86 renal allograft recipients were randomly assigned to cyclosporin (Cy) for 90 days followed by azathioprine and prednisolone (Aza and P), or to Aza and P from day 0, as part of the second Oxford trial of short-term Cy use. All 62 patients whose grafts functioned for at least 120 days were included in this study. Serum creatinine was significantly higher in Cy-treated patients than in control patients from day 28 to day 90. Serum uric acid was also significantly higher in Cy-treated patients over the same period. Both creatinine and uric acid fell to the level of the control group after conversion to Aza and P. Serum uric acid was significantly higher for a given level of creatinine during Cy treatment than in either the control patients or the Cy-treated patients after their treatment had been changed to Aza and P. These data imply that Cy affects both the glomerular filtration rate and renal tubular function but that these effects are largely reversible.

14 hypertensive men with type II diabetes sequentially received, in random order, hydrochlorothiazide 50 mg twice a day, propranolol 80 mg twice a day, and both drugs in combination. The 3-week treatment periods were separated by a 1-week washout period. Hydrochlorothiazide significantly increased fasting glucose by 31% (p less than 0.05) and glycosylated haemoglobin (HbA1c) by 6.0% (p less than 0.10). A similar treatment period of propranolol 80 mg twice a day caused no significant increases. However, when both drugs were taken in combination, fasting glucose rose by 56% and HbA1c by 14.7% (p less than 0.01). The hyperglycaemic effect of hydrochlorothiazide and its potentiation by propranolol were independent of serum potassium and of endogenous insulin secretion as measured by urine C-peptide excretion. The combination of hydrochlorothiazide and propranolol thus seems to cause serious disturbances in glycaemic control in type II diabetics by mechanisms independent of insulin secretion.

A volunteer participating in a study of eproxindine, a new antiarrhythmic agent, had a sudden cardiorespiratory arrest and died. Subsequently it became known that he had received a depot injection of flupenthixol on the day before his death; an interaction between these two drugs seems likely. This incident illustrates that it is impossible to guarantee absolute safety in volunteer studies if details of medical history are withheld.

The analgesic effects of buccal and intramuscular morphine were compared in a prospective, double-blind, double-dummy study in forty patients who experienced pain after elective orthopaedic operations. Each patient simultaneously received a buccal tablet and an intramuscular injection, only one of which contained morphine sulphate (13.3 mg); the patients were randomly allocated to two equal groups so twenty patients received each active preparation. The two preparations produced a similar degree of postoperative analgesia, assessed by the mean reduction in pain score and the pain relief score. Peak plasma morphine concentrations were slightly lower after buccal than after intramuscular administration but they declined more slowly; consequently, the drug's bioavailability was 40-50% greater after buccal than after intramuscular administration. The adverse effects of buccal morphine were generally less than those of intramuscular morphine.

Oestrogen receptor concentrations were measured in primary tumours of 291 postmenopausal breast cancer patients with high risk of recurrence. These patients were a subset of the 1650 patients participating in the Danish Breast Cancer Cooperative Group's trial of adjuvant treatment with tamoxifen (30 mg daily for one year). A cut-off point of 10 fmol/mg cytosol protein and the use of a Cox proportional hazards model distinguished between patients with long recurrence-free survivals and those with early recurrent disease. The use of this model also showed that patients with an oestrogen-receptor content below 100 fmol/mg did not benefit from the endocrine therapy, while those with concentrations above 100 fmol/mg had a significantly longer recurrence-free survival. This finding is consistent with the response of advanced breast cancer to endocrine treatment.

Thalidomide was given to 15 patients with severe orogenital ulceration (OGU). 4 patients underwent a double-blind controlled trial with glutethimide as placebo and 11 were treated openly. Treatment with thalidomide produced complete resolution of ulcers in 14 and significant improvement in the remaining patient. No peripheral neuropathies developed. Patients did not respond to glutethimide. Thalidomide is an effective treatment for severe OGU. Adequate contraceptive measures should be taken during treatment.

Q fever is an important cause of morbidity in Australian meatworkers; recently there have been sharp outbreaks of Q fever in abattoirs in several states. In an attempt to control Q fever by vaccination, 924 nonimmune volunteers at two South Australian abattoirs were inoculated with one dose of a purified, formalin-inactivated, Coxiella burneti, Henzerling strain, phase 1 vaccine. Some 56% of workers in one abattoir, and 64% in the other, seroconverted after vaccination. In the 18 months after vaccination, no Q fever occurred in fully vaccinated subjects, whereas there were 34 cases in 1349 unvaccinated workers. Transient local reactions were noted in most vaccinated subjects; only a few had mild general reactions. No cases of vaccine-enhanced disease were observed. Vaccination of susceptible individuals with a purified C burneti phase 1 vaccine appears to be safe and effective in preventing Q fever in the abattoir.

A prospective trial in 80 patients randomly allocated to four antimalarial treatment regimens--mefloquine plus pyrimethamine-sulfadoxine ('Fansidar'); mefloquine plus qinghaosu; mefloquine, fansidar, and qinghaosu; and qinghaosu alone--was carried out on Hainan Island, China, in patients with chloroquine-resistant falciparum malaria. A radical cure with slight side-effects was obtained with mefloquine plus fansidar; the addition of qinghaosu greatly increased the rate of parasite clearance with no additional side-effects. Qinghaosu alone had a rapid rate of parasite clearance, no side-effects, but a high recrudescence rate. These antimalarial drugs seem to act at different stages of the asexual parasite cycle and their most efficient use may depend on when in the course of the disease they are given. Because of the continuing appearance of drug-resistant strains of Plasmodium falciparum combination drug therapy is now indicated, but which drugs and how best they should be used remains to be decided.

The results of a controlled trial in which 38 patients with severe acute inflammatory polyradiculoneuropathy took part indicate that plasma exchange favourably influenced the course of the disease. Significant benefits were seen in time until onset of improvement, course of muscular weakness, improvement in disability grades over the first 2 months, and working capacity after 1 month. Cost-benefit analysis showed that the exchange treatment resulted in net financial savings. The results suggest that plasma exchange may have a role in the treatment of severe acute inflammatory polyradiculoneuropathy.