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Biomedical subjects

T K Young

Publications and source records attributed to T K Young.

At least 37 records · Page 2Linked to original sources

Absence of association between genetic variation in the LIPC gene promoter and plasma lipoproteins in three Canadian populations.

The promoter sequence variant -480T in the hepatic lipase gene (LIPC) has been shown to be significantly associated with low post-heparin hepatic lipase activity. Some studies have also found that the -480T variant is associated with elevation in plasma HDL cholesterol. We tested for associations of LIPC -480T with plasma lipoprotein traits in samples taken from three distinct Canadian populations: 657 Alberta Hutterites, 328 Ontario Oji-Cree and 210 Keewatin Inuit. Plasma HL activity was not available for analyses. The LIPC -480T allele frequencies in these three groups, respectively, were 0.219, 0.527 and 0.383, and the prevalence of LIPC -480T/T homozygotes was, respectively, 0.042, 0.274 and 0.167. No significant association was found between LIPC -480T and plasma HDL cholesterol or apolipoprotein AI concentration, after adjusting for covariates including gender and body mass index. There was no consistent relationship between the population mean plasma HDL cholesterol concentration and the population LIPC -480T frequency. Our findings are consistent with the idea that the common promoter variation in LIPC, which has been reported to be associated with variation in post heparin HL activity and HDL triglyceride concentration, is not always associated with variation in plasma HDL cholesterol concentration, possibly due to yet unspecified environmental or genetic factors.

Adolescent↗

G-protein beta3 subunit gene splice variant and body fat distribution in Nunavut Inuit.

The GNB3 825T allele encodes a product that has enhanced activation of heterotrimeric G proteins in vitro and could play a role in adipogenesis. We therefore evaluated the possibility that the GNB3 825T allele was associated with obesity in a sample of 213 healthy Canadian Inuit. We found that body weight, body mass index, waist girth, hip girth, subscapular skinfold thickness, and triceps skinfold thickness were significantly higher in subjects with the GNB3 825T/T genotype than in subjects with other genotypes. Furthermore, two anthropometric ratios, namely that of waist to hip circumference and that of subscapular to triceps skinfold thickness, were not significantly different across genotypes. This suggested that the increased deposition of fat in subjects with the GNB3 825T/T genotype was generalized and not localized to particular subregions. There was no association of this genetic variation with blood pressure. The GNB3 825T/T genotype accounted for between 1.6% and 3.3% of the total variation (< or =13% of attributable variation) of the obesity-related traits. The potential for a genetic marker of obesity creates opportunities for future studies in the Inuit, not just to confirm the associations, but also to examine prospectively the influence of interventions and possible relationships between GNB3 825T and longer term complications of obesity.

Adolescent↗

Survivors of sexual abuse: clinical, lifestyle and reproductive consequences.

BACKGROUND: In recent years, an increase in the prevalence of sexual abuse of women has been reported in Canada and elsewhere. However, there are few empirical data on the extent of the problem in Canadian aboriginal populations. The authors investigated the presence of a reported history of sexual abuse and other health determinants in a sample of women attending a community health centre with a substantial aboriginal population. This allowed determination of whether reported sexual abuse and its associated demographic and health-related effects were different for aboriginal and non-aboriginal women. METHODS: A sample of 1696 women was selected from women attending a community health centre in a predominantly low-income inner-city area of Winnipeg for a cross-sectional survey designed to study the association between sexual behavior and cervical infections. The survey was conducted between November 1992 and March 1995 and involved a clinical examination, laboratory tests and an interviewer-administered questionnaire. A substudy was conducted among 1003 women who were asked 2 questions about sexual abuse. RESULTS: The overall response rate for the main study was 87%. Of the 1003 women who were asked the questions about sexual abuse, 843 (84.0%) responded. Among the respondents, 368 (43.6%) were aboriginal. Overall, 308 (36.5%) of the respondents reported having been sexually abused, 74.0% of the incidents having occurred during childhood. The prevalence was higher among aboriginal women than among non-aboriginal women (44.8% v. 30.1%, p < 0.001). Women who had been sexually abused were younger when they first had sexual intercourse, they had multiple partners, and they had a history of sexually transmitted diseases. In addition, non-aboriginal women who had been sexually abused were more likely than those who had not been abused to have been separated or divorced, unemployed and multiparous and to have used an intrauterine device rather than oral contraceptives. Aboriginal women who had been sexually abused were more likely than those who had not been abused to have been separated or divorced, unemployed and multiparous and to have used an intrauterine device rather than oral contraceptives. Aboriginal women who had been sexually abused were more likely than those who had not been abused to have had abnormal Papanicolaou smears. The proportion of smokers was higher among the abused women than among the non-abused women in both ethnic groups. INTERPRETATION: A history of sexual abuse was associated with other clinical, lifestyle and reproductive factors. This suggests that sexual abuse may be associated with subsequent health behaviors, beyond specific physical and psychosocial disorders. Aboriginal and non-aboriginal women who have suffered sexual abuse showed substantial differences in their subsequent health and health-related behaviours.

