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Biomedical subjects

S L Hui

Publications and source records attributed to S L Hui.

At least 73 records · Page 4Linked to original sources

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↗

Effects of age and menopause on vertebral bone density.

Vertebral bone density was assessed with dual photon absorptiometry in 280 white females, aged 19-87, without symptoms of osteoporosis. Those who had not experienced a menstrual period for at least one year were classified as postmenopausal, and those menstruating normally were deemed premenopausal. The remainder were considered perimenopausal. Regression links were fit: (1) to the entire data set, (2) to two groups by age (less than 50, 50+), (3) to three groups by age (less than 40, 40-54, 55+) and (4) to three groups by menopausal status. Only that regression which considered menopausal status had a significantly better fit than the simple linear model with slopes of +0.04% per year for the premenopausal (ns, different from zero), -1.8% per year for the perimenopausal (P less than 0.05) and -0.6% per year for the postmenopausal (P less than 0.05). These data suggest that the loss of trabecular bone is accelerated around the time of the onset of menopause, and slows somewhat thereafter, although continuing to be significant. However, the findings of this study are based on cross-sectional data, and there remains a need for prospective studies of vertebral bone around the time of menopause.

Adult↗

Effects of megakaryocyte colony-stimulating factor on terminal cytoplasmic maturation of human megakaryocytes.

Suspensions of enriched human megakaryocytes (MK) devoid of MK progenitors (CFU-MK) undergo complete cytoplasmic maturation in vitro. MK were cultured in the presence of normal human AB serum (NABS) to mimic "normal" development. The rate of maturation was not statistically altered by higher concentrations (10%-20%-30%) of NABS, or by the addition of bovine serum albumin (1.5%-3.0%), but was accelerated in the presence of aplastic anemia serum (AAS). Sera from eight different patients with severe aplastic anemia were effective in accelerating terminal differentiation. MK-CSF, a glycoprotein isolated from AAS, specifically augments MK colony formation by two- to sixfold. Similar doses of MK-CSF were ineffective in altering terminal cytoplasmic maturation. Anti-MK-CSF, a polyclonal antibody prepared against purified MK-CSF, neutralizes the ability of both purified MK-CSF and AAS to promote MK colony formation. However, AAS adsorbed with anti-MK-CSF still retained its ability to accelerate terminal differentiation. Apparently, AAS contains at least two separate humoral factors, which can regulate in vitro human megakaryocytopoiesis: MK-CSF, which stimulates proliferation of the progenitors (CFU-MK), and a maturation factor, which accelerates cytoplasmic maturation of morphologically recognizable megakaryocytes.

Anemia, Aplastic↗

Diuretic-induced laboratory abnormalities that predict ventricular ectopy.

In order to determine which of the many diuretic-induced laboratory changes might be associated with an increased risk of ventricular ectopy (VE), we performed logistic regression analyses of patient data from a large computerized medical record system. Study variables included serum Ca2+, K+, Cl-, HCO-3, glucose, cholesterol, albumin, uric acid, and hematocrit. Controlling variables included race, use of diuretics, blood pressure, smoking history, age, and weight. (In one analysis we also included cardiac drug history and evidence of pre-existing cardiovascular disease). Separate analyses were performed for males and females. For the retrospective cohort-like design, we analyzed data for 9561 patients with complete data. For the case-control design we analyzed data from 4786 patients. Diuretic usage predicted ventricular ectopy in women, but not men. Serum uric acid and hematocrit were the only significant laboratory predictors of ventricular ectopy in each of the four analyses. Abnormalities in these variables might provide an explanation for the greater incidence in sudden (and presumably arrhythmic) deaths reported in MRFIT study patients with mild hypertension.

Arrhythmias, Cardiac↗

The influence of age on bone mineral regulating hormones.

The objective of this study was to determine the effect of age on the blood levels of 1,25-dihydroxyvitamin D (1,25(OH)2D) and immunoreactive parathyroid hormone (iPTH) in normal, healthy males and females. A total of 855 normal subjects (361 males and 494 females) were studied. The results show that for healthy males, blood concentrations of 1,25(OH)2D remained essentially constant with increasing age up to age 65, and then the concentrations decreased significantly. For healthy females, 1,25(OH)2D increased up to age 65, and then decreased at a significant rate. Serum iPTH in males increased with advancing age, but the rate of increase was greater after age 65. In females a significant increase in iPTH concentrations did not occur until after age 65. Serum creatinine increased in both males and females with advancing age.

