Randomized, double-blind study of grepafloxacin versus amoxycillin in patients with acute bacterial exacerbations of chronic bronchitis.

This randomized, multicentre, double-blind, double-dummy study compared the efficacy and safety of grepafloxacin and amoxycillin in acute bacterial exacerbations of chronic bronchitis (ABECB). Patients were randomized to receive grepafloxacin 400 mg or 600 mg od, or amoxycillin 500 mg tds, for 7 or 10 days. The trial recruited 656 patients, of whom 566 (86%) completed the study. Clinical success rates at the 2 week follow-up visit for the population evaluable for clinical efficacy were 82% (165/202 patients) in the grepafloxacin 400 mg group, 85% (175/206) in the grepafloxacin 600 mg group and 85% (172/203 patients) in the amoxycillin group. The 95% confidence interval confirmed the equivalence of the two grepafloxacin doses and amoxycillin, with no significant difference between the grepafloxacin groups. The microbiological success rates at follow-up showed equivalence between the grepafloxacin 400 mg and amoxycillin groups: 86% (144/168 isolates) and 83% (162/195), respectively. The grepafloxacin 600 mg group achieved a statistically significantly higher eradication rate (92%, 150/164; 95% CI 2.0%, 16.1%) than the amoxycillin group in the follow-up assessment for microbiological and clinical efficacy (evaluable population). There was no significant difference between the two grepafloxacin treatment groups (95% CI -13.3%, 0.9%; P= 0.087). All three treatment regimens successfully eradicated the pathogens most commonly isolated during the study, including Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae. Grepafloxacin had a good safety profile, comparable to that of amoxycillin, although grepafloxacin 600 mg was associated with a higher incidence of nausea, dyspepsia and taste perversion than amoxycillin. It can be concluded that grepafloxacin 400 mg or 600 mg od is as effective as amoxycillin 500 mg tds in the treatment of ABECB.

Female circumcision: an assault?

PIP: The question that arises is whether assault is sometimes committed in the guise of quasi medical operations whose desirability is as yet unchallenged in the courts. Female circumcision is a procedure that raises this question. In the UK legal system assault has been defined as "any hurt or injury calculated to interfere with the health or comfort of the prosecutor." The degree of hurt can be relatively minor and has been held to include a hysterical or nervous condition resulting from the act complained of. The law insists that some acts remain assaults in the eyes of the law, despite the fact that the victim has consented to their being carried out. Recently there has been a restatement of the circumstances in which the courts will permit consent to render lawful what could otherwise constitute an assault. For example, injuries sustained in dangerous exhibitions such as knife throwing will not be unlawful. Then, too, it is considered in the public interest to allow some acts of harm, e.g., parents and teachers may practice lawful chastisement on children without being guilty of an assault. Yet, if the injury is unreasonable they may lose this protection. The most relevant area for physicians is that of "unreasonable surgical interference," where it is clearly in the public interest that certain necessary procedures should be carried out without giving rise to liability for assault, i.e., if the patient has consented. The consent must be acceptable to the courts, must have been given freely and after a comprehensive explanation of the contemplated procedure. If these requriements are not satifsifed, the courts may disregard the consent. In a few exceptional cases the courts as well as the doctors will become involved in determining whether a procedure is desirable. What is acceptable depends on the state of knowledge and existing values at the time. In regard to female circumcision, it is difficult to think of arguments in favor of the practice. Although circumcision of the male is an accepted procedure on grounds of religion and medical grounds, neither of these apply to the female. The operation apparently involves the removal of the clitoris and additional areas of the foreparts of the labia, leaving behind raw areas which are stitched together. This painful procedure, which is known in many instances to have led to longterm difficulties in sexual relationships and childbirth, is now being studied by the UN Human Rights Body. This is clearly a procedure that should be ruled to be unlawful, and the consent of the woman should not be allowed to defend it. The current concern with upholding the traditions of ethnic groups should not overrule the humanitarian considerations.^ieng

Physicochemical-activity relationship in practice. 2. Rational selection of benzenoid substituents.

A rational method is presented for the selection of substituents to be introduced into a benzenoid ring system of a biologically active compound in order to a defined physicochemical parameter space. The method, which may be readily programmed for use on a computer, relies on maintaining a minimum distance between compounds in the multidimensional physicochemical parameter space. The series of compounds produced will then have a well-spread set of minimally correlated physicochemical parameter values and could thus be used for the reliable correlation of the variation in the biological activities of the members of the series with changes in these physicochemical parameters. Some examples of the use of the present method under various conditions are given, and it is compared with alternatives in the literature.

The selection of arylamidinourea antimalarials by their predicted physicochemical properties.

1 A small group of arylamidinoureas for which the predicted physicochemical properties were widely spaced and uncorrelated was selected for study.2 The antimalarial activity of each compound was measured against three species of plasmodium. Three corresponding regression equations were calculated relating the potency of each compound to its predicted physicochemical properties.3 The potency of further test compounds was forecast for each species, by using the corresponding regression equation. These forecasts were compared with the measured activity of the test compounds, and were better than would be expected by chance.4 It is suggested that only a few compounds in a series need be studied initially in order to derive regression equations with worthwhile predictive properties, if the compounds are selected according to appropriate criteria.