Reversible malabsorption caused by high doses of cyclamate.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to S Meryn.
Explore the source record for details and available documents.
1. The effect of hibernation on cerebral cortical concentrations of cholecystokinin and vasoactive intestinal peptide was investigated in the golden mantled ground squirrel (Citellus lateralis). 2. During hibernation, cortical brain weight decreased to 83% of the non-hibernating weight. 3. The concentration of the small form of CCK was significantly reduced. The concentration of the large forms of immunoreactive CCK did not significantly change during hibernation. The molecular forms of CCK appeared the same both before and during hibernation. 4. Of note, the concentration of vasoactive intestinal peptide significantly increased during hibernation. 5. Since there was a three-fold reduction in the ratio of large to small forms of CCK during hibernation, this suggests that post-translational processing of the precursor peptides are markedly reduced during hibernation.
About 5% of normal subjects fail to produce increased hydrogen breath concentration after ingestion of the non-digestible carbohydrate lactulose (low hydrogen producers). The existence of low hydrogen producers limits the diagnostic use of hydrogen (H2) breath tests. We studied the effects of lactulose and of magnesium sulphate (MgSO4) pretreatment on stool-pH and on hydrogen exhalation after oral loading with lactulose or lactose in 17 hydrogen producers and 12 low hydrogen producers. In seven hydrogen producers acidification of stool pH by lactulose pretreatment (20 g tid) decreased hydrogen exhalation and three of seven (43%) became low hydrogen producers. In contrast, after pretreatment of eight low hydrogen producers with magnesium sulphate (5 g twice daily) all eight produced hydrogen after a lactulose load. Similarly four lactose intolerant low hydrogen producers had abnormal lactose hydrogen breath tests after MgSO4 pretreatment. MgSO4 pretreatment neither resulted in false positive lactose hydrogen breath tests in five lactose tolerant hydrogen producers, nor increased the hydrogen exhalation in five additional hydrogen producing controls after ingestion of lactulose. The results of these studies confirm that hydrogen production from lactulose decreases when the colonic pH is lower (lactulose pretreatment), and increases when colonic pH is higher (MgSO4 pretreatment). In low hydrogen producers the lacking increase of H2 exhalation after ingestion of non-digestible carbohydrates can be overcome by MgSO4 pretreatment, thus increasing the sensitivity of the test by avoiding false negative hydrogen breath tests in low hydrogen producers with disaccharide malabsorption or maldigestion. The underlying mechanism of this remarkable effect of MgSO4 pretreatment warrants further investigation.
The effects of hibernation on pancreatic insulin, glucagon, somatostatin, and pancreatic polypeptide was investigated in the golden mantled ground squirrel (Citellus lateralis). During hibernation, pancreatic organ weight decreased to 57% of the nonhibernating weight. The content of all four pancreatic hormones during hibernation was significantly reduced. The concentrations of insulin, pancreatic polypeptide and somatostatin, but not of glucagon, were significantly reduced during hibernation. The maintenance of the pancreatic glucagon concentration during hibernation may be related to its role in counter-regulation and carbohydrate homeostasis during fasting.
The concentrations and molecular forms of pancreatic polypeptide (PP) and glucagon were determined in USP XX and single-peak insulin preparations. In USP insulin the concentration of PP was 7 ng mg-1 insulin; on gel chromatography the PP immunoreactivity fractionated into two peaks of about equal size. One of the PP peaks was in the region of 4200 dalton PP, and the other PP peak eluted earlier in the region of a 7000-10,000 dalton peptide. The concentration of PP in single-peak insulin was 0.8 ng mg-1 insulin; the immunoreactivity eluted in a single peak in the region of [125I]PP. The concentration of glucagon in each preparation was 55 ng mg-1 insulin. On gel chromatography the immunoreactive glucagon in each insulin preparation eluted in the region of [125I]glucagon.
Human poly (C) avid serum ribonuclease (RNase) differs in physico-chemical, electrophoretic, and catalytic properties from ribonuclease activity encountered in liver preparations. The first is reported as "secretory type", the latter, because it is undetectable in body fluids, as "nonsecretory type". We determined RNase activity in 11 hepatoma patients. A statistical difference from a normal control of corresponding age was encountered in both age groups investigated (51-60 years, P less than 0.05; 61-70 years, P less than 0.01). The circumstances mentioned above make the tumor itself unlikely to be the source of RNase elevation. Besides a diminished synthesis of RNase inhibitor by hepatoma cells, tumor-derived polyamines could contribute to enhanced RNase activity. The influence of polyamines on RNase activity has already been demonstrated by in vitro experiments. Simultaneous estimation of polyamines and RNase is required to elucidate in vivo circumstances.
