32 previously untreated patients with multiple myeloma received vincristine, doxorubicin ('Adriamycin'), and dexamethasone (VAD) as first-line therapy. The overall response rate was 84%, with 28% of all patients entering complete remission. Response was rapid, with near-maximum response occurring after two courses of treatment and rapid improvement in bone-marrow function. Median response duration was 18 months and this seemed to be unaffected by initial prognostic criteria or by degree of remission achieved. The projected median survival was 44 months, with 75% of all patients and 83% of responders being alive at 2 years. Side-effects due to steroids were common, but there was only 1 treatment-related death. The high response rate and lack of toxicity offer an advantage over other forms of initial treatment, although other strategies will be necessary to prolong the duration of response.

Granulocyte colony-stimulating factor (G-CSF) was administered by continuous subcutaneous infusion to 15 patients with non-myeloid malignancies treated by high-dose chemotherapy and autologous bone marrow infusion. G-CSF was given at variable dosage based on neutrophil count. Sustained serum levels of G-CSF were achieved. Neutrophil recovery was accelerated in G-CSF treated patients compared with 18 historical controls and exceeded 0.5 x 10(9)/l at a mean of 11 days after marrow infusion compared with 20 days for controls, a significant difference. This reduction led to significantly fewer days of parenteral antibiotic therapy, 11 versus 18 days in controls, and less isolation in reverse-barrier nursing, 10 versus 18 days.

To evaluate the efficacy of pyrimethamine on the blood stage (suppressive prophylaxis) and liver stage (causal prophylaxis) of Plasmodium falciparum in pregnant women, in vivo and in vitro field studies were conducted in Ilorin, Nigeria, from Jan 1 to June 30, 1988. For pregnant women with P falciparum infections who received 25 mg of pyrimethamine weekly for suppressive prophylaxis, 67% (59/88) of in vivo and 60% (6/10) of in vitro tests showed pyrimethamine resistance. A second group of parasitaemic and parasite-free pregnant women was enrolled to evaluate the efficacy of pyrimethamine as a primary tissue schizonticide; after receiving a curative dose of chloroquine (25 mg/kg), half the women were given 25 mg of pyrimethamine weekly and half received no prophylaxis. Parasitologic failure rates did not differ between the pyrimethamine-treated (8/34) and the control (11/37) groups during the 16-week follow-up. Thus, pyrimethamine is not effective for suppressive or causal prophylaxis in pregnant women in Ilorin.

The effect of gamma-hydroxybutyric acid (GHB) on ethanol withdrawal syndrome in alcoholics was investigated in a randomised double-blind study. Patients with withdrawal symptoms were treated either with GHB (orally in a syrup preparation) (11 patients) or with the syrup alone (12). GHB treatment (50 mg/kg) led to a prompt reduction in withdrawal symptoms, such as tremors, sweating, nausea, depression, anxiety, and restlessness. The only side-effect was dizziness. GHB may be useful in the management of alcohol withdrawal syndrome in man.

A randomised controlled trial with a factorial design was done to examine the effects of dietary intervention in the secondary prevention of myocardial infarction (MI). 2033 men who had recovered from MI were allocated to receive or not to receive advice on each of three dietary factors: a reduction in fat intake and an increase in the ratio of polyunsaturated to saturated fat, an increase in fatty fish intake, and an increase in cereal fibre intake. The advice on fat was not associated with any difference in mortality, perhaps because it produced only a small reduction (3-4%) in serum cholesterol. The subjects advised to eat fatty fish had a 29% reduction in 2 year all-cause mortality compared with those not so advised. This effect, which was significant, was not altered by adjusting for ten potential confounding factors. Subjects given fibre advice had a slightly higher mortality than other subjects (not significant). The 2 year incidence of reinfarction plus death from ischaemic heart disease was not significantly affected by any of the dietary regimens. A modest intake of fatty fish (two or three portions per week) may reduce mortality in men who have recovered from MI.

