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Showing papers in "Best Practice & Research in Clinical Gastroenterology in 2003"


Journal ArticleDOI
TL;DR: In vitro or in vivo experimental studies in which the antimicrobial activity of selected Lactobacillus and Bifidobacterium strains has been documented are analyzed.
Abstract: Probiotic lactic acid strains are live micro-organisms that, when consumed in adequate amounts as part of food, confer a health benefit on the host. The scientific basis for the use of selected probiotic strains has only recently been firmly established, and appropriate and well-conducted experimental in vitro and in vivo studies, as well as clinical studies, are now beginning to be published, especially with regard to the effectiveness of probiotic strains in antagonizing pathogens. In particular, experimental data have allowed new insights into selected probiotic strains that express strain-specific probiotic properties and into the mechanism of action of these strains. The objective of this review is to analyse the in vitro or in vivo experimental studies in which the antimicrobial activity of selected Lactobacillus and Bifidobacterium strains has been documented.

350 citations


Journal ArticleDOI
TL;DR: The results of recent experimental studies support the assumption that alcohol significantly modulates the mucosal immune system of the gut and that alcohol contributes to the tendency in alcoholics to develop diarrhoea.
Abstract: Consumption of large quantities of alcoholic beverages leads to disturbances in the intestinal absorption of nutrients including several vitamins. The inhibition of the absorption of sodium and water caused by alcohol contributes to the tendency in alcoholics to develop diarrhoea. Excessive alcohol consumption (even a single episode) can result in duodenal erosions and bleeding and mucosal injury in the upper jejunum. An increased prevalence for bacterial overgrowth in the small intestine may contribute to functional and/or morphological abnormalities of this part of the gut and also to non-specific abdominal complaints in alcoholics. The mucosal damage caused by alcohol increases the permeability of the gut to macromolecules. This facilitates the translocation of endotoxin and other bacterial toxins from the gut lumen to the portal blood, thereby increasing the liver's exposure to these toxins and, consequently, the risk of liver injury. The results of recent experimental studies support the assumption that alcohol significantly modulates the mucosal immune system of the gut.

308 citations


Journal ArticleDOI
TL;DR: The evidence for the anti-infective effects of probiotics is summarized and the effect of orally delivered probiotics on non-immunological and immunological defence mechanisms in the host, especially in the gastrointestinal tract is discussed.
Abstract: Several clinical studies have demonstrated the therapeutic and/or prophylactic efficacy of specific probiotics against acute viral gastroenteritis and antibiotic-associated diarrhoea (including Clostridium difficile infection). Emerging evidence also suggests beneficial effects against Helicobacter pylori infection. The evidence of efficacy against traveller's diarrhoea remains, however, inconclusive. The precise mechanisms by which probiotics potentiate host gastrointestinal defences and mediate protection are not fully known. There is evidence to suggest, however, that probiotics might contribute to host defence by reinforcing non-immunological defences and stimulating both specific and non-specific host immune responses. Little is known about the relative importance of the probiotic-stimulated mechanisms in host protection. This review summarises the evidence for the anti-infective effects of probiotics and discusses the effect of orally delivered probiotics on non-immunological and immunological defence mechanisms in the host, especially in the gastrointestinal tract.

231 citations


Journal ArticleDOI
TL;DR: Studies on GLUT1 null mice and Fanconi-Bickel patients suggest that there is another exit pathway for glucose and galactose that may involve exocytosis and there are no known defects of fructose absorption.
Abstract: Carbohydrates are mostly digested to glucose, fructose and galactose before absorption by the small intestine. Absorption across the brush border and basolateral membranes of enterocytes is mediated by sodium-dependent and -independent membrane proteins. Glucose and galactose transport across the brush border occurs by a Na(+)/glucose (galactose) co-transporter (SGLT1), whereas passive fructose transport is mediated by a uniporter (GLUT5). The passive exit of all three sugars out of the cell across the basolateral membrane occurs through two uniporters (GLUT2 and GLUT5). Mutations in SGLT1 cause a major defect in glucose and galactose absorption (glucose-galactose Malabsorption), but mutations in GLUT2 do not appear to disrupt glucose and galactose absorption. Studies on GLUT1 null mice and Fanconi-Bickel patients suggest that there is another exit pathway for glucose and galactose that may involve exocytosis. There are no known defects of fructose absorption.

