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Manfred V Singer

Publications and source records attributed to Manfred V Singer.

33 records · Page 2Linked to original sources
PubMed2005

Alcoholic pancreatitis.

A history of excessive alcohol consumption is found in the majority of patients with chronic pancreatitis, and numerous research efforts revealed insights into the pathogenesis of alcohol-induced pancreatic damage. However, the exact mechanisms underlying the disease are not yet clarified, and the origin of alcoholic chronic pancreatitis continues to be the topic of speculation and investigation. This article provides an overview about the epidemiology of alcoholic chronic pancreatitis, the epidemiologic association of alcohol intake and pancreatitis and the clinical course of the disease. Finally, this article summarizes several hypothetical concepts that try to explain the early and late pathophysiological mechanisms of acute and chronic pancreatitis.

Alcohol Drinking↗
PubMed2004

Poorly differentiated small cell carcinoma of the pancreas. A case report and review of the literature.

Small cell carcinoma (SCC) of the pancreas is a rare malignancy with an extremely poor prognosis. We present the case of a 74-year-old man with a 2-month history of upper abdominal discomfort who was diagnosed with SCC of the pancreas tail, involvement of peripancreatic and mesenteric lymph nodes and multiple liver metastases (extended disease). A CT scan and a positive somatostatin receptor scintigraphy showed no evidence of a primary lung tumour. The diagnosis of a SCC was confirmed by biopsy. Local tumour control could be achieved by gemcitabine once a week and a long-acting somatostatin analogue once a month, but liver metastasis showed progress. Thus, 5-fluorouracil on a weekly basis was started. The patient died 8 months after diagnosis and had not been hospitalised in the meantime.

Aged↗
PubMed2004

Predictors of disease-related concerns and other aspects of health-related quality of life in outpatients with inflammatory bowel disease.

OBJECTIVE: Disease-related concerns are a major dimension of health-related quality of life in inflammatory bowel disease (IBD). The aim of this study was to assess the concerns of IBD patients in an outpatient sample, and to determine the impact of psychological and disease factors on concerns and on other variables of health-related quality of life. METHODS: Seventy-two outpatients with IBD were assessed with regard to disease-related concerns [with the Rating Form of IBD Patients' Concerns (RFIPC)], psychological symptoms and somatic complaints non-specific to IBD as dependent variables. Coping with illness, health locus of control, and disease variables were assessed as predictor variables. Multiple regression analyses determined the independent contribution of each predictor on the dependent variables. RESULTS: Women reported more intense concerns than men. No difference in concerns was found between patients with Crohn's disease and ulcerative colitis. The highest predictive value for the RFIPC total score was found for depressive coping. It explained a greater proportion of variance on the RFIPC total score (23%) than demographic (10%) and disease variables (7%), and comparably impinged on RFIPC subscores. Furthermore, depressive coping was significantly associated with psychological distress, the self-rated health status and somatic complaints non-specific to IBD. CONCLUSIONS: Our findings suggest that in IBD psychological variables, particularly depressive coping, are more predictive than medical variables for disease-related concerns and other variables of health-related quality of life. Further studies are needed to examine the effects that the way of coping with disease have on long-term outcome in IBD.

Adaptation, Psychological↗
PubMed2003

Hepatitis B core antigen is a potent inductor of interleukin-18 in peripheral blood mononuclear cells of healthy controls and patients with hepatitis B infection.

Clearance of hepatitis B virus infection (HBV) infection implies a polyclonal vigorous T-helper 1 (Th1) and cytotoxic T-lymphocyte (CTL) response. Interleukin-18 (IL-18), a monokine that shares functional abilities with IL-12, is a potent inductor of interferon-gamma (IFN-gamma) by Th1 and natural killer (NK) cells. However, the role and regulation in HBV infection of IFN-gamma have not been defined. This study therefore sought to determine hepatitis B core antigen (HBcAg)-mediated regulation of IL-18 production in peripheral blood mononuclear cells (PBMCs) from healthy controls (HC) and patients with chronic hepatitis B (CHB) or acute hepatitis B (AHB); 31 HC, 27 patients with CHB and 8 patients with AHB infection were included in the study. HBcAg-mediated induction of IL-18 was determined by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and specific enzyme-linked immunosorbent assay (ELISA). HBcAg induced IL-18 gene transcription and dose-dependent secretion of mature IL-18 protein in HC, CHB, and AHB. HBcAg-dependent IL-18 levels were abrogated by inhibition of Caspase-1, but not by blockade of CD40-CD154 interaction. Serum levels of IFN-gamma correlated inversely with viremia in patients with CHB (rho = - 0.54, P < 0.05), but not with serum levels of IL-12 or IL-18. Interestingly, in PBMCs of HBeAg-negative patients, HBcAg induced significantly higher amounts of IL-18 than in those of HBeAg-positive patients. A variant, lacking the histone-like arginine-rich domain, did not induce IL-18 in either HC or CHB in vitro. Taken together, these results indicate that HBcAg induces IL-18 secretion by induction of Caspase-1. Differential regulation in HBeAg-negative and positive patients suggests an important role of IL-18 in CHB infection.

