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Objective To assess the possible benefit of hormone replacement therapy (HRT) in the secondary prevention of ischaemic heart disease. Design A prospective randomised trial of transdermal HRT in women with definite ischaemic heart disease. Setting A regional cardiac unit. Population Postmenopausal women with angiographically ischaemic heart disease. Methods A total of 255 postmenopausal women with angiographically proven ischaemic heart disease were recruited and randomised; 134 were treated with transdermal HRT and 121 acted as controls. The women were seen at six monthly intervals. The primary end points, which were determined by a blinded assessor, were admission to hospital with unstable angina, proven myocardial infarction or cardiac death. A total of 53 (40%) patients withdrew from the HRT group and eight (7%) from the control group. The mean duration of follow up was 30.8 months. Main outcome measures Admission to hospital with unstable angina, proven myocardial infarction or cardiac death. Results During follow up, there were 53 primary end-point events in the HRT group and 37 in the control group. Using an intention-to-treat analysis, the primary end-point event rate was 15.4 events per 100 patient years for the HRT group compared with 11.9 for the control group (event rate ratio 1.29 (95% CI 0.84–1.95, P= 0.24)). Using a per-protocol analysis, there was an event rate ratio of 1.49 (0.93–2.36, P= 0.11) for the HRT arm compared with the control arm. Particularly during the first two years of follow up, the HRT group had a higher, but not statistically significant, event rate than the control group. Conclusion Our findings suggest that transdermal HRT should not be commenced for the purpose of secondary prevention in postmenopausal women with angiographically proven ischaemic heart disease.

Summary Background Vitamin E (α-tocopherol) is thought to have a role in prevention of atherosclerosis, through inhibition of oxidation of low-density lipoprotein. Some epidemiological studies have shown an association between high dietary intake or high serum concentrations of α-tocopherol and lower rates of ischaemic heart disease. We tested the hypothesis that treatment with a high dose of α-tocopherol would reduce subsequent risk of myocardial infarction (MI) and cardiovascular death in patients with established ischaemic heart disease. Methods In this double-blind, placebo-controlled study with stratified randomisation, 2002 patients with angiographically proven coronary atherosclerosis were enrolled and followed up for a median of 510 days (range 3-981). 1035 patients were assigned α-tocopherol (capsules containing 800 IU daily for first 546 patients; 400 IU daily for remainder); 967 received identical placebo capsules. The primary endpoints were a combination of cardiovascular death and non-fatal MI as well as non-fatal Ml alone. Findings Plasma α-tocopherol concentrations (measured in subsets of patients) rose in the actively treated group (from baseline mean 34·2 μmol/L to 51·1 μmol/L with 400 IU daily and 64·5 μmol/L with 800 IU daily) but did not change in the placebo group. α-tocopherol treatment significantly reduced the risk of the primary trial endpoint of cardiovascular death and non-fatal Ml (41 vs 64 events; relative risk 0·53 [95% Cl 0·34-0·83; p=0·005). The beneficial effects on this composite endpoint were due to a significant reduction in the risk of non-fatal Ml (14 vs 41; 0·23 [0·11-0·47]; p=0·005); however, there was a non-significant excess of cardiovascular deaths in the α-tocopherol group (27 vs 23; 1·18 [0·62-2·27]; p=0·61). All-cause mortality was 36 of 1035 α-tocopherol-treated patients and 27 of 967 placebo recipients. Interpretation We conclude that in patients with angiographically proven symptomatic coronary atherosclerosis, α-tocopherol treatment substantially reduces the rate of non-fatal MI, with beneficial effects apparent after 1 year of treatment. The effect of α-tocopherol treatment on cardiovascular deaths requires further study.

The first recorded case of beta-blocker overdose complicated by rhabdomyolysis is described.

It has been established that following bilateral olfactory bulb ablation there occurs a performance deficit in rats exposed to aversive learning procedures. Associated with the behavioural deficit, there occurs a reduction in total cortical norepinephrine (NE). If the behavioural deficit observed is a sequitur or correlate of the NE reduction, then drug therapy aimed at increasing NE availability in the cortex should overcome the reduction in performance. Amitriptyline increases NE availability by inhibiting uptake mechanisms and increases the rate of synthesis of NE. Rats, previously bulb ablated, were treated with amitriptyline over a 10 to 14 day period and tested in aversive situations. It was demonstrated that the drug treated rats showed improved performance early in acquisition, and that the performance improvement was maintained when the treatment period was extended to 14 days. These results indicate that amitriptyline was inducing a true pharmacological effect, and that the improved performance could be correlated with increased NE availability in the cerebral cortex.

Changes in endogenous norepinephrine (NE) levels after bilateral olfactory bulb section have been found to occur in the rat brain. Since olfactory tract projections are confined to the ventral adrenergic pathway, and this pathway projects to the pyriform cortex, it was decided to examine the distribution of endogenous NE between the pyriform cortex and the remaining neocortex. It was demonstrated that significant reductions in NE content occurred in both brain regions, although the greater reduction occurred in the pyriform cortex. there were no significant changes in hypothalamic NE. It is concluded that sensory deprivation plus olfactory system damage induce specific changes in central function, which relate to noradrenergic pathways.

Summary A patient presenting with subacute thyroiditis who had evidence of chlamydial infection is reported.