Discontinuation of cost sharing in Uganda

OBJECTIVE: To assess the effects of ending cost sharing on use of outpatient services and how this was perceived by health workers and members of a health unit management committee. METHODS: From 10 districts across Uganda, 78 health facilities were selected. Attendance at these facilities was assessed for eight months before and 12 months after cost sharing ended. The data represented 1 966 522 outpatient visits. Perceptions about the impact of ending cost sharing were obtained from the 73 health workers and 78 members of the health unit management committee who were available. FINDINGS: With the end of cost sharing, the mean monthly number of new visits increased by 17 928 (53.3%), but among children aged <5 years the increase was 3611 (27.3%). Mean monthly reattendances increased by 2838 (81.3%) among children aged <5 years and 1889 (24.3%) among all people. Attendances for immunizations, antenatal clinics, and family planning all increased, despite these services having always been free. Health workers reported a decline in morale, and many health unit management committees no longer met regularly. CONCLUSION: Use of all services increased - even those that had never before been subject to fees. The loss of some autonomy by the health facility and diminished community governance of health facilities may have long term negative effects.     

Dose-dependent localization of TCDD in isolated centrilobular and periportal hepatocytes

Dose-response relationships for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suggest a differential sensitivity of liver cell types to the induction of cytochrome P450 gene expression, and that the induction of hepatic protein CYP1A2 causes sequestration of TCDD. In addition, immunolocalization of hepatic CYP1A1/1B1/1A2 proteins is not uniform after exposure to TCDD. The mechanism for the regio-specific induction of hepatic P450s by TCDD is unknown, but may involve the differential distribution of participants in the AhR-mediated pathway and/or regional P450 isozymes, as well as, non-uniform distribution/sequestration of TCDD. Therefore, this study examined the effects of TCDD in unfractionated, centrilobular and periportal hepatocytes isolated from female Sprague-Dawley rats acutely exposed (3 days) to a single oral dose of 0.01-10.0 microg [3H]TCDD/kg. A dose- dependent increase in concentration of TCDD was accompanied by a dose- dependent increase in CYP1A1, CYP1A2, and CYP1B1 mRNA expression and associated enzymes in all liver-cell populations. Centrilobular hepatocytes showed a 2.7- to 4.5-fold higher concentration of TCDD as compared to the periportal hepatocytes at doses up to 0.3 microg TCDD/kg. Centrilobular hepatocytes also exhibited an elevated MROD activity as compared to the periportal hepatocytes at doses up to 0.3 microg TCDD/kg. Furthermore, centrilobular hepatocytes showed an elevated concentration of induced CYP1A2 and CYP1B1 mRNA as compared to periportal hepatocytes within the 0.01- and 0.3-microg TCDD/kg- treatment groups. This is the first study to demonstrate that a dose- dependent difference in distribution of TCDD exists between centrilobular and periportal cells that might be related to regional differences in P450 induction.      

Contribution of genetic and nutritional factors to DNA damage in heavy smokers

Prior epidemiological evidence suggests that genes controlling the metabolism of carcinogens and antioxidant/nutritional status are associated with lung cancer risk, possibly through their ability to modulate DNA damage by carcinogens. We performed a cross-sectional analysis of 159 heavy smokers from a cohort of subjects enrolled in a smoking cessation program. A total of 159 blood samples were analyzed to determine the relative contributions of genetic polymorphisms [CYP1A1 MspI and exon 7 and glutathione S-transferase M1 (GSTM1)] and plasma micronutrients to polycyclic aromatic hydrocarbon-DNA (PAH-DNA) adduct levels. DNA damage in smokers was affected by genetic polymorphisms and nutritional status. Smokers with the CYP1A1 exon 7 valine polymorphism had significantly higher (2-fold, P < or = 0.03) levels of DNA damage than those without. In parallel models, PAH-DNA adducts were inversely associated with plasma levels of retinol (beta = -0.93, P = 0.01), beta-carotene (beta = -0.18, P = 0.09), and alpha- tocopherol (beta = -0.28, P = 0.21) in 159 subjects. The association between smoking-adjusted plasma beta-carotene levels and DNA damage was only significant in those subjects lacking the GSTM1 detoxification gene (beta = -0.30, P = 0.05, n = 75). There was a statistical interaction between beta-carotene and alpha-tocopherol; when beta- carotene was low, alpha-tocopherol had a significant protective effect (beta = -0.78, P = 0.04) on adducts, but not when beta-carotene was high (beta = -0.16, P = 0.57). Plasma alpha-tocopherol was significantly correlated with beta-carotene (r = 0.36, P = 0.0005) and less strongly with retinol (r = 0.20, P = 0.0005). These results suggest that several micronutrients may act in concert to protect against DNA damage and highlight the importance of assessing overall antioxidant status. In conclusion, a subset of smokers may be at increased risk of DNA damage and possibly lung cancer due to the combined effect of low plasma micronutrients and genetic susceptibility factors. The use of biological markers to assess efficacy of interventions and to study mechanisms of micronutrients is timely given the current debate regarding the use of chemopreventive agents in high risk populations.      

