The convergence of regenerative medicine and rehabilitation: federal perspectives.

Regenerative rehabilitation is the synergistic integration of principles and approaches from the regenerative medicine and rehabilitation fields, with the goal of optimizing form and function as well as patient independence. Regenerative medicine approaches for repairing or replacing damaged tissue or whole organs vary from utilizing cells (e.g., stem cells), to biologics (e.g., growth factors), to approaches using biomaterials and scaffolds, to any combination of these. While regenerative medicine offers tremendous clinical promise, regenerative rehabilitation offers the opportunity to positively influence regenerative medicine by inclusion of principles from rehabilitation sciences. Regenerative medicine by itself may not be sufficient to ensure successful translation into improving the function of those in the most need. Conversely, with a better understanding of regenerative medicine principals, rehabilitation researchers can better tailor rehabilitation efforts to accommodate and maximize the potential of regenerative approaches. Regenerative rehabilitative strategies can include activity-mediated plasticity, exercise dosing, electrical stimulation, and nutritional enhancers. Critical barriers in translating regenerative medicine techniques into humans may be difficult to overcome if preclinical studies do not consider outcomes that typically fall in the rehabilitation research domain, such as function, range of motion, sensation, and pain. The authors believe that encouraging clinicians and researchers from multiple disciplines to work collaboratively and synergistically will maximize restoration of function and quality of life for disabled and/or injured patients, including U.S. Veterans and Military Service Members (MSMs). Federal Government agencies have been investing in research and clinical care efforts focused on regenerative medicine (NIH, NSF, VA, and DoD), rehabilitation sciences (VA, NIH, NSF, DoD) and, more recently, regenerative rehabilitation (NIH and VA). As science advances and technology matures, researchers need to consider the integrative approach of regenerative rehabilitation to maximize the outcome to fully restore the function of patients.

Longitudinal health surveillance in a cohort of Gulf War veterans 18 years after first exposure to depleted uranium.

As part of a longitudinal surveillance program, 35 members of a larger dynamic cohort of 79 Gulf War I veterans exposed to depleted uranium (DU) during combat underwent clinical evaluation at the Baltimore Veterans Administration Medical Center. Health outcomes and biomonitoring results were obtained to assess effects of DU exposure and determine the need for additional medical intervention. Clinical evaluation included medical and exposure histories, physical examination, and laboratory studies including biomarkers of uranium (U) exposure. Urine collections were obtained for U analysis and to measure renal function parameters. Other laboratory measures included basic hematology and chemistry parameters, blood and plasma U concentrations, and markers of bone metabolism. Urine U (uU) excretion remained above normal in participants with embedded DU fragments, with urine U concentrations ranging from 0.006 to 1.88 µg U/g creatinine. Biomarkers of renal effects showed no apparent evidence of renal functional changes or cellular toxicity related to U body burden. No marked differences in markers of bone formation or bone resorption were observed; however, a statistically significant decrease in levels of serum intact parathyroid hormone and significant increases in urinary calcium and sodium excretion were seen in the high versus the low uU groups. Eighteen years after first exposure, members of this cohort with DU fragments continue to excrete elevated concentrations of uU. No significant evidence of clinically important changes was observed in kidney or bone, the two principal target organs of U. Continued surveillance is prudent, however, due to the ongoing mobilization of uranium from fragment depots.

Surveillance results of depleted uranium-exposed Gulf War I veterans: sixteen years of follow-up.

As part of a longitudinal surveillance program, 35 members of a larger cohort of 77 Gulf War I veterans who were victims of depleted uranium (DU) "friendly fire" during combat underwent a 3-day clinical assessment at the Baltimore Veterans Administration Medical Center (VAMC). The assessment included a detailed medical history, exposure history, physical examination, and laboratory studies. Spot and 24-h urine collections were obtained for renal function parameters and for urine uranium (U) measures. Blood U measures were also performed. Urine U excretion was significantly associated with DU retained shrapnel burden (8.821 mug U/g creatinine [creat.] vs. 0.005 mug U/g creat., p = .04). Blood as a U sampling matrix revealed satisfactory results for measures of total U with a high correlation with urine U results (r = .84) when urine U concentrations were >/=0.1 mug/g creatinine. However, isotopic results in blood detected DU in only half of the subcohort who had isotopic signatures for DU detectable in urine. After stratifying the cohort based on urine U concentration, the high-U group showed a trend toward higher concentrations of urine beta(2) microglobulin compared to the low-U group (81.7 v. 69.0 mug/g creat.; p = .11 respectively) and retinol binding protein (48.1 vs. 31.0 mug/g creat.; p = .07 respectively). Bone metabolism parameters showed only subtle differences between groups. Sixteen years after first exposure, this cohort continues to excrete elevated concentrations of urine U as a function of DU shrapnel burden. Although subtle trends emerge in renal proximal tubular function and bone formation, the cohort exhibits few clinically significant U-related health effects.

Health surveillance of Gulf War I veterans exposed to depleted uranium: updating the cohort.

A cohort of seventy-four 1991 Gulf War soldiers with known exposure to depleted uranium (DU) resulting from their involvement in friendly-fire incidents with DU munitions is being followed by the Baltimore Veterans Affairs Medical Center. Biennial medical surveillance visits designed to identify uranium-related changes in health have been conducted since 1993. On-going systemic exposure to DU in veterans with embedded metal fragments is indicated by elevated urine uranium (U) excretion at concentrations up to 1,000-fold higher than that seen in the normal population. Health outcome results from the subcohort of this group of veterans attending the 2005 surveillance visit were examined based on two measures of U exposure. As in previous years, current U exposure is measured by determining urine U concentration at the time of their surveillance visit. A cumulative measure of U exposure was also calculated based on each veteran's past urine U concentrations since first exposure in 1991. Using either exposure metric, results continued to show no evidence of clinically significant DU-related health effects. Urine concentrations of retinol binding protein (RBP), a biomarker of renal proximal tubule function, were not significantly different between the low vs. high U groups based on either the current or cumulative exposure metric. Continued evidence of a weak genotoxic effect from the on-going DU exposure as measured at the HPRT (hypoxanthine-guanine phosphoribosyl transferase) locus and suggested by the fluorescent in-situ hybridization (FISH) results in peripheral blood recommends the need for continued surveillance of this population.