447 infants, born to mothers positive for hepatitis B e antigen and hepatitis B surface antigen (HBsAg), received hepatitis B immunisation. A higher rate of hepatitis B virus (HBV) infection was found at birth in infants delivered vaginally (96/385, 24.9%) than in infants delivered by caesarean section (6/62, less than 10%). At birth, serum HBV-DNA was detected in 13 of 67 infants delivered vaginally, but in none of 30 infants delivered by caesarean section. Caesarean section combined with hepatitis B immunisation is advisable in infants of mothers who are chronic HBsAg carriers with high serum HBV-DNA levels.

In a randomised trial, infants living in a large village in The Gambia were immunised either at 4 months of age with 40,000 plaque forming units (PFU) of the Edmonston-Zagreb (EZ) measles vaccine or at the usual age of 9 months with 6000 TCID50 of a conventional Schwarz measles vaccine. Measles developed in 2 of 119 children who received the EZ vaccine, in 1 before and in the other after 9 months of age. In the Schwarz group measles developed in 7 of 120 children--in 5 before and in 2 after 9 months of age. Serological responses measured at 5 months after vaccination and at 18 months of age were satisfactory in both groups although in the Schwarz group levels were on average 2-fold higher than in the EZ group. The frequencies of fever, cough, vomiting, and diarrhoea were no higher in the EZ vaccinees in the 3 weeks following vaccination than in age-matched non-immunised controls. Long-term morbidity as assessed by clinic attendances and weight at 18 months of age was much the same in the two groups. The EZ measles vaccine is thus safe and clinically and serologically effective when used in a high dose to immunise young Gambian infants.

In a randomised study of 558 children in an urban African community, the protective effect of the Edmonston-Zagreb (EZ) measles vaccine given in a dose of 40,000 plaque forming units from the age of 4 months was compared with the effects of a standard dose (6000 tissue culture infectious units) of Schwarz measles vaccine given from the age of 9 months. During two years of follow-up, all 14 clinical cases of measles occurred in the Schwarz group; 10 of the children contracted measles before vaccination and 4 after measles vaccination. Thus the EZ vaccine provided significant protection against measles both before and after the usual age of vaccination. Among the children who were exposed to measles at home, those given EZ vaccine were better protected than either unvaccinated children or those given the Schwarz vaccine.

The effect of percutaneous electrical stimulation in preventing immobilisation-induced muscle atrophy was determined from measurements of quadriceps mass, composition, and rate of protein synthesis in seven men who had a fracture of one tibia immobilised in a long-leg cast for 6 weeks. These features were compared with those of fourteen men with similar injuries who did not use an electrical stimulator. In men who did not use the stimulator, quadriceps cross-sectional area (CSA) at midthigh, measured by ultrasonography, fell by a mean (SD) 17 (10)% and the rate of muscle protein synthesis was 23 (10)% lower on the immobilised than on the control side (0.037 [0.016] vs 0.048 [0.02]%/h). In contrast, in those who used the stimulator, quadriceps CSA (55.5 [7.3]) cm2 control leg, 50.9 [9.0] cm2 immobilised leg) and the rate of muscle protein synthesis (0.053 [0.009] %/h control leg, 0.059 [0.012] %/h immobilised leg) were similar on the two sides. The results suggest that brief periods of low-voltage percutaneous electrical stimulation will reduce quadriceps atrophy secondary to knee immobilisation, and that the mechanism includes prevention of the fall in muscle protein synthesis that usually occurs on immobilisation.

In a preliminary study, carriers of hepatitis B virus were treated with a preparation of the plant Phyllanthus amarus for 30 days. 22 of 37 (59%) treated patients had lost hepatitis B surface antigen when tested 15-20 days after the end of the treatment compared with only 1 of 23 (4%) placebo-treated controls. Some subjects have been followed for up to 9 months. In no case has the surface antigen returned. Clinical observation revealed few or no toxic effects. The encouraging results of this preliminary study recommend continued evaluation of this plant and the active principles isolated from it.

240 patients with active tuberculous pericardial effusion received a 4-drug daily antituberculosis regimen for 6 months and have been studied for 24 months or longer. Those willing were randomly allocated to open pericardial biopsy and complete drainage of pericardial fluid on admission or percutaneous pericardiocentesis as required. All patients were randomly allocated to prednisolone or matching placebo for the first 11 weeks, on a double-blind basis. Complete open drainage on admission abolished the need for pericardiocentesis (p less than 0.01) but did not influence the need for pericardiectomy for subsequent constriction or the risk of death. Among patients who did not have open drainage on admission, 2 (3%) of 76 given prednisolone compared with 10 (14%) of 74 given placebo died of pericarditis (p less than 0.05), 6 (8%) and 9 (12%) respectively required pericardiectomy, 7 (9%) and 17 (23%) repeat pericardiocentesis (p less than 0.05), and 3 (4%) and 7 (9%) open surgical drainage. By 24 months, apart from the 16 who died from pericarditis, all but 3 patients (2%) had a favourable status.

