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Betteridge, D. J.; Bhatnager, D.; Bing, R. F.; Durrington, P. N.; Evans, G. R.; Flax, H.; Jay, R. H.; Lewis-Barned, N.; Mann, J.; Matthews, D. R.
doi: 10.1136/bmj.304.6838.1335pmid: 1611329
OBJECTIVE--To compare the efficacy and safety of cholestyramine, an anion exchange resin, and pravastatin, a new hydrophilic specific inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, in the treatment of heterozygous familial hypercholesterolaemia. DESIGN--Double blind, double dummy, placebo controlled study with three parallel groups. SETTING--Six specialist lipid clinics in the United Kingdom. PATIENTS--128 patients aged 18-70 with heterozygous familial hypercholesterolaemia diagnosed on strict biochemical and clinical findings. MAIN OUTCOME MEASURES--Total plasma cholesterol, triglyceride, and lipoprotein subfractions and biochemical and haematological safety parameters. RESULTS--Pravastatin (40 mg/day) led to a 25% reduction in total plasma cholesterol concentration and a reduction in low density lipoprotein cholesterol concentration of 30%. Cholestyramine (24 g/day) led to similar reductions in concentrations of total cholesterol (23%) and low density lipoprotein cholesterol (31%). No consistent changes occurred in high density lipoprotein cholesterol values with either compound. Plasma triglyceride concentrations showed a small rise (18%) on resin therapy. No serious adverse drug reactions occurred during the study. CONCLUSIONS--Pravastatin seems to be a highly effective, well tolerated drug for severe hypercholesterolaemia. Patients chosen for this study were recruited on the basis that they could tolerate a full dose of cholestyramine, and in this situation cholestyramine was also highly effective in lowering plasma low density lipoprotein cholesterol concentrations.
Hibberd, A. D.; Pearson, I. Y.; McCosker, C. J.; Chapman, J. R.; Macdonald, G. J.; Thompson, J. F.; O'Connell, D. L.; Mohacsi, P. J.; McLoughlin, M. P.; Spratt, P. M.
doi: 10.1136/bmj.304.6838.1339pmid: 1611330
OBJECTIVES--To measure the potential for cadaver organ retrieval in New South Wales and to determine the reasons for potential donors failing to become actual donors. DESIGN--Prospective audit of all patients dying in five hospitals in New South Wales between 1 December 1989 and 30 November 1990; quality assurance of the data by independent medical specialist and if disagreement by study committee. PATIENTS--2879 patients (100% of all deaths) yielding 364 patients with coma and 181 potential donors. OUTCOME MEASURES--Realistic medically suitable potential donor rate, missed potential donor rate, rate of potential donors with permission refused, donor rate, reasons for realistic medically suitable potential donors failing to become actual donors. RESULTS--2879 deaths yielded 73 medically suitable potential donors, resulting in 19 actual donors, 30 missed potential donors, 19 potential donors with permission refused, and five in whom adequate resuscitation failed. The most common reason for a potential donor failing to become an actual donor was a decision by the senior medical practitioner to withdraw or not to institute ventilatory or haemodynamic support (26/73). The second major obstacle was refusal of permission by the next of kin (17/73). Assuming that the potential donor rate was that implied by the observed donor rate (13/million population/year) the projected missed potential donor rate was 9/million population/year (95% confidence interval 4 to 15) and the projected rate of potential donors with permission refused was 13/million population/year (95% confidence interval 5 to 22). Assuming that the rate of potential donors in the study hospitals was the same as in the other New South Wales hospitals, the projected donor rate for New South Wales was 18/million population/year (10 to 26); the projected missed potential donor rate was 15/million population/year (7 to 23); and the projected rate of potential donors with permission refused was 18/million population/year (10 to 27). CONCLUSIONS--The donor rate could be increased 70%-80% by overcoming the reluctance of medical practitioners to resuscitate missed potential donors and increased further by gaining permission for organ retrieval from the next of kin.
Brada, M.; Ford, D.; Ashley, S.; Bliss, J. M.; Crowley, S.; Mason, M.; Rajan, B.; Traish, D.
doi: 10.1136/bmj.304.6838.1343pmid: 1611331
OBJECTIVE--To assess the risk of second brain tumour in patients with pituitary adenoma treated with conservative surgery and external beam radiotherapy. DESIGN--Long term follow up of a cohort of patients with pituitary adenoma and comparison of tumour occurrence with population incidence rates. SETTING--The Royal Marsden Hospital. SUBJECTS--334 patients with pituitary adenoma treated with conservative surgery and radiotherapy (median dose 45 Gy) and followed up for 3760 person years. MAIN OUTCOME MEASURES--Second intracranial tumour and systemic malignancy. RESULTS--Five patients developed a second brain tumour: two had astrocytoma, two meningioma, and one meningeal sarcoma. The cumulative risk of developing a second brain tumour over the first 10 years after treatment was 1.3% (95% confidence interval 0.4% to 3.9%) and over 20 years 1.9% (0.7% to 5.0%). The relative risk of a second brain tumour compared with the incidence in the normal population was 9.38 (3.05 to 21.89). There was no excess risk of any other type of second primary malignancy. CONCLUSIONS--There is an increased risk of second intracranial tumour in patients with pituitary adenoma treated with surgery and radiotherapy. Although radiation is likely to be the most important factor contributing to the excess risk, further study is required in a cohort of similar patients not receiving radiation.
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