215 citations


Journal ArticleDOI
TL;DR: The mechanisms by which probiotic bacteria may inhibit colon cancer are still poorly understood, but, several potential mechanisms are being discussed in the literature, and these will also be addressed in this review.
Abstract: Although a myriad of health-promoting effects have been attributed to the probiotic lactic acid bacteria, perhaps the most interesting and controversial is that of anticancer activity, the vast majority of studies in this area dealing with protective effects against colon cancer. There is no direct experimental evidence for cancer suppression in humans as a result of the consumption of probiotic cultures in fermented or unfermented dairy products, but there is a wealth of indirect evidence, based largely on laboratory studies. Reports in the literature regarding the anticancer effects of lactic acid bacteria fall into the categories of in vitro studies, animal studies, epidemiological studies and human dietary intervention studies. Examples of these reports will be given in the current paper. The mechanisms by which probiotic bacteria may inhibit colon cancer are still poorly understood, but, several potential mechanisms are being discussed in the literature, and these will also be addressed in this review.

203 citations


Journal ArticleDOI
TL;DR: The human gastrointestinal tract is colonized by a dense population of microorganisms, referred to as the bacterial flora, which provides a functional barrier between these organisms and the host, and bacterial translocation is a common event in the healthy person.
Abstract: The human gastrointestinal tract is colonized by a dense population of microorganisms, referred to as the bacterial flora. Although the gut provides a functional barrier between these organisms and the host, bacterial translocation is a common event in the healthy person. However, in critically ill patients, with various underlying diseases, this bacterial translocation may lead to infections and consequently to a further reduction in general health status. The mechanism of bacterial translocation is widely, and somehow controversially investigated in vitro and in animal models. In human studies, several diseases have been associated with bacterial translocation. However, methodological shortcomings, insufficient populations and conflicting results leave many open questions. This is also reflected in the various published therapeutic strategies. To overcome this problem more investigations in humans are needed, especially in techniques for detecting bacterial translocation.

188 citations


Journal ArticleDOI
TL;DR: Experimental data indicate that some probiotics reduce pathological alterations in paracellular permeability to large molecules or bacteria, stimulate mucosal immunity, display a trophic action on the mucosa, reduce mucus degradation and interact with mediators of inflammation.
Abstract: Probiotics can be defined as microbial cells that have a beneficial effect on the health and well-being of the host. Since the gastrointestinal mucosa is the surface of contact with probiotics, it seems evident that the first effects of probiotics relate to digestive function. A brief review of the literature indicates that probiotics have very few effects on the main physiological functions of the gastrointestinal tract, which are digestion, absorption and propulsion. The main action of probiotics can be summarised as a reinforcement of the intestinal mucosal barrier against deleterious agents. Experimental data indicate that some probiotics reduce pathological alterations in paracellular permeability to large molecules or bacteria, stimulate mucosal immunity, display a trophic action on the mucosa, reduce mucus degradation and interact with mediators of inflammation. Yoghurt may help lactose digestion, and some data needing confirmation indicate a stimulation of water absorption and an acceleration of intestinal transit by some bacteria.

188 citations


Journal ArticleDOI
TL;DR: Although the safety of commercial probiotics is excellent, this aspect of the pharmacology should be studied in more detail, especially in immunocompromised hosts.
Abstract: Probiotics have been defined as non-pathogenic micro-organisms that, when ingested, exert a positive influence on host health or physiology. Their pharmacology is more complex than that of inert drugs but is now being studied in detail. Some strains have a high survival capacity until they reach the faeces, whereas others are rapidly killed by acid and bile (a characteristic that can be used for the delivery of active intracellular components). Potential translocation and permanent colonization are rare but possible events; and should come under closer scrutiny. Mechanisms of action can be direct or indirect through modifications of the endogenous flora or through immunomodulation. The active components are poorly known but include bacterial formylated peptides, peptidoglycan cell wall constituents and nucleotides. Although the safety of commercial probiotics is excellent, this aspect should be studied in more detail, especially in immunocompromised hosts.

