The acute effects of inhaled nitric oxide (NO) (40 ppm in air) on pulmonary (PVR) and systemic (SVR) vascular resistance were compared with those of an intravenous infusion of prostacyclin (24 micrograms/h) in 8 patients with severe pulmonary hypertension and 10 cardiac patients with normal values of PVR. 10 healthy volunteers were studied non-invasively. In the patients with pulmonary hypertension, PVR fell significantly after inhaled NO and after prostacyclin. PVR also fell significantly in the cardiac patients after inhaled NO. Although SVR fell substantially after prostacyclin in patients with pulmonary hypertension, inhaled NO had no effect on SVR in any patient or volunteer. Inhaled NO therefore seems to be both a selective and effective pulmonary vasodilator.

Ivermectin seems to be a safe and effective treatment for onchocerciasis when given in a single dose, but less is known about the effects of repeated doses. Also, there seem to be differences in its effectiveness in anterior and posterior segment ocular disease. The ocular effects of ivermectin were studied in 586 villagers who were taking part in a double-blind, placebo-controlled, randomised trial in Sierra Leone. Only those who had received four doses, with 6-month intervals, of ivermectin or placebo were eligible. The 296 ivermectin-treated subjects and the 272 who received placebo were comparable with respect to age, sex, Onchocerca infection, blindness, and visual impairment before treatment. After treatment, the ivermectin group had less anterior segment disease than the placebo group, with significantly lower prevalences of microfilariae in the anterior chamber and cornea, and punctate keratitis (all p less than 0.001), and iritis (p less than 0.05). There was no significant difference in the prevalence of sclerosing keratitis, optic atrophy, or chorioretinitis between the groups. Visual acuities tended to be better in the ivermectin group, but the difference was not significant. There was a small but significant (p less than 0.01) excess of vascular sheathing in the ivermectin group. These differences persisted when subjects who were blind or visually impaired at baseline were excluded from analysis. The long-term effects of ivermectin, particularly on posterior segment disease, need further evaluation. In the mean time, the mass distribution of ivermectin should be promoted for all communities with hyperendemic onchocerciasis at risk of anterior segment disease.

For more than 15 years, Norway has had the highest incidence of meningococcal disease in northern Europe, with 80% of cases being due to serogroup B meningococci. The case-fatality has remained high, at about 10%. In this study, an outer membrane vaccine, which had previously been shown to induce an increase in bactericidal antibodies to the parent strain, was assessed in a large-scale, randomised, double-blind trial. From October, 1988, 171,800 students in secondary schools volunteered to take part in a double-blind, placebo-controlled, efficacy trial with school as the randomisation unit. Hospitals and clinics that routinely receive patients with infectious disease were asked to report urgently all cases of suspected meningitis and/or septicaemia in 13-21-year-old students in Norway. These cases were registered and further investigated according to a detailed protocol. 89 out of the 221 cases investigated by June 3, 1991, were shown to be severe systemic disease due to group B meningococci. 36 cases in 35 schools took part in the trial (11 schools with vaccinated students and 24 with students given placebo). The calculated rate of protection was thus 57.2% (p = 0.012, one-sided test). The findings suggest that, although the vaccine conferred protection against group B meningococcal disease, the effect was insufficient to justify a public vaccination programme.

When tested under conditions of moderate transmission of typhoid fever, a liquid formulation of the oral typhoid fever vaccine Ty21a had a protective efficacy of 96% in Egypt, and an enteric coated capsule formulation had an efficacy of 67% in Chile. We compared the two formulations under conditions of intense transmission of typhoid fever in Indonesia in a randomised, double-blind trial. 20,543 subjects (age range 3-44 years) received either three doses of enteric coated capsules containing placebo or live Ty21a, or three doses of lyophilised placebo or live Ty21a reconstituted with phosphate buffer. During 30 months of follow-up, the rate of blood-culture-positive typhoid fever among controls was 810/100,000 per year. Rates of typhoid fever were 379/100,000 per year for subjects who received the liquid formulation of vaccine and 468/100,000 per year for subjects who received enteric coated capsules. The protective efficacies of the liquid and enteric coated formulations were 53% and 42%, respectively. Neither formulation protected against infection with Salmonella paratyphi A. No major side-effects were noted, but the overall incidence of side-effects was greater in the vaccine groups. Under conditions of intense transmission, Ty21a protected against typhoid fever; however, because Ty21a will not protect all individuals, there is a need for additional approaches to prevent the disease.

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.

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.

The efficacy in acute migraine of oral sumatriptan was assessed in a double-blind, randomised, placebo-controlled, crossover study of 61 patients (mean age 39 [SD 10] years). 41 completed treatment of four attacks, two with sumatriptan 100 mg and two with placebo. The response rate (reduction in headache from moderate or severe to mild or absent at 2 h) was 51% (45/89) with sumatriptan and 10% (9/93) with placebo (p less than 0.01); rescue medication was needed at 2 h in 41% and 88%, respectively. Of 28 patients headache-free at 24 h, 11 (39%) had recurrent headache within 24 h. There were no substantial side-effects. Thus, sumatriptan is an effective well-tolerated treatment for acute migraine attacks.

To assess whether chronic pulmonary colonisation with Pseudomonas aeruginosa in cystic fibrosis is preventable, 26 patients who had never received anti-pseudomonas chemotherapy were randomly allocated to groups receiving either no anti-pseudomonas chemotherapy or oral ciprofloxacin and aerosol inhalations of colistin twice daily for 3 weeks, whenever Ps aeruginosa was isolated from routine sputum cultures. During the 27 months of the trial, infection with Ps aeruginosa became chronic in significantly fewer treated than untreated subjects (2 [14%] vs 7 [58%]; p less than 0.05) and there were significantly fewer Ps aeruginosa isolates in routine sputum cultures in the treated group (49/214 [23%] vs 64/158 [41%]; p = 0.0006). Thus, chronic colonisation with Ps aeruginosa can be prevented in cystic fibrosis by early institution of anti-pseudomonas chemotherapy.