Endoscopic treatment of biliary tract disease.
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Biomedical subjects
Publications and source records attributed to A M Zfass.
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Cimetidine prophylaxis significantly reduced the risk of gastrointestinal bleeding after severe head injury in this prospective, double-blind clinical trial. Cimetidine effectively reduced both the volume and the acidity of gastric secretions after brain injury without producing adverse side effects. The most common endoscopic finding was superficial, erosive, mucosal lesions in the proximal stomach. Cimetidine prophylaxis was not shown to reduce the incidence of these lesions in this study but did diminish their severity and the likelihood that they would complicate the management of these patients.
Isolated gastric smooth muscle cells were prepared from the stomach of Bufo marinus by successive incubation in collagenase without added trypsin. Contraction was determined by image-splitting micrometry and expressed as the mean percentage decrease in cell length from control. Peak contractile response was attained within 30 s. Dose-response curves constructed from peak responses showed that the maximal responses to CCK-OP (37.2 +/- 3.8%), acetylcholine (35.3 +/- 2.5%), and Ca2+ (42.3 +/- 0.9%) were similar. The D50s for octapeptide of cholecystokinin (CCK-OP) and acetylcholine were around 10(-12) M and 10(-11) M, respectively. The response to a combination of submaximal concentrations of acetylcholine and CCK-OP exceeded the individual responses but did not exceed the maximal response to either agent alone. A low concentration of atropine (5 X 10(-10) M) inhibited specifically the maximal response to acetylcholine. A high concentration of atropine (5 X 10(-8) M) inhibited partially the maximal response to CCK-OP but had no effect on the maximal response to Ca2+. It was concluded that 1) dispersed gastric smooth muscle cells are highly sensitive to stimulation; 2) CCK-OP has a direct (myogenic) contractile effect on gastric smooth muscle; and 3) the effect of CCK-OP and acetylcholine are mediated by separate receptors.
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The effects of synetic porcine vasoactive intestinal peptide (VIP) on pancreatic and biliary secretion and on glucose, insulin and calcium blood levels were examined in the dog and compared with the effects of natural porcine VIP. Synthetic VIP was a secretin-like partial agonist of pancreatic and biliary secretion with efficacies relative to secretin of 0.27 and 0.41, respectively. Consistent with its weak secretin-like action, synthetic VIP augmented the pancreatic response to CCK-OP and the submaximal but not the maximal response to secretin. Synthetic VIP also produced a dose-dependent increase in blood glucose levels and a synchronous and proportionate increase in blood insulin levels. A slight increase in total calcium levels was equivocal. The effects of antural VIP on pancreatic and biliary secretion and on glucose and insulin blood levels were identical to those of synthetic VIP. The identity of effects supports the validity of the postulated structure of porcine VIP. Although elicited at high doses, the effects of VIP on exocrine and endocrine secretion may be relevant physiologically in the context of a neurocrine or paracrine role for VIP.
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The effect of somatostatin on colonic secretion induced by 10(-8) M vasoactive intestinal peptide (VIP), 10(-2) M theophylline, and 2 X 10(-3) M dibutyryl cyclic AMP was studied in muscle-stripped everted open rat colon sacs. The secretory response to VIP, measured as the decrease in net absorptive flow rate (microliters 30 min-1 mg-1 of dry weight), was maximal and equalled the responses to theophylline or dibutyryl cyclic AMP. Somatostatin (10(-5) M) blocked completely the secretory response to VIP but only partially the secretory response to theophylline or dibutyryl cyclic AMP. This difference in the extent of inhibition suggested that somatostatin exerted an inhibitory effect both before and after the point of generation of intracellular cyclic AMP. In order to test the hypothesis that one component of the action of somatostatin involved inhibition of the production of cyclic AMP, measurements of this nucleotide were made in isolated rat colon cells. Control levels of cyclic AMP measured by radioimmunoassay (12.6 +/- 1.6 pmoles per 10(6) cells) were not affected by 10(-5) M somatostatin. VIP (5 X 10(-8) M) increased cyclic AMP levels 2-fold (P less than 0.01) and this increase was blocked by somatostatin. The results indicated that somatostatin inhibits colonic secretion by exerting effects at two sites: one site lies at, and another beyond, the point of generation of intracellular cyclic AMP.
