Lymphocytes Entering Peyer's Patches Alternative Strategies i n Crohn's Disease T i m i n g of Surgery for Gallstone Pancreatitis Shock Waves: Waves of the Future for Gallstone Treatment? Reply to Selected Summary: Flexible Sigmoidos­copy Training—Is Some Enough? (GASTROENTER­OLOGY 1986;91:489-90)

BOOK REVIEWS CORRESPONDENCE NOTICES CLASSIFIED ADS

R.L. R O E H R K A S S E , I .M. R O B E R T S , A. W A L D ,

T . S . T A L A M O , A N D H. M E N D E L O W

C O . E L S O N , M.F. K A G N O F F , C. F I O C C H I ,

A.D. B E F U S , A N D S. T A R G A N

K. D H A R M S A T H A P H O R N

R.L. O W E N

G.J. SÖMJEN A N D T. G I L A T

740

746

769

770 772

776

777

778

779 780 781

782

784 787 793 796

NO. 4, OCTOBER 1986

AMERICAN GASTROENTEROLOGICAL ASSOCIATION

The Future of Digestive Diseases Research: Is There Cause for Concern? The Presidential Address

LIVER A N D BILIARY TRACT

Results of a Randomized Trial of End-to-Side Por­tacaval Shunt and Distal Splenorenal Shunt i n A l ­coholic Liver Disease and Variceal Bleeding

T-Lymphocyte Sensitization to Hepatocyte A n t i ­gens i n Auto immune Chronic Active Hepatitis and Primary Bi l iary Cirrhosis. Evidence for Different Underlying Mechanisms and Different Antigenic Determinants as Targets

Foscarnet Decreases Serum and Liver Duck Hepa­tit is Β Virus D N A i n Chronically Infected Ducks Serum Bile A c i d Concentrations During Pregnancy and Their Relationship to Obstetric Cholestasis

A L I M E N T A R Y TRACT

Somatomedin-C Levels i n Growth-Impaired Chi l ­dren and Adolescents W i t h Chronic Inflammatory Bowel Disease

|.S. T R I E R 797

H. A.J. H A R L E Y , T . M O R G A N , A . G . R E D E K E R , 802

T.B. R E Y N O L D S , F. V I L L A M I L , J.M. WEINER,

A N D A. Y E L L I N

S. V E N T O . C.J. O ' B R I E N , B.M. M c F A R L A N E , 810

I. G. M c F A R L A N E , A . L . W . F . E D D L E S T O N , A N D

R. W I L L I A M S

A . H . S H E R K E R , K. H I R O T A , Μ. O M A T A , A N D 818

K. O K U D A

M. L U N Z E R , P. B A R N E S . Κ. B Y T H , AND 825

M. O ' H A L L O R A N

B.S. K I R S C H N E R A N D M.M. S U T T O N 830

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C O N T E N T S G A S T R O E N T E R O L O G Y Vol . 91, No

Effects of Topical 5-Aminosalicylic A c i d and Pred­nisolone on Prostaglandin E 2 and Leukotriene B 4

Levels Determined by E q u i l i b r i u m In Vivo Dialysis of Rectum i n Relapsing Ulcerative Colitis

Abnormal Sensory Perception i n Patients W i t h Esophageal Chest Pain Influence of the Oropharyngeal Microflora on the Measurement of Exhaled Breath Hydrogen

Transferrin Receptors in the Human Gastrointesti­nal Tract. Relationship to Body Iron Stores Effect of Ethanol on Intestinal Calcium Transport i n Chicks Distr ibut ion and Molecular Heterogeneity of Ga-lanin i n Human, Pig, Guinea Pig, and Rat Gastro­intestinal Tracts

Effects of Corticotropin-Releasing Factor on Plasma M o t i l i n and Somatostatin Levels and Gastrointesti­nal M o t i l i t y i n Dogs A b o l i t i o n of Gas Reflux and Transient Lower Esophageal Sphincter Relaxation by Vagal Block­ade i n the Dog

Esophageal Peristaltic Dysfunction i n Peptic Esophagitis I n h i b i t i o n of Gastric A c i d Secretion by Brain Pep­tides i n the Dog. Role of the Autonomic Nervous System and Gastrin Role of the Unstirred Layer i n Protecting the M u ­rine Gastric Mucosa From Bile Salt

Kinetic Assay of Human Gastric Lipase on Short-and Long-Chain Triacylglycerol Emulsions

Circadian Variation i n the Propagation Velocity of the Migrating Motor Complex

Intestinal Hydrolysis of Aspartylphenylalanine— The Metabolic Product of Aspartame

Arctic Trichinosis Presenting as Prolonged Diarrhea

Three-Dimensional Organization of the Lymphatics i n the Rabbit Appendix . A Scanning Electron and Light Microscopic Study

Electron Microscopic Study of Neuropeptide Y-Containing Nerve Elements of the Guinea Pig Small Intestine

Protection by Metals Against Ethanol-Induced Gas­tric Mucosal In jury i n the Rat. Comparative Bio­chemical and Pharmacologic Studies Implicate Protein Sulfhydryls

Gastric Mucosal Protection Against Ulcerogenic Factors i n the Rat Mediated by Capsaicin-Sensitive Afferent Neurons

Nature and Course of Pancreatitis Caused by 6-Mercaptopurine i n the Treatment of Inflammatory Bowel Disease

