Since hypertensive disorders of pregnancy are common, blood pressure is frequently measured in all pregnant women. Many authorities recommend that Korotkoff phase IV (K4, muffling of sound) is taken as the diastolic identification point measured on mercury sphygmomanometry in pregnancy because of reports that phase V (K5, disappearance of sound) is at or near to zero cuff pressure in some pregnant women. We compared the identification and reproducibility of K4 and K5 by observers unaware of each other's results.

Polymorphism in the gene for angiotensin-converting enzyme (ACE), especially the DD genotype, is associated with risk for cardiovascular disease. Glomerulosclerosis has similarities to atherosclerosis, and we looked at ACE gene polymorphism in patients with kidney disease who were in a trial of long-term therapy with an ACE inhibitor or a beta-blocker.

Excimer laser coronary angioplasty is reported to give excellent procedural results for treatment of complex coronary lesions, but this method has not been compared with balloon angioplasty in a randomised trial.

Endoscopic sphincterotomy is sometimes done unnecessarily in patients with suspected choledocholithiasis. Our aims were to assess the diagnostic accuracy of endoscopic ultrasonography and endoscopic retrograde cholangiography (ERC) and to find out whether endoscopic ultrasonography may help to prevent unnecessary sphincterotomy or surgical explorations.

The spread of chloroquine resistance poses a serious problem in Africa, where falciparum malaria transmission is the highest in the world. Pyronaridine, an acridine derivative, has been used successfully to treat malaria in China for over 20 years. We compared the efficacy of pyronaridine and chloroquine in African adult patients with acute uncomplicated falciparum malaria in Yaoundé, Cameroon, where chloroquine resistance is well established.

For the patient with diabetes, hypoglycaemia unawareness--ie, the warning signs of falling blood glucose are missing--is potentially dangerous. One study has suggested that, in healthy volunteers, caffeine might be a helpful treatment. Our study looked at two effects of caffeine ingestion (250 mg) on the brain--namely, a decrease in cerebral blood flow and an increase in brain glucose use--to see if the recognition of and physiological responses to hypoglycaemia were altered in patients with insulin-dependent diabetes mellitus (IDDM).

The role of housedust-mite (HDM) allergen (Der p1) in the pathogenesis of atopic dermatitis is controversial. We tested the hypothesis that atopic dermatitis improves if amounts of HDM allergen in the home are reduced.

Up to a third of patients have early rebleeding from oesophageal varices after endoscopic variceal ligation. Octreotide infusion is effective for control of variceal bleeding. We investigated the efficacy of octreotide infusion as an adjunct to endoscopic variceal ligation to prevent early rebleeding from varices. 100 consecutive patients admitted with endoscopically confirmed oesophageal varices and active bleeding or signs of recent haemorrhage were randomly assigned endoscopic variceal ligation alone or octreotide (50 micrograms intravenous bolus injection followed by intravenous infusion at 50 micrograms per h for 5 days) plus endoscopic variceal ligation. Three patients in each group were excluded. Bleeding was controlled in 44 of 47 patients who received variceal ligation alone and in 45 of 47 who received combined treatment (p = 1.0). Recurrent bleeding was documented in 18 (38% [24-52]) patients who received variceal ligation alone and in four (9% [3-21] who received combined treatment (p = 0.0007). The relative risk of rebleeding was lower (0.22 [0.08-0.60]) in the combined therapy group. Ten patients in the variceal ligation group and one in the combined therapy group required balloon tamponade for massive haematesis and haemodynamic instability (p = 0.0039). The in-hospital and 30-day mortality rates were higher in the variceal ligation group than in the combined therapy group (19 vs 9% and 23 vs 11%), but the differences did not reach significance. The relative risks of in-hospital (0.5 [0.04=5.3]) and 30-day (0.45 [0.17-1.2]) mortality were lower in the combined therapy group. Octreotide significantly reduces recurrent bleeding and the need for balloon tamponade in patients with variceal haemorrhage treated by endoscopic variceal ligation.

The effect of dihydropyridines in patients with unstable angina is discouraging. To find out the effect of the non-dihydropyridine-like calcium-channel blocker diltiazem, a randomised, double-blind trial was conducted comparing diltiazem with glyceryl trinitrate, both given intravenously, in 129 patients with unstable angina. The endpoints were refractory angina or myocardial infarction, individually and as a composite endpoint. Refractory angina alone or together with myocardial infarction occurred significantly less commonly in the diltiazem group. While patients were on the trial drugs the numbers with refractory angina were 6 (10%) in the diltiazem group versus 17 (28%) in the glyceryl trinitrate group (relative risk 0.36, p = 0.02), and the numbers with refractory angina and myocardial infarction were 9 (15%) versus 23 (38%) (relative risk 0.40, p = 0.007). Over 48 h the number were: refractory angina 8 (13%) versus 18 (30%), relative risk 0.45, p = 0.03, and refractory angina and myocardial infarction 12 (20.0%) versus 25 (41%), relative risk 0.49, p = 0.02. Patients in the diltiazem group had better (p < 0.05) event-free survival while taking the drugs. Heart-rate pressure product was reduced significantly only by diltiazem (p < 0.05). The incidence of bradyarrhythmias did not differ significantly. Atrioventricular conduction disturbances occurred in 5 (8%) patients in the diltiazem group but were not seen in the glyceryl trinitrate group (p = 0.03). These disturbances could be reversed by decreasing the dose of the drug or withdrawing it. No temporary pacemakers were required. Headache requiring an analgesic or dose adjustment occurred significantly less in the diltiazem group: 3 (5%) versus 15 (25%), relative risk 0.20 (p < 0.004). These results indicate that intravenous diltiazem, compared with intravenous glyceryl trinitrate, significantly reduces ischaemic events and can be used safely in patients with unstable angina.

