PubMed Health⌕ Search

Biomedical subjects

Manfred V Singer

Publications and source records attributed to Manfred V Singer.

At least 19 recordsLinked to original sources
PubMed2006

Role of the jejunum versus ileum on intestinal gas dynamics during a balanced meal in healthy subjects.

Under physiological conditions, the human gut adapts intestinal gas propulsion and evacuation to prevent intestinal gaseous complaints In this study we aimed to determine influences of the jejunum versus ileum on intestinal gas dynamics during a balanced meal. Paired studies were randomly performed with seven women and three men, ages 28-42. A mixed liquid meal was infused (1 kcal/min) into the duodenum. After 30 min, gas was infused (12 ml/min) into the jejunum or ileum for 150 min. Gas expulsion was measured, and perception and girth changes were assessed. Postprandial intestinal gas propulsion was uneventful and recovery complete, with -7+/- 58 and -92+/- 44 ml final intestinal gas retention for jejunal and ileal gas infusion, respectively. Neither significant differences in abdominal perception nor changes in abdominal girth were seen. During a balanced meal, intestinal gas is effectively propulsed aborally, and this does not depend on the site of the small intestinal stimulation.

Adult↗
PubMed2006

Life-threatening intoxication with methylene bis(thiocyanate): clinical picture and pitfalls. A case report.

BACKGROUND: Methylene bis(thiocyanate) (MBT) is a microbiocidal agent mainly used in industrial water cooling systems and paper mills as an inhibitor of algae, fungi, and bacteria. CASE PRESENTATION: We describe the first case of severe intoxication following inhalation of powder in an industrial worker. Profound cyanosis and respiratory failure caused by severe methemoglobinemia developed within several minutes. Despite immediate admission to the intensive care unit, where mechanical ventilation and hemodialysis for toxin elimination were initiated, multi-organ failure involving liver, kidneys, and lungs developed. While liver failure was leading, the patient was successfully treated with the MARS (molecular adsorbent recirculating system) procedure. CONCLUSION: Intoxication with MBT is a potentially life-threatening intoxication causing severe methemoglobinemia and multi-organ failure. Extracorporeal liver albumin dialysis (MARS) appears to be an effective treatment to allow recovery of hepatic function.

Journal Article↗
PubMed2006

Enteropancreatic reflexes mediating the pancreatic enzyme response to nutrients.

The observation that in dogs electrical stimulation of the vagus nerve elicited a strong secretory activity of the pancreas, prompted I. P. Pavlov in 1888 to conclude that the pancreatic secretory response to nutrients is mediated by enteropancreatic reflexes involving the vagus nerves. It took, however, more than 90 years until by studying the latency of pancreatic amylase response to exogenous and endogenous stimuli for the first time experimental evidence was provided for the actual existence of cholinergic vago-vagal enteropancreatic reflexes. Follow-up studies, based on stepwise extrinsic denervation of the pancreas, ruled out possible splanchnic pathways for enteropancreatic reflexes. In more recent years, experiments utilizing specific antagonists demonstrated a physiological role for both cholinergic M1 and cholecystokinin (CCK) receptors within the enteropancreatic reflex. At least a significant portion of the cholinergic fibres of the enteropancreatic reflex end on muscarinic receptors of the subtype M1. CCK, the most important hormone stimulating pancreatic enzyme secretion, appears to act at least in part on CCK receptors located on vagal afferent nerves, which in turn elicit a vago-vagal reflex, implying that CCK exerts its effect on the pancreas at least in part through vago-vagal reflexes. Furthermore, pharmacological blockade of CCK receptors totally abolished the early pancreatic amylase response to intestinal nutrients, suggesting that the activation of (probably vagal) CCK receptors is essential to run the enteropancreatic reflex.

Animals↗
PubMed2006

Effect of high- and low-caloric mixed liquid meals on intestinal gas dynamics.