Adult↗
PubMed2003

Animal models in gastrointestinal alcohol research-a short appraisal of the different models and their results.

Alcohol-related diseases of the gastrointestinal tract play an important role in clinical gastroenterology. However, the mechanisms and pathophysiology underlying the effects of ethanol on the organs of the digestive tract are not yet completely understood. Animal models represent an essential tool for investigating alcohol-related diseases because they give researchers the opportunity to use methods that cannot be used in humans, such as knockout technology. However, there is still a need for new animal models resembling the human condition, since for some alcohol-related diseases such as chronic alcoholic pancreatitis, the ideal animal model does not yet exist. In this chapter, we provide an overview of the most commonly used animal models in gastrointestinal alcohol research. We will also briefly discuss the current concepts of the pathophysiological mechanisms involved in acute and chronic alcoholic damage of the oesophagus, stomach, small and large intestine, pancreas and liver.

Alcohol Drinking↗
PubMed2003

Alcohol-related diseases of the oesophagus and stomach.

This chapter deals with the most clinically relevant alcohol-related diseases of the oesophagus and stomach. Despite the early findings of W. Beaumont 170 years ago that excessive drinking is associated with gastric bleeding, systematic studies on the action of alcohol and alcoholic beverages on the function of the stomach have only been performed in the last 15 years. The aim of this review is to summarize the data on the effect of acute and chronic alcohol consumption/abuse on the oesophagus and stomach.

Alcohol Drinking↗
PubMed2003

A comparative study on alcohol-preferring rat lines: effects of deprivation and stress phases on voluntary alcohol intake.

BACKGROUND: Voluntary alcohol intake in rats can be influenced by alcohol deprivation phases and stress. We investigated the magnitude of the effects of both deprivation and stress (forced swimming in cold water and foot-shock had been chosen as stressors distinct in their physical and psychological features) on alcohol intake and the influence of these experiences on the time course of alcohol drinking behavior. For the alcohol drinking procedure, a long-term model of alcohol self-administration originally developed for heterogeneous Wistar rats was used and was compared with different alcohol-preferring rat lines. METHODS: Adult male Alko alcohol (AA), alcohol-preferring (P), high-alcohol-drinking (HAD), and unselected Wistar rats were given ad libitum access to water, 5%, and 20% alcohol solutions for 6 months. A deprivation phase of 14 days was performed after 8 weeks of access to alcohol. After 16 weeks and 22 weeks of alcohol access, all animals were subjected to forced swimming and foot-shock, respectively, for 3 consecutive days, while alcohol intake was still being measured. RESULTS: Alcohol deprivation led to a significant increase in alcohol intake in Wistar rats and P rats. No alcohol deprivation effect was observed in HAD and AA rats; after deprivation, however, their preference for the 20% alcohol solution increased, immediately in the HAD rats and gradually over time in the AA rats. Repeated swim stress caused an increase in alcohol intake in Wistar rats but no changes in the alcohol-preferring rat lines. Foot-shock stress increased alcohol consumption in all lines of rats, but the most pronounced effects were observed in HAD and P rats. CONCLUSIONS: Wistar, HAD, P, and AA rats differentially respond to alcohol deprivation and stress, showing that the genetic background of these different rat lines profoundly affects relapse-like drinking and stress-induced drinking.

Alcohol Drinking↗
PubMed2003

Control of pancreatic exocrine secretion via muscarinic receptors: which subtype(s) are involved? A review.

