Anthropometric measures and their association with risk factors for cardio-metabolic diseases in Kenyan adults.

BACKGROUND: The prevalence of cardio-metabolic diseases (CMD) is drastically increasing worldwide. Anthropometric measures of fat accumulation are correlated with CMD and Metabolic Syndrome (MS), but few studies have addressed this association in sub-Saharan African populations. AIM: To investigate the association between anthropometric features, MS and other CMD risk factors in a population from Kenya. SUBJECTS AND METHODS: In this cross-sectional study including 1405 Kenyans, anthropometric measurements including visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT) were carried out. Fasting blood glucose and standard oral glucose tolerance test, fasting serum insulin and plasma lipids were analysed. Homeostatic model assessment of insulin resistance was calculated. Systolic and diastolic blood pressures were measured. RESULTS: CMD risk factors and MS were associated with all anthropometric features, except for high-density lipoprotein cholesterol levels (p < 0.05). The strongest association between MS and anthropometrics was seen with SAT (ß = 1.45 ± 0.32 in men and 0.88 ± 0.14 in women, both p < 0.05). CONCLUSIONS: Anthropometric measures, especially features of central obesity such as VAT and SAT, are relevant indicators of cardio-metabolic health in Kenyan populations. SAT is the strongest predictor of MS. These results highlight the need for further research on the pathological implication of VAT and SAT, in order to understand patterns of fat distribution and cardio-metabolic health among different ethnic groups.

HMGCR is a genetic modifier for risk, age of onset and MCI conversion to Alzheimer's disease in a three cohorts study.

Several retrospective epidemiological studies report that utilization of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) inhibitors called statins at mid-life can reduce the risk of developing sporadic Alzheimer's disease (AD) by as much as 70%. Conversely, the administration of these inhibitors in clinically diagnosed subjects with AD confers little or no benefits over time. Here, we investigated the association between AD and HMGCR rs3846662, a polymorphism known to be involved in the regulation of HMGCR exon 13 skipping, in a founder population and in two distinct mixed North American populations of converting mild cognitively impaired (MCI) subjects (Alzheimer's disease Cooperative study (ADCS) and Alzheimer's disease Neuroimaging Initiative (ADNI) cohorts). Targeting more specifically women, the G allele negative (G-) AD subjects exhibit delayed age of onset of AD (P=0.017) and significantly reduced risk of AD (OR: 0.521; P=0.0028), matching the effect size reported by the apolipoprotein E type 2 variant. Stratification for APOE4 in a large sample of MCI patients from the ADCS cohort revealed a significant protective effect of G negative carriers on AD conversion 3 years after MCI diagnosis (odds ratio (OR): 0.554; P=0.041). Conversion rate among APOE4 carriers with the HMGCR's G negative allele was markedly reduced (from 76% to 27%) to levels similar to APOE4 non-carriers (27.14%), which strongly indicate protection. Conversion data from the independent ADNI cohort also showed significantly reduced MCI or AD conversion among APOE4 carriers with the protective A allele (P=0.005). In conclusion, HMGCR rs3846662 acts as a potent genetic modifier for AD risk, age of onset and conversion.

Generation and validation of a normative, age-specific reference curve for lumbar spine trabecular bone score (TBS) in French women.