High-caloric meals can evoke postprandial abdominal complaints involving disturbances in intestinal gas balance. We aimed to determine the influence of the caloric content of meals on intestinal gas dynamics. Eight healthy subjects (five women, three men; age range, 25-43 years) underwent paired studies with low (1 kcal/min)- and high (3 kcal/min)-caloric meal infusion 35% fat, (45% carbohydrate, 20% protein) into the duodenum in random order and proximal jejunal gas infusion. Gas evacuation, perception, and abdominal girth were assessed. The low-caloric meal caused neither gas retention (-7 +/- 58 ml) nor girth changes (0 +/- 0 mm). In contrast, the high-caloric meal led to significant gas retention (705 +/- 56 ml) and increased abdominal perimeter (7 +/- 1 mm; P < 0.001 vs. the low-caloric meal for both). Thus, a high caloric load of nutrients arriving at the duodenum modulates both intestinal gas transit and abdominal perimeter.

Adult↗
PubMed2006

Severe TNF receptor-associated periodic syndrome due to 2 TNFRSF1A mutations including a new F60V substitution.

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is typically characterized by episodic fever, myalgia, skin rash, conjunctivitis, and abdominal cramps. Recently, mutations in the TNFRSF1A gene on chromosome 12p13 encoding tumor necrosis factor receptor type 1 have been linked to this autoinflammatory syndrome. We report the case of a 29-year-old white woman who experienced periodic inflammatory manifestations with fever up to 40 degrees C, leukocytosis, and elevation of C-reactive protein level (>100 mg/L) in conjunction with acute peritonitis of unknown origin since the age of 19 years. The patient had undergone 2 laparotomies with appendectomy and left hemicolectomy. Familial Mediterranean fever was excluded by sequencing of the MEFV gene. In view of the possibility of TRAPS, sequence analysis of the TNFRSF1A gene was also performed. The patient carried a novel T-->G substitution in exon 3, leading to the replacement of phenylalanine by valine at amino acid position 60 (F60V), as well as the common R92Q low-penetrance mutation, encoded by exon 4. Upon the next flare, the patient started corticosteroid therapy, resulting in complete relief and normalization of elevated C-reactive protein levels. To the best of our knowledge, we report the first case of compound heterozygosity for 2 TNFRSF1A gene mutations, including a novel one that causes a severe form of TRAPS that responds to anti-inflammatory treatment. A history of recurrent sterile peritonitis should prompt genotyping for periodic fever syndromes.

Adult↗
PubMed2006

Duodenal infusion of different nutrients and the site of gaseous stimulation influence intestinal gas dynamics.

OBJECTIVE: Excessive intestinal gas can be involved in postprandial abdominal symptom generation, but whether the small bowel influences intestinal gas dynamics, depending on the ingested meal, remains to be demonstrated. We compare the intestinal response to a proximal and distal small intestinal gas challenge during different duodenal nutrient components. MATERIAL AND METHODS: We randomly studied 32 healthy subjects, twice, on different days with a gas mixture infused at 12 ml/min either directly into the proximal jejunum or into the ileum; during duodenal lipids, amino acids, glucose, at 1 kcal/min each, or saline (n=8 for each group). Gas evacuation was monitored continuously and abdominal perception and girth changes were assessed. RESULTS: In response to the jejunal gas challenge, duodenal lipids delayed intestinal gas clearance more potently than amino acids (733+/-26 ml and 541+/-108 ml final gas retention; p<0.001), but when gas was directly infused into the ileum the retained volumes were much smaller (271+/-78 ml and 96+/-51 ml; p<0.001). During duodenal glucose, intestinal gas clearance following jejunal or ileal gas infusion was not significantly influenced. Abdominal perception in response to the jejunal and ileal gas challenge only increased slightly during duodenal lipids (2.0+/-0.3 score and 2.3+/-0.6 score; p<0.05 versus control). CONCLUSION: Postprandial intestinal gas clearance is hampered by duodenal lipids and amino acids but not by glucose. Specific inhibitory effects are more pronounced when gas is infused into the jejunum, which underlines the importance of the small intestine in postprandial gas retention.

Adult↗
PubMed2006

Effects of low-dose warfarin and regional chemotherapy on survival in patients with pancreatic carcinoma.