K. L A U R I T S E N , L .S . L A U R S E N . K. B U K H A V E ,

A N D J. R A S K - M A D S E N

J.E. R I C H T E R , C F . B A R I S H . A N D D.O. C A S T E L L

D.G. T H O M P S O N . J.D. O ' B R I E N . A N D

J.M. H A R D I E

D. B A N E R J E E . P.R. F L A N A G A N , J. C L U E T T . A N D

L S . V A L B E R G

D.D. B I K L E , E . A . G E E , A N D S.J. M U N S O N

F.E . B A U E R . T . E . A D R I A N , N.D. C H R I S T O F I D E S ,

G-L. F E R R I , N. Y A N A I H A R A . J.M. P O L A K . A N D

S.R. B L O O M

L. B U E N O . M.J. F A R G E A S . M. G U E ,

T . L . P E E T E R S . V. B O R M A N S , AND

J .FIORAMONTI

C.J. M A R T I N , J. P A T R I K I O S , A N D J. D E N T

P.J. K A H R I L A S , W.J. DODDS, W.J. H O G A N ,

M. K E R N . R.C. A R N D O R F E R . A N D A. R E E C E

H.J. L E N Z , R. K L A P D O R , S.E. H E S T E R ,

V.J. W E B B . R.F. G A L Y E A N , J.E. RIVIER, A N D

M.R. B R O W N

W.C. D U A N E , M.D. L E V I T T , N.A. S T A L E Y ,

A.P. M c H A L E , D.M. W I E G A N D . A N D

C A . F E T Z E R

Y. G A R G O U R I , G. PIERONI, C. R I V I E R E ,

J-F. S A U N I E R E . P.A. L O W E , L . S A R D A , A N D

R. B E R G E R

D. K U M A R , D. W I N G A T E , A N D Y. R U C K E B U S C H

N.A. T O B E Y A N D W.D. H E I Z E R

J. V I A L L E T , J.D. M a c L E A N , C A . G O R E S K Y ,

M. S T A U D T , G. R O U T H I E R , A N D C. L A W

Ο. O H T A N I , A. O H T S U K A , A N D R.L . O W E N

E. F E H E R A N D G. B U R N S T O C K

D. D U P U Y AND S. S Z A B O

P. H O L Z E R A N D W. S A M E T Z

C.J. H A B E R . S.J. M E L T Z E R , D.H. P R E S E N T , A N D

B.I. K O R E L I T Z

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December 1986 C O N T E N T S xi

CASE REPORTS Liver Abscess i n Crohn's Disease. Report of Four Cases and Review of the Literature Radiation-Induced Intestinal Pseudoobstruction

Fragile Papilloma (Papillary Adenoma) of the Gall­bladder. A Cause of Recurrent Biliary Colic

CLINICAL TRENDS A N D TOPICS Gastrointestinal Hormones and Gastrointestinal and Pancreatic Carcinomas

PROGRESS ARTICLE Effect of Ursodeoxycholic A c i d and Chenodeoxy-cholic A c i d on Cholesterol and Bile A c i d Metabolism

EDITORIALS Growth Retardation i n Chronic Inflammatory Bow- D M . M O C K

el Disease Variceal Bleeding: W h i c h Shunt? J.M. HENDERSON

SELECTED SUMMARIES Interaction of the Vagus and Enterogastrone to In­hib i t A c i d How D O Solids and Liquids Empty From the Stomach? Dietary-Induced Alterations i n Intestinal Trans­port—Or You Are What You Eat Diagnosis of Inflammatory Bowel Disease W i t h Sucralfate

HBV Vaccines Without HBsAg: Immune M i m i c r y Via Ant i id io type Antibodies Nuclear Bomb Explosions and the Age of Gallstones

Resection of Colorectal Metastases to Liver

BOOK REVIEWS CORRESPONDENCE NOTICES CLASSIFIED ADS PROGRAM OF THE MEETING OF THE AMERICAN MOTILITY SOCIETY

S . H . M I R - M A D J L E S S I . M.C. M c H E N R Y , A N D

R . G . F A R M E R

L . E . PERINO, M.D. S C H U F F L E R , S.). M E H T A ,

A N D G.T. E V E R S O N

Y. NIV, K. K O S A K O V . A N D B. S H C O L N I K

C M . T O W N S E N D , JR., P. S I N G H , A N D

I . C T H O M P S O N

G . S . T I N T , G. S A L E N , A N D S. S H E F E R

987

994

999

1002

1007

1019

1021

1024

1025

1026

1027

1027

1028

1029

1031 1035 1037 1040 1041

NO. 5, NOVEMBER 1986

A L I M E N T A R Y TRACT Gastrointestinal Lesions i n Hereditary Hemorrhagic Telangiectasia

Autoradiographic Localization of μ- and δ-Type Opio id Receptors i n the Gastrointestinal Tract of the Rat and Guinea Pig

Chronic Antra l Gastritis i n Duodenal Ulcer. Natu­ral History and Treatment W i t h Prostaglandin E a

P. V A S E A N D O. G R O V E 1079

E. N I S H I M U R A , A.M.J. B U C H A N , A N D 1084

C . H . S . M c I N T O S H

W - M . HUI, S-K. L A M , J. HO, M.M-T. NG, I. L U I , 1095

C - L . L A I , A . S - F . L O K , W-Y. L A U , G-P. POON,

S. CHOI, A N D T - K . C H O I

Page 11: Diffuse somatostatin-immunoreactive D-cell hyperplasia in

xii C O N T E N T S G A S T R O E N T E R O L O G Y Vol. 91, No. 6

Colonic Transit Scintigraphy. A Physiologic A p ­proach to the Quantitative Measurement of Colon­ic Transit i n Humans

Variations of Gastric Transmucosal Potential Dif­ference and Lesion Formation During Hemorrhagic Shock i n the Rat

Anorectal Ergotism: Another Cause of Solitary Rectal Ulcers

Porosity of the Basement Membrane Overlying Peyer's Patches i n Rats and Monkeys Effects of Intra luminal Epidermal Growth Factor on Mucosal Proliferation i n the Small Intestine of A d u l t Rats

Bethanechol Increases the Diagnostic Y ie ld i n Pa­tients W i t h Esophageal Chest Pain Clostr idium difficile Cytotoxin Inhibits Protein Synthesis i n Fibroblasts and Intestinal Mucosa Cholecystokinetic and Pancreozymic Effect of O-Sulfated Gastrin Compared W i t h Nonsulfated Gas­t r i n and Cholecystokinin