UNLABELLED: Age-related changes in lumbar vertebral microarchitecture are evaluated, as assessed by trabecular bone score (TBS), in a cohort of 5,942 French women. The magnitude of TBS decline between 45 and 85 years of age is piecewise linear in the spine and averaged 14.5%. TBS decline rate increases after 65 years by 50%. INTRODUCTION: This study aimed to evaluate age-related changes in lumbar vertebral microarchitecture, as assessed by TBS, in a cohort of French women aged 45-85 years. METHODS: An all-comers cohort of French Caucasian women was selected from two clinical centers. Data obtained from these centers were cross-calibrated for TBS and bone mineral density (BMD). BMD and TBS were evaluated at L1-L4 and for all lumbar vertebrae combined using GE-Lunar Prodigy densitometer images. Weight, height, and body mass index (BMI) also were determined. To validate our all-comers cohort, the BMD normative data of our cohort and French Prodigy data were compared. RESULTS: A cohort of 5,942 French women aged 45 to 85 years was created. Dual-energy X-ray absorptiometry normative data obtained for BMD from this cohort were not significantly different from French prodigy normative data (p = 0.15). TBS values at L1-L4 were poorly correlated with BMI (r = -0.17) and weight (r = -0.14) and not correlated with height. TBS values obtained for all lumbar vertebra combined (L1, L2, L3, L4) decreased with age. The magnitude of TBS decline at L1-L4 between 45 and 85 years of age was piecewise linear in the spine and averaged 14.5%, but this rate increased after 65 years by 50%. Similar results were obtained for other region of interest in the lumbar spine. As opposed to BMD, TBS was not affected by spinal osteoarthrosis. CONCLUSION: The age-specific reference curve for TBS generated here could therefore be used to help clinicians to improve osteoporosis patient management and to monitor microarchitectural changes related to treatment or other diseases in routine clinical practice.

A comparison of the assessment and management of cardiometabolic risk in patients with and without type 2 diabetes mellitus in Canadian primary care.

AIM: To investigate the cardiometabolic risk (CMR) assessment and management patterns for individuals with and without type 2 diabetes mellitus (T2DM) in Canadian primary care practices. METHODS: Between April 2011 and March 2012, physicians from 9 primary care teams and 88 traditional non-team practices completed a practice assessment on the management of 2461 patients >40 years old with no clinical evidence of cardiovascular disease and diagnosed with at least one of the following risk factor-T2DM, dyslipidaemia or hypertension. RESULTS: There were 1304 individuals with T2DM and 1157 without. Pharmacotherapy to manage hyperglycaemia, dyslipidaemia and hypertension was widely prescribed. Fifty-eight percent of individuals with T2DM had a glycated haemoglobin (HbA1c) ≤7.0%. Amongst individuals with dyslipidaemia, median low-density lipoprotein cholesterol (LDL-C) was 1.8 mmol/l for those with T2DM and 2.8 mmol/l for those without. Amongst individuals with hypertension, 30% of those with T2DM achieved the <130/80 mmHg target, whereas 60% of those without met the <140/90 mmHg target. The composite glycaemic, LDL-C and blood pressure (BP) target outcome was achieved by 12% of individuals with T2DM. Only 17% of individuals with T2DM and 11% without were advised to increase their physical activity. Dietary modifications were recommended to 32 and 10% of those with and without T2DM, respectively. CONCLUSIONS: Patients at elevated CMR were suboptimally managed in the primary care practices surveyed. There was low attainment of recommended therapeutic glycaemic, lipid and BP targets. Advice on healthy lifestyle changes was infrequently dispensed, representing a missed opportunity to educate patients on the long-term benefits of lifestyle modification.

[Evaluation of the implementation of an educational curriculum: optimal interventions for the adoption of an educational program of health in elementary schools]. / Evaluation de l'implantation d'un curriculum scolaire: Pistes d'interventions pour optimiser l'adoption et l'implantation de programmes d'éducation à la santé dans les écoles primaires.

A multiple case study design is used to explain the level of implementation of a "Heart Health" curriculum by grade four teachers of eight schools in a Montreal multiethnic and underprivileged district. An interview and logbook examine the following variables: 1) personal characteristics of the teachers; 2) organizational characteristics of the schools; 3) characteristics of the program; 4) collaboration between the health and educational sectors; and 5) curriculum level of use and fidelity of implementation. The results show in particular that the personal characteristics of the teachers and the characteristics of the program explain the level of implementation of the Heart Health curriculum.

Evaluation of two dose individualisation methods for carboplatin.

