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Biomedical subjects

M V Singer

Publications and source records attributed to M V Singer.

At least 37 records · Page 2Linked to original sources
PubMed2001

Central and peripheral neural control of pancreatic exocrine secretion.

Efferent vagal impulses act on the exocrine pancreas via pancreatic ganglia, where the impulses are modulated and modified, and terminate via postganglionic fibers at the acinar cells. Acinar muscarinic receptors of the subtype M1 play an important role for the mediation of the stimulatory vagal influences on pancreatic exocrine secretion. In dogs, a potentiative interaction exists between the two most important mediators of the pancreatic exocrine response to intraduodenal stimuli, efferent vagal impulses and CCK. In contrast to humans and rats, in which all action of CCK on pancreatic enzyme output is vagally mediated, CCK acts in dogs in part as a classical humoral factor independent of the cholinergic system. Although several peptides found in pancreatic nerve cell bodies or fibers can stimulate or inhibit pancreatic exocrine secretion, their physiological importance in the neural control of the exocrine pancreas needs to be further evaluated.

Animals↗
PubMed2000

Lipopolysaccharide/endotoxin induces IL-18 via CD14 in human peripheral blood mononuclear cells in vitro.

IL-18 shares activities with IL-12 in generating T-helper 1 cells and cytokine response. It mediates LPS/endotoxin lethality by IL-12 independent interferon-gamma synthesis and it induces bacteria-related organ failure. As peripheral blood mononuclear cells (PBMC) are potent producers of IL-18, we studied the regulation of IL-18 upon exposure to LPS and Staphylococcus aureus (SAC) in vitro. Freshly isolated PBMC constitutively expressed IL-18 mRNA. After unstimulated preincubation for 48 h, however, IL-18 transcripts were nearly not detectable by RT-PCR, but inducible by LPS or SAC (P<0.01). Both LPS and SAC were potent stimuli of IL-18 protein secretion (P<0.01). LPS-mediated IL-18 gene expression and secretion was CD14-dependent and significantly inhibited by co-incubation of PBMC with neutralizing CD14 antibody (P<0.01). We conclude that LPS-driven IL-18 is dependent on the expression of costimulatory factors and that IL-18 inhibition might attenuate IL-18-related toxic effects.

Adult↗
PubMed2000

Esophageal motility disorders in critically ill patients: a 24-hour manometric study.

OBJECTIVE: Impaired tubular esophageal motility is involved in the pathogenesis of gastroesophageal reflux disease, which, in turn, has been shown to cause nosocomial pneumonia in critically ill patients. As multiple factors are involved, this pilot study was undertaken to evaluate whether, similarly, impaired esophageal motility may contribute to nosocomial infections by determining esophageal motility in critically ill patients undergoing mechanical ventilation and sedation in comparison to that of a healthy control group. DESIGN: Open, single-centered study. PATIENTS AND METHODS: Fifteen consecutive ventilated intensive care unit (ICU) patients with different diseases and three regimens of analgo-sedation were included: group 1: no analgo-sedation, group 2: ketamine and benzodiazepines, and group 3: fentanyl and benzodiazepines. Six healthy volunteers were studied as controls. Twenty-four hour esophageal anterograde (propulsive) and retrograde motility changes were assessed by a manometry system. RESULTS: The frequencies of contractions were 0.67 +/- 0.1/min (no analgo-sedation) 0.093 +/- 0.02 (ketamine) and 0.076 +/- 0.01 (fentanyl) (p < 0.05 as compared to controls). The amplitudes (% of maximum) were 98 % (control), 58 % (analgo-sedation), 38 % (ketamine) and 42 % (fentanyl; p < 0.05 for the comparison of fentanyl and ketamine with controls). Whereas the percentage of propulsive contractions was significantly decreased in patients (no sedation: 45 %, ketamine: 34 %; fentanyl: 35 %, p < 0.05) as compared to controls (72 %), the percentage of retrograde contractions increased: no sedation: 29 %, ketamine: 34 % and fentanyl: 37 % as compared to controls: 10 %, p < 0.05. Analysis according to the underlying diseases showed marked inhibition of motility parameters within any disease group in comparison with controls. CONCLUSIONS: Irrespective of the underlying disease, propulsive motility of the esophageal body is significantly reduced during any kind of sedation in critically ill patients. Possibly central as well peripheral drug-related effects are involved in such a depression. Twenty-four hour motility recordings appear to be a valuable and feasible method to quantify and analyze esophageal motor disorders in critically ill patients.