Colonic Dysfunction Dur ing Cholera Infection

Mechanism of Increased Exocrine Pancreatic Secre­t ion i n Pancreatic Juice-Diverted Rats Bone Metastases i n Malignant Gastrinoma

Delayed Rectal Sensation W i t h Fecal Incontinence. Successful Treatment Using Anorectal Manometry Circadian Variation of Susceptibility to Gastric Mucosal In jury by Ac id i f i ed A s p i r i n or Absolute Ethanol i n the Rat

Healing and Relapse of Reflux Esophagitis D u r i n g Treatment W i t h Ranitidine

Increased HLA-DR Expression by Enterocytes i n Children W i t h Celiac Disease

Scintigraphic Measurements of Canine Ileocolonic Transit. Direct and Indirect Effects of Eating

Cholinergic Mediat ion of γ-Aminobutyric A c i d - I n ­duced Gastrin and Somatostatin Release From Rat A n t r u m

Role of Aldosterone i n the Regulation of Sodium and Chloride Transport i n the Distal Colon of So­dium-Depleted Rats Identification and Characterization of Brush-Border Membrane-Bound Neutral Metalloendopeptidases From Rat Small Intestine

Bile Salt Malabsorption i n Pancreatic Insufficiency Secondary to Alcohol ic Pancreatitis

B. K R E V S K Y , L . S . M A L M U D , F. D ' E R C O L E , 1102

A . H . M A U R E R , A N D R.S. F I S H E R

K. T A K E U C H I , Τ. O H N O , A N D S. O K A B E 1113

V . F . E C K A R D T , G. K A N Z L E R , A N D 1123

W. R E M M E L E

S.G. M c C L U G A G E , F .N. L O W , A N D M.L. Z I M N Y 1128

M.H. U L S H E N , L . E . L Y N - C O O K , AND 1134

R.H. R A A S C H

T . T . N O S T R A N T , J. S A M S , A N D T. H U B E R 1141

C. P O T H O U L A K I S , G. T R I A D A F I L O P O U L O S , 1147

M. C L A R K , C. F R A N Z B L A U , A N D J.T. L a M O N T

P. C A N T O R , L. P E T R O N I J E V I C , J.F. P E D E R S E N , 1154

A N D H. W O R N I N G

P. S P E E L M A N , T . B U T L E R , I. K A B I R , A. A L I . 1164

A N D J. B A N W E L L

K. S H I R A T O R I , Y . F . C H E N , W.Y. C H E Y , 1171

K . Y . L E E , A N D T - M . C H A N G

J.C. B A R T O N , B.I. H I R S C H O W I T Z , P.N. M A T O N . 1179

A N D R.T. J E N S E N

W.D. B U S E R A N D P.B. MINER, JR. 1186

C . E . O L S O N , A . H . S O L L , AND P.H. G U T H 1192

H.R. K O E L Z , R. B I R C H L E R , A. B R E T H O L Z , 1198

B. BRON, Y. C A P I T A I N E , G. D E L M O R E .

H.F . F E H R , I. F U M A G A L L I , J. G E H R I G ,

J.J. G O N V E R S , F. H A L T E R , B. H A M M E R ,

L. K A Y A S S E H , E . K O B L E R , G. M I L L E R ,

G. MÜNST, S. P E L L O N I , S. R E A L I N I ,

P. SCHMID, M. V O I R O L , A N D A . L . B L U M

F. A R N A U D - B A T T A N D I E R , 1206

N. C E R F - B E N S U S S A N , R. A M S E L L E M , A N D

J. S C H M I T Z

R.C. S P I L L E R , M.L. B R O W N . S.F. P H I L L I P S . 1213

A N D F. A Z P I R O Z

R.F. H A R T Y A N D P.A. F R A N K L I N 1221

J. H A L E V Y , M.E. BUDINGER, J.P. H A Y S L E T T , 1227

A N D H.J. BINDER

I-S. S O N G , M. Y O S H I O K A , R.H. E R I C K S O N , 1234

S. M I U R A , D. G U A N , A N D Y . S . K I M

S.K. D U T T A , K. A N A N D , A N D T.R. G A D A C Z 1243

Page 12: Diffuse somatostatin-immunoreactive D-cell hyperplasia in

December 1986 C O N T E N T S xiii

Cholinergic Modula t ion of the Release of Seroto­n i n i n the Gastric Interstitial F l u i d . A n I n Vivo Study i n Rabbits

LIVER A N D BILIARY TRACT A New Method to Assay Des-y-Carboxyprothrom-b i n . Results Obtained i n 75 Cases of Hepatocellu­lar Carcinoma Sex Hormone-Related Functions i n Regenerating Male Rat Liver

Effect of Glucagon on Alcohol Dehydrogenase Ac­t i v i t y i n Rat Hepatocyte Culture

Demonstration of a Transcellular Vesicle Pathway for Bi l iary Excretion of I n u l i n i n Rat Liver

CASE REPORTS Magnetic Resonance Imaging Diagnosis of B u d d -Chiari Syndrome

M e t h y l tert-Butyl Ether Fails to Dissolve Retained Radiolucent Common Bile Duct Stones

Esophageal Cryptosporidiosis i n a C h i l d W i t h Ac­quired Immune Deficiency Syndrome

EDITORIALS Asiatic Cholera: Nature's Experiment?

