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R S Yang

Publications and source records attributed to R S Yang.

At least 19 recordsLinked to original sources
PubMed2006

Bone mineral density in long-term Chinese heart transplant recipients: a cross-sectional study.

Osteoporosis, which usually peaks during 6 to 12 months after transplantation, remains an important concern after heart transplantation. Immunosuppressants contribute to this phenomenon. Glucocorticoids are well documented to cause bone loss, but the role of cyclosporine (CsA) remains controversial, especially among long-term recipients on low doses of steroid. We herein report a cross-sectional study of bone mineral density (BMD) among long-term Chinese heart transplant recipients. We enrolled 41 patients of mean age 50.15 +/- 13.58 years with a mean follow-up of 57.02 months. Lumbar spine and femoral neck BMD were measured by dual energy x-ray absorptiometry. Trough CsA levels (C(0)) and markers of mineral metabolism, including bone-specific alkaline phosphatase and urinary N-telopeptide, were determined by immunoassay. Sixty six percent of subjects showed bone loss at the femoral neck, significantly more than those in the lumbar spine. Those receiving a higher CsA dosage (<2.5 mg/kg/d) showed greater femoral neck BMD, but lower serum creatinine values. Our results demonstrated that bone loss remains long after transplantation, though bone markers are within normal limits.

Adult↗
PubMed2005

Home-based trunk-strengthening exercise for osteoporotic and osteopenic postmenopausal women without fracture--a pilot study.

OBJECTIVES: To investigate whether a 12-week home-based programme of trunk-strengthening exercise could benefit spinal mobility, function and quality of life for osteoporotic and osteopenic postmenopausal women without fracture. DESIGNS: Randomized controlled clinical trial. SETTING: Department of Physical Therapy in National Taiwan University Hospital. SUBJECTS: Twenty-eight postmenopausal women (mean age 60.3+/-9.3 years) diagnosed with osteoporosis or osteopenia without fracture history were recruited for this study. Subjects were randomly assigned into exercise or control groups, each consisting of 14 subjects. INTERVENTIONS: The 12-week exercise programme included strengthening routines for the trunk extensor and flexor muscles. The subjects performed three sets of 10 repetitions for each of the exercises, with programmes carried out three times per day at home. MAIN OUTCOME MEASUREMENTS: Muscular strength, spinal range of motion (ROM) and motion velocity, Oswestry Disability Questionnaire (ODQ) and quality of life (QOL) were measured before the start and after completion of the exercise programme. RESULTS: Statistically significant improvements were demonstrated in spinal ROM and motion velocity in the sagittal and frontal planes for the exercise group (p<0.05). Further, the strength of the trunk flexors and extensors increased after exercise training (p<0.05). ODQ measure was significantly reduced in the exercise group (p<0.05), while the controls showed no significant change. Subjects in the exercise group showed better satisfaction in some domains of the Short-Form-36 Health Survey quality of life questionnaire (p<0.05). CONCLUSIONS: This 12-week home-based trunk-strengthening exercise programme could improve trunk mobility and strength, and enhance QOL in osteoporotic and osteopenic postmenopausal women without vertebral fracture. Future study should recruit more cases or more severe subjects to verify the results.

Bone Diseases, Metabolic↗
PubMed2004

High incidence rate of hip fracture in Taiwan: estimated from a nationwide health insurance database.

