In a prospective, double-blind, randomised trial, 401 patients with a first acute myocardial infarction were treated within 4 h of onset of symptoms with 80 mg recombinant pro-urokinase or single-chain urokinase plasminogen activator (rscu-PA; proposed INN saruplase) intravenously given as a 20 mg bolus followed by 60 mg infusion for 60 min (198 patients), or 1.5 million IU streptokinase infused over 60 min (203 patients). The first two angiograms were taken at 60 min and at 90 min. Angiography was repeated at 24-36 h. Patency rates at 60 min were 71.8% for rscu-PA and 48.0% for streptokinase (p less than 0.001) and at 90 min they were 71.2% and 63.9%, respectively (p = 0.15). At 24-36 h 6/121 patients treated with rscu-PA and 5/114 patients treated with streptokinase showed reocclusion of the vessel. At the end of the thrombolytic infusion (60 min) fibrinogen concentration had decreased to 0.44 (0.23-1.27) g/l (median, 1st and 3rd quartile) in patients treated with rscu-PA and to 0.17 (0.06-0.27) g/l in patients treated with streptokinase (p less than 0.001). Concentrations of fibrin(ogen) degradation products rose to 96 (24-240) mg/l after rscu-PA and to 240 (192-360) mg/l after streptokinase (p less than 0.001). Bleeding complications were less common in the rscu-PA than in the streptokinase group (p less than 0.01). Thus intravenous rscu-PA led to higher patency rate, earlier reperfusion, less disturbance of haemostasis, and fewer bleeding complications than did intravenous administration of streptokinase.

12 adult patients with perennial asthma and chronic skin infection were found to have immediate hypersensitivity to Trichophyton spp. 10 patients were tested by bronchial provocation and gave immediate bronchial reactions to an extract of T tonsurans. Double-blind, placebo-controlled nasal challenge of 8 patients demonstrated that the upper airways of these patients were also sensitive to this dermatophyte antigen. In addition to perennial asthma most of the patients had persistent eosinophilia and chronic rhinosinusitis. The results suggest that absorption of fungal antigen can give rise to IgE antibody production, sensitisation of the airways, and symptomatic asthma and rhinosinusitis. Several patients had many of the features of late onset or "intrinsic" asthma.

In a double-blind trial, 0.5% podofilox (podophyllotoxin) or placebo was applied by patients to their own genital warts in up to four treatment cycles. At some time during the study, 25 of the 56 podofilox treated patients and none of the 53 placebo group were completely wart-free. At the end of the treatment, 73.6% of the original warts in podofilox treated patients were gone compared with only 8.3% of those in the placebo group (mean percentage of total original wart area was reduced by 82.3% compared with 4.2%). 82% of the treated warts in the podofilox group and 13% in the placebo group had resolved at 6 weeks. Recurrence was observed in 34% of the previously resolved warts. Consistent with this rate of recurrence, new warts developed in a third of the subjects in each group at sites remote from the treatment site. There were no systemic adverse reactions, although transient inflammation, erosion, pain, and burning were common.

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.

Mortality rates from the Large Bowel Cancer Project are presented with special reference to patients older than 70 years. The in-hospital mortality rate among those who underwent curative resection for colorectal carcinoma was 7%. Unlike long-term prognosis, which is influenced by pathological features, in-hospital mortality is influenced largely by clinical factors. Age was an adverse factor (78% of deaths occurred among those aged over 70, who formed 46% of the study population), as was obstruction or perforation. 55% of deaths were due to cardiopulmonary complications. Educating patients to seek treatment early, careful preoperative assessment and postoperative monitoring of cardiopulmonary function, and, in selected patients, use of local treatments rather than wide resections may help to reduce mortality in elderly patients.

Tumour-infiltrating lymphocytes (TIL) were isolated and expanded from small tumour biopsy samples of twenty-eight patients (thirteen with malignant melanoma, seven with renal cell carcinoma, and eight with non-small-cell lung cancer). The patients were treated with autologous expanded TIL (about 10(10)) and continuous infusions of recombinant human interleukin-2(1-3 x 10(6) U/m2 per 24 h). 29% of the patients with renal cell cancer and 23% of those with melanoma achieved objective tumour responses lasting 3-14 months. Toxic side-effects were limited, and no patient required intensive-care monitoring. Adoptive immunotherapy with TIL and interleukin-2 may be an effective systemic approach to the treatment of some patients with malignant melanoma and renal cell carcinoma.

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.