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T V Nguyen

Publications and source records attributed to T V Nguyen.

At least 55 records · Page 3Linked to original sources

Osteoporosis in elderly men and women: effects of dietary calcium, physical activity, and body mass index.

Dietary calcium intake and physical activity are considered practical measures for prevention of osteoporosis. However, their associations with bone mineral density (BMD) in the elderly are not clear. The present study examined the association between osteoporosis and these two factors in relation to body mass index (BMI) in a cross-sectional, epidemiological study involving 1075 women and 690 men, aged 69 +/- 6.7 years (mean +/- SD). Dietary calcium intake (median of 580 mg/day) was inversely related to age (p = 0.01), positively related to physical activity index (PAI) (p = 0.01), femoral neck BMD (p = 0.01) in women, and higher lumbar spine (p = 0.003) and femoral neck BMD (p = 0.03) in men. Quadriceps strength was negatively associated with age (p < 0.0001) and positively related to BMI (p < 0.0001) and BMD (p < 0.0001) in both men and women. The PAI was associated with quadriceps strength (p < 0.0001) and femoral neck and lumbar spine BMD in women (p < 0.001) and with femoral neck BMD in men (p = 0.04); however, these associations were not significant after adjusting for age, BMI, quadriceps strength, and dietary calcium. Women in the top tertile of quadriceps strength (> or =23 kg) and dietary calcium intake (> or =710 mg/day) had 15% higher BMD than those in the lowest tertiles (< or =15 kg and < or =465 mg/day); the difference was comparable in men (11%). Among subjects with the lowest tertiles of BMI (< or =23 kg/m2 for women and < or =24 kg/m2 for men), quadriceps strength (< or =15 kg for women and < or =28 kg for men), and dietary calcium intake (< or =465 mg/day), 64% and 40% of women and men, respectively, were classified as having osteoporosis (based on a 2.5-SD reduction from the young-normal mean). The prevalence was only 12% in women and 1.5% in men among those in the highest tertiles of the three factors. Adequate dietary calcium intake and maintaining a physically active lifestyle in late decades of life could potentially translate into a reduction in the risk of osteoporosis and hence improve the quality and perhaps quantity of life in the elderly population.

Aged↗

Genetic epidemiological approaches to the search for osteoporosis genes.

Important progress has been made in the identification of specific environmental factors and estimation of hereditary components in bone density, quantitative ultrasound (QUS), and bone turnover indices. By contrast, the search for specific genes that regulate bone mass has progressed rather slowly, and the results are more difficult to interpret and reproduce. This article reviews the genetics of osteoporosis and problems plaguing genetic research. It is argued that the search for genes involved in the expression of osteoporotic phenotypes should be based on linkage studies in relatively homogeneous populations. Strategies for increasing the power of studies, such as making use of information from extended pedigrees and multivariate analysis, are discussed. With the advent of a comprehensive human genetic linkage map, a complete identification of genes for osteoporosis appears feasible. Understanding the genetic mechanisms and their interactions with environmental factors should allow more focused and cost-effective osteoporosis prevention and treatment strategies.

Adult↗

Hormonal and biochemical parameters and osteoporotic fractures in elderly men.

