A double-blind, randomised trial of acyclovir versus placebo was conducted in 31 patients with initial and 85 patients with recurrent genital herpes. 17 patients with initial and 42 with recurrent disease were treated with 200 mg acyclovir by mouth five times a day for 5 days, and the remaining patients received matching placebo. In patients with initial genital herpes shedding virus acyclovir significantly reduced the duration of viral shedding, itching, and pain, the time to crusting and complete healing, and new lesion formation compared with controls. In patients with recurrence disease acyclovir significantly reduced the duration of viral shedding, time to complete healing, and new lesion formation. The reported incidence of adverse events was similar in both acyclovir and placebo groups. Oral acyclovir is effective and well tolerated in patients with initial and recurrent genital herpes and can be used in outpatient therapy.

23 unselected patients with mild to moderate essential hypertension, whose average supine blood pressure after two months' observation on no treatment was 154/99 mm Hg, were entered into an eight week double blind randomised crossover study of one month's treatment with slow release potassium tablets (60 mmol/day) versus placebo without alteration of dietary sodium or potassium intake. By the fourth week mean supine blood pressure had fallen by 4% on potassium supplementation compared with placebo. Urinary potassium excretion increased from 62 +/- 4.7 mmol/24 h on placebo to 118 +/- 7.4 mmol/24 h on potassium. The fall in blood pressure was not related to urinary sodium excretion before entry to the trial or while on placebo. Moderate potassium supplementation caused a small but significant fall in blood pressure in patients with mild to moderate essential hypertension and could be additive to the effects of moderate sodium restriction. This increase in potassium intake could be achieved with a potassium-based salt substitute and a moderate increase in vegetable and fruit consumption. Moderate dietary sodium restriction with dietary potassium supplementation may obviate or reduce the need for drug treatment in some patients with mild to moderate hypertension.

In a study designed to compare the Mantoux with the tine and 'Imotest' multiple-puncture tuberculin tests 200 subjects underwent a Mantoux test (10 IU PPD-Weybridge) and, simultaneously, either a tine test or an imotest. All tests were read after 72 h by two observers independently. The false-negative rate for the Mantoux was estimated by immediate repetition of the Mantoux in subjects with an initially negative Mantoux but positive multiple-puncture test. When the criterion for a positive reaction was at least 5 mm of induration for the Mantoux and at least 2 mm of induration for the multiple-puncture tests, the false-negative rate of 27% for the imotest was significantly higher than the 4% for the tine and 5% for the Mantoux (p less than 0.001 in each case). Positive multiple-puncture tests were always associated with a Mantoux test that was positive on either the first or second application. Observers agreed in their interpretation of 98% of all tests, and there were no significant differences between testers in frequency of false-negative results for any test. The tine test, when carefully applied and correctly interpreted, gives results which correlate well with those given by the standard Mantoux test. The imotest is less reliable and has no advantages over the tine test.

Multiresistant strains of Haemophilus ducreyi, the aetiological agent of chancroid, are prevalent in Nairobi, Kenya, where tetracyclines and sulphonamides are no longer very effective in the treatment of chancroid. The following regimens (given three times daily for seven days) were compared in a double-blind randomised trial--amoxycillin 500 mg, amoxycillin 500 mg and clavulanic acid 125 mg, and amoxycillin 500 mg and clavulanic acid 250 mg. 68 of 100 ulcers were culture-positive for H. ducreyi. All strains of H. ducreyi produced beta-lactamase. At day 7 none of the amoxycillin-treated patients had responded clinically or bacteriologically, whereas all but 2 of 56 patients treated with an amoxycillin/clavulanic-acid regimen had responded clinically and H. ducreyi had been eradicated from their ulcers. The combination of amoxycillin-clavulanic acid appears to be very effective for the treatment of chancroid. The results of this study accord with H. ducreyi as the primary pathogen of chancroid.

90 patients on medication for mild hypertension were randomly allocated to diet and control groups and kept under surveillance by their own doctors every 2 weeks for 12 weeks to test the short-term effectiveness of a diet free from sodium additives as an alternative to medication. Mean urinary sodium excretion was reduced 37.0 mmol/24 h in the diet group and 161.0 mmol/24 h in the control group, with average K/Na ratios of 3.9 and 0.50. Both groups had a fall in mean systolic and diastolic blood pressure, but the diet group finished on half of the initial amount of medication, with 1 patient in 3 off medication and 4 out of 5 having either stopped or reduced the dose. The control group remained on almost the full amount of medication, with 2 patients out of 3 having made no reduction. The diet group had a mean weight loss of 2.1 kg, a rise in serum potassium, and a fall in serum bicarbonate. There was no increase in overall frequency of muscle cramp, and the diet group reported feeling happier, less depressed, and less dependent on analgesics. Two-thirds of the diet group intend to continue to diet indefinitely. Reduction of sodium intake permitted drug treatment to be substantially reduced without side-effects or loss of blood-pressure control.

To investigate the need for and effects of phototherapy in full-term otherwise healthy babies with physiological jaundice, 40 consecutive babies with serum bilirubin levels of 250 mumol/l or more were assigned at random to two treatment groups. Phototherapy was started in the early group (n = 20) when serum bilirubin was 250 mumol/l and in the late group (n = 20) when serum bilirubin reached 320 mumol/l; however, only 3 of the late group required treatment. Phototherapy prevented a further rise in bilirubin in almost all treated babies, but the difference in peak bilirubin level between early and late treatment groups was not significant. Early phototherapy produced a more rapid decline in bilirubin; levels fell to below 250 mumol/l in a median of 28 h with early treatment and 54 h with late treatment. In each group the ratio of boys to girls was 2/1 and boys remained jaundiced for significantly longer. Phototherapy therefore curtailed the rise and duration of hyperbilirubinaemia, but the effect was small. Jaundice subsided spontaneously in most of these mature infants, especially girls. Phototherapy can separate mother from baby, and it is physiologically stressful. Treatment may be safely withheld until serum bilirubin exceeds 320 mumol/l.

