ISSN:0257-2753    

DOI:10.1159/000171482

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The physiology of the mesenteric circulation is described emphasizing important aspects of microcirculatory function and the factors which regulate blood flow to the bowel. Next, the pathophysiology of intestinal ischemia is considered with special focus on the disturbed mechanisms involved in ischemic disorders, such as active oxidant formation and inhibition of intrinsic protective systems. The histopathology of small intestinal and colonic ischemia and infarction is described. Finally, clinical issues are addressed including the diagnostic challenge and the management of these life-threatening disorders.

ISSN:0257-2753    

DOI:10.1159/000171483

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Gastroduodenal mucosa possesses an array of defensive mechanisms and nonsteroidal anti-inflammatory drugs (NSAIDs) have a deleterious effect on most of them. This results in a mucosa less able to cope with even a reduced acid load. The presence of acid appears to be a conditio sine qua non for NSAIDs injury. Acid not only injures the mucosa by back-diffusing from the lumen to cause tissue acidosis but also serves to increase drug absorption. Although much of the experimental work has been done using salicylates, it is now well accepted that almost all the NSAIDs are capable of causing mucosal damage. These compounds appear to cause gastro-duo-denal damage, by two main mechanisms: a physiochemical disruption of the gastric mucosal barrier and a systemic inhibition of gastric mucosal protection, through inhibition of cyclo-oxygenase activity of gastrointestinal (GI) mucosa. A reduced synthesis and secretion of mucus and bicarbonate, an impairment of mucosal blood flow and an increase of acid secretion represent the main consequences of NSAID-induced prostaglan-din (PG) deficiency. Additional mechanisms which may add to the damage have been demonstrated. These include uncoupling of oxidative phosphorylation, reduced mucosal cell proliferation and DNA synthesis as well as neutrophil activation. Recent work has demonstrated that, after administration of NSAIDs, neutrophil adherence to the vascular endothelium occurs, with consequent reduced mucosal perfusion and release of tissue-damaging mediators. Since PGs are well-established modulators of inflammatory response, it is evident that NSAIDs induce damage to GI tract via a mechanism identical to that by which they exert their anti-inflammatory action. In this context, it is very difficult to imagine an effective NSAID completely devoid of gastrointestinal side effects. Although NSAIDs with tissue-selective effects on cyclo-oxygenase are available and compounds with reduced topical irritancy have been developed, gastroduodenal damage still represents an important effect of this class of drugs, because no NSAID is completely devoid of GI side effects.

ISSN:0257-2753    

DOI:10.1159/000171523

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Gastrin plays a central role in the regulation of acid secretion. It is released by meals in quantities sufficient to explain mealstimulated acid secretion. Gastrin stimulates acid secretion mainly by releasing histamine from the enterochromaffin-like (ECL) cell. Whether gastrin has any functional direct effect on the parietal cell remains to be shown. Gastrin stimulates not only the function but also the growth of the ECL cell, and long-term hypergastrinemia may lead to ECL cell carcinoids. The role of the ECL cell in human gastric carcinogenesis is controversial, but it seems wise to avoid long-term iatrogen hypergastrinemia especially in young persons. Interestingly, the oxyntic mucosal D cell, on which gastrin has a negative trophic effect, may play a role in gastric stump carcinoma, and thus hypogastrinemia may also dispose to gastric cancer.

ISSN:0257-2753    

DOI:10.1159/000171484

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Endoscopic ultrasonography is an exciting new field, with a rapidly expanding literature describing a wide variety of applications. Despite remarkable advances in the field, a number of crucial issues remain to be resolved. These include the limited availability of educational programs for training, enormous initial start up costs for centers related to the cost of equipment and the lack of interchangeability with processors, paucity of outcomes research studies, and technical limitations of the currently available devices. The aim of this article is to review the basic principles, instrumentation, applications, and potential problems related to endoscopic ultrasound and to attempt to define the realistic role for this tool in contemporary medical practice.

ISSN:0257-2753    

DOI:10.1159/000171485

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

All nonsteroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal (GI) side effects. One focus of development was to design new drugs with reduced propensity for GI damage. With aspirin as the prototype, research efforts to develop NSAIDs with the efficacy but not the gastroduodenal damaging effects of aspirin have been partially successful. Techniques used to minimize gastric irritant potential include developing new drug classes, enteric coatings, nonacidic drugs, and prodrugs. Properties associated with the mucosal damaging effects of NSAIDs (potent inhibition of prostaglan-din synthesis, solubility at low pH, and acid characteristic) are not found in the newer prodrugs such as droxicam and nabumetone. Droxicam was developed as a prodrug of piroxicam with equal efficacy, in addition to improved GI tolerance. Prodrugs may offer new molecules with pharmacological profiles and efficacy to toxicity ratios more acceptable to clinicians and patients alike.

