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Biomedical subjects

M J Shield

Publications and source records attributed to M J Shield.

At least 19 recordsLinked to original sources
PubMed1997

Association of upper gastrointestinal toxicity of non-steroidal anti-inflammatory drugs with continued exposure: cohort study.

OBJECTIVES: To determine the profile of risk of upper gastrointestinal toxicity during continuous treatment with, and after cessation of, non-steroidal anti-inflammatory drugs. DESIGN: Cohort study with a prospectively constructed, population based, record linkage database containing details of exposure to all community dispensed non-steroidal anti-inflammatory drugs and also all admissions to hospital for upper gastrointestinal diagnoses. SETTING: The population of Tayside, Scotland. SUBJECTS: 52,293 subjects aged 50 and over who received one or more non-steroidal anti-inflammatory between 1 January 1989 and 31 December 1991 and 73,792 subjects who did not receive one during the same period (controls). MAIN OUTCOME MEASURES: Admission to hospital for upper gastrointestinal bleeding and perforation, and admission for other upper gastrointestinal diagnoses. RESULTS: About 2% of the non-steroidal anti-inflammatory cohort were admitted with an upper gastrointestinal event during the study period compared with 1.4% of controls. The risk of admission for upper gastrointestinal haemorrhage and perforation was constant during continuous non-steroidal anti-inflammatory exposure and carried over after the end of exposure. The results were similar for admissions for all upper gastrointestinal events. CONCLUSION: This study provides evidence that non-steroidal anti-inflammatory toxicity persists with continuous exposure. There seems to be carryover toxicity after the end of prescribing. These findings have implications for the management of patients requiring non-steroidal anti-inflammatory drugs.

Age Factors↗
PubMed1995

Novel applications of misoprostol.

Misoprostol, a prostaglandin E1 analogue, is currently licensed primarily to prevent non-steroidal anti-inflammatory drug-associated gastric and duodenal ulcers. Further work shows the drug prevents triggering of a variety of inflammatory processes and the release of tissue damaging cytokines and other mediators involved in conditions as diverse as asthma and osteoarthritis. Thus, misoprostol may help restore or maintain normal homeostasis and limit inhibitory effects on essential repair processes. Therapeutic implications include limitation of renal, hepatic, gastrointestinal and radiation-induced tissue injury and prevention of inflammatory and allergic disorders, including the late phase inflammatory response in asthma, either alone or in synergy with other agents.

Adjuvants, Immunologic↗
PubMed1993

The prevention and healing of acute non-steroidal anti-inflammatory drug-associated gastroduodenal mucosal damage by misoprostol.

This double-blind study assessed the acute development of NSAID-associated gastroduodenal (GD) damage and its prevention by misoprostol. Patients requiring chronic NSAID therapy were stratified into two groups depending on initial endoscopic appearance, Group I: normal (n = 223); Group II: non-ulcer lesions (n = 78). After 2 weeks of therapy with NSAID and either misoprostol 400-800 micrograms daily or placebo the incidence of severe mucosal damage (including ulcers) was significantly reduced by misoprostol (odds ratio; 95% CI). Group I: 4.52; 1.94, 10.51 (P = 0.018); Group II: 10.93; 1.09, 109.60 (P = 0.014); Groups I and II combined: 5.95; 3.23, 10.94 (P = 0.0003). Misoprostol exerted a significant protective effect against progression of minor to severe damage in Group II (P < 0.001). Endoscopic findings did not correlate significantly with gastrointestinal symptoms and misoprostol did not interfere with the NSAID efficacy. Significant GD damage occurs early in the course of NSAID treatment and misoprostol significantly reduces the incidence of such damage.

Adult↗
PubMed1993

Anti-inflammatory drugs and their effects on cartilage synthesis and renal function.