Previous trials to assess the efficacy of lumbar traction for back pain have been methodologically flawed. To avoid these shortcomings, we conducted a randomised controlled trial in which high-dose traction was compared with sham traction. The sham traction was given with a specially developed brace that tightens in the back during traction. To the patient, the experience is that of traction. The patients and outcome assessor were blinded for the assigned treatment. 151 patients with at least six weeks of non-specific low back pain were randomised. Intention to treat analysis showed no differences between the groups on all outcome measures (patients' global perceived effect, severity of main complaints, functional status and pain); all 95% confidence intervals included the value zero. The number of withdrawals from treatment, loss to follow-up, and protocol deviations was low. Consequently, the per-protocol analysis showed results similar to the intention to treat analysis. Subgroup analyses did not show any group for which traction might seem promising. Our data do not support the claim that traction is effective for patients with low back pain.

In ischaemic stroke, thrombolytic drugs speed the recanalisation of intracerebral arteries. The effects of aspirin are not known. A trial was conducted to determine whether, separately or together, streptokinase and aspirin have clinical benefits in acute ischaemic stroke similar to those in acute myocardial infarction. 622 patients with acute ischaemic stroke within 6 hours of symptom onset were randomised with a 2 x 2 factorial design to (i) a 1-hour intravenous infusion of 1.5 MU streptokinase, (ii) 300 mg/day buffered aspirin for 10 days, (iii) both active treatments, or (iv) neither. Early results raised a question whether the trial should be continued. Streptokinase (alone or with aspirin) was associated with an excess of 10-day case fatality (odds ratio 2.7; 95% confidence interval 1.7-4.3; 2p < 0.00001). Of the four groups randomised, only patients allocated to streptokinase plus aspirin had a significantly higher risk of early death than those given neither streptokinase nor aspirin (odds ratio 3.5; 95% CI 1.9-6.5; 2p < 0.00001). Streptokinase (alone or with aspirin) and aspirin (alone or with streptokinase) reduced, albeit not significantly, the incidence of combined six-month case fatality and severe disability: odds ratio for streptokinase 0.9 (95% CI 0.7-1.3) and odds ratio for aspirin 0.9 (95% CI 0.6-1.3). The risk of early death with thrombolytic treatments should be weighed against the potential benefit of a marginal reduction of severe disability after the first six months.

Retinopathy of prematurity (ROP) is a potentially blinding disease of preterm infants. 21 days of computer-recorded transcutaneous oxygen (TcPO2) data were compared in 31 infants with stage 3 or greater ROP and 38 infants with no ROP or stage 1 or 2. In a multiple logistic regression adjusted for significant perinatal factors (birthweight, gestation, and intraventricular haemorrhage), babies with stage 3 or higher ROP showed an increased variability of TcPO2 in week 1 (p < 0.01) and 2 (p = 0.012) but not week 3. Variability of TcPO2 in the first 2 weeks of life is a significant predictor of severe ROP.

Irrational prescribing is a habit which is difficult to cure. However, prevention is possible and for this reason the WHO Action Programme on Essential Drugs aims to improve the teaching of pharmacotherapy to medical students. The impact of a short problem-based training course in pharmacotherapy, using a WHO manual on the principles of rational prescribing, was measured in an international multi-centre randomised controlled study of 219 undergraduate medical students in Groningen (Netherlands), Kathmandu (Nepal), Lagos (Nigeria), Newcastle (Australia), New Delhi (India), San Francisco (USA), and Yogyakarta (Japan). The manual and the course presented the students, who were about to enter the clinical phase of their studies, with a normative model for pharmacotherapeutic reasoning in which they were taught to generate a "standard" pharmacotherapeutic approach to common disorders, resulting in a set of first-choice drugs called P(ersonal)-drugs. The students were then taught how to apply this set of P-drugs to specific patient problems on the symptomatic treatment of pain, using a six-step problem-solving routine. The impact of the course was measured by tests before training, immediately after, and six months later. After the course, students from the study group performed significantly better than controls in all patient problems presented (p < 0.05). The students not only remembered how to solve old problems, but they could also apply their skills to new problems. Both retention and transfer effect were maintained at least six months after the training session in all seven medical schools. In view of the impossibility of teaching students all basic knowledge on the thousands of drugs available, this approach seems to be an efficient way of teaching rational prescribing. However, the method should be accompanied by a change in teaching methods away from the habit of transferring knowledge about the drugs towards problem-based teaching of therapeutic reasoning.

Surgery for intractable epilepsy is a widely used treatment that is not readily assessed by randomised trials. We evaluated the impact of epilepsy surgery on seizures, medication use, employment, and the quality of life in 248 adults and adolescents consecutively referred to one medical centre between 1974 and 1990. Outcomes were determined through self-administered questionnaire and medical record review for 202 surgery and 46 non-surgery patients whose treatment was usually determined by the presence or absence of an epileptogenic focus. Surgery and non-surgery patients differed at baseline only in median monthly seizure frequency (surgery lower than non-surgery). After adjustment for baseline covariates, surgery patients at follow-up had greater decline in average monthly seizure frequency (-11.9 vs - 1.5; difference -10.4, 95% CI -20.5, -0.3) and took fewer antiepileptic medications (average number 1.4 vs 2.0; difference -0.67, 95% CI -0.94, -0.40). Although quality-of-life scores were higher (p < 0.05) with surgery on 5 of 11 scales that were administered only at follow-up, there were no significant differences in employment status or prospectively assessed quality of life. Relative to a non-surgery group, patients treated surgically had better seizure control with less antiepileptic medication. The impact of epilepsy surgery on quality of life and employment needs to be assessed in larger prospective studies.