The pharmacokinetics of carboplatin are usually evaluated by measuring plasma concentrations of ultrafiltered platinum (UP). This approach, however may be less reliable than measuring the plasma concentration of total platinum (TP). In a group of 14 patients, which constituted a reference group, the clearance of TP was highly correlated with creatinine clearance, as estimated by the method of Cockroft and Gault. This relationship, together with only morphological and biological parameters, was used to estimate TP clearance, Vc and AUC, in a validation group of 8 patients. Estimated TP clearance was 97.9 +/- 18% of the actual value. The TP pharmacokinetic parameters of the reference group were used to estimate those of the validation group, using only two or three plasma concentration measurements (Bayesian approach). With the Bayesian approach, the estimated TP clearance was up to 99.9 +/- 2.7% of the actual value. In conclusion, estimation of TP pharmacokinetics may be reliably estimated as an alternative to UP in clinical practice.

Cancer in Circumpolar Inuit. Background information for cancer patterns in Canadian Inuit.

The cancer pattern among Inuit in the Circumpolar area is remarkably different from those of other populations in the world. The current paper summarizes the most important risk factors in Canadian Inuit residing in the Northwest Territories, northern Quebec (Nunavik) and Labrador, particularly during the time period 1969-1988 covered by the study. Factors considered include: the geographic area and physical environment; population and human environment, including fertility and life expectancy; lifestyle and diet, including tobacco and alcohol use; other lifestyle factors, and health conditions; and health services and cultural accessibility. Development of the cancer registry and population databases supporting the analysis of cancer rates is described. The information in the present paper is needed to interpret cancer incidence patterns and differences among the Circumpolar Inuit of Canada, Alaska and Greenland.

Matching words to concepts in two languages: a test of the concept mediation model of bilingual representation.

A categorization paradigm was used to investigate the relations between lexical and conceptual connections in bilingual memory. Fifty-one more fluent and less fluent English-French bilinguals viewed category names (e.g., vegetable) and then decided whether a target word (e.g., peas) was a member of that category. The category names and target words appeared in both English and French across experimental conditions. Because category matching requires access to conceptual memory, only relatively fluent bilinguals, who are able to directly access meaning for their second language, were expected to be able to use category information across languages. The performance of less-fluent bilinguals was expected to reflect reliance on lexical-level connections between languages, requiring translation of second-language words. The results provided evidence for concept mediation by more-fluent bilinguals, because categorization latencies were independent of the language of the category name. However, the performance of less-fluent bilinguals indicated that they did not follow a simple lexical translation strategy. Instead, these subjects were faster at categorizing words in both languages when the language of the category name matched the language of the target word, suggesting that they were able to access limited conceptual information from the second language. A model of the development of concept mediation during second language acquisition is described.

Relation between infant feeding and infections during the first six months of life.

We assessed the effect of the method of feeding on respiratory and gastrointestinal illnesses during the first 6 months of life among 776 infants born in New Brunswick, Canada. During a 1-year period, these infants were drawn from the offspring of a population of primiparous women in the province who, after at least 36 weeks of pregnancy, gave birth to one normal infant weighing 2500 gm or more. Data were collected by means of a self-administered standardized questionnaire mailed to every mother a week before her infant reached 6 months of age. The crude incidence density ratio (IDR) revealed a protective effect of breast-feeding on respiratory illnesses (IDR = 0.66; 95% confidence interval (CI), 0.52 to 0.83), on gastrointestinal illnesses (IDR = 0.53; 95% CI, 0.27 to 1.04) and on all illnesses (IDR = 0.67; 95% CI, 0.54 to 0.82). The protective effect of breast-feeding on respiratory illnesses persisted even after adjustment for age of the infant, socioeconomic class, maternal age, and cigarette consumption (adjusted IDR = 0.78; 95% CI, 0.61 to 1.00). Moreover, if we distinguished ear infection from other respiratory illnesses, we observed a separate protective effect for these two types of events. The results of this retrospective cohort study suggest a protective effect of breast-feeding in our population during the first 6 months of life.

Comparison of two dose prediction models for cisplatin.

