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Biomedical subjects

G Watkinson

Publications and source records attributed to G Watkinson.

At least 19 recordsLinked to original sources
PubMed1989

Risk factors and prognosis in primary biliary cirrhosis.

The relationship between survival and 25 clinical and histologic variables was studied in 195 patients (171 women, 24 men) who satisfied stringent criteria for the diagnosis of primary biliary cirrhosis. The mean duration of follow-up was 6 yr (range 0-17). One hundred and sixteen patients died, 84% as the result of liver disease and 16% from nonhepatic causes. Using the Kaplan-Meier estimate, we calculated the mortality from liver disease to be 40% after 5 yr and 60% after 10 yr. Ascites, serum bilirubin level, variceal hemorrhage, and age were identified as independent clinical risk factors, and extent of hepatic fibrosis, bilirubinostasis, and Mallory's hyalin were identified as independent histologic risk factors correlating with reduced survival.

Adult↗
PubMed1988

Double-blind comparison of two dosage regimens of misoprostol in the treatment of duodenal ulceration.

A multicenter double-blind study was conducted in 416 patients (306 male, 110 female) with active endoscopically proven duodenal ulcers who were randomly allocated to receive the prostaglandin E1 methyl ester analog (Misoprostol/Cytotec), either in a dose of 400 micrograms twice daily (206 patients) or 200 micrograms four times daily (210 patients). No significant difference in the healing rates between the two groups was observed at four or eight weeks. In patients treated twice daily, the ulcer healing rate at four weeks for the intent-to-treat cohort was 124/205 (60.5%) and for the evaluable cohort was 96/136 (69.1%). In patients treated four times daily, the healing rate was 124/207 (59.9%) for the intent-to-treat cohort and 96/148 (64.9%) for the evaluable cohort. Similarly, the healing rates achieved at eight weeks for the twice- and the four-times-daily dosages in the intent-to-treat cohort were 72.2% and 74.4%, respectively, and for the evaluable cohort were 88.0% and 86.6%, respectively. Significantly more patients receiving misoprostol twice daily were free of ulcer pain after four weeks of treatment than were those receiving misoprostol four times daily, namely, 71.4% as compared with 57.9%, respectively (P = 0.003) and for a median period of 21 as compared with 17 days (P = 0.002). Diarrhea was more common in patients receiving the drug twice daily, (15.5%) than in those treated four times daily (5%) (P = 0.001). Diarrhea, three or more stools daily, was often transient and self-limiting and only necessitated withdrawal from the trial in nine (4.4%) of those treated with misoprostol twice daily and in one patient (0.5%) of those treated four times daily.(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗
PubMed1988

Abetalipoproteinaemia in adults: role of vitamin therapy.

The retinal and neurological complications of abetalipoproteinaemia may be preventable by replacing vitamins A and E from an early age, but their role in adult presentations is less clear. Two adult females with abetalipoproteinaemia have received 8 and 10 years respectively of replacement therapy with vitamins A, E and linoleic acid. In Case 1, visual function improved objectively on commencing therapy but has subsequently deteriorated and her neuropathy has slowly progressed. The rate of progression of neurological impairment in Case 2 was slowed but not halted by therapy, and her severe visual disturbance was unaffected. Replacement by fat soluble vitamins has only a limited role in the management of abetalipoproteinaemia once irreversible neurological/retinal damage has occurred.

Abetalipoproteinemia↗
PubMed1988

A clinical trial of the efficacy and acceptability of D-fenfluramine in the treatment of neuroleptic-induced obesity.

Twenty-nine overweight schizophrenic patients maintained on depot neuroleptic injections who wished to lose weight took part in a double-blind, placebo-controlled trial of 30 mg D-fenfluramine. All subjects received dietary advice. Sixteen patients completed the 12-week trial. Rate of weight loss was significantly greater in those taking D-fenfluramine. Side-effects were reported, but no deterioration in mental state was noted.

Adult↗
PubMed1988

The therapeutic efficacy of misoprostol in peptic ulcer disease.