Adult↗
PubMed2000

Gene expression of TNF-receptors in peripheral blood mononuclear cells of patients with alcoholic cirrhosis.

BACKGROUND/AIMS: Elevated concentrations of tumor necrosis factor receptors have been detected in alcoholic cirrhosis, but it remains unknown whether or not peripheral blood mononuclear cells are a source of tumor necrosis factor receptors and reflect the clinical disease activity of patients with advanced alcoholic liver disease. METHODS: Twenty-two abstinent patients in different stages of alcohol-induced cirrhosis according to the criteria of the Child-Pugh classification (Child-Pugh stage A: 4, Child-Pugh stage B: 10, Child-Pugh stage C: 8) were compared with four healthy individuals. Semi-quantitative reverse transcriptase-polymerase chain reaction was used for the measurement of the expression of tumor necrosis factor-alpha, soluble tumor necrosis factor receptors-p55, -p75, interleukin-10 and inducible nitric oxide synthase in unstimulated peripheral blood mononuclear cells. RESULTS: Unstimulated peripheral blood mononuclear cells of patients with alcoholic cirrhosis demonstrate a stage-dependent enhanced RNA expression of tumor necrosis factor-alpha (healthy controls 0/4, Child-Pugh stage A 2/4, stage B 10/10, stage C 8/8; p<0.01). The mRNA expression of TNF-receptors-p55/-p75 is significantly higher in patients with severe alcoholic cirrhosis (Child-Pugh stage B or C patients) than healthy controls (p<0.05), while peripheral blood mononuclear cells from patients with Child-Pugh stage A show a similiar pattern of gene expression to healthy controls. No significant up-regulation of interleukin-10 was found. Inducible nitric oxide synthase was detectable in Child-Pugh stage C (p<0.05). CONCLUSIONS: Unstimulated peripheral blood mononuclear cells of patients with severe alcoholic cirrhosis (Child-Pugh stage B and C) demonstrate a systemic leukocyte activation and gene expression of tumor necrosis factor-alpha and tumor necrosis factor receptors-p55/-p75, which is correlated with the activity of the disease. Our data confirm previous studies that reported a correlation between plasma levels of pro-inflammatory cytokines and the severity of alcoholic cirrhosis. The role of interleukin-10 and inducible nitric oxide synthase in the pathogenesis of alcoholic cirrhosis remains to be fully elucidated.

Antigens, CD↗
PubMed2000

[Preoperative laboratory diagnosis in pancreatic surgery--what is necessary?].

Some aspects of preoperative laboratory investigations are discussed in pancreatic surgery. Diagnosis of acute pancreatitis is not a major diagnostic problem with pancreatic enzyme measurement and with further regard to medical history and clinical presentation. However, early assessment of the prognosis of acute pancreatitis still remains a clinical challenge. The determination of C-reactive protein (CRP) and lactate dehydrogenase (LDH) is used successfully in clinical practice. The values of different serum markers are described in prognostic evaluation of acute pancreatitis, and some direct and indirect pancreatic-function tests are compared in preoperative management of patients with chronic pancreatitis. The most sensitive direct pancreatic-function test is the secretin-pancreozymin test (SP-test), among the indirect function tests estimation of faecal elastase 1 is superior. The significance of tumor marker measurement is described in pancreatic cancer.

Chronic Disease↗
PubMed2000

[Chronic abdominal pain and eosinophilia in a young African patient].

