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Biomedical subjects

M V Singer

Publications and source records attributed to M V Singer.

At least 55 records · Page 3Linked to original sources
PubMed1998

[Therapy of Crohn disease in internal medicine: short bowel syndrome and toxic megacolon].

In most cases a short-bowel syndrome is the consequence of extensive bowel resection for Crohn's disease with loss of gastrointestinal function. After operation the patients should be adapted to enteral feeding as soon as possible. The nutritional management is determined by the type of intestinal resection and length of remaining small and large bowel. Total parenteral nutrition for life-time is necessary in patients with less than 50 cm of small bowel. Toxic megacolon is a rare complication seen in Crohn's disease. Conservative therapy includes high doses of intravenous steroids, electrolyte replacement and hydration, antibiotics, decompression of the bowel as well as vigorous surveillance for potential complications. About 50% of the patients with toxic megacolon recover with conservative treatment alone. Surgical intervention should be performed not later than 48 hours after unsuccessful conservative therapy.

Colectomy↗
PubMed1998

Pancreatic bicarbonate response to intraduodenal tryptophan in dogs: role of muscarinic M1-receptors and cholecystokinin.

CONCLUSIONS: In dogs, 1. Activation of cholecystokinin-receptors is needed for an adequate pancreatic bicarbonate response to secretin; 2. Cholinergic nerve fibers ending on M1-receptors are probably of little or no importance for the bicarbonate response to secretin in the given dose; 3. The bicarbonate response to tryptophan, given with a secretin background, is controlled by cholinergic M1-fibers and by cholecystokinin; 4. M1-fibers mainly mediate the bicarbonate response to low loads of tryptophan, whereas cholecystokinin controls the response to low and high loads of tryptophan; and 5. Both mediators interact in a synergistic manner. METHODS: In six conscious dogs with chronic gastric and duodenal fistulas, we compared the action of the M1-receptor antagonist telenzepine (20.25-81.0 nmol/kg/h), the cholecystokinin-receptor antagonist L-364,718 (0.025-0.1 mg/kg/h), and combinations of both on the pancreatic bicarbonate response to graded loads of intraduodenal tryptophan (0.37-10.0 mmol/h), given against a background of secretin (20.5 pmol/kg/h). RESULTS: Secretin significantly (p < 0.05) stimulated the pancreatic bicarbonate output above basal levels. All doses of L-374,718, but not telenzepine, significantly decreased the bicarbonate response to secretin by up to 64%. Additional administration of telenzepine together with L-364,718 had no further inhibitory effect on the secretin-stimulated bicarbonate output as compared to L-364,718 given alone. All loads of tryptophan significantly increased the bicarbonate output over that seen with secretin alone (= incremental bicarbonate response to tryptophan). Telenzepine significantly decreased the incremental bicarbonate response to the two lower loads (0.37-1.1 mmol/h) of tryptophan (by 82-124%); L-364,718 decreased the incremental bicarbonate response to all loads of tryptophan (by 50-118%). The incremental bicarbonate output, as well as the 180-min integrated bicarbonate response to all loads of tryptophan, were abolished by all combinations of both antagonists.

Animals↗
PubMed1998

Induction of tumour necrosis factor (TNF) receptor type p55 and p75 in patients with chronic hepatitis C virus (HCV) infection.

