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Biomedical subjects

J Simons

Publications and source records attributed to J Simons.

At least 19 recordsLinked to original sources
PubMed1992

Treatment of primary hypercholesterolaemia with pravastatin: efficacy and safety over three years.

OBJECTIVE: To assess the efficacy, safety and tolerability of pravastatin over three years of treatment. DESIGN: An open, multicentre randomised study. SETTING: Subjects receiving tertiary care at three hospital lipid clinics. PATIENTS: Subjects with primary hypercholesterolaemia (type IIa) or combined hyperlipidaemia (type IIb), already stabilised on a cholesterol-lowering diet, with low density lipoprotein (LDL) cholesterol levels of greater than 4.7 mmol/L and triglyceride levels of less than 4.5 mmol/L. Sixty-one subjects were randomly assigned to the treatment groups: 60 completed 12 weeks and 46 completed 30-36 months of treatment. INTERVENTIONS: Subjects were randomly assigned to receive either pravastatin 20 mg/day, pravastatin 40 mg/day or cholestyramine 16 g/day for a period of 12 weeks. Subsequently, dose titration of pravastatin up to 40 mg/day was permitted, if required, and all groups received supplementary therapy with other lipid-lowering drugs. MAIN OUTCOME MEASURES: Lipids, lipoproteins, haematological and biochemical safety parameters were measured at regular intervals. Adverse events were monitored. RESULTS: There were significant reductions in total and LDL cholesterol levels with all treatments over 12 weeks (P < 0.001). The mean reductions (+/- SD) in LDL cholesterol were 26% +/- 14% in the group taking pravastatin 20 mg/day (n = 21), 30% +/- 8% in the group taking pravastatin 40 mg/day (n = 21) and 34% +/- 13% in the group taking resin (n = 18). The percentage changes in LDL cholesterol were independent of age, baseline cholesterol level or lipid phenotype. High density lipoprotein (HDL) cholesterol levels were significantly increased, by 8%-18% with all treatments (P < 0.001). Triglyceride levels were reduced by high-dose pravastatin only (7% +/- 29%), but were found to increase with resin (45% +/- 63%). During long-term treatment over 36 months, still greater reductions in total and LDL cholesterol were found in patients taking pravastatin (n = 35), but not in those taking resin (n = 11). There was an apparent decrease in effect beyond 18 months in both groups, possibly related to reduced compliance with diet or cholestyramine intake. Eight subjects allocated to pravastatin and seven allocated to resin withdrew (one and two subjects respectively because of drug-induced adverse events). Adverse events during 12 weeks' monotherapy with pravastatin included central nervous system (CNS) symptoms (12%), gastrointestinal (GIT) symptoms (7%) and an acute hepatitic reaction (one subject). Of those in the resin therapy group, 22% developed GIT symptoms. Myalgia occurred in three subjects using a combination of pravastatin and clofibrate, but this resolved fully upon clofibrate withdrawal. CONCLUSIONS: Pravastatin was found to be a relatively effective, safe and well tolerated lipid-lowering drug. Still greater LDL reduction was achieved with pravastatin combination therapy and this was essentially maintained over three years.

Adult↗
PubMed1992

Successful management of primary hypercholesterolaemia with simvastatin and low-dose colestipol.