We have studied the concentration of various gastrointestinal peptides in a crude porcine secretin (Boots) preparation and pure natural porcine secretin (GIH, Kabi) preparation. Boots secretin was found to contain 140.3 ng secretin, 1.27 ng human pancreatic polypeptide (hPP), 1.03 ng gastrin, 137.4 ng cholecystokinin (CCK), 241 microU insulin, 1.86 ng vasoactive intestinal polypeptide (VIP), 2.22 ng glucagon and 6.60 ng somatostatin (SRIF) per Crick Harper unit Boots secretin. Sephadex gel filtration demonstrated that the immunoreactivity was due to the hormone per se. GIH secretin contained 240 ng secretin per clinical unit (CU) and less than detectable concentrations of hPP, gastrin, CCK, insulin, VIP, glucagon and SRIF. To determine the clinical significance of having contaminating peptides in Boots secretin, we investigated the effect(s) in 4 subjects. Determined in a highly gastrin-specific assay, the mean plasma gastrin response to Boots secretin administration was slightly, but not significantly greater than the GIH secretin response at 1 and 2.5 minutes. However, in some subjects false positive elevations in plasma gastrin immunoreactivity occurred when some commercially available kit gastrin assays were employed. After intravenous injection of Boots secretin, mean plasma hPP levels rose significantly more than after GIH secretin administration. The mean peak plasma insulin level after GIH secretin administration was significantly higher than after Boots secretin. Neither secretin preparation caused a change in plasma glucose, glucagon and SRIF levels. From these results, it is suggested that GIH secretin be used as the preparation of choice in provocative testing for diagnosing gastrinoma or deficiencies of exocrine pancreatic function.
The possible pharmacokinetic interactions between pirenzepin and theophylline were investigated in an open single blind trial. Aminophylline (6.5 mg/kg body weight) was administered intravenously in five healthy male volunteers before and after chronic oral pirenzepin therapy (50 mg twice daily 5 days before to 2 days after giving aminophylline). To study the theophylline pharmacokinetics, serum and urine samples were collected up to 48 hours after aminophylline administration. It was demonstrated, that pirenzepin does not affect theophylline pharmacokinetics. Therefore, pirenzepin may be combined with aminophylline or theophylline without the risk of an interaction, which usually affect the coadministration of other antiulcer drugs, e.g. cimetidine, with theophylline.
The clinical picture and course of inflammatory bowel disease are influenced by nutritional abnormalities and malnutrition. Interest at present concentrates on high-fibre low-refined sugar diets, elimination diets with identification of specific food intolerance and low-residue diets. All three failed to show significant positive effects on the course of the disease, need for hospitalisation, surgical procedures required or post-operative recurrence. Only a low lactose diet seems to be justified, since we found lactose intolerance in 25-35% of patients with inflammatory bowel disease, as compared with 5-10% in the normal population. In 25 patients with Crohn's disease (CD) a reduction in inflammatory activity and improvement of nutritional status was obtained with parenteral nutrition (PN). Nevertheless, longer follow up periods revealed no additional benefit in comparison with conventional therapies. Furthermore, the combination of PN and total bowel rest resulted in the same improvement as with PN alone. 25 patients with CD manifesting an acute phase of the condition were treated with tube feeding (TF) as primary therapy. TF reduced CD activity and improved nutritional status in 15 patients with small bowel disease, whereas the patients with colonic disease and extraintestinal manifestations did not react. A comparison of the effect of PN and TF in 10 patients with CD showed no significant difference with regard to clinical course and objective parameters. In view of the high costs and risks of complications of PN, TF is recommended as primary therapy for the acute phase of CD. The importance of substitution therapy, especially of vitamin D, is documented.
In vitro culture of human peripheral blood lymphocytes with the beta-adrenergic catecholamine isoproterenol for 24 hours, induced homologous beta-adrenergic desensitization, i.e. a large decrease in the number of beta-adrenergic binding sites and loss of the adenylate cyclase response to isoproterenol, without altering the effectiveness of prostaglandin E1 to stimulate the enzyme. Lymphocyte cultures pulsed for 24 hours with isoproterenol, washed free of the agent and cultured in hormone-free medium for 48 hours still showed marked suppression of the beta-adrenergic adenylate cyclase response and a lack of beta-receptors. When prednisolone was added to the isoproterenol-depleted resuspension medium of desensitized lymphocytes, however, the beta-adrenergic system recovered fully within 48 hours. Treatment of desensitized lymphocytes with prednisolone in the continuous presence of isoproterenol failed to restore beta-adrenergic responsiveness of the cells. The results are discussed with respect to the reconstituting effect of prednisolone on beta-adrenergic responsiveness in bronchial asthma after therapy induced tachyphylaxis.
In order to study the pathogenesis of thrombocytopenia in patients with hairy cell leukemia (HCL), levels of platelet-associated IgG (PAIgG), platelet life span (MLS), and the sequestration site of autologous 111In-labeled platelets were measured in nine patients with HCL. Splenectomized patients (n = 4) had a higher platelet count (x = 122.5 X 10(9)/l; range, 80-190 X 10(9)/l) as well as higher levels of PAIgG (x = 10.7%; range, 5.8-16.9%), than nonsplenectomized patients (platelets x = 76 X 10(9)/l, range 40-100 X 10(9)/l; PAIgG x = 3.2%, range 2.2-4.2%). A normal recovery of 111In-labeled platelets was found in splenectomized patients, whereas a very low recovery was observed in the nonsplenectomized group (x = 70.2%, range, 50-82.5%, versus x = 22.4%, range, 15-28.2%). The MLS was borderline normal in all patients. The site of sequestration was the spleen in nonsplenectomized patients. The low recovery of 111In-labeled platelets in nonsplenectomized patients suggests "hypersplenism" with pooling as a major cause of thrombocytopenia, in addition to impaired thrombocytopoiesis and possible immune-mediated platelet destruction.
