Since November 1989, Japanese Red Cross blood centres throughout the country have screened donors for hepatitis C virus (HCV) with an Ortho enzyme-linked immunosorbent assay for antibody to the C100-3 viral peptide. Simultaneously, the centres started to screen for units with high-titre (greater than or equal to 2(6)) antibody to hepatitis B virus core antigen (HBcAb) in the absence of hepatitis B virus surface antigen and antibody. To test the effectiveness of this policy, the incidence of post-transfusion non-A, non-B hepatitis (PTNANBH) and post-transfusion hepatitis B (PTHB) after screening had been introduced (November, 1989, to December, 1990, inclusive) was compared with the incidence before screening (January, 1988, to October, 1989, inclusive). Incidence of PTNANBH in patients who had received 1-10 unit transfusions was 4.9% (58/1189) before screening vs 1.9% (15/784) afterwards. Incidence in those who had 11-20 unit transfusions was 16.3% (64/392) vs 3.3% (4/124). Incidence of PTHB was 0.25% (4/1597) before screening; no cases have been detected subsequently. These results show the effectiveness of the first-generation anti-HCV test and indicate the value of screening for high-titre HBcAb in addition to HBV surface antigen testing in HBV endemic areas.

Many patients with angina pectoris whose symptoms are not completely controlled by beta-blockers are treated with several types of drugs, but it is not clear whether addition of a calcium-channel antagonist and/or a nitrate confers any advantage over beta-blockade alone. 18 patients receiving atenolol for stable angina pectoris completed a double-blind, randomised, crossover trial of atenolol treatment plus placebo, isosorbide mononitrate, nifedipine, and mononitrate and nifedipine (triple therapy). The patients were assessed subjectively and by treadmill exercise testing and 24 h ambulatory electrocardiographic recordings at the end of each 4-week treatment period. There were no significant differences among the treatment periods in angina attack rates, glyceryl trinitrate consumption, exercise duration to onset of angina or 1 mm ST depression, or duration of symptomless ischaemia. Total exercise duration was longer on atenolol plus mononitrate than on atenolol alone (mean difference 46 [95% confidence interval 18-88] s; p = 0.005), atenolol plus nifedipine (36 [2-71] s; p = 0.04), or triple therapy (28 [6-61] s; not significant). In 12 patients the exercise time was shorter on triple therapy than on atenolol plus mononitrate alone. Although "maximum" antianginal treatment with two or three drugs is commonly accepted, this approach confers no substantial advantage over optimum beta-blockade as monotherapy. If a second drug is needed, there is a slight advantage in favour of isosorbide mononitrate, but if this is not effective, treatment should be changed rather than added. Many patients with angina pectoris seem to be pharmacologically overtreated.

Epidemiological studies have revealed an increased risk of cancer, notably soft-tissue sarcomas and non-Hodgkin's lymphomas, in people occupationally exposed to chlorophenoxy herbicides, including those contaminated by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD). We report here a historical cohort study of mortality in an international register of 18,910 production workers or sprayers from ten countries. Exposure was reconstructed through questionnaires, factory or spraying records, and job histories. Cause-specific national death rates were used as reference. No excess was observed in all-cause mortality, for all neoplasms, for the most common epithelial cancers, or for lymphomas. A statistically non-significant two-fold excess risk, based on 4 observed deaths, was noted for soft-tissue sarcoma with a standardised mortality ratio (SMR) of 196 and 95% confidence interval (Cl) 53-502; this was concentrated as a six-fold statistically significant excess, occurring 10-19 years from first exposure in the cohort as a whole (SMR = 606 [165-1552]) and, for the same time period, as a nine-fold excess among sprayers (SMR = 882 [182-2579]). Risks appeared to be increased for cancers of the testicle, thyroid, other endocrine glands, and nose and nasal cavity, based on small numbers of deaths. The excess of soft-tissue sarcomas among sprayers is compatible with a causal role of chlorophenoxy herbicides but the excess does not seem to be specifically associated with those herbicides probably contaminated by TCDD.