OBJECTIVE: To examine whether a small dose of bile acid sequestrant used in combination with a hydroxymethylglutaryl coenzyme A reductase inhibitor is more effective in reducing serum and low-density lipoprotein (LDL) cholesterol levels than inhibitor used alone. DESIGN: A randomised, double-blind study. SETTING: Subjects receiving tertiary care at a hospital lipid clinic. PATIENTS: Subjects with severe primary hypercholesterolaemia (types IIa and IIb), already stabilised on a cholesterol-lowering diet, with serum cholesterol levels of 7.0 mmol/L or more and triglyceride levels of 6.0 mmol/L or less. Sixty-four subjects were randomly assigned to the treatment groups; three withdrew before any outcome observations; 61 completed the trial and their results were analysed. INTERVENTIONS: Subjects were randomly assigned to receive either colestipol placebo or colestipol 5 g or 10 g each morning in fixed dosage for 18 weeks. They simultaneously received incremental doses of simvastatin: placebo for six weeks, then 20 mg/night for six weeks, then 40 mg/night for a final six weeks. MAIN OUTCOME MEASURES: Lipids, lipoproteins, and haematological and biochemical safety parameters were measured at the end of each treatment period. Adverse events were monitored. RESULTS: Respective maximum reductions (95% confidence intervals) in serum cholesterol, LDL cholesterol and apolipoprotein B (apo-B) values in subjects taking combination therapy were 41% (38%-45%), 50% (46%-53%) and 43% (39%-46%), compared with lesser reductions of 32% (26%-37%), 38% (31%-45%) and 37% (32%-41%) in those taking simvastatin monotherapy. The percentage changes in LDL cholesterol with combination therapy were independent of baseline cholesterol level or lipid phenotype. Combination therapy reduced serum triglyceride levels by up to 24% (15%-32%) and increased high-density lipoprotein (HDL) cholesterol levels by up to 9% (3%-15%). Three subjects withdrew within a few weeks because of severe gastrointestinal side effects related to colestipol; 19 experienced milder gastrointestinal side effects, 15 were taking combination therapy. CONCLUSIONS: A combination of low-dose colestipol and simvastatin was found to be more effective in reducing serum and LDL cholesterol than simvastatin used alone. Such combination therapy offers the possibility of improved cholesterol lowering without the need for full dosage of either drug.

Anticholesteremic Agents↗
PubMed1992

Multiple medication use in the elderly. Use of prescription and non-prescription drugs in an Australian community setting.

OBJECTIVE: To document the extent of polypharmacy or multiple medication use in the elderly. DESIGN: Cross-sectional examination of an age cohort of a community. SETTING: Community-based study in Dubbo, NSW, in 1988-1989. SUBJECTS: All non-institutionalised residents aged 60 years and over, numbering 1237 men and 1568 women. MAIN OUTCOME MEASURES: Assessment of use of prescription and non-prescription drugs, recent hospitalisation, years of education, psychosocial variables. RESULTS: 18% of men and 25% of women were currently using three or more classes of prescription drugs. The corresponding values for two or more classes of non-prescription drugs were 29% and 44%. Of those who were using multiple prescription drugs 56% of men and 76% of women were also using multiple non-prescription drugs. In a multiple logistic model, the following possible predictors of multiple drug use were included: hospitalisation in the last six months, age, sex, depression, life satisfaction and education. Multiple prescription drug use was significantly predicted by recent hospitalisation (odds ratio [OR] = 2.40; 95% confidence interval [CI], 1.63-3.56), increasing age (e.g. 70-79 years versus 60-69 years; OR = 2.54; CI, 1.97-3.25), female sex (OR = 1.59; CI, 1.25-2.01) and increasing depression (e.g. highest tertile of depression scale versus lowest; OR = 2.52; CI, 1.84-3.42). Multiple non-prescription drug use was significantly predicted by female sex (OR = 2.38; CI, 1.95-2.92) and increasing depression (OR = 2.77; CI, 2.16-3.56). For prescription items, non-prescription items, and both categories in combination levels of use 20% above the population average have been documented. CONCLUSIONS: Polypharmacy in the elderly population appears to be predicted by recent hospitalisation, increasing age, female sex and increasing depression. There is potential for drug-drug interaction to occur, but the findings suggest target areas for preventive action.

Aged↗
PubMed1992

Health status and lifestyle in elderly Hawaii Japanese and Australian men. Exploring known differences in longevity.

