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Gastrointestinale Erkrankungen
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One hundred years have passed since Felix Hoffman, working at Bayer Industries, reported the successful synthesis of acetylsalicylic acid as the first nonsteroidal antiinflammatory drug (NSAID).1,2 At the suggestion of Hermann Dreser, Bayer's chief pharmacologist at the time,3 the compound was called “aspirin” and was purported to represent a convenient mechanism for the delivery of salicylic acid in the treatment of rheumatic diseases, menstrual pain, and fever.2 Approximately 40 years elapsed before Douthwaite and Lintott4 provided endoscopic evidence that aspirin could cause gastric mucosal damage. Numerous reports have corroborated this observation,5–8 and the introduction of more potent agents . . .
H. pylori is one of the most common bacterial infections in human beings, and its discovery 20 years ago altered the diagnosis and treatment of gastroduodenal disease. This review considers current knowledge about the epidemiology and transmission of H. pylori, as well as the role of this infectious agent in the pathogenesis of upper gastrointestinal tract disease. Diagnostic approaches, indications for therapy, and measures of therapeutic efficacy are reviewed.
In the decades since the major forms of idiopathic inflammatory bowel disease were defined on the basis of clinical manifestations, investigators have been challenged to identify the fundamental pathophysiologic processes underlying these enigmatic disorders, and clinicians have struggled to provide effective therapy for the often dismaying clinical manifestations. Clinical experience has led to the generally accepted notion that Crohn's disease and ulcerative colitis are distinct, if not discrete, entities. However, whether these are fundamentally different diseases or part of a mechanistic continuum remains an unanswered question, with both conceptual and practical management implications.
Helicobacter pylori infects more than half of the world's population, making it one of the most prevalent infections. H pylori is now accepted as the most common cause of histologic gastritis and is responsible for the majority of cases of peptic ulcer disease and gastric cancer. Approximately 1 in G (17%) persons with H pylori infection will develop peptic ulcer disease, and each year 1% to 2% of these will experience a major or life-threatening complication, such as bleeding perforation, or gastric outlet obstruction. Peptic ulcer disease should no longer be regarded as a chronic, recurring, lifelong disease, but rather as a curable infectious disease. The diagnosis and therapy of this common infectious disorder have become increasingly straightforward In this article, we discuss the possible outcomes of long-standing infection, the various diagnostic tests available, including whom and when to test, and the combination drug regimens approved for cure.
Gastroesophageal reflux (GER) occurs in 2 distinct forms that differ in pathophysiology, clinical presentation, natural history, and therapy: mild GER (with no or minimal esophagitis) and classic, severe reflux (at risk for erosive esophagitis). A minority of subjects (< 20%) have the classic, potentially severe pattern of GER caused by reduced lower esophageal sphincter (LES) pressure and prolonged acid reflux, particularly at night, but also during the day. Evaluation and management must be catered to patients with this pattern of reflux. In contrast, symptoms in mild reflux (the majority) often occur during the day after meals in an upright posture (upright reflux); resting LES pressure is usually normal (reflux episodes are related to transient relaxation of the LES) and little reflux occurs at night. Acid reflux, which occurs mostly during the day, overlaps with the normal range and esophagitis is rare; however, symptoms can be distressing. Optimal management is controversial because no outcome trials have been conducted to address management in primary care settings. However, clinical clues can help differentiate mild and severe reflux and guide management decisions. This article provides a detailed approach to current management of GER syndromes.
Stress-related mucosal disease develops in patients in the intensive care unit and can result in clinically important bleeding, which is associated with increased mortality. Patients in the intensive care unit without either mechanical ventilation or coagulopathy, which are the primary risk factors for such bleeding, do not seem to need or to benefit from prophylactic acid suppression for stress-related mucosal disease. Although histamine-2-receptor antagonists significantly reduce clinically important bleeding in patients in the intensive care unit and are widely used for prophylaxis, their benefits are limited by the rapid development of tolerance. Previous data suggested that agents that elevate the intragastric pH may increase the susceptibility of patients in the intensive care unit to nosocomial pneumonia. However, the largest study to date showed that intravenous histamine-2-receptor antagonists may not significantly increase the risk of ventilator-associated pneumonia or mortality compared with sucralfate, an agent that does not affect intragastric pH. Intravenous proton pump inhibitors are more potent and longer-acting inhibitors of gastric acid production than intravenous histamine-2-receptor antagonists. The ability of proton pump inhibitors to prevent stress-related mucosal disease and clinically important bleeding seems to be clinically meaningful. Preliminary findings have shown that intermittent administration of intravenous pantoprazole, the first proton pump inhibitor available by this route in the United States, is as effective in raising intragastric pH on the first day as a continuous infusion of a histamine-2-receptor antagonist in clinical trials conducted within an intensive care unit setting. This suggests that for stress ulcer prophylaxis, intermittent dosing with an intravenous proton pump inhibitor may be an alternative to high-dose continuous infusions of a histamine-2-receptor antagonist. These agents must be compared in clinical trials conducted in an intensive care unit setting.
