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Five patients with gastroesophageal refluxdisease (GERD), who also had chronic functional diarrheaand postprandial urgency, unexpectedly noted rapidrelief of their diarrhea and urgency when they took lansoprazole for their heartburn. To determineif this surprising result was not fortuitous, all 20patients seen during the next six months for chronicdiarrhea and postprandial urgency due to irritable bowel syndrome (IBS) or functional diarrheawere treated with inhibitors of gastric secretion: 14with proton-pump inhibitors and 6 with H2blockers. All patients had rapid, marked improvement. Usually within three days, their symptomsabated and they usually had one to three formed stoolsper day. Relief continued during the one to six monthsthey were followed on therapy. Five patients stopped therapy, had recurrent diarrhea, and rapidrelief upon resuming therapy. Thus, inhibition ofgastric secretion effectively controls the diarrhea andpostprandial urgency associated with IBS or functional diarrhea, probably by diminishing thegastrocolic or gastroenteric reflex.

Acute and chronic pancreatitis are challenging diseases for the general physician. They must be diagnosed accurately, and their specific causes identified. Their prognoses and expected courses must be appreciated, and their multiple, often serious complications recognized. In this way the physician can institute proper therapies in a timely fashion so as to minimize mortality and morbidity, prevent recurrent disease, optimally preserve pancreatic function, maintain optimal nutrition, and correct the serious, often life-threatening complications. The general physician also should know when to seek help from the gastroenterologist or surgeon when managing difficult patients with these diseases. Acute pancreatitis usually resolves, and pancreatic function is preserved adequately. The inflammatory process of chronic pancreatitis, however, often destroys much more of the organ and its normal functioning, frequently leaving the patient with pancreatic endocrine or exocrine insufficiency.

During the past decade, the diagnosis and treatment of peptic ulcer disease (PUD) have undergone major changes. Previously considered a disorder primarily of mucosal disruption by gastric acid, PUD now is recognized as multifactorial in etiology, with a major factor thought to be the presence in the stomach of a spiral-shaped bacterium known as Helicobacter pylori (HP). Since 1982 when Marshall and Warren 38 first isolated and cultured this organism, thousands of articles have been written showing associations between HP and most cases of chronic gastritis and gastroduodenal ulceration. 21,38 Etiologic links between the organism and neoplastic processes such as gastric lymphoma and adenocarcinoma also have been suggested. 16,31 This article discusses many aspects of HP infection, its relationship to PUD and other gastrointestinal disorders, methods for detection, and various treatment strategies.

While several endothelial cell adhesion molecules (CAM) have been implicated as mediators of the leukocyte-endothelial cell adhesion observed in inflamed microvessels, P-selectin appears to be the major CAM that accounts for the very rapid (minutes) leukocyte rolling observed in these vessels. P-selectin can be rapidly mobilized from a preformed storage pool (WeibelPalade bodies) within endothelial cells by different stimuli, including histamine, thrombin, hydrogen peroxide, and leukotrienes. The objective of this study was to determine whether bradykinin, a well-known participant in inflammatory reactions can elicit P-selectin expression in the gastrointestinal microvasculature. The dual radiolabelled antibody technique was used to quantify endothelial cell P-selectin expression in rat metentery, small intestine, large intestine, pancreas and stomach. Intraperitoneal administration of bradykinin (25-200 lag) induced a dose-dependent up-regulation of P-selectin in most of the gastrointestinal organs. The increased P-selectin in these vascular beds occured within 15 min after bradykinin administration; no increases were noted 3 hrs after bradykinin. In order to determine whether the bradykinin B 2 receptor mediates the increased P-selectin expression elicited by bradykinin, some animals were pretreated with a Bz-receptor antagonist (HOE). In all gastrointestinal organs, HOE completely prevented the bradykinin-induced increase in P-selectin expression. These findings indicate that bradykinin can mobilize the preformed pool of P-selectin in vascular endothelial ceils and that bradykinin-mediated P-selectin involves the engagement of B~-receptors. Supported by P01 DK43785

