In a population-based study, disease progression and survival were evaluated in untreated patients with newly diagnosed cancer of the prostate without distant metastases. Complete follow-up was achieved in 223 of 227 (98%) consecutively diagnosed, eligible patients of all ages. After 5 years, the cumulative progression-free survival (with 95% confidence interval) was 71.8 (65.5-78.1)% and survival corrected for causes of death other than prostatic cancer was 93.8 (88.3-97.6)%. Univariate and multivariate analyses showed no association between age at diagnosis and the natural course. Local progression was less common in localised, non-palpable tumours than in larger tumours. The rate of progression was 18.7 (6.1-57.1) times higher and that of disease-specific death 216.0 (31.2-1496) times higher in patients with poorly than in those with highly differentiated tumours. It is concluded that tumour grade at diagnosis is an excellent predictor of local and distant progression. The low death rate, especially in patients with highly and moderately differentiated tumours, means that any local or systemic therapy intended for patients with early prostatic cancer must be evaluated in clinical trials with untreated controls for comparison.

In a randomised, double-blind study the efficacy and toxicity of oral fluconazole 50 mg daily and ketoconazole 200 mg daily were compared for the treatment of oropharyngeal candidiasis in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC). 20 episodes (18 patients) were treated with fluconazole and 20 episodes (19 patients) with ketoconazole. Pretreatment clinical features and laboratory test results were similar in both groups. 17 episodes (85%) in the fluconazole group and 16 (80%) in the ketoconazole group could be evaluated. There was clinical cure at the end of therapy in all fluconazole-treated and 12 of 16 (75%) ketoconazole-treated episodes. Cultures were negative at the end of therapy in 87% of the fluconazole group and 69% of the ketoconazole group. 1 patients stopped taking fluconazole because of severe nausea. 1 of 18 fluconazole-treated and 4 of 19 ketoconazole-treated patients had transient rises in alanine or aspartate aminotransferase. Fluconazole seemed more effective than ketoconazole in the treatment of oral thrush among AIDS and ARC patients.

In a single-blind, placebo-controlled, randomised trial in 20 patients with stable angina pectoris, intravenous theophylline ethylenediamine (aminophylline), 7 mg/kg, increased the time to onset of angina by 46%, the heart-rate/blood-pressure product (an index of myocardial oxygen consumption) at 1 mm ST segment depression by 22%, and exercise duration by 24%. In a subsequent double-blind placebo-controlled trial in 8 patients a single oral dose of theophylline (375 mg) increased the time to onset of angina by 56%, the heart-rate/blood-pressure product at 1 mm ST segment depression by 22%, and the exercise duration by 35%. Infusion of theophylline ethylenediamine during angiography (10 patients) did not affect the diameter of epicardial coronary arteries. The beneficial effects of theophylline may be due to redistribution of coronary blood flow from non-ischaemic to ischaemic myocardium.

31 patients with thrombocytosis associated with myeloproliferative disorders were included in a prospective trial of long-term interferon therapy. 6 patients (19%) had side-effects which required withdrawal of interferon within one year. 22 patients (71%) achieved and maintained a complete response (platelet count less than 440 x 10(9)/l) for at least twelve months, with reduction or abolition of symptoms associated with thrombocytosis and a significant fall in bone-marrow megakaryocytes. At twelve months, 25 patients were randomly allocated to maintenance or withdrawal of interferon. Thrombocytosis recurred rapidly when treatment was stopped, but a second remission could be achieved by resumption of interferon therapy.

The anti-pruritic effects of rifampicin (10 mg/kg) and phenobarbitone (3 mg/kg) were assessed in 22 patients with primary biliary cirrhosis in a crossover randomised clinical trial. Each agent was given for 14 days, with a 30-day washout period between treatments. 21 patients completed the course of rifampicin and 18 that of phenobarbitone; rifampicin was withdrawn from 1 patient when anaemia and renal failure developed, whereas 3 patients stopped taking phenobarbitone because of a rash and the 4th merely refused the drug. Rifampicin had a greater anti-pruritic effect than phenobarbitone. The symptom improved in 19 patients taking rifampicin and in 8 taking phenobarbitone, the degree of improvement being greater with rifampicin than with phenobarbitone. Pruritus disappeared in 9 patients receiving rifampicin, and three of them were free of itch when switching over to phenobarbitone. Both drugs were equally effective in inducing hepatic microsomal function but rifampicin has the additional effect of reducing cholestasis. Its anti-pruritic effect should be tested in long-term clinical trials.

