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Biomedical subjects

S L Hui

Publications and source records attributed to S L Hui.

At least 19 recordsLinked to original sources

Role of physical activity in the development of skeletal mass in children.

A group of 118 children, aged 5.3-14 years, were enrolled in a prospective study of calcium supplementation and bone mass. At entry to the study, questionnaires regarding the child's usual physical activity were administered to the children and their mothers. Repeated activity assessments at 6 month intervals indicated good within-person agreement for total activity and for most individual activities. Consistent positive associations were observed between bone mineral densities (BMD) in the radius, spine, and hip and most activities. A summary measure (total hours of weight-bearing activity) was significantly related to BMD in the radius and hip, independently of age or gender effects. Self-reported sports and play activities were associated with BMD, but neither time spent watching television nor hours of physical education classes were associated either positively or negatively with skeletal mass. These data suggest that important increments in skeletal mass may result from physical activity during childhood.

Adolescent

Validation techniques for logistic regression models.

This paper presents a comprehensive approach to the validation of logistic prediction models. It reviews measures of overall goodness-of-fit, and indices of calibration and refinement. Using a model-based approach developed by Cox, we adapt logistic regression diagnostic techniques for use in model validation. This allows identification of problematic predictor variables in the prediction model as well as influential observations in the validation data that adversely affect the fit of the model. In appropriate situations, recommendations are made for correction of models that provide poor fit.

Benzothiadiazines

Practice randomization and clinical research. The Indiana experience.

Thoughtful preparation of a research laboratory is an early step in designing a program for scientific investigation. The Division of General Internal Medicine at Indiana University has maintained a "laboratory" for outpatient clinical investigation for more than 15 years. In this report, we describe the structure and function of the General Medicine Practice in the Regenstrief Health Center on the campus of the Indiana University School of Medicine in Indianapolis. Specifically, we discuss the ongoing random allocation of subjects, the local resources for data management and tracking of patients' use of clinical services, and how combining this information system into a randomized primary care system has fostered successful ventures in clinical investigation.

Health Services Research

Predictors of bone mass in perimenopausal women. A prospective study of clinical data using photon absorptiometry.

STUDY OBJECTIVE: To determine whether clinically available data on risk factors are adequate to identify perimenopausal women with either low or high bone mass. DESIGN: Cross-sectional observational study of a cohort of perimenopausal women (mean age, 50.8 years). SETTING: Community volunteers in a university hospital. SUBJECTS: One hundred twenty-four white volunteers established as perimenopausal by history and serum concentrations of estrogens and follicle-stimulating hormone. MEASUREMENTS AND MAIN RESULTS: Models were constructed to predict bone mass in the radius, lumbar spine, and hip using risk factors (age, height, weight, calcium and caffeine intake, alcohol and tobacco use, and urinary markers of bone turnover). Although highly significant predictive models were developed for all skeletal sites, none of the models correctly identified more than 70% of women with low bone mass at any site. However, for the radius, a model was constructed that never overestimated bone mass by more than 0.10 g/cm. A small subgroup (7%) with short stature, low body weight, low calcium intake, and who were heavy smokers always had low radial bone mass. Using these models, about 30% of our population could be assessed without bone mass measurements. Predictions for the spine and femur were less efficient, suggesting that direct measurements are required if therapy decisions are to be based on bone mass at these sites. CONCLUSIONS: Risk factors for osteoporosis are of limited use in identifying women with low bone mass around the time of menopause. Measurements of bone mass are probably necessary if the risk for osteoporosis is to be the basis for deciding on estrogen replacement therapy.

Absorptiometry, Photon

The contribution of bone loss to postmenopausal osteoporosis.

We have addressed the relative importance of peak bone mass and subsequent rate of loss in determining postmenopausal women's bone mass in old age, by examining longitudinal measurements of radial mid-shaft bone mass on various samples of healthy white postmenopausal women. Using both the variance estimate of age-specific rates of bone loss and the population variance in bone mass, we determined that rates of loss could contribute importantly to future bone mass. However, since we found a small negative correlation between initial bone mass and rate of loss, it was necessary to estimate the effect of bone loss as the complement of the contribution of initial bone mass. We found that the influence of bone loss (relative to initial bone mass) increases as the women age, such that by about age 70, the contribution of initial bone mass and rate of loss approached equality. However, estimated rates of bone loss were not very stable over time, so it was difficult to identify long-term 'fast-losers'. We conclude that the rate of postmenopausal bone loss is an important contributor to osteoporosis at old age, but it is difficult to identify long-term fast-losers, thereby reducing the clinical value of assessments of rates of change in bone mass early in the postmenopause.

