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Biomedical subjects

J F Munro

Publications and source records attributed to J F Munro.

At least 19 recordsLinked to original sources

Appraisal of the clinical value of serotoninergic drugs.

Principal objectives in obesity management comprise the prevention of weight gain, the promotion of weight loss, and the treatment of obesity-related complications, including diabetes, hypertension, and depression. Serotonin agonists reduce food intake. The resultant weight loss is variable and there appears to be no way of predicting good responders, nor is there evidence that additional weight loss attributable to drug therapy is sustained once treatment is discontinued, although nonpharmacological strategies for preventing weight regain are worthy of exploration. Serotonin agonists are of clinical value if there is a short-term need for weight reduction or if long-term pharmacotherapy can be justified. This implies that sometimes the dangers of the obese state outweigh the potential hazards of drug treatment. Clearly, if the same agent also improves diabetic control, blood pressure, or depression then a longer term usage is more readily justified. The extent to which this may be achieved by the currently available 5-HT agonists is discussed.

Appetite Depressants

Medical clinic referral letters. Do they say what they mean? Do they mean what they say?

Consecutive general practitioner referrals to three general medical clinics were examined prospectively to assess whether the reason for referral was being correctly interpreted by consultants. The resultant data revealed that although this was not always the case, such misunderstandings did not appear to affect subsequent management. Explicit reasons for referral in the referral letter however could improve both the quality and value of out-patient consultations.

Communication

The effects of a new beta-adrenoceptor agonist BRL 26830A in refractory obesity.

Beta-adrenoceptor agonists have recently been shown to promote substantial loss of adipose tissue in laboratory animals. One of these BRL, 26830A, increases thermogenesis in human volunteers and has been shown to enhance the rate of weight reduction in patients adhering to a strict reducing regimen. Forty-three post-menopausal or sterilized female subjects suffering from refractory obesity participated in a double-blind placebo-controlled study, the treatment group receiving BRL 26830A 50 mg qid. Two subjects were withdrawn because they developed an unpleasant sensation of tremor and in all, 17 of the 20 who received BRL 26830A mentioned this side effect. There was no change in erect or supine blood pressure or in resting heart rate. There was no significant difference in weight change during the 6-week study. It is concluded that BRL 26830A does not appear to promote weight reduction in subjects unable to adhere strictly to their dietary regime.

Adrenergic beta-Agonists

Pre-conceptual dietary management for maternal phenylketonuria.

Experience of preconceptual dietary management of maternal hyperphenylalaninaemia is limited. Two Edinburgh mothers with hyperphenylalaninaemia and borderline IQ have received dietary advice to maintain normal plasma Phe concentration both before conception and during pregnancy, in an attempt to prevent foetal abnormality. Satisfactory compliance was only obtained after intensive in-patient instruction and the diets were maintained for long periods prior to conception. Intellectual and psychological factors were very important and the availability of "same day" biochemical reports useful in encouraging the mothers. Both infants have normal Phe concentrations and satisfactory growth and development parameters at present. Further follow-up continues but these cases provide further evidence in favour of the use of preconceptual dietary advice in the management of maternal hyperphenylalaninaemia.

Adolescent

Placebo controlled double-blind trial of fluvoxamine maleate in the obese.

Obesity and depression are common disorders which may co-exist. The management of the combination is complicated because some antidepressants cause weight gain fenfluramine, an effective antiobesity agent, may cause depression. Fluvoxamine is an antidepressant which, like fenfluramine, inhibits serotonin re-uptake within the brain. Forty obese female subjects with refractory obesity participated in a double-blind placebo controlled trial. During the twelve week study, those subjects receiving fluvoxamine achieved a mean weight loss greater than, but not significantly different from, that of the placebo group. The result suggests that fluvoxamine may be particularly useful in the management of obese patients requiring treatment with an antidepressant.

Adolescent

A comparison of the pharmacokinetics of propranolol in obese and normal volunteers.

The pharmacokinetics of intravenous and oral propranolol have been compared in six obese and six normal subjects matched for age and sex. After intravenous administration there was no difference in plasma clearance but the volume of distribution was greater (V = 339 l vs 198 l) and the half-life was longer (t1/2 = 5.0 h vs 3.0 h) in the obese group. No important difference in the rate of oral absorption was observed. A trend towards higher systemic availability in the obese group (35% vs 27%) was not statistically significant.

