Biomedical subjects
Publications and source records attributed to K Gyr.
Vasoactive intestinal polypeptide (VIP), a basic polypeptide mainly found in neural tissue, has been associated with specific endocrine pancreatic tumors. In the present study, a sensitive and specific radioimmunoassay for VIP is described and its clinical application discussed.
The pathogenesis of Crohn's disease is unknown, but immunologic mechanisms appear to play at least a partial role. Prompted by favourable experience with cyclosporin A in autoimmune diseases, the authors used it in steroid resistant acute Crohn's disease and started a pilot study comparing cyclosporin A with prednisone. Initial experience shows that cyclosporin A is effective in at least some patients with acute Crohn's disease. Side effects have thus far been minimal. However, oral dosage of the drug is difficult and regular determinations of the trough blood concentration are indispensable. A trough blood concentration of 200 ng/ml appears to be necessary to obtain full therapeutic activity. The lower antipyretic effect of cyclosporin A compared to prednisone may initially mask a favourable therapeutic effect. The effectiveness of cyclosporin A compared with prednisone cannot yet be evaluated.
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Two women were admitted for increasing abdominal pain, vaginal discharge, and severe or moderate chronic ascites. Diffuse peritonitis without evidence of liver disease was found in both cases, and in one the ascites and vaginal discharge contained Chlamydia trachomatis. Both patients responded to doxycycline, and this and the laboratory findings pointed strongly to C trachomatis as the aetiological agent. C trachomatis may cause severe peritoneal infections with chronic ascites formation in the absence of liver disease in women with the Fitz-Hugh-Curtis syndrome. Prompt diagnosis and antibiotics lead to rapid cure.
Exocrine pancreatic function was assessed by means of the Lundh test in 14 patients with acute cholera and 18 patients with acute infectious non-cholera diarrhoea within the first 24 h of their admission. Mean tryptic activity amounted to 39.8 +/- 4.8 microEq/min/ml in the cholera group and to 64.4 +/- 11.0 microEq/min/ml in the non-cholera group. None of these patients shared a value below the lower limit of normal. In fact, the mean tryptic activity per 2 h was significantly higher than that reported previously in a control group from the Bengal area. It is therefore concluded that the exocrine pancreatic function is preserved and responds to food stimulation in various types of acute infectious diarrhoea, including cholera. These findings provide the pathophysiological background for the recent observation that oral rehydration solutions containing high-molecular-weight nutrients such as rice powder are at least as efficient or even more potent than the WHO-recommended glucose-electrolyte formula in acute diarrhoea.
We studied the effect of four graded doses of SMS 201-995, a synthetic octapeptide somatostatin analogue (27, 80, 240, and 720 ng/kg/h) on the basal and secretin-plus-cerulein-stimulated exocrine pancreatic function and pancreatic polypeptide (PP) release in five healthy volunteers. Duodenal fluid secretion and bicarbonate output under basal and stimulated conditions were not significantly affected by any dose of SMS. The basal and stimulated enzyme secretion were decreased in a non-dose-dependent manner by all SMS doses used in the study and showed a 75% inhibition of the secretin-plus-cerulein-stimulated trypsin and amylase output. The cerulein-stimulated PP release was significantly suppressed by all four SMS doses. SMS appears to be a strong inhibitor of pancreatic enzyme secretion, at the same time affecting the PP release.
We determined the effects of exogenous somatostatin-14 (100 and 200 ng/kg/h; mimicking postprandial somatostatin concentrations) on pancreatic responses to a background infusion of secretion in combination with graded doses of CCK-8 in conscious dogs with chronic gastric and duodenal fistulas. The lower dose of somatostatin-14 (S-14), which produced S-14 plasma levels lower than measured after a meal, did not change basal or stimulated pancreatic secretion. The upper dose of S-14, which produced plasma S-14 concentrations slightly above the postprandial range, caused inhibition of pancreatic fluid and protein secretion to low doses of CCK-8 (p less than 0.05). The inhibition was surmountable with higher doses of CCK-8. We interpret these data as indicating that circulating S-14 is not an important hormonal regulator of exocrine pancreatic secretion.