Cisplatin toxicity could be decreased by adjusting its dosage to each patient. For this purpose, a limited sampling method was established and validated based on a Bayesian approach taken using the values of assays during a 5-day continuous infusion of cisplatin. Using this method, a dosing model to achieve a target plasma concentration of total platinum (Pt) was evaluated retrospectively; the calculated dose of cisplatin was 95.0 to 104.8% of the actual dose. This model was then studied prospectively and the actual plasma Pt concentration reached at the end of the infusion was 94.9% of the target concentration. A strong correlation was observed between the clearance of Pt and the calculated clearance of creatinine or Cockroft index (p = 1.7 x 10(-11), and this correlation was used to develop another cisplatin dosing model. With this model the actual concentration reached at the end of the infusion was 85.3% of the theoretical concentration. The Bayesian approach gave reliable results for most clinical uses, whereas the creatinine based model has to be improved.

Response to HMG CoA reductase inhibitors in heterozygous familial hypercholesterolemia due to the 10-kb deletion ("French Canadian mutation") of the LDL receptor gene.

The 10-kb deletion ("French Canadian mutation") of the low-density lipoprotein (LDL) receptor gene is the most common mutation causing familial hypercholesterolemia among subjects of French Canadian descent. In affected subjects, it results in a null allele of the LDL receptor gene and provides a unique opportunity to examine single-allele regulation of this gene in humans. We sought to ascertain the response of inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase in subjects with the French Canadian mutation of the LDL receptor gene and to correlate this response with biochemical variables and the haplotype of the nondeletion LDL receptor allele. The prevalence of non-responders to high doses of HMG CoA reductase inhibitors (defined as < 15% decrease in LDL cholesterol [LDL-C] from baseline values after dietary intervention) was ascertained in 105 patients heterozygous for the 10-kb deletion after excluding first-degree relatives and those on combined lipid-lowering therapy or other lipid-lowering agents. Lipoprotein cholesterol levels were examined after a diet period (30% calories as fat) and after receiving HMG CoA reductase inhibitors as mono-therapy for a minimum of 3 months. The mean reduction in total cholesterol was 45 +/- 23%, in LDL-C 33 +/- 15%, and in triglycerides 32 +/- 49% (all P < .005). There was a slight increase in high-density lipoprotein cholesterol of 8.5 +/- 18% (P > .05).(ABSTRACT TRUNCATED AT 250 WORDS)

[Research approaches in the meaning of suicide among teenage Inuit]. / Pistes de recherche sur les sens du suicide des adolescents inuit.

Is it possible to approach the suicide of teenage Inuit in the same way as in other communities, especially when taking into account the fact that suicide in Inuit is part of their traditions? The issue raised by the author essentially concerns the interpretation of data. This article offers new approaches to researching the meaning of suicide through a cultural viewpoint of the phenomenon and by taking into consideration the socio-political context. The author presents a new vision of suicide as an all-encompassing social fact that opens the door to more relevant interventions.

The effects of immunization against luteinizing hormone-releasing hormone on performance, sexual development, and levels of boar taint-related compounds in intact male pigs.

The effect of a newly developed anti-LH-RH vaccine on the performance, sexual development, and incidence of boar taint-related compounds was investigated in young intact male pigs. At 29 kg BW, 40 crossbred intact males and 20 castrates were allocated to three groups. Castrates and half of the intact males were untreated. The remaining intact males were immunized against LH-RH at 29 kg and again at 89 kg BW. All pigs were slaughtered at 105 kg BW. Compared with control intact males, feed efficiency in castrates was decreased by 10%, muscle content was reduced by 5%, and carcass fat content was increased by 26%. Growth performance and carcass traits did not differ significantly between immunized and control intact males. Genital tract weight, measured at slaughter, was decreased (P < or = .002) by immunization. Plasma testosterone concentrations were not significantly affected at 89 kg BW, whereas they were sevenfold lower (P < .001) in immunized than in control intact males at 105 kg BW. Fat androsterone levels, measured at slaughter, were substantially reduced (P < .001) from .66 +/- .07 microgram/g in control to .21 +/- .01 microgram/g in immunized intact males. Rates of testicular steroid biosynthesis, measured in vitro, were decreased by immunocastration. Fat skatole levels were very low and did not differ significantly between the three groups. The present results demonstrate that anti-LHRH immunization was effective in reducing the level of androstenone, a boar taint-related compound, although having a limited effect on the performance of the animals.