Diagnosis of Primary Hepatocellular Carcinoma SELECTED SUMMARIES

Preoperative Chemotherapy i n Esophageal Cancer Differing Incidence and Long Latency of Malignan­cy After Gastric Surgery Effect of Cholecystokinin on Gastric Emptying

Pigment i n the Center of Cholesterol Gallstones— Colorful , but Pathogenically not Important? Feeding and Epidermal Growth Factor Insul in and the Colon Heterogeneity of Goblet Cells i n the H u m a n Colon

Reply to Selected Summary: Resection of Colorec­tal Metastases to Liver (GASTROENTEROLOGY 1986;91:1029-30)

BOOK REVIEWS CORRESPONDENCE CORRECTION NOTICES CLASSIFIED ADS

NO. 6, DECEMBER 1986

LIVER A N D BILIARY TRACT Randomized Tria l of Chlorambucil for Primary B i l ­iary Cirrhosis

M . P A I R E T , O. M E I R I E U , T . B A R D O N , A N D

Y . R U C K E B U S C H

J-P. S O U L I E R , D. G O Z I N , A N D

J-J. L e F R E R E

A. F R A N C A V I L L A , P.K. E A G O N , A. D i L E O ,

L . P O L I M E N O , C. P A N E L L A , A . M . A Q U I L I N O ,

M . I N G R O S S O , D . H . V A N T H I E L , A N D

T . E . S T A R Z L

Ε. M E Z E Y , J.J. P O T T E R , A N D D.L . R H O D E S

I. L O R E N Z I N I , S. S A K I S A K A , P.J. M E I E R , A N D

J.L. B O Y E R

A . C . F R I E D M A N , P. R A M C H A N D A N I ,

M. B L A C K , D.F . C A R O L I N E , P.D. R A D E C K I ,

A N D P. H E E G E R

C . Di P A D O V A , F . Di P A D O V A , W. M O N T O R S I ,

A N D R. T R I T A P E P E

P .G. K A Z L O W , K. S H A H , K.J. B E N K O V ,

R. D I S C H E , A N D N.S. L e L E I K O

S.F . P H I L L I P S

M.J. T O N G

J.H. H O O F N A G L E , G . L . D A V I S , D.F . SCHÄFER,

Μ. P E T E R S , M.I. A V I G A N , S . C P A P P A S ,

R.G. H A N S O N , G.Y. MINUK, G.M. D U S H E I K O ,

G. C A M P B E L L , R.N.M. M a c S W E E N , A N D

E . A . JONES

1250

1258

1263

1271

1278

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xiv C O N T E N T S G A S T R O E N T E R O L O G Y Vol. 91, No. 6

Dynamics of Hepatic Glycosaminoglycan Accumu­lation in Murine Schistosoma japonicum Infection Low-Protein-Concentration Ascitic Fluid Is Predis­posed to Spontaneous Bacterial Peritonitis Brain Edema in Rabbits With Galactosamine-Induced Fulminant Hepatitis. Regional Differences and Effects on Intracranial Pressure Detection of Hepatitis Β Virus Infection in Hepati­tis Β Surface Antigen-Negative Hemodialysis Pa­tients by Monoclonal Radioimmunoassays Reflex Regulation of Flow Resistance in the Feline Sphincter of Oddi by Hydrostatic Pressure in the Biliary Tract

A L I M E N T A R Y T R A C T

Life Events Stress and Psychosocial Factors in Men With Peptic Ulcer Disease. A Multidimen­sional Case-Controlled Study Effect of Transection and Pacing on Human Jeju­nal Pacesetter Potentials Peptide Y Y Release by Fatty Acids Is Sufficient to Inhibit Gastric Emptying in Dogs

Effect of Intragastric Infusions of Ethanol and Wine on Serum Gastrin Concentration and Gastric Acid Secretion

Prevalence and Incidence of Inflammatory Bowel Disease in Family Members Structural Features of Absorptive Cell and Micro­villus Membrane Preparations From Rat Small Intestine Early Microcirculatory Stasis in Acute Gastric Mu­cosal Injury in the Rat and Prevention by 16,16-Dimethyl Prostaglandin E 2 or Sodium Thiosulfate

Central Nervous System Influence of Prostaglandin E 2 on Jejunal Water and Electrolyte Transport in Conscious Dogs

Rat Pancreatic Zymogen Granules. A n Actively Acidified Compartment

Charge Selectivity of Rat Intestinal Capillaries. In­fluence of Polycations Comparison of the 1-Gram [ 1 4C]Xylose, 10-Gram Lactulose-H 2, and 80-Gram Glucose-H 2 Breath Tests in Patients With Small Intestine Bacterial Overgrowth

Influence of Food and Marker Length on Gastric Emptying of Indigestible Radiopaque Markers in Healthy Humans

Superficially Invasive Squamous Cell Carcinoma of the Esophagus. A Study of Seven Cases in Mem­phis, Tennessee

Altered Calcium-Handling Properties of Jejunal Smooth Muscle From the Nematode-Infected Rat Central a:2-Adrenergic Control of the Pattern of Small Intestinal Motility in Rats