At least five morphological types of endocrine cells can be identified by electron microscopy in the rat stomach, most of which can decarboxylate 5-hydroxytryptophan to serotonin. To identify which o f these cells can synthesize 5-hydroxytryptamine from l-tryptophan, the physiological precursor of 5-hydroxytryptamine biosynthesis, pieces of rat stomach were incubated in organ culture with l-[ 3 H]tryptophan, with and without inhibitors, and were processed for light microscopic and electron microscopic radioautography. l-[ 3 H]tryptophan labeled all EC cells heavily, but labeled other endocrine cells-ECL, A-like, G, and D-only lightly. The labeling of EC cells was markedly reduced when 5-hydroxytryptamine synthesis was inhibited by either p-chlorophenylalanine or carbidopa, but was not appreciably reduced when protein synthesis was inhibited with cycloheximide. The labeling of Alike, G, and D cells by l-[ 3 H]tryptophan was similar to that produced by l-[ 3 H]leucine and was almost abolished by cycloheximide. The labeling of ECL cells by l-[ 3 H]tryptophan was shown by grain counts to be greater than the labeling of A-like and parietal cells, to persist after incubations with cycloheximide, but to be inhibited by p-chlorophenylalanine or carbidopa. Amine-fluorescence studies also indicated that ECL cells could synthesize some 5-hydroxytryptamine, and biochemical studies showed that the oxyntic mucosa could synthesize 5-hydroxytryptamine. Incubations of mucosa with 5-[ 3 H]hydroxytryptamine usually produced little or no labeling of endocrine cells. Thus, this study demonstrates that all EC cells can readily synthesize 5-hydroxytryptamine from tryptophan and therefore, as previously suggested from topographical and cytochemical studies, probably represent the argentaffin cells of light microscopy. This study also suggests that ECL cells can also synthesize and store some 5-hydroxytryptamine, but presumably not enough normally to be detected by conventional argentaffin, chromaffin, or amine-fluorescent techniques, which usually demonstrate few reactive cells in oxyntic glands, were ECL cells abound.

Rat fundic mucosa contains numerous APUD endocrine cells that can take up 5-hydroxytryptophan (5-HTP) and decarboxylate it to 5-hydroxytryptamine (serotonin), detectable by its formaldehyde-induced yellow fluorescence. To identify these cells by electron microscopy, pieces of rat gastric mucosa were incubated with DL-5-HTP. Some specimens were fixed in 4% formaldehyde-0.5% glutaraldehyde, while others were frozen, freeze-dried, and exposed to paraformaldehyde vapors. Thick sections of the Epon-embedded specimens were examined and photographed by fluorescence microscopy, and fluorescing and nonfluorescing cells were identified by electron microscopy in serial thin sections. Control specimens, not incubated with 5-HTP, revealed fluorescence of only the mast cells and EC cells, which were abundant in the pylorus, but rare in fundic mucosa. Specimens incubated with 5-HTP also exhibited numerous yellow fluorescent endocrine cells in fundic mucosa, which cells were found to be the ECL cells; the A-like cells did not fluoresce. In pyloric mucosa, many G and D (D1) cells also exhibited weak or moderate fluorescence after 5-HTP incubation. Thus, this study supports the contention of previous radioautographic studies that the ECL, but not the A-like, cells are the APUD endocrine cells of rat fundic mucosa, that G and D cells also possess some APUD activity, and that EC cells represent the enterochromaffin cells, which normally synthesize and store demonstrable quantities of serotonin.