Misoprostol, a synthetic methyl ester analogue of prostaglandin E1 (PGE1) is both a powerful inhibitor of gastric secretion and is able to protect the gastroduodenal mucosa from damage produced by alcohol, aspirin, naproxen and tolmetin. The results of 12 double-blind, randomized, placebo- and cimetidine-controlled trials involving 4000 patients have been reviewed here and show that misoprostol, given in a dosage of 800 micrograms daily in two or four divided doses, is able to produce rates of complete ulcer healing and pain relief in both gastric and duodenal ulcer which are significantly superior to placebo therapy and comparable to those achieved with high or conventional doses of cimetidine. One further large trial has shown that misoprostol is able to heal a significant proportion of duodenal ulcers refractory to treatment with H2 receptor antagonists. In the compromised patient, two trials have suggested that misoprostol is able to abolish the adverse effects of smoking on duodenal ulcer, although this effect was not apparent in the gastric ulcer trials or in other duodenal ulcer trials. Similarly, while in volunteers pretreatment with misoprostol is able to protect the gastric mucosa from alcohol damage, there is little clinical evidence to support improved ulcer healing in the patient who abuses alcohol. Further studies in these areas should be conducted. Misoprostol could well have an important role to play in the protection of the gastroduodenal mucosa from damage produced by non-steroidal anti-inflammatory drugs (NSAIDs) in arthritic patients compelled to take these drugs for long periods. A series of double-blind placebo-controlled trials in healthy volunteers have shown that pretreatment with, or simultaneous administration of, 800 micrograms daily of misoprostol, reduces significantly mucosal damage produced by aspirin, tolmetin and naproxen. Two controlled clinical trials in a large number of arthritic patients have shown firstly, that misoprostol 800 micrograms daily is able to reduce significantly aspirin-induced mucosal bleeding as compared with placebo and secondly, in an endoscopically, placebo-controlled trial that it reduced significantly the frequency and severity of aspirin-induced mucosal lesions, accelerated the healing of erosions and ulcers and in other patients was able to protect the undamaged mucosa from injury. Misoprostol is well tolerated--a dose related, usually self limiting, diarrhoea occurred in a small proportion of patients but only rarely enforced withdrawal. Because of its uterotropic effects misoprostol should not be given to women of child bearing age unless they are taking adequate contraceptive measures. It has no other systemic effects and no clinically significant adverse haematology or biochemical abnormalities, or drug interactions have been reported. It does not seem to induce hypergastrinaemia. Misoprostol is, therefore, a safe and effective drug in the treatment of chronic peptic ulcer and could have a beneficial action in duodenal ulcers refractory to treatment with H2-receptor antagonists. It could benefit compromised groups of ulcer patients who are smokers or alcohol users amd certainly has been shown to protect the gastroduodenal mucosa against damage induced by NSAIDs in healthy volunteers and arthritic patients.

Alprostadil↗
PubMed1988

The OMGE multinational inflammatory bowel disease survey 1976-1986. A further report on 3175 cases.

This presentation describes the progress during 1982-1986 of the OMGE Multinational Survey of patients with inflammatory bowel disease. After a brief description of the study design and protocol, the status of the survey in 1986 is presented. In all, 40 centres contributed 3175 cases at that time, data collection being meticulous via previously designed proformata. Diagnostic criteria are next discussed. Little change between 1976 and 1986 is noted, with wide congruence of diagnostic thought, now codified into a simple (and recommended) OMGE diagnostic scoring system. Patients seen prior to 1978 were reviewed in 1986. Where attempted, a follow-up of over 86% was achieved, usually more than 4 years after the original presentation involving no less than 5215 'patient-years' of observed follow-up. Following these overall considerations, details of four subprojects are annexed, each of which was presented as a 'free paper' at the 8th World Congress and concerning, respectively, the changing natural history of IBD, risks of perforation and toxic megacolon in the 1980s, IBD in elderly patients, and features associated with recurrence in Crohn's disease.

Colitis, Ulcerative↗
PubMed1988

The natural history of inflammatory bowel disease: has there been a change in the last 20 years?

This presentation reviews the course and outcome of disease in 2657 cases of inflammatory bowel disease (IBD) registered into the OMGE multinational survey and considers whether there are differences between the natural history of IBD observed in this series and that observed in earlier large-scale series. It is concluded that several such differences exist. The current mortality from ulcerative colitis (4% in 10 years) is similar to that from Crohn's disease and quite different from that recorded in earlier series (over 20% in 10 years). This may be because the disease itself has changed (the proportion of patient-years with severe attack has fallen from 14.6% in the 1960s to under 10% in the present series). It may also be because of increasing use of maintenance sulphasalazine (since the attack rate per year is significantly lower than patients on maintenance therapy). Finally, cancer is now equally common in Crohn's disease and ulcerative colitis patients; whilst perforation is more common in Crohn's disease (possibly because ulcerative colitis patients now tend to come to surgery earlier).

Colitis, Ulcerative↗
PubMed1988

Perforation of the intestine in inflammatory bowel disease. An OMGE survey.

