56 patients with frequently recurring genital herpes were treated in a randomised double-blind trial with either oral acyclovir 200 mg four times a day or placebo for 12 weeks. 29 patients received the drug and 27 the placebo. The mean recurrence rate per month of treatment was 1.4 in the placebo-treated patients and 0.05 in the acyclovir group. Median time to the first recurrence after the start of therapy was 14 days in the placebo group compared with 100 days in the acyclovir group. After the end of treatment the recurrence rate was similar in the two groups. Prophylactic oral acyclovir seems to be an effective treatment for patients with frequently recurring genital herpes.

The saccharin clearance time technique was used to determine the effect upon nasal mucociliary transport of sine wave oscillations. Nasal air was oscillated at 8 Hz, 14 Hz, and 20 Hz by a loudspeaker attached to a nasal mask. Mucociliary transport was significantly increased at all frequencies with an overall mean rise of 161%. Because sine waves have zero mean pressure and flow, the improvement is more likely to be caused by changes in mucus viscoelasticity or ciliary function rather than by a direct physical effect on mucus velocity. This simple and comfortable technique may have practical application in patients with overproduction or retention of mucus within the nasal passages or intrathoracic airways.

222 patients with disseminated breast cancer have been randomised to receive either a combination of hormone therapies using tamoxifen, aminoglutethimide with hydrocortisone, and danazol (TAD), or tamoxifen alone. The response to the combination was significantly better (43%) than that to tamoxifen alone (31%). Patients who relapsed after response or failed to respond to tamoxifen were subsequently treated with aminoglutethimide and then, if possible, with danazol. Some patients who received TAD were subsequently treated with alternative endocrine therapy, which was usually medroxyprogesterone acetate. Of the 111 patients who initially received tamoxifen, 43 responded to the tamoxifen and/or subsequent endocrine therapy. Of the 111 patients who initially received TAD, 50 responded. Although the duration of response to TAD was the same as for tamoxifen, the TAD patients achieved remission more quickly. The total time in endocrine remission for patients receiving TAD is 303 months to date, compared with 264 months for patients receiving tamoxifen. Survival for patients randomised to receive TAD or tamoxifen is the same.

Albumin excretion rates (AER) were measured in 30 insulin-dependent diabetics during a 16-week double-blind, randomised, placebo-controlled study of the specific thromboxane synthetase inhibitor UK-38,485.6 of 15 subjects in the active group had microalbuminuria (defined as mean pretreatment AER 20-150 micrograms/min); in these patients AER fell from 32 +/- 3 micrograms/min to 11 +/- 1 micrograms/min at 8 weeks and 9 +/- 1 micrograms/min at 16 weeks. The AER rose again (to 29 +/- 8 micrograms/min) within 12 weeks of stopping the drug. There was no significant change in the 10 patients with microalbuminuria who received placebo. There was a strong correlation between change from baseline values and the baseline values themselves in the active, but not in the placebo group, and the change from baseline differed significantly between the two groups. There was no change in glycosylated haemoglobin or mean blood glucose levels during the study. In a separate study UK-38,485 caused significant suppression of thromboxane B2 synthesis in diabetic and non-diabetic subjects.

52 patients with serious urinary tract infections were randomised to receive either aztreonam (35) or gentamicin (17). In the aztreonam group 23 patients had unqualified cures, 6 cures with relapse, and 6 cures with reinfection; the comparable numbers in the gentamicin group were 9, 1, and 4. There were no failures with aztreonam and 3 with gentamicin. The most important determinant of outcome was the presence or absence of urological abnormalities. 11 further patients, with renal failure or gentamicin-resistant isolates, treated with aztreonam were all cured. Toxic effects were limited to symptomless liver-function-test abnormalities with aztreonam , whereas deterioration in renal function occurred in 4 gentamicin-treated subjects. Urinary colonisation with group D streptococci occurred in 14 of 46 aztreonam -treated patients (1 required treatment) compared with only 1 of 17 gentamicin-treated patients. 97% of 309 consecutive gram-negative urinary isolates tested, including 50 Pseudomonas aeruginosa, were susceptible in vitro to aztreonam and 91% to gentamicin. Aztreonam may prove an effective and safe alternative to the aminoglycosides.