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Esophageal and gastric function was measured in a patient who swallowed a household acid solution. Dysphagia, transient ulceration of the esophagus with luminal narrowing, and complete loss of peristalsis without loss of lower esophageal sphincter function were noted. Gastric dysfunction appeared 2 weeks after ingestion with complete obstruction, necessitating antral resection. The proximal stomach was relatively spared.
Five carboxyl-terminal fragments of secretin ranging in size from 6 to 21 amino acid residues were tested for pancreatic secretory activity in the rat. None of the fragments displayed activity when given alone but each displayed significant activity when given after secretin. This apparent activity was shown to be the result of displacement of secretin bound to the walls of the injection catheter. The activity was abolished by dissolving secretin in 2% bovine serum albumin. The finding emphasizes the ease with which secretin can bind to plastic surfaces and consequently the need to reevaluate previous dose-response studies and the caution required in the design of future studies.
The nature of histamine receptors in gallbladder muscle and examined using specific histamine-receptor agonists and antagonists. The H2-receptor antagonist, metiamide, augmented the contractile response to histamine indicating that gallbladder muscle possessed stimulatory H1 receptors and inhibitory H2 receptors. The independent inhibitory character of H2 receptors was confirmed by (1) induction of relaxation with histamine after H1-receptor blockade and the suppression of this relaxation with metiamide, and (2) induction of relaxation with a specific H2-receptor agonist, 4-methyl histamine and the suppression of this relaxation with metiamide. Further, blockade of H2 but not of H1 receptors augmented the response to the octapeptide of cholecystokinin. The nature of this effect was such that the apparent affinity of the octapeptide for its own receptor was increased. The finding raised the possibility that in their native unoccupied state, H2 receptors may modify the response to hormonal agents.
The effect of methacholine, theophylline, and cyclic adenyl and guanyl nucleotides on gastric secretion from antral and proximal duodenal mucosa of the guinea pig was studied. Both 2 mM dibutyryl (db) cAMP and 5 mM theophylline produced significant increases in gastrin secretion, 4.3 +/- 0.7 (P less than 0.001) and 9.3 +/- 2.4 pg mg-1 min-1 (P less than 0.005) respectively, above basal gastrin secretion (1.5 +/- 0.4 pg mg-1 min-1). The combined effect of the two agents was additive (14.5 +/- 3.6 pg mg-1 min-1). Db cGMP (2 mM) had no effect on gastrin secretion. Methacholine produced a dose-related increase in gastrin secretion which at maximum equaled the combined effect of theophylline and db cAMP. The results suggest that gastrin secretion is mediated in part by intracellular cAMP but do not exclude a cooperative involvement of cGMP.
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The clearance rates of synthetic human gastrin-17-I were measured in man, dog, and cat. Half-life of disappearance and acid secretory potency (D50) were also measured in man and dog. The clearance rates in dog and cat were, respectively, 3 and 8 times more than in man. Accordingly, the half-life of gastrin-17 in the dog (3.5 min) was 3 times shorter than in man (9.5 to 10.5 min). The D50 for acid secretion was proportional to the clearance rate and yielded approximately similar increments of serum gastrin, indicating an equal sensitivty to gastrin-17 at cellular level in the three species. An inverse allometric relation between clearance rate and body weight was consistent with the known greater efficiency of metabolic and eliminatory processes in species of small size. Recent studies of the disposal of other gastrointestinal hormones indicate that the concepts developed theoretically for secretory stimulants and confirmed experimentally for gastrin-17 may have wider applicability.
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