Rat gastric oxyntic glands contain argyrophil "enterochromaffin-like" endocrine cells that synthesize and store histamine and also have APUD ability—they can take up exogenous l-5-hydroxytryptophan (5-HTP), can decarboxylate it to 5-hydroxytryptamine (5-HT, serotonin) by the enzyme DOPA-decarboxylase, and can store the amine. Previous cytochemical studies suggested that these cells correspond to both the ECL and A-like cells, the two predominant endocrine cells identified by electron microscopy (EM) in rat oxyntic glands. In a recent study, however, we demonstrated that the ECL but not the A-like cell exhibited APUD ability when rat gastric mucosa was incubated with H3-5-HTP and studied by EM radioautography. The purpose of the present study was to identify by EM radioautography the histamine-synthesizing endocrine cells in the rat stomach. Pieces of rat (male Sprague-Dawley) gastric mucosa were incubated in organ culture with l-H3-histidine (50 μCi, 1.8 × 10 −5 M) with and without inhibitors and were processed for LM and EM radioautography. H3-histidine labeled the ECL cells heavily but the A-like and other endocrine cells only lightly. The labeling of ECL cells was only modestly reduced by cycloheximide, an inhibitor of protein synthesis, whereas the labeling of A-like and other endocrine cells was almost abolished. In contrast, the labeling of ECL cells was markedly reduced by 4-bromo-3-hydroxybenzyloxyamine (NSD-1055), an inhibitor of histidine decarboxylase and DOPA decarboxylase, but was not appreciably affected by carbidopa, an inhibitor of only the DOPA decarboxylase. Incubations with H3-histamine (50 μCi, 0.9 × 10 −5 M) failed to label endocrine cells. Thus, this study demonstrates that the ECL but not the A-like cell is the histamine-synthesizing endocrine cell of the rat stomach.

Because thrombus formation at the site of endothelial injury has been thought to be a critical step in the pathogenesis of bacterial endocarditis, the effect of aspirin on experimental valvular thrombosis and bacterial endocarditis in rabbits was evaluated. Aortic valvular injury and thrombosis were induced in aspirin-treated and control rabbits with intracardiac catheters. A subsequent inoculation of Streptococcus viridans resulted in the development of infective endocarditis. Rabbits were sacrificed as early as 6 hr, and the effectiveness of aspirin was determined by the weight of the sterile vegetations and the quantitation of bacteria in the thrombotic vegetation. Aspirin, in levels in excess of 50 mg/dl did not attenuate the evolution of infective endocarditis, since the formation of sterile thrombotic vegetation and bacterial endocarditis in aspirin-treated rabbits was similar to those in controls.

The oxyntic glands of rat and mouse stomachs contain argyrophil "enterochromaffin-like" endocrine cells that synthesize and store histamine and also have APUD ability—they can take up exogenous L-5-hydroxytryptophan (5-HTP), can decarboxylate it to 5-hydroxytryptamine (5-HT, serotonin) by the enzyme DOPA decarboxylase, and can store the amine. Previous cytochemical studies have suggested that these cells correspond to both the ECL and A-like cells, the two predominant endocrine cells identified by electron microscopy in rat and mouse oxyntic glands. The purpose of this study was to identify by EM radioautography the APUD and thereby the enterochromaffin-like cells in the oxyntic glands of these rodents. Pieces of rat and mouse gastric mucosa were incubated in organ culture with H3-5-HTP, H3-5-HTP and carbidopa (an inhibitor of DOPA decarboxylase), and H3-5-HT and were processed for LM and EM radioautography. Additional pieces of rat gastric mucosa were incubated with 5-HTP, freeze-dried, and processed by the Falck-Hillarp technique to permit the detection of 5-HT by fluorescence microscopy. After H3-5-HTP incubations, the EeL cells of both the rat and mouse oxyntic glands were labeled by EM radioautography, but the A-like cells of only the mouse were so labeled. Since this labeling was inhibited by carbidopa and since exogenous H3-5-HT failed to label endocrine cells, the labeling must have resulted from the uptake of exogenous H3-5-HTP and its intracellular conversion to H3-5-HT. The failure of some rat oxyntic endocrine cells to form and store 5-HT from exogenous 5-HTP was also demonstrated by the Falck-Hillarp technique and by LM radioautography. Thus, this study demonstrates that only the ECL and not the A-like cell of rat oxyntic glands is an APUD and therefore enterochromaffin-like cell, and that despite their morphologic similarities, the A-like cells of the rat and mouse have metabolic differences.