Comparison of the short term efficacy and tolerability of lovastatin and simvastatin in the management of primary hypercholesterolemia.

OBJECTIVES: To compare the safety and efficacy of lovastatin and simvastatin in patients with primary hypercholesterolemia. METHODS: Fourteen Canadian centres participated in this double-blind, randomized, parallel-design study with a six-week screening period, a four-week placebo baseline period and an 18-week active treatment period. Patients were included in the study if their total cholesterol (TC) was at least 6.2 mmol/L and total triglycerides (TG) were 4.0 mmol/L or less at baseline. Half of the patients were in stratum I (TC 6.2 to 7.8 mmol/L at baseline and placebo period) and half in stratum II (TC greater than 7.8 mmol/L). The initial dose of lovastatin or simvastatin (20 and 10 mg/day, respectively) was doubled if the patient's cholesterol was greater than 5.2 mmol/L after six and/or 12 weeks, to a maximum of 80 mg/day lovastatin or 40 mg/day simvastatin. Of 298 randomized patients, two had baseline data only (and were excluded from the efficacy analysis), while 77 were treated with lovastatin and 74 with simvastatin in stratum I, and 72 were on lovastatin and 75 on simvastatin in stratum II. RESULTS: In stratum I, both lovastatin and simvastatin lowered TC (-26.0% in both the lovastatin and simvastatin groups), low density lipoprotein (LDL) cholesterol (-33.4% in lovastatin and -34.4% in simvastatin), TG (-11.4% in lovastatin and -16.2% in simvastatin), apolipoprotein (apo)-B (-24.8% in lovastatin and -26.3% in simvastatin) and the TC:high density lipoprotein (HDL) cholesterol ratio (from 6.65 to 4.73 in lovastatin and from 6.45 to 4.46 in simvastatin), and increased HDL cholesterol (+3.6% in lovastatin and +7.8% in simvastatin) and apo-A1 (+6.3% in lovastatin and +9.0% in simvastatin) with P < 0.001 in all within-group tests except for HDL cholesterol (P < 0.05). Similar results were obtained in stratum II for TC (-30.7% in lovastatin and -30.3% in simvastatin), LDL cholesterol (-37.6% in lovastatin and -36.8% in simvastatin), TG (-21.9% in lovastatin and -16.9% in simvastatin), apo-B (-32.0% in lovastatin and -31.7% in simvastatin), TC:HDL cholesterol ratio (from 8.62 to 5.47 in lovastatin and from 8.96 to 5.77 in simvastatin), HDL cholesterol (+9.7% in lovastatin and +7.5% in simvastatin) and apo-A1 (+7.2% in lovastatin and +8.8% in simvastatin), with P < 0.001 in all within-group tests. Serious adverse events (clinical and laboratory) were reported in four patients in the lovastatin group and three in the simvastatin group. The most reported nonserious adverse effects were gastrointestinal tract (15 patients in the lovastatin group and 16 in the simvastatin group) and musculoskeletal (14 patients in the lovastatin group and 11 in the simvastatin group). Medication was withdrawn in eight patients. CONCLUSIONS: Both lovastatin and simvastatin were found to be effective and well tolerated in each stratum. However, there were no significant differences between lovastatin and simvastatin in the treatment of moderate or severe primary hypercholesterolemia.

Effect of passive immunization against testosterone on reproductive hormone secretion and ovarian function in dairy cows and pubertal beef heifers.

