A comparison of once and twice daily atenolol for angina pectoris

We have studied the effects of four doses of atenolol in 11 patients with stable angina pectoris using a symptom-limited exercise test and angina diaries. The doses 100 mg twice daily and 50 mg, 100 mg and 200 mg once daily were given double-blind and randomised within patients following run-in on placebo. Measurements were made 12 hours after the last twice daily dose and 24 hours after the last once daily dose. Exercise tolerance was improved by 40-74% and exercise duration before the onset of angina by 61-94% (P less than 0.01). Maximal heart rate was reduced further by a total daily dose of 200 mg than by lower doses, but no extra benefit was derived by giving the drug twice daily. The largest increase in exercise tolerance was obtained during treatment with 50 mg once daily. Atenolol was shown to be an effective anti-anginal agent when given once daily, and there were no major differences between the doses studied.     

Diastolic forward blood flow in the pulmonary artery detected by Doppler echocardiography

The etiology of diastolic motion of the pulmonary valve seen on the M-mode echocardiogram has been the subject of much debate. To further investigate diastolic events in the pulmonary artery, the patterns of diastolic pulmonary artery blood flow velocity were studied using pulsed Doppler echocardiography in patients with a normal heart. Two diastolic waveforms were found, one in early diastole related to passive filling of the right ventricle and one in late diastole related to atrial contraction. These waveforms were also related to the two recognized phases of diastolic pulmonary valve motion detected by M-mode echocardiography. The presence of biphasic diastolic blood flow in the pulmonary artery was confirmed by electromagnetic flow velocimetry in four additional patients with various cardiac diseases and normal right heart pressures. It is concluded that both atrial contraction and passive right ventricular filling produce blood flow in the pulmonary artery.     

The alpha-2-antiplasmin Arg407Lys polymorphism is associated with Abdominal Aortic Aneurysm

Introduction

Abdominal Aortic Aneurysm (AAA) involves dilatation of the abdominal aorta, with a natural history of expansion and eventual rupture. We have previously shown that AAA patients form denser clots with smaller pores, which are more resistant to fibrinolysis. The aim of this study was to use functional polymorphisms of the fibrinolytic system to identify how changes to proteins involved in fibrinolysis may play a role in the development of AAA.

Methods

Caucasian subjects ≥ 55 years (602 AAA patients and 490 matched controls) were genotyped for four polymorphisms (α-2-antiplasmin α2AP Arg6Trp and Arg407Lys, Thrombin-activatable fibrinolysis inhibitor TAFI Thr325Ile and tissue plasminogen activator tPA 7351C → T). DNA was extracted from blood, and genotype identified using real time PCR. Fibrin clot structure was analysed by permeation and turbidity in a subset of patients and controls.

Results

Genotypes across the study population were in Hardy-Weinberg Equilibrium. The two α2AP polymorphisms, Arg6Trp and Arg407Lys were in linkage disequilibrium (P < 0.0001), and possession of a 407Lys allele negatively associated with AAA (odds ratio 0.833, CI95 0.7-0.991, P = 0.040). The TAFI Thr325Ile and the tPA 7351C → T polymorphisms were not associated with AAA. The α2AP 407Lys allele was not associated with in-vitro fibrinolysis times in plasma from patients with AAA.

Conclusion

Possession of the α2AP 407Lys allele was negatively associated with AAA, and thus changes in α2AP may affect aneurysm growth and development. These data indicate that the regulation of plasmin activity (through binding to α2AP), rather than plasmin generation (TAFI, tPA), may play a role in AAA.     

Aetiologic factors in lymphoid malignancies: a case-control epidemiological study

A prospective case-control study of the aetiologic factors involved in the production of lymphoid malignancies has been conducted within a defined geographical area covering six health districts in the Yorkshire Region. Among the aspects investigated were past medical events, occupations and certain social factors. A number of possible causal relationships have been identified including Jewish religion, past solvent exposure and ingestion of amphetamines, although the latter did not achieve statistical significance in this study. In addition several new associations have been identified, most notably with the occurrence of adult eczema/dermatitis and with treatment by radiation or steroids. The feasibility of conducting such a broadly based epidemiological investigation has been established.