A 20-year-old African female was hospitalized several times for diffuse chronic abdominal pain. The following exclusions were made: Acute adnexitis (by laparoscopy), acute appendicitis (by appendectomy), gastric ulcerations (by esophagogastroduodenoscopy) as well as Crohn's disease and ulcerative colitis. However, once taking a closer microscopical look at the mucosa, that otherwise appeared colonoscopically to be normal, multiple eggs of schistosomiasis mansoni (S. mansoni) were found in the colon as well as the rectum. Thus, the diagnosis of an intestinal bilharziosis was finely established. In retrospect even the sample taken for the appendix could have indicated this diagnosis already earlier on. Both the antibodies (ELISA/IFAT) and the specific immunoglobulins (IgE) for S. mansoni proved significantly positive. Therapy of choice was a single oral dosage of praziquantel. Migration and tourism have considerably increased the range of tropical and infectious diseases that need to be included into differential diagnosis. This case report focuses on intestinal bilharziosis as a potential underlying cause of chronic abdominal pain in immigrants of endemically affected areas. Direct diagnosis is the most important diagnostic method. The adult worms are usually inaccessible, so the method of choice to assess both diagnosis and the degree of activity of a chronic infection is evidence of living eggs in the stool. Alternatively, in case of lack of direct evidence diagnosis can be established by endoscopy and rectal biopsy.

Abdominal Pain↗
PubMed2000

Effects of M1 and CCK antagonists on latency of pancreatic amylase response to intestinal stimulants.

In six conscious dogs with gastric and duodenal cannulas, secretin (164 pmol. kg(-1). h(-1) iv) was given to provide a flow of pancreatic juice of approximately 1 drop/s. Amylase activity was measured in each drop before and after rapid intravenous injection of caerulein (7.4 pmol/kg) or intraduodenal injection of L-tryptophan (1 mmol), sodium oleate (3 mmol), and HCl (3 mmol). All experiments were repeated in the presence of the M1 receptor antagonist telenzepine (81 nmol. kg(-1). h(-) iv) and the cholecystokinin (CCK) receptor antagonist L-364718 (0.1 mg/kg iv). Latency of amylase response (time between injection of stimulant and sustained increase in amylase activity greater than mean + 3 SD of prestimulatory activity) to tryptophan (17 +/- 7 s; n = 6) and oleate (16 +/- 5 s) was significantly (P < 0.05) shorter than to caerulein (28 +/- 4 s) and HCl (120 +/- 47 s). Telenzepine significantly increased the latency of amylase response to tryptophan and oleate by >10-fold but not the latency to caerulein or HCl. L-364718 abolished the amylase response to all stimulants. These findings indicate that the early amylase response to intraduodenal tryptophan and oleate is mediated by a neural enteropancreatic reflex ending on M1 receptors rather than by hormone release. However, the activation of (possibly vagal) CCK receptors is essential to run the reflex. The early amylase response to intraduodenal HCl is probably mediated by the release of CCK into the blood circulation.

Amylases↗
PubMed2000

Pancreatic secretory response to intraileal amino acids: studies in dogs with an in situ neurally isolated ileum.

BACKGROUND: Intraileal carbohydrates and lipids affect the pancreatic exocrine secretion, but the effect of intraileal amino acids and the role of the extrinsic nerves of the ileum as mediators of the pancreatic bicarbonate and enzyme output are unknown. METHODS: Four dogs underwent total extrinsic denervation of the entire ileum. Thomas-like cannulas were placed into the stomach, duodenum (to collect pure pancreatic juice), and at the jejuno-ileal junction. Eight neurally intact control dogs received only the three fistulas. After recovery, in both sets of dogs, dose-response studies of the pancreatic secretory response to intraileal infusion with graded loads of tryptophan (0.12-10.0 mmol/h) were performed, given against an intravenous (iv) background of secretin (20.5 pmol/kg/h) and cerulein (29.6 pmol/kg/h). On separate days, control experiments with intraileal infusion of 0.15 M NaCl were performed. RESULTS: In both sets of dogs, iv secretin plus cerulein significantly (p < 0.05) increased pancreatic bicarbonate and protein output above basal. Intraileal tryptophan caused a dose-dependent decrease in the pancreatic bicarbonate and protein response to secretin plus cerulein. In the dogs with denervated ileum, this inhibition was significantly stronger than in the intact animals. In both sets of dogs, the 225-min integrated bicarbonate (IBR) and protein response (IPR) to all loads of tryptophan were significantly lower than in control experiments. Both IBR and IPR were significantly lower in the denervated as compared with the intact animals. CONCLUSIONS: 1) Extrinsic denervation of the entire ileum is a valuable preparation to study the role of nerves in the control of pancreatic exocrine secretion; 2) both in the intact and denervated animals the amino acid tryptophan induces an "ileal brake" of the hormonally stimulated pancreatic bicarbonate and protein output; 3) the extrinsic nerves of the ileum are probably not the dominant mediators of the inhibitory action of intraileal tryptophan but rather counteract this effect.