Should sperm donors be paid? A survey of the attitudes of the general public

Gamete donation in assisted reproduction is an accepted treatment option for certain infertile couples. Traditionally, men donating spermatozoa have been paid a nominal fee, whilst women donating oocytes have not. The issue of payment for sperm donors has recently attracted attention following the Human Fertilisation and Embryology Authority's (HFEA) suggestion that such payment may be withdrawn. Prior to the final meeting of the HFEA working party which is examining this issue, here we report the results of a survey designed to solicit opinion on whether sperm donors should be paid, to identify social or other factors which influence this opinion, and to examine the influence of financial incentive on potential donors. We surveyed 717 individuals in three distinct groups: the general public, students (potential donors), and infertility patients (potential recipients). The majority of the potential donor group (students) was in favour of paying sperm donors, as were infertility patients. In contrast the general public was not. The opinion of the general public on this issue was influenced by their prior knowledge of whether donors were paid: those of the general public favouring the payment of sperm donors had a prior awareness that such payments were made. Although not in favour of paying sperm donors, the general public overwhelmingly approved of the use of donated spermatozoa for the treatment of infertile couples, and thought that ways should be sought to increase the availability of donor spermatozoa for the treatment of infertility and for research purposes. Within the potential donor group (students), the majority indicated that financial reward was an important factor which would influence their decision to donate spermatozoa. As the majority of both the potential recipients and potential donors feels that sperm donors should be paid, perhaps the views of these groups should carry significant weight when the decision whether or not to withdraw payment is taken. This is especially the case in view of the fact that the majority of the general public is in favour of the use of donated spermatozoa for the treatment of infertile couples.      

Continuous antihistamine treatment controls allergic inflammation and reduces respiratory morbidity in children with mite allergy

BACKGROUND: Allergic reaction is characterized by a complex inflammatory process. Some of the new antihistamines have antiallergic effects and can affect the inflammatory cell recruitment via adhesion molecule downregulation. We aimed to assess in a 12-month study whether continuous treatment with an antihistamine (terfenadine) can reduce respiratory symptoms and local inflammation in children with mite allergy. METHODS: The study was double-blind and placebo-controlled: it involved two parallel groups of children suffering from rhinoconjunctivitis and/or mild intermittent asthma due to mite allergy. They received either terfenadine (1 mg/kg per body weight per day) or placebo for 1 year. Nasal, conjunctival, and bronchial symptoms were recorded by diary cards; at each of the programmed control visits, a nasal scraping for inflammatory cells and ICAM-1 was performed. Some additional clinical parameters were also recorded: days of school absence, extra visits for acute respiratory symptoms, and days of hospital admission. RESULTS: Only children treated with terfenadine achieved significant control of symptoms (P<0.05 in 8 out of 12 months) and allergic inflammation, as shown by inflammatory cell infiltrate and ICAM-1 expression at nasal level (P<0.001), and had significantly fewer extra visits and school absences than the placebo group (P<0.03). No side-effects were reported in either group. CONCLUSIONS: The present study demonstrates that continuous terfenadine treatment (1 mg/kg body weight per day) could decrease respiratory symptoms and allergic inflammation, and it had an additional antiallergic effect in reducing ICAM-1 expression on nasal epithelial cells. Therefore, the present results confirm the efficacy of a long-term therapeutic strategy in controlling allergic inflammation.