179 citations


Journal ArticleDOI
TL;DR: Corticosteroids are effective in selected patients with alcoholic hepatitis and pentoxifylline appears to be a promising anti-inflammatory therapy.
Abstract: Alcoholic liver disease (ALD) remains a major cause of morbidity and mortality worldwide. For example, the Veterans Administration Cooperative Studies reported that patients with cirrhosis and superimposed alcoholic hepatitis had a 4-year mortality of >60%. Interactions between acetaldehyde, reactive oxygen and nitrogen species, inflammatory mediators and genetic factors appear to play prominent roles in the development of ALD. The cornerstone of therapy for ALD is lifestyle modification, including drinking and smoking cessation and losing weight, if appropriate. Nutrition intervention has been shown to play a positive role on both an inpatient and outpatient basis. Corticosteroids are effective in selected patients with alcoholic hepatitis and pentoxifylline appears to be a promising anti-inflammatory therapy. Some complementary and alternative medicine agents, such as milk thistle and S-adenosylmethionine, may be effective in alcoholic cirrhosis. Treatment of the complications of ALD can improve quality of life and, in some cases, decrease short-term mortality.

160 citations


Journal ArticleDOI
TL;DR: The overall costs of a successful intestinal transplantation are already lower after 2 years when compared with the cost of a prolonged HPN programme, and the overall mortality rate of SBS patients on HPN is about 30% after 5 years, which is still lower than the 5-year survival rate of intestinal grafts.
Abstract: The incidence of patients with short-bowel syndrome (SBS) has increased over the years due to progress of intensive care medicine and parenteral nutrition techniques. These techniques have significantly improved the prognosis of neonates, children and adults who have lost major parts of their intestinal tract. Long-term survival is possible and does not depend primarily on the length of the remaining bowel but on complications such as parenteral nutrition-associated cholestasis, recurrent septicaemia, central venous catheter infections, and the motility of the remaining intestine. Thus, the overall related mortality in infants with SBS ranges from 15 to 25%, and in adults from 15 to 47%, depending on the age of the patients, the underlying disease, and the duration on total parenteral nutrition. Home parenteral nutrition (HPN) significantly decreases the complication rate and improves the psychological situation of the patient. Additionally, HPN reduces in-hospital cost significantly. Nevertheless, the annual costs/patient are between $100000 and $150000. The mortality rate of SBS patients on HPN is about 30% after 5 years, which is still lower than the 5-year survival rate of intestinal grafts, and it is about equal to patients' survival after intestinal transplantation. However, the overall costs of a successful intestinal transplantation are already lower after 2 years when compared with the cost of a prolonged HPN programme.

134 citations


Journal ArticleDOI
TL;DR: Controlled trials indicate a benefit of both the yeast Saccharomyces boulardii and bacteria Lactobacillus rhamnosus GG in the prevention of antibiotic-associated diarrhoea and recurrent Clostridium difficile disease, but more studies are needed before there can be a widespread endorsement of probiotics for these two conditions.
Abstract: Probiotics are living organisms which, when ingested, have a beneficial therapeutic effect. Examples are bacteria, especially Lactobacillus rhamnosus GG, and the yeast Saccharomyces boulardii. Controlled trials indicate a benefit of both of these in the prevention of antibiotic-associated diarrhoea. Other less effective probiotics are Lactinex, Enterococcus faecium and bifidobacteria. In the difficult clinical problem of recurrent Clostridium difficile disease, S. boulardii as an adjunct to antibiotics has shown benefit in controlled trials. There is, however, less convincing evidence for the efficacy of Lactobacillus GG in this disease. Additional controlled trials and safety studies are needed before there can be a widespread endorsement of probiotics for these two conditions.

Journal ArticleDOI
TL;DR: If designed carefully and with absolute attention to biological safety in its broadest sense, the development of genetically modified probiotics has the potential to revolutionize alimentary health.
Abstract: Probiotic micro-organisms have been used for many years. Originating as food supplements, they are now most often administered orally and offer an attractive alternative for treating of intestinal disorders. A better understanding of the mechanisms by which these micro-organisms act has now opened up possibilities for designing new probiotic strains. Through genetic engineering, it is possible not only to strengthen the effects of existing strains, but also to create completely new probiotics. These need not necessarily be composed only of bacterial products but can also include elements of regulatory systems or enzymes derived from a foreign-human-source. If designed carefully and with absolute attention to biological safety in its broadest sense, the development of genetically modified probiotics has the potential to revolutionize alimentary health.