The objective of this study was to describe the incidence rate of hip fracture from 1996 to 2000 in Taiwan, based on an inpatient database of the National Health Insurance Program. A total of 54,199 patients, who had a first-time admission for a diagnosis of hip fracture (ICD9 code 820.0 through 820.9, 820.21, 820.22, and 820.31) on discharge from January 1996 through December 2000 and aged 50 to 100 years, were identified and included in the study. The results showed that the age-specific incidence rates of hip fractures were higher with increasing age in both genders, in an exponential manner after 65 years of age. The incidence was 1.6 times higher and rose about 5 years earlier among women than among men. Thus in these 5 years the age-adjusted incidence rates (95% confidence interval) of hip fracture in Taiwan were 225 (95% CI, 188-263) per 100,000 in men and 505 (95% CI, 423-585) per 100,000 in women (adjusted to US white population of 1989), as compared with US white rate of 187 in men and 535 in women. More than half of the fractures were peritrochanteric, and the recorded cause in most cases was a fall on the same level, from slipping, tripping, or stumbling (ICD9 E885). A total of 37.8% patients had hip hemiarthroplasty, 51.2% had open reduction of fracture with internal fixation, and 10.5% had closed reduction of fracture with internal fixation. We concluded that, using the data from a nationwide health insurance database of Taiwan, we found a high annual incidence rate of hip fracture for both men and women in 5 consecutive years. These incidence rates were higher than other reports on Chinese populations reported in the past 10 years and similar to that of Western countries. With the rapid aging of the populations of Taiwan and other Asian countries in the years to come, our results clearly demonstrated the impact of osteoporosis and hip fracture in this region.

Age Factors↗
PubMed2003

Effects of different exercise modes on mineralization, structure, and biomechanical properties of growing bone.

Weight bearing during exercise plays an important role in improving the mechanical properties of bone. The effect on bone of non-weight-bearing exercise such as swimming remains controversial. To investigate the effects of exercise mode on growing bone, 29 male Wistar rats (7 wk old) were randomly assigned to a running exercise group (Run, n = 9), a swimming exercise group (Swim, n = 10), or a nonexercise control group (Con, n = 10). During an 8-wk training session (20-60 min/day, 5 days/wk), the Run rats were trained at progressively increasing running speeds (12-22 m/min), and weights attached to the tail of the Swim rats were progressively increased from 0 to 2% of their body weight. The bone mineral density of the proximal tibiae of the Run rats was significantly higher than in the Swim (P < 0.05). Femoral wet weights of the two exercise groups were significantly higher than in the control group (P < 0.05). Interestingly, the percent difference between the tissue wet weight and dry weight (water content ratio), which is related to bone mechanical properties, was significantly higher in the tibiae of the Swim rats and the femora of both exercise groups compared with controls (P < 0.05). Extrinsic as well as intrinsic biomechanical material properties were measured in a three-point bending test. Bone mechanical properties of the tibiae and femora of rats in the Swim and Run groups were significantly greater than those in the control group (P < 0.05). In summary, different modes of exercise may benefit bone mechanical properties in different ways. The specific effects of swimming exercise (non-weight-bearing exercise) on bone require further study.

Algorithms↗
PubMed2002

Spinal performance and functional impairment in postmenopausal women with osteoporosis and osteopenia without vertebral fracture.

Previous studies have paid much attention to the impact on functional impairment or quality of life from vertebral fractures secondary to osteoporosis, but little research has addressed the function of osteoporotic women without fractures. The purposes of this study were: (1) to describe spinal performance and functional impairment in postmenopausal women with osteoporosis and osteopenia without vertebral fracture, and (2) to investigate the relationship between them. Thirty postmenopausal women diagnosed as having osteoporosis or osteopenia were recruited who fulfilled the following criteria: (1) menopause for at least 6 months; (2) no vertebral fracture; (3) no medication that would interfere with calcium intake. Measurements included assessment of functional impairment and spinal performance including trunk extension/flexion isokinetic strength, spinal range of motion (ROM) and movement velocity in three planes (sagittal, frontal and transverse). The results showed that spinal ROM and velocity were significantly reduced in the osteoporosis group compared with the osteopenia group ( p<0.05), but no significant difference in trunk strength was shown. Functional impairment level showed a slight difference between the two groups ( p = 0.042). There was a significant correlation between spinal ROM and motion velocity with bone mineral density; however, functional impairment correlated with motion velocity only in the transverse plane (trunk rotation) ( p<0.05). Spinal strength did not show any correlation with other parameters. It was concluded that spinal motion performance declined and functional impairment increased in relation to the severity of bone mineral loss in postmenopausal women without vertebral fracture, but their physical performance was not correlated with functional impairments.