Low testosterone has been associated with hip fracture in men in some studies. However, data on other hormonal parameters and fracture outcome in men is minimal. This study examined the association between free testosterone (free T) estradiol (E2), sex hormone-binding globulin (SHBG), 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), insulin-like growth factor I (IGF-I), and fracture in 437 elderly community-dwelling men. Age, height, weight, quadriceps strength, femoral neck bone mineral density (FN BMD), and fracture data (1989-1997) also were obtained. Fractures were classified as major (hip, pelvis, proximal tibia, multiple rib, vertebral, and proximal humerus) or minor (remaining distal upper and lower limb fractures). Fifty-four subjects had a fracture (24 major and 30 minor). There was no association between minor fractures and any hormonal parameter. Risk of major fracture was increased 2-fold for each SD increase in age, decrease in weight and height, and increase in SHBG, and risk of major fracture was increased 3-fold for each SD decrease in quadriceps strength, FN BMD, and 25(OH)D (univariate logistic regression). Independent predictors of major fracture were FN BMD, 2.7 (1.5-4.7; odds ratio [OR]) and 95% confidence interval [CI]); 25(OH)D, 2.8 (1.5-5.3); and SHBG, 1.7 (1.2-2.4). An abnormal value for three factors resulted in a 30-fold increase in risk but only affected 2% of the population. It is not immediately apparent how 25(OH)D and SHBG, largely independently of BMD, may contribute to fracture risk. They may be markers for biological age or health status not measured by methods that are more traditional and as such may be useful in identifying those at high risk of fracture.

Aged↗

Interpretation of bone mineral density measurement and its change.

Bone mineral density (BMD), an important measurable predictor of osteoporotic fractures, is used as a surrogate definition of osteoporosis, and often as an end point in clinical trials. However, BMD is measured with random error and random fluctuation within individuals. This study addresses two specific questions: Given an observed level of BMD for an individual, what is the individual's likely "true" level? To what extent does an observed BMD change reflect a real change? A Bayesian model was formulated to address these questions, using data from the Dubbo Osteoporosis Epidemiology Study, past clinical trials, and a short-term reliability study in individuals ages 60 yr and older. Measurements of lumbar spine and femoral neck BMD by dual X-ray absorptiometry are highly reliable, with coefficients of reliability ranging from 0.90 to 0.99. Consequently, for an individual, there is good agreement between observed and "true" BMD values. However, the 90% confidence interval for the true level in elderly people and those with low measured BMD values is particularly wide. Using the cutoff of 2.5 standard deviations below the young normal mean as a definition of osteoporosis, the rates of false positives and false negatives can be as high as 20% among individuals ages 80 yr and older. In a typical clinical trial with an overall average increase in BMD of 2%, for a subject whose baseline femoral neck BMD is 0.80 g/cm(2), no conclusion of significant change could be drawn until an observed increase of at least 5.5% or an observed decrease of at least 7.5%. If two measurements were taken at baseline and follow-up, the true change could be detected with an observed increase of 3.5% or an observed decrease of 5%. On the other hand, there needs to be an observed increase of 6.2 and 8.5% before one can be 90% certain that a true increase of 2 and 5%, respectively, has occurred in an individual. This analysis suggests that the diagnosis of osteoporosis based on a single measurement of BMD and point estimates of changes in BMD may be inappropriate and unreliable. We propose that the current practice of informing individuals who have BMD measurements about their actual T- and Z-scores be replaced with a system of reporting in which their osteoporosis probability risk category is conveyed. Also, assessment of change in an individual should take into account the overall change in a population.

Absorptiometry, Photon↗

Influence of echocardiographic scan plane location and number on the accuracy of three-dimensional left ventricular volume and shape determination.

Quantitative 3-dimensional (3-D) echocardiography provides accurate assessment of left ventricular (LV) volume, shape, and function, but depends on manual endocardial border tracing. This study determined the minimal number of borders that need to be traced to obtain an accurate analysis of not only the volume of the left ventricle but also its shape, using the integrated methods for quantitative 3-D echocardiography developed by our laboratory. Transthoracic 3-D echocardiographic studies were obtained in 9 normal subjects and 6 patients with heart disease by freehand scanning. The LV endocardium was manually traced in 17 +/- 5 imaging planes and reconstructed in 3 dimensions. The volume and shape of each reconstruction were compared with values measured from surfaces reconstructed from 8 subsets containing 2 to 7 borders; each subset was acquired from different combinations of spatially distributed parasternal and apical views. Accurate measurements were obtained from data sets having > or = 5 borders, regardless of whether the image planes were predominantly apical or parasternal views. In conclusion, the LV border should be traced in > or = 5 imaging planes to obtain accurate measurements of volume and shape. The piece-wise smooth reconstruction method and freehand scanning using a magnetic field tracing system allow the borders to be acquired from whatever combination of acoustic windows and views provides optimal image quality.

