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INTRODUCTION.: Age-related differences in force steadiness have been extensively examined and used as an index of motor function. However, the functional relevance of steadiness remains unclear. PURPOSE.: The aim here was to evaluate the relations among hand strength, steadiness, and function across the adult life-span. METHODS.: Seventy-five adults (45 women; 18-89 yr) performed 3 strength, 2 steadiness, and 4 functional tests with both hands. Strength was measured during index finger abduction, precision pinch, and handgrip, and steadiness was measured during index finger abduction and precision pinch. Functional tests included the Grooved Pegboard test, the game Operation, a scissor task, and a tracing task. Results. Moderate correlations were observed between both steadiness tasks and performance on the Grooved Pegboard test (R= 0.57 and R= 0.46, respectively) and the game Operation (R2=-0.47 and R= -0.57, respectively). CONCLUSIONS.: The relation between measures of steadiness and hand function suggests that the physiological mechanisms responsible for differences in steadiness also contribute to differences in the performance of fine motor tasks with the hand. Language: en

Background. The efficacy and safety of converting maintenance renal transplant recipients from calcineurin inhibitors (CNIs) to sirolimus (SRL) was evaluated. Methods. Eight hundred thirty renal allograft recipients, 6 to 120 months posttransplant and receiving cyclosporine or tacrolimus, were randomly assigned to continue CNI (n=275) or convert from CNI to SRL (n=555). Primary endpoints were calculated Nankivell glomerular filtration rate (GFR; stratified at baseline: 20-40 vs. >40 mL/min) and the cumulative rates of biopsy-confirmed acute rejection (BCAR), graft loss, or death at 12 months. Enrollment in the 20 to 40 mL/min stratum was halted prematurely because of a higher incidence of safety endpoints in the SRL conversion arm. Results. Intent-to-treat analyses at 12 and 24 months showed no significant treatment difference in GFR in the baseline GFR more than 40 mL/min stratum. On-therapy analysis of this cohort showed significantly higher GFR at 12 and 24 months after SRL conversion. Rates of BCAR, graft survival, and patient survival were similar between groups. Median urinary protein-to-creatinine ratios (UPr/Cr) were similar at baseline but increased significantly after SRL conversion. Malignancy rates were significantly lower at 12 and 24 months after SRL conversion. Post hoc analyses identified a subgroup with baseline GFR more than 40 mL/min and UPr/Cr less than or equal to 0.11, whose risk-benefit profile was more favorable after conversion than that for the overall SRL conversion cohort. Conclusions. At 2 years, SRL conversion among patients with baseline GFR more than 40 mL/min was associated with excellent patient and graft survival, no difference in BCAR, increased urinary protein excretion, and a lower incidence of malignancy compared with CNI continuation. Superior renal function was observed among patients who remained on SRL through 12 to 24 months, particularly in the subgroup of patients with baseline GFR more than 40 mL/min and UPr/Cr less than or equal to 0.11.

Background. Two major routes by which cytotoxic T lymphocytes induce apoptosis in target cells are the perforin-granzyme and the Fas ligand/Fas pathways. Intragraft expression of message for these immune activation genes has been shown to correlate very closely with clinical rejection. We have immunolabeled fine-needle aspiration biopsy samples using a panel of cytotoxic T-cell activation markers to evaluate the immunocytochemical identification of the protein products of these genes in the verification of human renal allograft rejection. Methods. In this retrospective pilot study, 140 fineneedle aspiration biopsy samples from 50 human renal allografts were labeled using alkaline phosphatase/ anti-alkaline phosphatase immunocytochemistry incorporating monoclonal antibodies to perforin, granzyme B, and Fas ligand. Levels of positive labeling for these markers were compared with the original clinical diagnosis of rejection. Results. An excellent correlation with clinical rejection was obtained when all three antibodies were positive. The false positive rate for each antibody was sufficient to make any one alone or in combination with one other unreliable for diagnosing rejection. When all three antibodies gave positive labeling, agreement with clinical rejection status was superior to using conventional morphological cytology. Conclusions. In addition to providing valuable morphological information regarding the composition of inflammatory leukocyte populations and the preservation status of renal parenchymal cells, fine-needle aspiration biopsy samples may be labeled using combined perforin, granzyme B, and Fas ligand immunocytochemistry to offer a safe and reliable method for diagnosing rejection with an excellent level of accuracy. Acute and chronic rejection are still the major causes of renal allograft loss despite major advances in immunosuppression and transplant management. Acute rejection has been shown to be the strongest predictive factor of subsequent chronic rejection (1). Furthermore, a recent study has shown that kidneys undergoing an early acute rejection episode have poorer long-term survival even if the serum creatinine returns to the preacute episode level; the likelihood of chronic rejection is even greater if the serum creatinine fails to return to the baseline (2). Thus, the early diagnosis and treatment of acute cellular rejection remains of critical importance. The current gold standard for the diagnosis of rejection is needle-core biopsy (NCB) histopathology used in conjunction with clinical findings. Fine-needle aspiration cytology (FNAC) is used as a less-invasive method than NCB for investigating causes of suboptimal graft function including rejection and acute tubular necrosis. Fine-needle aspiration biopsy may be practiced safely on a daily basis to study changes in the composition and function of intragraft cell populations before, during, and after acute rejection episodes (3).