Aged↗
PubMed2002

Effects of caffeine and exercise on the development of bone: a densitometric and histomorphometric study in young Wistar rats.

High doses of caffeine will induce calcium loss and influence the normal development of bone, whereas the proper exercise has positive effects on bone metabolism. This study investigated the possible effects of exercise to antagonize the caffeine-induced impairment of bone development in young male Wistar rats. A total of 32 male rats (5 weeks old) were divided randomly into four groups: group 1 rats were fed caffeine; group 2 rats were prescribed an exercise program; group 3 rats were fed caffeine and prescribed an exercise program; and group 4 rats served as the control group. The caffeine was fed via the animals' dietary water and the dosage was 10 mg/100 g body weight per day, 3 days a week. The exercise program was carried out on a treadmill for 10 weeks (5 days/week, 1 h/day, 70% VO(2)max). Body weight was measured weekly. After sacrifice, the tibia length was measured and the tibia was processed for histomorphometric analysis. Bone mineral density was measured by dual-energy X-ray absorptiometer at three different sites of the tibia. In addition, the calcium content of the right femur was measured by atomic absorptiometry. The results showed that both exercise and caffeine significantly lowered the body weight gain. Rats fed with caffeine (groups 1 and 3) had a significantly longer tibia as compared with the non-caffeine-fed rats (groups 2 and 4) (p = 0.0149). The histomorphometry study showed that thickness of the growth plate in the proliferative zone, the hypertrophic zone, and total growth plate was greater in caffeine-fed groups than in non-caffeine-fed groups. The cell number in the proliferative zone was higher in the caffeine-fed groups. Area ratio of trabeculae in the primary spongiosa of rats in groups 1 and 2 were significantly greater than the control group. Caffeine feeding (groups 1 and 3) induced a lower area ratio of bone trabeculae in the secondary spongiosa, whereas exercise training (groups 2 and 3) increased the thickness of the trabeculae. The exercise program counteracted the negative effect of caffeine on the trabecular thickness, but did not correct the trabecular bone ratio. The bone mineral density (BMD) of the tibia was significantly lower in caffeine-fed rats, and the exercise program did not show any counteracting effect on the caffeine-induced BMD reduction. The calcium content assay showed that caffeine feeding decreased the weight and total calcium content of the femur. Again this exercise program did not counterbalance the negative effects of caffeine. In conclusion, high doses of caffeine seemed to stimulate the growth of long bone. However, it caused more serious negative effects on bone, including bone mineral loss, lower BMD, and lower calcium content. Exercise training at 70% VO(2)max had little antagonizing effect on caffeine-induced impairment of bone formation. Therefore, the best way to prevent caffeine-induced negative effects on bone development is to lower caffeine exposure.

Animals↗
PubMed2001

Effects of gender and age differences on the distribution of bone content in the third lumbar vertebra.

STUDY DESIGN: A cross-sectional study on the distribution of bone mineral content in the third lumbar vertebrae. OBJECTIVES: To evaluate the effects of age and gender on the distribution of bone mineral content in the third lumbar vertebrae. SUMMARY OF BACKGROUND DATA: Compression fractures occur mainly at the vertebral body. Variations in the distribution of bone mass in a vertebra, if undefined, may bias the ability of the acquired bone mineral density values, which was usually measured posteroanteriorly, to predict the risk of fractures. METHODS: The bone mineral content of the whole L3, including the L3 vertebral body and the posterior segment, was measured using a lateral approach with a dual energy radiograph absorptiometer on 177 healthy Taiwanese adults including 65 men and 55 premenopausal and 57 postmenopausal women. RESULTS: The proportion of bone mineral content in the vertebral body was significantly lower in premenopausal women than in age-matched men (39.1 +/- 0.9% vs. 50.0 +/- 1.7%, P < 0.0001). Furthermore, whereas postmenopausal women showed a decreased proportion of bone mineral content in the vertebral body with increased age (about -0.0022 per year, P = 0.0001), premenopausal women and men showed a sustained proportion. CONCLUSIONS: The proportion of bone mineral content distributed in the body of L3 vertebrae was lower in women than in men. The discrepancy of this parameter between the genders was even larger with increased ages.

