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The aim of this study was to determine the extent to which poor physical functioning, low participation in physical activity, and muscle atrophy observed among patients on hemodialysis are evident in the earlier stages of chronic kidney disease (CKD). We enrolled adults in three groups: no CKD, Stages 3 to 4 CKD, and hemodialysis. Outcomes measured were physical activity, muscle size, thigh muscle strength, physical performance, and self-reported physical function. Patients with CKD had muscle area intermediate between the no CKD and hemodialysis groups, but they had low levels of physical activity that were similar to the hemodialysis group. Physical activity and muscle size were significantly associated with all outcomes. Kidney function was not significantly associated with muscle strength or physical performance after adjustment for physical activity and muscle size. In conclusion, interventions aimed to increase muscle mass and energy expenditure might have an impact on improving physical function of CKD patients. [ABSTRACT FROM AUTHOR]

Context: Evidence exists that high-volume hospitals (HVHs) have lower mortality rates than low-volume hospitals (LVHs) for certain conditions. However, few employers, health plans, or government programs have attempted to increase the number of patients referred to HVHs.Objectives: To determine the difference in hospital mortality between HVHs and LVHs for conditions for which good quality data exist and to estimate how many deaths potentially would be avoided in California by referral to HVHs.Design, Setting, and Patients: Literature in MEDLINE, Current Contents, and First-Search Social Abstracts databases from January 1, 1983, to December 31, 1998, was searched using the key words hospital, outcome, mortality, volume, risk, and quality. The highest-quality study assessing the mortality-volume relationship for each given condition was identified and used to calculate odds ratios (ORs) for in-hospital mortality for LVHs vs HVHs. These ORs were then applied to the 1997 California database of hospital discharges maintained by the California Office of Statewide Health Planning and Development to estimate potentially avoidable deaths.Main Outcome Measures: Deaths that potentially could be avoided if patients with conditions for which a mortality-volume relationship had been treated at an HVH vs LVH.Results: The articles identified in the literature search were grouped by condition, and predetermined criteria were applied to choose the best article for each condition. Mortality was significantly lower at HVHs for elective abdominal aortic aneurysm repair, carotid endarterectomy, lower extremity arterial bypass surgery, coronary artery bypass surgery, coronary angioplasty, heart transplantation, pediatric cardiac surgery, pancreatic cancer surgery, esophageal cancer surgery, cerebral aneurysm surgery, and treatment of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). A total of 58,306 of 121,609 patients with these conditions were admitted to LVHs in California in 1997. After applying the calculated ORs to these patient populations, we estimated that 602 deaths (95% confidence interval, 304-830) at LVHs could be attributed to their low volume. Additional analyses were performed to take into account emergent admissions and distance traveled, but the impact of loss of continuity of care for some patients and reduction in the availability of specialists for patients remaining at LVHs could not be assessed.Conclusions: Initiatives to facilitate referral of patients to HVHs have the potential to reduce overall hospital mortality in California for the conditions identified. Additional study is needed to determine the extent to which selective referral is feasible and to examine the potential consequences of such initiatives. [ABSTRACT FROM AUTHOR]

