In a randomised controlled trial in 427 men with chronic stable angina continuous use of 5 mg transdermal glyceryl trinitrate (GTN) showed no advantage over placebo in terms of efficacy (anginal attack rates and sublingual GTN consumption) or quality of life (as measured with the sickness impact profile and a health index of disability). Patients on the active drug reported headaches more frequently than patients on placebo, and a higher proportion of them withdrew from the trial because of headache. Quality-of-life measurements showed a significant adverse effect of active treatment, principally in the social interaction dimension of the sickness impact profile. A similar effect was observed in placebo patients when crossed to active treatment in a 4-week single-blind period. The results suggest no benefit in the relief of chest pain from 5 mg transdermal GTN when used continuously.

Fourteen patients with a history of mania satisfying DSM-III criteria were entered into a randomised double-blind placebo-controlled crossover trial, spending four weeks on each of lithium and placebo. All patients had been well and stable on lithium for at least 18 months and were not taking any other psychotropic drugs. Seven patients (50%) had a relapse of their manic illness and a further two had to be withdrawn because they recognised signs of incipient relapse. One of these became overtly manic after restarting lithium. The seven definite and the two possible relapses occurred in the placebo phase; this finding was unlikely to have arisen by chance. The relapses started 13-19 days after placebo substitution. These results have important implications in the management of lithium prophylaxis by all doctors, particularly those who, for any reason, are considering withdrawal of lithium from their patients.

The impact of B subunit killed whole-cell (BS-WC) and killed whole-cell-only (WC) oral cholera vaccines was assessed in a randomised double-blind trial in rural Bangladesh. 62,285 children aged 2-15 years and women aged over 15 ingested three doses of one of the vaccines or placebo. During the first year of follow-up there was a 26% reduction of all visits for treatment of diarrhoea in the BS-WC group and a 22% reduction in the WC group. The reduction of all admissions for fatal or severely dehydrating diarrhoea was 48% in the BS-WC group and 33% in the WC group. Overall mortality rates were 26% lower in the BS-WC group and 23% lower in the WC group during the first year, and reductions of mortality were observed only in women vaccinated at ages over 15 years. However, no differences in cumulative mortality were evident at the end of the second year of surveillance.

Glucagon in solution with a surfactant (deoxycholic acid 1% w/v) was administered by intranasal spray to 6 healthy fasting subjects and 6 insulin-dependent diabetics with insulin-induced hypoglycaemia. In the normal subjects, intranasal glucagon increased plasma glucose levels, with a dose-response effect. In the diabetic patients, plasma glucose levels showed a mean increase of 100% above nadir values in approximately 26 min in response to 7.5 mg intranasal glucagon; hypoglycaemic symptoms were relieved within about 7 min. These results suggest that intranasal glucagon is effective and may represent an alternative to parenteral glucagon or glucose or to oral sugar as the first-line treatment of hypoglycaemic episodes in insulin-dependent diabetics.

GR43175, a selective 5-HT1-like agonist, was given as an intravenous infusion in an open dose-ranging study to treat 46 attacks of severe migraine in 34 patients. The highest dose, 2 mg infused over 10 min in 24 severe attacks, resulted in rapid and complete relief of symptoms in 17 attacks (71%) and in improvement to a non-migrainous residual headache in 7 attacks. Treatment was well tolerated, the only adverse effects being transient feelings of heaviness and pressure, predominantly in the head. GR43175 may represent an important advance in the treatment of acute migraine.

To compare the efficacy of once daily monotherapy with that of standard combination antibiotic therapy for the initial management of patients suspected of serious bacterial infections, 105 patients were randomised to treatment with ceftriaxone alone (53 patients) or to a combination of cefuroxime and gentamicin (52 patients). There was no difference between the groups in proportions responding to therapy or proportions dying from infection, except when non-evaluable patients were excluded from the group with definite bacterial infection, in which case response was better among those treated with ceftriaxone. The groups did not differ in number of side-effects, but therapy had to be discontinued because of treatment failure, an adverse effect, or death in 1 of 53 patients given ceftriaxone and in 11 of 34 given the combination. Use of ceftriaxone was 107.36 pounds ($182.51) cheaper per patient, and saved 40 minutes of nursing and drug administration time per patient per day. Thus 2 g ceftriaxone given once a day is at least as effective and costs less in time and money than gentamicin plus cefuroxime for the initial treatment of patients with serious systemic bacterial infections.