Adult↗

Mortality after all major types of osteoporotic fracture in men and women: an observational study.

BACKGROUND: Mortality increases after hip fractures in women and more so in men. Little is known, however, about mortality after other fractures. We investigated the mortality associated with all fracture types in elderly women and men. METHODS: We did a 5-year prospective cohort study in the semi-urban city of Dubbo, Australia, of all residents aged 60 years and older (2413 women and 1898 men). Low-trauma osteoporotic fractures that occurred between 1989 and 1994, confirmed by radiography and personal interview, were classified as proximal femur, vertebral, and groupings of other major and minor fractures. We calculated standardised mortality rates from death certificates for people with fractures compared with the Dubbo population. FINDINGS: 356 women and 137 men had low-trauma fractures. In women and men, mortality was increased in the first year after all major fractures. In women, age-standardised mortality ratios were 2.18 (95% CI 2.03-2.32) for proximal femur, 1.66 (1.51-1.80) for vertebral, 1.92 (1.70-2.14) for other major, and 0.75 (0.66-0.84) for minor fractures. In men, these ratios were 3.17 (2.90-3.44) for proximal femur, 2.38 (2.17-2.59) for vertebral, 2.22 (1.91-2.52) for other major, and 1.45 (1.25-1.65) for minor fractures. There were excess deaths (excluding minor fractures in women) in all age-groups. INTERPRETATION: All major fractures were associated with increased mortality, especially in men. The loss of potential years of life in the younger age-group shows that preventative strategies for fracture should not focus on older patients at the expense of younger women and of men.

Age Distribution↗

An integrated strategy for evaluation of metabolic and oxidative defects in neurodegenerative illness using magnetic resonance techniques.

The number of physiologic and metabolic phenomena amenable to analysis using magnetic resonance (MR) techniques is increasing every year. MR techniques can now evaluate tissue parameters relevant to TCA cyclemetabolism, anerobic glycolysis, ATP levels, blood-brain barrier permeability, macrophage infiltration, cytotoxic edema, spreading depression, cerebral blood flow and volume, and neurotransmitter function. The paramagnetic nature of certain oxidation states of iron leads to the ability to map out brain function using deoxyhemoglobin as an endogenous contrast agent, and also allows for mapping of local tissue iron concentrations. In addition to these metabolic parameters, the number of ways to generate anatomic contrast using MR is also expanding; and in addition to conventional anatomic scans, mapping of axonal fiber tracts can also be performed using the anisotropy of water diffusion. A strategy for integration of these multifarious parameters in a comprehensive neurofunctional exam in neurodegenerative illness is outlined in this paper. The goals of the integrated exam, as applied to a given neurodegenerative illness, can be subdivided into three categories: etiology, natural history, and therapeutic end points. The consequences of oxidative stress and/or mitochondrial dysfunction are explored in the context of the various parameters that can be measured using the integrated MR exam.

Animals↗

Hormonal and biochemical parameters in the determination of osteoporosis in elderly men.

The extent to which changes in several hormonal and biochemical parameters are involved in the pathogenesis of osteoporosis in men remains controversial. This study examined the roles of free testosterone (T), estradiol (E2), sex hormone-binding globulin (SHBG), 25-hydroxyvitamin D, PTH, and insulin-like growth factor I in the determination of bone mineral density (BMD) in 437 community-dwelling elderly men. Age, height, weight, quadriceps strength, and femoral neck (FN) and lumbar spine (LS) BMD were also obtained. In multiple regression analysis, after adjusting for age and weight, low E2 (P = 0.01), and high SHBG (P = 0.0002) levels were common determinants of FN and LS BMD. In addition, high PTH (P = 0.03) was an independent predictor of FN BMD, and low free T (P = 0.02) was an independent predictor of LS BMD. Low free T was associated with FN BMD in univariate analysis only. The hormonal measurements collectively accounted for 5% and 7% of the age- and weight-adjusted variance of FN and LS BMD, respectively. The sex steroids, SHBG and insulin-like growth-I were found to be interrelated using a technique of path analysis that examines the intercorrelation between these variables. A subject with any one abnormal serum parameter had a 4-fold increase in the risk of osteoporosis, whereas three abnormal parameters were associated with an 11-fold increased risk, although the latter group only applied to 1% of the study population. Although the precise causal effects these biochemical parameters may have on the development of osteoporosis remains to be determined, the present findings support an important interrelated role for these hormonal and biochemical parameters on changes in bone density in elderly men.

