Stereological analysis of the parietal cell during acid secretion and inhibition.
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Biomedical subjects
Publications and source records attributed to F G Moody.
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A twenty-six year old white male on long-term sodium warfarin (Coumadin therapy for recurrent thrombophlebitis had sudden onset of severe groin pain, right iliac hematoma, and a femoral nerve palsy. A review of the twelve previously reported cases of this hemorrhagic complication indicates that immediate surgical decompression may be necessary to prevent residual disability.
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Stress ulcers are multiple, superficial erosions which occur mainly in the fundus and body of the stomach. They develop after shock, sepsis, and trauma and are ofter found in patients with peritonitis and other chronic medical illness. Stress ulcers should be differentiated from reactivation of chronic duodenal or gastric ulcers. Cushing's ulcer following head injury, or drug-induced gastritis. Digestive symptoms are usually absent, hemorrhage is the most common manifestation, and perforation and obstruction are rare. The presence of luminal acid and ischemia are necessary for the production of stress ulcer, while disruption of the gastric mucosal barrier by refluxed duodenal content may contribute to the pathogenesis. Endoscopy is the mainstay of the diagnostic procedure, and angiography should be used if endoscopy fails to identify the bleeding lesions. Medical management should include volume replacement, nasogastric aspiration, and the use of antacid. Selective intraarterial infusion of pitressin has shown encouraging preliminary results. Surgical treatment is reserved only for those patients who continue to bleed despite all medical management. The operation of choice is open to question. We prefer vagotomy, pyloroplasty, and oversewing the ulcers as an initial operation. Since the result of all forms of therapy has been poor, it seems resonable to try to prevent ulcer development. The use of vitamin A, hyperalimentation, and growth hormones is still in an experimental stage. Large clinical studies with case control are necessary before recommendations can be made. The use of potent and frequent antacid to buffer the gastric content has shown promising results; however, these observations need to be confirmed in a properly controlled and randomized study.
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Surgical education has been exposed to increasing challenges as students have moved from the highly structured environment of a university hospital into a variety of clinical settings within the community. Presented with a general surgical service that uses ten relatively autonomous teaching services in seven hospitals, we have developed a computer-based evaluation system designed to provide quality control and a feed-back loop for trainee, teacher, and service. Trainees were rated by comparing them to their peers, with the chief resident as a reference standard. Profiles of each teaching service also were developed and compared one to the other. The results of both studies over a one year period are presented.
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The effects of intra-arterial infusion of E. coli endotoxin at 1.0 mg. per minute on the gastric total and mucosal blood flows, electrical potential difference, and ionic fluxes across the gastric mucosa were studied in an exteriorized, chambered preparation of canine fundic stomach. Gamma-labelled microsphere technique was used in addition to venous drainage and plasma aminopyrine clearance for the measurement of total and mucosal blood flow, respectively. In spite of normal systemic blood pressure throughout the experiment, E. coli endotoxin infusion caused a significant decrease in total gastric blood flow and in the fractional distribution of flow to the mucosae. There was no significant arteriovenous shunting of microspheres. Significant reduction in potential difference and hydrogen-ion back diffusion also was noted after endotoxin infusion, possibly as a consequence of reduced mucosal blood flow. The results indicate that significant gastric mucosal ischemia can occur and may represent a mechanism in the development of gastric erosions in endotoxemia, even in the absence of systemic hypotension.
The effects of topical application of carbenoxolone at neutral and acidic pH were compared in exteriorized, chambered segments of canine gastric corpus. When dissolved in saline at pH 7.5 to 8.0, 0.25% carbenoxolone caused a rapid drop in gastric potential difference of 56 +/- 2 mv and greatly increased permeability to H+ ions. Blood flow, as measured by radioactive microspheres, was not changed by carbenoxolone treatment, but subsequent exposure to isotonic HC1 caused an abrupt rise in flow. Application of 0.25% carbenoxolone suspension in isotonic HC1 caused no change in potential difference, permeability, or blood flow. Neither carbenoxolone preparation had a significant effect on aspirin-induced H+ back-diffusion or injury.
