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T V Nguyen

Publications and source records attributed to T V Nguyen.

At least 91 records · Page 5Linked to original sources
PubMed1996

Potential mechanisms by which nonsteroidal anti-inflammatory drugs elevate blood pressure: the role of endothelin-1.

To determine whether endothelin-1 (ET-1) contributes to hypertension associated with non-steroidal anti-inflammatory drug (NSAID) usage in healthy, elderly, normotensive individuals a randomised, double-blind, placebo-controlled, crossover trial of indomethacin was undertaken in 41 healthy, elderly individuals with stable normotension or controlled hypertension (blood pressure (BP) < or = 160/90 mm Hg). The main outcome measures were systolic and diastolic BP, heart rate, cardiac output, weight, creatinine clearance, plasma renin activity, aldosterone, endothelin-1 and arginine vasopressin concentrations and 24 h urinary endothelin-1 and 6 keto prostaglandin F1 alpha outputs. Analysis of covariance was used to evaluate the effect of indomethacin on BP and related parameters. Indomethacin treatment for 1 month increased systolic (+/- s.e.m.: 4.1 +/- 2.2 mm Hg; 95% confidence interval 0 to 8.3 mm Hg) and diastolic BP (2.7 +/- 1.1 mm Hg; 0.4 to 4.9 mm Hg) without altering cardiac output (P = 0.59), implying an increase in total peripheral resistance. Indomethacin treatment produced a small increase in weight (1.4 +/- 0.4 kg; 0.6 to 2.2 kg), a small reduction in renal function (creatinine clearance: 6.8 +/- 1.8 mis/min; 3.3 to 10.3 mis/min) but a significant (83%) increase in daily urinary endothelin-1 production (13.1 +/- 3.4 ng/ml; 6.4 to 19.8 ng/ml) without altering plasma ET-1 concentration, suggesting increased renal synthesis. In conclusion, renal paracrine effects of ET-1 may contribute to NSAID-induced blood pressure elevation in humans.

Aged↗
PubMed1996

Genetic influences on central abdominal fat: a twin study.

INTRODUCTION: Recent studies of regional fat distribution have focused on the clinical importance of central abdominal obesity. Central adiposity is strongly related to insulin resistance, non-insulin dependent diabetes mellitus (NIDDM), dyslipidaemia and cardiovascular disease. While significant genetic influences on body mass index (BMI), total body and subcutaneous fat have been demonstrated, the inheritance of central abdominal obesity, has not been studied. OBJECTIVE: To assess genetic effects on regional fat distribution and associated metabolic parameters. DESIGN AND SUBJECTS: We directly measured total body, central abdominal (C-abd) and non-abdominal fat using dual energy X-ray absorptiometry in 50 monozygotic (MZ) and 36 dizygotic (DZ) female twins, of age (mean +/- SD), 44 +/- 12 and 47 +/- 14 y; BMI 24 +/- 5 and 24 +/- 3 kg/m2; C-abd fat 33 +/- 9 and 32 +/- 9%, respectively. Total variance in all parameters was independent of zygosity and genetic analyses of regional adiposity were performed before and after adjusting for age and percentage total body fat. RESULTS: A genetic influence was observed on the population variance in total fat, C-abd fat (C-abd fat rMZ = 0.66 vs rDZ = 0.20, p = 0.03) and non abdominal fat. After adjusting C-abd fat for age and total body fat there was a independent genetic influence on C-abd fat accounting for approximately 70% of the population variance (rMZ = 0.61 vs rDZ = 0.40, p = 0.001). CONCLUSION: The majority of inter-subject variance in central abdominal fat in non-obese individuals is due to genetic factors. The inheritance of abdominal obesity, with its associated metabolic consequences, may contribute to the familial aggregation of insulin resistance, diabetes and cardiovascular disease.

Abdomen↗
PubMed1995

Application of a tumor suppressor (C-CAM1)-expressing recombinant adenovirus in androgen-independent human prostate cancer therapy: a preclinical study.

Recently, we demonstrated that an androgen-regulated cell adhesion molecule, C-CAM, acts as a tumor suppressor in prostate cancer development. In this study, we further explored the possibility of applying C-CAM as a potential agent for developing prostate cancer gene therapy using an adenoviral delivery system. We found that prostate cancer cells, in general, were sensitive to adenoviral infection. In vitro characterization indicated that C-CAM1 protein was detected only in C-CAM1 adenovirus-infected cells but not in antisense control virus-infected cells, and the levels of expression showed dose dependency. Because of the stability of the protein, C-CAM expression in viral-infected cells appeared to be a long-lasting event, indicating that C-CAM may be superior to many other known tumor suppressors that have a short protein half-life. Most importantly, the delivery of a single dose of C-CAM adenovirus was able to repress the growth of PC-3-induced tumors in nude mice for at least 3 weeks. Taken together, these data indicate that C-CAM is a potential candidate for human prostate cancer therapy.

