Biomedical subjects
Publications and source records attributed to J Collier.
A case is described of NMS during treatment with sulpiride. The subsequent psychosis resolved during treatment with carbamazepine. It is proposed that this patient may have suffered from a supersensitivity psychosis, and that resolution of her post-NMS psychosis could have been spontaneous.
NG monomethyl-L-arginine (L-NMMA), a specific inhibitor of the synthesis of endothelium-derived nitric oxide (NO), was infused into the brachial arteries of healthy volunteers to study the role of NO in the control of forearm blood flow. L-NMMA caused a 50% fall in basal blood flow and attenuated the dilator response to infused acetylcholine but not that to glyceryl trinitrate. These results indicate that the dilator action of endothelium-derived NO contributes to the control of basal and stimulated regional blood flow in man. Impairment of production of NO might account for the abnormalities in vascular reactivity that characterise a wide variety of disease states.
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Endothelium derived relaxing factor (EDRF) has been identified as nitric oxide, synthesised from the amino acid L-arginine, a process which is inhibited by the L-arginine analogue NG-monomethyl L-arginine (L-NMMA). We have studied the effect of local infusions of L-NMMA on venous reactivity in healthy volunteers. Studies were performed using the veins on the back of the hand. The diameter of a single dorsal hand vein was measured in healthy subjects who had taken 600 mg of aspirin 30 min before the experiment. Changes in diameter were recorded during local infusions of noradrenaline, bradykinin, acetylcholine, glyceryl trinitrate, L- and D-arginine and its NG-monomethyl derivatives. L-NMMA (100 nmol.min-1) stereospecifically inhibited vasodilatation induced by acetylcholine and bradykinin (p less than 0.02) but not that induced by the endothelium independent vasodilator glyceryl trinitrate. L-NMMA (100 nmol.min-1) potentiated the venoconstrictor effect of a high dose of acetylcholine (100 nmol.min-1) without affecting the action of noradrenaline and without having a direct venoconstrictor effect in doses up to 10 mumol.min-1. These results show that the venous effects of certain vasodilators in man are mediated through the release of nitric oxide (EDRF) synthesised from L-arginine. They also highlight differences in basal and stimulated production of nitric oxide between arteries and veins.
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In a study of 28 attenders of a sexual and marital clinic, the relationship between marital distress and both general and specific sexual dysfunctions was investigated. It was found that for men there was a much closer relationship between sexual and marital problems than for women. In particular, it was noted that the specific male sexual dysfunctions of impotence and premature ejaculation played a much larger part in marital discord than did the female dysfunctions of anorgasmia and vaginismus.
A considerable volume of animal pharmacologic data support the view that increased flux through the polyol pathway provides a unifying hypothesis for the major complications of diabetes. An extensive clinical program has been established to verify the extrapolation of the animal pharmacologic findings to man. Clinical data accumulated to date confirm the biochemical and electrophysiologic effects, and encouraging evidence of a drug effect in diabetic neuropathy and retinopathy has already been observed. In the large, controlled safety data base already available, the long-term clinical use of sorbinil is devoid of significant adverse effects in terms of both subjective side effects and laboratory parameters. The only clinically important adverse reaction reported to date has been a hypersensitivity reaction in the early weeks of therapy, which is similar to that seen with other hydantoins.
A bone resorptive agent extracted from the tissues surrounding orthodontically-treated teeth is purified using ultrafiltration and isoelectric focusing. A two-fold increase in release of 45Ca could be achieved with as little as 0.6 microgram/ml of this material.
The feasibility, face validity and repeatability of a self-complete questionnaire to assess patients' attitudes and beliefs about asthma was evaluated in 45 adult patients attending a hospital asthma clinic. The questionnaire consisted of 40 statements with which the patient agreed or disagreed by placing an 'X' along a visual analogue line. Patients completed questionnaires at their clinic consultation and then were interviewed to ascertain whether questionnaire responses agreed with a verbal description of their attitudes and beliefs. Repeatability was assessed by having patients complete an identical questionnaire four weeks after their interview. The questionnaire responses showed excellent agreement with interview findings, suggesting that face validity was good. Repeatability also appeared satisfactory in that agreement between responses on the first and second questionnaires was significant for 31 of the 40 items. Many patients (22%) incorrectly used the analogue line response scale making feasibility unacceptably low. However, subsequent studies showed this problem could be overcome by the use of a four-point Likert response scale. These findings suggest that this questionnaire is a satisfactory instrument for assessing patients' attitudes and beliefs about asthma. Its face validity appeared good and, with certain modifications, it was both feasible and repeatable.
Analysis of the names of students from London medical schools taking their final examinations in June 1982, 1983 and 1984 has revealed that racial and sexual discrimination operate when students are selected for medical education. On the basis of name the ratios of European to African, Asian or Arabic students vary significantly between the two extreme schools (P less than 0.01), and for any school the proportion tends to be consistent from year to year. Differences also occur between the proportion of females at each school. Furthermore, the pattern of racial and sexual discrimination at each school shows a highly significant rank correlation (r = 0.77). The admission policies at the different London medical schools need to be reviewed.
Extensive animal data now exist to indicate potential benefit of sorbinil in the treatment of the major complications of diabetes mellitus. A clinical programme has been constructed to explore this therapeutic potential and encouraging evidence of drug effect has already been observed in patients with neuropathy and retinopathy. Two small preliminary studies in patients with painful neuropathy have shown that clinically significant reduction of pain was more frequently achieved with sorbinil than with placebo. A 6-month study of patients with retinopathy, using vitreous fluorophotometry as the criterion of retinal damage, showed significant (p = 0.03) benefit for the sorbinil group compared with the placebo group. Drug evaluation in these areas is complex and difficult but it is anticipated that the accumulation of additional data will further substantiate the efficacy suggested by these early findings. The only clinically important adverse effect of sorbinil is the hypersensitivity reaction. This usually occurs during the initial weeks of therapy and is similar to that seen with phenytoin. The long term use of sorbinil is without significant adverse effects.
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