6264 hours of ambulatory ST segment monitoring of 150 unselected patients with proven coronary artery disease, who were off all routine anti-anginal treatments, showed 598 ischaemic episodes, of which 446 (75%) were silent (symptom-free). Most (68%) ischaemic episodes occurred between 0730 and 1930, with a peak in the morning and a lesser peak in the evening. Two subgroups were studied further in double-blind controlled trials: 33 patients had a total of 1313 hours of ST segment monitoring while treated with nifedipine; and 41 patients a total of 1581 hours while treated with atenolol. Nifedipine did not alter the circadian pattern of ischaemic episodes; atenolol abolished the morning peak, and the peak incidence of ischaemia then occurred in the evening. Circadian patterns for total duration of ischaemic episodes corresponded closely to those of episodes of ischaemia, and were similarly altered by treatment. The circadian pattern of silent ischaemic episodes and their total duration were very similar to those of total ischaemia for the group as a whole and the different subgroups. This circadian distribution of ischaemic episodes and the observed changes with treatment resemble the reported circadian variation of acute myocardial infarction and sudden death.

Blood circulation was measured by laser doppler flowmetry in fasciocutaneous flaps of 24 patients who underwent reconstructive surgery for mammary carcinoma. 19 of the 24 patients had clinical signs of deficient circulation in the flaps. 14 patients were treated with electrical nerve stimulation (ENS) and 10 with placebo-ENS. Varying degrees of necrosis developed in 8 of the 10 patients who received placebo stimulation but in none of those treated with ENS. In the 5 patients with good capillary refilling and no signs of stasis or oedema before treatment, only minor increases in blood flow occurred after ENS.

83 patients with human immunodeficiency virus (HIV) infection (CDC groups II, III, or IV-A) were randomised in a crossover trial of sodium-diethyldithiocarbamate (ditiocarb sodium, 'Imuthiol') (10 mg/kg body weight given orally once a week) against placebo. Each arm of the trial lasted 16 weeks. The disease did not progress to CDC-defined acquired immunodeficiency syndrome in the ditiocarb group but did so in 4 patients in the placebo group (3 between week 0 and 16, 1 between week 17 and 32). Ditiocarb was also associated to a significantly greater extent than placebo with relief of constitutional symptoms, improvement in clinical status (including shrinkage of enlarged spleen and lymph nodes), and improvement in immune function (as measured by CD4+ cell count and skin test reactivity). When placebo was replaced by ditiocarb, similar improvements were observed, whereas symptoms slowly reappeared and CD4+ cell levels progressively declined when ditiocarb treatment was replaced by placebo.

Fourteen patients suffering sixteen episodes of septic shock requiring inotrope and/or vasopressor support were randomised to receive a 30 micrograms/kg naloxone intravenous bolus followed by a 30 micrograms/kg/h infusion or an equivalent volume placebo bolus and infusion for 8-16 h in a double-blind study. pH and pulmonary wedge pressure were kept constant, and inotrope and/or vasopressor were titrated to maintain a preselected mean blood pressure. Inotrope/vasopressor requirements in the naloxone-treated group were significantly lower than those in the control group at 8 h (eight patients in each group, p less than 0.005) and at 16 h (five patients in each group, p less than 0.02). Late but significant improvements in stroke volume (p less than 0.02) and heart rate (p less than 0.05) were also noted in the eight naloxone-treated patients.

The survival benefit of second-look laparotomy after completion of primary chemotherapy in patients with epithelial ovarian cancer has been assessed in a prospective randomised trial of 166 patients. Patients were randomised into three groups. All were initially treated with cisplatin (100 mg/m2 x 5) after primary laparotomy. Group A (n = 53) was scheduled to have a second-look laparotomy, followed by cyclical oral chlorambucil. Group B (n = 56) was scheduled to have a second-look laparotomy, followed by total abdominal and pelvic irradiation, and group C (n = 57) received oral chlorambucil as for group A but had no second-look operation. With a median follow up of 46 months (range 21-64), no differences in survival were noted between the three groups. The median survival for group A was 21 months (95% CI 11-31 months), for group B 15 months (11-19), and for group C 17 months (8-26). Thus second-look laparotomy after completion of first-line single-agent cisplatin chemotherapy did not confer any survival benefit on patients with epithelial ovarian cancer.