Adult↗

Delayed feedback of physician performance versus immediate reminders to perform preventive care. Effects on physician compliance.

In an academic general medicine clinic, we performed a randomized, controlled trial to compare (1) the effects of supplying monthly feedback reports of compliance with preventive care protocols by 135 internal medicine house staff with (2) the effects of specific reminders given to them at the time of patient visits. The protocols were randomly divided into two groups, A and B, and half the house staff were given feedback for Group A and half for Group B. Thus, each group served as a control for the other. Each feedback group was also randomly assigned to receive reminders for either Group A or B protocols. House staff receiving feedback more often complied with fecal occult blood testing, mammography, pneumococcal vaccination, use of metronidazole, and combined Group A and B protocols than did controls (P less than 0.01). There was also significantly more compliance with the same protocols by house staff receiving reminders, but the increase for fecal occult blood testing, pneumococcal vaccination, and combined Group A protocols was twice that seen in physicians given feedback alone. In addition, reminders alone increased compliance with oral calcium supplementation. Overall compliance with the preventive care protocols was low: 10-15% in physicians receiving neither feedback nor reminders, increasing to 15-30% in those receiving reminders. Physician compliance with suggested preventive care protocols can be increased by both delayed feedback and immediate reminders, but reminders have a greater effect.

Clinical Competence↗

Terminal cytoplasmic maturation of human megakaryocytes in vitro.

Several studies suggest that serum factors (thrombopoietins) regulate thrombopoiesis by altering the number, size, ploidy, and maturation rate of megakaryocytes (MK). Various in vivo systems have been used to quantitate these events. In this study, an in vitro system was developed to monitor terminal cytoplasmic maturation of isolated human MK. MK enriched by elutriation, which eliminated the MK progenitors, were suspended in culture with serum from either normal donors (NABS) or patients with aplastic anemia (AAS). In cultures composed of small platelet glycoprotein-positive mononuclear cells and morphologically immature MK, development was characterized by sequential shifts in MK through morphologically recognizable maturation stages I, II, III, and IV over eight days of incubation (I and II only; then I, II, III; II, III, IV; III and IV; then IV only). Platelet formation coincided with the appearances of stage IV cells. Cultures composed of a mixture of all stages followed a similar maturation sequence, only at an accelerated rate. AAS resulted in the more rapid appearances of the mature cells in either system. This study indicates that human MK can undergo terminal cytoplasmic maturation in vitro, and that altering culture conditions (AAS for NABS) can accelerate the rate of maturation. Three major events occur during megakaryocytopoiesis: proliferation of the progenitor cells, polyploidization, and cytoplasmic maturation. Now it is possible to study the terminal steps of differentiation independent of proliferative events.

Anemia, Aplastic↗

Bone mass and sex steroid concentrations in postmenopausal Caucasian diabetics.

We have evaluated radial bone mass and sex steroid concentrations in a group of postmenopausal white type 2 diabetics, that group at greatest risk of developing osteoporosis. The linear regression of midshaft bone mass on age for 79 patients showed a rate of loss about half the rate for normals. These data suggest that bone is lost at a slower rate by this group, and the difference cannot be explained by obesity or glucose control alone. A subset of 40 of these subjects was chosen for further study. As expected, these women had significantly higher bone mass than normals; in addition, they were significantly heavier (82.4 +/- 2.7 kg v 65.3 +/- 1.8 kg, P less than .001), and had higher body mass index (32.1 +/- 1.0 kg/m2 v 25.2 +/- 0.6 kg/m2, P less than .001), than controls. Serum estrone concentrations were higher (49.8 +/- 3.7 pg/mL v 28.5 +/- 1.8 pg/mL, P less than .001); serum androstenedione (0.28 +/- 0.03 ng/mL v 0.51 +/- 0.04 ng/mL, P less than .001), and serum testosterone (0.18 +/- 0.02 ng/mL v 0.26 +/- 0.02 ng/mL, P less than .02) concentrations were lower among diabetics than controls. Serum estradiol (15.1 +/- 1.7 pg/mL v 15.3 +/- 1.0 pg/mL, P greater than .5) was not significantly different. Multiple regression analysis indicates that the excess level of estrone concentration among diabetics increased with the degree of obesity. The explanation for the lower concentration of the other sex steroids among diabetics is not known.

Aged↗