Amino Acids↗
PubMed1999

[How to proceed? ERCP in acute pancreatitis?].

The standard treatment of acute pancreatitis is primarily supportive, including a well standardized conservative therapy and additionally specific interventions in complicated disease. The role of early endoscopic retrograde cholangiopancreatography in acute pancreatitis has been discussed for about 20 years. The etiology of pancreatitis plays an important role in making the decision for early interventional treatment. The results of clinical trials about early interventional treatment of acute biliary pancreatitis demonstrate that the outcome of patients without signs of biliary stone impaction or acute cholangitis is burdened by more severe complications than in patients treated conservatively. Urgent endoscopic retrograde cholangiopancreatography, endoscopic sphincterotomy and stone extraction within 72 hours of admission reduces the frequency of major complications only in patients with acute biliary pancreatitis with obstructive jaundice or biliary sepsis.

Acute Disease↗
PubMed1999

Immunological changes of mild acute pancreatitis in late-stage alcoholic chronic pancreatitis.

The exact immunological mechanisms underlying alcoholic chronic pancreatitis are unclear. To investigate the role of the tumor necrosis factor (TNF) receptor pathway the serum levels of TNF-alpha, soluble TNF receptors -p55/-p75, and CRP were determined by ELISA in 34 patients with late-stage alcoholic chronic pancreatitis and 28 controls. The disease activity (Balthazar scoring system) of acute pancreatitis on the background of late-stage chronic pancreatitis correlated with an increase of functionally active TNF receptor -p55/-p75 serum levels. Unstimulated peripheral blood mononuclear cells are one source of soluble TNF receptors and demonstrated a systemic leukocyte activation. The marked enhancement of soluble TNF receptors suggests that alcoholic chronic pancreatitis may be characterized by transient peaks of in situ TNF-alpha production preceding a long-lasting release of soluble TNF receptors. The data demonstrate immunological changes characteristic of acute pancreatitis in late-stage alcoholic chronic pancreatitis.

Acute Disease↗
PubMed1999

Effect of 7-day therapy with different doses of the proton pump inhibitor lansoprazole on the intragastric pH in healthy human subjects.

BACKGROUND: Systematic, randomized, and controlled studies on the effect of low to high doses of the proton pump inhibitor lansoprazole on intragastric acidity and plasma gastrin levels have not previously been performed. METHODS: We investigated the effect of 7-day therapy with different doses of lansoprazole (15 mg once or twice daily, 30 mg once or twice daily, and 15 mg three times daily) on intragastric acidity and meal-stimulated daytime plasma gastrin levels in 12 healthy Helicobacter pylori-negative human subjects in a randomized, double-blind, placebo-controlled, 6-way crossover study. On days 1, 2, and 7 of the study 24-h intragastric pH-metry and 12-h integrated daytime plasma gastrin determinations were done. RESULTS: Lansoprazole in a dose regimen of 1 x 30 mg/day, 3 x 15 mg/daily, and 2 x 30 mg/day significantly (P < 0.05) increased the intragastric 24-h median pH on days 1, 2, and 7 of therapy as compared with placebo. Lansoprazole in doses of 1 x 15 mg/day and 2 x 15 mg/day significantly increased the intragastric 24-h median pH on days 2 and 7 but not on day 1 of therapy. Doses of 3 x 15 mg and 2 x 30 mg lansoprazole daily significantly increased the intragastric 24-h median pH on days 2 and 7 of treatment as compared with 1 x 30 mg lansoprazole daily. Except for 1 x 15 mg lansoprazole on day 1 of therapy, all given dose regimens of lansoprazole (15-60 mg/day) significantly (P < 0.05) stimulated the 12-h integrated meal-stimulated daytime plasma gastrin response (pM x min) on days 1, 2, and 7 of therapy as compared with placebo. CONCLUSION: A dose of 1 x 30 mg/day is nearly as potent as higher dose regimens of lansoprazole. Thus it most likely is the optimum dose for therapy of gastric and duodenal peptic lesions. A dose of 1 x 15 mg lansoprazole daily is a potent inhibitor of gastric acid output and could be a therapeutic dose for prevention of peptic lesions (that is, reflux oesophagitis or ulcers).