A test for autonomic denervation based on the local sweat response to 0.1 ml 1% acetylcholine administered intradermally, which depends on an intact local sympathetic supply, is described. Diabetic autonomic neuropathy affects the longest fibres first and thus the test was applied to the feet. After painting a standard site on the dorsum of the foot with iodine and starch, acetylcholine was injected intradermally in the centre. The normal response, visible to the eye, is a uniform distribution of dark spots of iodine discolouration at the sites of sweat production. In diabetic autonomic neuropathy this pattern is lost to a varying degree. In a photographic image magnified x 10, the spots were counted in sixty 2.5 cm squares in a grid centred on the injection site. 50 normal volunteers aged 18-69 were tested. No effect of age or sex was found. Five or more squares with less than 6 spots was the definition of abnormal. 24 diabetic men who complained of impotence were investigated with the sweatspot test, a pupil test, and cardiovascular autonomic function tests. 13 had abnormal sweatspot tests with scores up to sixty squares with less than 6 spots. In keeping with the increased length of the sympathetic fibres to the feet compared with those to the iris, there was a 30% false-negative rate for the pupil test if the sweatspot test is taken as standard. Agreement between the cardiovascular tests and the sweatspot test was seen in only 17 patients. The sweatspot test appears to be a more sensitive indicator of autonomic neuropathy than the commonly used cardiovascular tests.

30 patients with rapidly relapsing duodenal ulceration were studied to assess the possible benefit of hypnotherapy in relapse prevention. After the ulcer had healed on treatment with ranitidine, the drug was continued for a further 10 weeks during which time patients received either hypnotherapy or no hypnotherapy. The two randomly selected groups were comparable in terms of age, sex, smoking habits, and alcohol consumption. Follow-up of both groups of patients was continued for 12 months after the cessation of ranitidine. After 1 year, 8 (53%) of the hypnotherapy patients and 15 (100%) of the control subjects had relapsed. The results of this study suggest that hypnotherapy may be a useful therapeutic adjunct for some patients with chronic recurrent duodenal ulceration.

A birth control vaccine incorporating a synthetic peptide antigen representing the aminoacid sequence 109-145 of the C-terminal region of the beta subunit of human chorionic gonadotropin (hCG-beta) was submitted to a phase 1 clinical trial. Thirty surgically sterilised female volunteers, divided into five equal groups for different vaccine doses, received two intramuscular injections six weeks apart. Over a six-month follow-up there were no important adverse reactions, and potentially contraceptive levels of antibodies to hCG developed in all subjects. In the highest vaccine dose group, the results gave promise of a contraceptive effect of six months' duration.

To evaluate the effectiveness of immune serum globulin (ISG) in preventing non-A, non-B hepatitis, 291 heart surgery patients who received blood from voluntary donors were randomly assigned to receive either ISG or no additional protection. ISG was given intramuscularly before and 1 week after transfusion. 98 controls and 100 in the ISG group completed the study. Post-transfusion non-A, non-B hepatitis developed in 11 (11.2%) controls but in only 3 (3.0%) of the ISG group (p = 0.0203). 8 (72.7%) of control group with hepatitis had symptoms, and in 5 (45.4%) the disease became chronic. The disease was self-limiting in all 3 ISG patients affected, and only 1 of them had symptoms. Among those with non-A, non-B hepatitis aminotransferase levels were higher in the controls than in the ISG patients. Incubation periods longer than 8 weeks correlated with a tendency for the disease to become chronic. ISG recipients had shorter as well as more homogeneous incubation periods. ISG could be a safe, low-cost means for preventing post-transfusion non-A, non-B hepatitis which does not call for the discarding of donated blood.

After tissue heart valve replacement 108 patients were randomised to standard anticoagulant control with rabbit brain thromboplastin (Dade C reagent, therapeutic range 18-24 s; international normalised ratio 2.5-40) and 102 to a less intensive regimen controlled with human brain thromboplastin (Manchester Comparative Reagent, therapeutic range 26-30 s; INR 2.0-2.25). Treatment was continued for three months, outcome measures being major or minor embolism or haemorrhage. 2 patients in each group had major embolic events and 11 in each group had minor embolic events. The 95% confidence intervals on the differences are -3.4% to 3.2% for major embolism and -9.3% to 8.2% for minor embolism. Haemorrhagic complications were significantly more frequent with standard treatment (15 patients) than with the less intensive regimen (6 patients); and of the 5 patients with major haemorrhagic complications, all were in the standard treatment group, again a significant difference. The less intensive regimen is thus no less effective and safer than standard anticoagulant therapy in patients with tissue heart valve replacement.

