Efficacy and safety of famciclovir for treating mucocutaneous herpes simplex infection in HIV-infected individuals. Collaborative Famciclovir HIV Study Group.

OBJECTIVE: To compare the efficacy and safety of 7 days' treatment with famciclovir 500 mg twice a day versus acyclovir 400 mg five times a day, for mucocutaneous herpes simplex virus (HSV) infection in HIV-infected individuals. DESIGN: Randomized, double-blind, parallel-group study to demonstrate equivalence for the primary efficacy parameter. SETTING: Forty-eight hospital-based or specialist public-health clinics in 12 countries. PATIENTS: Two-hundred and ninety-three HIV-positive patients with recurrent HSV infection (orolabial or genital) starting treatment within 48 h of first appearance of herpetic lesions. MAIN OUTCOME MEASURES: Proportion of patients developing new lesions during treatment (primary outcome measures); Time to complete healing of lesions, time to cessation of viral shedding, time to loss of lesion-associated symptoms, number of withdrawals due to treatment failure (secondary outcome measures). RESULTS: Equivalence was defined prospectively and famciclovir was equivalent to acyclovir in preventing new lesion formation: new lesions occurred in 16.7% and 13.3% of patients, respectively [difference, 3.4%; 95% confidence interval (CI), -4.8-11.5]. The groups were comparable in time to complete healing (median 7 days for both groups; hazard ratio, 1.01; 95% CI, 0.79-1.29; P = 0.95), cessation of viral shedding (median of 2 days [hazard ratio = 0.93; 95% C.I. 0.68, 1.27; p = 0.64]), and loss of lesion-associated symptoms (median 4 days; hazard ratio, 0.99; 95% CI, 0.75-1.30; P = 0.93). Similar numbers in each group withdrew because of treatment failure. There were no differences between groups in the incidence of adverse events. CONCLUSIONS: Famciclovir given twice a day is as effective and well tolerated as high-dose acyclovir for mucocutaneous HSV infections in HIV-infected individuals, and has the convenience of less frequent dosing.

Effect of an oral potassium channel activator, BRL 38227, on airway function and responsiveness in asthmatic patients: comparison with oral salbutamol.

BACKGROUND: Potassium (K+) channel activators, such as cromakalim, open ATP sensitive K+ channels and relax airway smooth muscle in vitro and inhibit induced bronchoconstriction in vivo in animals. The prolonged half life of cromakalim gives it potential as an oral bronchodilator. The effect of orally administered BRL 38227 (the active enantiomer of cromakalim), at doses of 0.125, 0.25, and 0.5 mg, on airway function and airway responsiveness to histamine and methacholine has been investigated in asthmatic patients. METHODS: Seventeen patients with asthma were studied in three separate randomised double blind, placebo controlled studies. In the first study eight patients with moderately severe asthma were given 0.125, 0.25, and 0.5 mg of BRL 38227 or placebo, and responses to histamine were assessed before and five hours after treatment. In the second study responses to methacholine were measured before and five hours after 0.125 and 0.5 mg of BRL 38227 or placebo were given to nine patients with mild asthma. In the third study the effect of 0.5 mg of BRL 38227 or placebo was assessed in eight patients with mild asthma. Responses to histamine were measured before treatment and two and five hours after treatment. To provide a positive control study eight subjects who had taken part in studies 1 and 3 were also given oral salbutamol (8 mg) in a placebo controlled, double blind study. Responses to histamine were assessed before and two hours after treatment. RESULTS: BRL 38227 did not cause significant bronchodilatation or changes in airway responsiveness in any of the studies. Headache was reported in 19 of 25 of patients receiving (in some cases twice) 0.5 mg of BRL 38227. By contrast, oral salbutamol gave significant protection against histamine challenge (geometric mean 2.23 doubling dilutions). CONCLUSIONS: After a single oral dose of BRL 38227 no beneficial effect on airway function was detected, despite a high incidence of side effects, which indicates that the orally administered K+ channel activator BRL 38227 may not be useful in the management of asthma.