G.R. O L D S , C. F I N E G A N , A N D T . F . K R E S I N A 1335

B.A. R U N Y O N 1343

P.G. T R A B E R , D.R. G A N G E R , A N D A . T . B L E I 1347

Y . K . FUJITA, Κ. K A M A T A , Η. K A M E D A , 1357

K.J. I S S E L B A C H E R , AND J.R. W A N D S

A. T H U N E , Ε. T H O R N E L L , A N D J. S V A N V I K 1364

M. F E L D M A N , P. W A L K E R , J.L. G R E E N , A N D 1370

K. W E I N G A R D E N

H M . R I C H T E R , III A N D Κ.Α. K E L L Y 1380

T . N . P A P P A S , H.T. D E B A S , A . M . C H A N G , AND 1386

I .L . T A Y L O R

W.L. P E T E R S O N , C. B A R N E T T , A N D 1390

J.H. W A L S H

B. A. L A S H N E R , A .A. E V A N S , J.B. K I R S N E R , 1396

A N D S.B. H A N A U E R

D.J. BJORKMAN, C . H . A L L A N , S.J. HÄGEN. 1401

A N D J.S. T R I E R

G. P I H A N , D. MAJZOUBI, C. H A U D E N S C H I L D , 1415

J.S. T R I E R , A N D S. S Z A B O

M.P. PRIMI AND L. B U E N O 1427

C. N I E D E R A U , R.W. Van D Y K E , 1433

B. F. S C H A R S C H M I D T , A N D J.H. G R E N D E L L

D. N. G R A N G E R , P.R. K V I E T Y S , M A . P E R R Y , 1443

A N D A . E . T A Y L O R

C. E. K I N G AND P.P. T O S K E S 1447

H. J. S M I T H AND M. F E L D M A N 1452

L.W. S C H M I D T , P.J. D E A N , AND R.T. W I L S O N 1456

A . E . F O X - R O B I C H A U D A N D S.M. C O L L I N S 1462

M.J. F A R G E A S , J. F I O R A M O N T I , A N D 1470

L. B U E N O

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D e c e m b e r 1986 C O N T E N T S xv

Folic A c i d Malabsorption i n Atrophic Gastritis. Possible Compensation by Bacterial Folate Synthesis

Phenotypic Analysis of Lamina Propria Lympho­cytes. Predominance of Helper-Inducer and Cyto­lyt ic T-Cell Phenotypes and Deficiency of Sup-pressor-Inducer Phenotypes i n Crohn's Disease and Control Patients

A Laboratory Index for Predicting Relapse i n Asymptomatic Patients W i t h Crohn's Disease

Production of Secretory Immunoglobul in A in Rat Self-Fil l ing B l i n d Loops. Local Secretory Immuno­globul in A Immune Response to Luminal Bacterial Flora

Oncogene Alterations i n Primary Human Colon Tumors Growth Characteristics of Autochthonous Experi­mental Colonic Tumors as Assessed by Serial Co­lonoscopic Measurement i n Rats

Intestinal Adaptation. Different Growth Responses to Disaccharides Compared W i t h Monosaccharides i n Rat Small Bowel

Famil ial Visceral Neuropathy W i t h Autosomal Dominant Transmission

Effect of Cigarette Smoke on Esophageal Epitheli­u m of the Rabbit

CASE REPORTS Colonic Varices. Report of an Unusual Case Diag­nosed by Radionuclide Scanning, W i t h Review of the Literature Chronic Mesenteric Vascular Insufficiency W i t h Gastric Ulceration Monozygotic Triplets W i t h Crohn's Disease of the Colon

CLINICAL TRENDS A N D TOPICS Gallstone Dissolution Therapy. Current Status and Future Prospects

SELECTED SUMMARIES Intrinsic Reflexes Between the Esophagus and Stomach To Treat or not to Treat

Hepatic Vi tamin A Metabolism

Move Over Acetaldehyde, Here Come the Fatty A c i d Ethyl Esters!

Fibrosis and Granulomas i n the Liver Due to Bac­terial Cell Wal l Components Risks and Benefits of Percutaneous Transhepatic Bil iary Drainage Reply to Selected Summary: How Do Solids and Liquids Empty From the Stomach? (GASTROEN­TEROLOGY 1986;91:1025-6)

R.M. R U S S E L L , S.D. K R A S I N S K I ,

I .M. S A M L O F F , R.A. JACOB, S C . H A R T Z , A N D

S.R. B R O V E N D E R

S.P. JAMES, C. F I O C C H I . A . S . G R A E F F , AND

W. S T R O B E R

C. B R I G N O L A , M. C A M P I E R I , G. B A Z Z O C C H I .

P. F A R R U G G I A , A. T R A G N O N E , A N D

G.A. L A N F R A N C H I

S. L I C H T M A N , P. S H E R M A N , A N D

G. F O R S T N E R

R.J. A L E X A N D E R , J.N. B U X B A U M , A N D

R.F . R A I C H T

S.R. H A M I L T O N , S-Z. Z H A N G ,

D. O ' C E A L L A I G H , A N D D. M c A V I N C H E Y

E. WESER, J. B A B B I T T . Μ. H O B A N , AND

A. V A N D E V E N T E R

E . A . M A Y E R , M.D. S C H U F F L E R , J.I. R O T T E R .

P. H A N N A , AND M. M O G A R D

R.C. O R L A N D O . J.C. B R Y S O N . A N D

D.W. P O W E L L

H. GUDJONSSON. D. Z E I L E R , R.L . G A M E L L I .

AND M.D. ΚΛΥΕ

R.D. C H E R R Y . M. JABBARI. C A . G O R E S Κ Y,

M. H E R B A , D. R E I C H . A N D P.E. B L U N D E L L

J. P U R R M A N N . J. B E R T R A M S , F. B O R C H A R D ,

B . M I L L E R , S . C L E V E L A N D , T . S T O L Z E , AND

G. S T R O H M E Y E R

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G A S T R O E N T E R O L O G Y 1986;91:733-9

Diffuse Somatostatin-Immunoreactive D-Cell Hyperplasia in the Stomach and Duodenum

G. E. H O L L E , W. SPANN, W. EISENMENGER, J. RIEDEL, and L. PRADAYROL Surgical University Clinic and Policlinic, Munich-Center, Munich; University Institute of Forensic Medicine, Munich, Federal Republic of Germany; and I N S E R M U 151, CHU-Ranguil, Toi'lou^e France

This paper presents the first case of extensive, dif­fuse, somatostatin-immunoreactive D-cell hyperpla­sia in the human stomach and duodenum. It oc­curred in a 37-yr-oId woman, who showed clinical signs of dwarfism, obesity, dryness of the mouth, and goiter. The density of the distribution of Ό cells was increased 39-fold in the stomach fundus, 23-fold in the proximal antrum, 25-/oJd in the distal antrum, and 31 -fold in the upper duodenum in comparison with normal values. At the same time, the gastrin-immunoreactive cells were increased 2.3-fold in the antrum. Although the range in size of the D cells was within normal limits in all regions examined, the G cells showed pronounced hypertro­phy of up to 127%. A possible relationship between the immuno-histochemicaJ findings and the clinical picture is discussed.

