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Biomedical subjects

M J Langman

Publications and source records attributed to M J Langman.

At least 55 records · Page 3Linked to original sources
PubMed1994

Risks of bleeding peptic ulcer associated with individual non-steroidal anti-inflammatory drugs.

Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of peptic ulcer complications, but it is not clear whether some drugs are more likely than others to cause such complications. We compared previous use of NSAIDs in 1144 patients aged 60 and older admitted to hospitals in five large cities with peptic ulcer bleeding and in 1126 hospital controls and 989 community controls matched for age and sex. Peptic ulcer bleeding was strongly associated with use of non-aspirin NSAIDs of any type during the 3 months before admission (411 cases, 351 controls; odds ratio 4.5 [95% CI 3.6 to 5.6]). The odds ratios for peptic ulcer bleeding were lowest for ibuprofen (2.0 [1.4-2.8]) and diclofenac (4.2 [2.6-6.8]), and intermediate for indomethacin, naproxen, and piroxicam (11.3 [6.3-20.3], 9.1 [5.5-15.1], and 13.7 [7.1-26.3]). Azapropazone and ketoprofen carried the highest risks (31.5 [10.3-96.9] and 23.7 [7.6-74.2]). Risks also increased with drug dose (low dose 2.5 [1.7-3.8], intermediate 4.5 [3.3-6.0], and high 8.6 [5.8-12.6]) for all drugs combined. Appropriate clinical strategies could prevent many episodes of peptic ulcer bleeding: NSAIDs should be used only in patients who do not respond to other analgesics; the lowest possible doses should be used; and the least toxic NSAIDs should be selected.

Aged↗
PubMed1994

Lack of effect of H2-receptor antagonists on the pharmacokinetics of alcohol consumed after food at lunchtime.

The possibility of a pharmacokinetic interaction between H2-receptor antagonists and alcohol consumed at lunchtime, was investigated in 24 healthy non-alcoholic male subjects, each receiving ranitidine 150 mg four times daily, cimetidine 400 mg four times daily, famotidine 20 mg four times daily and placebo in an open, four-way cross-over study. The subjects consumed 50 g alcohol after a standard lunch on the eighth day of dosing with study medication. Blood samples taken during the 6 h after alcohol consumption were analysed for alcohol concentrations by gas liquid chromatography using head space analysis. None of the H2-receptor antagonists had any statistically significant effects on any of the pharmacokinetic parameters for alcohol. Mean Cmax (95% CI) results for ranitidine were 547 (516, 580), cimetidine 531 (501, 563), famotidine 563 (530, 598) and placebo 529 (499, 561) mg l-1.

Adult↗
PubMed1993

Sex differences in the incidence of colorectal cancer: an exploration of oestrogen and progesterone receptors.

Sex differences exist in the site specific incidences of colorectal cancer. The increased incidence of colonic cancer in women with breast cancer and the protective effect of increasing parity suggest a role for sex hormones. To explore the molecular basis, the expression of messenger RNA for oestrogen and progesterone receptors in the large bowel has been studied. With northern and dot blot analyses mRNA coding for oestrogen receptor and progesterone receptor in large bowel cancers and corresponding normal mucosa and in adenomatous polyps has been identified. There were no significant differences in receptor mRNA concentrations between males and females or between cancers, normal mucosae, and polyps, except for rectal cancers, which had higher progesterone receptor concentrations than corresponding normal tissue. Oestrogen and progesterone receptor mRNA concentrations were strongly correlated in both cancers and normal tissues. Enzyme immunoassay for oestrogen receptor gave values of 1.2-7.4 fmol/mg total protein, an amount similar to that seen in normal breast tissue. Oestrogen receptor protein and mRNA for oestrogen receptor and progesterone receptor are present in the large bowel.

Adenocarcinoma↗
PubMed1992

Continuous intravenous famotidine for haemorrhage from peptic ulcer.

Peptic ulcer bleeding often stops spontaneously but rebleeding may be catastrophic. Emergency surgery carries risks so safe medical therapies are needed. Since platelet function and plasma coagulation are both pH sensitive and since pepsin lyses clot at low pH the maintenance of gastric pH close to neutrality might influence rebleeding rates. Previous trials with H2 antagonists have been inadequate although a 1985 meta-analysis did support an important clinical effect. We report here a large multicentre trial of famotidine in ulcer bleeding. 1005 patients admitted to one of sixty-seven hospitals in the UK or Eire with haemorrhage from peptic ulcer with endoscopic signs of oozing, black slough, fresh clot or visible vessel were randomly allocated to famotidine (10 mg bolus followed by 3.2 mg/h intravenously) or matching placebo for 72 h. This famotidine regimen had previously been shown to maintain pH near 7 in such patients. 497 patients received famotidine and 508 placebo. The treatment groups were similar in respect of age, sex, ulcer site, and signs and severity of bleeding. Case fatality (6.2% famotidine vs 5.0% placebo), rebleeding (23.9% vs 25.5% placebo), and surgery (15.5% vs 17.1% placebo) rates were not significantly different between the two groups. This trial suggests that potent inhibition of gastric secretion does not influence the natural history of peptic ulcer haemorrhage.

