30 patients with corneal epithelial defect due to removal of corneal foreign bodies were randomly allocated to receive either chloramphenicol with continuous application of an eyepad or chloramphenicol without the eyepad. Almost all corneal defects were healed at 24 h, and all were healed by 48 h, with no statistically significant difference between the two groups. Discomfort at 24 h was greater in the eyepad group than in the control group. An eyepad seems to confer no benefit in healing and is uncomfortable.

To examine whether antipyretic therapy in young children is associated with potential risks (interference with enhanced host defences at febrile temperatures) or benefits (improved comfort and behaviour), a randomised, double-blind, placebo-controlled trial of paracetamol was conducted among 225 children 6 months to 6 years of age who presented with acute (less than or equal to 4 days) fever (greater than or equal to 38 degrees C per rectum) without evident bacterial focus of infection. Parents were asked to give paracetamol liquid 10-15 mg/kg or placebo every 4 h as needed for fever and to avoid bathing, sponging, or other pharmacological agents. Parents kept temperature and symptom diaries and recorded changes in child comfort and behaviour according to a pretested, 5-category Likert-type questionnaire 1-2 h after every dose. There were no significant differences between treated and placebo groups in mean duration of subsequent fever (34.7 vs 36.1 h) or other symptoms (72.9 vs 71.7 h). Paracetamol-treated children were more likely to be rated by their parents as having at least a 1-category improvement in activity (38 vs 11%; p = 0.005) and alertness (33 vs 12%; p = 0.036) but no significant differences were noted in mood, comfort, appetite, or fluid intake. That overall improvement in behaviour and comfort with paracetamol was not impressive is underscored by the inaccuracy of parents' "guess" at the end of the trial as to which agent their child had received-45% correct guesses for paracetamol and 52% for placebo. The data suggest that the clinically relevant hazards and benefits of paracetamol antipyresis have been exaggerated.

An open clinical trial of amocarzine was carried out in onchocerciasis patients in Ecuador and Guatemala. Administration after food was more effective than that during fasting. The most effective and best tolerated regimen, 3 mg/kg twice daily after food for 3 days (in 312 patients), killed 73% of 1477 female worms at nodulectomy 4 months after treatment. The mean microfilarial skin count was greatly reduced within a week (6-11% Of day 0 value on day 8) and it remained low at least 6 months (14-18% on day 180). Follow-up of a higher dose 3 day regimen taken while fasting showed microfilaridermia of 7-9% of the day 0 value 2 years after treatment.

In a randomised phase I trial of a recombinant vaccina virus vaccine expressing the gp160 envelope gene of the human immunodeficiency virus (HIVAC-1e) 35 healthy, HIV-seronegative males, 31 of whom had a history of smallpox immunisation and 4 of whom were vaccinia naive, were vaccinated and then boosted 8 weeks later with HIVAC-1e or standard NY strain vaccinia virus. The frequency, duration, and titre of virus isolation from the vaccination site and occurrence of local side-effects were similar between the two groups of vaccinees. Vaccinia-naive (vac-n) subjects shed virus from the vaccination site for longer and at a higher titre than did vaccinia-primed (vac-p) individuals (19 vs 7 days and 10(7) vs 10(5) pfu/ml, respectively). In-vitro T-cell proliferative responses to one or more HIV antigen preparations developed in 13 of 16 vaccinia-primed subjects inoculated with HIVAC-1e. T-cell responses were, however, transient and in no subject did antibodies to HIV become detectable. The 2 vaccinia-naive subjects vaccinated with HIVAC-1e showed strong T-cell responses to homologous and heterologous strains of whole virus and to recombinant gp160 protein that remained detectable for over a year; antibodies to HIV envelope also developed in both. Recombinant vaccinia virus vaccines induce T-cell priming to the foreign gene products in most individuals. If used as the sole immunising agent they will be most efficacious in vaccinia-naive individuals.

The efficacy of co-trimoxazole for the treatment of Plasmodium falciparum parasitaemia in children younger than 5 years of age was evaluated in Malawi. 46 children with P falciparum parasitaemia, 37% of whom also met clinical criteria for a diagnosis of acute lower respiratory tract infection, were treated with 20 mg/kg co-trimoxazole twice daily for five days. Parasitaemia (mean clearance time 2.7 days) and symptoms were rapidly abolished and improvement was maintained during follow-up for 14 days. Co-trimoxazole may be an effective single treatment for febrile illness in young children in areas where malaria is endemic, resources are few, and diagnosis must rely on clinical findings alone.

The part that candida plays in antibiotic-associated diarrhoea was investigated in 24 elderly inpatients (mean age 74 years) who tested negative for Clostridium difficile toxin and other intestinal pathogens. 7 had intestinal overgrowth of Candida species (greater than or equal to 10(5) cfu/ml). None of the 24 matched, antibiotic-treated controls without diarrhoea had candida overgrowth. All 5 patients with diarrhoea and candida overgrowth treated with oral nystatin responded with resolution of diarrhoea and lowering of faecal counts to less than 10(4) cfu/ml within 7 days of start of antifungal therapy despite continuation of antibacterial therapy. In the other 2 patients with candida overgrowth, the diarrhoea subsided spontaneously and faecal candida counts returned to normal (less than 10(4) cfu/ml) after antibacterial agents were withdrawn. In patients without candida overgrowth, diarrhoea persisted until antibiotics were withdrawn, at a mean of 16 days after study entry.