During an outbreak of meningococcal meningitis in Saudi Arabia, oral rifampicin (four doses in two days) was compared with a single intramuscular dose of ceftriaxone for prophylaxis in family contacts of patients with meningococcal disease. Pharyngeal samples were taken for culture before and 1 and 2 weeks after administration. Both follow-up cultures indicated that ceftriaxone was significantly more effective. At 1 week the eradication rates for ceftriaxone and rifampicin were 97% and 75%; at 2 weeks they were 97% and 81%, respectively. No serious side-effects were associated with either agent. Ceftriaxone may provide an effective alternative to rifampicin for prophylaxis in meningococcal contacts.

23 patients with clinically active late Lyme disease were randomly assigned to intravenous treatment with either penicillin or ceftriaxone. Of the 10 treated with penicillin, 5 were judged treatment failures; of the 13 who received ceftriaxone, only 1 did not respond. An additional 31 patients were subsequently treated with ceftriaxone 4 g/day (n = 17) or 2 g/day (n = 14); success rates in both groups were comparable to those in the cohort randomised to ceftriaxone. Patients unresponsive to ceftriaxone were more likely to have received corticosteroid treatment.

The ability of four vagotonic physical manoeuvres to terminate paroxysmal junctional tachycardias was tested in 35 patients with inducible and sustained arrhythmia. Each manoeuvre was used up to three times in an attempt to terminate an induced tachycardia and was judged to be effective if it terminated two out of the three induced episodes. The Valsalva manoeuvre in the supine position was effective in 19 (54%), right carotid sinus massage in 6 (17%), left carotid sinus massage in 2 (5%), and the diving reflex in 6 (17%) cases. 4 of the 6 patients who responded to right carotid sinus massage and all patients who responded to the diving reflex also responded to the Valsalva manoeuvre. The Valsalva manoeuvre while standing was effective in 9 (20%) patients only. Patients in whom the manoeuvres terminated the tachycardias were significantly younger than those who did not respond (median age: 30 vs 45 years, p less than 0.01). Physical manoeuvres were much more successful in terminating atrioventricular re-entry tachycardias (19/24) than atrioventricular nodal re-entry tachycardias (3/11, p less than 0.01). Efficacy of the manoeuvres was related to their bradycardic effect in sinus rhythm.

562 patients whose duodenal ulcers had healed in a series of double-blind controlled trials of various medical treatments were enrolled in a long-term endoscopic follow-up. 436 were followed for up to four years or until relapse. Relapse rates did not differ between the groups treated with cimetidine, ranitidine, pirenzepine, or placebo. At six and twelve months but not subsequently, there was a significant advantage for tripotassium dicitrato-bismuthate. Relapse rates were at all times higher in smokers than in non-smokers.

Two drug strategies for the control of malaria in children aged 3-59 months have been compared in a rural area of The Gambia--treatment of presumptive episodes of clinical malaria with chloroquine by village health workers, and treatment combined with fortnightly chemoprophylaxis with 'Maloprim' (pyrimethamine/dapsone) which was also given by village health workers. Treatment alone did not have any significant effect on mortality or morbidity from malaria. In contrast, treatment and chemoprophylaxis reduced overall mortality in children aged 1-4 years, mortality from probable malaria, and episodes of fever associated with malaria parasitaemia. A high level of compliance with chemoprophylaxis was obtained and no harmful consequences of chemoprophylaxis were observed.

To assess the value of antithyroid drugs as an adjunct to radioactive iodine for the treatment of hyperthyroidism the incidence of relapse or hypothyroidism after a mean follow-up of 5 1/2 years (range 2-7 years) was reviewed retrospectively for 206 patients, some treated with and others without antithyroid drugs after radioiodine therapy. Allocation to treatment group had been random, and both groups were similar in all respects except for the adjunctive treatment with antithyroid drugs. All doses of 131I had been calculated by one physician. Compared with those who received 131I alone, those starting on antithyroid drugs within 8 days after 131I had a lower incidence of hypothyroidism but a higher incidence of early post-treatment recurrence or persistence of hyperthyroidism, and a considerably lower incidence of remission.