Absorptiometry, Photon↗
PubMed2001

A clonal growth model: time-course simulations of liver foci growth following penta- or hexachlorobenzene treatment in a medium-term bioassay.

A combination of experimental and simulation approaches were used to analyze the clonal growth of preneoplastic, enzyme-altered foci during liver carcinogenesis in an initiation-promotion regimen. Male Fisher 344 rats, 8 weeks of age, were initiated with a single dose (200 mg/kg, i.p.) of diethylnitrosamine (DEN). Beginning 2 weeks later, animals were exposed to daily gavage consisting of 0.1 mmol/kg pentachlorobenzene (PECB) or hexachlorobenzene (HCB) in corn oil vehicle for 6 weeks. Partial hepatectomy was performed 3 weeks after initiation. Experimental data including liver weight, hepatocyte density (number of hepatocytes/unit volume), 5-bromo-2'-deoxyuridine-labeling index for analysis of cell division rate, and number and volume of glutathione-S-transferase pi-positive foci were collected 23, 26, 28, 47, or 56 days after initiation. Model parameters describing liver growth were obtained directly from the experimental data. The probability of mutation/division of normal cells and the growth rate of initiated cells were inferred by a comparison of model outcomes with the observed time courses of foci development. To describe the time-dependent increases in foci volume and the concomitant reduction of foci number observed in all treatment groups, the calibrated model for the DEN controls incorporated the hypothesis of two initiated cell populations (referred to as A and B cells) within the framework of the two-stage model. The B cells are initiated cells that have a selective growth advantage under conditions that inhibit the growth of A cells and normal hepatocytes. The parameter values defined in the DEN controls were used to evaluate experiments involving the administration of PECB or HCB. Both PECB and HCB caused a significant increase in foci volume compared with the DEN controls. HCB treatments resulted in increased proliferation of normal hepatocytes, which was not observed for PECB under the same treatment regimen. The best description of the data resulted from the model incorporating the hypothesis that PECB and HCB promoted the growth of foci via increased net growth rates of B cells. We present here a biologically based clonal growth simulation platform to describe the growth of preneoplastic foci under experimental manipulations of initiation-promotion studies. This simulation work is an example of quantitative approaches that could be useful for the analysis of other initiation-promotion studies.

Animals↗
PubMed2001

Pharmacokinetics, metabolism, and carcinogenicity of arsenic.