Somatostatin is widely distributed in neurons and fibers in the central nervous system, especially in the hypothalamic region (1) and throughout the nervous

Received October 2, 1985. Accepted March 13, 1986. Address requests for reprints to: G. E . Holle, M.D., Lecturer in

Pathophysiology, Ludw. Max. University, Munich; Surgical Uni­versity Clinic and Policlinic, Munich-Center, Gastroenterology Research Laboratory, Pettenkoferstrasse 8a, 8000 Munich 2, Fed­eral Republic of Germany.

This work was supported by the Deutsche Forschungsgemein­schaft, Bad Godesberg, F .R.G. , Ho 936/1-2.

A n extract of this paper was presented at the 18th meeting of the European Association of Gastroenterology and Endoscopy and was awarded the first prize for the best presentation, March 14, 1986.

The authors thank Professor E . Wünsch of the Max-Planck Institute for Biochemistry, Martinsried, F .R .G. for the somato­statin 28 and gastrin 17 and 34; Professor W. G. Forssmann, of the Anatomy Institute at the University of Heidelberg, F .R.G. for the gastrin-antibody serum; Mrs. A. Ruhfus for skillful technical assistance; and Mrs. Jennifer Grüner for translation assistance.

© 1986 by the American Gastroenterological Association 0016-5085/86/$3.50

system of the digestive tract. It is also produced and stored in considerable amounts in the D cells in the intestinal mucosa and in the pancreas (2,3). Here, it may act (in part) in a paracrine, mainly inhibitory manner (4), but stimulated somatostatin also enters the circulation (5). Somatostatin controls hormones of the gastrointestinal tract and the pancreas (6), the endocrine function of the anterior pituitary (7), the thyroid gland (8), the salivary gland (9), and the urinary excretory system. It achieves homeostasis of nutrients in a wide range (10,11) and influences functional maturation, growth, and behavior (12-14).

Taking into account some deviations in different laboratories, somatostatin blood levels are highest in the portal vein at 100 pg/ml. This is a clear indica­tion of the extensive production of somatostatin in the upper gastrointestinal tract. In the general circu­lation, physiologic levels in the fasting state are —29 ± 5 pg/ml, and in the postprandial state after carbo­hydrate, protein, and fat they are 48 ± 7, 74 ± 8, and 80 ± 9 pg/ml, respectively (15). The level is highest after a mixed meal (16). At these levels somatostatin influences insulin and glucagon release, indicating its endocrine function (17). The somatostatin present in the cerebrospinal fluid ranges —35.4 pg/ml (18).

Since 1979, pathological increased levels of cir­culating somatostatin have been described in spo­radic cases of solid somatostatin tumors and in somatostatinomas containing subpopulations of other endocrine cells (19,20). Like gastrinomas, the tumors were mostly malignant and with few excep­tions were predominantly located in the pancreas: two tumors in the duodenum (21,22) and one in the jejunum (23). The clinical symptoms were heteroge­neous and depended on the serum somatostatin levels and probably on the composition of the dif­ferent molecular weight forms of the circulating

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hormones (24,25), the hormonal heterogeneity of some somatostatinomas, and probably on the vary­ing degrees of target organ resistance to the increased hormone levels (26).

Case Report A 37-yr-old woman died suddenly exhibiting nau­

sea and dyspnea. A n autopsy was performed within 6 h. The fresh, macroscopically inconspicuous stomach was prepared for the purpose of studying the normal distribu­tion of special cell populations, including the peptide hormone cells in the stomach mucosa.

Retrospective inquiry into the case history revealed the following. From early infancy on, the woman showed retarded growth, but she was slender until puberty. Later, she became obese. She was hypokinetic and except for an appendectomy, a tonsillectomy, and a motoring accident 7 mo before death, she never felt i l l . She sometimes used contraceptives and had irregular menstrual cycles. On the whole, she displayed retarded sexual behavior and became increasingly lethargic and sleepy. Weight, and especially thirst, increased continuously until they reached patholog­ical levels (>3L/day of liquids, some of which was cola-fl­avored soda). At death she was 146 cm tall and weighed 97 kg-

During the time when she was hospitalized for her accident, the following was observed: extreme dryness of the oral cavity and an unstable blood pressure reading between 120/80 mmHg and 180/110 mmHg. Some abnor­mal laboratory results were available from the 4-6-mo period before death (numbers in parentheses are normal values): a 2-globulin, 12.30 relative % (4.7-9.5 relative %) ; serum cholesterol, 243 mg/dl (<220 mg/dl); γ-glutamyl-transpeptidase, 27.4 U/L (4-18 U/L); potassium level, 3.29 mmol/L (3.5-5.0 mmol/L). Urinalysis and creatinine clear­ance, as well as fasting glucose levels (82.0 and 95.0 mg/dl, normal = 50-120 mg/dl), were normal. She had very fragile bones with very thin corticalis. A slight trauma resulted in a humerus fracture followed by a very pro­longed healing process.

Autopsy showed bilateral pulmonary embolism as the cause of death. The weights of various organs were as follows: brain, 1394 g; heart, 394 g; lungs, 660 g; liver, 2115 g; and spleen, 256 g. The enlargements were between 7% and 46%. The pancreas was of normal size and weight, she had a nodular goiter of considerable size, and abscess cavities were found at the upper pole of the left kidney.