Adult↗

Effects of parathyroid hormone infusion on glucose tolerance and glucose-stimulated insulin secretion in normal and uremic rats.

We used thyroparathyroidectomized (TPTX) rats with hypocalcemia to evaluate the effects of parathyroid hormone (PTH) infusion on glucose tolerance and glucose-stimulated insulin secretion in normal and uremic rats. Animals were subjected to oral glucose tolerance test (OGTT) and glucose-stimulated insulin secretion before and after TPTX or after their plasma calcium level was normalized by PTH infusion, vitamin D injection or calcium load. In both normal and uremic groups, TPTX produced a significant increase in area under the cure (AUC) of plasma glucose from 0 to 6 h in response to an oral glucose challenge and decrease plasma insulin level in response to glucose-stimulated insulin secretion. Before TPTX, uremic animals have a normal basal plasma insulin level (29 +/- 3 versus 31 +/- 2 microU/ml) and a normal glucose-stimulated insulin secretion, but significantly increase plasma glucose AUC in response to OGTT as compared with normal rats. TPTX worsen the response of glucose intolerance in uremic rats. After PTH infusion, vitamin D injection or calcium load, all rats in the response of OGTT and glucose-stimulated insulin secretion are recovered to the level before TPTX including normal and uremic rats, but uremic rats still have an abnormal glucose tolerance in response to OGTT. Uremic rats have a low basal plasma glucose level as compared with normal rats. TPTX significantly increase basal plasma glucose level in normal and uremic rats, but the uremic rats with TPTX have been found to elevate basal plasma glucose level to the range of normal rats. The basal plasma glucose level of normal rats with TPTX was recovered to the range before TPTX by PTH infusion, vitamin D injection or calcium load, but PTH infusion, vitamin D injection or calcium load did not decrease the level of basal plasma glucose in uremic rats with TPTX. All TPTX rats, including intact kidney or five-sixths Nx rats, were treated three times weekly by subcutaneous injection of 8 micrograms/kg L-thyroxin. These results indicate that uremia may produce thyroid dysfunction and PTH infusion did not affect the glucose tolerance in OGTT and glucose-stimulated insulin secretion in normal and uremic rats. In addition to PTH, other uremic toxins may be responsible for the glucose intolerance of uremia.

Animals↗

Factors associated with adult periodontitis in a dental teaching clinic population.

Exposure to a number of environmental, behavioral and sociodemographic variables has been associated with increased prevalence and severity of adult periodontitis. However, it is not possible easily to identify the individuals most susceptible to this chronic disease. A case control study was conducted among a population of adults to determine what factors were associated with increased prevalence of moderate to advanced periodontitis. Clinical and radiographic data were obtained from dental charts and structured interviews were conducted by telephone to collect sociodemographic and behavioral data. Statistical modeling was completed for the total study population (35-87-year-olds) and for two age-stratified subpopulations. Significant crude disease associations were observed between periodontitis and numerous explanatory variables. However, after adjustment for age and gender, few variables remained significant. Age stratification indicated that young adults (35-54 years) were affected differently from older adults (> or =55 years) by exposures to certain variables. Young moderate smokers had a 3.15 times increased risk of periodontitis and young heavy smokers had a 7.33 times increased risk compared to never-smokers. Older single adults had a 3.07 times increased risk compared to those with partners.

Adult↗

F5 Q506 mutation and the low prevalence of cardiovascular disease in Canadian Inuit.