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1999

Maleic acid and succinic acid in fermented alcoholic beverages are the stimulants of gastric acid secretion.

Alcoholic beverages produced by fermentation (e.g., beer and wine) are powerful stimulants of gastric acid output and gastrin release in humans. The aim of this study was to separate and specify the gastric acid stimulatory ingredients in alcoholic beverages produced by fermentation. Yeast-fermented glucose was used as a simple model of fermented alcoholic beverages; it was stepwise separated by different methods of liquid chromatography, and each separated solution was tested in human volunteers for its stimulatory action on gastric acid output and gastrin release. Five substances were detected by high-performance liquid chromatography and were analyzed by mass spectrometry and 1H-13C nuclear magnetic resonance spectroscopy. At the end of the separation process of the five identified substances, only the two dicarboxylic acids, maleic acid and succinic acid, had a significant (P < 0.05) stimulatory action on gastric acid output (76% and 70% of fermented glucose, respectively), but not on gastrin release. When given together, they increased gastric acid output by 100% of fermented glucose and by 95% of maximal acid output. We therefore conclude that maleic acid and succinic acid are the powerful stimulants of gastric acid output in fermented glucose and alcoholic beverages produced by fermentation, and that gastrin is not their mediator of action.

Adult↗
PubMed1999

Cytokine gene expression in peripheral blood mononuclear cells reflects a systemic immune response in alcoholic chronic pancreatitis.

BACKGROUND: Recent data provide evidence of a systemic inflammatory response in severe acute pancreatitis; in contrast, the exact immune mechanisms underlying chronic pancreatitis remain unclear. METHODS: To investigate the immune response in the clinical features of chronic pancreatitis, we investigated the gene expression of tumor necrosis factor-alpha (TNF-alpha), tumor necrosis factor receptor (TNFR)-p55 and -p75 and inducible nitric oxide synthase (iNOS) in peripheral blood mononuclear cells (PBMC) of 18 patients with late-stage alcoholic chronic pancreatitis of different disease activity (Balthazar criteria). RESULTS: Semiquantitative reverse transcriptase-polymerase chain reaction revealed a significantly enhanced gene expression of TNF-alpha (P < 0.05), TNFR-p55 (P < 0.05) and TNFR-p75 (P < 0.01) in unstimulated PBMC of patients with advanced chronic pancreatitis (11/18 with calcifications) compared to healthy controls (n = 8). No significant difference was found between patients with mild acute pancreatitis and patients with an inactive quiescent pancreatitis. Moreover, no expression of inducible nitric oxide synthase was detectable. CONCLUSIONS: The enhanced gene expression of TNFR-p75, TNFR-p55 and TNF-alpha in unstimulated PBMC demonstrates an enhanced leucocyte activation in patients with late-stage chronic pancreatitis and suggests a pathogenetic role of the cytotoxic TNF-alpha pathway in the clinical features of alcoholic chronic pancreatitis. The pathogenetic role of nitric oxide in chronic pancreatitis remains to be fully elucidated.

Adult↗