Journal ArticleDOI
TL;DR: Intestinal failure and its most important cause, short-bowel syndrome (SBS), are rare clinical entities leading to a vast complex of symptoms and complications with significant morbidity and mortality.
Abstract: Intestinal failure and its most important cause, short-bowel syndrome (SBS), are rare clinical entities leading to a vast complex of symptoms and complications with significant morbidity and mortality. Both conditions occur as the result of a massive reduction in enteral nutrient absorptive capacity. Disease manifestation is based on aetiological and anatomical characteristics such as remaining intestinal length and the presence of a functionally intact colon. Congenital and perinatal conditions, for example, intestinal atresia, necrotizing enterocolitis (NEC) and intestinal volvulus are the most important causes in children. The aetiology in adults is based on diseases inducing loss of intestinal function or loss of intestinal surface area after extensive surgical resections. The most frequent causes are mesenteric infarction, radiation enteritis and Crohn's disease. Knowledge of the epidemiology of intestinal failure and SBS is limited, being mainly based on the extrapolated figures of home parenteral nutrition centres and single-centre studies. At present, the incidence of SBS is estimated to be 2-5 per million.

Journal ArticleDOI
TL;DR: The abdominal compartment syndrome is an emergency condition which is defined as elevation of IAP above 20 to 25 mmHg and the presence of systemic consequences andTherapeutic considerations include the maintenance of adequate hydration status, avoidance of drugs known to impair intestinal perfusion, stimulation of gastric and intestinal motility and various nutritional aspects.
Abstract: Ileus refers to the partial or complete blockage of the small and/or large intestine either by functional (adynamic or paralytic ileus) or mechanical bowel obstruction. The diffuse gastrointestinal dysmotility during functional and mechanical ileus may result in intestinal dilatation, increased luminal pressure and gut wall ischaemia which may lead to increased intra-abdominal pressure (IAP). Any type of ileus may promote abdominal fluid sequestration with severe systemic hypovolaemia, intestinal bacterial overgrowth with the evolution of bacterial translocation and systemic invasive infections and inflammation of the intestinal wall with concomitant release of cytokines and the development of the systemic inflammatory response syndrome. The most serious complications of ileus are mediated by an increase in IAP. Intra-abdominal hypertension has been found in up to 20% of critically ill patients and may lead to a broad pattern of systemic consequences with multiple organ dysfunction, including cardiovascular, hepatic, pulmonary, renal and neurological function. The abdominal compartment syndrome is an emergency condition which is defined as elevation of IAP above 20 to 25 mmHg and the presence of systemic consequences. Therapeutic considerations include the maintenance of adequate hydration status, avoidance of drugs known to impair intestinal perfusion, stimulation of gastric and intestinal motility and various nutritional aspects. Colonic tube placement after decompressive colonoscopy may be effective in reducing intestinal dilatation. In the abdominal compartment syndrome the 'open abdominal approach' with decompressive laparotomy by opening the peritoneal cavity and temporary abdominal closure is the therapy of choice.

Journal ArticleDOI
TL;DR: It is very common in critically ill and perioperative patients, but also occurs in pancreatitis, renal failure and sepsis, and treatment options include aggressive fluid resuscitation and careful choice of vasoactive drugs.
Abstract: Non-occlusive mesenteric ischaemia is characterized by gastrointestinal ischaemia with normal vessels. In gastroenterology it is recognized as rare disease occasionally causing acute bowel infarction or ischaemic colitis. From intensive care literature this disorder is recognized as an early phenomenon during circulatory stress. This early mucosal ischaemia then leads to increased permeability, bacterial translocation, and further mucosal hypoperfusion. The damage is produced mainly during reperfusion following ischaemia with fresh inflow of oxygen and outflow of waste products into the systemic circulation. The mechanisms underlying non-occlusive mesenteric ischaemia include macrovascular vasoconstriction, hypoperfusion of the tips of the villi and shunting. It is very common in critically ill and perioperative patients, but also occurs in pancreatitis, renal failure and sepsis. Treatment options include aggressive fluid resuscitation and careful choice of vasoactive drugs. Control of reperfusion damage and new endothelin-antagonists are potentially useful new treatment options.