94 diabetic patients established on treatment with porcine (n = 47) or bovine (n = 47) insulin took part in a double-blind crossover trial, in which 6-week periods of treatment with the appropriate animal insulin were compared with periods of treatment with biosynthetic human insulin (BHI). 6 patients withdrew during the trial, in 3 cases because of hypoglycaemia while taking BHI. In bovine-insulin-treated patients, the mean glucose level (mean of seven capillary-blood samples over 1 day), the modified M index, and total daily insulin requirement were the same on BHI and bovine-insulin treatment. For porcine-insulin-treated patients, mean glucose level and the modified M index were slightly higher on BHI than on porcine-insulin treatment (9.7 vs 9.0 mmol/l and 79.6 vs 65.0, respectively), despite an average increase of 2.3 units/day of BHI after 6 weeks of such treatment. Hypoglycaemic episodes were not significantly more or less frequent on BHI in either group of patients. In both groups fasting blood glucose was higher during BHI treatment than during animal-insulin treatment (14.2 vs 12.8 mmol/l [bovine group]; 12.1 vs 9.6 mmol/l [porcine group]). In bovine-insulin-treated patients blood glucose before the evening insulin injection was higher on BHI than on bovine insulin (11.6 vs 10.0 mmol/l). BHI appears to be a safe alternative to porcine or bovine insulin. Differences in the pharmacokinetics of BHI may account for the observed differences in blood-glucose responses.

In a double-blind controlled trial 43 patients with relapsing-remitting multiple sclerosis were treated either with anti-lymphocyte globulin, prednisolone, and azathioprine, or with placebo preparations. Treatment began with a combination of the three medicaments but after 1 month was continued for another 14 months with azathioprine (3 mg/kg dialy) only. There was a marginally beneficial effect of immunosuppression on the overall relapse rate and clinical progression. However, there were significant effects on in-vitro lymphocyte function and in the visual evoked potentials in favour of the group receiving suppressive treatment. Placebo-treated patients of the HLA A3 tissue type had significantly more relapses than placebo-treated patients who were not of type HLA A3. Nevertheless, HLA-A3-positive patients treated with immunosuppression had significantly fewer relapses than A3-positive placebo-treated patients.

The haematological and clinical effects of medroxyprogesterone acetate in homozygous sickle-cell (SS) disease were assessed in a 2-year controlled crossover trial completed by 23 patients. Haematological indices remained steady during the placebo phase, but during the medroxyprogesterone-acetate phase fetal haemoglobin, total haemoglobin, red-cell mass, and red-cell survival rose significantly, and reticulocytes, irreversibly-sickled-cell counts, and total bilirubin fell significantly. Painful crises were significantly less frequent during the medroxyprogesterone-acetate than the placebo phase. These results are compatible with an inhibition of in-vivo sickling in patients with SS disease during medroxyprogesterone-acetate treatment. The mechanisms of such an effect require further study.

To confirm the findings of uncontrolled trials that methylprednisolone pulse therapy (MPPT) is a safe treatment for active rheumatoid disease, a double-blind trial was conducted in which 20 patients with active rheumatoid disease were randomly allocated to receive an infusion of either 1 g methylprednisolone or placebo. Methylprednisolone produced significant improvement in all clinical variables measured, a benefit which was sustained for at least 6 weeks. The placebo produced only transient improvement in some of the clinical variables measured. when the 10 placebo groups patients were later given an infusion of 1 g methylprednisolone, they too showed significant clinical benefit. The methylprednisolone also gave rise to improvements in some haematological and biochemical variables.

Initial clinical studies in 32 Senegalese subjects have demonstrated the efficacy of ivermectin in Onchocerca volvulus infection (river blindness). Although O. volvulus microfilariae in skin snips were not reduced in number after single oral doses of 5 micrograms or 10 micrograms/kg body-weight, they were greatly reduced in all subjects after single oral doses of 30 micrograms or 50 micrograms/kg and were eliminated completely in 6 of th 8 subjects who received the 50 micrograms/kg dose. All subjects tolerated the drug well. Transient pruritus which did not require treatment was observed on the day the dose was given in 2 of the 8 subjects after the 30 micrograms/kg dose and in 4 of the 8 who received the 50 micrograms/kg dose. Ivermectin produced no abnormal laboratory results.

31 adults took part in a randomised, placebo-controlled, double-blind trial of intravenous acyclovir therapy (500 mg/m2 intravenously 3 times daily for 5 days) for acute herpes zoster. Acyclovir reduced pain, decreased erythema, prevented the formation of new lesions, and healed skin faster than did placebo. The duration of viral shedding was also significantly shorter in acyclovir recipients (2 days versus 5 days). However, 6(35%) of 17 acyclovir recipients had recurrence of pain after the drug was discontinued, and acyclovir did not appear to affect post-herpetic neuralgia. Acyclovir therapy was associated with a transient rise in serum creatinine levels, and may have been related to nausea and vomiting. Intravenous acyclovir was effective therapy for acute herpes zoster but the ideal treatment regimen might be a lower daily dose given for a longer period.