Aged↗
PubMed1992

Review of company postmarketing surveillance studies.

OBJECTIVES: To review postmarketing surveillance studies sponsored by the pharmaceutical industry since the introduction of voluntary guidelines in 1987 and to evaluate their contribution to monitoring drug safety. DESIGN: Retrospective analysis of the information submitted to the Medicines Control Agency on postmarketing surveillance studies. SETTING: United Kingdom. MAIN OUTCOME MEASURES: Study designs, projected and actual sample sizes, provision of interim and final reports, number of suspected serious adverse reactions reported, identification of new drug safety hazards. RESULTS: 31 studies had been conducted under the guidelines, of which 27 were prospective and four retrospective. Nine studies had at least one comparator group, the remainder were uncontrolled. The median projected sample size for the studies was 5600 patients. Only five studies had achieved at least 75% of the projected sample size. 11 studies had been abandoned, predominantly because of difficulties in recruitment, and 15 were ongoing. One study had identified an important new safety hazard. CONCLUSIONS: Company postmarketing surveillance studies have made only a limited contribution to the assessment of drug safety, principally because of weak study designs and difficulties in recruitment. The guidelines require modification to take this experience into account.

Drug Industry↗
PubMed1992

Omeprazole versus placebo for acute upper gastrointestinal bleeding: randomised double blind controlled trial.

OBJECTIVE: To investigate the possible therapeutic role of omeprazole, a powerful proton pump inhibitor, in unselected patients presenting with upper gastrointestinal bleeding. DESIGN: Double blind placebo controlled parallel group study. Active treatment was omeprazole 80 mg intravenously immediately, then three doses of 40 mg intravenously at eight hourly intervals, then 40 mg orally at 12 hourly intervals. Treatment was started within 12 hours of admission and given for four days or until surgery, discharge, or death. SETTING: The medical wards of University and City Hospitals, Nottingham. SUBJECTS: 1147 consecutive patients aged 18 years or more admitted over 40 months with acute upper gastrointestinal bleeding. MAIN OUTCOME MEASURES: Mortality from all causes; rate of rebleeding, transfusion requirements, and operation rate; effect of treatment on endoscopic appearances at initial endoscopy. RESULTS: Of 1147 patients included in the intention to treat analysis, 569 received placebo and 578 omeprazole. No significant differences were found between the placebo and omeprazole groups for rates of transfusion (302 (53%) placebo v 298 (52%) omeprazole), rebleeding (100 (18%) v 85 (15%)), operation (63 (11%) v 62 (11%)), and death (30 (5.3%) v 40 (6.9%)). However, there was an unexpected but significant reduction in endoscopic signs of upper gastrointestinal bleeding in patients treated with omeprazole compared with those treated with placebo (236 (45%) placebo v 176 (33%) omeprazole; p less than 0.0001). CONCLUSIONS: Omeprazole failed to reduce mortality, rebleeding, or transfusion requirements, although the reduction in endoscopic signs of bleeding suggests that inhibition of acid may be capable of influencing intragastric bleeding. Our data do not justify the routine use of acid inhibiting drugs in the management of haematemesis and melaena.

Age Factors↗
PubMed1992

Liver disease in a district hospital remote from a transplant centre: a study of admissions and deaths.

The profile of liver disease admissions and associated deaths in a district general hospital was studied to determine whether patients with end stage liver disease are appropriately referred for consideration of liver transplantation. Admission details were provided by the Office of Population Censuses and Surveys (OPCS) and their accuracy was assessed by case note analysis. According to OPCS, 77 patients with liver disease were admitted on 113 occasions between 1 January 1987 and 31 December 1989. The case notes of 74 (96%) were retrieved and examined. Only 64 (86%) had primary liver disease. Twenty four (31%) died of liver failure. Alcohol was the aetiological agent in two thirds. According to accepted criteria, 11 patients were suitable for liver transplant assessment but only three had been referred to a transplant centre. Of the remaining eight, five died during the study period. Two of the three patients referred died without transplantation; one underwent transplant and survived. There is discrepancy between OPCS data and true disease aetiologies, with approximately 40% under reporting of alcoholic liver disease. If this population is representative of the situation nationally, substantial numbers of patients with end stage liver disease might benefit from liver transplantation, but are not referred to a centre.

England↗
PubMed1992

Postmarketing surveillance of the safety of cimetidine: 10 year mortality report.

