Comparative trial of short-course ofloxacin for uncomplicated typhoid fever in Vietnamese children

An open, randomised comparison of 2 or 3 days of oral ofloxacin (10 mg/kg/day) for uncomplicated typhoid fever was conducted in 235 Vietnamese children. Multi-drug-resistant Salmonella typhi was isolated from 182/202 (90%) children and 5/166 (3%) tested isolates were nalidixic acid-resistant (Na(R)). Eighty-nine of 116 children randomised to 2 days and 107/119 randomised to 3 days were blood culture-positive and eligible for analysis. There were 12 (13.5%) failures in the 2-day group (six clinical failures, four blood culture-positive post treatment, two relapses) compared with eight (7.5%) failures in the 3-day group (four clinical failures, one blood culture-positive post treatment, three relapses) (OR 1.9, 95% CI 0.7-5.5,p = 0.17). There were no significant differences in the mean (95% confidence interval) fever clearance times (h) [92 (82-102) vs 101 (93-110), p = 0.18] or duration of hospitalisation (d) [7.6 (7.2-8.1) vs 8.0 (7.6-8.4), p = 0.19] between the two groups. There was one failure in the four eligible children infected with an Na(R) isolate of S. typhi. No adverse events were attributable to the ofloxacin. These results extend previous observations on the efficacy of short courses of ofloxacin for children with uncomplicated multi-drug-resistant typhoid fever.     

Hemochromatosis and femoral head aseptic osteonecrosis: a nonfortuitous association?

Chondrocalcinosis, chronic pseudo-osteoarthritis arthropathy, and osteoporosis are classic osteoarticular complications of hemochromatosis (HC). Within HC, femoral head aseptic osteonecrosis (FHAO) is not notified in textbooks. We describe 3 cases of FHAO occurring in this setting in 3 patients homozygous for the C282Y mutation on HFE gene who had no other risk factors for FHAO. FHAO was diagnosed 9 years before (Case 1), concomitantly with (Case 3), or 9 years after HC (Case 2). In one case, FHAO occurred although phlebotomies were regularly carried out. There are scarce data available in the literature on HC and FHAO. Our observations suggest FHAO may be an indicator for HC, and iron balance should be determined before considering FHAO as idiopathic. Thus phlebotomy may not be protective against the occurrence of FHAO. Studies are needed to determine the prevalence of HC in consecutive patients with FHAO.     

Human thiopurine S-methyltransferase pharmacogenetics: variant allozyme misfolding and aggresome formation

Thiopurine S-methyltransferase (TPMT) catalyzes the S-methylation of thiopurine drugs. TPMT genetic polymorphisms represent a striking example of the potential clinical value of pharmacogenetics. Subjects homozygous for TPMT*3A, the most common variant allele for low activity, an allele that encodes a protein with two changes in amino acid sequence, are at greatly increased risk for life-threatening toxicity when treated with standard doses of thiopurines. These subjects have virtually undetectable levels of TPMT protein. In this study, we tested the hypothesis that TPMT*3A might result in protein misfolding and aggregation. We observed that TPMT*3A forms aggresomes in cultured cells and that it aggregates in vitro, functional mechanisms not previously described in pharmacogenetics. Furthermore, there was a correlation among TPMT half-life values in rabbit reticulocyte lysate, aggresome formation in COS-1 cells, and protein aggregation in vitro for the three variant allozymes encoded by alleles that include the two TPMT*3A single-nucleotide polymorphisms. These observations were compatible with a common structural explanation for all of these effects, a conclusion supported by size-exclusion chromatography and CD spectroscopy. The results of these experiments provide insight into a unique pharmacogenetic mechanism by which common polymorphisms affect TPMT protein function and, as a result, therapeutic response to thiopurine drugs.     

Pediatric cortical dysplasia: correlations between neuroimaging, electrophysiology and location of cytomegalic neurons and balloon cells and glutamate/GABA synaptic circuits

Seizures in cortical dysplasia (CD) could be from cytomegalic neurons and balloon cells acting as epileptic 'pacemakers', or abnormal neurotransmission. This study examined these hypotheses using in vitro electrophysiological techniques to determine intrinsic membrane properties and spontaneous glutamatergic and GABAergic synaptic activity for normal-pyramidal neurons, cytomegalic neurons and balloon cells from 67 neocortical sites originating from 43 CD patients (ages 0.2-14 years). Magnetic resonance imaging (MRI), (18)fluoro-2-deoxyglucose positron emission tomography (FDG-PET) and electrocorticography graded cortical sample sites from least to worst CD abnormality. Results found that cytomegalic neurons and balloon cells were observed more frequently in areas of severe CD compared with mild or normal CD regions as assessed by FDG-PET/MRI. Cytomegalic neurons (but not balloon cells) correlated with the worst electrocorticography scores. Electrophysiological recordings demonstrated that cytomegalic and normal-pyramidal neurons displayed similar firing properties without intrinsic bursting. By contrast, balloon cells were electrically silent. Normal-pyramidal and cytomegalic neurons displayed decreased spontaneous glutamatergic synaptic activity in areas of severe FDG-PET/MRI abnormalities compared with normal regions, while GABAergic activity was unaltered. In CD, these findings indicate that cytomegalic neurons (but not balloon cells) might contribute to epileptogenesis, but are not likely to be 'pacemaker' cells capable of spontaneous paroxysmal depolarizations. Furthermore, there was more GABA relative to glutamate synaptic neurotransmission in areas of severe CD. Thus, in CD tissue alternate mechanisms of epileptogenesis should be considered, and we suggest that GABAergic synaptic circuits interacting with cytomegalic and normal-pyramidal neurons with immature receptor properties might contribute to seizure generation.     

Health related quality of life of adolescents in Vietnam: cross-cultural adaptation and validation of the Adolescent Duke Health Profile

Quality of life (QOL) of adolescents has been scarcely documented in a general population sample. The study was aimed at translating and adapting the Adolescent Duke Health Profile to Vietnamese, validating the questionnaire, determining reference value, and identifying determinants of poor QOL. Following a cross-cultural methodology, the Adolescent Duke Health Profile (ADHP) had content adapted to Vietnamese by alteration of 2 out of 17 items. Test-retest validity was checked in 408 adolescents. Construct validity and internal consistency were assessed in a 1408 probability sample of adolescents in Vietnam, and determinants were analysed by multiple linear regression. The ADHP showed satisfactory internal consistency (Cronbach's alpha=0.87-0.92) and satisfactory construct validity in relation with drug abuse or not, or with parent situation living in couple or alone. Test-retest reliability was acceptable (ICC=0.7-0.8) and major determinants were age, sex, education, chronic disease, alcohol and drug use. This works provide a validated, simple health related QOL scale suited to adolescent population with reference values. Taking into account determinants identified will help program prevention and intervention health policy and to evaluate the effect of these actions.     

Factors associated with declining HIV testing and failure to return for results among pregnant women in Vietnam

In a cross-sectional study, 53.2% of 500 antenatal attendees at Hai-Phong Hospital accepted HIV testing and 55.3% returned for results. Factors associated with declining included opinions about providing testing or that only high-risk pregnant women need testing, intention to decline testing, being a housewife, perception of poor healthcare support, and worry about husband's disapproval. Low educational level was associated with not returning for results. Testing programmes need to address husbands' attitudes, low education levels, and perceptions of risk.