Journal ArticleDOI
TL;DR: This chapter focuses the attention of physicians on overt and covert signs of psychosocial distress in the patient and family with chronic illness.
Abstract: Psychosocial issues in children, adolescents and families who suffer with chronic illnesses require careful identification and treatment. Since more of these young people survive into adulthood, their risk of psychosocial distress and psychiatric illness is increased, although many adapt well. The literature is vast, but limited in its usefulness: criteria for the variables described, including chronicity and severity, are poorly defined; outcome measures are not standardized; and few randomized controlled clinical trials exist. This chapter focuses the attention of physicians on overt and covert signs of psychosocial distress in the patient and family with chronic illness. Common issues for all chronic diseases are discussed and a non-categorical approach is taken. The importance of the family as a focus of intervention is highlighted. The meaning and treatment of unexplained medical symptoms, non- adherence with treatment recommendations, school refusal, sexuality and substance use and abuse are discussed.

Journal ArticleDOI
TL;DR: Modulation of the gut flora with probiotics may prove useful in the prevention and control of inflammatory bowel diseases.
Abstract: Epidemiology suggests some relationship between the establishment of the gut flora and the risk of developing inflammatory bowel disease. Unrestrained activation of the immune system against commensal bacteria appears to be responsible for the chronicity of these diseases. In animal models, broad-spectrum antibiotics reduce the bacterial load and militate against intestinal inflammation. Several bacterial species found in of the common microflora, including anaerobes, are able to invade the colonic wall when there is dysfunction of the colonic mucosal barrier. Most aerobes provoke focal areas of acute inflammation, but some anaerobes in the predominant flora induce diffuse a fibrogenic transmural response. Current research aims to identify the probiotics that might act against these bacteria. Colonization with specific probiotic strains, including a bacterium genetically engineered to secrete interleukin-10, prevents spontaneous colitis in susceptible mice. Certain lactobacilli exhibit anti-inflammatory properties naturally, i.e. without previous genetic manipulation. Prebiotics may increase colonization by lactobacilli and can prevent mucosal inflammation. Modulation of the gut flora with probiotics may prove useful in the prevention and control of inflammatory bowel diseases.

Journal ArticleDOI
William J. Sandborn1
TL;DR: Anti-tumour necrosis factor therapies are effective for the treatment of Crohn's disease and are being investigated for ulcerative colitis.
Abstract: Tumour necrosis factor (TNF) plays an important role in mediating the inflammation of inflammatory bowel disease, in particular, Crohn's disease. Strategies aimed at reducing tumour necrosis factor in patients with inflammatory bowel disease include the mouse/human chimeric monoclonal antibody infliximab, the humanized monoclonal antibody CDP571, the human soluble TNF p55 receptor onercept, the human monoclonal antibody D2E7 (adalimumab), the anti-TNF human antibody Fab′ fragment–polyethelene glycol (PEG) conjugate CDP870, and the small molecules thalidomide and CNI-1493 (MAP-kinase inhibitor). Infliximab is effective for treating active Crohn's disease, maintaining remission, closing fistulas, maintaining fistula closure, and treating ankylosing spondylitis. Infliximab is also being investigated for the treatment of ulcerative colitis. Side-effects occurring in patients treated with infliximab include human anti-chimeric antibodies, infusion reactions, delayed hypersensitivity reactions, formation of autoantibodies, and, in rare circumstances, drug-induced lupus and serious infections, including tuberculosis. CDP571 is effective for treating active Crohn's disease, steroid sparing, and possibly for closing fistulas and maintaining remission. Side-effects occurring in patients treated with CDP571 include anti-idiotype antibodies, infusion reactions and the formation of autoantibodies. A controlled trial of etanercept in patients with Crohn's disease was negative. Pilot studies with onercept, thalidomide, and CNI-1493 have suggested benefit for Crohn's disease. There are no published data on the efficacy of adalimumab (D2E7) or CDP870 for either Crohn's disease or ulcerative colitis. Anti-tumour necrosis factor therapies are effective for the treatment of Crohn's disease and are being investigated for ulcerative colitis.