Materials and Methods

After removal of its contents, the stomach was opened at the greater curvature, washed in ice water, prepared in 10 longitudinal strips, fixed in Bouin's fluid for 24 h, dehydrated, and embedded in paraffin. From the total material (including corpus-fundus, the total antrum, and the upper duodenum), complete sagittal sections from the surface to the muscle layers were prepared alternately as follows for differential cell counts: (a) hematoxylin and eosin dye for the total gland cells; (b) modified Zim­mermann dye for the parietal cells and mucous neck cells;

(c) Masson-Fontana for the enterochromaffin cells; and (d) the peroxidase-antiperoxidase method after Sternberger (27) for gastrin-immunoreactive cells and somatostatin-immunoreactive cells.

The antisera came from rabbits after immunization with (a) synthetic human gastrin 17 and 34 from E. Wünsch (prepared and tested by W. G. Forssmann) and (b) syn­thetic somatostatin 28 (octacosapeptide) from E. Wünsch. L. Pradayrol prepared and tested the somatostatin 28 antibody serum by radioimmunoassay to exclude cross-reactivity against 18 gastrointestinal hormones at the 100-ng level. A l l antisera were used in a dilution of 1:1000, with an incubation time of 72 h. Sections incubated with antiserum inactivated by addition of an excess of the respective antigen (50 μg of synthetic somatostatin 28 per milliliter of diluted antiserum) were used as controls.

Cell counts were carried out according to the method jointly developed with A. Schauer (28). In an area of 5000-8000 nuclei-containing gland cells, the specific cells were identified on a drawing microscope, outlined, counted, and determined by percentage of the total num­ber of gland cells. The count method gives as a result the density of the cell population in the tissue. Each counted tissue block (~2 cm in length) was subdivided into an oral and aboral measuring area. The total antrum was exam-

MAC MAC

AW Anterior Wall PW Posterior Wall

A Antrum Py Pylorus

MIC minor curvature side MAC major curvature side

I II III IV

Fundus prox. Antrum dist. Antrum Duodenum

-10 tissue blocks

Figure 1. Diagram of the measuring fields in the stomach fundus-corpus, the proximal and distal antrum, and the prox­imal duodenum. Every numbered tissue block is sub­divided into an oral and aboral measuring area.

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September 1986 D - C E L L H Y P E R P L A S I A IN D W A R F I S M A N D O B E S I T Y 735

Size of Somatostatin u D-CeUs in the stomach Fundus, prox. Antrum, dist. Antrum and Duodenum

Figure 2. Evaluation of somatostatin-immuno-reactive U cells in the upper gastroin­testinal tract of patient D.R. in compar­ison with normal values (N). Top panel: size of D cells ascertained as an average of 100-150 cells . Bottom panel: percentage of D-cell population of each in an area of 500-8000 total mucosal gland cells.

80-

70

60

50 PA d A

Number 7< 20η

F Fundus pA prox. Antrum dA dist. Antrum D Duodenum

SD 10 tissue blocks so n=12

F p A d A D

Number % of Somatostatin i.r. D-Cett Population in the

Stomach Fundus, Antrum and Duodenum

ined completely. Counting results for our patient were given from four representative circular strips: (a) the distal fundus, (b) the proximal antrum, (c) the distal antrum, and (d) the proximal duodenum (Figure 1). The data express the mean values of the results of all measured areas of the 10 and 8 tissue blocks from each total circumference.

G cells and D cells were surface analyzed using the semicomputerized Leitz ASM analytical system. The mean values of 100-150 nucleus-containing cells were deter­mined for each examination. The mucosal thickness and the length of the histologic antrum were determined with the same equipment. The control values for comparison were taken from a separate study on the normal distribu­tion of gastrin- and somatostatin-immunoreactive cells in the human stomach from 12 healthy subjects of different age and sex who died in accidents (G. E. Holle et al., in preparation). Bioptic material was also compared from peptic ulcer patients preoperatively and postoperatively (29,30).

Results I n the present case, the stomach was of normal

size and shape. The length of the histologic antrum ranged f rom 4.5 cm at the lesser curvature to 6.2 cm at the major curvature. The mucosal thickness was 1066 ± 118 μτη i n the stomach fundus, 869 ± 73 μτη i n the proximal antrum, and 833 ± 63 μτη i n the distal antrum. The tubular-shaped course of the fundus glands showed high parietal cell numbers w h i c h were between 20% and 30% of the total number of fundus gland cells. The anatomic arrange­ment of the pyloric glands was regular. Likewise, scattered islets w i t h inflammatory inf i l t ra t ion i n the gastric antrum were w i t h i n the normal range. The density of the somatostatin-immunoreactive D-cell populat ion was 2.38% ± 1.78% i n the fundus-corpus, 14.46% ± 2.89% i n the proximal antrum,

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Size of Gastrin i.r Cells in the Stomach Fundus, Antrum and Duodenum

no

100

80

70

LO

20-

pA d A

# p<0,01

- Γ -Ο

* p<0.01 * * p<0.05

Figure 3. Evaluation of gastrin immunoreactive cells in the upper gastrointestinal tract of patient D.R. in comparison with normal values (N). Top panel: size of G cells ascertained as an average of 150 cells. Bottom panel: percentage of G-cell population of each in an area of 5000-8000 total mucosal gland cells.

F Fundus pA prox. Antrum dA dist. Antrum D Duodenum

OR. patient Ν Normal

so 10tissue blocks SD η = 12

F pA dA D

Number % of Gastrin i.r. Cell Population in the Stomach Fundus, Antrum and Duodenum

15.58% ± 3.59% in the distal antrum, and 1.53% ± 0.57% in the proximal duodenum. In comparison with the density of the somatostatin-immunorea-ctive cells in normal stomachs (0.06% in the fundus, 0.62% in the antrum, and 0.07% in the upper duo­denum), this means a 39-fold increase in the density of the somatostatin-immunoreactive cells in the stomach fundus, a 23-fold increase in the proximal antrum, a 25-fold increase in the distal antrum, and a 21-fold increase in the upper duodenum (Figure 2).

