The development of a simple rapid technique for placing drugs into male Holtzman rat lateral cerebral ventricle permitted comparison of 1.v. and intracerebroventricular drug administration on gastric acid secretion and stress-induced (by cold plus restraint) gastric hemorrhage. The anticholinergic drugs, atropine sulfate and atropine methylbromide, produced inhibition of gastric secretion when administered i.v. or intracerebroventricularly and were more effective in reducing volume than in reducing acidity of gastric secretion. Clonidine (16.0 ug), a centrally acting antihypertensive agent, reduced gastric secretion volume to 0.4 ml after 1.v. administration and to 0.8 ml after intracerebroventricular administration from a control value (saline injection) of 4.9 ml for both routes of administration. The antisecretory activity of three CNS depressants, chlorpromazine, chlordiazepoxide and imipramine, was greater by i.v. than by intracerebroventricular administration. All stomachs of control animals subjected to 2 hr of cold-plusrestraint showed gastric hemorrhage and atropine sulfate and atropine methylbromide effectively reduced stress-induced gastric hemorrhage after 1.v. or intracerebroventricular administration. Atropine sulfate (256.0 ug) administered i.v. inhibited 37.5% of stress-induced hemorrhage, while intracereb roventricular administration inhibited gastric hemorrhage by 87.5%.

The iron binding capacity (expressed as a ratio to the basal value) of gastric secretion stimulated with a continuous histamine infusion (40 ug/kg/hr) in patients with duodenal peptic ulcers was determined by the method of Morgan, Weir, Gatenby and Scott. The ratios of the first and second post histamine hr (1.14 and 1.14, resp.) were essentially unity, but for a "flushed gastric secretion" obtained by washing the stomach for 3 to 4 min after collecting basal secretion, the ratio was highly significant (1.93). Flushing is known to stimulate mucus secretion and from what is known of the properties of gastric iron binding, this capacity is apparently of mucoid origin.

The effect on gastric secretion of test solutions of saline (0.09 and 3%) and glucose (18.5%) infused into the distal duodenum over a 4 min period after stimulation with pentagastrin (6 μg/kg/hr 1.v.) was evaluated by measuring the secretory volume, acid, pepsin and electrolyte concentrations. With the hypotonic saline and the hypertonic glucose, acid output was reduced in both control and ulcer groups but with the hypertonic saline, output was reduced in the ulcer group with no change in the controls. In all cases, the responses were rapid (immediate or within 5 min from the start of the infusion) and the hydrogen ion concentration was constant suggest ing that the inhibition of acid was due to the decreased volume of gastric juice. Sodium, chloride and potassium concentrations remained constant is all the groups while pepsin output and concentration were both reduced by all 3 test solutions. Since the responses to varying duodenal osmolarity are similar in control subjects and duodenal ulcer patients, there is no evidence of impaired inhibiti in the ulcer group.

The effects of various protease inhibitors were studied in 70 adult dogs in which chronic peptic ulceration similar to that seen in man was produced by placing the antrum on the colon as an antiperstaltic diverticulum. In the control group (given gelatin capsules), ulcers developed in 8 of the 10 dogs (6 had perforated ulcers). In the group receiving carrageenan, ulceration developed in 2 of the 10 dogs and both ulcers perforated. When SN-263 (sulfated amylopectin) was given, ulceration developed in 3 of the 10 dogs with perforation developing in 2 dogs. In the group receiving charcoal, ulcers developed in 4 of 10 dogs with perforation in 2 dogs. In the group receiving antacids, 5 dogs had ulcers and all were perforated; the size and numbers of ulcers were the same as the

control group. In the group receiving cellulose sulfate, 8 of 10 dogs had ulcers with perforation occurring in 7; the size and number of the ulcers were the same as the control group. All 10 dogs receiving Amberlite IRC-50 showed severe ulceration and perforation and the average number of ulcers per dog was almost three times that of the control group and all of the dogs in this group died within a 2-3 week period. Protease inhibitors may be considered in the treatment of chronic peptic ulceration in man.