Journal ArticleDOI
TL;DR: Effective control of C. difficile in the hospital requires both antibiotic control and prevention of environmental seeding and bacterial spread, which is less than ideal.
Abstract: Clostridium difficile causes a spectrum of diseases ranging from diarrhoea to pseudomembranous colitis, primarily in the hospitalized elderly, although community-acquired infection is probably under-documented. Host factors are increasingly recognized as critical determinants of disease expression. Exposure to antibiotics, particularly those adversely affecting anaerobic gut flora, appears to create a niche which is exploited by C. difficile. Several retrospective and intervention studies have indicated that third-generation cephalosporins have a high propensity to induce C. difficile diarrhoea. Conversely, some broad-spectrum antibiotics, including ureidopenicillins (e.g. piperacillin-tazobactam) and ciprofloxacin, are less likely to induce C. difficile infection. Effective control of C. difficile in the hospital requires both antibiotic control and prevention of environmental seeding and bacterial spread. Epidemic C. difficile strains are widely distributed in the hospital environment, both as a cause and result of nosocomial diarrhoea. Current treatment options are antibiotic-based, which is less than ideal. Although many biotherapeutic approaches have been tried few have shown real benefit.

Journal ArticleDOI
TL;DR: There appears to be a good correspondence between the events that induce relapse and loss of control over alcohol-taking behaviour in laboratory animals and those that provoke relapse and Loss of control in humans.
Abstract: Addictive behaviour evolves only on the basis of voluntary drug intake. As a consequence, when designing an animal model that covers several aspects of alcohol dependence and other alcohol related-diseases a necessary precondition is that the animal has voluntary access to alcohol. Animal models on voluntary alcohol consumption have a long-standing tradition in biomedical research on alcoholism. However, preference studies allow only limited conclusions regarding alcohol dependence and addictive behaviour. Therefore, new animal models have been developed that mimic different aspects of human alcohol dependence such as craving, relapse and loss of control over drinking. These models include the reinstatement model, the alcohol deprivation model and the point-of-no-return model. These models have now been pharmacologically validated using anti-craving compounds that are used clinically for treating alcoholics. In conclusion, there appears to be a good correspondence between the events that induce relapse and loss of control over alcohol-taking behaviour in laboratory animals and those that provoke relapse and loss of control in humans.

Journal ArticleDOI
TL;DR: Gallstone formation may be prevented by reducing gallbladder stasis (oral/enteral feeding or prokinetic agents), altering bile composition, or by means of a prophylactic cholecystectomy.
Abstract: Abnormal liver function tests in patients with intestinal failure (IF) may be due to the underlying disease, IF or the treatments given (including parenteral nutrition (PN)). PN-related liver disease in children usually relates to intrahepatic cholestasis and in adults to steatosis. Steatosis may be consequent upon an excess of carbohydrate, lipid or protein, or upon a deficiency of a specific molecule. Pigment-type gallstones are common in adults and children with IF; these develop from biliary sludge that forms during periods of gallbladder stasis. Ileal disease/resection, parenteral nutrition, surgery, rapid weight loss and drugs all increase the risk of developing gallstones. Gallstone formation may be prevented by reducing gallbladder stasis (oral/enteral feeding or prokinetic agents), altering bile composition, or by means of a prophylactic cholecystectomy. Calcium oxalate renal stones are common in patients with a short bowel and retained functioning colon and are consequent upon increased absorption of dietary oxalate; they are prevented by a low-oxalate diet. An osteopathy may occur with long-term parenteral nutrition.

Journal ArticleDOI
TL;DR: No data is available on the use of biologicals for the prevention of post-operative Crohn's disease and well designed and well powered multicentre trials to investigate the efficacy of different drugs for recurrence prophylaxis are needed.
Abstract: The majority of patients with Crohn's disease require resectional surgery in the course of their disease. Most of them will suffer symptomatic recurrence in the years after their operation, leading to new complications and sometimes repeated surgery. Clinical risk factors for early and evolutive recurrence have not been well identified. Smoking, perforating behaviour of the disease and ileal or ileocolonic location seem to predispose to early and aggressive recurrence. No clear prophylactic drug regime has been identified. Sulfasalazine and 5-ASA are only mildly protective and meta-analysis of all studies does not show superiority over placebo. Glucocorticosteroids are not efficacious. Nitroimidazole antibiotics, metronidazole and ornidazole prevent early endoscopic recurrence and postpone symptomatic relapse but are not well tolerated. Immunosuppression with azathioprine or 6-MP is attractive but hard data concerning their efficacy are still lacking. No data are available on the use of biologicals for the prevention of post-operative Crohn's disease. We need well designed and well powered multicentre trials to investigate the efficacy of different drugs for recurrence prophylaxis.