BACKGROUND: The Keewatin Inuit have a very low age-adjusted mortality rate from vascular diseases compared to the general population of Canada. Interethnic differences in both genetic and lifestyle factors have been offered as explanations for this observation. We previously found that compared to white subjects, the Inuit had a significantly increased prevalence of 4 candidate alleles for atherosclerosis-related phenotypes, namely AGT T235, FABP2 T54, PONI R192, and APOE E4, and a significantly decreased prevalence of 2 candidate alleles for atherosclerosis-related phenotypes, namely ACE D and MTHFR 677T. METHODS: We tested the hypothesis that 165 Canadian Inuit would have a significantly different frequency of the thrombosis-associated F5 Q506 allele compared with reference controls. RESULTS: We found a complete absence of F5 Q506 in 165 Inuit, which was significantly different from the frequency of 3.92% observed in regional control White subjects. CONCLUSIONS: The aggregate of results from our studies in Inuit to date suggests that the beneficial influence of the low prevalence of any or all of the ACE D, MTHFR 677T and F5 Q506 outweighs the deleterious influence of the high prevalence of any or all of the other disease-associated alleles. However, it remains possible that other genetic and/or environmental factors determine the low susceptibility to vascular disease in the Inuit.

Adolescent↗

Effects of zinc deficiency on endogenous antioxidant enzymes and lipid peroxidation in glomerular cells of normal and five-sixths nephrectomized rats.

We evaluated the effects of zinc deficiency on the activities of endogenous antioxidant enzymes and lipid peroxidation in rat glomerular cells (GCs). Male Sprague-Dawley rats (n = 48) were fed a zinc-deficient diet and deionized distilled water for 1 week to induce zinc deficiency. Half of the rats (zinc-deficient group) continued on this diet for 4 weeks, and the other half (zinc-replete group) were maintained on the same diet but with zinc-supplemented water (150 mg/Lzinc sulfate solution). Half of each group underwent five-sixths nephrectomy, while the other half underwent a sham operation. Another 12 normal rats (controls) were fed standard rat chow (containing 23.4% protein and 70 ppm zinc) and drank deionized distilled water. The zinc-deficient rats, including sham and five-sixths nephrectomized rats, showed severe growth retardation and poor appetite. Their mean plasma zinc concentrations were half that of normal control rats, but their plasma copper concentration was significantly higher than that of the control rats. Zinc supplementation corrected the abnormality of plasma zinc and copper concentrations and the loss of body weight in zinc-deficient rats. Zinc-deficient rats exhibited lower renal creatinine clearance and higher GC-malondialdehyde (GC-MDA) than zinc-replete rats. The remnant kidney of all five-sixths nephrectomized rats, including zinc-deficient and zinc-replete rats, showed a compensatory elevation in renal creatinine clearance and increased GC-MDA concentrations. Zinc concentrations in the renal cortex were decreased in zinc-deficient rats and the activities of GC-superoxide dismutase and GC-glutathione peroxidase were increased, while zinc-replete rats exhibited normal activities of GC-superoxide dismutase and GC-glutathione peroxidase. We suggest that zinc deficiency enhances the formation of reactive oxygen species but does not affect the activities of endogenous antioxidant enzymes in glomerular cells.

Animals↗

Suicide among Manitoba's aboriginal people, 1988 to 1994.

OBJECTIVE: To compare and contrast the characteristics of suicides among aboriginal and nonaboriginal people in Manitoba. DESIGN: Retrospective review of all suicides, based on a confidential analysis of records held by the Office of the Chief Medical Examiner. SETTING: Manitoba between 1988 and 1994. OUTCOME MEASURES: Standardized suicide rates, age- and sex-specific suicide rates, blood alcohol level at time of death, psychiatric help-seeking behaviour before suicide and residence on a reserve. RESULTS: Age-standardized suicide rates were 31.8 and 13.6 per 100,000 population per year among aboriginal and nonaboriginal people, respectively. The mean age of aboriginal people who committed suicide was 27.0 (standard deviation [SD] 10.8) years, compared with a mean age of 44.6 (SD 18.8) years for nonaboriginal people who committed suicide (p < 0.001). Blood alcohol levels at the time of death were a mean of 28 (SD 23) mmol/L among aboriginal people and 12 (SD 20) mmol/L among nonaboriginal people (p < 0.0001). Before their death, 21.9% of nonaboriginal suicide victims had sought psychiatric care whereas among aboriginal suicide victims 6.6% had sought care (p < 0.0001). Although the suicide rate was higher among aboriginal people living on reserve than among those living off reserve (52.9 v. 31.3 per 100,000 per year), both of these rates were substantially higher than the overall rates among nonaboriginal people. There were no significant differences in mean age, sex, blood alcohol level and previous psychiatric care among aboriginal people who committed suicide living on and off reserve. CONCLUSIONS: There was a high rate of suicide among Manitoba's aboriginal people between 1988 and 1994; this rate was comparable to earlier estimates of national suicide rates among aboriginal people. The reserve environment does not, by itself, account for the high suicide rate among Manitoba's aboriginal people. Further study of help-seeking behaviour and the association between alcohol abuse and suicide, particularly among aboriginal peoples, is indicated.