There is evidence that TNF-alpha contributes to the pathogenesis of chronic viral hepatitis. The cellular effects of this cytokine are regulated by two specific receptors, and membranous shedding of these receptors reflects activation of the TNF system. We performed a study of TNF-alpha and functionally active soluble TNF-receptors (TNFR-p55 and -p75) in 105 patients with chronic HCV infection. In HCV RNA-positive patients a significant enhancement of TNF-alpha and both receptor types was observed compared with controls (TNF-alpha 83.8+/-91.7 pg/ml versus 18.8+/-8.4 pg/ml, P<0.001; TNFR-p55 1.4+/-0.4 ng/ml versus 0.9+/-0.2 ng/ml, P<0.0001; TNFR-p75 6.4+/-2.4 ng/ml versus 2.9+/-0.6 ng/ml, P<0.0001, respectively). The enhanced serum levels of TNF-alpha and TNFRs were reflected by a significant expression of TNFR-specific mRNA in peripheral mononuclear cells of HCV-infected patients (P<0.001). Serum aminotransferases correlated with soluble TNFR-p75 (P<0.001) but not with TNFR-p55 and TNF-alpha. We demonstrated an association of the degree of histological inflammation with both TNFRs (P<0.01). Furthermore, enhanced hepatocellular expression of TNF-alpha and TNFRs could be demonstrated by immunohistochemical staining in HCV-infected patients. Sixty-eight out of 105 patients were treated with interferon-alpha (IFN-alpha) (3x10(6)U x 3/week). Pretreatment levels of TNF-alpha and TNFRs did not differ between responders and non-responders. Our results demonstrate that TNF-alpha and TNFRs are enhanced in chronic HCV infection and reflect histological activity of the disease. This up-regulation of TNFRs might modify host response and potentially contribute to liver damage in chronic HCV infection.

Adult↗
PubMed1998

Involvement of chloride channels in the receptormediated activation of longitudinal colonic muscle.

In gastrointestinal smooth muscle, intracellular Cl- is maintained at levels higher than its electrochemical equilibrium. Therefore, Cl- efflux through receptor-mediated opening of Cl- channels should result in membrane depolarization and may be sufficient to activate voltage-sensitive calcium channels (VSCCs). To determine the contribution of Cl- channels to receptor-mediated contraction of the longitudinal muscle layer of the rabbit distal colon, we studied the mechanical response of muscle strips to substance P, carbachol and potassium depolarization following the depletion of Cl- i, and in the presence of the Cl- channel blocker 5-nitro-2-(3-phenylpropyl-amino)-benzoate (NPPB). A 60-min incubation of tissues in a HEPES-buffered solution in which NaCl had been replaced by Na isethionate (or Na gluconate) in equimolar amounts resulted in disappearance of phasic contractions, and in a partially reversible reduction of the tonic response to substance P and carbachol, but not to KCl depolarization. When the agonist was applied to tissues in control solution, or to Cl-(-)depleted tissues in a solution in which Na+ was acutely replaced in equimolar amounts by N-methyl-D-glucosamine, the mechanical response to substance P and carbachol was almost abolished. Acute Na+ replacement alone without prior Cl- depletion did not abolish phasic contractions, but reduced the tonic response to substance P and carbachol. Similar to the effect of Cl- depletion, incubation of tissues in NPPB (6.6 x 10(-5) M) reduced the tonic response to substance P and carbachol, and abolished phasic contractions. These findings are consistent with a contribution of a Cl- channel to the receptor-mediated activation of colonic smooth muscle. In addition, the data suggest that transient Cl- channel mediated depolarizations may play a role in the generation of phasic contractions.

Animals↗
PubMed1998

Action of pure ethanol and some alcoholic beverages on the gastric mucosa in healthy humans: a descriptive endoscopic study.

BACKGROUND AND STUDY AIMS: The action of ethanol and alcoholic beverages on the gastric mucosa in healthy humans is largely unknown. This study was designed to compare the effects of beer, white wine, whisky, and the comparable pure ethanol solutions on the gastric and duodenal mucosa in a controlled, randomized, double-blind endoscopic investigation. MATERIALS AND METHODS: In 47 healthy human volunteers, 100 ml of beer, or white wine, or whisky, or a comparable pure ethanol solution (4%, 10%, 40% vol/vol), or isotonic saline as a control, were sprayed on the antral mucosa. The endoscopic appearance of the gastric and duodenal mucosa was assessed before, immediately after, and 30, 60, 240 minutes and 24 hours after instillation. The lesions were scored using an endoscopic grading system (0-5; 0 = normal mucosa and 5 = ten or more hemorrhagic lesions). RESULTS: Pure ethanol damaged the gastric mucosa in a dose-dependent fashion. The lesions occurred within 30 minutes, and reached a maximum after 60 minutes (antral score for 4% = 1.3; 10% = 1.8; 40% 3.8; control = 1.5). Beer, wine and whisky also induced gastric mucosal injury, but to a lesser extent than the comparable ethanol solutions. The 24-hour integrated endoscopic scores for beer and wine were significantly lower (P < 0.05) than the corresponding ethanol content. In the case of pure ethanol > 10% and whisky, the lesions were still present 24 hours later (antral score for 10% = 1.5; 40% = 2.0; whisky = 2.3; control = 0). No lesions were observed in the duodenum. None of the volunteers reported any abdominal pain during the whole investigation. CONCLUSIONS: Intragastric application of 4%, 10%, and 40% vol/vol pure ethanol induces gastric, but not duodenal, mucosal lesions in a dose-dependent fashion. Beer, white wine, and whisky induce gastric mucosal lesions to a lesser degree than the corresponding ethanol content. Lesions induced by higher ethanol concentrations (> 10%) and whisky take more than 24 hours to heal. The lesser damage caused by alcoholic beverages may be due to the protective action of unknown nonalcoholic ingredients.

