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J Simons

Publications and source records attributed to J Simons.

At least 37 records · Page 2Linked to original sources
PubMed1999

Vitamin E ingestion does not improve arterial endothelial dysfunction in older adults.

Endothelial dysfunction is thought to be an important early event in atherogenesis, related in part to reduced bioavailability of nitric oxide in the arterial wall. Endothelial function may be impaired in the presence of oxidised low density lipoprotein. The use of vitamin E as an anti-oxidant might enhance the bioavailability of nitric oxide in this situation. The effect of vitamin E 1000 IU/day on arterial endothelial physiology was studied in 20 asymptomatic older subjects, aged 45-70 years, who showed evidence of age-related endothelial dysfunction. Endothelial function was assessed non-invasively using brachial ultrasound and the primary outcome measure was flow-mediated endothelium-dependent dilatation (FMD) in response to reactive hyperaemia. A double-blind, placebo-controlled, randomised crossover design was employed. After 3 weeks of stabilisation on a standard fat-reduced diet, subjects received vitamin E or placebo for 10 weeks in random order, separated by a washout period of 8 weeks. There were no significant changes in blood pressure, plasma lipid or lipoprotein concentrations. Plasma alpha-tocopherol increased from 50+/-3 (mean+/-S.E.M.) to 91+/-6 micromol/l (P < 0.001) with vitamin E ingestion. Total plasma F2alpha-isoprostanes, a measure of free radical-induced lipid peroxidation, were not altered by vitamin E ingestion (0.86+/-0.26 versus 0.82+/-0.25 nmol/l, P > 0.6). FMD was not significantly different between the placebo and vitamin E periods (2.7+/-0.6% versus 2.4+/-0.4%). Variation in FMD was not correlated with change in plasma alpha-tocopherol (r = - 0.03, P > 0.8). The study was powered to detect a minimum change in FMD of 2%. Glyceryl trinitrate endothelium-independent dilatation was not significantly changed with vitamin E (13.7+/-1.3% versus 13.6+/-1.4%,). These results exclude a major impact of medium-term supplementation with vitamin E on arterial endothelial function when age-related dysfunction is already present.

Aged↗
PubMed1999

The A1166C mutation in the angiotensin II type I receptor and hypertension in the elderly.

1. Using a nested case-control study of 661 non-institutionalized elderly (> or = 60 years) residents of Dubbo, New South Wales, Australia, the aim of this study is to determine whether the A1166C polymorphism of the angiotensin II type I (AT1) receptor gene is associated with hypertension in the elderly. 2. Individuals were classified as isolated systolic hypertension (ISH, n = 146), systolic diastolic hypertension (SDH, n = 188), or normotensive, age- and sex-matched controls (n = 327). AA, CC and AC genotypes were determined using restriction fragment length polymorphism analysis of DNA generated by nested polymerase chain reaction. 3. A univariate analysis (chi 2) was complemented by a logistic regression analysis, facilitating adjustment for potential confounders. The unadjusted genotype and allele frequencies in ISH or SDH subjects did not differ significantly from the control subjects (chi 2 = 3.0, P = 0.55, 4 d.f.; chi 2 = 3.0, P = 0.23, 2 d.f., respectively). After adjustment for potential confounders neither genotype nor allele predicted ISH or SDH in this cohort. 4. From this study we conclude that the A1166C polymorphism of the AT1 receptor gene is not a marker for ISH nor for SDH in this large, elderly community sample.

Angiotensin II↗
PubMed1999

Analysis of chromosome 22q as an aid to the diagnosis of rhabdoid tumor: a case report.

Malignant rhabdoid tumor is a highly aggressive tumor of childhood that may present as a soft-tissue primary tumor. We report a soft-tissue neoplasm that was polyphenotypic by immunohistochemical expression of epithelial, mesenchymal, and neural markers and did not meet the criteria for any of the usual pediatric small round-cell tumors. The findings raised the diagnosis of rhabdoid tumor, leading to testing for WT1 mRNA and protein expression, which were positive, as has been reported for renal rhabdoid tumor. This tumor had the typical clinical behavior of rhabdoid tumor with therapy resistance and early tumor-related death. Multicolor spectral karyotyping of this neoplasm showed a balanced translocation between chromosomes 1 and 22 with breakpoints at 1p36 and 22q11-12. The latter region is commonly involved in rhabdoid tumor. This change was also identified by fluorescence in situ hybridization. This case suggests that studies of chromosome 22 may be required to distinguish rhabdoid tumor from other soft-tissue tumors.