OBJECTIVE: To report the effect of regional combination chemotherapy in a cohort of patients with inoperable pancreatic carcinoma treated with or without low-dose warfarin. MATERIAL AND METHODS: A retrospective analysis was performed on 180 patients with pancreatic carcinoma. Patients received one of seven regimens of chemotherapy. Unrelated to the type of chemotherapy, some patients received 1.25 mg warfarin daily. The primary end-point was median survival. RESULTS: Treatment with warfarin resulted in improved median survival from the start of regional therapy (warfarin versus no warfarin: 5.0 versus 2.3 months, n = 111 versus 69; p < 0.0001). This effect was not dependent on the type of chemotherapy used. Among the seven regimens examined, the one consisting of regional gemcitabine and mitomycin-C with systemic gemcitabine was associated with the longest median survival of 5.1 months from the start of regional therapy (p = 0.006) and 12.7 months from diagnosis. This regimen combined with warfarin was associated with improved median survival (7.1 months, n = 32). CONCLUSIONS: Treatment with low-dose warfarin improved survival irrespective of the chemotherapy received. Of the regimens examined, the combination of regional gemcitabine and mitomycin-C with systemic gemcitabine was associated with the longest survival time. Survival was increased further by the addition of warfarin. These data provide a rationale, based on safety and efficacy, for a definitive study on the use of warfarin and combined regional and systemic chemotherapy in patients with pancreatic carcinoma.

Antibiotics, Antineoplastic↗
PubMed2005

Low-dose exposure of intestinal epithelial cells to formaldehyde results in MAP kinase activation and molecular alteration of the focal adhesion protein paxillin.

We investigated the potential pathophysiological role of non-lethal formaldehyde concentrations on human intestinal epithelial HT-29 cells. Expression levels of actin, tubulin and detectable cytokeratin isoforms 5, 13, 18, 19 and 20 were not affected after 24h of exposure to 1mM formaldehyde. By contrast, cellular organization of cytoskeletal constituents was already changed after 60 min. Within 15 min, formaldehyde induced profound tyrosine phosphorylation of the focal adhesion protein paxillin and of proteins at about 120-130 kDa. Concomitantly, phosphorylation of ERK-1/2 and p38 MAP kinase occurred. Paxillin was not only tyrosine phosphorylated but underwent a sustained molecular weight shift representing serine/threonine phosphorylation that was independent of MAP kinase activity and EGF-R-mediated signalling. Our data show that exposure of intestinal epithelial cells to low-dose formaldehyde is followed by rapid and profound signalling events. The data suggest a modifier role of environmental or endogenous formaldehyde for epithelial cell functions.

Alkaline Phosphatase↗
PubMed2005

Sclerosing cholangitis following severe trauma: description of a remarkable disease entity with emphasis on possible pathophysiologic mechanisms.

AIM: Persistent cholestasis is a rare complication of severe trauma or infections. Little is known about the possible pathomechanisms and the clinical course. METHODS: Secondary sclerosing cholangitis was diagnosed in five patients with persistent jaundice after severe trauma (one burn injury, three accidents, one power current injury). Medical charts were retrospectively reviewed with regard to possible trigger mechanisms for cholestasis, and the clinical course was recorded. RESULTS: Diagnosis of secondary sclerosing cholangitis was based in all patients on the primary sclerosing cholangitis (PSC)-like destruction of the intrahepatic bile ducts at cholangiography after exclusion of PSC. In four patients, arterial hypotension with subsequent ischemia may have caused the bile duct damage, whereas in the case of power current injury direct thermal damage was assumed to be the trigger mechanism. The course of secondary liver fibrosis was rapidly progressive and proceeded to liver cirrhosis in all four patients with a follow-up >2 years. Therapeutic possibilities were limited. CONCLUSION: Posttraumatic sclerosing cholangitis is a rare but rapidly progressive disease, probably caused by ischemia of the intrahepatic bile ducts via the peribiliary capillary plexus due to arterial hypotension. Gastroenterologists should be aware of this disease in patients with persistent cholestasis after severe trauma.

Accidents↗
PubMed2005

Effect of acute hyperglycemia on intestinal gas transit and tolerance in nondiabetic humans.