Long-term zidovudine therapy in patients with human immunodeficiency virus (HIV) infection can cause a destructive mitochondrial myopathy with histological features of ragged-red fibres (RRF) and proliferation of abnormal mitochondria. In 9 zidovudine-treated patients with this myopathy we found severely reduced amounts (up to 78% reduction vs normal adult controls) of mitochondrial DNA (mtDNA) in muscle biopsy specimens by means of Southern blotting. In 2 HIV-positive patients who had not received zidovudine, muscle mtDNA content did not differ from that in the 4 controls. Depletion of mtDNA seems to be reversible, since 1 patient showed a substantial reduction in RRF and a concomitant pronounced increase in muscle mtDNA content after zidovudine therapy was discontinued. Depletion of muscle mtDNA is probably due to zidovudine-induced inhibition of mtDNA replication by DNA polymerase gamma and is not a secondary effect of HIV infection.

To compare the safety and efficacy of subcutaneous and intravenous infusion of opioid analgesics, a randomised, double-blind, crossover trial was carried out in inpatients. 15 patients with severe cancer pain received two 48 h infusions of hydromorphone--one subcutaneously and one intravenously in randomly allocated order. The study was made double-blind by the use of two infusion pumps throughout; during the active subcutaneous infusion the intravenous pump delivered saline and vice versa. Serial measurements of pain intensity, pain relief, mood, and sedation by means of visual analogue scales showed no clinically or statistically significant difference between the two infusion routes. Side-effects were slight, and the mean number of morphine injections for breakthrough pain did not differ significantly between the routes (4.8 [SD 4.5] for intravenous vs 5.3 [5.6] for subcutaneous). Plasma hydromorphone concentrations measured at 24 h and 48 h of infusion showed stable steady-state pharmacokinetics; the mean bioavailability from subcutaneous infusion was 78% of that with intravenous infusion. Because of the simplicity, technical advantages, and cost-effectiveness of continuous subcutaneous opioid infusion into the chest wall or trunk, intravenous opioid infusion for the management of severe cancer pain should be abandoned.

In a comparison of spontaneous continuous arteriovenous haemofiltration (CAVH) and pump-driven haemofiltration (PDHF) for acute renal failure after surgery, 116 patients admitted to a surgical intensive care unit were assigned CAVH (48) or PDHF (68). The method of assignment was that a patient was treated by PDHF if he or she was the only patient requiring treatment at that time (only one pump was available); any other patient coming to the unit would be treated by CAVH. The groups were slightly unbalanced because there were fewer simultaneous cases than expected. The main endpoints were survival rate, control of uraemia, and additional application of haemodialysis. There were no differences between the patient groups in age, duration of treatment, severity of illness, serum creatinine concentration at the start of treatment, or cause of acute renal failure. Both treatments adequately controlled uraemia and fluid overload. However, the survival rate was significantly higher with PDHF than with CAVH (6 [12.5%] vs 20 [29.4%]; p less than 0.05). The daily ultrafiltrate volume was significantly higher with PDHF than with CAVH (15.7 [95% confidence interval 13.6-17.8] vs 7.0 [6.6-7.4] l/day; p less than 0.05). The volume of ultrafiltrate in patients with ischaemic or sepsis-induced acute renal failure was correlated with the survival rate. This finding suggests that the better survival rate in the PDHF group was due to faster elimination of toxic mediators (of molecular weight 800-1000 daltons) through the filter membrane by high-volume haemofiltration.

To find out whether non-specific immunosuppression is beneficial in multiple sclerosis (MS) a randomised, placebo-controlled, single-masked trial was carried out in nine university centres. 168 patients with clinically or laboratory-supported definite MS in progressive phase (deterioration by at least 1.0 on the expanded disability status scale [EDSS] in the previous year) were randomised to receive intravenous cyclophosphamide and oral prednisone (n = 55); daily oral cyclophosphamide, alternate day prednisone (22 weeks), and weekly plasma exchange (20 weeks) (n = 57); or placebo medications and sham plasma exchange (n = 56). All patients were followed for at least 12 months (mean 30.4 months) by a monitoring neurologist, who was aware of treatment allocation, and an evaluating neurologist, who was not. The primary analysis was a comparison of rates of treatment failure (worsening of evaluating neurologist's assessment of EDSS by 1.0 or more on two consecutive 6-monthly assessments). There were no significant differences among the groups in this primary analysis (19 [35%] treatment failures with cyclophosphamide; 18 [32%] with plasma exchange; 16 [29%] with placebo). Nor were there any differences in the proportions improved, stabilised, or worsened at each 6 month assessment or in the mean change in the EDSS at the final assessment (0.81 cyclophosphamide; 0.69 plasma exchange; 0.69 placebo). A slight trend favouring the plasma exchange group at 12-24 months of follow-up was not sustained at the final assessment. This study fails to confirm previous reports that immunosuppressive treatments result in stabilisation or improvement in progressive MS.

A programme of antiepileptic treatment in a rural and semi-urban region in Kenya was assessed. Patients with generalised tonic-clonic seizures were treated according to one of two simple drug protocols. Health workers screened cases reported by key informants in the community. From the 529 patients identified by health workers as having active seizures 302 patients aged 6-65 years were recruited by a psychiatrist for therapy with carbamazepine or phenobarbitone. Treatment was supervised largely by primary health workers, and the programme was monitored by a research team, which assessed the effectiveness of treatment. Of the 249 patients who completed the study, 53% became seizure-free in the second 6 months of therapy, and another 26% had substantially (50% or more reduction) fewer seizures than in the 6 months before therapy. The similarity of these findings to those obtained in newly diagnosed patients in the developed world, the low drop-out rate, the low rate of withdrawal due to adverse effects, and the acceptable compliance with therapy indicate that health workers can monitor therapy adequately. Most patients had had several years of delay before starting therapy for their epilepsy, yet they responded well--a finding that does not support the suggestion that the disorder becomes intractable if not treated early.