Chromosomes, Human, Pair 22↗
PubMed1999

Eligibility and response guidelines for phase II clinical trials in androgen-independent prostate cancer: recommendations from the Prostate-Specific Antigen Working Group.

PURPOSE: Prostate-specific antigen (PSA) is a glycoprotein that is found almost exclusively in normal and neoplastic prostate cells. For patients with metastatic disease, changes in PSA will often antedate changes in bone scan. Furthermore, many but not all investigators have observed an association between a decline in PSA levels of 50% or greater and survival. Since the majority of phase II clinical trials for patients with androgen-independent prostate cancer (AIPC) have used PSA as a marker, we believed it was important for investigators to agree on definitions and values for a minimum set of parameters for eligibility and PSA declines and to develop a common approach to outcome analysis and reporting. We held a consensus conference with 26 leading investigators in the field of AIPC to define these parameters. RESULT: We defined four patient groups: (1) progressive measurable disease, (2) progressive bone metastasis, (3) stable metastases and a rising PSA, and (4) rising PSA and no other evidence of metastatic disease. The purpose of determining the number of patients whose PSA level drops in a phase II trial of AIPC is to guide the selection of agents for further testing and phase III trials. We propose that investigators report at a minimum a PSA decline of at least 50% and this must be confirmed by a second PSA value 4 or more weeks later. Patients may not demonstrate clinical or radiographic evidence of disease progression during this time period. Some investigators may want to report additional measures of PSA changes (ie, 75% decline, 90% decline). Response duration and the time to PSA progression may also be important clinical end point. CONCLUSION: Through this consensus conference, we believe we have developed practical guidelines for using PSA as a measurement of outcome. Furthermore, the use of common standards is important as we determine which agents should progress to randomized trials which will use survival as an end point.

Androgens↗
PubMed1999

Growing pains.

Explore the source record for details and available documents.

Academies and Institutes↗
PubMed1998

On the Ground Electronic States of TiF and TiCl

The low-lying electronic states of TiF and TiCl have been studied using high level ab initio techniques. Both are found to have two low-lying excited electronic states, 4Sigma- (0.080 eV (TiF) and 0.236 eV (TiCl)) and 2Delta (0.266 eV (TiF) and 0.348 eV (TiCl)), and 4Phi ground states at the highest CCSD(T)/6-311++G(2d,2f) level of theory. Our theoretical predictions of 4Phi ground electronic states for TiF and TiCl support recent experimental findings by Ram and Bernath, and our calculated bond lengths and vibrational frequencies are in reasonable agreement with their experimental data. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

Effects of atorvastatin monotherapy and simvastatin plus cholestyramine on arterial endothelial function in patients with severe primary hypercholesterolaemia.

Endothelial dysfunction is an important early event in atherogenesis. Changes in arterial endothelial physiology were studied in patients with severe primary hypercholesterolaemia participating in an ongoing clinical trial evaluating atorvastatin and simvastatin. Endothelial function was assessed non-invasively using brachial ultrasound and the primary outcome measure was flow-mediated endothelium-dependent dilatation (FMD) in response to reactive hyperaemia. Patients were studied upon entry while still using simvastatin 40 mg daily and again after a 10-week washout (baseline). Over the next 30 weeks, 20 patients received atorvastatin titrated up to 80 mg daily and 12 patients received simvastatin titrated up to 40 mg daily (plus cholestyramine 4 g daily in 10/12), followed by a final ultrasound study. During simvastatin washout, total and low density lipoprotein (LDL) cholesterol rose by a median 23-29% and 30-34%, respectively. During atorvastatin therapy, total and LDL cholesterol fell by a median of 41 and 46%, respectively, triglycerides fell by 45%, and high density lipoprotein (HDL) cholesterol rose by 10%. During simvastatin plus cholestyramine therapy, the respective median changes were - 32, - 39, - 44 and + 11%. Patients at baseline showed evidence of impaired FMD and this improved significantly on either treatment, from a median + 2.2 to + 5.5% on atorvastatin and from + 1.8 to + 4.5% on simvastatin plus cholestyramine (P < 0.01 for both treatments). Typical response in healthy subjects would be from + 8 to + 9%. FMD at baseline was correlated with HDL cholesterol (r=0.49, P < 0.01). Change in FMD was inversely correlated with baseline FMD (r=-0.54, P < 0.001). Endothelial dysfunction in primary hypercholesterolaemia was improved by treatment with atorvastatin or simvastatin plus cholestyramine and this effect may result in the prevention of future coronary events.