In all regions, the size of the somatostatin-immu­noreactive D cells was normal, with 77 ± 9 μπι2 in the fundus, 74 ± 7 μπι2 in the proximal antrum, 65 ± 9 μ,πι2 in the distal antrum, and 73 ± 5 / im 2 in the upper duodenum. In the antrum, somatostatin-immunoreactive D-cell sizes had a tendency to be­come smaller from the oral to the aboral area, but the differences are not significant.

In comparison to D-cell distribution, the fundus-

corpus showed only a few scattered G cells. The G cells in the proximal antrum amounted to 10.51% ± 2.58%, in the distal antrum 12.51% ± 3.34%, and in the proximal duodenum 1.95% ± 0.99%. This means a 2.3-fold increase in the number of G cells over the normal values. In addition, the G-cell sizes were increased by —127% compared with normals, with mean values of 106 ± 4.8 μπι2 in the stomach fundus, 108 ± 7.6 μπι2 in the proximal antrum, 102 ± 7.33 μπι2 in the distal antrum, and 94 ± 13 μπι2 in the upper duodenum (Figure 3). The soma­tostatin/gastrin quotient, which is normally —0.12, was far above 1 in all test regions.

Discussion The present study gives the first description of

an excessive, diffuse somatostatin-immunoreactive D-cell hyperplasia in the stomach and duodenum,

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Figure 4. D cells in the stomach fundus-corpus approximate to parietal and chief cells. Stain: PAP, 1 χ 1000.

Fgure 5. D-cell hyperplasia in the stomach antrum. Stain: PAP, 1 x 250.

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w i t h values between 20 and 40 times above nor­mal . The diagnosis was ascertained postmortem i n a w o m a n w i t h m u l t i p l e c l in ica l features, e.g., dwarfism (the height of an 11-yr-old female ch i ld) , obesity, dryness of the m o u t h , and goiter. There was no evidence available as to whether a possible re­tarded splanchnic c i rcula t ion result ing f r o m an i n ­creased serum somatostatin level was responsible for the thrombosis.

The cytochemistry showed strong reactivity w i t h somatostatin 28 ant ibody serum (Figures 4 and 5). L. Pradayrol detected, extracted, and described the structure of somatostatin 28 f r o m the intestine (31), as we recognize somatostatin 28 as the m a i n biolog­ically active molecular f o r m i n the intestine (32). Hypothalamus and pancreas have been found to contain equimolar amounts of somatostatin 14 and somatostatin 28 (33). However , somatostatin 28 binds w i t h 3.2 times greater aff inity to receptors involved i n the control of g r o w t h hormone secretion, and it acts there w i t h o u t pr ior cleavage to the smaller molecule (34). We should assume that i n our case, somatostatin 28 predominated i n the mucosa of the stomach and d u o d e n u m as w e l l as i n the general c irculat ion.

Analogous to the elevated serum-gastrin levels i n Z o l l i n g e r - E l l i s o n s y n d r o m e a n d a n t r a l G-cel l hyperplasia, we conclude f r o m the extensive soma­tostatin cell hyperplasia i n the upper gastrointestinal tract of our patient, that elevated serum somatostatin levels may have been present. As our patient under­went continuous s t imula t ion through polyphagia, we are even more convinced. Pathological increases of somatostatin serum levels of between 40-fold and 100-fold greater than normal values are k n o w n f r o m somatostatinomas (9000-1300 pg/ml) . These were accompanied by very l o w basal serum growth hor­mone levels (0.8 ng/ml) , w i t h o u t any response to st imulat ion i n hypothalamic and pi tu i tary func­tional tests (20,21).

I n considering the retarded g r o w t h of our patient i n relation to a possible hypersomatostatinemia, we conclude that the endocrine abnormali ty i n the up­per gastrointestinal tract must have existed since early infancy, possibly as a developmental defect (35). It is k n o w n that c i rculat ing hormones have the abil i ty to interfere w i t h certain centers i n the central nervous system (36). E s p e c i a l l y i n the para­ventricular region of the t h i r d ventricle , h ighly per­meable fenestrated capillaries pierce the blood-brain barrier (37) and permit a t h r o t t l i n g of the growth hormone release and t h y r o t r o p i n release (possibly also growth hormone releasing hormone) through chronica l ly increased somatostatin b lood levels (38,39). A parallel mechanism is k n o w n f r o m ectopic growth hormone releasing hormone-producing t u ­

mors accompanied by acromegaly (40,41). The latter can be influenced by somatostatin administration into the general c irculation.

Further research, especially concerning circulat­ing somatostatin serum levels [for example, i n idio­pathic growth hormone deficiency patients (42) or in disorders of the thyrot ropin releasing hormone-thyrotropin system], could probably help to clarify syndromes like the one under discussion. By this connection, the mucosa of the gastrointestinal tract should be recognized as an integral endocrine organ, and a gut-brain axis can be assumed.

References 1. Eide R, Hökfelt Τ. Localisation of hypophysiotropic peptides

and other biologically active peptides within the brain. Ann Rev Physiol 1979;41:587-602.

2. Polak JM, Pearse A G E , Grimelius L, Bloom SR, Arimura A. Growth hormone release inhibiting hormone in gastrointesti­nal and pancreatic D-cells. Lancet 1975; i:1220-2.

3. Vinik AI, Gaginella T S , O'Dorisio T M , et al. The distribution and characterization of somatostatin-like immunoreactivity in epithelial cells, submucosa and muscle of the rat stomach and intestine. Endocrinology 1981;109:1921-6.

4. Larsson L T , Goltermann H, De Magistris L, et al. Somatostatin cell processes as pathway for paracrine secretion. Science 1979;205:1393-5.

5. Guzman S, Lonovics J, Chayvialle JA, Hejtmanick K E , Rayford PL, Thompson JC. Effects of gastrin on circulating levels of somatostatin, pancreatic polypeptide and vasoactive intesti­nal peptide in dogs. Endocrinology 1980;107:231-6.

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