The present report gives an overview of the experimental, pharmacological and molecular investigations that have been undertaken during the past two decades to characterize and identify the muscarinic receptor subtype(s) involved in the cholinergic control of pancreatic exocrine secretion in humans and different animal species. The results published in the literature clearly indicate that both M1 and M3 receptors contribute to the regulation of pancreatic enzyme secretion, although contradictory conclusions have been drawn from secretory studies using specific M1 and M3 receptor antagonists in vivo and in vitro. Binding studies using specific M1 and M3 receptor antagonists have supported the existence of both M1 and M3 receptors on pancreatic acinar cells, which was confirmed by the demonstration of specific mRNA for both receptor subtypes in rat pancreatic acinar cells. In addition, experimental evidence exists that nonacinar (possibly presynaptic) M1 receptors also contribute to the control of pancreatic enzyme secretion. The role of the different muscarinic receptor subtypes in the control of pancreatic fluid and bicarbonate output, however, still needs to be clarified. Future research should cover the evaluation of the relative contribution of the different receptor subtypes to the regulation of pancreatic exocrine function, the localization of the receptors involved as well as possible species differences.

Animals↗
PubMed2002

Responsiveness of intestinal epithelial cell lines to lipopolysaccharide is correlated with Toll-like receptor 4 but not Toll-like receptor 2 or CD14 expression.

BACKGROUND AND AIMS: Luminal bacteria have been implicated in the pathogenesis of inflammatory bowel diseases. Exposure of intestinal epithelial cells (IEC) to bacterial components potentially initiates intestinal inflammation by release of chemokines and recruitment of inflammatory cells. We analyzed receptor expression and signaling pathways involved in activation of human primary IEC and carcinoma-derived cell lines by lipopolysaccharide (LPS). MATERIALS AND METHODS: HT-29/p, HT-29/MTX, and Caco-2 cells were stimulated by LPS. IL-8 content in supernatants was analyzed by ELISA, and expression of CD14, Toll-like receptor (TLR) 2 and TLR 4 was determined by RT-PCR. Presence of TLR 4 protein was assessed by western blot analysis. LPS response was modulated by sCD14, LPS-binding protein, neutralization of CD14, and inhibitors of early signal activation. RESULTS: LPS dose-dependently induced secretion of IL-8 in undifferentiated HT-29/p cells while Caco-2 and permanently differentiated HT-29/MTX cells were unresponsive. Differently to HT-29/MTX, both HT-29/p and Caco-2 cells constitutively expressed transcripts for CD14. However, CD14 was not required for LPS-mediated induction of IL-8 in HT-29/p cells since neutralizing anti-CD14 antibodies left IL-8 levels unchanged. Unresponsiveness of Caco-2 and HT-29/MTX cells to LPS persisted in the presence of sCD14 and/or LPS-binding protein. Neither cell line expressed TLR 2 transcripts while only responsive HT-29/p cells expressed TLR 4 mRNA and TLR 4 protein. Butyrate down-regulated TLR 4 expression and significantly diminished LPS-dependent IL-8 secretion. Inhibition of G protein dependent kinase activation reduced IL-8 levels to 50%; the phosphatidyl-inositol-3'-kinase inhibitor LY294002 abrogated the response. CONCLUSION: Responsiveness of IEC lines to LPS is positively correlated with TLR 4 expression. Strategies targeting TLR 4 expression or TLR 4 mediated signaling may antagonize IEC activation by LPS.

Cross Reactions↗
PubMed2002

Enhanced production of IL-18 in butyrate-treated intestinal epithelium by stimulation of the proximal promoter region.

