Three intravenous bisphosphonates were compared in the treatment of cancer-associated hypercalcaemia. 48 patients were randomly allocated to one of three treatment groups (each with 16 subjects)--30 mg pamidronate or 600 mg clodronate, both as single intravenous infusions; or etidronate as three infusions of 7.5 mg/kg per day for three consecutive days. Patients were rehydrated with normal saline before bisphosphonate treatment. All three bisphosphonates lowered serum calcium by inhibiting bone resorption; pamidronate was the most potent in this respect. By comparison with the other groups, more patients in the pamidronate group became normocalcaemic, and the effect on serum calcium was apparent sooner and lasted longer.

A randomised controlled trial compared the effectiveness and toxicity in pulmonary tuberculosis of two drug regimens containing rifampicin and isoniazid given daily or twice-weekly for 4 months after a 2-month period of intensive treatment with daily isoniazid, rifampicin, and pyrazinamide. 667 patients with newly diagnosed pulmonary tuberculosis were randomly allocated to continue daily treatment with isoniazid (400 mg) and rifampicin (600 mg) or to twice-weekly treatment with isoniazid (900 mg) and rifampicin (600 mg). 544 of the 667 patients (81%) completed the 6-month course (287 of 337 [85%] treated daily and 257 of 330 [79%] treated twice-weekly). Drug toxicity was not a great problem; the treatment was permanently discontinued in only 2% of patients. There was no significant difference at the end of months 5 and/or 6 of chemotherapy between the groups treated daily and twice-weekly in the proportions with bacteriological failure (at least one positive sputum culture with more than 20 colonies) or who had died from tuberculosis (17 [6%] vs 10 [3%]). Nor was there a significant difference in the relapse rate (17 [7%] treated daily vs 10 [4%] treated twice-weekly) during follow-up of 12 months. Thus, the twice-weekly regimen was at least as effective as the daily regimen for treatment of pulmonary tuberculosis.

In a randomised, placebo-controlled, double-blind study, 822 obese patients of both sexes were given either dexfenfluramine (dF), 15 mg twice daily (404), or placebo (418) in addition to a calorie-restricted diet for 1 year. Patients in both groups lost weight significantly in the first 6 months; after 6 months dF patients had a higher cumulative mean weight loss. Dropout rates were lower in dF patients than in placebo patients, mainly because of dissatisfaction with weight loss in the latter group. More than twice as many dF patients as placebo patients achieved a given weight loss; but more dF patients than placebo patients had transient side-effects (tiredness, diarrhoea, dry mouth, polyuria, and drowsiness).

A randomised, double-blind, placebo-controlled study of L-tyrosine was done in ten subjects with narcolepsy and cataplexy. Of twenty-eight visual analogue scales rating mood and arousal, the subjects' ratings in the tyrosine treatment (9 g daily) and placebo periods differed significantly for only three (less tired, less drowsy, more alert). Ratings of daytime drowsiness, cataplexy, sleep paralysis, night-time sleep, overall clinical response, and measurements of multiple sleep latency and tests of speed and attention did not differ significantly between tyrosine and placebo periods. Dietary supplementation with tyrosine 9 g daily for 4 weeks seems to have a mild stimulant action on the central nervous system but this effect is not clinically significant in the treatment of the narcoleptic syndrome.

A carefully designed set of simulators showing cervical effacement and dilatation was used to assess the error within and between observers in a group of 36 midwives and 24 obstetricians. No observer was correct in every case. There was no significant difference between the obstetricians and the midwives in assessment of effacement or overall assessment of dilatation. However, midwives were significantly more likely than obstetricians to assess dilatation inaccurately by more than 1 cm. Inaccuracy was greatest in the simulators 5-7 cm dilated. These findings have implications for labour management and teaching.

In a double-blind randomised study, eight healthy men received equimolar amounts of human or porcine insulin by infusion (50 mU/kg per hour). Insulin potencies, in terms of the amount of glucose infused to maintain euglycaemia, were almost identical. Hypoglycaemia (blood glucose concentration 2 mmol/l or below) was then induced and the symptoms and hormonal counter-regulatory responses were recorded. The number of sympathoadrenergic (but not neuroglycopenic) symptoms was significantly greater with porcine than with human insulin, as was the integrated noradrenaline response. Glucagon, growth hormone, cortisol, and adrenaline responses were similar for the two insulins.

In a blind trial, 77 patients were randomised to receive first cadaver kidney allografts that had been perfused either with a pair of CD45 monoclonal antibodies (mAbs), in an attempt to reduce the immunogenicity of passenger leucocytes, or with control human albumin solution. No complications of mAb perfusion were observed. Patient and allograft survival were similar in both groups. Rejection episodes were recorded in 7 (18%) of the patient with mAb perfused allografts compared with 24 (63%) of the controls.

The effect of psychosocial intervention on time of survival of 86 patients with metastatic breast cancer was studied prospectively. The 1 year intervention consisted of weekly supportive group therapy with self-hypnosis for pain. Both the treatment (n = 50) and control groups (n = 36) had routine oncological care. At 10 year follow-up, only 3 of the patients were alive, and death records were obtained for the other 83. Survival from time of randomisation and onset of intervention was a mean 36.6 (SD 37.6) months in the intervention group compared with 18.9 (10.8) months in the control group, a significant difference. Survival plots indicated that divergence in survival began at 20 months after entry, or 8 months after intervention ended.

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.

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.