The carcinogenicity of arsenic in humans has been unambiguously demonstrated in a variety of epidemiological studies encompassing geographically diverse study populations and multiple exposure scenarios. Despite the abundance of human data, our knowledge of the mechanism(s) responsible for the carcinogenic effects of arsenic remains incomplete. A deeper understanding of these mechanisms is highly dependent on the development of appropriate experimental models, both in vitro and in vivo, for future mechanistic investigations. Suitable in vitro models would facilitate further investigation of the critical chemical species (arsenate/arsenite/MMA/DMA) involved in the carcinogenic process, as well as the evaluation of the generation and role of ROS. Mechanisms underlying the clastogenic effects of arsenic, its role in modulating DNA methylation, and the phenomenon of inducible tolerance could all be more completely investigated using in vitro models. The mechanisms involved in arsenic's inhibition of ubiquitin-mediated proteolysis demand further attention, particularly with respect to its effects on cell proliferation and DNA repair. Exploration of the mechanisms responsible for the protective or anticarcinogenic effects of arsenic could also enhance our understanding of the cellular and molecular interactions that influence its carcinogenicity. In addition, appropriate in vivo models must be developed that consider the action of arsenic as a promoter and/or progressor. In vivo models that allow further investigation of the comutagenic effects of arsenic are also especially necessary. Such models may employ initiation-promotion-progression bioassays or transgenic animals. Both in vitro and in vivo models have the potential to greatly enhance our current understanding of the cellular and molecular interactions of arsenic and its metabolites in target tissues. However, refinement of our knowledge of the mechanistic aspects of arsenic carcinogenicity is not alone sufficient; an understanding of the pharmacokinetics and target tissue doses of the critical chemical species is essential. Additionally, a more thorough characterization of species differences in the tissue kinetics of arsenic and its methylated metabolites would facilitate the development of more accurate and relevant PBPK models. Improved models could be used to further investigate the existence of a methylation threshold for arsenic and its relevance to arsenic carcinogenicity in humans. The significance of alterations in relative tissue concentrations of SAM and SAH deserves further attention, particularly with respect to their role in modulating methyltransferases involved in arsenic metabolism and DNA methylation. The importance of genetic polymorphisms and nutrition in influencing methyltransferase activities must not be overlooked. In vivo models are necessary to evaluate these factors; transgenic or knockout models would be particularly useful in the investigation of methylation polymorphisms. Further evaluation of methylation polymorphisms in human populations is also warranted. Other in vivo models incorporating dietary manipulation could provide valuable insight into the role of nutrition in the carcinogenicity of arsenic. With more complete knowledge of the pharmacokinetics of arsenic metabolism and the mechanisms associated with its carcinogenic effects, development of more reliable risk assessment strategies are possible. Integration of data, both pharmacokinetic and mechanistic in nature, will lead to more accurate descriptions of the interactions that occur between the active chemical species and cellular constituents which lead to the development of cancer. This knowledge, in turn, will facilitate the development of more accurate and reliable risk assessment strategies for arsenic.

Animals↗
PubMed2001

Assessing interaction thresholds for trichloroethylene in combination with tetrachloroethylene and 1,1,1-trichloroethane using gas uptake studies and PBPK modeling.

The volatile organic solvents trichloroethylene (TCE), tetrachloroethylene (perchloroethylene, PERC), and 1,1,1-trichloroethane (methylchloroform, MC) are widely distributed environmental pollutants and common contaminants of many chemical waste sites. To investigate the mode of pharmacokinetic interactions among TCE, PERC, and MC and to calculate defined "interaction thresholds", gas-uptake experiments were performed using a closed-chamber exposure system. In each experiment, two rats (Fischer 344, male, 8-9 weeks old) were exposed to different initial concentrations of TCE, PERC, and MC, applied singly or as a mixture, and their concentration in the gas phase of the chamber was monitored over a period of 6 h. A physiologically based pharmacokinetic (PBPK) model was developed to test multiple mechanisms of inhibitory interactions, i.e., competitive, non-competitive, or uncompetitive. All mixture exposure data were accurately described by a system of equations in which a PBPK model was provided for each chemical and each was regarded as an inhibitor of the others' metabolism. Sensitivity-analysis techniques were used to investigate the impact of key parameters on model output and optimize experimental design. Model simulations indicated that, among these three chemicals, the inhibition was competitive. The PBPK model was extended to assess occupationally relevant exposures at or below the current threshold-limit values (TLVs). Based on 10% elevation in TCE blood levels as a criterion for significant interaction and assuming TCE exposure is set at TLV of 50 ppm, the calculated interaction thresholds for PERC and MC were 25 and 135 ppm, respectively. TLV exposures to binary TCE/PERC mixture were below the 10% significance level. The interaction threshold for TCE and MC co-exposure would be reached at 50 and 175 ppm, respectively. Such interactive PBPK models should be of value in risk assessment of occupational and environmental exposure to solvent mixtures.

Administration, Inhalation↗
PubMed2001

Contact stress on polyethylene components of a new rotating hinge with a spherical contact surface.