Aged

Bone mass and anthropometric measurements in adult females.

Bone mass and anthropometrics were measured in 342 adult female twins, aged 25-79 (mean = 44.1 years) for the purpose of: (1) identifying which anthropometric measurements were most strongly associated with bone mass at various skeletal sites, and (2) determining the accuracy of combinations of these measurements in the prediction of bone mass. Among the eight skinfolds measured, the subscapular site was more strongly correlated with all bone mass measurements than any other skinfold. Similarly, calf circumference (among four sites) and biacromial width (among five frame size measurements) provided the strongest correlations within these groups of anthropometrics with all bone sites. The somewhat surprising consistency of these results was then tested in multivariable models for the prediction of bone mass. For the entire study group, each of the anthropometric measurements (subscapular skinfold, calf circumference and biacromial width) were independent, significant predictors of bone mass, even when height, weight and age were included in the models. These data suggest that frame size, muscularity and adiposity have independent effects on the skeleton, and that single measurements of each of these anthropometric characteristics are associated with all skeletal sites.

Adipose Tissue

Ibuprofen-associated renal impairment in a large general internal medicine practice.

The authors determined the incidence of ibuprofen-associated renal impairment and risk factors for its development in 1908 patients treated with ibuprofen using data from a computerized medical records system. Renal impairment occurred in 343 patients (18%). Multivariable analysis revealed six independent predictors of renal impairment: age, prior renal insufficiency, coronary artery disease, male gender, elevated systolic blood pressure, and diuretic use. They then tested the degree to which ibuprofen contributed to the development of renal impairment by evaluating a control group of 3933 acetaminophen recipients. Neither ibuprofen nor acetaminophen was among the independent predictors of risk when all patients were considered (adjusted odds ratio, 1.05; 95% Cl, 0.88-1.26). However, two subsets of at risk patients had an ibuprofen effect: patients greater than or equal to 65 years of age who received ibuprofen were at greater risk of renal impairment as compared to acetaminophen recipients (adjusted odds ratio, 1.34; 95% Cl, 1.05 to 1.72) as were patients with coronary artery disease (adjusted odds ratio, 2.54; 95% Cl, 1.38 to 4.68). Their results suggest that elderly patients and patients with coronary artery disease are at risk for ibuprofen-associated renal impairment and therefore should have their renal function monitored when ibuprofen and possibly other nonsteroidal anti-inflammatory drugs are prescribed.

Acetaminophen

Baseline measurement of bone mass predicts fracture in white women.

STUDY OBJECTIVE: To determine if a single bone mass measurement of the radius is predictive of future fractures at any site. DESIGN: Observational study of a cohort of free-living subjects and a cohort of retirement-home residents with an average follow-up of 6.7 years and 5.5 years, respectively (range, 1 to 15 years for both cohorts). SETTING: General community and a retirement home. SUBJECTS: Volunteer sample of white women (386 free-living and 135 living in a retirement home) who were free of disease and were not receiving medication known to affect bone metabolism. In terms of physical condition subjects ranged from the totally independent to the wheelchair-bound. MEASUREMENTS AND MAIN RESULTS: A radial bone mass measurement was done at the initial visit. Subsequent non-spine fractures were reported by the subjects at follow-up visits, which were less than a year apart in most cases, and verified with medical records. Cox regression was used to model time to first fracture as a function of age and bone mass. These analyses showed that for every 0.1 g/cm decrement in bone mass, the relative risk of fracture was 2.2 (CI, 1.7 to 2.8) for the free-living and 1.5 (CI, 1.2 to 1.9) for the retirement-home residents. Baseline age did not predict the risk of fracture in either cohort, and controlling for baseline age did not reduce the relative-risk estimates of bone mass. Similar analyses also showed that bone mass was a statistically significant predictor for first hip fractures (n = 30) among the nursing-home residents (relative risk, 1.9; CI, 1.4 to 2.7) and first forearm fractures (n = 10) among the free living (relative risk, 3.6; CI, 1.9 to 6.8). For both cohorts, the 8-year probability of any nonspine fracture was about 80% for subjects with initial bone mass less than 0.6 g/cm and was less than 10% for subjects with initial bone mass greater than 0.8 g/cm. Similarly, those in the retirement home with bone mass below 0.6 g/cm had a 6-year probability of hip fracture of 43%, compared with a 17% risk for those with greater bone mass. CONCLUSION: A single bone mass measurement of the radius is predictive of future nonspine fractures at all sites, and at both the forearm and the hip. Baseline age was not a significant predictor of fracture within either cohort. Relative-risk estimates were not dissimilar across fracture sites.