Journal ArticleDOI
TL;DR: It has now been established that the acinar cell is capable of metabolizing alcohol and that direct toxic effects of alcohol and/or its metabolites on acinar cells may predispose the gland to injury in the presence of an appropriate trigger factor.
Abstract: Alcoholic pancreatitis is a major complication of alcohol abuse. Until recently, it was generally accepted that alcoholic pancreatitis was a chronic disease from the outset. However, evidence is now emerging in support of the 'necrosis-fibrosis' hypothesis that alcoholic pancreatitis begins as an acute process and that repeated episodes of acute injury lead to the changes of chronic pancreatitis (acinar atrophy and fibrosis) resulting in exocrine and endocrine dysfunction. The treatment of acute pancreatitis follows the regimen of bed rest, nasogastric suction, analgesia and intravenous support. The role of additional therapeutic measures such as prophylactic antibiotics, antioxidants and enteral nutrition in severe cases has not yet been precisely defined. The treatment of chronic pancreatitis involves attention to its three cardinal features: pain, maldigestion and diabetes. With respect to the pathogenesis of alcoholic pancreatitis, the focus of research over the past 30 years has shifted from the sphincter of Oddi and ductular abnormalities to the acinar cell itself. It has now been established that the acinar cell is capable of metabolizing alcohol and that direct toxic effects of alcohol and/or its metabolites on acinar cells may predispose the gland to injury in the presence of an appropriate trigger factor. A significant recent development relates to the characterization of pancreatic stellate cells, increasingly implicated in alcoholic pancreatic fibrosis. This chapter summarizes the natural history, clinical features, current trends in treatment as well as recent advances in our understanding of the pathogenesis of alcoholic pancreatitis.

Journal ArticleDOI
TL;DR: This chapter is an overview of the literature on serological markers of inflammatory bowel diseases (IBD), focusing on anti-neutrophil cytoplasm autoantibodies (ANCA) and anti- Saccharomyces cerevisiae mannan antibodies (ASCA).
Abstract: This chapter is an overview of the literature on serological markers of inflammatory bowel diseases (IBD), focusing on anti-neutrophil cytoplasm autoantibodies (ANCA) and anti- Saccharomyces cerevisiae mannan antibodies (ASCA). The methodology for ANCA and ASCA testing is first introduced. The value of these markers as diagnostic tools is then discussed. Other chapters are devoted to the potential role of ANCA and ASCA in disease monitoring, disease stratification and as subclinical markers in families. Finally reviewed are other antibodies recently tested in clinical trials such as pancreatic antibodies and antibodies directed against bacterial antigens. The role of these antibodies in the pathophysiology of IBD still needs to be assessed. We also need to identify the ASCA immunogen(s) eliciting the antibody response.

Journal ArticleDOI
TL;DR: The message for prevention is that one should take care to have good oral hygiene and to avoid smoking, heavy drinking and drinking to intoxication.
Abstract: Excessive alcohol consumption and heavy smoking are the main risk factors for upper digestive tract cancers. Cancer risk is dose-dependent and alcohol and smoking have synergistic effects. Alcohol is not carcinogenic. However, its first metabolite-acetaldehyde-has recently been shown to be a local carcinogen in humans. Microbes representing normal human gut flora are able to produce acetaldehyde from ethanol. This results in high local acetaldehyde concentrations in the saliva and contents of the large intestine. Asian heavy drinkers with a genetic deficiency for detoxifying acetaldehyde form an exceptional human 'knockout' model for long-term acetaldehyde exposure. The risk of alcohol-related digestive tract cancers is particularly high among this population. All mechanisms that have an effect on salivary or intracolonic acetaldehyde concentration are of importance. The message for prevention is that one should take care to have good oral hygiene and to avoid smoking, heavy drinking and drinking to intoxication.

