Efficacy and safety of two dosages of cotrimoxazole as preventive treatment for HIV-infected Malawian adults with new smear-positive tuberculosis

OBJECTIVE: To assess the efficacy and safety of two different dosages of cotrimoxazole (CTX) in prophylaxis in HIV-positive new smear-positive pulmonary tuberculosis (TB) patients in Blantyre, Malawi. METHOD: Randomized, double-blind trial using 480 and 960 mg of CTX given to new TB patients, who were followed up until the end of the tuberculosis treatment. The primary outcome was survival. The outcome in the two groups was also compared with an unselected cohort of similar patients registered in Zomba, Malawi in 1995 and new smear-positive patients registered in the National Tuberculosis Programme in 1999. The secondary outcome was the occurrence of (opportunistic) events, especially bacterial pneumonia. RESULTS: There were no statistically significant differences in mortality and bacterial pneumonia between the groups receiving the two different dosages. The case fatality rate at the end of the tuberculosis treatment was 15.4% in the 480 mg group and 14.0% in the 960 mg group. This was lower than the case fatality rate in the Zomba cohort (19.2%, P = 0.10) and lower than the case fatality rate in the national programme (21.0%, P < 0.001). CTX was well tolerated. Compliance was fair. CONCLUSIONS: CTX prophylaxis may have a beneficial effect on mortality and morbidity in HIV-infected smear-positive tuberculosis patients in Malawi. The efficacy of both dosages is not significantly different. The intervention is cheap and easy to implement. These results would support implementation of CTX in this patient group until better strategies are available or evidence is convincingly presented to suggest that its benefit is marginal.     

Head injury in child abuse: evaluation with MR imaging

To evaluate the usefulness of magnetic resonance (MR) imaging in the diagnosis of head injury in child abuse, the authors compared the findings at head MR imaging and computed tomography (CT) in 19 abused children. Subdural hematomas (15 cases), cortical contusions (six cases), and shearing injuries (five cases) were demonstrated to particular advantage with MR imaging. CT remained superior in the detection of subarachnoid hemorrhage. MR imaging appears to be valuable in the assessment of patients with suspected intracranial injury due to child abuse.     

Self-deprivation: a test of the reward hypothesis

Self-deprivation refers to the observation that despite severe levels of water and food deprivation some rats dramatically reduce food and water intake when brain stimulation reward and the alternative reward are placed in competition. In order to determine if the rewarding properties of brain stimulation are responsible for self-deprivation, rats were implanted bilaterally with stimulating electrodes and subsequently tested for self-deprivation and preferences among various electrode locus/stimulation current combinations. According to the reward hypothesis, the relative degree of self-deprivation observed for each electrode/current pair should predict the order of preference for each combination when different electrode/current pairs are placed in competition. Likewise, across all combinations of electrodes and intensities, increasing preferences should be associated with increasing self-deprivation. The findings of the study provide support for the reward hypothesis of self-deprivation. The correlation between the self-deprivation and the preference measure was r = 0.62 (p less than 0.001), which rose to r = 0.80 (p less than 0.001) when floor and ceiling effects were taken into account. It was concluded that the rewarding aspects of brain stimulation are responsible for the self-deprivation phenomenon.     

Recommendations for reporting results of diagnostic genetic testing (biochemical,cytogenetic and molecular genetic)

Genetic test results can have considerable importance for patients, their parents and more remote family members. Clinical therapy and surveillance, reproductive decisions and genetic diagnostics in family members, including prenatal diagnosis, are based on these results. The genetic test report should therefore provide a clear, concise, accurate, fully interpretative and authoritative answer to the clinical question. The need for harmonizing reporting practice of genetic tests has been recognised by the External Quality Assessment (EQA), providers and laboratories. The ESHG Genetic Services Quality Committee has produced reporting guidelines for the genetic disciplines (biochemical, cytogenetic and molecular genetic). These guidelines give assistance on report content, including the interpretation of results. Selected examples of genetic test reports for all three disciplines are provided in an annexe.Diagnostic genetic testing is an extremely rapidly expanding area encompassing a broad range of laboratory investigations to analyse chromosomes (from classical karyotype to molecular cytogenetics), nucleic acids (DNA, RNA), proteins and metabolites used to detect heritable or somatic mutations, genotypes or phenotypes related to disease and health. Genetic testing requires particular consideration in that it is usually performed only once in a patient''s lifetime, and the results may have considerable importance for lifetime decisions not only for the individuals being tested but also for children and family. Interpreting and reporting variation in germline chromosomes, DNA sequences or their products is a heavy clinical responsibility for prediction of susceptibility to disease, patient diagnosis, prognosis, counselling, treatment or family planning. Providing a set of reporting frameworks that can be customised for different testing contexts but share some common principles could be beneficial to the practice of a number of laboratories, including non-OECD members and/or laboratories that do not participate in External Quality Assessments (EQA), and to laboratories with blurred boundaries between research and genetic testing services.Although several guidelines already exist for reporting the results of genetic testing,^1,2,3 these focus on molecular genetic testing and do not cover the other two branches of laboratory genetics, namely biochemical genetics and cytogenetics. Based on recent surveys of EQA results presented by some European EQA providers and the request from genetic laboratories for comprehensive reporting guidelines, it was considered that a unifying attempt to harmonise the reporting practice of genetic tests in Europe and neighbouring countries would be welcome.     