Aged↗

Vitamin D receptor gene polymorphisms and the risk of fractures in older women. For the Study of Osteoporotic Fractures Research Group.

The association between vitamin D receptor gene polypmorphisms and bone mineral density is controversial. The relationship between vitamin D receptor genotype and risk of fracture is uncertain. To determine whether vitamin D receptor polymorphisms were associated with the risk of hip, vertebral, and other (nonhip, nonvertebral) fractures in elderly women, we conducted a case-cohort study within a prospective study of 9704 community-dwelling women aged 65 years and older. Vitamin D receptor allele and genotype frequencies in women who experienced first incident hip (n = 181), vertebral (n = 127), and other (n = 223) fractures were compared with those of control women selected randomly from the cohort. Average length of follow-up was 6.5, 3.7, and 5.4 years for women in hip, vertebral, and other fracture analyses, respectively. Vitamin D receptor polymorphisms were determined by polymerase chain reaction amplification of genomic DNA using TaqI and ApaI restriction site endonuclease digestion. All nonvertebral fractures were confirmed by X-ray reports; hip fractures were validated by review of X-ray films. Vertebral fractures were defined by morphometry using lateral spine radiography at baseline and an average of 3.7 years later. Allele or genotype frequencies did not differ between fracture cases and their respective controls. Vitamin D receptor genotype (defined by TaqI, ApaI, or the combination of TaqI and ApaI) was not significantly associated with the risk of hip, vertebral, or other fractures. For example, compared with the referent group of women with TT genotype, those with Tt and tt genotypes had similar age- and weight-adjusted risks of fracture at the hip (hazard ratios 0.9, 95% confidence interval [CI] 0.6-1.3, and 0.8, 95% CI 0.5-1.2, respectively), spine (odds ratios 1.1, 95% CI 0.7-1.8, and 0.7, 95% CI 0.4-1.3, respectively), or other skeletal site (hazard ratios 1.0, 95% CI 0. 7-1.4, and 1.0, 95% CI 0.7-1.5, respectively). These findings were not altered in additional analyses including those adjusted for and stratified by age, ethnic ancestry, calcaneal bone density, dietary calcium intake, use of calcium supplements, use of vitamin D supplements, and oral estrogen use. We conclude that Vitamin D receptor polymorphisms defined by TaqI and ApaI are not associated with the risk of fracture in older women. Our results suggest that determination of these vitamin D receptor polymorphisms is not a clinically useful test for the prediction of fracture risk in elderly women.

Aged↗

Clustering of insulin resistance, total and central abdominal fat: same genes or same environment?