Epon embedding was used with the Falck-Hillarp Technique in a study of rat gastric endocrine cells in order to improve morphological resolution. The epon embedding not only produced excellent morphological results, but also resulted in the long-term preservation, now for 10 years of the serotonin-associated fluorescence in the gastric endocrine and mast cells.

Polymorphonuclear neutrophils (PMN) from patients with chronic granulomatous disease of childhood have impaired bactericidal activity and are deficient in diphosphopyridine nucleotide, reduced form of, (NADH) oxidase. Since hydrocortisone had been shown to inhibit NADH oxidation, experiments were undertaken to determine the effect of hydrocortisone on several parameters of human PMN function. The phagocytic and bactericidal capacity of PMN with or without hydrocortisone (2.1 mM) was determined by quantitation of cell-free, cell-associated, and total bacteria. Phagocytosis of Staphylococcus aureus and several gram-negative rods was unimpaired by the presence of hydrocortisone in the media. In contrast, killing of bacteria was markedly impaired by hydrocortisone. After 30 min of incubation, there were 20-400 times as many bacteria surviving in hydrocortisone-treated PMN as in simultaneously run controls without hydrocortisone. The defect of intracellular killing noted in the presence of hydrocortisone was not related to impaired degranulation. Quantitative kinetic studies of degranulation revealed no difference in the release of granule associated acid phosphatase in hydrocortisone-treated and control PMN after phagocytosis. Electron microscopy of PMN also indicated that the presence of hydrocortisone had no effect on the extent of degranulation after phagocytosis. These observations were confirmed by studies using histochemical techniques to detect lysosomal enzymes. After phagocytosis, hydrocortisone-treated PMN demonstrated less NADH oxidase activity, oxygen consumption, and hydrogen peroxide production than postphagocytic control PMN. In addition, Nitro blue tetrazolium dye reduction was diminished in hydrocortisone-treated PMN. Thus, impairment of NADH oxidase activity in normal human PMN by hydrocortisone results in reduced intracellular killing of bacteria, diminished postphagocytic oxygen consumption, decreased ability to reduce Nitro blue tetrazolium, and decreased hydrogen peroxide production. These abnormalities are similar to those seen in the PMN of patients with chronic granulomatous disease of childhood.

This study describes the fine structure of endocrine cells observed in normal human stomachs. Four morphological types could be identified. ECL cells constituted the majority of endocrine cells observed in each section of the body, but were not positively identified in the pylorus. G cells constituted the majority of endocrine cells observed in most sections of the pylorus, but were not observed in the body. EC cells were infrequent in the body, but were readily observed in the pylorus, especially in the lower portions of the glands. D cells were scattered in both the body and pylorus in moderate numbers. From 5 to 20% of endocrine cells observed in each section could not be classified. The significance of the different morphological types of gastric endocrine cells remains uncertain.

Per oral mucosal biopsies obtained from the body and pyloric antrum of normal stomachs and from the body of atrophic stomachs of pernicious anemia patients were studied by light and electron microscopy. The atrophic mucosae contained numerous endocrine-like (enterochromaffin) cells both in the islets of ectopic intestinal epithelium and in the nonintestinalized atrophic glands. The proliferation of such cells, which metabolize pharmacologically potent amines and peptides, probably plays a significant role in the physiology of these stomachs.