BACKGROUND: Acute hyperglycemia usually inhibits gastrointestinal motility and hyperinsulinemia may contribute to specific inhibitory effects. However, the influences on postprandial intestinal gas dynamics have not been investigated. AIMS: To compare effects of euglycemic hyperinsulinemia and acute fasting hyperglycemia on intestinal gas dynamics in nondiabetics. METHODS: On 3 separate days, 10 healthy volunteers were evaluated in randomized order with duodenal glucose, intravenous glucose or saline infusion. Rectal gas evacuation was continuously measured; perception and abdominal girth changes were separately evaluated. After 60 min equilibration, proximal jejunal gas infusion (12 ml/min) was started for 150 min. RESULTS: Acute hyperglycemia failed to cause significant intestinal gas retention (72 +/- 64 ml and 53 +/- 29 ml final gas retention vs. saline); in contrast, gas clearance was expedited, with a maximal effect between 30 and 105 min (p < 0.001 vs. control). Euglycemic hyperinsulinemia did not significantly influence intestinal gas clearance and no relevant changes of abdominal girth or abdominal and rectal perception were seen, as compared to control (p > 0.05 for all parameters). CONCLUSION: Accelerated intestinal gas clearance under hyperglycemia is one physiologic factor to avoid postprandial intestinal gas accumulation. Specific underlying mechanisms, which need further investigation, may be disturbed in symptomatic patients.

Abdomen↗
PubMed2005

The effect of ethanol and alcoholic beverages on gastric emptying of solid meals in humans.

AIMS: The systematic study of the effect of pure ethanol, alcoholic beverages, and their non-alcoholic components on gastric emptying of solid meals in humans. METHODS: 16 fasting healthy male subjects received once weekly 300 ml of the following solutions in random order: 4 and 10% (v/v) ethanol, beer, red wine, 5.5 and 11.4% (w/v) glucose, and water. The test solutions were given either together with a low caloric (270 kcal, n = 8) or a high caloric (740 kcal, n = 8) solid meal. Ultrasonography of the antrum was used to determine gastric emptying. RESULTS: Gastric half emptying time (t(1/2) ) of the high caloric solid meal with water was 131.3 +/- 7 min. The ingestion of 4 and 10% (v/v) ethanol (158.8 +/- 9.3 and 165.6 +/- 6.2 min, respectively), beer (163.1 +/- 11 min), and red wine (186.3 +/- 8.4 min) resulted in a significantly longer t(1/2) than water. The lag phases after 4 and 10% (v/v) ethanol, beer, and red wine were not significantly different from that of water (48.1 +/- 6.5 min). Compared with water, the ingestion of 5.5 and 11.4% (w/v) glucose resulted in a significantly longer t(1/2) (153.8 +/- 5 and 168.1 +/- 14.4 min, respectively) by increasing the duration of the lag phase. The high caloric meals resulted in a 2-fold prolongation of t(1/2) when compared with the low caloric meals. The effect of the solutions on the gastric emptying times, however, was similar for both test meals. CONCLUSIONS: (i) Ethanol in low concentrations of 4 and 10% (v/v) prolongs gastric emptying of solid meals; this inhibitory effect is not dose-dependent. (ii) Alcoholic beverages (beer and red wine) also result in a prolongation of gastric emptying. The inhibitory effect of red wine, but not of beer, is more pronounced than that of the corresponding ethanol concentration and amount. (iii) The inhibitory effect of ethanol and alcoholic beverages is mainly induced by a prolongation of the gastric emptying phase (without affecting the lag phase), whereas 5.5 and 11.4% (w/v) glucose prolong the lag phase in a dose-dependent manner. (iv) The inhibitory effect of ethanol, beer, and red wine on gastric emptying does not depend on the caloric content of the meal.

Adult↗
PubMed2005

-137 (G/C) IL-18 promoter polymorphism in patients with inflammatory bowel disease.