OBJECTIVE: To contrast health status and lifestyle in two elderly populations with differing longevity. DESIGN: Comparison of two cross-sectional data sets. SETTING: Non-institutionalised subjects. SUBJECTS: Men aged 60-81 years resident in Dubbo, New South Wales (n = 1183, 1988-1989) and Japanese men of the same ages resident in Hawaii (n = 1376, 1980-1982). MAIN OUTCOME MEASURES: Cardiovascular and non-cardiovascular disease prevalence, risk factors, social and health status. RESULTS: A history of heart attack, angina and stroke was twice as prevalent in Dubbo men as in Hawaii Japanese. Other diseases were many times more prevalent in Dubbo--liver disease sixfold, prostate and renal disease twofold, and arthritis 1.5-fold. Hypercholesterolaemia and untreated hypertension were more prevalent in Dubbo (threefold and 1.5-fold respectively). Current smoking was similar in both groups, while diabetes was twice as prevalent in the Hawaii Japanese. More Dubbo men were widowed or lived alone, and fewer remained in paid employment. Dubbo men had more limited physical mobility. CONCLUSIONS: Elderly Dubbo men have an excess of cardiovascular disease and associated risk factors, as well as an excess of non-cardiovascular disease, compared with Hawaii Japanese. This may account, in part, for a higher total mortality rate in elderly Australians compared with Japanese. Some of this disease burden may be amenable to risk factor intervention.

Aged↗
PubMed1992

Age-specific correlation analysis of longitudinal physical fitness levels in men.

This study investigated the age-specific tracking of adult health- and performance-related fitness scores. In addition, the independent contribution of adolescent physical characteristics to the explanation of adult fitness scores was also studied. The sample consisted of 173 adults observed at age 30 years. These subjects had been followed at annual intervals from age 13 to age 18 years and were remeasured at age 30 years. At each age nine fitness tests were administered together with the recording of anthropometric dimensions, biological maturation, sports participation and family characteristics. Tracking was measured by the inter-age correlations at each age between 13 and 18 years and the performance scores at 30 years. The independent contribution of characteristics observed during adolescence to the explanation of adult fitness was investigated through stepwise multiple regression analysis and discriminant analysis with the adult fitness scores as the dependent variables and the fitness, maturation, anthropometric characteristics, sports participation and family background as the independent variables. 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Dubbo Study of the elderly: hypertension and lipid levels.

Untreated hypertension in age groups below 60 years has been shown to be associated with significant elevations in serum cholesterol and triglyceride levels. Drug therapy of hypertension has also been shown to have adverse effects on lipoproteins. We have investigated lipid and lipoprotein levels in a community-based sample of men and women 60 years and older belonging to one of the following groupings: (a) normal blood pressure (n = 1075); (b) untreated hypertension (n = 329); (c) drug-treated hypertension (n = 880). Serum lipid, lipoprotein, apolipoprotein or plasma glucose levels did not vary significantly between untreated hypertensives and normotensives of either sex. In a multiple regression model controlling for possible influences of age, overweight, alcohol and tobacco usage, and presence of coronary heart disease, anti-hypertensive drug therapy significantly predicted increased serum triglycerides (P less than 0.001) and reduced high density lipoprotein (HDL) cholesterol levels (P less than 0.01) in both sexes, reduced apolipoprotein A-I levels in males (P less than 0.001), and increased apolipoprotein B (P less than 0.01) and plasma glucose levels (P less than 0.001) in females. Adjusted triglycerides were 20% higher and HDL cholesterol was 7% lower in the presence of anti-hypertensive drug therapy. These effects were partially consistent with the known actions of thiazide diuretics and beta-blockers which were used by more than 50% and 40% of subjects, respectively.

Adrenergic beta-Antagonists↗
PubMed1992

Lipoprotein(a) levels in chronic renal disease states, dialysis and transplantation.

Lipoprotein(a) is an independent risk factor for cardiovascular disease. Lipoprotein(a) levels were measured in 196 patients (103 Male [M]: 93 Female [F]) with chronic renal diseases and in 116 controls. Median levels of Lipoprotein(a) [Lp(a)] were found to be significantly elevated in patients with untreated chronic renal disease (285,285 mg/L; M,F; range 30-1675 mg/L) and in those treated with continuous ambulatory peritoneal dialysis (320, 603; M,F; range 50-1450) compared with controls (70,51; M,F; range 1-750; p less than 0.01 Males, p less than 0.001 Females). Lp(a) levels in patients treated by haemodialysis (133,35; M,F; range 5-685) and renal transplantation (100,95; M,F; range 10-1700) were not significantly different from controls. Lipoprotein(a) levels correlated inversely with serum albumin in the combined dialysis group (r = -0.34, p less than 0.001), and with urinary protein loss in the combined transplant and chronic renal diseases groups (r = 0.29, p less than 0.01). This correlation of Lp(a) with protein metabolism suggests a similarity with changes in other apolipoprotein-B containing lipoproteins in nephrosis. These findings may be relevant to the increased risk of atherosclerosis in patients with chronic renal disease and to their optimum mode of renal replacement therapy.

