The effect of fluconazole and ketoconazole on the metabolism of sulphamethoxazole

1 Cytochrome P450-mediated bioactivation of sulphamethoxazole to a hydroxylamine has been implicated in the hypersensitivity reactions associated with co-trimoxazole administration. Inhibiting the formation of the hydroxylamine may be one method of preventing the high frequency of toxicity which is observed in HIV-infected patients. Therefore, in this study, we have investigated the ability of fluconazole and ketoconazole, known cytochrome P450 inhibitors, to inhibit the formation of sulphamethoxazole hydroxylamine.
2 Ten healthy male volunteers were given co-trimoxazole (800  mg sulphamethoxazole and 160  mg trimethoprim) alone or 1  h after either fluconazole (150  mg) or ketoconazole (200  mg) in a randomized fashion with a washout period of at least 1 week between each phase. Urine was collected for 24  h, and sulphamethoxazole and its metabolites were quantified by electrospray LC-MS.
3 Ketoconazole had no effect on the urinary recovery of sulphamethoxazole or any of its metabolites. In contrast, fluconazole significantly ( P <0.001) inhibited the formation of sulphamethoxazole hydroxylamine by 50.0±15.1%. Fluconazole also inhibited the oxidation of sulphamethoxazole to the 5-methylhydroxy and 5-methylhydroxy acetate metabolites by 69.9±15.8% and 64.0±12.0%, respectively, but had no effect on the amount of sulphamethoxazole, N₄-acetyl sulphamethoxazole, or sulphamethoxazole N₁-glucuronide excreted in urine.
4 The potential clinical benefit of using fluconazole to prevent hypersensitivity to co-trimoxazole in patients with AIDS needs to be assessed in a prospective study using both metabolite formation and the clinical occurrence of adverse reactions as end-points.     

Parental influences on young girls’ fruit and vegetable, micronutrient, and fat intakes

Objective To evaluate parents’ fruit and vegetable intake and their use of pressure to eat in child feeding as predictors of their 5-year-old daughters’ fruit and vegetable, micronutrient, and fat intakes.Subjects Data were obtained from 191 non-Hispanic white families with 5-year-old girls.Design Parent data included reports of pressure in child feeding and their own fruit and vegetable intake. Girls’ intakes of fruits and vegetables, selected micronutrients, and fat were the main outcomes of interest.Statistical analysis Structural equation modeling was used to test a model describing relationships among parents’ fruit and vegetable intake, parents’ use of pressure in child feeding, and daughters’ fruit and vegetable, micronutrient, and fat intakes.Results The model provided a good fit to the data, revealing that girls’ fruit and vegetable intake was positively related to their parents’ reported fruit and vegetable intake. Parents who consumed fewer fruits and vegetables tended to report greater pressure in child feeding and had daughters who consumed fewer fruits and vegetables. Girls’ reported fruit and vegetable intakes were positively related to their micronutrient intakes and negatively associated with fat intake.Applications/conclusions This research demonstrates that parents’ own fruit and vegetable intake may encourage fruit and vegetable intake in their daughters, leading to higher micronutrient intakes and lower dietary fat intakes. Conversely, pressure to eat may discourage fruit and vegetable intake among young girls. J Am Diet Assoc. 2002;102:58–64.     

Satisfaction and Job Stress in General Practice

This paper investigates sources of job satisfaction and dissatisfactionin general practice and identifies pressures and difficultiesexperienced by general practitioners in their work. The studyrevealed wide spread job satisfaction based on three separate(but independent) aspects of general practice: clinical, psychosocialor managerial. Despite this, significant pressures were experiencedand, in common with previous studies over the last 20 years,this research found continuing problems affecting young generalpractitioners in particular. The main pressures currently experiencedwere uncertainty and insecurity about work, isolation, poorrelationships with other doctors, disillusion with the roleof the general practitioner, and an awareness of changing demands.These pressures were related to experience in general practice,amount of study leave and practice organization. Like previousstudies, it also appears from this research that continuingeducation could play an important role in attenuating thesediffi culties. It is argued that the emphasis should be on developingsupport, confidence and better contacts between general practitioners,as well as teaching knowledge and skills.     

Patient Characteristics Associated with the Labelling of Asthma

Patient characteristics associated with the asthma label wereinvestigated in 262 children, aged 8 years, who reported wheezingillness in the previous 12 months. Children were first identifiedby a screening questionnaire administered to the parents ofall 8 year old schoolchildren in Croydon, south London. Interviewswere conducted with those reported to have had a wheezing illnessin the previous 12 months to obtain details of the child's illness,medical care, demographic and socioeconomic characteristics.Multivariate analysis showed that the likelihood of being labelledasthmatic was increased in those who had a parental historyof hayfever [odds ratio (OR) = 2.24, 95% confidence interval(Cl) = 1.22–4.14] or at least two allergic provoking factors(OR = 3.83, 95% Cl = 1.44–10.15). No significant associationswere found between asthma labelling and children's socioeconomiccharacteristics or use of general practitioner services. Thesefindings suggest that wheeze is likely to be labelled asthmawhen the clinical history suggests an allergic aetiology.