Adult↗
PubMed1998

Risk factors for ischemic stroke: Dubbo Study of the elderly.

BACKGROUND AND PURPOSE: One in 10 deaths in Australia is due to stroke. The predictors of ischemic stroke have not been well defined, although hypertension, atrial fibrillation, and previous stroke have been consistently reported. We report on 98 months' follow-up in a prospective study of cardiovascular disease in the Australian elderly, the Dubbo Study. METHODS: The cohort, first examined in 1988, was composed of 2805 men and women 60 years and older. The prediction of ischemic stroke by potential risk factors was examined in a Cox proportional hazards model, after linkage to hospital and death records. RESULTS: Three hundred six men and women manifested an ischemic stroke event (ICD-9-CM 433 to 437), and 95 subjects suffered a fatal stroke event. In the multivariate model, the significant independent predictors of stroke were advancing age, female sex (48% lower risk), being married (30% lower risk), prior history of stroke (227% higher risk), use of antihypertensive drugs (37% higher risk), belonging to the highest category of blood pressure reading (67% higher risk), presence of atrial fibrillation (58% higher risk), HDL cholesterol (36% lower risk for each 1-mmol/L increment), impaired peak expiratory flow (77% higher risk for tertile I than for tertile III), physical disability (59% higher risk), and depression score (41% higher risk for tertile III than for tertile I). CONCLUSIONS: These findings suggest that morbidity and mortality associated with ischemic stroke can be predicted by various clinical indicators, some of which may be amenable to intervention. The matters of impaired peak expiratory flow, depression score, and ischemic stroke require further study.

Aged↗
PubMed1997

Relationship of peak expiratory flow rate with mortality and ischaemic heart disease in elderly Australians.

OBJECTIVE: To evaluate the relationships of mortality and ischaemic heart disease (IHD) with peak expiratory flow rate (PEF) in the elderly. DESIGN: Prospective study with median follow-up of 83 months. SETTING: Dubbo, a New South Wales country town (population, 30500). SUBJECTS: Non-institutionalised residents born before 1930 (i.e., aged 60 years and over at study entry). Participation rate was 73% (1235 men and 1570 women). MAIN OUTCOME MEASURES: Baseline demographic, psychosocial and standard cardiovascular risk factors, including PEF; all-causes mortality, IHD mortality and IHD events (hospitalisations with any manifestation of IHD) by tertile of PEF. RESULTS: More subjects with PEF in the lowest tertile (I) had a past history of respiratory disease, were current cigarette smokers and were taking antihypertensive drugs. During follow-up, 321 men (26%) and 252 women (16%) died. All-causes mortality was three (men) to four (women) times higher for those in PEF tertile I than for those in tertile III. IHD mortality and IHD events showed similar trends. In a proportional hazards model adjusted for age, height, smoking status and other risk factors or confounders, the hazard ratios (95% confidence interval) for men in PEF tertile I versus tertile III were: all-causes mortality, 1.62 (1.14-2.30); IHD mortality, 1.75 (0.96-3.20); and IHD events, 1.12 (0.82-1.53). For women, respective hazard ratios were 1.92 (1.23-3.00), 2.58 (1.24-5.39), and 1.16 (0.83-1.63). CONCLUSIONS: We confirm an independent, inverse relationship between PEF and all-causes and IHD mortality. The data suggest a potential benefit for coronary risk factor management in subjects with existing airways disease and further support the case for antismoking programs.

Aged↗
PubMed1997

Phenotype of mice lacking functional Deleted in colorectal cancer (Dcc) gene.

The DCC (Deleted in colorectal cancer) gene was first identified as a candidate for a tumour-suppressor gene on human chromosome 18q. More recently, in vitro studies in rodents have provided evidence that DCC might function as a receptor for the axonal chemoattractant netrin-1. Inactivation of the murine Dcc gene caused defects in axonal projections that are similar to those observed in netrin-1-deficient mice but did not affect growth, differentiation, morphogenesis or tumorigenesis in mouse intestine. These observations fail to support a tumour-suppressor function for Dcc, but are consistent with the hypothesis that DCC is a component of a receptor for netrin-1.