Diagnosis of lung cancer by examination of induced sputum specimens for malignant cells may be a valuable alternative to diagnosis by bronchoscopy. Patients suspected of having lung cancer were recruited and randomly distributed into two groups, one group (n = 34) having sputum induced by use of an ultrasonic nebuliser before bronchoscopy, and the other (n = 33) undergoing ordinary expectoration before bronchoscopy. 25 patients in the induced-sputum group were diagnosed as having primary lung cancer; induced sputum was positive for malignant cells in 21 of these patients (84%), whereas bronchoscopy was positive in 23 (92%) (not significantly different). In comparison, ordinary sputum was positive in 15 of 29 patients (52%) diagnosed as having primary lung cancer, whereas bronchoscopy was positive in 28 (97%) (p less than 0.001). Induction of sputum by an ultrasonic nebuliser was an effective procedure for diagnosis of primary lung cancer.

Numerous studies have shown that patients are usually dissatisfied with the information they receive during clinical consultations with medical specialists. Therefore, a randomised study design has been used to assess the role of personal letters to patients outlining their cancer consultation. Compared with the control group, patients receiving letters were more satisfied with the amount of information given, and tended to have greater and more accurate recall of the consultation. A survey of referring doctors revealed general support for the idea of sending to cancer patients letters that outline the substance of their consultations. The study shows that letters to patients are a useful method of improving patient satisfaction and recall in clinical consultations. They also provide a permanent record of the consultation, which can be kept for future reference, and encourage greater patient involvement in their care.

To test whether interferon can prevent acute non-A, non-B hepatitis from becoming chronic, a prospective controlled trial was conducted in 25 patients; 11 were treated for an average of 30 days with a mean of 52 megaunits of interferon and 14 acted as controls. 4 patients in the treatment group who continued to have raised serum aminotransferase concentrations after a year's follow-up were given a second course of interferon. Follow-up at 3 years has revealed that all but 1 of those treated showed normal serum aminotransferase, whereas only 3 controls showed such change (p less than 0.02). Serum hepatitis C virus RNA became undetectable in 10 of 11 treated and in only 1 of 12 control patients, which suggests that interferon prevents the progression of acute non-A, non-B hepatitis to chronicity by eradicating HCV.

The use of Edmonston-Zagreb high-titre (EZ-HT) vaccine at age 6 months has been recommended for countries in which measles before the age of 9 months is a substantial cause of death, but little is known about the long-term effects of high-titre live measles vaccines given early in life. In a randomised vaccine trial in a rural area of Senegal, children were randomly assigned at birth to three vaccine groups: EZ-HT at 5 months (n = 336); Schwarz high-titre (SW-HT) at 5 months (n = 321); and placebo at 5 months followed by standard low-titre Schwarz vaccine at 10 months (standard: n = 358). All children were prospectively followed for 24-39 months in a well-established demographic surveillance system. Child mortality after immunisation was significantly higher in the two groups which received high-titre vaccines than in the group given the standard vaccine. The relative risk of death was 1.80 (95% confidence interval [CI] 1.18-2.74; p = 0.007) in the EZ-HT group and 1.51 (0.97-2.34; p = 0.07) in the SW-HT group compared with the standard group. The three vaccine groups were comparable as regards various social, family, and health characteristics, and there was no difference in mortality between children who received the standard vaccine and those who were eligible for the trial but did not take part for various reasons. The higher risk of death in the two high-titre vaccine groups remained significant in multivariate analyses. These findings suggest a need to reconsider the use of high-titre measles vaccines early in life in less developed countries.

Fasting is an effective treatment for rheumatoid arthritis, but most patients relapse on reintroduction of food. The effect of fasting followed by one year of a vegetarian diet was assessed in a randomised, single-blind controlled trial. 27 patients were allocated to a four-week stay at a health farm. After an initial 7-10 day subtotal fast, they were put on an individually adjusted gluten-free vegan diet for 3.5 months. The food was then gradually changed to a lactovegetarian diet for the remainder of the study. A control group of 26 patients stayed for four weeks at a convalescent home, but ate an ordinary diet throughout the whole study period. After four weeks at the health farm the diet group showed a significant improvement in number of tender joints, Ritchie's articular index, number of swollen joints, pain score, duration of morning stiffness, grip strength, erythrocyte sedimentation rate, C-reactive protein, white blood cell count, and a health assessment questionnaire score. In the control group, only pain score improved score. In the control group, only pain score improved significantly. The benefits in the diet group were still present after one year, and evaluation of the whole course showed significant advantages for the diet group in all measured indices. This dietary regimen seems to be a useful supplement to conventional medical treatment of rheumatoid arthritis.