A 45-min gastrin assay with a minimum detection limit of 50 pg/ml plasma has been developed which makes use of delayed addition of labeled tracer. The precision of the rapid assay compares favorably with standard methods for measurement of plasma gastrin concentrations in excess of 100 pg/ml. The rapid method can be used for emergency preoperative diagnosis of Zollinger-Ellison syndrome and as an aid in localizing gastrinomas before or during surgery.
In order to improve barium coating of the mucus layer covering the alimentary tract, various surface active substances are added to commercially available contrast media. The action of additives can be expressed in part by their hydrophilic-lipophilic balance (HLB). In an experimental study using human colonic mucus and barium sulfate USP, surfactants of varying HLB (range, 3-11) were used to study the range of HLB resulting in optimal coating. The best coating occurred with an HLB of 7. Quality of coating may be predicted based on knowledge of the HLB of various surface active additives.
The influence of morbid obesity and of gastric surgery operation in circulating peptide hormone concentrations was studied in 26 patients. Plasma hormone levels were determined in the fasting state and after a standardized test meal before and six to nine months after gastric surgery. Before surgery fasting and postprandial blood glucose and hormone levels did not significantly differ in morbidly obese subjects from those in obese or normal subjects, except that in morbidly obese subjects, postprandial gastrin concentration remained at peak levels and did not return to fasting levels 120 minutes after the test meal. An average weight loss of 92 lb following the gastric surgery operation was accompanied by a decrease of fasting glucose and insulin levels and a decreased postprandial insulin response. There were no significant differences in plasma levels of pancreatic glucagon, of pancreatic polypeptide in the basal state, or of pancreatic glucagon after the test meal between the preoperative and postoperative groups. As compared to preoperative values, fasting gastrin levels decreased after surgery, the postprandial release of gastrin was virtually absent, and that of pancreatic polypeptide reduced. The significance of altered postprandial pancreatic polypeptide response and of the reversal of prolonged postprandial hypergastrinemia to a state of low circulating gastrin levels following gastric surgery on gastrointestinal secretion and mucosa remain to be determined.
The prevalence and titer of antibodies to pancreatic hormones in 21 diabetics treated with USP insulin preparations before 1964 (Group 1) and in another 21 diabetics treated with more highly purified insulin preparations after 1974 (Group 2) were determined. All subjects in Group 1 had antibodies to insulin, 11 had antibodies to pancreatic polypeptide (PP) and 3 to glucagon. In Group 2, 17 had antibodies to insulin, 5 to PP, and 1 to glucagon. Antibodies to somatostatin (SRIF) were not detectable in either group. Group 1 subjects had higher titers of antibodies to insulin, glucagon, and PP than Group 2 subjects. Of note, the Group 1 subjects with the highest insulin antibodies also had the greatest prevalence and highest titers of antibodies to glucagon and PP. In order to address the question of possible differences in immune responsivity between Group 1 and 2 subjects, antibody titers to 4 ubiquitous viral agents were determined. There was no significant difference in viral antibody titers between the groups.
Recent studies have suggested that decreased excitatory neurotransmission in the brain may contribute to the overall neural inhibition which characterizes the syndrome of hepatic encephalopathy (HE), and that vasoactive intestinal polypeptide (VIP) and cholecystokinin (CCK) may promote neural excitation in the brain. To determine if brain levels of these neuropeptides are altered in HE, measurements were made of the concentrations of immunoreactive VIP (iVIP) and immunoreactive CCK (iCCK) in cerebral cortex, cerebellum and hypothalamus isolated from normal rabbits and rabbits with galactosamin-induced hepatic coma. Hepatic coma was associated with reduced concentrations of iVIP, small molecular weight iCCK and large molecular weight iCCK in the cerebral cortex but not in the cerebellum or hypothalamus. These findings are compatible with decreased VIP- and CCK-mediated neural excitation occurring in the syndrome of HE.
Explore the source record for details and available documents.
The influence of morbid obesity and gastric bypass operation on pancreatic polypeptide (PP), pancreatic glucagon and enteroglucagon was studied in six morbidly obese patients before and 6-9 months after surgery. Hormone plasma levels were determined in the fasting state and after a standardized test meal. Fasting levels of PP, pancreatic glucagon and enteroglucagon were not significantly different between the pre- and post-operative state as well as compared to normal controls. The postprandial response showed a significant reduction of PP, a significant increase of enteroglucagon and no change of pancreatic glucagon after surgery compared with the preoperative values.