Animals↗
PubMed1997

Skeletal maturation, somatic growth and physical fitness in girls 6-16 years of age.

The importance of chronological age (CA) and skeletal age (SA) in explaining variation in somatic dimensions, and the independent contributions of CA, SA, stature (ST) and weight (WT) to variability in physical fitness were investigated in a sample of 6593 girls 6-16 years of age. Body dimensions included lengths, breadths, circumferences, skinfolds, and Heath-Carter somatotype, while fitness tests included measures of health- and performance-related fitness, and cardiovascular and lung functions. Age-specific correlations were calculated between SA and anthropometric dimensions, fitness tests and cardiovascular and lung functions, while age-specific stepwise multiple regressions were used to investigate the relative importance of SA, CA, ST and WT in explaining fitness and cardiovascular and lung functions. SA is most highly correlated with lengths and then with breadths, circumferences and skinfolds in this order. SA per se or in interaction with CA is the only significant predictor of somatic characteristics. Among fitness items, physical working capacity and static strength correlate highest with SA. Bent arm hang, leg lifts and sit-ups correlate negatively with SA but values are low, while all other components correlate at non-significant or low levels. Results of the multiple regression analysis indicate that, with few exceptions, CA, SA, ST and WT and their interactions explain less than 10% of the variance in most physical fitness items. However, for PWC, arm pull strength, and bent arm hang, the interaction terms explain between 12% and 67% of the variance.

Adolescent↗
PubMed1997

Development and tracking in fitness components: Leuven longtudinal study on lifestyle, fitness and health.

In the Leuven Growth Study of Belgian Boys the growth and physical performance of Belgian boys followed longitudinally between 12 and 19 years were studied. Subsequently, a subsample (n = 240) of Flemish-speaking males were reexamined at 30 and 35 years. A first question relates to the individual growth patterns in a variety of physical fitness characteristics. The three strength tests (static, functional, explosive) show curves that are qualitatively similar to those for height and weight. Their adolescent spurts occur after the height spurt. Flexibility and the two speed tests appear to reach maximum velocities prior to the height and weight spurts. Longitudinal principal component analysis was applied to the study of growth patterns of several somatic and motor characteristics. The results for height show three components sufficient to provide an adequate representation of the original information. The first component characterizes the general position of an individual growth curve. Components 2 and 3 reflect fluctuation in percentile level during the age period studied and can be conceived as indices of stability and are related to age at peak height velocity (APHV) and peak height velocity (PHV), respectively. Relationships between somatic characteristics, physical performance, and APHV have been studied in a sample of 173 Flemish boys, measured yearly between +/- 13 and +/- 18 years and again as adults at 30 years of age. The sample was divided into three contrasting maturity categories based on the APHV. There are consistent differences among boys of contrasting maturity status during adolescence in body weight, skeletal lengths and breadths, circumferences, and skinfolds on the trunk. There are no differences in skinfolds on the extremities. None of the differences in somatic dimensions and ratios among the three contrasting maturity groups are significant at 30 years of age except those for subscapular skinfold and the trunk/extremity skinfold ratio. During adolescence, speed of limb movement, explosive strength and static strength are negatively related to APHV; thus, early maturers performed better than late maturers. However, between late adolescence and adulthood (30 years), the late maturers not only caught up to the early maturers, but there were significant differences for explosive strength and functional strength in favor of late maturers. Finally, age-specific tracking, using inter-age correlations, of adult health- and performance-related fitness scores were investigated. In addition, the independent contribution of adolescent physical characteristics to the explanation of adult fitness scores was also studied. Tracking between age 13 and age 30 years was moderately high (46% of variance explained) for flexibility, low to moderate (between 19% and 27% of variance explained) for the other fitness parameters and low for pulse recovery and static strength (7% to 11% of variance explained). Between age 18 and age 30 years the tracking was high for flexibility, moderately high for explosive and static strength, and moderate for the other fitness parameters except for pulse recovery. The amount of variance of adult fitness levels explained increased significantly when other characteristics observed during adolescence entered the regressions or discriminant functions.

Adolescent↗