4997 of 7354 pregnant women had no clinical indication for an elective ultrasound examination at 12 weeks' gestation. 2482 of these women were randomly selected for ultrasound screening at 15 weeks and the remainder received the same standard antenatal care without the scan. Labour was less often induced among screened women both for all reasons (5.9% vs 9.1%, p less than 0.0001) and for suspected post-term pregnancy (1.7% vs 3.7%, p less than 0.0001). Earlier detection of twins had no effect on neonatal outcome. Among babies born to screened women, fewer were of birthweight less than 2500 g (59 vs 95, p = 0.005) and mean birthweight was 42 g higher (p 0.008). For babies born to screened women who smoked it was 75 g higher (p 0.012) and for those of non-smokers 26 g (not significant). The reason for the differences in mean birthweight could be that screened women reduced smoking in response to watching their fetus on the scan.

13,318 patients admitted to fifty-two coronary care units with suspected acute myocardial infarction were considered for inclusion in a double-blind study comparing recombinant tissue-type plasminogen activator (rt-PA) 100 mg plus heparin with placebo plus heparin. 8307 (62%) were excluded, mainly because their symptoms had begun more than 5 h previously, but all excluded patients were followed up at least until hospital discharge. 2516 patients were randomly allocated to rt-PA and 2495 to placebo. At one month the overall case fatality rates were 7.2% and 9.8%, respectively, a relative reduction of 26% (95% confidence interval 11-39%). 6.3% of patients given rt-PA had a bleeding complication (1.4% major) compared with 0.8% given placebo (0.4% major). However, the incidence of stroke was similar--1.1% in the rt-PA group and 1.0% in the placebo group. Subset analysis showed that patients who had a normal electrocardiogram (ECG) at the time of randomisation (17.5% of the whole trial population) had a low case fatality rate (1.6% in those given rt-PA compared with 3.0% in those given placebo). In those with an abnormal ECG at entry, rt-PA was associated with a 24.5% relative reduction in 1 month fatality (95% confidence interval 9-37%).

The clinical value of therapeutic suggestions during general anaesthesia was assessed in a double-blind randomised placebo-controlled study. 39 unselected patients were allocated to suggestion (n = 19) or control (n = 20) groups who were played either recorded therapeutic suggestions or a blank tape, respectively, during hysterectomy. The patients in the suggestion group spent significantly less time in hospital after surgery, suffered from a significantly shorter period of pyrexia, and were generally rated by nurses as having made a better than expected recovery. Patients in the suggestion group, unlike those in the control group, guessed accurately that they had been played an instruction tape.

The genes encoding the A (toxic) subunit of cholera toxin were deleted from pathogenic Vibrio cholerae O1 strain 569B by recombinant techniques, leaving intact production of immunogenic, non-toxic B subunit. The resultant strain, CVD 103, evaluated for safety, immunogenicity, and efficacy as a live oral vaccine, was highly attenuated and elicited strong antibacterial and antitoxic immune responses; a single dose significantly protected volunteers against challenge with pathogenic V cholerae O1 of either serotype or biotype. A further derivative, CVD 103-HgR, which has an Hg++-resistance gene to differentiate it from wild-type vibrios, was also well-tolerated, immunogenic, and protective; moreover, faecal excretion of this derivative was significantly lower than that of CVD 103, which should minimise environmental spread of the vaccine. CVD 103-HgR is a candidate for expanded clinical trials in endemic areas.

Between 1979 and 1981 the UK Trial of Early Detection of Breast Cancer enrolled women aged 45-64 living in eight locations in the United Kingdom. Annual screening by clinical examination of the breast, with mammography in alternate years, was provided over 7 years for 45,841 women; 63,636 were offered teaching in breast self-examination and were provided with a self-referral clinic; and 127,117, for whom no extra services were provided, form a comparison population. Over the 7 years from the start of the trial a reduction in the risk of dying from breast cancer in women offered screening relative to that in the comparison population was observed. The reduction was 14% (RR 0.86, 95% CI 0.69-1.08) when no allowance was made for underlying differences in breast cancer mortality between the populations, but rose to 20% (RR 0.80, 95% CI 0.64-1.01) when adjusted for differences in pretrial mortality rates. These differences fall short of statistical significance. No reduction in mortality was observed during the first 5 years but thereafter the gap widens. These results, though in themselves inconclusive, are consistent with the hypothesis that screening can achieve a worthwhile mortality reduction. No difference in mortality has so far been observed between women offered teaching in breast self-examination and the comparison population.