Adolescent↗

Are Canadian Inuit at increased genetic risk for coronary heart disease?

The Keewatin Inuit of the Northwest Territories of Canada have a very low age-adjusted mortality rate from coronary heart disease. We hypothesized that this apparent protection from disease has a genetic basis. We determined the prevalence of the disease-associated alleles of five candidate genes for atherosclerosis-related phenotypes. Surprisingly, four of the five alleles studied, namely AGT T235, FABP2 T54, PON R192 and APOE E4, were significantly more frequent in a sample of 175 Keewatin Inuit than among a representative control sample of whites living in the region. The high frequencies of these disease-associated alleles suggests either that they have no relationship with disease susceptibility in the Inuit, or that some unmeasured genetic and/or environmental factors mitigate disease susceptibility that is associated with these alleles. This highlights the difficulty in extrapolating findings from one population to another. Also, very modest genotype-phenotype associations were observed between APOE genotype (P = 0.016) and plasma low-density lipoprotein cholesterol concentration and between FABP2 genotype and plasma 2-h postprandial, glucose concentration (P = 0.048). The relationship between APOE alleles and plasma low-density lipoprotein cholesterol was the same as has been previously reported in many study samples. However, the relationship between FABP2 alleles and plasma 2-h postprandial glucose concentrations was the opposite to that reported in other studies. This suggests that differences in environment, such as the type of fatty acid consumed, interacts with functional differences in gene products involved in candidate metabolic pathways to produce phenotypic differences.

Adolescent↗

Regulation of thyroid hormones in the secretion of insulin and gastric inhibitory polypeptide in male rats.

The effect of thyroid hormones on glucose-induced secretion of gastric inhibitory polypeptide (GIP) and insulin was studied. Male rats were thyroidectomized (Tx) or sham Tx. Sham Tx rats were injected with either propylthiouracil ([PTU] 20 mg/kg intraperitoneally) or saline for 2 weeks. In addition, thyroid-intact rats were injected intravenously with triiodothyronine ([T3]5 microg/kg) or saline 10 minutes before an oral glucose load (3.2 g/kg). Blood samples were collected from each animal via a jugular catheter at 0, 10, 20, 30,45, 60, and 90 minutes following glucose ingestion. Plasma levels of GIP and insulin were measured by specific radioimmunoassays (RIAs). Thyroidectomy-induced hypothyroidism increased the basal level of plasma GIP, but decreased that of insulin. Insulin levels at 10, 20, and 30 minutes following oral glucose were lower in hypothyroid rats than in euthyroid rats. Conversely, GIP levels at 60 and 90 minutes following glucose ingestion in PTU-induced hypothyroid rats were higher than those in euthyroid rats. Furthermore, glucose-stimulated insulin secretion was unaltered by pretreatment with T3, whereas the glucose-induced increase in plasma GIP was completely abolished by preinjection of T3 in thyroid-intact rats. These results suggest that thyroid functions are involved in the regulation of insulin and GIP secretion in rats.

Animals↗

Comparison of survey and physician claims data for detecting hypertension.

Using linked data from the Manitoba (Canada) Heart Health Survey (MHHS) and physician service claims files we assessed the degree to which self-reported hypertension and clinically measured hypetension agreed with physician claims hypertension, and examined the likely sources of disagreement. The overall agreement between survey and claims data for hypertension detection was moderate to high: 82% (kappa = 0.56) for self-reported and physician claims hypertension, and 85% (kappa = 0.60) for clinically measured and physician claims hypertension. In the comparison between self-report and physician claims, those who were classified as obese, diabetic, or a homemaker were significantly more likely to have a hypertension measure not confirmed by the other. Disagreement between clinically measured and physician claims was also more common among the obese and homemakers, as well as those on medication for heart diseases, elevated cholesterol levels (LDL), and 35 years of age and older. The high overall level of agreement among these three measures suggest that each may be used with confidence as an indication of hypertension; however, the agreement appears lower among individuals presenting a more complicated clinical profile.