Adult↗
PubMed1998

Vancomycin control measures at a tertiary-care hospital: impact of interventions on volume and patterns of use.

OBJECTIVE: Evaluate vancomycin prescribing patterns in a tertiary-care hospital before and after interventions to decrease vancomycin utilization. DESIGN: Before/after analysis of interventions to limit vancomycin use. SETTING: 420-bed academic tertiary-care center. INTERVENTIONS: Educational efforts began August 10, 1994, and involved lectures to medical house staff followed by mailings to all physicians and posting of guidelines for vancomycin use on hospital information systems. Active interventions began November 15, 1994, and included automatic stop orders for vancomycin at 72 hours, alerts attached to the medical record, and, for 2 weeks only, computer alerts to physicians following each vancomycin order. Parenteral vancomycin use was estimated from the hospital pharmacy database of all medication orders. Records of a random sample of 344 patients receiving vancomycin between May 1, 1994, and April 30, 1995, were reviewed for an indication meeting published guidelines. RESULTS: Vancomycin prescribing decreased by 22% following interventions, from 8.5 to 6.8 courses per 100 discharges (P<.05). The estimated proportion of vancomycin ordered for an indication meeting published guidelines was 36.6% overall, with no significant change following interventions. However, during the 2 weeks that computer alerts were in place, 60% of vancomycin use was for an approved indication. CONCLUSIONS: Parenteral vancomycin prescribing decreased significantly following interventions, but the majority of orders still were not for an indication meeting published guidelines. Further improvement in the appropriateness of vancomycin prescribing potentially could be accomplished by more aggressive interventions, such as computer alerts, or by targeting specific aspects of prescribing patterns.

Algorithms↗
PubMed1998

A review: acute and chronic effects of ethanol and alcoholic beverages on the pancreatic exocrine secretion in vivo and in vitro.

Whereas oral or intraduodenal ethanol causes a moderate stimulation of pancreatic bicarbonate and enzyme output, intravenous ethanol inhibits basal and hormonally stimulated pancreatic exocrine secretion in humans, dogs, cats, pigs, rabbits, and rats. This inhibition could be mediated by inhibitory cholinergic mechanisms or be the result of a direct cellular effect of ethanol. In vitro investigations have specified several signaling molecules that may be involved in the action of ethanol on stimulus-secretion coupling in the exocrine pancreas, including cyclic adenosine monophosphate, intracellular calcium, and cholecystokinin and somatostatin receptors. In difference to pure ethanol solutions and distilled spirits, beer strongly stimulates pancreatic enzyme output, probably by nonalcoholic fermentation products. During chronic alcoholism, the ethanol-induced inhibition is replaced by an enhanced enzyme output that causes intraductal protein precipitation. In vitro investigations suggest that this increase is reversible after alcohol withdrawal. The occurrence of protein precipitates is considered to be a crucial step in the development of chronic alcoholic pancreatitis in humans. Other ethanol-induced secretory alterations that may contribute to the development of alcoholic pancreatitis are a decreased secretion of trypsin inhibitor, an increased cholinergic tone, and changes in the concentration of lithostathine.

