An open randomised trial was conducted to compare ceftazidime (120 mg/kg/day) with "conventional therapy" (chloramphenicol 100 mg/kg/day, doxycycline 4 mg/kg/day, trimethoprim 10 mg/kg/day, and sulphamethoxazole 50 mg/kg/day) in the treatment of severe melioidosis. A paired restricted sequential trial designed to detect a reduction in mortality from 80 to 40% in culture-positive patients surviving greater than 48 hours was stopped after 22 months. Of the 161 patients entered into the study, 65 had bacteriologically confirmed melioidosis and 54 of these were septicaemic. Ceftazidime treatment was associated with a 50% (95% CI 19-81%) lower overall mortality than conventional treatment (74% vs 37%; p = 0.009) and should now become the treatment of choice for severe melioidosis.

UK 69 578 is a competitive inhibitor of endopeptidase 24.11 (the enzyme that degrades atrial natriuretic factor) in vitro. In vivo, UK 69 578 has renal and cardiovascular effects similar to low-dose atrial natriuretic factor infusion, and may be a useful agent in hypertension and heart failure.

Granulocyte-macrophage colony-stimulating factor (GM-CSF), given to accelerate recovery from cytopenia induced by high-dose (7 g/m2) cyclophosphamide, reproducibly brought about a dramatic increase (up to 1000-fold) in the number of peripheral blood granulocyte-macrophage colony-forming units (CFU-GM). These circulating progenitors were harvested by leucapheresis and reinfused, together with autologous bone marrow cells, in seven patients with cancer after total body irradiation and melphalan. Complete haemopoietic recovery occurred in all seven transplanted patients in a very short time: mean (SD) 9.1 (0.9) days (range 8-11) to achieve more than 0.5 x 10(9)/l neutrophils, 9.9 (1.7) days (range 8-13) to over 1 x 10(9)/l neutrophils, 10.7 (2.6) days (range 9-16) to over 0.5 x 10(11)/l platelets, and 13.6 (4.2) days (range 13-21) to over 1.0 x 10(11)/l platelets. A reduction in the severity of mucositis was also observed. The rapid haematological recovery made possible by this approach promises to increase the therapeutic index of high-dose chemoradiotherapy regimens and to widen their role as treatment for chemoradiosensitive tumours.

A randomised, controlled trial was carried out to determine whether suckling immediately after birth reduces the frequency of post-partum haemorrhage (PPH), the mean blood loss, and the frequency of retained placenta. The trial subjects were attended by traditional birth attendants (TBAs), and randomisation was by TBA and not by mother. 68 TBAs attended a course on third stage management and data collection; 19 had to be excluded from the trial. 23 TBAs in the early suckling group and 26 in the control group recorded blood loss in 2104 and 2123 deliveries of liveborn singletons, respectively. The frequency of PPH (loss greater than 500 ml) was 7.9% in the suckling group and 8.4% in the control group and the mean blood loss 258 ml and 256 ml, respectively. Neither of these results differed significantly between the groups. Analysis of the results by individual TBA showed no significant difference between the groups. The frequency of PPH in women of higher parity and in those with multiple pregnancies and stillbirths was high, as expected, which seems to validate the results. The frequency of retained placenta was too low to be analysed.

To test the hypothesis that non-steroidal anti-inflammatory drugs (NSAIDs) accelerate the progression of osteoarthritis by reducing synthesis of vasodilator prostaglandins, thereby diminishing joint perfusion, 105 osteoarthritis patients awaiting hip arthroplasty were treated prospectively with a strong or weak prostaglandin synthesis inhibitor, indomethacin or azapropazone, respectively. Pain and radiological joint space were monitored during the period up to arthroplasty and the condition of the excised femoral head was determined. As judged by radiological and histopathological data, the two treatment groups were at a similar pathophysiological end-point when they came to arthroplasty. In the indomethacin group the affected hips lost joint space more rapidly than did the contralateral hips, a difference not seen in the azapropazone group. The patients receiving azapropazone, who had higher concentrations of synovial vasodilator prostaglandins, took longer than the indomethacin group to reach the arthroplasty end-point. Potent inhibitors of prostaglandin synthesis may be inappropriate in the management of osteoarthritis of the hip.

The effects of probenecid, a known inhibitor of glucuronidation, on the pharmacokinetics of zidovudine were assessed in eight subjects receiving zidovudine as treatment for human immunodeficiency virus infection. Zidovudine plasma concentrations were measured while subjects were receiving zidovudine alone, after 3 days of zidovudine plus 500 mg probenecid every 8 h, and after 3 days of zidovudine plus 500 mg probenecid plus 260 mg quinine sulphate every 8 h. A median increase of 80% in the area under the zidovudine plasma concentration/time curve occurred with the addition of probenecid. Quinine sulphate prevented the probenecid effect but had no effect on zidovudine kinetics when taken without probenecid by four other subjects. All of the effects were secondary to changes in zidovudine metabolism, since neither probenecid nor quinine changed the renal elimination of zidovudine. Probenecid could be used in combination with zidovudine to extend the interval between doses and reduce the daily requirement for zidovudine, thus enhancing convenience and reducing costs.

Availability of new DNA markers, more tightly linked to the Huntington's disease (HD) locus than the original G8 (D4S10) probes, has improved predictive accuracy for both presymptomatic and prenatal exclusion testing. 50 predictive tests were carried out on high-risk individuals. 6 of these were on first-trimester chorionic villus biopsy specimens; in 2 cases the HD gene was not transmitted to the fetus while in 4 cases no exclusion could be made. The remaining 44 tests were on adults with either 25 or 50% risk of manifesting the disease; 19 had a greatly increased risk and 25 a substantially decreased risk of HD. Family structures in Scotland are suitable for testing about 75% of potentially affected individuals, and the new generation of DNA markers makes virtually all families fully informative.

The efficacy in acute childhood diarrhoea of oral rehydration therapy (ORT) based on staple foods (maize, millet, wheat, sorghum, rice, or potato) was compared with that of standard ORT based on glucose. 266 children aged 1-5 years, with a history of acute diarrhoea for 48 h or less, moderate to severe dehydration, and no complications, were assigned to treatment with one of the food-based oral rehydration salt solutions (ORS) or standard ORS. The mean stool output over the first 24 h of treatment in the group receiving standard ORS was significantly higher than that of any other treatment group, and the groups receiving food-based ORT showed substantial reductions in stool output compared with the standard ORT group. Abnormalities in electrolyte concentrations were corrected in all treatment groups with similar efficiency. The digestibility of the food-based ORS was assessed by the stool pH, glucose content before and after acid hydrolysis, and osmolality; there were no significant differences between the standard ORS and food-based ORS groups. Food-based ORT should be more acceptable to users in developing countries since the mixtures are similar to traditional weaning foods and since, unlike standard ORT, it reduces stool output substantially.