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The validity of using radioactive microspheres (15 +/- 5-mum diameter) to measure gastric blood flow and its partition between gastric wall layers was investigated in anesthetized dogs with a chambered segment of gastric corpus. Total flow measured by a venous effluent technique demonstrated close correlation with microsphere-measured flow (r = 0.98, slope = 0.95) in 12 dogs given histamine, gastrin, or isoproterenol. In 12 histamine-stimulated dogs, mucosal flow measured by aminopyrine clearance and by microspheres also showed good agreement (r = 0.96, slope = 0.83). No evidence was found to indicate that microspheres altered hemodynamic or gastric function. In all experiments less than 1% of the total gastric radioactivity passed through arteriovenous shunts. The mucosa always contained a statistically adequate number of spheres (greater than 400), but the submucosa and muscularis frequently did not. Microspheres of all sizes mixed adequately in large arteries, but a significant difference was found in the distribution of 16- and 26 mum spheres between mucosa and submucosa, presumably because of streaming of the larger spheres past mucosal arteries. It was concluded that, with the techniques developed in our laboratory, microspheres could be a highly useful tool for quantitating gastric regional blood flow under a variety of experimental conditions.
Exposure of the mucosal surface of exteriorized chambered fundic segments of dog stomach to p-chloromercuribenzene sulfonate (PCMBS) resulted in predictable gross and microscopic structural changes. The first visible response after PCMBS (10 mM) in isosmotic HCl was an intense release of periodic acid-Schiff-stainable mucus. Within 2 min, radioactive PCMBS was found within cells along the entire depth of the gastric glands. Surface cells at 15 min revealed vacuolization of the cell cytoplasm, dilation of the perinuclear and intercellular spaces, mitochondrial swelling, loss of microvilli, and plasmalemma irregularities. Tight junctions, Golgi, and mucous granules appeared unaltered. However, in advanced injury, mucous granules became less dense and their membranes, which were usually smooth, became fragmented and convoluted at this point. Necrotic parietal cells were extruded into the lumen. Damage, however, only rarely extended into the deeper glandular and connective tissue areas.
p-Chloromercuribenzene sulfonate, a polar organic mercurial which presumably penetrates cell membranes with great difficulty, led to a profound decrease in acid recovered from exteriorized segments of dog gastric fundus stimulated by exogenous histamine. Trapping of secreted hydrogen ions by Tris buffer did not significantly reduce the back-diffusion component of apparent inhibition. Sodium-for-hydrogen exchange was close to unity before and after inhibition.
The effect of aspirin (20 mM.), sodium taurocholate (40 mM.), and ethanol (24 per cent w/v) on gastric mucosal blood flow was studied in an exteriorized, chambered preparation of canine fundic stomach. Gastric mucosal blood flow was measured by gamma-labeled microspheres and plasma aminopyrine clearance. All three test solutions caused a significant increase in microsphere-measured mucosal blood flow. The degree of increase in gastric mucosal blood flow was proportional to the severity of gross mucosal injury, being greatest with bile salt and least with ethanol. Plasma aminopyrine clearance determined only a small fraction of mucosal flow measured by microspheres following injury, particularly in sodium taurocholate and ethanol experiments, where the net hydrogen ion back diffusion was greatest. The results suggest that increased gastric mucosal blood flow may be a secondary defensive response to the damage caused by these irritants and that the plasma aminopyrine clearance is unreliable in quantitating mucosal blood flow changes in the presence of mucosal injury.
Gastric mucosal blood flow was simultaneously determined by aminopyrine clearance and gamma-labeled microspheres (15 +/- 5 mu in diameter) in anesthetized dogs prepared with a chambered segment of stomach greater curvature. Paired flow measurements were made in 11 dogs (n = 28) secreting in response to intravenous histamine (1mug per kg per min), in 11 (n = 21) nonsecreting dogs given intravenous isoproterenol (0.5 or 1.0 mug per kg per min), and in 9 (n = 10) dogs given no drugs to stimulate secretion or blood flow (resting dogs). Eight additional injections were done in dogs receiving various combinations of isoproterenol and histamine. Isotonic HCl was maintained on the mucosal surface during all experiments. Regression analysis demonstrated a highly significant linear correlation between clearance and microsphere-measured flow in the histamine (P less than 0.001, r = 0.96) and isoproterenol (P less than 0.001, r = 0.78) experiments, with clearance averaging 83% of microsphere flow during histamine stimulation but only 25% during isoproterenol. The relationship between clearance and microsphere flow was not significantly different for the resting and isoproterenol experiments. Mucosal perfusion measured by microspheres was about 5 times the resting value for both histamine and isoproterenol-stimulated dogs. Perfusion calculated from aminopyrine clearance averaged 46, 38, and 90% of the microsphere value in the resting, isoproterenol, and histamine experiments, respectively. Pooled data from secreting dogs demonstrated a fairly constant ratio of microsphere-measured flow to clearance (1.25 +/- 0.06 mean +/- SEM), regardless of the secretory rate. Our results indicate that aminopyrine clearance reflects only a small fraction of mucosal blood flow in the nonsecreting stomach, even in the presence of exogenous acid.