411 patients were entered into a prospective, randomised controlled trial of adjuvant chemotherapy after gastrectomy for adenocarcinoma. After a follow-up of at least 5 1/2 years there has been no survival advantage for those receiving adjuvant 5-fluorouracil and mitomycin C with or without an induction course of 5-fluorouracil, vincristine, cyclophosphamide, and methotrexate compared with those undergoing surgery only. There have been 366 deaths, including 22 from treatment-related conditions. A multivariate analysis of prognostic factors demonstrated that stage of disease, nodal and resection margin involvement, and the presence of residual disease are significant determinants of survival. Weight loss before surgery had a significant independent influence on survival. The combination of preoperative symptoms and intraoperative findings may be used to select patients for radical or palliative procedures.

In 434 operations for valvular heart disease, patients were randomised to receive Björk-Shiley, Edwards-Duromedics, or Medtronic-Hall mechanical prostheses. At a median follow-up time of 37.5 months there were no differences in hazard of death or non-embolic events. In the first six postoperative months the incidence of thromboembolism was about the same for the three valves. Subsequently, however, the incidence of thromboembolism for the Edwards-Duromedics valve was 3.9 times higher than for the Björk-Shiley valve, and for the Medtronic-Hall valve 2.6 times higher than for the Björk-Shiley valve.

33 patients with refractory irritable bowel syndrome were treated with four 40-minute sessions of hypnotherapy over 7 weeks. 20 improved, 11 of whom lost almost all their symptoms. Short-term improvement was maintained for 3 months without further formal treatment. Hypnotherapy in groups of up to 8 patients was as effective as individual therapy.

235 infants of HBeAg-carrier mothers in Hong Kong were assigned to four study groups. Groups I, II, and III received hepatitis-B (HB) vaccine at birth and at 1, 2, and 6 months. Group I also received seven monthly injections of HB immunoglobulin (HBIg), and group II received one HBIg injection at birth. Group III received vaccine only and group IV received placebo for both vaccine and HBIg. At the age of 3 years, all infants of the three treatment groups were significantly protected against the HB virus (HBV) carrier state compared with the placebo group (p less than 0.0001); the protective efficacy rates in groups I, II, and III were 87%, 80%, and 65%, respectively. At all times, group I was significantly better protected than group III. In groups III and IV, infants of mothers with serum HBV DNA levels of 5 pg/ml or above were at a significantly higher risk of acquiring the HBV carrier state than those whose mothers had HBV DNA levels below 5 pg/ml. This difference was not significant in groups given HBIg. Of the 183 infants who initially escaped HBV infection, 73 (40%) had transient and 8 (4%) chronic HBV infection between 6 and 36 months. Vaccinated infants who had actively formed anti-HBs remained well protected against the HBV carrier state. However, infants in groups I and II with no active anti-HBs response to vaccine became at risk for the HBV carrier state when the passively acquired anti-HBs antibodies had disappeared. HBIg should be included in HB vaccination schedules for all infants of HBeAg-positive mothers.

30 patients (10 normotensive, 20 hypertensive) with stable angina and positive treadmill exercise tests entered a double-blind, placebo-controlled crossover trial of metoprolol, 100 mg twice daily. At the end of each treatment phase, blood pressure was monitored for 24 h and Holter and real-time electrocardiographic (ECG) monitoring were carried out and an activity diary kept for 48 h. Blood samples for catecholamine measurement were taken after 30 min supine, 60 min standing, and at the first silent ischaemic event, triggered by the real-time ECG monitor, by means of an ambulatory blood withdrawal pump. Metoprolol lowered blood pressure and heart rate in both normotensive and hypertensive subjects, and reduced the frequency and duration of silent ischaemic episodes in hypertensive subjects. Plasma noradrenaline measured during silent ischaemia while the patients were resting was significantly higher than the control supine level without ischaemia. These findings suggest that noradrenergic hyperactivity may have a role in coronary vasoconstriction and that treatment which neutralizes sympathetic tone may be especially beneficial in treatment of silent ischaemia in hypertensive patients.

111 untreated subjects (mean [SEM] age 58.4 [1.0] years; 93 male, 18 female) with diastolic blood pressure between 90 and 100 mm Hg were seen fortnightly, and after four pre-diet visits they were randomised into a low sodium intake group (53 subjects; diet containing less than 80 mmol sodium/day plus 8 placebo tablets daily) or a normal sodium intake group (55 subjects; same dietary sodium plus 8 slow-release sodium chloride [10 mmol] tablets daily). 103 subjects completed the intervention phase of 8 weeks. Urinary sodium fell significantly in the low sodium group but not in the normal sodium group. Urinary potassium excretion did not change in either group. Mean (SEM) systolic and diastolic blood pressure fell by 6.1 (1.1) and 3.7 (0.6) mm Hg, respectively, in the low sodium group, but by only 0.6 (1.0) and 0.9 (0.6) mm Hg in the normal sodium group. Multivariate analysis allowing for the effects of pre-diet blood pressure, weight, and age, reduced the effect of lowering the sodium intake on the systolic pressure from 5.5 (SEM 1.5) mm Hg to 4.8 (1.3) mm Hg (p less than 0.005) but the effect on diastolic pressure was not changed significantly.