The management of the irritable bowel syndrome (IBS) remains unsatisfactory. For abdominal pain, antispasmodics are, at best, of only modest efficacy. Tricyclic antidepressants in low dose are useful (with the number needed to treat being three), but side effects and patient concerns regarding use of a centrally acting agent for depression remain limitations. Selective serotonin reuptake inhibitors are of uncertain efficacy in IBS. Opioid agonists, especially loperamide, are useful for diarrhea but not for pain in IBS; rebound constipation also remains a problem. Bile salt sequestering agents are not of established value in IBS but seem to be useful clinically in a small group of IBS patients with diarrhea. Aloestron, a 5HT(3) antagonist, should be reserved, if available, for women with severe diarrhea predominant IBS who have failed to respond to conventional therapy, and started at a low dose. Fiber and bulking agents may help constipation in some trials, but the evidence that they are efficacious in IBS is equivocal; they are frequently prescribed as first-line drugs for IBS regardless of the primary bowel disturbance but often increase bloating, gas, and pain. Laxatives are not of established value in IBS but are often taken by patients with constipation predominant IBS. Tegaserod, a partial 5HT(4) agonist, is now available in the United States and other countries for use in women with IBS whose primary bowel symptom is constipation; its efficacy in men and in those with alternating bowel habits is unknown. Probiotics are of uncertain efficacy. Chinese herbal medicine data are insufficient. Other new drugs in development include the cholecystokinin antagonists and novel visceral analgesics. Both current and potential therapies for IBS are reviewed in this article.
Inflammatory bowel disease (IBD) comprises a group of idiopathic diseases of the intestine characterized by chronic inflammation of the bowel with periods of exacerbation and remission. The 2 major categories of IBD are ulcerative colitis and Crohn's disease, and each disease is distinct both clinically and histologically. The exact cause of IBD remains unknown, but several theories have been proposed. Primary care physicians are frequently confronted with the initial diagnosis and management of patients with IBD, and medical treatment options have rapidly expanded in recent years. This article reviews the epidemiology and pathogenesis of IBD; its clinical presentations and complications, which are essential to understanding this complex disease; and the available treatment options.
Evidence for the effectiveness of antacids, histamine-2 receptor antagonists, bismuth salts, sucralfate and prokinetic therapy in non-ulcer dyspepsia is conflicting.
To conduct a systematic review evaluating these therapies in non-ulcer dyspepsia.
Electronic searches were performed using the Cochrane Controlled Trials Register, Medline, EMBASE, Cinahl and SIGLE until September 2002. Dyspepsia outcomes were dichotomized into cured/improved vs. same/worse.
Prokinetics [14 trials, 1053 patients; relative risk reduction (RRR), 48%; 95% confidence interval (95% CI), 27-63%] and histamine-2 receptor antagonists (11 trials, 2164 patients; RRR, 22%; 95% CI, 7-35%) were significantly more effective than placebo. Bismuth salts (RRR, 40%; 95% CI, - 3% to 65%) were superior to placebo, but this was of marginal statistical significance. Antacids and sucralfate were not statistically significantly superior to placebo. A funnel plot suggested that the prokinetic and histamine-2 receptor antagonist results could be due to publication bias.
The meta-analyses suggest that histamine-2 receptor antagonists and prokinetics are superior to placebo. These data are difficult to interpret, however, as funnel plot asymmetry suggests that the magnitude of the effect could be due to publication bias or other heterogeneity-related issues.
Potential interventions for gastroesophageal reflux disease include lifestyle modifications, antacids, mucosal protectants, prokinetic (promotility) agents, H2 receptor antagonists (H2RAs) and, the agents of choice in 2003, proton pump inhibitors (PPIs). This article reviews the current state of the art in use of these agents. Lifestyle changes, though sound in their intent and in many cases based on solid laboratory research, can today be considered only adjuncts to pharmacologic therapy. The mainstay of pharmacologic therapy in 2003 is antisecretory therapy. Both H2RAs and PPIs inhibit acid secretion and raise intragastric pH. H2RAs only block one receptor, have limited effect on acid reduction, and are relatively weak inhibitors of meal-stimulated acid secretion. PPIs provide superior control of intragastric pH over a 24-hour period compared with H2RAs and effect greater symptom relief and healing.
Through effects on gastrointestinal motor and secretory function as well as visceral sensation, serotonin (5-HT) plays a key role in the pathogenesis of irritable bowel syndrome (IBS). In particular, 5-HT3 and 5-HT4 receptors appear to be very important in IBS. This article critically appraises the evidence supporting the use of the 5-HT3 receptor antagonist alosetron in the treatment of women with diarrhea-predominant IBS. The safety profile and restricted-use program for alosetron is also reviewed. This discussion is followed by a comprehensive review of the efficacy and safety data in support of tegaserod for women with constipation-predominant IBS.
Various agents are used for the medical management of chronic constipation but few have been carefully studied. This review examines available data concerning several bulk and fiber products, lubricating agents, stimulants, and osmotic laxatives, alone and in combination. Popular therapeutic options for initial treatment of chronic constipation are dietary fiber and medicinal bulk. Subsequent treatments if fiber is not successful or tolerated would include saline osmotic laxatives, lactulose, or stimulants like senna or bisacodyl. Recent data demonstrate polyethylene glycol laxative to be safe and effective as an initial or second-line agent for chronic constipation. Indications and use of surgery and biofeedback are also discussed.