Context: Patients receiving dialysis commonly experience malnutrition, reduced muscle mass (sarcopenia), and fatigue for which no effective treatment has been identified. Anabolic steroids are known to increase muscle mass and strength in healthy individuals, but their effect on the sarcopenia and fatigue associated with long-term dialysis has not been evaluated.Objective: To assess the effects of an anabolic steroid, nandrolone decanoate, on lean body mass (LBM), functional status, and quality of life in dialysis patients.Design: Randomized, double-blind, placebo-controlled trial conducted between April 1996 and July 1997.Setting: Hospital-based outpatient dialysis unit.Patients: Twenty-nine patients undergoing dialysis for at least 3 months.Intervention: Nandrolone decanoate, 100 mg (n = 14), or placebo (n = 15) by intramuscular injection once a week for 6 months.Main Outcome Measures: Weight, LBM, fatigue, grip strength, walking and stair-climbing times, and treadmill performance after 3 and 6 months of treatment.Results: Lean body mass increased significantly in patients given nandrolone compared with patients given placebo (mean change [SD], +4.5 [2.3] kg; P<.001 compared with baseline). This effect was significantly greater than the change in LBM in the placebo group (mean change [SD], +1.9 [1.6] kg; P = .003 compared with baseline; P = .005 compared with nandrolone group). Serum creatinine levels increased in the nandrolone group (+168 [203] mmol/L [1.9 [2.3] mg/dL]; P = .02) but not in the placebo group (-4.0 [177] mmol/L [0.04 [2.0] mg/dL]; P = .95), suggesting an increase in muscle mass. Time to complete the walking and stair-climbing test decreased from 36.5 to 32.7 seconds in the nandrolone group, while those in the placebo group increased from 38.7 to 42.1 seconds (P = .05). Peak oxygen consumption increased in the individuals in the nandrolone group who performed treadmill tests, but not to a statistically significant degree. Grip strength did not change in either group.Conclusions: Treatment with nandrolone for 6 months resulted in a significant increase in LBM associated with functional improvement in patients undergoing dialysis. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic kidney disease (CKD) treated with dialysis have reduced levels of physical functioning. Little is known of the physical functioning in patients prior to initiation of renal replacement therapy (RRT). The purpose of the study was 2-fold: (i) to document physical functioning of patients with CKD not requiring RRT, using objective laboratory tests, physical performance measures and self-reported functioning; and (ii) to determine the correlations between these measures of physical functioning and renal function., Methods: Thirty-two patients with CKD (mean estimated glomerular filtration rate [eGFR] 29.9 +/- 17.0) were recruited for the study. Subjects completed symptom-limited treadmill test (peak oxygen uptake [VO2peak]), physical performance measures (gait speed, sit-to-stand and 6-minute walk) and the SF-36 Health Status Questionnaire (physical functioning scale [PF] and physical composite scale [PCS]). Descriptive and correlational analyses were performed on the data., Results: VO2peak (O2 17.8 +/- 6.7 ml/kg body weight per minute), physical performance measures and self-reported functioning were reduced compared with sedentary age-predicted norms. Significant correlations were found between VO2peak and all other physical functioning measures; however, only maximal gait speed and PCS correlated significantly with eGFR., Conclusions: Patients with CKD have reduced physical functioning as measured using objective laboratory tests (VO2peak), physical performance measures and self-reported functioning. Given that low physical functioning predicts outcomes in dialysis patients, interventions to maintain or improve physical functioning are warranted prior to initiation of dialysis.

Background: Physical performance measures, particularly gait speed, have been useful as predictors of loss of independence, institutionalization, and mortality in older nonuremic individuals. Gait speed has not been evaluated as a predictor of these important outcomes in patients on hemodialysis, nor have the determinants of gait speed in the dialysis population been studied., Methods: We performed a cross-sectional analysis to determine whether demographic, clinical, or nutritional status variables were related to physical performance in a group of 46 hemodialysis patients treated at three University of California San Francisco-affiliated dialysis units. Three physical performance measures were examined, including gait speed, time to climb stairs, and time to rise from a chair five times in succession. Forward stepwise linear-regression analysis was performed with each physical performance measure as the dependent variable and the following candidate predictor variables: age, gender, body mass index, dialysis vintage, Kt/V, albumin, blood urea nitrogen, creatinine, hematocrit, lean body mass, phase angle, ferritin, and the following comorbidities: hypertension, diabetes mellitus, coronary artery disease, peripheral vascular disease, and cerebrovascular disease., Results: Subjects included 31 men and 15 women aged 22 to 87 years (mean +/- SD, 52 +/- 17). The mean gait speed for the group was 113.1 +/- 34.5 cm/s (low compared with norms established for persons of similar age). Results of multivariable regression showed that age, albumin, and Kt/V were important determinants of gait speed in this population. Overall, the model explained 52% of the variability in gait speed (r = 0.72, P < 0.0001). Qualitatively similar results were obtained using stair-climbing time or chair-rising time as the dependent variables, except that comorbidity was more important than age for stair climbing. The addition of physical activity level to the models did not eliminate the associations of albumin or Kt/V with physical performance., Conclusions: Physical performance is significantly impaired in ambulatory hemodialysis patients and is related to age, serum albumin, and dialysis dose. Prospective studies are needed to determine whether modification of dialysis dose or nutritional interventions can improve physical performance in patients on hemodialysis.

Background: Patients on dialysis are less physically active than sedentary persons with normal kidney function. To assess the consequences of inactivity and the results of efforts to increase activity in the end-stage renal disease (ESRD) population, valid instruments to measure physical activity and physical functioning in this group are needed., Methods: We performed a cross-sectional study to establish the validity in ESRD of several questionnaires designed to measure physical activity or physical functioning in the general population. Questionnaires studied included the Stanford 7-day Physical Activity Recall questionnaire (PAR), the Physical Activity Scale for the Elderly (PASE), the Human Activity Profile (HAP), and the Medical Outcomes Study Short Form 36-item questionnaire (SF-36). Physical activity was measured using three-dimensional activity monitors (accelerometers) over a seven-day period (the "gold standard"). Patients also underwent physical performance tests, including measurement of gait speed, stair climbing time, and chair rising time. Study questionnaires were administered, and questionnaire results were compared with each other and with activity monitor and physical performance test results., Results: Thirty-nine maintenance hemodialysis patients participated in the study. Dialysis patients scored worse than previously published healthy norms on all tests. All questionnaires correlated with seven-day accelerometry and with at least one measure of physical performance. The HAP correlated best with accelerometry (r = 0.78, P < 0.0001). Seventy-five percent of the variability in physical activity measured by accelerometry could be explained by a model that combined information from the HAP and the PASE. The HAP and the physical functioning scale of the SF-36 were about equally well correlated with physical performance measures., Conclusions: These questionnaires are valid in patients on hemodialysis and should be used to study the physical activity and rehabilitation efforts in this population further.