This presentation assesses the incidence of perforation of the intestine in patients with inflammatory bowel disease by reviewing the incidence of this complication in a total of 3175 patients from the OMGE inflammatory bowel disease multi-national survey. Amongst 1928 patients with ulcerative colitis, perforation was noted in only 5 (0.3%), which is much lower than in previous series (from 1% to 2%). By contrast, 19 of 1247 patients with Crohn's disease had perforated (1.5%). The survey thus suggests that the incidence of perforation in ulcerative colitis has fallen in the last 2 decades, probably as a result of the widespread implementation of early surgery. The risk of perforation of Crohn's disease remains quite high.

Colitis, Ulcerative↗
PubMed1988

Inflammatory bowel disease in the elderly patient.

Studies of inflammatory bowel disease (IBD) undertaken in the 1960s reported a highly unfavourable course and prognosis in patients over the age of 60 years. However, recent surveys have suggested that the pattern of IBD in the elderly patient is similar to the overall pattern of disease in other age groups. We have, therefore, reviewed data relating to 2657 patients from the OMGE series with particular reference to the pattern of disease in 244 patients (9.1% of the total group) aged over 60 years at the time of registration into the survey. The course and outcome of disease in these 244 patients were similar to other age groups in terms of response to therapy, major complications, and rate of recourse to surgery. However, the death rate in the elderly (2.4%) was higher than that in younger patients (0.8%). We concur with recent studies that the course of IBD is now more favourable in elderly patients than hitherto suspected. The cause is probably multifactorial, involving both a change in therapy and a change in the natural history of the disease.

Age Factors↗
PubMed1988

Factors affecting recurrence after surgery for Crohn's disease.

The prospect of recurrence following surgery for Crohn's disease (CD) poses an important and difficult problem in routine clinical practice. Out of the 1247 CD patients registered in the OMGE multinational inflammatory bowel disease survey, a high proportion came to surgery. A detailed study has been undertaken of 154 patients (77 who did recur matched with 77 who did not recur) who had undergone surgery for CD. An assessment was made which established a 'risk factor' (RF) for each item of patient information. Findings indicated the risk of recurrence to be higher in patients under 20 years both at onset of disease (RF, 2.2:1) and at time of their operation (RF, 2.7:1) and in patients with distal colonic Crohn's disease (RF, 1.8:1). Histopathologic findings, number of previous operations, and symptomatic status prior to operation did not appear to affect the subsequent risk of recurrence. The margin of clearance at operation appeared to affect further recurrence. Amongst patients with 10cm or more margin of clearance (i.e. histopathologically normal bowel) only 21% recurred during follow-up, versus 50% in those with a smaller margin of clearance.

Age Factors↗
PubMed1987

Misoprostol in peptic ulcer disease.

Misoprostol, a synthetic prostaglandin E1 (PGE1) methyl ester analog has potent antisecretory and cytoprotective effects on the gastric and duodenal mucosa which should make it an effective drug in the treatment of gastric and duodenal ulcer. In two multicenter, randomised, double-blind, controlled studies involving over 900 patients with endoscopically proven benign gastric ulcer and in six similar studies involving over 2000 patients with active duodenal ulcers, differing doses of misoprostol have been compared with either placebo therapy or with conventional doses of cimetidine. In these studies misoprostol 800 mcg daily given as two or four divided doses has been shown to produce rates of complete ulcer healing and pain relief which were significantly superior to placebo therapy and comparable to those achieved with cimetidine. Drug related adverse effects were infrequent. A dose related diarrhea occurred in a small proportion of patients which seldom necessitated suspension of therapy. Because of the known uterotropic effect of prostaglandins the drug should not be used in pregnant women or women of child bearing age unless they are using adequate contraceptive measures. No clinically significant adverse, hematological or biochemical effects have been reported. Two studies suggested that misoprostol reduced the adverse effect of smoking on the healing of duodenal ulcer. In addition, misoprostol has been shown to protect the gastro-duodenal mucosa from the damaging effects of alcohol and non-steroidal anti-inflammatory drugs. This action may prove of value in the treatment of ulcer patients who are inveterate smokers, alcohol users or who are compelled to consume non-steroidal anti-inflammatory drugs for pain relief from rheumatic and allied diseases.

Alprostadil↗
PubMed1987

Enhanced oral bioavailability of meptazinol in cirrhosis.