OBJECTIVE: To assess the nonlinear contact stress of a new rotating hinge of our knee prosthesis at various rotation angles. DESIGN: The contact surface between the metal tibial bearing and the ultra-high-molecular weight polyethylene plate of a conventional rotating hinge is of cylindrical design. We have designed a new type of rotating hinge with a congruous spherical contact surface. BACKGROUND: The endoprosthesis for reconstruction of limb after wide resection of malignant tumor around knee usually incorporates a rotating hinge. Our new rotating hinge with a spherical contact surface incorporates the benefits of an increased contact surface and potentially increased rotational stability during axial loading. METHODS: We utilized the ABAQUS finite element program to assess the nonlinear contact stress of this new rotating hinge at rotation angles of 0 degrees, 4 degrees and 8 degrees, based on a contact force of about 2800 N. RESULTS: The results show that von Mises stress for the finite element model of the polyethylene component of this rotating hinge ranges from 4.90 x 10(-6) to 8.22 MPa at the aforementioned rotational angles. The von Mises stress is about 1.31--1.82 MPa on the major parts of the ultra-high-molecular weight polyethylene plate, including both flanks. There is a mild stress concentration on the outer edge of polyethylene component, especially at 4 degrees and 8 degrees of rotation. The maximum values of von Mises stress at the contact surface at 0 degrees, 4 degrees and 8 degrees of rotation are 5.92, 7.49 and 8.22 MPa, respectively. These contact stresses are within the safety range of the ultra-high-molecular weight polyethylene (compressive yield strength, 14 MPa). CONCLUSIONS: This new rotating hinge has an evenly distributed contact stress during axial load because of congruous contact design.

Finite Element Analysis↗
PubMed2001

Toxicological interactions among arsenic, cadmium, chromium, and lead in human keratinocytes.

To evaluate health effects of chemical mixtures, such as multiple heavy metals in drinking water, we have been developing efficient and accurate hazard identification strategies. Thus, in this study, we determine the cytotoxicity of arsenic, cadmium, chromium, and lead, and characterize interactions among these metals in human epidermal keratinocytes. Three immortal keratinocyte cell lines (RHEK-1, HaCaT, and NM1) and primary keratinocytes (NHEK) were used. A statistical approach applying an additivity response surface methodology was used to test the validity of the additivity concept for a 4-metal mixture. Responses of the 4 keratinocyte strains to the metal mixture were highly dose-dependent. A growth stimulatory effect (hormesis) was observed in RHEK-1, NM1, and NHEK cells with the metal mixture at low concentrations (low ppb range). This hormesis effect was not significant in HaCaT. As the mixture concentration increased, a trend of additivity changed to synergistic cytotoxicity in all 4 cell strains. However, in NHEK, RHEK-1, and HaCaT, at the highest mixture concentrations tested, the responses to the metal mixtures were antagonistic. In NM1, no significant antagonistic interaction among the metals was observed. To explore a mechanistic basis for these differential sensitivities, levels of glutathione and metallothioneins I and II were determined in the keratinocyte cell strains. Initial data are consistent with the suggestion that synergistic cytotoxicity turned to antagonistic effects because at highest mixture exposure concentrations cellular defense mechanisms were enhanced.

Arsenic↗
PubMed2001

Rhodostomin, a snake venom disintegrin, inhibits angiogenesis elicited by basic fibroblast growth factor and suppresses tumor growth by a selective alpha(v)beta(3) blockade of endothelial cells.