OBJECTIVE: There is strong evidence that genetic factors contribute to the susceptibility for inflammatory bowel diseases (IBD). Recently, IL-18 promoter polymorphisms were characterized as risk factors for inflammatory diseases such as sepsis, asthma and adult-onset Still's disease. The aim of this study was to determine whether the -137 (G/C) IL-18 promoter polymorphism was associated with IBD susceptibility. MATERIAL AND METHODS: For association analysis, 470 patients with Crohn's disease (CD), 235 unrelated patients with ulcerative colitis (UC) and 347 controls were enrolled. Furthermore, 233 UC and 470 CD trios were included for segregation analysis. Genotyping was performed by application of the TaqMan MGB biallelic discrimination system. RESULTS: When comparing genotype frequencies of CD and UC patients versus controls, no significant difference was found (p=0.089 and p=0.078, respectively). However, the Cochran-Armitage trend test revealed a rising probability for CD and UC with increasing number of G alleles (p=0.030 and 0.028, respectively) for the case-control analysis. On the contrary, the family-based transmission disequilibrium test (TDT) did not show an association of the G allele with CD or UC in 470 CD and 233 UC trios (p=0.53 and p=0.79, respectively). CONCLUSION: The -137 (G/C) IL-18 promoter polymorphism is not a susceptibility factor for IBD in a German cohort.

Adult↗
PubMed2005

Influence of age at drinking onset on long-term ethanol self-administration with deprivation and stress phases.

BACKGROUND: Onset of alcohol use during adolescence has potentially long-lasting consequences, e.g., prospective alcohol dependence. To obtain new insight into the effects of early chronic ethanol consumption, we compared the drinking behavior of two adult male Wistar rat groups: one that initiated alcohol consumption during adolescence (adolescent group) and the other that initiated their drinking during adulthood (adult group) in a model of long-term alcohol self-administration. We investigated the magnitude of the effects of deprivation and stress on alcohol intake and the influence of these events on the alcohol drinking behavior across time. METHODS: Heterogeneous Wistar rats aged 31 days (adolescents) and 71 days (adults) were given ad libitum access to water, as well as 5% and 20% ethanol solutions during an observation period of 30 wk. A deprivation phase of 14 days was instituted after eight wk of access to alcohol. After 16 and 26 wk of alcohol access, all animals were subjected for three consecutive days to forced swimming and electric foot shocks, respectively. RESULTS: At the onset of drinking, adolescent animals consumed less alcohol and showed lower preference than adults. The deprivation phase was followed by increased intake of highly concentrated ethanol solution without appreciable differences between age groups. Repeated swim stress produced a slight increase in ethanol consumption in both animal groups; however, alcohol intake was not significantly different between groups, whereas the foot shock stress-induced increase in alcohol intake was significantly higher in the animal group that initiated alcohol consumption during adolescence. After swim stress, the drinking behavior of the adolescent group resembled that of the adult group. In particular, the adolescent group increased their preference for 20% ethanol solution for the remainder of the experiment. CONCLUSIONS: Age of voluntary alcohol drinking onset does not appear to be a strong predictor for prospective alcohol intake and relapse-like drinking behavior under the present experimental conditions. However, male Wistar rats that initiated alcohol consumption during adolescence seem to be more susceptible to acute stressor-specific effects in terms of alcohol consumption.

Age Factors↗
PubMed2005

Comorbid alcohol and nicotine dependence: from the biomolecular basis to clinical consequences.

This article represents the proceedings of a symposium presented at the 12th Congress of the International Society for Biomedical Research on Alcoholism held in Heidelberg/Mannheim, Germany, on October 1, 2004. The organizers and cochairs were Nassima Ait-Daoud, MD, and Gerhard A. Wiesbeck, MD. The presentations included the following:L (1) The Role of Nicotinic Acetylcholine Receptors in Alcohol-Seeking Behavior, by Przemyslaw Bienkowski, MD, PhD; (2) Utilization of Linkage Analysis Combined with Microarray Technology to Identify Genes and Mechanisms Underlying Nicotine and Alcohol Use and Abuse in Humans and Rodents, by Ming D. Li, PhD; (3) Smoking and Alcoholic Chronic Pancreatitis: The Underestimated Risk?, by Roland H. Pfützer, MD; (4) Anticraving Medication in Alcohol and Nicotine Dependence, by Otto M. Lesch, MD, PhD; and (5) Pharmacotherapy for Promotion of Abstinence from Nicotine Among Alcohol-Dependent Individuals, by Bankole A. Johnson, DSc, MD, PhD.

