126 patients with blood pressure which was unacceptably high despite a conventional stepped-care regimen (diuretic, beta-blocker, and vasodilator) took part in a comparative assessment of different approaches to the treatment of refractory hypertension. One of four regimens was used: oral diazoxide, minoxidil, captopril, or quadruple therapy (diuretic + beta-adrenoceptor blocker + hydralazine + prazosin). Despite the severity of hypertension, blood pressure could be controlled in almost all these patients, and no patient died from cerebrovascular disease while on treatment. 2 patients died of renal failure and 5 patients required long-term haemodialysis. Ischaemic heart disease remained a problem and caused the death of 10 patients. Diazoxide was the most effective treatment but was the most difficult and unpleasant to use. Captopril was the best-tolerated but failed to control blood pressure in 6 of 15 patients. Our experience indicates that there are now sufficient therapeutic alternatives to achieve acceptable blood-pressure control in almost all patients with "refractory" hypertension, although no treatment is ideal.

A highly purified preparation of hyaluronidase (GL enzyme) was given in a double-blind, placebo-controlled, randomised study to 192 consecutive patients within 12 h of suspected myocardial infarction. Compared with those receiving placebo, patients with definite myocardial infarction given GL enzyme had significantly less change in QRS complexes; in those with anterior infarction the development of Q waves was less prominent. At 4 months the overall mortality among those with definite and possible myocardial infarction receiving GL enzyme (6 out of 83 patients, 7.2%) was lower than that in those receiving placebo (11 out of 79, 14%); this difference was not significant. No adverse effects were observed.

The influence of intravenous GL enzyme (hyaluronidase) on the outcome of myocardial infarction was assessed in a controlled trial among 483 patients presenting within 6 h of the onset of symptoms. There was a consistent trend towards reduced mortality throughout the period of follow-up among GL enzyme treated patients. When the fate of all patients entering the trial was considered, irrespective of final diagnosis, the reduction in mortality at 6 months (27 of 240 GL enzyme patients, 45 of 243 placebo) was statistically significant (p = 0.025).

79 patients with suspected myocardial infarction entered a randomised trial to establish the safety of early intravenous administration of a highly purified hyaluronidase preparation (GL enzyme) and to assess its effects on eventual infarct size as measured by electrocardiographic, enzymatic, and scintigraphic criteria. Of the 71 patients with infarction, 35 received GL enzyme and 36 placebo within 6 h of the onset of chest pain. GL enzyme injected into a peripheral vein produced no adverse changes in the clinical, haemodynamic, biochemical, or haematological variables studied. GL enzyme reduced precordial electrocardiographic indices of infarct size as reflected by a diminution (p less than 0.02) in the degree of both R wave loss and Q wave development. In addition, the number of leads developing pathological Q waves (N delta Q greater than or equal to 2), a sign of progression from ischaemia to necrosis, was reduced (p less than 0.05) after GL enzyme treatment. However, there were no significant differences in infarct size as measured by cumulative creatine kinase MB isoenzyme release or technetium-99m pyrophosphate scintigraphic infarct area, or in clinical outcome during the hospital stay. Interpretation of the enzymatic and scintigraphic data was complicated by chance bias in pre-treatment randomisation which resulted in more (p less than 0.05) patients with severe haemodynamic impairment (and hence probably larger infarct sizes) entering the GL enzyme group. Nonetheless, a favourable effect of GL enzyme on infarct size was demonstrated by precordial electrocardiographic QRS mapping, here each patient acts as his or her own control.

72 patients severely immunocompromised by their underlying disease (marrow aplasia, acute leukaemia, or solid tumour) or by the treatment they were receiving, or both, were randomised to receive antifungal prophylaxis with either oral ketoconazole or conventional doses of oral amphotericin B and nystatin. All patients also had gut decontamination with non-absorbable antibiotics, skin antisepsis, sterile food, and oral cotrimoxazole. Protection against fungal infection was significantly superior with ketaconazole. When patients who had received allogeneic bone-marrow transplant were studied separately, there was no significant difference between the two treatments, probably because there was a fall-off in ketoconazole absorption from the end of the third week after the transplant. However, ketoconazole greatly reduced the likelihood of fungal infection in non-transplant patients.

Field studies were conducted in Kisumu, Kenya, to assess the susceptibility of local strains of Plasmodium falciparum to pyrimethamine alone (by a standard 7-day in-vivo test and a 48 h in-vitro field test) and to sulfadoxine-pyrimethamine (by a 7-day in-vivo test). Both in-vivo (10/11) and in-vitro (19/21) tests demonstrated that pyrimethamine resistance was very common. Parasite susceptibility to sulfadoxine-pyrimethamine was uniformly greater when 24 isolates were tested in vivo, thus indicating that this drug combination remains valuable despite the high frequency of resistance to pyrimethamine alone.

A phase-I clinical trial of a murine monoclonal antibody that specifically suppresses growth of human gastrointestinal tumours in athymic mice was conducted in four patients, who were given 15-200 mg purified antibody. The monoclonal antibody persisted in the circulation for more than a week when more than 15 mg was given. Antibodies against mouse immunoglobulin developed in three of the four patients. In one patient who received autologous mononuclear cells that had been mixed with monoclonal antibody by way of a hepatic-artery catheter, hepatic metastases became smaller and their echogenic characteristics changed, and there was heavier monocyte infiltration in the histological appearance of a resected metastasis.