Background: Patients on dialysis have reduced exercise tolerance compared with age-matched sedentary controls. The reasons for this debility have not been fully elucidated, but physical inactivity could be a contributing factor. The purpose of the current study was to determine whether patients on hemodialysis are less active than healthy sedentary controls and to explore clinical correlates of physical activity level in a group of hemodialysis patients., Methods: Thirty-four hemodialysis patients and 80 healthy sedentary individuals participated in the study. Physical activity was measured for seven days with a three-dimensional accelerometer and with an activity questionnaire., Results: Vector magnitude values from the accelerometer for the dialysis and control subjects were 104,718 +/- 9631 and 161,255 +/- 6792 arbitrary units per day, respectively (P < 0.0001, mean +/- SEM). The estimated energy expenditure values derived from the questionnaire were 33.6 +/- 0.5 kcal/kg/day and 36.2 +/- 0.5 kcal/kg/day (P = 0.002). The difference between patients on dialysis and controls increased with advancing age. Among the dialysis subjects, some measures of nutritional status correlated with physical activity level, including serum albumin concentration (r = 0.58, P = 0.003), serum creatinine concentration (r = 0.37, P = 0. 03), and phase angle derived from bioelectrical impedance analysis (r = 0.40, P = 0.02)., Conclusions: Patients on hemodialysis are less active than healthy sedentary controls, and this difference is more pronounced among older individuals. There is an association between the level of physical activity and nutritional status among patients on dialysis. These findings are of great concern, given the trend toward increasing age in incident dialysis patients and the well-known association between inactivity and increased mortality in the general population.

Background: The link between dialysis "vintage" (length of time on dialysis in months to years) and survival has been difficult to define, largely because of selection effects. End-stage renal disease (ESRD) is thought to be a wasting illness, but there are no published reports describing the associations between vintage and body composition in hemodialysis patients., Methods: We explored the relationships among vintage, nutritional status, and survival in a 3009 patient cohort of prevalent hemodialysis patients. Body weight, total body water, body cell mass, and phase angle by bioelectrical impedance analysis were the body composition parameters of interest. We examined vintage as an explanatory variable in multiple linear regression analyses (adjusted for age, gender, race, and diabetes) using body composition parameters and biochemical indicators of nutritional status as dependent variables. Proportional hazards regression was used to evaluate the association of vintage and survival with and without adjustment for case mix and laboratory variables., Results: Dialysis vintage was 3.8 +/- 3.7 (median 2.6) years. Body composition parameters tended to be lower after dialysis year 2. Linear estimates per year of vintage beyond year 2 include -0.66 kg body wt (P < 0.0001), -0.17 kg total body water (P = 0.0003), -0.14 kg body cell mass (P < 0.0001), and -0.07 degrees phase angle (P < 0.0001). In unadjusted analyses, vintage was not associated with survival, either as a linear or higher order term. The adjustment for case mix yielded a vintage term associated with an increased relative risk (RR) of death (RR 1.04 (95% CI, 1.01 to 1.07 per year). A further adjustment for laboratory data yielded a RR of 1.06 (95% CI, 1.03 to 1.09 per year)., Conclusion: Dialysis vintage is related to nutritional status in hemodialysis patients, with vintage of more than years associated with a significant decline in all measured nutritional parameters. Cross-sectional analyses probably underestimate these effects. A year accrued on dialysis is associated with a 6% increase in the risk of death, all else equal. Longitudinal assessments of nutritional status, including body composition, are required to better understand the natural history of wasting with ESRD and its implications for long-term survival.

Patients on dialysis have extremely limited exercise capacity, and poor physical functioning has been linked to low quality of life and high mortality in this population. The reason for the debility of patients on dialysis is far from clear despite years of study. The anemia of chronic renal disease is clearly a contributing factor, but uremic myopathy and resulting decreased muscle oxygen utilization have a significant impact on the physical functioning of patients on dialysis as well. Although it is likely that factors related to uremia adversely affect muscle function, some of the abnormalities demonstrated in uremic muscle are consistent with disuse atrophy. The clear contribution of anemia and the possible role of limited physical activity have led to studies of the effects of erythropoietin and aerobic exercise training on exercise capacity in end-stage renal disease patients. Both of these interventions result in increased exercise capacity. Thus vigorous treatment of anemia and uremia and encouragement of physical activity are important interventions to maximize the physical functioning of patients on dialysis. In addition, more studies are needed to clarify the causes of debility in this population and the impact of interventions on physical functioning, quality of life, and mortality.

