Chloroquine disposition in hypersensitive and non-hypersensitive subjects and its significance in chloroquine-induced pruritus

Twenty-one healthy Nigerian volunteers distributed into four groups participated in a study to determine the significance of chloroquine disposition in chloroquine-induced pruritus. It involved the administration of chloroquine with or without promethazine pre-administration to the subjects. Group I consisted of 8 chloroquine non-hypersensitive subjects receiving 2 tablets of chloroquine sulphate (300 mg base); Group II consisted of 5 chloroquine non-hypersensitive subjects receiving 2 tablets of chloroquine sulphate 30 minutes after 25 mg promethazine tablet pre-administration; Group III consisted of 5 chloroquine hypersensitive subjects treated as in Group II; Group IV consisted of 3 hypersensitive subjects treated as in Group I. Blood (5 ml) and urine samples were collected periodically for up to 6 days post-dose. The samples were analysed for chloroquine and some of its oxidation metabolites by a specific HPLC method. Probit plots of cumulative drug/metabolite ratios were done to determine if there is polymorphism in chloroquine metabolism. There was bimodality only in the distribution of chloroquine/monodesethylchloroquine ratios, suggesting polymorphism in the metabolic oxidation of chloroquine in these subjects. Higher levels of monodesethylchloroquine were obtained in Group IV subjects when compared with any of the other groups. The oral clearance rate, elimination half-life, and volume distribution at steady state of chloroquine in the study groups were not significantly different (P greater than 0.05). In the absence of promethazine there appears to be an extensive metabolism of chloroquine in hypersensitive individuals to produce monodesethylchloroquine which probably determines the degree of pruritus experienced by an individual.     

A European comparative study of marital status and socio-economic inequalities in suicide

We assess (i) whether being married is a protective factor against socio-economic inequalities in suicide, and (ii) whether any such buffering effect varies between countries. We used the data from a European cross-national comparison project, a prospective follow-up of several European population censuses matched with vital statistics. The data encompass 99.5 million person-years aged 30 and above and 25,476 suicides in Austria, Belgium, Denmark, Finland, Turin, Madrid, Norway and Switzerland. Standardised rates were computed and logistic regressions were used to assess educational inequalities. Among the non-married, the lower educational group had an increased risk of dying of suicide compared to the higher group (Odds Ratio (OR) = 1.45). Inequalities among the married were lower (OR = 1.29). In all countries or regions except Austria, the lower educational group had a higher risk of suicide mortality among the non-married than among the married. The buffering effect of being married was not observed for elderly individuals (65 and over). Among younger individuals, the buffering effect of being married on relative inequalities in suicide was stronger in Madrid, Denmark, Norway and Switzerland (but significant only for Denmark and Norway). There was no indication that countries with stronger welfare policies or lower divorce rate had a lower buffering effect. We conclude that being married protects against inequalities in suicide and that this protective effect is not affected by the level of social capital at the country level.     

General practice based teaching exchanges in Europe. Experiences from the EU Socrates programme 'primary health care'

This paper reviews the experience of international exchange of medical students for general practice. The experience is based on the EU Socrates programme 'Primary Health Care' that offers, since 1992, clinical attachments and research electives in primary care. This programme involves 11 university departments of general practice/primary care in eight countries: Austria - Vienna; Belgium - Gent; Germany Düsseldorf; Italy - Monza, Udine; Netherlands Nijmegen; Slovenia - Ljubljana; Sweden - G?teborg; and the UK - Edinburgh, Imperial College London and Nottingham. More than 150 students have taken part in the programme, most in the last four years. For clinical attachment communication to patients is essential, and students should be able to speak the language of the host university. A research elective in primary care is less demanding and requires students' ability to communicate in English. Despite marked differences in health care structure in the countries involved, it is quite possible to provide a valuable teaching environment in general practice, and the experience gained by students in the exchanges more than equals that what they would gain at home. The added value is in experiencing the influence of another health care system and of working in another academic primary care centre. A substantial number of research electives have been published in international peer reviewed scientific journals with the student as first (occasionally second) author and staff members of the student's host and home university as co-authors. A further benefit of the exchange programme lies in the transfer teaching innovations between universities.     

Cutaneous ulcers in association with sprue‐like enteropathy secondary to Losartan

Losartan is an angiotensin II receptor blocker (ARB) which may cause severe sprue‐like enteropathy (SLE) with skin manifestation. Clinicians should be informed of this side effect and its reversibility after cessation of the drug.     

Sex- and organ-specific toxicity in normal and malnourished rats fed thermoxidized palm oil.

The effects of free radical toxicity as induced by chronic consumption of thermoxidized palm oil (TPO) diet on organ size of normal animals, their first filial offspring and malnourished rats, were studied. Tissue- and sex-specific toxicity was revealed. The TPO diet significantly (P<0.01) reduced lung and kidney mass in normal male rats but female rats remained unaffected. Hearts of first filial offspring of both male and female rats were, however, enlarged while lung, liver and kidneys of first filial female offspring were additionally reduced in size (P<0.01). This information suggests that the observed toxicities could be cumulative for female offspring. Malnutrition protected against toxic injury because none of the kwashiorkoric animals rehabilitated on the toxic diet showed any overt symptoms of toxicity.