Alcoholic Beverages↗
PubMed1997

Interleukin-12 induction of Th1 cytokines is important for viral clearance in chronic hepatitis B.

Interleukin-12, a cytokine with an important role against intracellular pathogens, promotes Th1 cell development, cellmediated cytotoxicity, and interferon-gamma production. We investigated the immunoregulatory role of IL-12 in 72 chronic hepatitis B virus (HBV) carriers, 33 of whom were monitored longitudinally during interferon-alpha treatment. Serum levels of IL-12 heterodimer, IL-12 p40 subunit, IL-4, and Th1 cytokines were determined by specific ELISAs, and hepatitis B core antigen-specific T cell response by a proliferation assay. Chronic HBV carriers had higher serum levels of IL-12 and IL-12 p40 in comparison with controls (P < 0.01), suggesting that IL-12 production is not impaired. The longitudinal analysis revealed a further substantial increase (> 2.5x baseline level) of bioactive IL-12 and Th1 cytokines in patients who cleared HBV and seroconverted to anti- hepatitis B e, unlike the 23 nonresponders with persistent HBV replication (P < 0.01). The IL-12 peak followed the peak of hepatocytolysis by 9.8+/-2.8 wk and occurred either before or simultaneously with hepatitis B e seroconversion. Hepatitis B core antigen-specific T cell proliferation closely correlated with hepatocytolysis and increased significantly in all patients (8 responders and 15 nonresponders) who developed hepatitis flare, irrespective of the virological outcome. These results provide in vivo evidence that IL-12 may have an important role for viral clearance in chronic HBV infection.

Adult↗
PubMed1997

Pancreatic secretory response to intrajejunal tryptophan: studies in dogs with an autotransplanted entire jejunoileum.

In two sets of dogs with gastric, duodenal, and jejunal fistulas, we studied the effect of atropine (14 nmol/ kg/h) on the pancreatic secretory response to intrajejunal tryptophan (0.12-10.0 mmol/h; given against a secretin background) before (n = 7) and after extrinsic denervation of the jejunoileum (orthotopical autotransplantation; n = 6). Plasma levels of cholecystokinin were determined by radioimmunoassay. The incremental bicarbonate response to tryptophan was not significantly different between the two sets of dogs. Atropine had no effect on the incremental bicarbonate response to tryptophan. In both sets of dogs, intrajejunal tryptophan caused a dose-dependent increase in pancreatic protein output, which was reduced by atropine. The tryptophan-stimulated levels of plasma cholecystokinin were not significantly altered by denervation and or atropine. We conclude that in dogs (1) intrajejunal tryptophan stimulates pancreatic bicarbonate and protein secretion via release of hormones, (2) extrinsic denervation of the jejunoileum does not significantly alter the incremental bicarbonate and protein responses to intrajejunal tryptophan, (3) the cholinergic intrinsic nerves of the jejunoileum and the hormone cholecystokinin are probably involved in control of the pancreatic protein response to tryptophan, and (4) the release of cholecystokinin by intrajejunal tryptophan does not depend on the extrinsic and intrinsic cholinergic nerves of the jejunoileum.

Animals↗
PubMed1997

Gastroenteropancreatic effects of xenin in the dog.

Xenin is a 25 amino acid peptide detected in the gastric mucosa of various mammals. It has since been found in low concentrations in other tissues. Xenin plasma concentrations increase after meals. The present study reports some gastroenteropancreatic effects of this peptide in the dog. Intravenous infusion of 64 pmol/kg min synthetic xenin significantly inhibited pentagastrin-stimulated gastric acid secretion and stimulated exocrine pancreatic secretion of volume and protein. Further, intravenous infusion of xenin in a dose of 1.0 pmol/kg min stimulated jejunal motility in the anaesthetized dog. An intravenous infusion of 32 pmol/kg min xenin raised plasma concentrations of pancreatic polypeptide, vasoactive intestinal polypeptide, insulin and glucagon. The present experiments therefore indicate manifold bioactive properties of intravenously infused xenin in the dog, with jejunal motility the most sensitive target. Conclusions as to the physiological role of xenin cannot be drawn from the present experiments. The release of other hormonal peptides indicates a complex action of xenin.