Obesity, insulin resistance and disturbed glucose metabolism cluster within the Insulin Resistance Syndrome (IRS). Whether this reflects shared genetic or environmental factors detectable in 'normal' populations (not selected for IRS features) is unknown. This study estimated (i) genetic influences on IRS traits and (ii) shared and specific genetic and environmental factors on the relationships between these traits in healthy female twins. Fasting insulin, glucose, total and central fat were measured in 59 monozygotic (MZ) and 51 dizygotic (DZ) female twin pairs aged (+/- SD) 52 +/- 13 years. Body fat was measured by dual-energy X-ray absorptiometry, insulin resistance and secretion by a modified homeostasis model assessment. Using intraclass correlation coefficients and univariate model-fitting analyses, genetic influences were found in total fat, central fat, insulin resistance, fasting glucose and insulin secretion, with genetic factors explaining 64, 57, 59, 75 and 68% of their variance, respectively, using the latter technique. In matched analysis intra-pair differences in total and central fat related to intra-pair differences in insulin resistance (r2 = 0.19, P < 0.001). Multivariate model-fitting showed a close genetic relationship between total and central fat (r = 0.88). The genetic correlation between IR and central fat (0.41) was significantly greater than that for total fat (0.24), suggesting that central fat is not only a predictor of, but shares considerable genetic influence with, insulin resistance. In Cholesky analysis, these genetic influences were separate from those shared between central and total fat. In conclusion, both shared and specific genetic factors regulate components of the IRS in healthy females. However, there were discrete genetic influences on beta-cell insulin secretion, not shared with other IRS components, suggesting that a separate genetic propensity exists for Type 2 diabetes. These findings suggest we may understand the genetic and environmental influences on IRS from the study of the normal population.

Abdomen↗

Evidence for four distinct major protein components in the paraflagellar rod of Trypanosoma cruzi.

The major structural proteins present in the paraflagellar rod of Trypanosoma cruzi migrate on SDS-polyacrylamide gels as two distinct electrophoretic bands. The gene encoding a protein present in the faster migrating band, designated PAR 2, has been identified previously. Here we report the isolation and partial characterization of three genes, designated par 1, par 3, and par 4, that encode proteins present in the two paraflagellar rod protein bands. Peptide-specific polyclonal antibodies and monoclonal antibodies against the four proteins encoded by these genes shows that PAR 1 and PAR 3 are present only in the slower migrating paraflagellar rod band, and that PAR 2 and PAR 4 are present only in the faster migrating band. Analysis of the nucleotide sequence of these genes and the amino acid sequence of the conceptual proteins encoded by them indicates that par 2 shares high sequence similarity with par 3 and both are members of a common gene family, of which par 1 may be a distant member. Analysis of gene copy number and steady-state RNA levels suggest that the close stoichiometric ratio of the four PAR proteins is likely maintained by homeostatic regulation of RNA levels rather than gene dosage.

Amino Acid Sequence↗

Bone mass, lean mass, and fat mass: same genes or same environments?

The contributions of genetic and environmental factors to the association among bone mineral density (BMD), lean mass, and fat mass were assessed in the Sydney Twin Study of Osteoporosis (Australia), 1995-1996, in 57 monozygotic and 55 dizygotic female twin pairs of Caucasian background, aged 52.8 (standard deviation, 13) years. In multiple regression analysis, lean mass was a significant determinant of areal BMD; however, fat mass was a principal determinant of volumetric BMD. Univariate model-fitting analyses indicated that 80% and 65% of variance of lean mass and fat mass, respectively, were attributable to genetic factors. The estimated heritability of BMD for lumbar spine, femoral neck, and total body BMD was 78%, 76%, and 79%, respectively. Multivariate analyses suggested that, while the association between lean mass and fat mass was attributable mainly to environmental factors (re = 0.53, p < 0.01), the association among the three BMD sites was attributable to both genetic and environmental factors (rg = 0.64-0.75, p < 0.001; re = 0.57-0.70, p < 0.001). Furthermore, genetic factors that affect lean mass or fat mass have minor effects on BMD. It is concluded that lean mass and fat mass, as well as bone density, are under strong genetic regulation. However, the associations between BMD and fat mass or between lean mass and fat mass appear to be mediated mainly via environmental influences.

Absorptiometry, Photon↗

High-dose-rate brachytherapy for medically inoperable stage I endometrial cancer.