Expression of IL-18 in intestinal epithelial cells (IEC) has been implicated in Th1 cell-mediated chronic intestinal inflammation and anti-tumor immunity. However, physiological regulatory factors have not been identified. Besides their effects on proliferation and restitution, immunomodulatory functions have been attributed to short chain fatty acids (SCFA). We investigated the effect of SCFA (butyrate, propionate, acetate) on expression of IL-18 in IEC in vitro and in vivo. Expression of IL-18 mRNA and protein in human carcinoma-derived HT-29 and Caco-2 cells was analyzed by reverse transcription-PCR and Western blot. Transcriptional regulation of IL-18 gene expression was determined by transient transfection of wild-type and mutated IL-18 promoter. Further, in vivo expression of IL-18 in the intestine from butyrate-treated and untreated mice was assessed by immunohistochemistry. IL-18 mRNA and the IL-18 protein were expressed in IEC, while IL-18 secretion was not observed. Butyrate and acetate increased intracellular IL-18 content in a time- and dose-dependent fashion. In contrast to proinflammatory stimuli butyrate potently activated the IL-18 promoter, indicating that IL-18 is regulated at the transcriptional level by SCFA. Furthermore, a 108-bp sequence in the proximal region was identified to be essential for IL-18 promoter activation by butyrate. As proof of principle butyrate effects were confirmed in vivo by demonstration of increased IL-18 protein expression in IEC from butyrate-treated mice. In conclusion, SCFA up-regulate IL-18 protein expression in IEC, suggesting a potential regulatory contribution of these luminal constituents to T cell mediated inflammatory and neoplastic intestinal conditions.

Acetates↗
PubMed2002

Animal models in alcoholic pancreatitis--what can we learn?

Although the majority of patients with chronic pancreatitis present a history of excessive alcohol consumption, the pathophysiology underlying chronic alcoholic pancreatitis remains poorly defined. Since experimental animal models represent helpful tools in understanding human disease, numerous laboratory studies have been designed to study the effects of alcohol on the pancreas. In the present article we summarize the existing animal models that have been used to investigate the effects of acute and chronic alcohol application on the development of morphological alterations and pancreatic injury. Despite considerable experimental effort, acute or chronic ethanol feeding alone failed to cause acute or chronic pancreatitis in animals. However, ethanol-feeding and the combination with other procedures has demonstrated several mechanisms that play a role in ethanol-induced pancreatic injury. Among these ethanol-induced alterations and mechanisms are the reduction of pancreatic blood-flow and microcirculation, damaging effects of ethanol metabolites, increased pancreatic acinar cell expression of digestive and lysosomal enzymes, increased glandular enzyme content, additional nutritional factors, pancreatic duct obstruction, and limitations of pancreatic regeneration. Although no satisfactory animal model for alcoholic pancreatitis has been developed, these animal models have provided insights in several factors that predispose the pancreas to development of pancreatic injury and contribute to alcoholic pancreatitis.

Alcohol Drinking↗
PubMed2002

Effect of ethanol and alcoholic beverages on the gastrointestinal tract in humans.

Alcohol abuse ranks among the most common and severe environmental hazards to human health. Alcohol is a dependence producing drug and this dependence is associated with an increased risk of morbidity and mortality. While the social and behavioural consequences of alcoholism including psychiatric disorders are staggering, the manifestation of alcohol-related diseases is the most widespread somatic effect. In research conducted both at the social and individual level, alcohol was found to increase the risk of death from a number of specific causes, including injury from traffic accidents and other trauma, violence, suicide, liver cirrhosis, cancer of the liver, breast cancer, haemorrhagic stroke, alcoholic psychosis, alcohol dependence and chronic pancreatitis. The apparent beneficial effect of modest alcohol consumption (one to three drinks per day) on mortality and morbidity rates particularly relating to cardiovascular disease on the other side are of recent interest. Public health policy should aim at reducing the harm done by alcohol use, whilst recognizing its perceived and possible real benefits. The aim of this review is to introduce the reader to the definition of alcohol dependence and alcoholism, and summarize our knowledge about the effects of alcohol consumption on the gastrointestinal tract.

Alcoholic Beverages↗
PubMedDate not supplied

Submucosal hypoganglionosis causing chronic idiopathic intestinal pseudo-obstruction.

A 39-year-old woman presented with recurrent symptoms suggestive of intestinal obstruction. She was put on total parenteral nutrition (TPN) and consequently developed sepsis and endocarditis. TPN was stopped and a venting enterostomy was performed. Biopsies of mucosa and submucosa were taken at surgery; immunohistochemistry for neuronal proteins, protein gene product 9.5 (PGP 9.5) and the glial S-100-protein was done. Many enlarged nerve fiber strands were found in the submucosa. Few small ganglia containing a small number of nerve cells could be observed, suggesting hypoganglionosis. This patient with chronic idiopathic intestinal pseudoobstruction of neurogenic type had a defect in the submucous plexus, whereas visceral neuropathies are usually characterized by defects of the myenteric plexus with normal submucous plexus.

Adult↗