Adenosine Triphosphatases↗
PubMed1995

Influence of vitamin D receptor genotype on bone mineral density in postmenopausal women: a twin study in Britain.

OBJECTIVES: To investigate the possible association between vitamin D receptor genotype and bone mineral density in a large group of postmenopausal twins. DESIGN: Cross sectional twin study. SETTING: Twin population based in Britain. SUBJECTS: 95 dizygotic (non-identical) pairs of twins and 87 monozygotic (identical) pairs of twins aged 50-69 years, postmenopausal, and free of diseases affecting bone, recruited from a national register of twins and with a media campaign. MAIN OUTCOME MEASURES: Bone mineral density measured at the hip, lumbar spine, forearm, and for the whole body by dual energy x ray absorptiometry in relation to differences in the vitamin D receptor genotype. RESULTS: At all sites the values of bone density among dizygotic twins were more similar in those of the same vitamin D receptor genotype than in those of differing genotype, and the values in the former were closer to the correlations seen in monozygotic twins. Women with the genotype that made them at risk of osteoporotic fracture had an adjusted bone mineral density that was significantly lower by SD 0.5 to 0.6 at the hip, lumbar spine, and for the whole body. The results could not be explained by differences in age, weight, years since menopause, or use of hormone replacement therapy. CONCLUSIONS: The findings that in postmenopausal women in Britain bone density-particularly at the hip and spine-is genetically linked and specifically associated with the vitamin D receptor genotypes should lead to novel approaches to the prevention and treatment of osteoporosis.

Absorptiometry, Photon↗
PubMed1995

The contribution of vitamin D receptor gene alleles to the determination of bone mineral density in normal and osteoporotic women.

Bone mass and its mineral content are under genetic control. The vitamin D receptor (VDR) gene has been shown to be a major locus for genetic effects on bone mineral density (BMD), and polymorphisms in this gene accounted for a large proportion of genetic variance in BMD in an Australian population. In this study, we investigated whether similar associations are present in a North American population. We studied 139 normal healthy women (age 53.2 +/- 14.5, mean +/- SD) and 43 severely osteoporotic postmenopausal women (age 65.8 +/- 5.9). In the 127 of them with complete genetic studies, the distribution of genotypes, determined by polymerase chain reaction on leukocyte DNA samples, agreed closely with that in the Australian population. BMD was strongly related to age and weight, and, thus was adjusted for these parameters prior to genetic analysis. We found that age modulated the effect of VDR genotypes on femoral neck BMD (FN-BMD) (TaqI, p = 0.036; BsmI, p = 0.118; ApaI, p = 0.041) such that the effect of genotype was greatest among younger (premenopausal) women and declined with age so that there was no discernible difference by age 70. Among the younger women, a high FN-BMD was associated with the TT (or aa or bb) genotype while low FN-BMD was associated with the tt (or AA or BB) genotype.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Direct clinical and welfare costs of osteoporotic fractures in elderly men and women.

Osteoporosis is an increasing health care problem in all aging populations, but overall direct costs associated with the total fracture burden of osteoporosis remain uncertain. We have examined direct costs associated with 151 osteoporotic fractures occurring between 1989 and 1992 in a large cohort of elderly men and women followed prospectively as part of the Dubbo Osteoporosis Epidemiology Study. The median cost of hospital treated fractures was $A10,511 per fracture and for fractures treated on an outpatient basis $A455 in 1992 Australian dollars. Femoral neck fractures were the most expensive fractures ($15,984 median cost). There was no significant difference in costs between men and women for either hospital- or outpatient-treated fractures. Rehabilitation hospital costs comprised the largest proportion of costs (49%) for hospital-treated fractures. Community services comprised the major cost (40%) of outpatient-treated fractures. Univariate predictors of costs were quadriceps strength and bone density, although multivariate analysis showed quadriceps strength to be the best overall predictor of costs. The predicted annual treatment costs in Australia for atraumatic fractures occurring in subjects > or = 60 years was $A779 million or approximately $A44 million per million of population per annum. Estimated total osteoporotic fracture-related costs for the Australian population were much higher than previously reported. The majority of direct costs (95%) were incurred by hospitalized patients and related to hospital and rehabilitation costs. Extrapolation of these data suggests that the direct costs for hip fracture alone will increase approximately twofold in most Western countries by 2025. Improving the cost-effectiveness of treating osteoporotic fractures should involve reduced hospitalization and/or greater efficiency in community rehabilitation services. The costs of various approaches to osteoporosis prevention must be placed into the context of these direct costs and prevention should target men as well as women.