Parathyroid hormone-related peptide (PTHrP) is expressed in lactating rat mammary glands after suckling, as a result of increases in prolactin rather than suckling per se. In addition, PTHrP produced in the fetal parathyroid glands and placenta may be responsible for stimulation of placental calcium transport. In the current study, we used a radioimmunoassay for human PTHrP to measure levels of the peptide in (1) human breast milk, cow's milk, and two infant formulas; (2) sequential plasma samples in prepartum and postpartum lactating women; (3) women with pathologic hyperprolactinemia; and (4) human umbilical cord blood. In normal subjects, plasma PTHrP levels ranged from less than 2 to 5 pmol/liter. In contrast, human breast milk contained substantially increased levels of immunoreactive PTHrP. Similar elevations were found in cow's milk and in one infant formula. Column chromatography of breast milk demonstrated that PTHrP immunoreactivity included a region of adenylate cyclase stimulating activity, consistent with the presence of biologically active PTHrP. Plasma prepartum PTHrP values did not differ from corresponding postpartum values in lactating women. Women with hyperprolactinemia had a mean plasma PTHrP value in the high-normal range. Umbilical cord blood had considerably suppressed parathyroid hormone values but PTHrP levels that were indistinguishable from those in normal human plasma. Thus, PTHrP is present in high concentrations in breast milk but apparently does not gain access to the maternal circulation in significant amounts. In addition, women with pathologic hyperprolactinemia seem not to have increased levels of circulating PTHrP.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitation of initial uptake of the cholescintigraphy agents, 99mTc-Lidofenin, 99mTc-Disofenin, 99mTc-Mebrofenin, and 99mTc-Arclofenin, in short-term cultured rat hepatocytes revealed a marked reduction at 4 degrees C as compared with 37 degrees C. Depletion of adenosine triphosphate by preincubation of cells in sodium azide and 2-deoxyglucose reduced initial uptake of 99mTc-Disofenin at 37 degrees C by 50% (p less than 0.05), suggesting an energy-dependent mechanism. At 37 degrees C, 99mTc-Mebrofenin and 99mTc-Disofenin had the greatest rate of uptake. 99mTc-Disofenin and 99mTc-Lidofenin uptake was inhibited by 20 microM sulfobromophthalein, bilirubin, taurocholate, deoxycholate, chenodeoxycholate, and cholate, suggesting a common anionic transport mechanism. Uptake of 99mTc-Disofenin was unaffected by removal of NaCl from medium, suggesting that its transport did not proceed by the primary high-affinity uptake pathways associated with sulfobromophthalein and taurocholate, which require Cl- and Na+, respectively. 99mTc-Mebrofenin uptake was inhibited only modestly by taurocholate, deoxycholate, and bilirubin (p less than 0.05) and 99mTc-Arclofenin uptake was not inhibited by the organic anions studied. These results suggest that 99mTc-Mebrofenin and 99mTc-Arclofenin might be advantageous for cholescintigraphy in severely jaundiced patients. The relatively simple in vitro methodology described in this study may be useful in the design and screening of potential new agents before proceeding to animal studies or clinical trials.

During the time interval 1950 through 1980, 48 patients having a mean age of 60.2 years were treated primarily for melanoma of the vulva. In all but one patient, a surgical therapeutic approach was selected, including 40 modified Basset procedures and 23 pelvic lymphadenectomies. The 5-year survival rate of the eligible population was 54%. Although surgical staging according to the classification established by the International Federation of Gynecology and Obstetrics (FIGO) was of minimal value, microstaging, using Clark's and Breslow's stratifications for assessing dermal penetration, was of prognostic significance. Ten-year survival rates associated with Clark's level II, III, IV, and V tumors were 100, 83, 65, and 23%, respectively. Histologic growth patterns (5-year survival rates of 71 and 38% for superficial spreading and nodular melanomas, respectively) and groin nodal metastasis were cogent prognostic factors and indirectly were related to depth of local tumor invasion. Likewise, assessment of treatment failures demonstrated a positive correlation between recurrences (specifically at distant sites) and Clark's level of melanocytic penetration. Because of the unacceptably high (32%) local treatment failure rate despite radical vulvar resection, treatment modifications for vulvar melanoma are imperative.