Aged↗
PubMed1992

Lipoprotein(a) concentration in diabetes: relationship to proteinuria and diabetes control.

Diabetic patients are at increased risk of cardiovascular disease, particularly when proteinuria is present. Lipoprotein(a)[Lp(a)] levels were assessed in 37 patients with insulin dependent (IDDM) and in 75 patients with non-insulin dependent (NIDDM) diabetes who showed varying degrees of proteinuria and glycaemic control. Median Lp(a) in 112 diabetic patients was significantly greater than in 116 healthy controls (113 vs 48 mg/L; p less than 0.01). 86 of the patients had first morning urine albumin concentration less than 30 mg/L (normoalbuminuria = NA), 16 patients 30-200 mg/L (microalbuminuria = MA) and ten patients greater than 200 mg/L (albuminuria = ALB). There was no significant difference in median Lp(a) concentration between the three groups (NA = 108, MA = 163, ALB = 98 mg/L; p greater than 0.5). No significant difference in median Lp(a) or NIDDM treated with oral agents and/or diet (120, 98, 115 mg/L respectively; p greater than 0.7). When the 86 NA patients were divided on the basis of median fructosamine concentration (357 mumol/L), no significant difference was found in median Lp(a) levels between those grouped below or above this median (98 mg/L vs 118 mg/L; p greater than 0.5). Across all diabetics studied there was no significant correlation present between Lp(a) and urinary protein or glycaemic control. These cross-sectional results suggest that median Lp(a) concentration is increased in both IDDM and NIDDM patients, but this increase is not related to the degree of proteinuria or short-term glycaemic control.

Adolescent↗
PubMed1992

Poliovirus-specific major histocompatibility complex class I-restricted cytolytic T-cell epitopes in mice localize to neutralizing antigenic regions.

A major histocompatibility complex (MHC) class I-restricted cytotoxic T-lymphocyte (CTL) response is induced in BALB/c mice upon immunization with poliovirus serotype 1 (Mahoney strain). A similar class I-restricted response is also induced upon immunization with purified VP1 capsid proteins. Thus, poliovirus-specific MHC class I CTL responses can be induced independently of viral infection in murine hosts. In experiments using recombinant vaccinia virus vectors expressing different segments of the poliovirus capsid proteins and synthetic peptides, two regions of the VP1 capsid protein appear to contain epitopes recognized by this bulk CTL population. These epitope regions contain a Kd-restricted peptide-binding motif. Interestingly, each of these CTL epitopes is located near previously defined neutralizing antigenic sites.

Amino Acid Sequence↗
PubMed1992

Identification of T-helper epitopes in the VP1 capsid protein of poliovirus.

Poliovirus-specific T lymphocytes were isolated from virus-immunized mice of different H-2 haplotypes. Immunological characterization of this population indicates that the effector population involved in the observed poliovirus-specific proliferative response was that of CD4-positive T-helper cells. Proliferative responses also were induced within these T-lymphocyte populations upon stimulation with either purified VP1 capsid protein or VP1 synthetic peptides. By using these synthetic peptides, several T-helper epitopes were identified. Generally, proliferative responses were observed in three regions of VP1. Two regions spanning VP1 residues 86 to 120 and 201 to 241 were recognized by T lymphocytes from BALB/c (H-2d), C57BL/6 (H-2b), and C3H/HeJ (H-2k) backgrounds. Analyses using synthetic peptides of nonoverlapping sequences indicated that the region spanning residues 201 to 241 may contain several T epitopes and may account for the strong proliferative response observed. In addition, for two of the three haplotypes examined, T epitopes were observed within residues 7 to 24 of VP1. Additional epitopes which appeared to be restricted to specific H-2 backgrounds were identified. T epitopes within VP1 that are common between different strains of mice appeared to lie within previously identified neutralizing antigenic sites in poliovirus.