Aged↗
PubMed1995

Both of the beta-subunit carbohydrate residues of follicle-stimulating hormone determine the metabolic clearance rate and in vivo potency.

FSH is a glycoprotein hormone required for the development and maturation of the ovarian follicle and for spermatogenesis. FSH is glycosylated at asparagine residues 52 and 78 on the alpha-subunit and residues 7 and 24 on the beta-subunit. In vitro, the carbohydrate residue at position alpha 52 is required for signal transduction. To define the contribution of the carbohydrate residues to FSH potency in vivo, we assessed the MCR and in vivo bioactivity of site-specifically deglycosylated recombinant human FSH variants. The removal of the beta-subunit carbohydrate residues significantly (P < 0.05) affected the MCR and resulted in significantly (P < 0.05) reduced in vivo bioactivity. For all recombinant human FSH variants, a strong correlation (r = 0.90; P < 0.01) was observed between MCR and in vivo potency, indicating that the circulatory half-life of the hormone appears to be the primary determinant of in vivo bioactivity. Although the beta-subunit carbohydrate residues have the greatest effect in determining FSH potency in vivo; the alpha 52 residue, important in vitro, has no effect on either MCR or in vivo potency. This study highlights the difficulties of translating in vitro results to whole animal physiology.

Animals↗
PubMed1995

Effects of estrogen exposure and reproductive factors on bone mineral density and osteoporotic fractures.

The risk of osteoporotic fracture is related to peak bone mass achieved at skeletal maturity and subsequent bone loss. Although premature menopause is a risk factor for osteoporosis, the effect of exposure to endogenous estrogen during a woman's reproductive years is poorly characterized. We analyzed the relationship between reproductive factors and estrogen exposure on bone mineral density (BMD) and incidence of atraumatic fracture in data from 1091 women (age: 70 +/- 7.2 yr; mean +/- SD) participating in the Dubbo Osteoporosis Epidemiology Study. Age- and weight-adjusted BMD among women who had used estrogen replacement therapy (ERT) for more than 5 yr was higher at the lumbar spine and femoral neck by 13.7% and 10.2% (P < 0.001), respectively, compared with women who had used ERT for less than 5 yr or nonusers. Duration of exposure to estrogen (years of menstruation plus postmenopausal ERT use) was associated with higher BMD, such that BMD increased by 2-3% for every 10-yr increase in years of estrogen exposure; thus women who menstruated for more than 40 yr had a 6-8% higher BMD than did women who menstruated for less than 30 yr. Higher BMD was also significantly associated with high parity, such that nulliparous women had 5-6% lower BMD than did their peers of the same age and weight. The incidence of atraumatic fractures among non-ERT users was higher than that of ERT-users [odds ratio (OR): 1.06; 95% confidence interval (CI): 0.94-1.16] and was significantly lower among parous women than among nulliparous women (OR 0.94; 95% CI: 0.84-0.98) in univariate analysis. Longer duration of menstruation was associated with lower fracture incidence (OR for 1 SD = 6.6 yr: 0.93; 95% CI: 0.86-1.02). Moreover, when all of these factors were considered simultaneously, parity remained a significant determinant of fracture as well as femoral neck BMD. We conclude that high parity and longer duration of exposure to estrogen, either through natural menstruation or postmenopausal ERT, have protective effects on BMD and are associated with a reduced incidence of atraumatic fracture in a population-based study.

Aged↗
PubMed1995

A twin study of polycystic ovary syndrome.

OBJECTIVE: To examine the role of genetic and environmental factors in polycystic ovary syndrome (PCOS) by using the classic twin model. SETTING: Outpatient clinic of the Royal Hospital for Women, Paddington, Sydney, New South Wales, Australia. PATIENTS: A group of 19 monozygotic (MZ) and 15 dizygotic (DZ) twin pairs identified from the national twin register. INTERVENTIONS: Ultrasound, clinical, and biochemical parameters were used to define PCOS. RESULTS: Eleven pairs of twins (5 MZ, 6 DZ pairs) were scan-discordant (i.e., one twin had scan-PCOS and the co-twin did not). Model-fitting analysis suggested that fasting insulin level, androstanediol glucuronide, and body mass index (BMI) were significantly influenced by genetic factors. CONCLUSION: This study suggests that PCOS is not the result of a single autosomal genetic defect, but rather environmental factors, perhaps both intrauterine and extrauterine, are involved in the pathogenesis of this disorder or that PCOS may be an X-linked disorder or the result of polygenic factors. However, fasting insulin level, androstanediol glucuronide, and BMI did appear to be under significant genetic influence.