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The molecular forms of pepsinogen (Pg) in urine and their relations to six of the seven pepsinogens in gastric mucosa were studied in 180 patients with known renal or peptic ulcer disease by agar-gel electrophoresis. Of these patients, 152 excreted Pg 2, Pg 3, Pg 4, and Pg 5 and 28 excreted only Pg 2, Pg 3, and Pg 4. These two patterns which have been designated A and B, respectively, were absolutely constant among individual patients. of 23 patients from whom gastric mucosa was available, 19 had Pg 2, Pg 3, Pg 4, and Pg 5 in both their mucosa and urine, while 3 had only Pg 2, Pg 3, and Pg 4. Pg 6 and Pg 7 (or both) were found in the urine of only 8 of the 180 control subjects (5 of whom had proteinuria) and in 13 of 15 patients with renal disease and proteinuria. The demonstration of Pg 6 and Pg 7 in serum and the failure to find an inhibitor of these zymogens in normal urine is due neither to their failure to enter the circulation nor to their inhibition by urine.

RECENT TRENDS IN GASTRO-DUODENAL ULCER SURGERY. (Nor.) Krause, U. (U. Hosp. Uppsala, Sweden). Nord Med 83(3):65-73, 1970.

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The case reports of 4 pregnant women are described in whom the triad of hydramnios, elevated amniotic fluid bilirubin, and fetal small bowel obstruction were confirmed. Hydramnios and Zone II or III amniotic fluid spectral curves led to prenatal suspicion of fetal gastrointestinal obstruction (duodenal atresia in 3 fetuses and ileal atresia in 1) in all 4 patients. Definitive prenatal diagnosis of gastrointestinal obstruction was achieved in 2 patients in whom visualization of contrast media in the gut was not achieved following amniography in active, non anemic, normocephalic fetuses. Three of the four fetuses were born live and the findings suspicioned by amniotic fluid spectral curves enabled rapid diagnosis and definite management of the intestinal obstruction in the newborn infants.

ferences were seen by light or electron microscopy between control biopsies and those during cholera diarrhea, except for minimal acute inflammation around the crypts. During i.v. fluid therapy and maximal stool flows, dilation of capillaries by plasma and edema of lamina propria were seen in villus tips, and heightened goblet cell mucus production and loss were seen in dilated crypts. Results confirm previous demonstrations of epithelial integrity during human cholera diarrhea and the primary target of cholera exotoxin seemingly is the crypt epithelium which represents the chief site of net fluid loss in cholera.

Sixty patients with documented cytic fibrosis and me conium ileus were reviewed with special emphasis on their clinical and roentgenographic findings. Twenty-four patients had uncomplicated meconium ileus; 9 of these cases had a family history of cysti fibrosis. Roentgenographic examination prior to surgery showed a constant finding of uneven distention of intestinal loops (some were markedly dilated). Two patients were also found with incomplete intestinal obstruction at birth. In the complicated meconium group of 36 patients, complications occurred during prenatal period with characteristic sequelae of bowel obstruction by normal meconium. Nine patients had simple volvulus, whereas 23 had combined volvulus, gangrene, atresia, and peritonitis. Eleven patients exhibited calcification (mecon

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ium peritonitis) and small intestinal atresia. ditional plain film roentgen criteria for meconium ileus (bubbly-granular pattern, absence of airfilled levels) were found absent in many "uncomplicated" cases, while these criteria were confusingly present in some "complicated" cases. In "uncomplicated" cases, major problem was the inability to accurately distinguish small bowel from colon obstruction without barium enema examination, while in "complicated" cases, the major problem was inability to suspect complications unless calcifications or mass effect of volvulus could be seen. bizarre and broad range of roentgen findings reflects varying prenatal intestinal problems secondary to distal ileal meconium obstruction. Meconium ileus prognosis is grave with only 9 of 24 patients with complit s alive month following surgery; 5 patients currently alive. Of the complicated cases, 18 of 36 survived longer than 1 month with only 10 currently alive.

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The

EVALUATION OF THE EFFICIENCY OF BILE SALT RECIRCULATION IN PATIENTS WITH TERMINAL ILEOPATHIES BY MEANS OF DEOXYCHOLATE DETERMINATION IN DUODENAL ASPIRATES. (E.) Thaysen, E. H. (Aalborg Munic. Hosp., Denmark), A. Bruusgaard and B. Eriksen. Scand J Gastroent 5(1):39-47, 1970.