The supplementation of culture medium with platelet activating factor (PAF) on the subsequent implantation and pregnancy potential of pre-embryos produced by in-vitro fertilisation was studied. Pre-embryo culture medium was supplemented with 0 (control), 0.186, 0.93, or 1.49 mumol/1 PAF. Pre-embryos were transferred to PAF-containing medium 15-17 h after insemination (ie, just before syngamy) for 24 h and then transferred to the uterus. For 185 women receiving control pre-embryos, the pregnancy rate (positive beta human chorionic gonadotropin per oocyte retrieval) was 10.2%, while 166 women who received PAF treated pre-embryos (all concentrations combined) achieved a pregnancy rate of 17.5%. This difference was significant. The pregnancy rates per pre-embryo transferred were 6.1% and 9.4% for the control and PAF groups, respectively. The percentage of positive pregnancy tests that resulted in a viable pregnancy (presence of fetal heart at 8 weeks) was 78.9% in the controls and 75.9% in the PAF group. There was no difference in the average number of embryos transferred in either group. The increase in the pregnancy rate after a short exposure of pre-embryos to PAF in vitro suggests that PAF mediates pre-embryo development.

40 patients with premenstrual symptoms were randomly allocated to receive placebo patches or active treatment with transdermal oestradiol patches (2 x 100 micrograms) to suppress ovulation. Norethisterone 5 mg was given in each group from day 19-26 of the cycle to ensure a regular withdrawal bleed. Treatment was for 6 months with crossover at 3 months. Patients completed the Moos menstrual distress questionnaire (MDQ) and the premenstrual distress questionnaire (PDQ) daily throughout the study. 5 patients withdrew, 4 because of skin reactions and 1 because of considerable improvement with initial (active) treatment. After 3 months, both groups showed improvement in MDQ and PDQ scores. In general, between 3 and 6 months, patients who switched from active treatment to placebo had deteriorating scores while patients who switched from placebo to active treatment maintained or improved upon their initial gains. Significant improvements occurred after changing to active treatment in five of six negative MDQ symptom clusters and in six of ten PDQ symptoms.

The efficacy of a 10-day course of bovine colostrum with high antibody titre against the four known human rotavirus serotypes in protecting children against rotavirus infection was examined in patients admitted to hospital. Children aged 3 to 15 months were blocked in pairs according to ward accommodation (ie, isolation or open area). Each block contained 1 treated and 1 control child. The allocation to treatment or control (an artificial infant formula) was randomised. 9 of 65 control children but none of 55 treated children acquired rotavirus infection during the treatment period (p less than 0.001). The importance of protecting against rotavirus infection was highlighted by the fact that parents of symptomatic rotavirus-positive children sought medical attention seven times more often than did parents of symptomatic rotavirus-negative children (p less than 0.05).

101 critically ill patients admitted to five intensive-care units were allocated randomly to receive a continuous intravenous infusion of either propofol or midazolam for sedation for up to 24 h. In addition, morphine was given to provide analgesia. The mean duration of infusion was 20.2 h (range 3.0-24.5) in the propofol group and 21.3 h (4.0-47.0) in the midazolam group and infusion rates were 1.77 mg/kg/h (range 0.40-5.00) and 0.10 mg/kg/h (0.01-0.26), respectively. The infusion rates were adjusted as necessary, and the desired level of sedation was achieved easily in most patients in both groups. There were slight falls in arterial pressure, but there were no significant differences between the groups. Heart rate was lower in patients who received propofol. Some small changes occurred in biochemical and haematological variables in both groups, but they were not clinically significant. There was no indication that either drug substantially impaired adrenal steroidogenesis. When the infusion was discontinued, there was less variability in recovery of consciousness in patients who had received propofol. In a subgroup of patients, weaning from mechanical ventilation was achieved significantly faster after discontinuation of propofol than of midazolam. Propofol proved to be a satisfactory agent for sedation of these critically ill patients and compared favourably with midazolam.

An organic marine hydrocolloid (OMH) charged with calcium ('Ox-Absorb') was studied in vitro for oxalate binding and in patients with enteric hyperoxaluria to investigate oxalate excretion and the inhibitory activity on crystal formation of the urine. In-vitro experiments showed complete binding of oxalate to OMH. In clinical studies in nineteen patients with intestinal disorders and stone formation, urinary oxalate excretion was significantly lower during OMH treatment than off treatment. The activity product index of calcium oxalate was reduced on treatment. A pronounced rise in the inhibitory activity of urine was seen in two patients with very low pretreatment values. Most patients experienced virtual normalisation of bowel function, and in those with severe stone formation there was substantial clinical improvement. It is concluded that OMH has the capacity to bind oxalate in vitro and to reduce urinary oxalate excretion. These observations suggest a new promising treatment for enteric hyperoxaluria.

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.