Animals↗
PubMed1997

Alcoholic beverages produced by alcoholic fermentation but not by distillation are powerful stimulants of gastric acid secretion in humans.

BACKGROUND: The effect of commonly ingested alcoholic beverages on gastric acid output and release of gastrin in humans is unknown. AIM AND METHODS: In 16 healthy humans the effect of some commonly ingested alcoholic beverages produced by fermentation plus distillation (for example, whisky, cognac, calvados, armagnac, and rum) or by alcoholic fermentation (beer, wine, champagne, martini, and sherry) on gastric acid output and release of gastrin was studied. Gastric acid output was determined by the method of intragastric titration. Plasma gastrin was measured using a specific radioimmunoassay. RESULTS: None of the alcoholic beverages produced by fermentation plus distillation had any significant effect on gastric acid output and release of gastrin compared with control (isotonic glucose and distilled water). Alcoholic beverages produced only by fermentation significantly (p < 0.05) increased the gastric acid output by 57% to 95% of maximal acid output (MAO) and release of gastrin up to 5.1-fold compared with control. If beer, wine, and sherry were distilled, only their remaining parts increased gastric acid output by 53% to 76% of MAO and increased release of gastrin up to 4.3-fold compared with control. CONCLUSIONS: (1) Alcoholic beverages produced by fermentation but not by distillation are powerful stimulants of gastric acid output and release of gastrin; (2) the alcoholic beverage constituents that stimulate gastric acid output and release of gastrin are most probably produced during the process of fermentation and removed during the following process of distillation.

Adult↗
PubMed1997

Effects of telenzepine and L-364,718 on canine pancreatic secretion before and after vagotomy.

In six conscious dogs we compared the action of the M1-receptor antagonist telenzepine (20.25-81.0 nmol.kg-1.h-1), the cholecystokinin (CCK) antagonist L-364,718 (0.025-0.1 mg.kg-1.h-1), and combinations of both on the pancreatic secretory response to intraduodenal tryptophan, given against a secretin background before and after truncal vagotomy. Before vagotomy, the higher doses of telenzepine and of L-364,718 significantly (P < 0.05) decreased the protein response to tryptophan by up to 97%. After vagotomy, all doses of L-364,718 abolished the protein response, whereas telenzepine had no further effect. Before and after vagotomy, all combinations abolished the protein response. The plasma CCK-like immunoreactivity basally, during secretin, and in response to tryptophan was not altered by vagotomy, telenzepine, and/or L-364,718. These findings indicate that in dogs 1) potentiation exists between M1 receptors and CCK for stimulation of the pancreatic enzyme response to intraduodenal tryptophan, 2) the cholinergic fibers of the enteropancreatic reflex activated by tryptophan run within the vagus nerves and end at least in part on M1 receptors, 3) CCK acts in part independently of the vagal nerves, and 4) the CCK release by intestinal tryptophan is not influenced by vagotomy, telenzepine, and/or L-364,718.

Animals↗
PubMed1997

[Effects of peptide YY on functions of the gastrointestinal tract].

The present report gives a review about the localization, release and gastrointestinal actions of peptide YY in different animal species and in humans. Possible mechanisms of action, the physiological and pathophysiological significance of peptide YY and the role of peptide YY 3-36 are discussed. Finally, unanswered questions are specified.

Amino Acid Sequence↗
PubMed1997

[Sclerosing cholangitis after burn injury].

We present the case of a 57-year-old woman who developed persistent jaundice and cholestasis four weeks after a severe burn injury (34% of the body surface, 19% second degree, 15% third degree). In the endoscopic retrograde cholangiography four months later the characteristic picture of sclerosing cholangitis was found. A causal relation between the thermal injury and the development of sclerosing cholangitis is likely because of this coincidence and the absence of any preexisting disease, especially of the hepatobiliary system. Other cholestatic liver disease could be excluded. Possible pathogenetic mechanisms are discussed, especially the increased permeability of the gut mucosa after burn injuries with consecutive translocation of bacteria and toxins and their transport into the biliary tract.

Bile Ducts, Intrahepatic↗