Théophile Niyonsenga

Risk factors for encephalopathy and mortality during melarsoprol treatment of Trypanosoma brucei gambiense sleeping sickness.

This paper reviews the incidence of, and risk factors for, drug-induced encephalopathy and mortality (from all causes) during treatment with melarsoprol of 1083 patients with Trypanosoma brucei gambiense sleeping sickness in Nioki hospital (Zaire) between 1983 and 1990. Sixty-four patients (5.9%) developed encephalopathy and 62 (5.7%) died: 43 from reactive encephalopathy and 19 from other causes. Univariate and multivariate analyses showed that the administration of prednisolone reduced significantly the incidence of encephalopathy and mortality during treatment, especially in patients with trypanosomes observed in the cerebrospinal fluid (CSF) and/or with a CSF white blood cell (WBC) count of 100 or more per mm3. The risk of encephalopathy was associated more strongly with the CSF WBC count than with the presence of CSF trypanosomes. In the subgroup of patients with a CSF WBC count of 100 or more mm3, changing the melarsoprol regimen to 3 series of 3 injections instead of 3 series of 4 injections halved the mortality rate during treatment. Treatment of patients who do develop reactive encephalopathy with the heavy metal chelator dimercaprol, in addition to intravenous steroids and anticonvulsants, may be harmful. The data suggest that a further reduction of the total dose of melarsoprol may decrease toxicity without jeopardizing efficacy.

Gambiense trypanosomiasis: Frequency of, and risk factors for, failure of melarsoprol therapy

1083 patients with late-stage Trypanosoma brucei gambiense sleeping sickness were treated with melarsoprol in Nioki hospital, Zaire, between 1983 and 1990. Sixty-two (5.7%) died during treatment. Of the 1021 patients who survived the treatment, 63 (6.2%) subsequently relapsed, 58 (92%) of whom were diagnosed within 2 years of melarsoprol treatment. There was no evidence of an increase in the frequency of treatment failures during the study period, and the rate of relapses that we documented is comparable to that reported from Zaire more than 30 years ago. Relapses were more frequent among patients who had trypanosomes seen in the cerebrospinal fluid (CSF) at the time of the initial diagnosis (odds ratio [OR] = 2.76, 95% confidence interval [CI] = 1.65-4.63, P = 0.0001). Male patients had twice as many relapses as females (OR = 2.00, 95% CI = 1.19-3.36, P = 0.009), which was partly explained by males having trypanosomes in the CSF more often than females. There were important geographical variations in the frequency of relapses within the territory of the Nioki rural health zone, suggesting that the circulation of trypanosomes was geographically limited. Prednisolone treatment did not increase the risk of treatment failure, nor did decreasing the total dose of melarsoprol from 12 to 9 injections for patients with > or = 100 white blood cells/mm3 of CSF. Since patients with trypanosomes in the CSF are also those who are at the highest risk of melarsoprol-induced encephalopathy, more aggressive treatment regimens cannot be recommended.(ABSTRACT TRUNCATED AT 250 WORDS)

Spina bifida before and after folic acid fortification in Canada.

BACKGROUND In 1998, fortification of a large variety of cereal products with folic acid became mandatory in Canada. A multicentric study was carried out to assess the impact of this policy on the frequency of NTDs. The present analysis focused on spina bifida. METHODS The study population included approximately 2 million livebirths, stillbirths, and terminations of pregnancies because of fetal anomalies among women residing in seven Canadian provinces, from 1993 to 2002. Spina bifida cases were divided according to the upper limit of the defect: upper (cranial, cervical, or thoracic) and lower (lumbar or sacral) defects. Based on published results of red blood cell folate tests, the study period was divided into prefortification, partial fortification, and full fortification periods. RESULTS A total of 1,286 spina bifida cases were identified: 51% livebirths, 3% stillbirths, and 46% terminations. Prevalence decreased from 0.86/1,000 in the prefortification to 0.40 in the full fortification period, while the proportion of upper defects decreased from 32% to 13%. Following fortification, regional variations in the prevalence and distribution of sites almost disappeared. CONCLUSIONS Results confirmed the etiologic heterogeneity of spina bifida and the more pronounced effect of folic acid in decreasing the risk of the more severe clinical presentations.