Kinetic analysis was carried out after single intravenous (25 mg) and oral (200 mg) doses of the novel partial opioid agonist meptazinol (Meptid) in patients with non-cirrhotic liver disease (NCLD) and biopsy proven cirrhosis. Comparison was made with a group of patients with normal hepatic function. Elimination half-lives after the intravenous dose were slightly prolonged in the cirrhotics (n = 10; 4.2 +/- 0.6 h) compared with the control (n = 8; 2.7 +/- 0.2 h: p less than 0.05) and NCLD (n = 8; 3.2 +/- 0.5 h) groups. There was no significant difference in meptazinol plasma clearance between the groups (cirrhotics = 72 +/- 8 l/h; NCLD = 89 +/- 9 l/h; control = 83 +/- 10 l/h). After the oral dose, seven of 15 cirrhotic patients vomited but only one patient in each of the other groups was unable to tolerate the drug (p = 0.06). This may be explained by very much higher peak meptazinol concentrations in the cirrhotic (n = 8; 184 +/- 37 ng/ml, p less than 0.01) and NCLD (n = 8; 131 +/- 38 ng/ml, p less than 0.05) patients than those of the controls (n = 7; 53 +/- 12 ng/ml) reflecting a mean four-fold and two-fold increase in oral bioavailability respectively (cirrhotics: n = 8; 27.9 +/- 5.3%: p less than 0.001; NCLD: n = 7; 13.7 +/- 3.9% p less than 0.05; controls: n = 7; 6.5 +/- 1.3%). There was no evidence of accumulation after chronic dosing with 200 mg meptazinol four times daily for 13 doses in seven control, seven NCLD and six cirrhotic patients. There were no detectable differences in psychomotor function measured objectively using the Leeds Psychomotor Tester of subjectively by linear analogue scoring between the groups in all three parts of the study. The oral use of meptazinol in patients with chronic liver disease is associated more with the development of nausea and vomiting rather than excessive sedation. These data suggest that dosage reduction in cirrhotic patients is advisable particularly if the drug is taken by mouth.

Administration, Oral↗
PubMed1987

Peptic ulcer and cancer: an examination of the relationship between chronic peptic ulcer and gastric carcinoma.

The relationship between peptic ulceration and gastric carcinoma has been examined using data from two large autopsy surveys. The first consisted of over 13,000 autopsies performed in a single hospital over a 20-year period and analysed retrospectively; the second was a prospective series of over 7000 autopsies carried out at 17 centres during a single year. In both, a lower than expected occurrence of coexistent gastric cancer was found in subjects with pathologic evidence of active or past gastric and duodenal ulceration. A statistical association between chronic gastric ulcer and lung cancer was noted. This study has failed to identify an increased risk of gastric carcinoma in patients with chronic gastric ulcer.

Aged↗
PubMed1987

Colectomy for slow transit constipation.

A series of 21 patients (18 female) whose intractable constipation was treated by colectomy between 1976 and 1985 is reported. There was no mortality attributable to surgery in this series. Total colectomy with ileorectal anastomosis was the preferred operation, but it produced a satisfactory result in only 12 patients. Five patients were treated by a permanent ileostomy, as the primary procedure in two. Megarectum did not automatically preclude a good result from ileorectal anastomosis, but a poor result was associated with failure of either a rectal stump to conduct colonic movements or of the anal sphincter to relax. Long term follow-up is necessary for assessment of results since late relapse can occur.

Chronic Disease↗
PubMed1986

Adult celiac disease (celiac sprue), pernicious anemia and IgA deficiency. Case report and review of the relationships between vitamin B12 deficiency, small intestinal mucosal disease and immunoglobulin deficiency.

A 24-year-old man with addisonian pernicious anemia, adult celiac disease and selective IgA deficiency is presented to emphasize the differential diagnosis of vitamin B12 deficient megaloblastic anemia in association with small intestinal mucosal abnormalities and the relationships between immunoglobulin deficiency, pernicious anemia, and adult celiac disease.

Adult↗
PubMed1986

Pharmacokinetics and pharmacodynamics of intravenous midazolam in patients with severe alcoholic cirrhosis.

Midazolam kinetics and psychomotor function were studied after an intravenous dose of 0.075 mg/kg body weight in seven patients with alcoholic cirrhosis and eight control patients. Four of the seven cirrhotics died of complications of their liver disease within six months of the study. The metabolism of midazolam was significantly impaired in the cirrhotic patients (p less than 0.025). These patients also had evidence of greater sedation than the control group for up to six hours after the dose was administered (p less than 0.05). The clearance of midazolam did not correlate significantly with the serum albumin, or bilirubin, or with the kinetics of antipyrine, or indocyanine green. This study shows significant delay in the elimination of midazolam and decreased psychomotor function in patients with severe alcoholic liver disease. Caution is needed in using this drug for premedication in such patients before endoscopy.

Adult↗