In most developing countries, bacterial meningitis (BM) is associated with a high case-fatality rate. The search for a simple, convenient, and inexpensive antibiotic treatment remains a priority. In this study, a non-blinded, multicentre, randomised clinical trial of 528 cases of BM was done in two hospitals in Mali and Niger, between March, 1989, and May, 1990, to see whether a double injection of long-acting chloramphenicol (on admission to hospital and 48 h later) is as effective as a course of intravenous ampicillin (8 days, 4 times a day). The cumulative case-fatality rate on day 4 (principal end-point) among the chloramphenicol (254 patients) and ampicillin (274) groups were, respectively, 28% and 24.5% (relative risk 1.14, 95% confidence interval 0.86-1.52). No outbreak occurred during the study period. The hospital case-fatality rate was 33.1%. Main risk factors for death were associated with clinical condition on admission--ie, altered consciousness, convulsions, or dehydration. The case-fatality rates were 13% (21/161) for Neisseria meningitidis, 36.1% (48/133) for Haemophilus influenzae, and 67% (77/115) for Streptococcus pneumoniae. In a multiple logistic regression model, controlling for the differential distribution of potential risk factors (including bacterial species), there was no difference between treatment groups. Our findings suggest that long-acting chloramphenicol is a useful first-line presumptive treatment for BM in high-incidence countries.

Detection of Chlamydia trachomatis eye infection is largely unsatisfactory by standard laboratory methods. A polymerase chain reaction/enzyme immunoassay (PCR-EIA) that had previously been successful for diagnosis of genital C trachomatis infection was compared with direct antibody immunofluorescence (DFA) for detection of the organism in conjunctival scrapes. 234 Tanzanian children aged 1-7 years living in a village that had had no previous trachoma control programme were classified clinically as having no sign of trachoma (0) n = 97, follicular trachoma (TF) n = 100, or intense inflammatory trachoma with or without TF (TI +/- TF) n = 37. PCR-EIA detected C trachomatis in 24%, 54%, and 95% of subjects, respectively, compared with elementary body (EB) detection by DFA of 1%, 28%, and 60%, respectively. Overall prevalence of chlamydial eye infection was 22% by DFA compared with 48% by PCR-EIA. Of subjects with chlamydial DNA at pretreatment, 103 (92%) had no detectable chlamydial DNA at the end of 4 weeks of ocular tetracycline. The findings show that PCR-EIA is likely to affect trachoma diagnosis and epidemiology because of the increased sensitivity for detection of C trachomatis in all clinical groups; the less stringent requirements for specimen collection and transport make this method suitable for field use. Moreover, the semi-quantitative aspect of PCR-EIA may be useful for monitoring a decrease in chlamydial DNA after treatment.

To determine whether the long-acting injectable progestational contraceptive DMPA, depot-medroxyprogesterone acetate, alters the risk of breast cancer in women, a hospital-based case-control study was conducted in five participating hospitals in Nairobi, Kenya, Mexico City, Mexico, Bangkok, Thailand (two hospitals), and Chiang Mai, Thailand. 869 women with newly diagnosed breast cancer who were young enough to have used DMPA for contraception, and 11,890 women of similar age who had been admitted to hospital for conditions unrelated to steroid contraceptive use, were interviewed to obtain information about previous use of steroid contraceptives and suspected risk factors for breast cancer. DMPA had been used by 12.5% of cases and 12.2% of controls. Relative risk (95% Cl) in women who had ever used DMPA was 1.21 (0.96, 1.52). Risk was increased within the first 4 years of initial exposure, mainly in women under 35 years. This observation did not seem to result from selective surveillance for breast cancer in DMPA users. Risk did not increase with duration of use, and was not increased in women who had started to use DMPA more than 5 years previously. These results provide reassurance that women who have used DMPA for a long time and who initiated use many years previously are not at increased risk of breast cancer.