Adolescent↗
PubMed1994

[Anterior fontanel bone--a rare normal variant].

The anterior fontanel bone is a very rare true accessory bone. Radiographic demonstration is especially important in those babies suspected to have premature closure of the cranial sutures or fractures. The bone is considered as a normal variant. It does not interfere with cranial growth nor with the normal development of the child.

Cranial Sutures↗
PubMed1994

Do nonsteroidal anti-inflammatory drugs affect blood pressure? A meta-analysis.

PURPOSE: A meta-analysis of randomized trials studying the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on blood pressure. DATA SOURCES AND STUDY SELECTION: Eight databases were searched, yielding 38 randomized, placebo-controlled trials and 12 randomized but not placebo-controlled trials (comparing two or more NSAIDs). DATA EXTRACTION: Pooled mean treatment effects were computed in each trial for blood pressure, weight, creatinine clearance, plasma renin activity, and daily urinary excretion of sodium and prostaglandins. Meta-analyses of these variables were done for all randomized, controlled trials; for all randomized, uncontrolled trials; and for several subgroups. DATA SYNTHESIS: When pooled, NSAIDs elevated supine mean blood pressure by 5.0 mm Hg (95% CI, 1.2 to 8.7 mm Hg) but had no effect on variables other than blood pressure. Nonsteroidal anti-inflammatory drugs antagonized the antihypertensive effect of beta-blockers (blood pressure elevation, 6.2 mm Hg; CI, 1.1 to 11.4 mm Hg) more than did vasodilators and diuretics. Among NSAIDs, piroxicam produced the most marked elevation in blood pressure (6.2 mm Hg; CI, 0.8 to 11.5 mm Hg), whereas sulindac and aspirin had the least hypertensive effect. CONCLUSIONS: Nonsteroidal anti-inflammatory drugs may elevate blood pressure and antagonize the blood pressure-lowering effect of antihypertensive medication to an extent that may potentially increase hypertension-related morbidity. Although certain NSAIDs and antihypertensive agents could be more likely to produce these effects, the underlying mechanisms require further study.

Adult↗
PubMed1994

Prediction of bone density from vitamin D receptor alleles.

Bone density achieved in early adulthood is the major determinant of risk of osteoporotic fracture. Up to 60% of women suffer osteoporotic fractures as a result of low bone density, which is under strong genetic control acting through effects on bone turnover. Here we show that common allelic variants in the gene encoding the vitamin D receptor can be used to predict differences in bone density, accounting for up to 75% of the total genetic effect on bone density in healthy individuals. The genotype associated with lower bone density was overrepresented in postmenopausal women with bone densities more than 2 standard deviations below values in young normal women. The molecular mechanisms by which bone density is regulated by the vitamin D receptor gene are not certain, although allelic differences in the 3' untranslated region may alter messenger RNA levels. These findings could open new avenues to the development and targeting of prophylactic interventions. It follows that other pathophysiological processes considered to be subject to complex multifactorial genetic regulation may also be modulated by a single gene with pleiotropic transcriptional actions.

Adolescent↗
PubMed1994

Lifestyle factors and bone density in the elderly: implications for osteoporosis prevention.

Epidemiologic evidence suggests that lifestyle factors, such as exercise, calcium intake, and tobacco consumption, have effects on bone density. However, the influence of these factors in the elderly has not been well documented. To examine the effects of lifestyle factors in the elderly, we measured bone density (BMD) at the lumbar spine and proximal femur in 709 elderly men and 1080 women participating in the Dubbo Osteoporosis Epidemiology study (DOES), a community-based, longitudinal, epidemiologic study of osteoporosis in men and women over the age of 60. BMD was significantly higher in men than in women (20% at all sites). There was an age-related decline in BMD at the femoral neck in both sexes and at the lumbar spine in women. Between the ages of 60 and 80, the decrease in BMD at the femoral neck among women was 18.9%, which is almost twice the decrease in BMD among men (10.1%). Tobacco consumption was associated with a reduction in BMD at both sites in both sexes (5-8%), and this effect was independent of calcium intake or body weight. Exsmokers had BMD intermediate between that of current smokers and never smokers, suggesting the influence of tobacco was partially reversible. Quadriceps strength predicted bone density at the proximal femur in elderly men but not in women. Analyzing BMD (adjusted for age and weight) in tertiles of muscle strength and calcium intake revealed an interaction between calcium intake and muscle strength on bone density; BMD at the femoral neck among those with higher quadriceps strength and calcium intake was approximately 5% higher (P < 0.05) than in those with low quadriceps strength and calcium intake in both men and women.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