Angiogenesis consists of the proliferation, migration, and differentiation of endothelial cells, although angiogenic factor and integrin-extracellular matrix interaction modulate this process. We report here that a snake venom-derived disintegrin, rhodostomin, inhibited distinct steps in angiogenesis elicited by basic fibroblast growth factor (bFGF), and also suppressed in vivo murine melanoma tumor growth. Rhodostomin dose-dependently inhibited bFGF-induced human umbilical vein endothelial cell (HUVEC) proliferation as examined by cell number count, metabolic activity, and BrdU incorporation assays with submicromolar IC(50) values. However, it apparently did not affect the viability of murine B16F10 melanoma cells, even up to 50 microM. Rhodostomin also inhibited HUVEC migration and invasion evoked by bFGF, and tube formation of bFGF-treated HUVECs in Matrigel. Moreover, rhodostomin selectively inhibited bFGF-, but not vascular endothelial growth factor-associated angiogenesis in the chick chorioallantoic membrane model. Furthermore, rhodostomin blocked both bFGF- and B16F10-induced neovascularization in murine Matrigel plug model and suppressed the growth of subcutaneously inoculated B16F10 solid tumor, leading to a prolonged survival of the rhodostomin-treated C57BL/6 mice. The antiangiogenic effect of rhodostomin on bFGF-treated HUVECs is related to the integrin alpha(v)beta(3) blockade, as evidenced by its selective inhibition on the binding of 7E3, a monoclonal antibody (mAb) raised against alpha(v)beta(3,) but not that of P1F6, an alpha(v)beta(5) mAb toward both naive and bFGF-primed HUVECs. Moreover, 7E3 specifically blocked fluorescein isothiocyanate-conjugated rhodostomin binding to HUVEC, whereas P1F6 and anti-integrin alpha(2), alpha(3), alpha(4), or alpha(5) mAbs did not.

Angiogenesis Inhibitors↗
PubMed2001

A biologically based model of growth and senescence of Syrian hamster embryo (SHE) cells after exposure to arsenic.

We modified the two-stage Moolgavkar-Venzon-Knudson (MVK) model for use with Syrian hamster embryo (SHE) cell neoplastic progression. Five phenotypic stages are proposed in this model: Normal cells can either become senescent or mutate into immortal cells followed by anchorage-independent growth and tumorigenic stages. The growth of normal SHE cells was controlled by their division, death, and senescence rates, and all senescent cells were converted from normal cells. In this report, we tested the modeling of cell kinetics of the first two phenotypic stages against experimental data evaluating the effects of arsenic on SHE cells. We assessed cell division and death rates using flow cytometry and correlated cell division rates to the degree of confluence of cell cultures. The mean cell death rate was approximately equal to 1% of the average division rate. Arsenic did not induce immortalization or further mutations of SHE cells at concentrations of 2 microM and below, and chromium (3.6 microM) and lead (100 microM) had similar negative results. However, the growth of SHE cells was inhibited by 5.4 microM arsenic after a 2-day exposure, with cells becoming senescent after only 16 population doublings. In contrast, normal cells and cells exposed to lower arsenic concentrations grew normally for at least 30 population doublings. The biologically based model successfully predicted the growth of normal and arsenic-treated cells, as well as the senescence rates. Mechanisms responsible for inducing cellular senescence in SHE cells exposed to arsenic may help explain the apparent inability of arsenic to induce neoplasia in experimental animals.

Animals↗
PubMed2001

Effectiveness of a multidisciplinary rehabilitation program in elderly patients with hip fractures.

BACKGROUND AND PURPOSE: Hip fracture is a significant health challenge to the elderly, with a high risk of complications, long hospital stay, and functional deterioration. The purpose of this study was to evaluate the effectiveness of a multidisciplinary rehabilitation program (MRP) in older patients with hip fractures. METHODS: A before-and-after quasi-experimental design was used. Data were collected at a large teaching hospital in Taipei. The first 105 consecutive patients admitted received conventional care (control group). The next 50 consecutive patients received physical therapy, nurse-supervised exercise, and discharge planning (intervention group). Subjects were assessed upon admission, on the fourth postoperative day, and on the discharge day. The 155 patients recruited met the following criteria: 60 years of age or older, and hospitalized to receive either closed reduction and internal fixation, or hip arthroplasty. RESULTS: Compared with the control group, the intervention group had a shorter average hospital stay (9.9 vs 11.6 days, p = 0.01), earlier ambulation (5.7 vs 6.5 days postoperatively), and a lower rate of bowel incontinence (4.0% vs 23.8%) and pressure sores (14.0% vs 24.8%) during hospitalization. The intervention group experienced less decline in mobility (relative to pre-fracture status) than the control group. No significant difference was found in other outcome variables between the control and intervention groups. CONCLUSIONS: The findings of this study indicate that an MRP involving physical therapy, nurse-supervised exercise, and discharge planning positively affects health outcomes in older patients with hip fractures.