The rat stomach was shown some years ago to contain numerous endocrine cells with APUD abilitycells that could take up the amino acids l-5-hydroxytryptophan (5-HTP) or l-dihydroxyphenylolanine (l-DOPA) and could decarboxylase them to their respective amines, 5-hydroxytryptamine (5-HT, serotonin) and dopamine, by means of the enzyme DOPA-decarboxylase. In a recent study, most of the APUD endocrine cells in the rat oxyntic mucosa were shown by electron microscopic radioautography to be the enterochromaffinlike cells, while the A-like cells were shown to lack APUD ability. To identify the APUD cells in the pyloric mucosa, pieces of rat pylorus were incubated in organ culture with 3 H-5-HTP and were processed for light microscopic and electron microscopic radioautography. Additional specimens were incubated with 3 H-5-HTP and carbidopa, an inhibitor of DOPA-decarboxylase, used to block the decarboxylation of 3 H-5-HTP to 3 H-5-HT, or with 3 H-5-HT, used to determine where exogenous 3 H-5-HT localizes in the pyloric mucosa. The 3 H-5-HTP labeled all three types of endocrine cells identified within the pyloric glands-the G, enterochromaffin, and D cells. As this labeling was inhibited by carbidopa, and as exogenous 3 H-5-HT labeled these cells only lightly, the labeling must have resulted from the uptake and intracellular conversion of the 3 H-5-HTP to 3 H-5-HT. Thus despite their morphologic differences, all rat pyloric endocrine cells possess APUD ability, a property shared by many, but not all, of the peptide-and amine-producing endocrine cells located throughout the body.

Ulceration, inflammation, and hemorrhage of the upper gastrointestinal tract have been associated with the use of anti-inflammatory drugs, especially aspirin. 1 Mefenamic acid is a relatively new antiinflammatory analgesic agent 2 that has been thought to be remarkably safe from such gastrointestinal complications, 3-9 although it has many of the physicochemical and pharmacologic properties of aspirin, 2.10 and has been known to produce gastrointestinal ulceration in rats and monkeys when administered in very large doses. 11.12 We describe a patient who developed an unusual bleeding ulcer in the third portion of the duodenum, duodenitis, and antral gastritis while receiving mefenamic acid. PATIENT SUMMARY A 46-year-old black woman was admitted to the Hospital of the Medical College of Pennsylvania on Oct 22, 1974, with melena and hematemesis. The patient had suffered from osteoarthritis of the spine for one year. Two weeks prior to admission, her physician prescribed mefenamic acid (Ponstel Kapseals)

Clindamycin, rosamicin, josamycin, and metronidazole had similar inhibitory activity against 29 clinical isolates of Bacteroides fragilis, i.e., 100% of strains were inhibited by 0.8 microng of metronidazole or josamycin/ml and 100% by 1.6 microng of clindamycin or rosamicin/ml. Metronidazole was bactericidal against 97% of the isolates, and clindamycin or rosamicin (in concentrations of 1.6 microng/ml) was bactericidal against 80%. Erythromycin and josamicin were the least bactericidal agents in vitro. Thirty-two patients with pleuropulmonary and intraabdominal or pelvic infections caused by anaerobic bacteria were treated with clindamycin. Cure was achieved in 27 patients. In another group of 37 patients treated with parenteral clindamycin, diarrhea developed in 30% and was significantly more common in those patients with abdominal or pelvic infection. Only one patient developed pseudomembranous colitis. These observations suggest that clindamycin is an excellent and relatively safe antibiotic for treatment of infections caused by anaerobes when combined with surgery or with other antibiotics selected for activity against aerobic gram-negative bacilli.

SEVERAL recent studies suggest that lactase deficiency is common in the adult. It may be present as an isolated enzyme defect1 2 3 4 5 or may accompany organic disease of the small bowel.6 7 8 The symptoms attributed to lactase deficiency —abdominal cramps, distention, flatulence and diarrhea — result from a failure to hydrolyze and absorb ingested lactose. Increased intestinal peristalsis, with passage of acid, watery stools, may be due both to an osmotic shift of fluid into the lumen and to the action of lactic and acetic acids resulting from bacterial fermentation of lactose.9 These symptoms disappear when lactose is eliminated from the diet. . . .

A case of invasive gastric carcinoma mimicked idiopathic achalasia. Esophagoscopy, cineradiography, exfoliative cytology, manometry, and the methacholine (Mecholyl⌖) test were consistent w...