Amino Acid Sequence↗
PubMed1992

Physical activity and growth, maturation and performance: a longitudinal study.

The effects of increased physical activity upon physical growth, maturation and performance were investigated in samples of 32 active and 32 nonactive Belgian boys followed longitudinally from 13 to 18 yr of age. Active boys participated in sports activities for more than 5 h.wk-1.yr-1 during each of the first 3 yr of the study, in addition to compulsory physical education. Nonactive boys participated in less than 1.5 h.wk-1.yr-1 during the first 3 yr of the study, but did participate in required school physical education. Anthropometric dimensions included lengths, breadths, circumferences, and skinfolds. A physical fitness test battery was administered at each observation including nine health- and performance-related tests. Skeletal maturation was assessed; sociocultural determinants and sports participation were obtained through written questionnaires verified by a control interview. No significant effects of increased physical activity were observed on growth in somatic dimensions, including skinfolds, age at peak height velocity, skeletal maturation, and most of the physical fitness components. More active boys obtained better results from 14 yr onward only for pulse recuperation and for bent arm hang. These results can be generalized to the average population but do not necessarily apply for highly trained and selected elite athletes.

Adolescent↗
PubMed1991

Coronary risk factors six to twelve months after coronary artery bypass surgery. 1986 compared with 1990.

A 1986 study found that coronary risk factors were receiving insufficient attention in patients who had recently undergone coronary artery bypass grafting. This issue was readdressed in a like group of 100 patients from the same surgical unit three and a half years later, in 1990, to ascertain whether risk factor management had improved over the period. An increased proportion of patients in 1990 were undergoing active management of hypertension and hyperlipidaemia. Only 25% of patients in 1990 manifested hypercholesterolaemia (cholesterol levels greater than or equal to 6.5 mmol/L) compared with 60% in 1986. Five per cent of patients in 1990 manifested diastolic hypertension (diastolic pressure greater than or equal to 95 mmHg) compared with 23% in 1986. Such patients appear better managed in 1990 than they were in 1986.

Adult↗
PubMed1991

High level expression of functional full length human thyroid hormone receptor beta 1 in insect cells using a recombinant baculovirus.

We have cloned the human thyroid hormone receptor beta 1 (hThR beta) from the human breast cancer cell line T47D using the PCR technique. A recombinant baculovirus transfer vector pVL1392/hThR beta was constructed and the full length receptor was expressed in the insect cell line Spodoptera frugiperda (Sf9). Approx. 10-15 x 10(6) receptors are expressed/cell which implies a production level of 2.5-4.0 mg hThR beta/l of cell culture. The expressed hThR beta displayed a single class of binding sites for T3 with high affinity. Western blot analysis using a polyclonal antibody indicated that the molecular weight of the baculovirus expressed receptor is approx. 50 kDa. Crude nuclear extract of hThR beta labeled with [125I]T3 sedimented as a 4 S peak on a glycerol gradient. No receptor could be detected in the cytoplasm indicating its proper translocation to the nuclear compartment. An oligonucleotide containing a palindromic thyroid hormone response element is specifically recognized and retarded in a gel-mobility-shift assay in the presence of nuclear extract of Sf9 cells expressing hThR beta. These data suggest that hThR beta expressed in Sf9 cells is functional and displays characteristics virtually indistinguishable from those of the thyroid hormone receptor (ThR) extracted from mammalian cells. Furthermore, the data indicate that the baculovirus expression system is adequate for large-scale production of receptor for detailed structural and functional studies.

Animals↗
PubMed1991

Leakage after lateral condensation with finger spreaders and D-11-T spreaders.