Prevention of aortocoronary bypass occlusion by aspirin (ASA, 1 X 100 mg per day) was studied in a prospective double-blind trial of 83 patients. 60 (72%) were randomly allocated to ASA or placebo starting 24 h after operation. 90% of grafts in the ASA group and 68% in the placebo group were patent at four months. At least one anastomosis was occluded in 62% of the patients on placebo and in 27% of those on aspirin. Ventricular arrhythmias increased after surgery in more patients on placebo (12/18) than in patients on ASA (5/17). Platelet thromboxane formation on collagen tested before operation was significantly higher in patients in whom bypass occlusion developed (occlusion: 40 +/- 19, no occlusion: 25 +/- 13 ng/ml). A 100 mg dose of ASA per day effectively blocked platelet thromboxane formation and thromboxane-supported aggregation on collagen and was safe in the postoperative phase. No side effects were reported throughout the trial. The reduced toxicity with full efficacy favours a low and infrequent dosage of aspirin.

Adjuvant therapy after total mastectomy and axillary clearance in postmenopausal women with breast cancer and axillary node metastasis was assessed; chemo-endocrine therapy (cyclophosphamide, methotrexate, fluorouracil, prednisone, and tamoxifen; CMFp + T) was compared with endocrine therapy (prednisone and tamoxifen; p + T), and with no adjuvant treatment in 463 patients aged less than or equal to 65 years. Endocrine therapy was compared with no adjuvant therapy in 320 patients aged 66-80 years. At median follow-up of 36 months, disease-free survival was significantly longer in CMFp + T patients than in p + T or control patients; p + T also significantly increased disease-free survival. There were no significant differences in overall survival between the randomised groups. In analyses of patterns of first failure, chemo-endocrine therapy reduced local, regional, and distant relapses, whereas endocrine therapy reduced local and regional recurrences only.

Aphasic stroke patients were randomly allocated to either a speech therapy group receiving treatment twice a week for 24 weeks or a no-treatment control group. Patients in both groups improved and there were no significant differences in language recovery between the 104 patients allocated to the treatment group and the 87 allocated to the no-treatment group. This treatment regimen, which is representative of clinical practice, is ineffective for most aphasic stroke patients.

Since 1975 four rounds of screening with modern mammography for breast cancer have been carried out among 30 000 Nijmegen women born before 1940. The results up to the end of 1981 shows that the odds ratio of screened vs unscreened subjects among women who died from breast cancer compared with women who did not, was 0.48 (95% confidence interval 0.23-1.00) in all age groups.

Patients with tibial fractures which had remained un-united for at least 52 weeks were randomly allocated to either active or dummy pulsed magnetic field stimulators and treated in full leg plasters for 24 weeks with a non-weightbearing conservative regimen, as is usual with such techniques. Fractures in 5 of the 9 patients with working machines united and fractures in 5 of the 7 patients with dummy machines also united. These early results of this double-blind trial are compatible with a difference in success rate at 24 weeks on active treatment of + 33% to -61% (95% confidence limits) compared with the success rate on the dummy stimulators. The high proportion of fractures uniting in the control group suggests that conservative management of non-union is effective and this may explain much of the success attributed to pulsed magnetic field therapy.

BM 13.177, a sulphonamide derivative, prevented platelet aggregation by thromboxane A2 in vitro and selectively inhibited contraction of isolated rabbit femoral arteries induced by two stable endoperoxide analogues. In a double-blind placebo-controlled study, oral BM 13.177 inhibited platelet aggregation induced by arachidonic acid, low dose collagen, and the two stable endoperoxide analogues, and slightly prolonged the bleeding time. Generation of thromboxane or of other prostaglandins was not affected. No side-effects were seen. BM 13.177 appears selectively and safely to block platelet and vessel wall thromboxane receptors and should be useful in elucidating the role of thromboxane A2 in disease.

In an attempt to determine the safety, tolerance, and prophylactic antiviral activity of high doses of recombinant DNA leucocyte interferon A a double-blind parallel-group study was started in 16 renal transplant recipients. All 16 patients had early rejection episodes. In all 8 interferon-treated patients and 1 placebo-treated patient this rejection, which was of the acute vascular humoral type, was steroid resistant. 3 interferon-treated patients also had transient nephrotic syndrome.