Activities of Daily Living↗
PubMed2000

A physiologically based pharmacodynamic analysis of hepatic foci within a medium-term liver bioassay using pentachlorobenzene as a promoter and diethylnitrosamine as an initiator.

A stochastic clonal growth model for describing quantitative changes in size and number of putative preneoplastic lesions was modified to analyze the time-course information of cell proliferation and glutathione S-transferase pi (GST-P) foci within a medium-term bioassay. The study used F344 rats and a single initiating event using diethylnitrosamine (200 mg/kg ip) at Week 0. After a 2-week recovery period, chemical treatment began by gavage administration of pentachlorobenzene (PeCB; 100 micromol/kg/day, 7 days/week) in a corn oil vehicle and continued for 6 weeks. One week after beginning gavage dosing, a two-thirds partial hepatectomy was performed and the animals were serially euthanized at 48, 120, 168, 624, and 840 h postsurgery, which corresponds to 216, 288, 336, 792, and 1008 h following the beginning of PeCB treatment, respectively. For analysis, two types of models were evaluated for describing the time-course changes in GST-P foci. First, a sequential model describing the transformation of normal cells into a homogenous initiated cell population (i.e., one-cell model). Second, a two-cell model that describes a heterogeneous foci population by splitting the initiated cell population into two distinct types. In our study, the one-cell model was unable to adequately represent the time-course data for changes in both size and number of foci. In contrast, the two-cell model, which was parameterized to describe a negative selection mechanism, produced adequate simulations of both the size and number of foci. This model-based analysis suggested that the differences between PeCB-treated and untreated animals were primarily in parameters involving the rates of cell death.

Administration, Oral↗
PubMed2000

Efficacy of a 24-week aerobic exercise program for osteopenic postmenopausal women.

Osteoporosis is one of the most common skeletal disorders affecting postmenopausal women. The purpose of this study was to investigate whether a 24-week program of aerobic high-impact loading exercise was beneficial for enhancing physical fitness and bone mineral density (BMD) in osteopenic postmenopausal women. Forty-three postmenopausal women aged 48-65 years participated in this study. The BMD of the spine (L2-L4) and right femoral neck of each woman was below 1 SD of the mean of premenopausal women, as examined by dual X-ray absorptiometry. The assignment of subjects into exercise or control group was not randomized but based on each subject's anticipated compliance to the 6-month long exercise program. Twenty-two subjects joined the exercise group and attended the training programs and 21 served as the control group. Exercise programs included treadmill walking at an intensity above 70% of maximal oxygen consumption (VO2max) for 30 minutes, followed by 10 minutes of stepping exercise using a 20-cm-high bench. The program was conducted three times per week for 24 weeks. Physical fitness measurements included testing of flexibility, muscular strength and endurance, body composition, and cardiopulmonary fitness. The results showed that the quadriceps strength, muscular endurance, and VO2max in the exercise group had significant improvements, whereas no improvement was found in any of the physical fitness parameters in the control group. The BMD of the L2-L4 and the femoral neck in the exercise group increased 2.0% (P > 0.05) and 6.8% (P < 0.05) and those in the control group decreased 2.3% (P < 0.05) and 1.5% (P > 0.05), respectively. In conclusion, aerobics combined with high-impact exercise at a moderate intensity was effective in offsetting the decline in BMD in osteopenic postmenopausal women.

Absorptiometry, Photon↗