The purpose of the study was to determine the leakage after lateral condensation with the use of finger spreaders and D-11-T spreaders. Fifty root canals were instrumented, and laterally condensed with gutta-percha and Grossman's cement. In 20 canals finger spreaders were used for the condensation and in a further 20 canals D-11-T spreaders were used. After 24 h in 100% humidity, the roots were painted with nail polish except for their apical 2 mm, which remained exposed. Five canals were not obturated (negative control) and five canals were obturated and the apices sealed with sticky wax (positive control). The expressed root tips were suspended in 2% methylene blue dye for 48 h. The teeth were then split longitudinally and the apical leakage measured and compared for each group. The results obtained by the positive and negative control teeth confirmed the effectiveness of the methodology used. Average dye penetration for the finger spreaders was statistically significantly less than for the D-11-T spreaders. Dye penetration of more than 0.5 mm occurred in 6 roots for the finger spreaders and in 12 roots for the D-11-T spreaders.

Dental Leakage↗
PubMed1991

Dubbo study of the elderly: sociological and cardiovascular risk factors at entry.

A prospective study of elderly Australians commenced in 1988 in Dubbo, NSW. Its goals are to identify predictors of mortality, hospitalisation and placement in long-term care, with special focus on risk factors for cardiovascular disease. The study population were non-institutionalised subjects, comprising 1237 males and 1568 females 60 years and over. This report describes the baseline findings: demographic, educational and economic data; tobacco and alcohol usage, self-medication and other habits; medical contacts and past diagnosis; prescribed medication and in study diagnosis; psychosocial variables, functional health and social support; blood lipid and lipoprotein data; blood pressure, spirometry and glucose data; heights and weights. Where comparison has been feasible, the findings in Dubbo closely resemble those obtained from the rest of Australia. The findings presented provide the basis for aetiological studies of future outcomes.

Aged↗
PubMed1991

High density lipoproteins, genetic polymorphism for apo A-I and coronary artery disease.

HDL cholesterol and apolipoprotein A-I are associated with the development of coronary artery disease (CAD). The presence of a PstI site polymorphism adjacent to the gene encoding apo A-I (known as P2) has also been shown to be associated with CAD but this relationship is controversial. A case control study was conducted in an Australian population to re-examine whether the rare P2 allele is associated with CAD. Data were derived from 159 cases of angiographically confirmed CAD and 99 healthy controls. The proportion of CAD cases carrying the P2 allele did not differ significantly from controls (11% versus 9%). In a multiple logistic regression model controlling for the effects of age, country of birth, hypertension and hypotensive drugs, body mass index and lipid variables, the P2 allele failed to predict significantly the presence of CAD (odds ratio 1.83; 95% confidence interval 0.65-5.19).

Alleles↗
PubMed1991

The Dubbo study of the health of elderly: correlates of coronary heart disease at study entry.

A prospective study of the health of elderly Australians recently commenced in Dubbo, NSW, the study population comprising 1,237 males and 1,568 females 60 years and older. The prevalence rates of coronary heart disease (CHD) and its associated risk factors have been examined in the baseline data. The age-standardized rate of CHD was 23.8/100 in males and 18.1/100 in females. The prevalence rate increased with age until 79 years in males, thereafter declining. The rate increased steadily with age in females. In a multiple logistic model, the following possible predictors of CHD were included: age, cigarette smoking, use of alcohol, exercise, religiosity, years of education, hypertension, diabetes, family history of CHD, body mass index, lipid and lipoprotein variables. The presence of CHD in males was significantly predicted by age, hypertension (odds ratio, OR = 1.40), family history (OR = 2.05), and high density lipoprotein (HDL) cholesterol (OR = 0.78). The significant predictors in females were age, years of education (OR = 0.82), hypertension (OR = 1.45), family history (OR = 1.77), serum triglycerides (OR = 1.30), and HDL cholesterol (OR = 0.73). Hypertension was found to be a stronger predictor of CHD in the younger age group (60-69 years), while diabetes was a predictor of CHD in older males (70-79 years). Our findings require confirmation in the prospective study now in progress.

Age Factors↗