Multiparous dairy cows were divided in 3 groups from Day 5 up to Day 56 post partum: high energy level (Group H, n=10), low energy level (Group L, n=10) and low energy level plus anti-testosterone bovine immunoglobulins (Group LI, n= 10). Undernutrition decreased body weight, body condition score, milk yield and energy balance in Groups L and LI compared to Group H (P<0.05), but had no effect on secretory pattern of LH. Passive immunization against testosterone increased LH secretion in Group LI (P<0.05). Follicular score and the presence of follicles >/= 10mm on the ovary were not affected by underfeeding but were higher in Group LI than in Group L after immunization (P<0.01). The duration of the first luteal phase was shorter in Group H than in Groups L and LI and maximum progesterone levels reached were higher in Group LI than in Group H (P<0.01). Reproductive performance was not depressed by underfeeding and immunization. In the pubertal beef heifers maintained in anestrus by undernutrition had very low LH secretion. After passive immunization against testosterone, the increase of LH pulses number became almost significant (P=0.07). Following injection of exogenous LH, the number of follicles >/= 9mm was higher in immunized (Group I, n=8) than in control heifers (Group C, n=7). Group I developed a dominant follicle sooner and of greater size than Group C. Passive immunization against testosterone increased LH secretion and follicular development.

Impaired discrimination between stereoisomers of alpha-tocopherol in patients with familial isolated vitamin E deficiency.

We assessed whether patients with familial isolated vitamin E deficiency could discriminate between natural (RRR-) and synthetic (SRR-) stereoisomers of alpha-tocopherol labeled with six (d6) or three (d3) deuterium atoms, respectively. After oral administration of 20 mg of each of the stereoisomers, patients (seven) and controls (seven) had similar concentrations of both in chylomicrons, similar initial increases of both, and similar rates of decrease of d3-SRR-alpha-tocopherol in plasma. Patients and controls differed in their abilities to maintain plasma d6-RRR-alpha-tocopherol concentrations. Controls maintained plasma d6-RRR-alpha-tocopherol concentrations by preferentially secreting it in very low density lipoprotein (VLDL). Three of seven patients did not discriminate between the two stereoisomers and their plasma and lipoprotein d6-RRR-alpha-tocopherol concentrations declined rapidly. The remaining patients were intermediate between non-discriminators and controls in their ability to discriminate and maintain plasma d6-RRR-alpha-tocopherol concentrations. The degree of discrimination between the two stereoisomers in the patients was correlated with the age of onset of the neurologic disability (r2 = 0.64, P < 0.03). Estimates based on the rate of decrease of plasma d6-RRR-alpha-tocopherol in non-discriminators suggest that the entire plasma alpha-tocopherol pool of normal subjects is replaced daily. We suggest 1) that a hepatic alpha-tocopherol binding protein, which preferentially incorporates RRR-alpha-tocopherol into VLDL, is required to maintain plasma RRR-alpha-tocopherol concentrations; 2) that non-discriminators are lacking this protein, or have a marked defect in the RRR-alpha-tocopherol binding region of the protein; and 3) that patients who discriminate, but have difficulty maintaining plasma RRR-alpha-tocopherol concentrations, have a less severe defect, or perhaps a defect in the transfer function of the protein.

Probucol protects lipoprotein (a) against oxidative modification.

Probucol, which decreases cholesterol levels and has antioxidant properties, was administered orally to patients with familial combined hyperlipidemia and high plasma lipoprotein(a) [Lp(a)] levels. The drug had no effect on Lp(a) concentrations after 4 weeks, but was found to be distributed in both Lp(a) and low-density lipoprotein (LDL). Before treatment, in each case LDL and Lp(a) isolated from the same individual were readily oxidized by copper, resulting in increased electrophoretic mobility and enhanced uptake and degradation by macrophages of both lipoproteins. After probucol treatment, both lipoproteins acquired resistance to in vitro oxidation by copper. Furthermore, probucol prevented their enhanced uptake and degradation by the macrophages. It is surmised that oxidized Lp(a) may carry an atherogenic potential that could be opposed by probucol administration.