PURPOSE: The objective of this study was to determine the efficacy of high-dose-rate (HDR) brachytherapy in 36 medically inoperable patients with stage I endometrial cancer. METHODS AND MATERIALS: From October 1989 to August 1997, 36 patients presented with clinical stage I inoperable endometrial cancer. Surgery was precluded because of obesity and/or poor cardio-pulmonary reserve. Obesity was assessed using the body mass index (BMI) scale (kg/m2). Patients received 5 weekly HDR outpatient brachytherapy applications while under intravenous conscious sedation. Three-year clinical endpoints were calculated using the Kaplan and Meier method. Grade 3 and above complications were scored using the Radiation Therapy Oncology Group system. RESULTS: The median age, Karnofsky performance status, BMI, and weight were 65 years old, 80%, 47 kg/m2, and 268 lbs, respectively. Nineteen patients were inoperable due to morbid obesity (median weight and BMI: 316 lbs and 56 kg/m2) while the remaining patients had other significant medical problems. Two patients died from acute cardiovascular events within 30 days of the last insertion. With a median follow-up of 32 months the 3-year uterine control, disease-free survival, survival, and complications were 88, 85, 65, and 21%, respectively. CONCLUSION: Excellent uterine control rates (88%) were achieved using HDR brachytherapy for patients with medically inoperable endometrial cancer, but with significant acute and late morbidities. These toxicities were observed in a previous interim analysis that resulted in major modifications of the HDR program. No severe complications have developed since these changes were implemented. The current approach used for these challenging inoperable patients is a viable alternative to observation or hormonal therapy.

Adult↗

Femoral neck axis length, height loss and risk of hip fracture in males and females.

Hip axis length (HAL) has been proposed as an independent predictor of hip fracture risk in Caucasian females. Femoral neck axis length (FNAL) is a similar measure of femoral geometry but does not include acetabular structures. The aim of this study was to examine the association between hip geometry, using FNAL, and hip fractures in elderly males and females in relation to other anthropometric data. The study group comprised 123 females (23 hip fracture patients and 100 age-matched controls) and 137 males (13 hip fracture patients, 65 age-matched controls and 59 current-height-matched controls). All subjects had femoral neck bone mineral density measured by dual-energy X-ray absorptiometry. From these scans, FNAL was measured as the linear distance from the base of the greater trochanter to the apex of the femoral head. FNAL was correlated significantly with current height (r = 0.47 and r = 0.56 for females and males respectively; p < 0.0001) and peak height (r = 0.45 and r = 0.57 for females and males respectively; p < 0.0001) in both sexes. In females, FNAL in the fracture patients (91.5 +/- 5.4 mm, mean +/- SD) was not significantly different from FNAL in controls (89.7 +/- 5.4 mm; p = 0.2). Fracture patients had the same current height as controls and a trend towards a greater peak height (163 +/- 6 cm vs 160 +/- cm; p = 0.09). After adjusting FNAL for current or peak height there was no difference in FNAL between fracture patients and controls. In males, FNAL in the fracture patients (103.9 +/- 3.9 mm) was not significantly different from that of age-matched controls (103.4 +/- 6.3 mm; p = 0.79). Fracture patients had a significantly lower current height (168 +/- 6 cm) than the age-matched controls (174 +/- 6 cm; p = 0.0008) but had the same peak height. When adjusted for peak height there were no significant differences between height of hip fracture patients (102.0 +/- 4.9 cm), age-matched controls (102.1 +/- 5.1 cm) and current-height-matched controls (102.6 +/- 5.3 cm). Fracture patients had a significantly greater height loss (peak height minus current height) than either control group. In logistic regression analyses peak height in females and height loss in males but not FNAL were independent predictors of hip fracture. The greater height, FNAL and presumably HAL in males versus females is not associated with increased hip fracture risk. However, in this study of elderly males and females, peak height (females) and height loss (males) were independent risk factors for hip fracture. Moreover, FNAL appears to have limited utility in the prediction of hip fracture risk and any role of HAL in the prediction of hip fracture does not relate to its major component of femoral neck length.

Absorptiometry, Photon↗