Somatostatin, a peptide present in hypothalamus, gastric mucosa, and pancreas suppresses several gastrointestinal functions. Its short half life has prevented clinical use. We have therefore evaluated the effect of subcutaneous administration of a new synthetic somatostatin analogue, in comparison with a placebo, on pentagastrin stimulated acid secretion in six healthy volunteers. On different days, acid secretion was measured continuously, after a basal 30 minutes, for six hours during 3 micrograms/kg/h of intravenous pentagastrin. Acid secretion was measured with a marker technique (0.1% phenol red) to correct for duodenal volume loss. Blood was drawn in regular intervals to measure plasma somatostatin concentrations by radio immunoassay. One hour after starting the pentagastrin infusion, a single subcutaneous injection of either 100 micrograms somatostatin analogue, or placebo (isotonic saline) was given. In a follow up study, somatostatin was given subcutaneously in a dose of 200 micrograms. No difference in efficacy was observed between the two doses. A single subcutaneous injection of the somatostatin analogue significantly suppressed acid secretion for five hours (p less than 0.01). Maximal inhibition was approximately 75%. Mean elimination half life of the analogue was approximately 80 minutes. We suggest that the new somatostatin analogue might be useful for clinical use.
Several secretagogues of exocrine pancreatic secretion have been proposed to act as regulators of pancreatic D-cell function. To characterize this relationship, we measured incremental responses of protein, bicarbonate, and circulating somatostatin to graded doses of intravenous cholecystokinin (CCK-33), CCK-8, caerulein, bombesin, secretin, and intraduodenally perfused HCl, sodium oleate, and L-phenylalanine in conscious dogs with gastric and pancreatic fistulas and compared them with postprandial values (to a beef meal). Bombesin produced dose-related increases in somatostatin secretion (maximal, 46% of meal response), but caerulein, CCK-33, and CCK-8 released only small amounts of somatostatin at doses equivalent for pancreatic protein secretion. Secretin did not stimulate somatostatin release at any dose studied, whereas intraduodenal HCl at a load submaximal for pancreatic bicarbonate secretion increased somatostatin levels slightly (maximal, 16% of meal response). L-Phenylalanine and sodium oleate markedly increased protein secretion, but only oleate clearly stimulated somatostatin release (maximal, 11% of meal response). Our results suggest a greater quantitative importance of the intestinal phase for exocrine pancreatic stimulation than for somatostatin release.
The aim of this study was to identify the somatostatin (SST-14) dose dissolved in 0.1% human albumin solution equivalent to the commonly used therapeutic dose (3.5 micrograms kg-1 h-1) dissolved in saline in inhibiting pentagastrin-stimulated gastric acid secretion in healthy volunteers. Gastric acid secretion was stimulated for 3.5 h by intravenous pentagastrin (3 micrograms kg-1 h-1). 0.875 or 1.75 micrograms kg-1 h-1 SST-14 dissolved in 0.1% albumin was significantly (p less than 0.05) less effective in inhibiting stimulated gastric acid secretion than the standard therapeutic dose. There was no difference achieved in the degree of inhibition with albumin added or not to the 3.5 micrograms kg-1 h-1 dose of SST-14. However, an intermediate dose (2.625 micrograms kg-1 h-1) of SST-14, whether dissolved in albumin or saline alone, was as effective as the standard therapeutic SST-14 dose. We conclude that at these high does the absorption of a small quantity of SST-14 to glass and plastic surfaces of the infusion sets has no influence on the therapeutic effect.
