21 patients with severe persistent cyclical mastopathy of at least 5 years' duration were randomised to a control group who received general dietary advice or to an intervention group who were taught how to reduce the fat content of their diet to 15% of calories while increasing complex carbohydrate consumption to maintain caloric intake. Both groups were followed for 6 months with food records and measurement of plasma hormone and lipid levels. Severity of symptoms was recorded with daily diaries and patients were assessed at the beginning and end of the study by a physician who was unaware of their dietary regimen. After 6 months there was a significant reduction in the intervention group in the severity of premenstrual breast tenderness and swelling. Physical examination showed reduced breast swelling, tenderness, and nodularity in 6 of 10 patients in the intervention group and 2 of 9 patients in the control group.

Functional psychosis is conventionally subdivided into schizophrenia and manic depressive psychosis. Response to treatment is assumed to be a validating criterion for these diagnoses. The efficacy of pimozide (a dopamine antagonist neuroleptic), lithium, and a combination of the two was compared with that of placebo in a 4 week trial in 120 functionally psychotic patients each of whom was assessed for psychotic symptoms, manic symptoms, and depressive symptoms. The sample was subdivided into patients with predominantly elevated mood, predominantly depressed mood, and no consistent mood change. Pimozide reduced psychotic symptoms in all groups of patients. The only significant effect of lithium was to reduce elevated mood. Thus dopamine blockade seems relevant to the resolution of psychotic symptoms in all types of "functional" psychosis but the mode of action of lithium in psychotic patients concerns only mood. Application of standardised classifications of functional psychosis to these data did not change this conclusion.

48 patients over 6 years of age with strictly defined cerebral malaria were randomised to receive either a single intramuscular injection of phenobarbitone (3.5 mg/kg) or placebo in a double-blind, placebo-controlled study. Phenobarbitone significantly reduced the incidence of subsequent convulsions from 54% to 12.5%, without adverse effects. A single intramuscular injection of phenobarbitone is a simple, cheap, and effective method for prevention of convulsions in cerebral malaria.

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.

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.

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.

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.

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.

22 patients with amyotrophic lateral sclerosis were entered into a double-blind, randomised, placebo-controlled trial of treatment with branched-chain aminoacids. 11 received daily 12 g L-leucine, 8 g L-isoleucine, and 6.4 g L-valine, by mouth, and the remainder received placebo. During the one-year trial, patients in the placebo group showed a linear decline in functional status consistent with the natural history of the disease. Those treated with aminoacids showed significant benefit in terms of maintenance of extremity muscle strength and continued ability to walk.

16 chronic haemodialysis patients (group I), with non-microcytic anaemia (mean haemoglobin 7.2 g/dl, SD 1.0, range 5.8-9.8), moderate aluminium overload (serum aluminium 44 micrograms/l, SD 16, range 21-74), and normal or high iron stores (ferritin 800 micrograms/l SD 464, range 34-2013) were treated with intravenous desferrioxamine 1 g at the end of each dialysis for six months. 8 patients with similar characteristics served as controls (group II). After six months group I showed a rise in haemoglobin to 9.1 (SD 2.5) g/dl and a decrease in blood transfusion requirements, both significant, whereas group II showed no changes. Other significant changes observed in group I, but not group II, were a rise in reticulocytes and in red cell creatine and a fall in red cell protoporphyrin and serum ferritin. Ferritin decreased more in the patients whose anaemia improved. Minor increases in serum aluminium in group I did not differ from those in the control group. Desferrioxamine may benefit the anaemia of chronic haemodialysis patients through improvement of erythropoiesis. The effect seems not to be related to chelation of a heavy aluminium overload.

Small-scale trials of the Edmonston-Zagreb (E-Z) measles vaccine were undertaken to determine the dose necessary to immunise 4-6-month-old infants. Antibody responses, measured 16 weeks after vaccination, were dose dependent: 40,000 plaque forming units given subcutaneously resulted in positive responses in all infants and higher antibody levels than doses of 20,000 or 10,000 units (10,000 units gave a failure rate of 25%). In further trials the E-Z vaccine was compared with the Schwarz vaccine, both being given in subcutaneous doses of 40,000 plaque forming units. In infants aged 20 weeks the E-Z vaccine produced higher levels of measles antibody and in those aged 18 weeks its superiority showed in a lower proportion failing to respond (3 of 39 versus 19 of 35).

3801 children aged 5-11 months were entered into a blind placebo-controlled trial of pertussis vaccine. 954 were randomised to receive placebo (vaccine solvent), 1419 to receive a two-component vaccine containing formaldehyde detoxified lymphocytosis promoting factor (LPF) and filamentous haemagglutinin, and 1428 to receive an LPF-toxoid vaccine. After 7-13 weeks 3724 infants received a second dose. Immediate side-effects were mild. Small local reactions occurred more often in the vaccinated infants than in those who received placebo, especially after the second dose of the two-component vaccine. During 15 months of follow-up from 30 days after the second dose, culture-confirmed whooping cough (cough and a positive culture of Bordetella pertussis) occurred in 40 placebo, 27 LPF-toxoid vaccine, and 18 two-component vaccine recipients. The point estimate of protective efficacy was 54% (95% confidence intervals 26-72%) for the LPF-toxoid vaccine and 69% (47-82) for the two-component vaccine; protection against culture-confirmed whooping cough of over 30 days duration was 80% (59-91%) and 79% (57-90%), respectively.