Human responses to inhaled capsaicin are not inhibited by granisetron.

Cough is a common respiratory symptom, the mechanism of which is poorly understood. In this study the role of 5-HT3 receptors was investigated. Capsaicin-induced cough and increase in airways resistance were measured in six male volunteers before and after infusion with granisetron 160 micrograms kg-1 or placebo. Neither cough nor the increase in respiratory resistance was altered by the active treatment. These results suggest that 5-HT3 receptors are not involved in these two respiratory responses to inhaled capsaicin in humans.

Attenuation of nocturnal asthma by cromakalim.

In a randomised, double-blind, crossover study, single oral doses of cromakalim, a potassium-channel activator, or placebo were given to 23 patients with nocturnal asthma. There was a significant reduction (p less than 0.005) in the early morning fall in forced expiratory volume in 1 s (FEV1) after 0.5 mg cromakalim (fall 9.8% [SEM 3.2%]) compared with placebo (18.5 [2.8]%). In a repeat dosing study, administration of 0.25 mg and 0.5 mg cromakalim on 5 consecutive nights to a further group of 8 asthmatic subjects significantly reduced the early morning fall in FEV1 from 28.7 (6.5)% after placebo to 19 (4.2)% after 0.25 mg and 14.9 (6.5)% after 0.5 mg. Potassium-channel activators may be useful in the treatment of asthma, especially for nocturnal symptoms.

Induction of T-helper cell activity by fragments of rye grass pollen extract produced by digestion with chymotrypsin.

Rye grass pollen extract was digested by chymotrypsin to produce fragments with a molecular weight below 10,000, as demonstrated by polyacrylamide gel electrophoresis. Chymotryptic fragments did not react with either human or mouse IgG antibodies specific for rye grass pollen, nor did they induce an antibody response in mice with specificity for the parent extract. However, macrophage-presented fragments retained the ability to react with rye-specific T cells in a lymphoproliferation assay. Furthermore, these fragments induced the development of splenocytes capable of supporting dinitrophenyl specific antibody production. This implies that the fragments still react with, and induce, rye grass pollen extract-specific T-helper cells. The possibility that such fragments might have potential for use in immunotherapy for the specific treatment of allergy is discussed.

Assessment of anti-streptokinase antibody levels in human sera using a microradioimmunoassay procedure.

A high capacity, quantitative radioimmunoassay procedure has been developed to measure IgG antibodies to streptokinase (SK) in human serum. Results showed that the use of low concentrations of 125I-SK (100 ng/ml) and ambient temperature incubation conditions minimised degradation of the target labelled antigen and afforded antibody binding values which could be confidently related to the native intact SK protein. SK-complexed to plasminogen was also shown to retain the equivalent antigenic activity of native SK. Comparison of the absolute anti-SK levels with streptokinase resistance titres demonstrated that the two measurements of antibody correlated statistically but afforded quantitatively poor agreements. A survey of IgG levels to SK in sera from 93 normal healthy volunteers showed that all individuals displayed readily measurable anti-SK antibodies, with some 80% having IgG concentration capable of binding in excess of 1 microgram SK per ml serum.

A non-supervised training program for Carkhuff's discrimination and communication skills and its effects upon the reactions of others during brief interactions.

Used Carkhuff's Indices of Communication and Discrimination along with other measures to assess the level of communication and discrimination skills at various stages of communication training. Ss were 14 male and 9 female students in a psychology of adjustment class. Results indicated that: (a) treatment and control groups did not differ in communication skills before they went through training; (b) the treatment group offered higher levels of communication skill after it had completed training than did the control group before it began training; (c) the control group offered levels of communication skill equal to those of the treatment group once the control group also had completed training. A similar pattern was found for discrimination skill. The effects of training cannot be dismissed as paper-and-pencil artifacts because others who were ignorant of the growth conditions concept reacted differently in brief unstructured interactions to those who had completed training.