The pancreatic exocrine secretory response to increasing doses of exogenous caerulein with and without a background infusion of secretin was studied in 5 healthy volunteers. Caerulein over a full range of doses (2.3-37 pmol/kg/h) produced increasing enzyme secretion up to 18.5 pmol/kg/h, whereas 37 pmol/kg/h was clearly supramaximal and caused submaximal enzyme release. We conclude that maximal pancreatic enzyme secretion is achieved with lower caerulein doses than generally used in pancreatic function tests.
To investigate the value of plasma secretin determination in the diagnosis of impaired gastric secretion, blood samples were drawn for secretin assay (radioimmunoassay) at specified intervals before and after pentagastrin stimulation in 10 healthy volunteers and 11 subjects with suspected hypo- or achlorhydria (less than 10 mEq HCl/2 h). The tests were performed twice, once with and once without aspiration of gastric juice for estimation of acid output. In six other patients with proven achlorhydria, the test was performed once without gastric aspiration. The best discrimination of a single plasma secretion level between controls and patients with hypo- and achlorhydria was obtained 60 min after pentagastrin stimulation. All controls and four subjects with an acid output more than 10 mEq/2 h had secretin levels within normal limits. In contrast, 12 of the 13 subjects with hypochlorhydria had abnormally low basal corrected secretin levels at 60 min, including nine achlorhydria patients. It is concluded that secretin determinations after pentagastrin stimulation may be a valuable diagnostic and epidemiological tool to identify patients with impaired gastric secretion.
The effect of Nifedipine on hepatic venous pressure gradient (HVPG) was determined in 10 patients with portal hypertension due to cirrhosis of the liver, and in 7 control subjects, by hepatic vein catheterization. Twenty min. after sublingual application of 10 mg Nifedipine, patients and controls showed significant hemodynamic changes in the systemic circulation. In contrast, HVPG after Nifedipine was not statistically different from the basal values--neither in patients with portal hypertension (p = 16.6 +/- 5.2 mmHg vs 17.9 +/- 5.3 mmHg) nor in the control subjects (p = 2.9 +/- 1.1 mmHg vs. 1.0 mmHg). We conclude that calcium entry blockade by Nifedipine is not effective in acutely reducing portal venous pressure.
The pancreas has both exocrine and endocrine components. The exocrine component of the pancreas manufactures, stores, and packages digestive enzymes for digestion of food, whereas the endocrine secretes hormones that regulate the metabolism and utilization of the absorbed nutrient components. Both components are closely related, not only anatomically but also functionally. The available evidence to support the concept of a close interrelationship of endocrine and exocrine pancreatic function is summarized. It is shown that the endocrine part exerts a profound effect upon the digestive activities of the organ, and that impairment of endocrine function, such as diabetes, severely affects the exocrine component of the gland. Furthermore, dysfunction of the exocrine gland, as in chronic pancreatitis, progressively disturbs the function of the islet cell hormones. The interactions are governed by a complicated control system, the details of which are not yet clarified. As in any partnership, dysfunction of one partner severely affects the other and vice versa.
A report is presented on 2 tourists returning from the Indian Ocean area in whom clinically overt dengue fever was diagnosed. The epidemiology, pathogenesis and clinical course of the disease are discussed.
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The results during the period 1979-1984 of intestinal endoscopies with brush cytology and biopsy of the same lesion at the same time were evaluated to define the value of these methods. Results were reported as "cancer present" or "not present" or as "suspicious/proving" versus "nonsuspicious for cancer" and were analyzed separately. Biopsy was shown to be of greater sensitivity than cytology in the stomach and cytology more sensitive in the colon. The combination of biopsy and cytology improved sensitivity, especially in the esophagus, small intestine and colon, and may help to dispense with unnecessary repetitions of endoscopic evaluations. The specificity was found to be extremely high when the results were reported as "cancer present" or "not present", with only one false positive report in a patient with ischemic colitis. In more than 60% the final diagnosis was cancer if the initial report showed suspicion of cancer, but the specificity of these results was low.
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