Administration, Oral

Pharmacological approaches to the regulation of fat metabolism.

There are a variety of methods whereby pharmacotherapy can induce weight loss. These include reducing food intake, impairing absorption of nutrients, inhibiting lipid biosynthesis and increasing energy expenditure. Various drugs are currently being evaluated which exert these modes of action. There are a large number of existing thermogenic drugs, though for one reason or another, they do not appear to be of practical value in the management of obesity. Three novel agents are BRL 26830A, LY 104 119 and RO 16-8714. These agents are chemically similar and all have lipolytic effects particularly in brown adipose tissue. BRL 26830A has been evaluated in man with conflicting results. The possible advantages and limitations of thermogenic agents in human obesity are discussed. Although the animal results are encouraging, it is advisable to take a cautious view regarding their therapeutic potential.

2-Hydroxyphenethylamine

Intermittent protein-sparing fasting with abdominal belting.

In an attempt to minimize the weight regain that often follows effective weight reduction, a programme has been evaluated which involved the use of a nylon waist cord which could be readily tightened but not lengthened, during a regime of alternating periods of a liquid diet and a high-fibre natural diet combined with behavioural modification. Forty subjects completed the initial cycle of a liquid regime with an overall weight loss of 7.7 kg during the treatment period. Thirty-six of these subjects have been followed up for a mean of 12 months after the completion of the treatment programme. Five subjects are difficult to categorize having worn the cord for some but not all of this time. Fourteen have continued to wear the waist cord throughout and have achieved a further mean weight loss of 4.8 kg. This differs significantly from the 17 subjects who cut off the cord and who have regained a mean of 6.6 kg. The results suggest that an adjustable waist cord is a valuable aid to achieving successful and permanent weight reduction in some subjects.

Adult

Thyroxine malabsorption following intestinal bypass surgery.

Jejuno-ileal bypass surgery for morbid obesity results in small bowel malabsorption. This may produce various nutritional or mineral deficiencies. A patient who became hypothyroid following bypass surgery required a larger than normal dose of thyroxine, presumably because of impaired absorption. In such patients it is particularly important to measure serum thyrotrophin concentrations in assessing the replacement dose of thyroxine.

Dose-Response Relationship, Drug

The significance of gross elevations of the erythrocyte sedimentation rate in a general medical unit.

One hundred consecutive patients with an ESR of 100 mm or more in the first hour admitted to a general medical unit were studied. Their mean age was 67 years and forty-seven were male. Three patients recovered without a satisfactory diagnosis. In thirty-three of the remainder a single diagnosis was considered responsible for the elevation of the ESR, and in the others multiple diagnoses were found. Infection was found in 60% of patients, malignancy in 28% (including 7% with myelomatosis), rheumatoid disease in 20% and renal disease in 11%. 34% of patients died within 6 months of entry into the study. In the absence of rheumatoid disease or a paraproteinaemia, elevation of the ESR in excess of 60 mm in the first hour at 1 month or longer was associated with a particularly poor prognosis. This study has shown the diagnostic implications of an ESR of 100 mm or more in the first hour and the prognostic significance of a persistent elevation of the ESR.

Adult

Polymyalgia arteritica: a clinical review.

In a series of thirty-seven consecutive patients with polymyalgia arteritica, twenty-five had polymyalgia rheumatica and twelve had cranial arteritis. Some failed to respond promptly to low doses of prednisolone and it is recommended that the initial dose should be in the order of 40 mg daily. An ESR above 40 mm in the first hour was present in four patients 3 months after admission; three were found to have rheumatoid disease and one pulmonary tuberculosis. Symptomatic relapses occurred in fourteen patients on twenty-one occasions and all responded to an increase in the daily dose of maintenance prednisolone. Most occurred in the first year and were attributable to an excessively rapid reduction in steroid therapy. Relapses occurring in patients on a stable dose of prednisolone were commonly associated with the development of rheumatoid disease. In elderly patients who have relapsed, or who have had arteritic complications, life-long prednisolone therapy appears justifiable.

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