Adult↗

Estimating the burden of disease. Comparing administrative data and self-reports.

OBJECTIVES: A cardiovascular health survey of a representative sample of the adult population of Manitoba, Canada was combined with the provincial health insurance claims database to determine the accuracy of survey questions in detecting cases of diabetes, hypertension, ischemic heart disease, stroke, and hypercholesterolemia. METHODS: Of 2,792 subjects in the survey, 97.7% were linked successfully using a scrambled personal health insurance number. Hospital and physician claims were extracted for these individuals for the 3-year period before the survey. RESULTS: The authors found no benefits to using restrictive criteria for entrance into the study (ie, requiring more than one diagnosis to define a case). Using additional years of data increased agreement between data sources. Kappa values indicated high levels of agreement between administrative data and self-reports for diabetes (0.72) and hypertension (0.59); kappa values were approximately 0.4 for the other conditions. Using administrative data as the "gold standard," specificity was generally very high, although cases with hypertension and hypercholesterolemia (diagnosed primarily by laboratory or physical measurement) were associated with a lower specificity than the other conditions. Sensitivity varied markedly and was lowest for "other heart disease" and "stroke". For diabetes and hypertension, inclusion criteria calling for more than one diagnosis reduced the accuracy of case identification, whereas increasing the number of years of data increased accuracy of identification. For diabetes and hypertension, self-reports were fairly accurate in detecting "true" past history of the illness based on physician diagnosis recorded on insurance claims. CONCLUSIONS: This study demonstrates the feasibility of linking a large health survey with administrative data and the validity of self-reports in estimating the prevalence of chronic diseases, especially diabetes and hypertension. A linked data set offers unusual opportunities for epidemiologic and health services research in a defined population.

Adolescent↗

Factors associated with human papillomavirus infection detected by polymerase chain reaction among urban Canadian aboriginal and non-aboriginal women.

OBJECTIVES: To determine the prevalence and correlates of human papillomavirus (HPV) infection among women attending an ethnically mixed, predominantly low-income, inner-city primary care clinic. STUDY DESIGN: Cross-sectional survey (N = 1,477). Demographic, behavioral, and reproductive history data were collected by questionnaire. Cervical swabs were analyzed for gonorrhea and chlamydial infections, abnormal cytology, and HPV infection assessed by PCR followed by hybridization for types 6, 11, 16, 18, 31, 33, and 35. RESULTS: Human papillomavirus was detected in 33% of specimens, with no significant difference between Aboriginal (AB) and non-Aboriginal women. Adjusting for AB status, HPV infection was associated with marital status, condom use, number of sexual partners (last year and lifetime), age at first sexual intercourse, a history of sexual abuse, and current abnormal Papanicolaou (Pap) smear. In multivariate analyses excluding abnormal Pap smear as an independent variable, marital status and the number of lifetime sexual partners were found to be significant independent predictors of HPV infection. Comparing individuals with 20+ lifetime sexual partners and those with 1 or fewer partners, the odds ratio (OR) for HPV infection was 1.90 (95% confidence interval [CI] 1.66-2.17) among AB women and 1.54 among non-AB women (95% CI 1.36-1.73). The OR for infection with HPV types 6 and 11 was 1.39 (95% CI 1.22-1.58), whereas for the high oncogenic risk types of 16, 18, 31, 33, and 35, the OR was 1.82 (95% CI 1.65-2.01). CONCLUSIONS: No differences were found between AB and non-AB women in the detection of HPV DNA, despite the higher risk for cervical cancer and the prevalence of recognized behavioral and reproductive risk factors among AB women. This study also indicates that the association of sexual activity with HPV infection holds true for both high- and low-oncogenic HPV types.

American Indian or Alaska Native↗

The health of Canadians with diabetes.

OBJECTIVES: This article focuses on the prevalence of diabetes mellitus among Canadians, the health status of those with the disease, their socioeconomic characteristics, personal health behaviours, and use of health services. DATA SOURCE: The data are from the 1994/95 National Population Health Survey. ANALYTICAL TECHNIQUES: Weighted counts were used in computing the prevalence of diabetes and the proportions of people with the characteristics and health behaviours considered. MAIN RESULTS: In 1994/95, 3% of Canadians aged 12 and older--over 722,000 people--reported having diabetes that had been diagnosed by a health care professional. The prevalence of diabetes increases with age and is associated with low income. A higher percentage of adults with diabetes were overweight compared to those without the disease.

Adult↗