Alcohol Deterrents↗
PubMed2005

Anti-TGF-beta strategies for the treatment of chronic liver disease.

Permanent alcohol abuse may lead to chronic liver injury with deleterious sequelae such as liver cirrhosis and hepatocellular carcinoma. Mechanisms of fibrogenesis encompass recruitment of inflammatory cells at the site of injury and cytokine mediated activation of hepatic stellate cells (HSC) with accumulation of interstitial collagens. HSC transdifferentiation and accompanying apoptosis result in destruction of liver architecture and are therefore key steps of disease progression. TGF-beta represents the main profibrogenic cytokine in liver fibrosis and other fibroproliferative disorders by inducing extracellular matrix deposition as part of the wound healing response. In parallel, TGF-beta triggers hepatocytes that are strongly responsive for this cytokine, to undergo apoptosis, thereby providing space for HSC proliferation and generation of a collagenous matrix. Anti TGF-beta approaches were established and successfully utilized for the treatment of experimental fibrogenesis. Dominant negative TGF-beta receptors (TbetaR), generated by fusing the Fc domain of human IgG and the N-terminal (extracellular) fragment of TbetaRII (Fc:TbetaRII) were applied to suppress fibrosis. Similarly TGF-beta binding proteins like decorin, antagonistic cytokines such as bone morphogenetic protein-7, hepatocyte growth factor, IL-10, or IFN-gamma were as efficient as camostat mesilate, a protease inhibitor that possibly abrogated proteolytic activation of TGF-beta. Further, our group recently overexpressed Smad7 in bile duct ligation induced liver fibrosis and achieved efficient inhibition of intracellular TGF-beta signaling, thereby counteracting profibrogenic effects in cultured HSC and in vivo. A direct link between the effect of alcohol and TGF-beta exists through reactive oxygen species that are generated in liver cells by alcohol metabolism and represent activators of TGF-beta signaling. Thus, soluble TbetaRII expression reduced experimental fibrogenesis in vitro and in vivo partially by decreasing intracellular ROS and inhibiting NADH oxidase. Approaches that specifically target profibrogenic TGF-beta signaling are promising to treat alcoholic liver disease in the future. However, to ensure safety for the patients to be treated, approaches with strong specificity need to be established. Therefore, it is essential to delineate the profibrogenic actions of TGF-beta and the influence of alcohol abuse in molecular detail.

Animals↗
PubMed2005

Animal models and their results in gastrointestinal alcohol research.

Alcohol-induced diseases of the gastrointestinal tract play an important role in clinical gastroenterology. However, the precise pathophysiological mechanisms are still largely unknown. Alcohol research depends essentially on animal models due to the fact that controlled experimental studies of ethanol-induced diseases in humans are unethical. Animal models have already been successfully applied to disclose and analyze molecular mechanisms in alcohol-induced diseases, partially by using knockout technology. Because of a lack of transferability of some animal models to the human condition, results have to be interpreted cautiously. For some alcohol-related diseases like chronic alcoholic pancreatitis, the ideal animal model does not yet exist. Here we provide an overview of the most commonly used animal models in gastrointestinal alcohol research. We will also briefly discuss the findings based on animal models as well as the current concepts of pathophysiological mechanisms involved in acute and chronic alcoholic damage of the esophagus, stomach, small and large intestine, pancreas and liver.

Alcohol-Related Disorders↗
PubMed2005

Alcohol-related diseases of the esophagus and stomach.

The present review summarizes the clinically relevant effects of acute and chronic alcohol consumption on motility, mucosal inflammation and cancer of the esophagus and the stomach. Alcohol consumption results in a significant increase in the morbidity of these two organs, the most important probably being the significant increase in the development of esophageal cancer. This review refers to epidemiologic and systematic experimental data to elucidate the clinical impact of alcohol consumption as well as the underlying alcohol-induced pathophysiologic mechanisms for these esophageal and gastric diseases. Much research is still needed to clarify the effects of alcohol itself and the byproducts that result during the production of the different types of alcoholic beverages on dismotility and mucosal injury to the esophagus and stomach.

Alcohol Drinking↗