Adult

Cigarette smoking, obesity, and bone mass.

This study was designed to assess the effects of smoking on bone mass and bone loss and to ascertain whether these effects are independent of effects on adiposity and hormone concentrations. A total of 84 healthy, peri- and postmenopausal women were studied prospectively over 3 1/2 years. Heavy smokers had significantly (p less than 0.05) lower radial and vertebral bone mineral content than light or nonsmokers (who did not differ from each other). In regression models, which contained measurements of obesity, pack-years smoking remained a significant predictor of bone mass. However, there were no detectable effects of smoking on rates of bone loss at any site. Smokers appear to be at greater risk of osteoporosis due to their lower bone mass. However, this reduced bone mass is already present around the time of menopause, and rates of bone loss during this period do not appear to be influenced by smoking. Furthermore, we have previously shown in this population that menopausal serum estrogen concentrations (which determine rates of bone loss) do not differ between the smokers and nonsmokers. Further studies of larger groups are required to determine whether small differences in bone loss may exist, since the power to detect such differences was not ideal in this study.

Aging

Variance estimation for medical decision analysis.

We have derived the variance of an expected utility for a probability tree in medical decision analysis based on a Taylor series approximation of the expected utility as a function of the probability and utility values used in the decision tree. The resulting variance estimate is an algebraic expression of the variances associated with the probability and utility estimates used. We also derive expressions for the case where the input parameter estimates are not independent. We discuss the choice of input parameters and their variance estimates and give an example that compares two protocols for the treatment of chlamydial infection.

Analysis of Variance

Liposome-encapsulated 3H-5FU in rabbits.

We compared the pharmacokinetics of liposome-encapsulated tritiated 5-fluorouracil (3H-5FU-Lipo) to 3H-5FU in buffered saline (3H-5FU-PBS) after subconjunctival or intravitreal injection into rabbit eyes. Liposomes were prepared using phosphatidylcholine, phosphatidic acid, and alpha-tocopherol. Following a unilateral subconjunctival injection of either 3H-5FU-Lipo or 3H-5FU-PBS, rabbits were sacrificed at 0.5, 1, 4, and 8 hours. Significantly higher (p less than 0.05) drug levels were achieved with the encapsulated drug in the vitreous at all four time points and in the aqueous at three of four time points. Following bilateral intravitreal injections of 500 micrograms of 5FU in 0.1 ml, as either 3H-5FU-Lipo or 3H-5FU-PBS injected rabbits were sacrificed at 0, 6, 12, 24, and 48 hours. Vitreal drug levels were significantly higher (p less than 0.05) with encapsulated drug at all time points from 6 hours on. At 48 hours, the vitreal level with the encapsulated drug was 578 +/- 0.23 micrograms/ml compared with 1.06 +/- 0.07 micrograms/ml for 3H-5FU-PBS.

Analysis of Variance

Serum from patients with various thrombopoietic disorders alters terminal cytoplasmic maturation of human megakaryocytes in vitro.

Human bone marrow was depleted of progenitors (CFU-MK), but enriched for recognizable megakaryocytes (MK), and placed in cultures with serum from either normal donors (NABS) or patients with primary (PTS) or secondary (STS) thrombocytosis, autoimmune thrombocytopenia (ATS) or aplastic anemia (AAS). Mean MK diameters shifted during the 3-4 days of incubation. Endomitotic figure were visible and mean ploidy increased slightly during cytoplasmic maturation, where decreases in immature cells (stages 1 and 2) were accompanied by increases in the mature MK (stages 3 and 4). Cytoplasmic maturation was faster in AAS, ATS and STS than PTS or NABS; mean size and ploidy were similar in all cultures. Recognizable MK were not forced to undergo additional endoreduplication in response to stimulation. Only AAS augmented MK colony formation, which indicated that at least two humoral factors can regulate megakaryocytopoiesis at separate levels, the progenitors and morphologically recognizable MK.

Anemia, Aplastic

Computer predictions of abnormal test results. Effects on outpatient testing.