ISSN:0257-2753    

DOI:10.1159/000171525

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

One of the most serious side effects of nonsteroidal anti-inflammatory drugs (NSAIDs) is upper gastrointestinal mucosal damage that may result in erosions, ulcerations and other serious complications. NSAIDs reduce endogenous prostaglandins, and this reduction is relevant to their pharmacology and toxicity. The stomach and to some extent the duodenum are the major organs involved in the mucosal toxicity of NSAIDs. With the availability of the synthetic prostaglandin misoprostol, it has become possible to prevent NSAID-induced gastroduodenal ulcers without compromising the beneficial antirheumatic and analgesic effects of NSAID therapy. In fact, misoprostol is the only drug with established long-term efficacy in preventing NSAID-induced gastroduodenal ulcers in rheumatic patients. The purpose of this communication is to critically review the efficacy of gastric antisecretory drugs, mucosal protective drugs and misoprostol when used for the prevention of NSAID-induced ulcers, considering only data from well-controlled, randomized, double-blind clinical studies. The histamine H2-receptor antagonist ranitidine has been shown to be effective in preventing NSAID-induced duoenal ulcers, but has no efficacy in preventing NSAID-induced gastric ulcers. In a direct comparative trial with ranitidine, misoprostol (200 µg qid) was significantly more effective than ranitidine (150 mg bid) in preventing gastric ulcers in chronic NSAID users. The inactivity of ranitidine in preventing gastric ulcers indicates that the pathogenesis of NSAID-induced gastric ulcers is not related to gastric acid. Limited but conflicting data exist with omeprazole. The mucosal-coating drug sucralfate has not been found effective in preventing NSAID ulcers. In fact, in a direct comparative trial, misoprostol (200 µg qid) was significantly more effective than sucralfate (1 g qid) in preventing gastric ulcers in patients receiving chronic NSAID therapy. No meaningful data exist with organic bismuth salts, a group of drugs which has mucosal coating and protective properties. From this brief overview, we conclude: (1) mucosal-coating compounds have no therapeutic role in preventing NSAID-induced ulceration; (2) gastric antisecretory drugs are not effective in preventing NSAID-induced gastric ulcers, and (3) misoprostol is the only antiulcer drug proven to be effective for preventing NSAID-induced gastric and duodenal ulcers in patients receiving chronic NSAID. Misoprostol represents a major therapeutic advance for the management of NSAID-induced mucosal injur

ISSN:0257-2753    

DOI:10.1159/000171526

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Over the last 5 years, laparoscopy has revolutionized the surgical management of many abdominal disorders. Some of the problems being so treated include biliary tract disease, achalasia, gastroesophageal reflux, peptic ulcers, colonic disorders, appendicitis, and inguinal hernias. Patient acceptance is excellent and hospitalization is reduced. Safety, long-term efficacy, and cost efficiency are finally in the process of being objectively evaluated.

ISSN:0257-2753    

DOI:10.1159/000171486

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

In order to provide a systematic overview of the available information on the prevention of nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal mucosal injury, we performed a meta-analysis based on all the in extenso published randomized clinical trials comparing H2-blockers or misoprostol to placebo for the prevention of NSAID-induced gastrointestinal mucosal injury in arthritis patients or normal subjects. The main endpoints after NSAID therapy were considered the number of subjects developing gastric ulcer, or clinically relevant gastric lesions (i.e. more than 10 erosions or 1 ulcer), or duodenal ulcer, or clinically relevant duodenal lesions (i.e. more than 10 erosions or 1 ulcer). The total number of patients studied was 1,955, and that of normal subjects was 715. Results were analyzed by the DerSimonian and Laird method, as well as by the Peto one. The data available from the trials suggest that misoprostol prevention is of benefit in patients under NSAID treatment for the prevention of NSAID-induced gastroduodenal mucosal injury. The effect of prevention is statistically significant with both methods, and ranges from -42% (duodenal ulcer) to -79% (gastric ulcer). The prevention estimates for gastric and duodenal erosions are inbetween. H2-blockers seem to be less effective: prevention is not indeed demonstrable for the more relevant lesions, like gastric and duodenal ulcer.

ISSN:0257-2753    

DOI:10.1159/000171527

出版商:S. Karger AG    

年代:1995

数据来源: Karger

ISSN:0257-2753    

DOI:10.1159/000171487

出版商:S. Karger AG    

年代:1995

数据来源: Karger