A total of 9928 cimetidine users were identified from prescriptions in four centres and followed for 10 years. The 'all-cause' mortality ratio fell from 1.9 in year 1 to 1.0 in years 8 to 10. Most of the early excess in mortality was attributable to cimetidine being given in the late stages of many diseases, often to counter adverse gastric effects of other drugs. Specific causes of mortality during years 5-10 of the study, were generally unremarkable. Significant increases in mortality ratios were apparent, however, for oesophageal cancer (years 5-7, 2.3; years 8-10, 1.9); lung cancer (years 5-7, 1.1; years 8-10, 1.7); diseases of the oesophagus, stomach, and duodenum (years 5-7, 3.3; years 8-10, 2.3); and chronic liver disease (years 5-7, 2.4; years 8-10, 3.3). None of these increases in mortality seems to be attributable to an adverse effect of cimetidine use. Data are also presented for mortality from diseases of the nervous system. Eight deaths (of which one was miscoded) were certified as being from motor neurone disease, representing a mortality ratio of 2.6 for years 2-10 of the study which is of borderline statistical significance. This study confirms that cimetidine is safe. Mortality from some diseases increased over the study period, but selection rather than any adverse effect of the drug is likely to be the explanation.

Cimetidine↗
PubMed1992

Non-steroidal anti-inflammatory drugs and peptic ulcer.

Non-steroidal anti-inflammatory drugs have been clearly shown to increase the chances of peptic ulcer and its complications. Risk factors associated with this propensity are as yet poorly and inconsistently defined. Clinicians have long accepted that non-steroidal anti-inflammatory drug (NSAID) treatment may cause peptic ulcer and its complications. In assessing the chances it is necessary to define what we mean by risk, to examine the features which provide convincing evidence of causality and to determine whether the studies available are of a sufficient standard to be compelling.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

Omeprazole.

Explore the source record for details and available documents.

Gastroesophageal Reflux↗
PubMed1991

A comparison of roxatidine and ranitidine for the acute treatment of duodenal ulcer.

Roxatidine acetate is a new histamine H2-antagonist of about twice the potency of ranitidine on a weight-for-weight basis. Two hundred and thirty-two patients participated in a double-blind randomized trial of duodenal ulcer healing comparing 300 mg ranitidine nocte with 150 mg roxatidine nocte. Endoscopy was repeated fortnightly to 4 weeks in each of four participating centres. Usual exclusion criteria applied but NSAID users were allowed. There were no important demographic differences between treatment recipients. Three analyses were used: protocol (dropouts and violators not included), intention-to-treat I (dropouts considered failures), and intention-to-treat II (dropouts considered failures, but violators outcome included). Healing rates differed markedly (but not significantly) with each analysis. After 2 weeks of treatment ulcers had healed in 51% versus 45% using the intention to treat I analysis with roxatidine and ranitidine, respectively; by the protocol analysis the healing proportions were 60% and 55%. These differences between treatments were not significant. After 4 weeks of treatment healing rates ranged from 71% to 83% on roxatidine and between 69% and 84% on ranitidine depending on the analysis. Differential healing proportions of smokers and non-smokers were non-significant (83% vs. 79%). Both drugs were well tolerated and adverse events were similar with each agent. Roxatidine should prove as effective as ranitidine for acute duodenal ulcer treatment.

Adult↗
PubMed1991

Omeprazole.

Omeprazole is a potent and effective antisecretory drug. Benefits in gastric and duodenal ulceration nevertheless seem marginal because standard treatments are very effective. More obvious advantages are discernible in oesophageal reflux disease where more profound acid inhibition may be needed to obtain symptom relief. Fears of important adverse effects either through inducing ECL cell hyperplasia or outright carcinogenesis, do not seem firmly founded, nor is there convincing evidence of significant interactions with other xenobiotics. Nevertheless, continued caution seems justified.

Animals↗
PubMed1991

Physical activity at work and duodenal ulcer risk.

To determine whether the social class differences in duodenal ulcer frequency may be explained by differences in physical activity at work, the energy expenditure during work, smoking habits, and social class were compared in 76 recently diagnosed duodenal ulcer patients and in age and sex matched community controls. As anticipated, the relative risk of duodenal ulcer showed significant associations with smoking and social class. Social class and physical activity at work were associated with one another. After adjusting for age, sex, smoking, and social class, physically active work was still associated with duodenal ulcer, with relative risks for moderate and high activity compared with sedentary work being 1.3 (0.6-3.0) and 3.6 (1.3-7.8) respectively. Within each social class stratum, the relative risk of having a duodenal ulcer was greater in those with a high level of occupational activity than in those undertaking sedentary work.

Adult↗
PubMed1991

Antacids and ulcer healing. A review of the evidence.

There have been a number of controlled trials of antacids in the treatment of patients with peptic ulcer disease. As a general rule the size of studies has been small and there have been difficulties ensuring adequate binding, because of the formulation and taste of the antacids. Despite these difficulties, antacids appear to be effective ulcer healing agents with efficacies resembling those of other antiulcer drugs. Definite dose relationships are unclear but high doses of buffering capacity over 200 mmol/day appear unnecessary and are associated with increasingly frequent adverse effects. Low dose maintenance treatment is effective at limiting duodenal ulcer relapse.

Antacids↗