Growing evidence suggests that nonsteroidal anti-inflammatory drugs (NSAIDs), while able to alleviate inflammation, may damage articular cartilage, though both chondrodestructive and chondroprotective activities have been observed with different NSAIDs. Experiments conducted on explants of normal and osteoarthritic human cartilage have shown that certain NSAIDs at pharmacologic concentrations achievable in man consistently inhibit glycosaminoglycan (GAG) synthesis. The addition of the prostaglandin E1 analogue misoprostol consistently reversed these inhibitory effects in a dose-related manner. Paradoxically, with some NSAIDs, such as diclofenac and aspirin, misoprostol was also able to enhance GAG synthesis above control levels, especially in osteoarthritic cartilage. This supports findings from other work that NSAIDs exert effects other than through inhibition of cyclooxygenase, direct action on cell membranes being one of these alternative mechanisms of action. Additionally it is interesting to note and may be of clinical relevance that misoprostol on its own also stimulates GAG synthesis in explants of human osteoarthritic cartilage whilst exerting no apparent effect on healthy cartilage with a normal GAG turnover. With regard to renal aspects, the effects of NSAIDs are readily explicable in terms of interference with prostanoid synthesis. The consequent inhibition exerted on vasodilatory prostaglandins (PGs), which oppose vasoconstrictor action induced by substances such as thromboxane or leukotrienes, upsets the balance that maintains renal function. In situations in which there is reduced renal reserve, reduction of renal PG synthesis by NSAIDs will adversely affect maintenance of renal blood flow and glomerular filtration rate and excretion of sodium, potassium, and water. Patients with alcoholic cirrhosis manifest this type of compromised renal function and in them misoprostol reverses the adverse effects of indomethacin on renal hemodynamics and partially reverses indomethacin-induced renal sodium retention. Although the clinical significance of these data is not yet established, exogenous administration of specific PGs may be able to minimize the deleterious actions of NSAIDs.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1992

Misoprostol: new frontiers; benefits beyond the gastrointestinal tract.

Recent findings suggest that the protective role that misoprostol exerts in the gastrointestinal tract against nonsteroidal anti-inflammatory drug (NSAID) damage may be extended to a variety of other tissues and other noxious stimuli including those mediated by molecules such as interleukin 1 (IL-1), tumor necrosis factor (TNF), and endotoxin. The protective effects of misoprostol outside the gastrointestinal tract may involve prevention of triggering activities that would otherwise initiate a sequence of tissue damaging events. If this capacity of misoprostol to maintain homeostasis in a variety of settings is recognized, a cohesive pattern of action emerges. Numerous studies have shown that misoprostol is likely to act as a regulator within various cascades of immunological regulatory events. The in vitro and in vivo experimental data described in this paper suggest that the events which trigger episodes of pain and inflammation may be controllable by the administration of misoprostol. Mitigation of adverse effects of certain NSAIDs on renal function and cartilage metabolism has also been observed. Demonstration of this latter phenomenon in the clinical setting will greatly benefit the patient if it is shown to modify the arthritis disease process. The therapeutic applications of misoprostol beyond the gastrointestinal tract appear to be among the most interesting of therapeutic advances offered by any class of compound in the next decade. Because of the inflammatory and pain processes associated with arthritis disease progression, particular emphasis and confirmation through further clinical study should be placed on the potential effect of misoprostol on chondroprotection and synergy with NSAIDs.

Adjuvants, Immunologic↗
PubMed1985

Interim results of a multicenter international comparison of misoprostol and cimetidine in the treatment of out-patients with benign gastric ulcers.

An interim analysis has been performed of a multicenter randomized double-blind parallel-group comparison of misoprostol 50 micrograms (low dose), misoprostol 200 micrograms (high dose), and cimetidine 300 mg in out-patients with endoscopically diagnosed benign gastric ulcers. The drugs were administered q.i.d. for four weeks. Endoscopic assessments were made before treatment and at four weeks. Clinical assessments and laboratory tests were made before treatment and at two and four weeks. At the interim stage 421 subjects of the target 600 patients had been recruited by 22 principal investigators in 13 countries. Demographic data were similar for all groups with the exceptions of a lower proportion of males and smokers in the cimetidine group. Therapeutic success was defined as complete healing of all gastric ulcers. Cure rates at four weeks, for all eligible patients who received at least one dose of study medication (cohort 1), were significantly lower (P = 0.002) for misoprostol 50 micrograms (41.2%) than for misoprostol 200 micrograms (58.2%). There was no significant difference (P = 0.86) in cure rates between the high dose misoprostol and cimetidine (59.6%) groups. Cure rates were approximately 20% higher for non-smokers than smokers in both misoprostol groups, an effect not observed with cimetidine. In all three treatment groups the incidence of complaints, including diarrhea, was similar and therapy was well tolerated.

Adolescent↗
PubMed1981

How environmental mycobacteria may predetermine the protective efficacy of BCG.

A proposal is made that there are 2 mechanisms of cell mediated response to mycobacteria, both of which produce positive tuberculin tests and that one of them is more protective against mycobacterial infection than is the other. These are referred to respectively as the Listeria-type and the Koch-type of responses. Contact with environmental mycobacteria will induce one or other of these types of response and BCG vaccination will enhance it. Thus in those places where the environmental species prime for the Listeria-type of response subsequent BCG vaccination will afford good protection from both tuberculosis and leprosy. Where the Koch-type of response frequently results from environmental contact BCG will be ineffective. Evidence if presented that a large contact with Mycobacterium scrofulaceum is prejudicial to at least one marker of BCG efficacy in Burma.

Adolescent↗