Therapeutic effects of complex rearing or bFGF after perinatal frontal lesions

We investigated the effects of an enriched environment and/or basic fibroblast growth factor (bFGF) on recovery from neonatal frontal injury in rats. Rats received medial frontal lesions, or sham surgery, on postnatal day (P) 2/3. In the first set of experiments (Experiments 1 and 2), rats were housed in enriched environments that consisted of a large enclosure with multiple objects (or standard housing) for 90 days beginning at weaning (P22) or in adulthood (P110). In Experiment 3, the rats either received 7 days of subcutaneous bFGF beginning on the day after surgery or bFGF plus enriched housing beginning at weaning. After the 90-day housing period, the animals were tested on a spatial navigation task and a skilled reaching task. Early lesions of the medial frontal cortex caused severe impairments in spatial learning but this deficit was markedly reduced with enriched housing, bFGF, or a combination of both, with the latter being most effective. The housing effects varied with age, however: the earlier the experience began, the better the outcome. Enriched housing increased dendritic length in cortical pyramidal neurons, an effect that was greater in the lesion than the control animals, and enriched housing reversed the lesion-induced decrease in spine density. Enriched environment increased the thickness of the cortical mantle in both lesion and controls whereas bFGF had no effect. Experience thus can affect functional and anatomical outcome after early brain injury but the effects vary with age at experience and may be facilitated by treatment with bFGF.     

Predominance of nocturnal hypertension in pediatric renal allograft recipients

Hypertension is common in children with end-stage renal disease who have undergone renal transplantation. We performed ambulatory blood pressure monitoring (ABPM) in renal allograft recipients who were on stable maintenance immunosuppressive medications and were more than six months post-transplant. Echocardiographic measurement of left ventricular mass index (LVMI) was obtained at the time of ABPM. Twenty-nine children with a mean age of 14.8 yr (8-18 yr) were evaluated 4.3 yr (0.6-12.8 yr) after deceased donor (n = 13) or living donor (n = 16) transplantation. BP levels were higher during sleep compared with when awake using the 95th percentile to standardize mean BP for each period: mean BP was expressed as a standard deviation score (SDS) for each time period, awake vs. sleep: systolic (s) BP SDS were 0.43 +/- 1.3 vs. 1.29 +/- 1.2 (p < 0.001) and diastolic (d) BP SDS were 0.04 +/- 1.3 vs. 1.34 +/- 1.2 (p < 0.001). Significant differences between awake and sleep BP were also confirmed using the mean BP for each period expressed as a BPI. Hypertension (HTN) during sleep was more common than awake HTN. Based upon BPI, 21% had sHTN when awake compared with 48% during sleep and 7% had dHTN when awake compared with 41% during sleep (p < 0.05). Based upon mean BP load, 38% had sHTN when awake compared with 55% during sleep and 21% demonstrated dHTN when awake compared with 52% during sleep (p < 0.05). Left ventricular mass (LVM) was abnormally increased in six of 17 children (35%); LVM was not correlated with BP. Children prescribed angiotensin converting enzyme inhibitors or angiotensin II receptor blockers (ACEi/ARB) had significantly lower systolic BP compared with those on calcium channel blocking agents (CCB). Mean sSDS was -0.11 +/- 1.1 in those children on ACEi/ARB compared with 1.6 +/- 1.2 in those on CCB (p = 0.02): sSDS during sleep was significantly lower in the ACEi/ARB group compared with CCB (0.70 +/- 1.1 vs. 2.0 +/- 1.1, p = 0.04). Isolated nocturnal HTN is more common than daytime HTN among clinically stable pediatric renal allograft recipients. Detection and treatment of nocturnal HTN in pediatric allograft recipients could potentially affect graft survival.     

Progesterone for the prevention of preterm birth in women with multiple pregnancies: the AMPHIA trial

Background

Adequate vitamin D concentrations during pregnancy are necessary to neonatal calcium homeostasis, bone maturation and mineralization. The aim of study is to evaluate serum vitamin D concentrations in mothers and their newborns and effect of vitamin D deficiency on pregnancy outcomes.

Methods

552 pregnant women were recruited from Tehran University educating hospitals in the winter of 2002. Maternal and cord blood samples were taken at delivery. The serum was assayed for 25-hydroxyvitamin D3, calcium, phosphorus and parathyroid hormone.

Results

The prevalence of vitamin D deficiency in maternal and cord blood samples were 66.8% and 93.3%, respectively (<35 nmol/l). There was significant correlation between maternal and cord blood serum concentrations of vitamin D. In mothers with vitamin D deficiency, cord blood vitamin D concentrations was lower than those from normal mothers (P = .001). Also, a significant direct correlation was seen between maternal vitamin D intake and weight gain during pregnancy.

Conclusion

Consideration to adequate calcium and vitamin D intake during pregnancy is essential. Furthermore, we think it is necessary to reconsider the recommendation for vitamin D supplementation for women during pregnancy.