Impact of Alcohol Intake on Measures of Lipid Metabolism Depends on Context Defined by Gender, Body Mass Index, Cigarette Smoking, and Apolipoprotein E Genotype

Hyperlipidemia, smoking, and obesity are well-known risk factors for cardiovascular disease. Conversely, moderate alcohol intake is associated with lower atherosclerosis risk. However, the influence of taking alcohol on the interrelationships of these factors in a particular context has not been thoroughly investigated. In this study, we asked whether the association between plasma measures of lipid metabolism and alcohol intake is dependent on context defined by gender, age, body mass index (BMI), smoking, and apolipoprotein E (APOE) genotype. Data were obtained in a sample of 869 women and 824 men who participated in the Quebec Heart Health Survey. There was no evidence that variation among APOE genotypes influenced the association between LDL cholesterol (LDL-C) or HDL cholesterol (HDL)-C and alcohol, after adjustment for age and BMI. Further, the positive (LDL-C and BMI) and the negative (HDL-C and BMI) associations that were observed in men and women with the &egr;3/2 and &egr;3/3 genotypes were not modified by alcohol intake. However, in women with the &egr;4/3 genotype only, we found a significant influence of an alcohol by BMI interaction on the prediction of total cholesterol, LDL-C, HDL-C, apoA-I, and apoB, and this interaction was influenced by the status of smoking. Whereas the influence of an alcohol by BMI interaction on total cholesterol and LDL-C was significant in smokers, its influence on HDL-C was significant only in non-smokers. This study emphasizes the context dependency of the influence of alcohol on lipid metabolism and demonstrates how biological, environmental, and genetic factors interact to determine cardiovascular disease risk.

Neonatal survival rates in 860 singleton live births at 24 and 25 weeks gestational age. A Canadian multicentre study

Objective To determine the current survival rate of singleton living newborns born at gestational age of 24 and 25 weeks, using obstetric factors available to the physician before birth.

Epidemiological evidence for immunity following Trypanosoma brucei gambiense sleeping sickness

In order to investigate whether protective immunity appears after Trypanosoma brucei gambiense sleeping sickness, we undertook a retrospective cohort study of 3 remote villages in central Zaire (total population 1431), in which 38% of all adults had a past history of human African trypanosomiasis. Among adults previously diagnosed with trypanosomiasis and treated, the risk of a second episode of trypanosomiasis during the 10 years period of observation was only 15% (with a 24 months refractory period) and 30% (without a refractory period) of the risk of a first episode in adults never previously diagnosed. We could not demonstrate a similar difference among children, to some extent because only a few of them were diagnosed for a first time with trypanosomiasis. Our findings suggest that very significant immunity appears after Gambian sleeping sickness, and that developing a vaccine against this subspecies of trypanosomes is biologically plausible.

Bone mineral density measurement and osteoporosis treatment after a fragility fracture in older adults: regional variation and determinants of use in Quebec

BackgroundOsteoporosis (OP) is a skeletal disorder characterized by reduced bone strength and predisposition to increased risk of fracture, with consequent increased risk of morbidity and mortality. It is therefore an important public health problem. International and Canadian associations have issued clinical guidelines for the diagnosis and treatment of OP. In this study, we identified potential predictors of bone mineral density (BMD) testing and OP treatment, which include place of residence.MethodsOur study was a retrospective population-based cohort study using data from the Quebec Health Insurance Board. The studied population consisted of all individuals 65 years and older for whom a physician claimed a consultation for a low velocity vertebral, hip, wrist, or humerus fracture in 1999 and 2000. Individuals were considered to have undergone BMD testing if there was a claim for such a procedure within two years following a fracture. They were considered to have received an OP treatment if there was at least one claim to Quebecs health insurance plan (RAMQ) for OP treatment within one year following a fracture. We performed descriptive analyses and logistic regressions by gender. Predictors included age, site of fracture, social status, comorbidity index, prior BMD testing, prior OP treatment, long-term glucocorticoid use, and physical distance to BMD device.ResultsThe cohort, 77% of which was female, consisted of 25,852 individuals with fragility fractures. BMD testing and OP treatment rates were low and gender dependent (BMD: men 4.6%; women 13.1%; OP treatment: men 9.9%; women 29.7%). There was an obvious regional variation, particularly in BMD testing, ranging from 0 to 16%. Logistic regressions demonstrate that individuals living in long term care facilities received less BMD testing. Patients who had suffered from vertebral fractures, or who had received prior OP treatment or BMD testing, regardless of gender, subsequently received more BMD testing and OP treatments. Furthermore, increasing the distance between a patients residence and BMD facility precluded likelihood of BMD testing.ConclusionBMD testing rate was extremely low but not completely explained by reduced physical access; gender, age, social status, prior BMD testing and OP treatment were all important predictors for future BMD testing and OP treatment.