Deoxycholate concentration (mg/100 ml) in fasting duodenal aspirate following cholecystokinin stimulation (1.00 Ivy Dog Unit/kg i.v.) was determined by the method of Szalkowski and Mader in 6 ileectomized patients, 5 patients with terminal ileitis and 8 controls. The mean maximum deoxycholate concentrations for both the fleectomized group (79) and the terminal ileitis group (148) were significantly below that of the controls (335). The hypothesis that this indicates a compromised intestinal reabsorption of bile salts is further supported by the low serum cholesterol concentrations and the presence of steatorrhea in most of the patients examined.

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THE INTESTINAL INSULINOTROPIC ACTION AFTER JEJUNO-ILEOSTOMY. (E.) Rehfeld, J. F. (Bispebjerg Hosp., Copenhagen, Denmark), E. Juhl and F. Quaade. Scand J Gastroent 5(1):77-80, 1970. Glucose tolerance tests (p.o. and i.v.) were run on 3 patients before and after undergoing jejuno-ileostomy (preserving 37 cm of functioning jejunum and 12 cm of the distal ileum). In the oral glucose tolerance test, preoperatively 2 patients responded normally (1 patient was considered diabetic with a 3 hr value greater than 120 mg%), while postoperatively none of them had a rise and the immunoreactive insulin showed a rise both times (confirmed that the rise is greater after p.o. than after i.v. glucose). Glucose concentrations and insulin responses were almost identical before and after the operation for the 1.v. tests. An intestinal B-cell stimulation located in the duodenum and first part of the jejunum apparently does exist.

Small intestinal function (calcium, phosphorus and magnesium balance studies) and structure (biopsy) were studied in 6 children with vitamin D dependent rickets after vitamin D therapy and in 1 child before treatment. No symptoms of intestinal malabsorption or abnormalities (studied by light and electron microscopy) in the duodenal mucosa were detected in the treated children or in the untreated child. Comparison of data on the child examined before and after therapy revealed a rise in serum calcium (9 to 12.2 g/100 ml), exchangeable pool calcium (2.0 to 6.5 g), accretion to bone (0.22 to 0.84 g), and dietary calcium absorption (0 to 68% of intake), with a decrease in fecal calcium excretion (765 to 254 mg/day). Phosphorus fecal excretion decreased (265 to 34 mg/day) and magnesium intake exceeded the combined urinary and fecal excretion both before and after vitamin D therapy although serum magnesium remained normal throughout the study.

A case is presented of an 18-yr-old male patient who was treated with cholestyramine (4 g t.i.d., p.o.) and polysorbate-80 for diarrhea and mild transient steatorrhea following subtotal ileectomy. The diarrhea improved remarkably after cholestyramine, an ionic exchange resin sequesterer of inonized bile salts. Because it is nonionic, polysorbate-80 was not sequestered by cholestyramine, and could be administered concurrently. Improvement in fecal-fat excretion and triolein 1311 absorption was suggested even when polysorbate-80 was administered with cholestyramine, despite the tendency of cholestyramine to worsen these parameters. Together cholestyramine and polysorbate-80 may be useful in treating the diarrhea and steatorrhea of "cholerheic enteropathy".

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In Phase 1 of this study the charts of 83 patients with clearly established ulcerative colitis or Crohn's disease (drawn from all cases seen during the preceding 10 yr) were reviewed, and in Phase 2, the charts of a consecutive sampling of 35 outpatients and 5 inpatients with inflammatory bowel disease (21 with ulcerative colitis and 19 with Crohn's disease, representing all patients seen during a 2month period) were reviewed. Investigation revealed a high incidence of emotional disturbances and life crises prior to the onset of illness in both dis

eases (e.g. in Phase 2 patients, a serious life cri sis occurred during the 6-month period prior to the onset of disease in 86% of the ulcerative colitis p tients and in 68% of the Crohn's disease patients). There were no significant differences between patients with the two diseases in a large number of demographic, psychosocial, personality, behavioral, psychiatric, and physical disease characteristics. In both syndromes, there was a highly positive corre lation between the severity of emotional disturbance and the seriousness of the physical illness. results of the study support the theory that similar personality and life event factors contribute to, and may be necessary for, the development and sever ity of ulcerative colitis and Crohn's disease. The study indicates the need for early identification and treatment of emotional disturbance in both group of patients.

The

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