We developed statistical equations to predict abnormalities on eight commonly ordered diagnostic tests and we gave the predictions to 112 physicians practicing in an academic internal medicine practice. Half of each physician's patients were randomized to intervention status. All diagnostic tests were ordered by microcomputer, and when a physician ordered one of the eight study tests for an intervention patient, the computer displayed the probability (0% to 100%) that the test would be positive for the main abnormality being tested for. The physician could then cancel the test if desired. During a six-month controlled trial, when there were more than 15,000 scheduled patient visits, patient charges for the eight study tests were 8.8% less for the intervention patients. The largest reductions (greater than 10%) were for serum electrolyte level tests and complete blood cell counts, the two most commonly ordered tests. Physicians ordered fewer low-probability tests for intervention patients than for controls, suggesting that with timely predictive information, physicians can target tests to higher-risk patients.

Clinical Laboratory Techniques

Age and bone mass as predictors of fracture in a prospective study.

To study the effect of bone mass on the risk of fracture, we followed 521 Caucasian women over an average of 6.5 yr and took repeated bone mass measurements at the radius. We observed 138 nonspinal fractures in 3,388 person-yr. The person-years of follow-up and the incident fractures were cross-classified by age and bone mass. The incidence of fracture was then fitted to a log-linear model in age and bone mass. It was found that incidence of fracture increased with both increasing age and decreasing radius bone mass. When subsets of fractures were examined it was found that age was a stronger predictor of hip fractures, whereas midshaft radius bone mass was a stronger predictor of fractures at the distal forearm. We concluded that bone mass is a useful predictor of fractures but that other age-related factors associated with fractures need to be identified.

Adult

Sex steroids and bone mass. A study of changes about the time of menopause.

To examine the relationships between bone loss and sex steroids, 84 peri- and postmenopausal women were studied at 4-mo intervals for 3 yr. At each visit, measurements were made of bone mass at the midshaft and distal radius, of steroids, of gonadotropins, and of bone gla protein (BGP). Bone loss was approximately 1% per yr among late perimenopausal and postmenopausal groups, whereas the early perimenopausal group lost no bone. Mean serum estrogen and BGP concentrations predicted rates of bone loss. BGP was negatively correlated with the rate of bone loss (r = -0.45) and with mean estrogen concentrations (r = -0.40). Multivariate regressions showed estrogen concentrations to be strong independent predictors of the slope of bone mass over time. When BGP concentrations were added to the models, the significance of estrogen was reduced, suggesting that a portion of the estrogen effect was mediated through effects on rates of bone remodelling.

Adult

Free estradiol, free testosterone, and sex hormone-binding globulin in perimenopausal women.

To determine whether menstrual status had an effect on plasma sex hormone-binding globulin (SHBG) capacity and nonprotein-bound estradiol (% free E2) and testosterone (% free T), we measured these as well as plasma FSH, total E2, and T and the MCRs of E2 and T in a group of 78 perimenopausal women. The women were allocated to 4 groups: women with cycles whose plasma FSH level was less than 40 mIU/mL (A; n = 16), women with cycles whose plasma FSH level was greater than 40 mIU/mL (B; n = 19), women who were amenorrheic for less than 1 yr (C; n = 13), and women who were amenorrheic for more than 1 yr (D; n = 30). The mean plasma SHBG values were 51.4 +/- 5.7 (+/- SE), 48.3 +/- 4.3, 45.9 +/- 5.4, and 51.1 +/- 3.7 nM in groups 1-4 respectively, and were not significantly different from one another. The mean % free E2 and % free T values also were not different between the groups. However, the mean total E2 and free E2 (% free E2 X E2/100) concentrations were significantly (P less than 0.05) higher in both groups A and B than in groups C and D. The E2 concentration was also higher in group A than in group B. There were strong correlations between the E2 and free E2 concentrations between the T and free T (% free T X T/100); (P less than 0.0001) concentrations, between SHBG capacity and weight, and between the MCRs of both E2 and T and % free E2 and % free T. In normal women, the menopause is not associated with changes in SHBG or % free steroids. Hence, the measurement of E2 could be used to predict the mass of free E2 in these women.

Adult

A general approach to analyzing epidemiologic data that contain misclassification errors.

Misclassification is a common source of bias and reduced efficiency in the analysis of discrete data. Several methods have been proposed to adjust for misclassification using information on error rates (i) gathered by resampling the study population, (ii) gathered by sampling a separate population, or (iii) assumed a priori. We present unified methods for incorporating these types of information into analyses based on log-linear models and maximum likelihood estimation. General variance expressions are developed. Examples from epidemiologic studies are used to demonstrate the proposed methodology.

Analysis of Variance