Journal ArticleDOI
TL;DR: This practical, evidence-based review examines probiotics as therapy for inflammatory bowel disease in humans, finding some data exist that possibly show an efficacy of probiotic as maintenance therapy in chronic relapsing pouchitis.
Abstract: Intestinal bacteria play a key role in inflammatory bowel disease. Probiotics attempt to modify disease by favourably altering bacterial composition, immune status, and inflammation. Until recently, probiotic therapy was considered 'folk' medicine, but there now is emerging interest on the part of the general public and scientific communities in the use of probiotics in human disease. This practical, evidence-based review examines probiotics as therapy for inflammatory bowel disease in humans. There are very few such published randomized clinical trials, but some data exist that possibly show an efficacy of probiotics as maintenance therapy in chronic relapsing pouchitis. Obstacles to providing probiotic therapy include selection of appropriate strains, poorly regulated probiotic quality standardization, processing and human biologic factors which impair probiotic viability, difficulty in maintaining new bacterial populations in the gut, and local product unavailability. Studies have focused on specific inflammatory bowel disease subgroups, limiting general applicability for the practitioner. Basic research highlights the importance of bacteria in these conditions, and the possibility that probiotics will modify physiological parameters. Well-designed, randomized clinical studies are still required to define the role of probiotics as therapeutic agents in inflammatory bowel disease.

Journal ArticleDOI
TL;DR: Although predominant discussion centres on the physiological state, clinical reference is necessarily made to gastrointestinal disorders in which imbalance of vitamins and minerals consequently results in an additional detrimental impact on health.
Abstract: The main theme of this chapter concerns the precise biochemical mechanisms involved in stages up to, and including, gastrointestinal absorption of vitamins and certain selected minerals. Essential data regarding sequential events, immediately following absorption of these micronutrients, are also included. There is reference to water-soluble vitamins that are, in general, either coenzymes in various metabolic reactions or carriers of certain biochemical groupings. In contrast, fat-soluble vitamins frequently function as integral components of cell membranes; they, too, receive ample attention. It is appropriate, nevertheless, to recognize that some minerals required in very small amounts are closely allied biochemically with particular vitamins; these specific associations are apportioned emphasis at relevant places in the text. Although predominant discussion centres on the physiological state, clinical reference is necessarily made to gastrointestinal disorders in which imbalance of vitamins and minerals consequently results in an additional detrimental impact on health.

Journal ArticleDOI
TL;DR: There is substantial evidence that probiotics modulate Helicobacter pylori colonization of the gastric mucosa and the importance of lactic acid production by probiotics and their capacity to release bacteriocins or secrete antibiotics is presented.
Abstract: There is substantial evidence that probiotics modulate Helicobacter pylori colonization of the gastric mucosa. This chapter presents the data currently available to support an interaction between probiotics and H. pylori, the importance of lactic acid production by probiotics and their capacity to release bacteriocins or secrete antibiotics. The ability of probiotics to interfere with H. pylori adhesion to epithelial cells and their capacity to attenuate H. pylori-induced gastritis in man is addressed. Finally, the potential of probiotics to modify the H. pylori eradication rate and the antibiotic-associated gastrointestinal side-effects during H. pylori eradication therapy are reviewed.

Journal ArticleDOI
TL;DR: The identification of the IBD1 gene on chromosome 16 as NOD-2 is unquestionably an important scientific discovery and there is great optimism that important clinical applications will directly result.
Abstract: Considerable progress has been made in the last decade in studies of the genetics of the inflammatory bowel diseases, Crohn's disease and ulcerative colitis. Epidemiological data, notably concordance rates in twin pairs and sibling pairs, have provided strong evidence for the importance of the genetic contribution, particularly in Crohn's disease. These observations provided the catalyst for laboratory-based studies of the molecular genetics of Crohn's disease and ulcerative colitis around the world. The complementary strategies of genome-wide scanning and candidate gene-directed studies have led to the identification of a number of genetic markers which appear to predict disease susceptibility and behaviour. The identification of the IBD1 gene on chromosome 16 as NOD-2 is unquestionably an important scientific discovery. Although many issues with respect to gene function and expression remain to be resolved there is great optimism that important clinical applications will directly result.

Journal ArticleDOI
TL;DR: Emphasis on early stages of therapy to enhance intestinal adaptation is focused on as management during this time has a significant impact on the long-term outcome of these patients.
Abstract: Short-bowel syndrome is a challenging entity for the gastroenterologist, requiring integration of medical, nutritional, surgical and psychological therapies. Treatment must be based on the patient's age, remaining gastrointestinal anatomy, baseline nutritional status and underlying general health as well as the numerous complications which may arise. This chapter reviews physiological alterations that occur with short-bowel syndrome and how therapies can be tailored to most adequately meet the needs of these patients. Emphasis on early stages of therapy to enhance intestinal adaptation is focused on as management during this time has a significant impact on the long-term outcome of these patients.