Thiols can either enhance or suppress DNA damage induction by catecholestrogens

The estrogen metabolites catecholestrogens (or hydroxyestrogens) are involved in carcinogenesis and the development of resistance to methotrexate. This induction of drug resistance correlates with the relative efficiency of catecholestrogens in the generation of reactive oxygen species (ROS) and the induction of DNA strand breaks. Although antioxidants can neutralize ROS, the generation of these reactive species by catecholestrogens can be enhanced by electron donors like NADH. Therefore, this study was undertaken to determine the ability of different thiol agents (GSH, NAC, DTT, DHLA) to either inhibit or enhance the level of DNA damage induced by the H(2)O(2) generating system 4-hydroxyestradiol/Cu(II). Our results show that GSH, DTT, and DHLA inhibited the induction of the 4-hydroxyestradiol/Cu(II)-mediated DNA damage, with GSH showing the best potential. In contrast, the GSH precursor NAC at low concentrations was able to enhance the level of oxidative damage, as observed with NADH. NAC can reduce Cu(II) to Cu(I) producing the radical NAC&z.rad;, which can generate the superoxide anion. However, the importance of this pathway appears to be relatively minor since the addition of NAC to the 4-hydroxyestradiol/Cu(II) system generates about 15 times more DNA strand breaks than NAC and Cu(II) alone. We suggest that NAC can perpetuate the redox cycle between the quinone and the semiquinone forms of the catecholestrogens, thereby enhancing the production of ROS. In conclusion, this study demonstrates the crucial importance of the choice of antioxidant as potential therapy against the negative biological effects of estrogens.

Non-nutritive swallowing and respiration coordination in full-term newborn lambs.

Swallowing is a powerful inhibitor of respiratory rhythm in infants. The present study was aimed at investigating the influence of states of alertness on non-nutritive swallowing (NNS) frequency, on NNS and respiration coordination, and on bursts of NNS frequency in newborn lambs. Six full term newborn lambs were instrumented for electroencephalogram, eye movement, diaphragm and thyroarytenoid muscle electromyogram, nasal flow and electrocardiogram. Polysomnographic recordings were performed in non-sedated lambs, using radiotelemetry. NNS frequency was significantly higher during quiet wakefulness (W) and active sleep (AS) than during quiet sleep (QS). NNS mainly interrupted inspiration and the transition phases between expiration and inspiration, especially in W and AS. Bursts of NNS occurred significantly more often during AS. This study highlights the relevance of the ovine model to study ontogeny of NNS during sleep, and documents the influence of sleep on NNS and respiration coordination.

Biopsychosocial determinants of pregnancy length and fetal growth

The causes and mechanisms related to preterm delivery and intrauterine growth restriction are poorly understood. Our objective was to assess the direct and indirect effects of psychosocial and biomedical factors on the duration of pregnancy and fetal growth. A self-administered questionnaire was distributed to pregnant women attending prenatal ultrasound clinics in nine hospitals in the Montérégie region in the province of Quebec, Canada, from November 1997 to May 1998. Prenatal questionnaires were linked with birth certificates. Theoretical models explaining pregnancy length and fetal growth were developed and tested, using path analysis. In order to reduce the number of variables from the questionnaire, a principal component analysis was performed, and the three most important new dimensions were retained as explanatory variables in the final models. Data were available for 1602 singleton pregnancies. The biophysical score, covering both maternal age and the pre-pregnancy body mass index, was the only variable statistically associated with pregnancy length. Smoking, obstetric history, maternal health and biophysical indices were direct predictors of fetal growth. Perceived stress, social support and self-esteem were not directly related to pregnancy outcomes, but were determinants of smoking and the above-mentioned biomedical variables. More studies are needed to identify the mechanisms by which adverse psychosocial factors are translated into adverse biological effects.