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.
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.
The purpose of this study was to compare the biochemical and clinical effects of transdermal estrogen replacement therapy (tERT) in younger and older postmenopausal women. We treated 15 younger (less than 60 y) and 13 older (greater than or equal to 60 y) healthy postmenopausal women (45-72 y) with four successive 8-week regimens of tERT at doses of 0 to 150 micrograms/day, combined with cyclic oral medroxyprogesterone acetate (MPA). In both age groups, there were similar (p = .0001) dose-responsive increases in plasma estrogen levels and decreases in LH and FSH levels, although LH values were lower in older women both before and after tERT (p less than .02). The addition of MPA further suppressed LH and, to a lesser extent, FSH in both younger and older women. The ratio of estrogenized to nonestrogenized vaginal cells increased with tERT (p less than .007) in both age groups, but significant symptomatic improvement of vaginal irritation was noted only at the highest tERT dose. Adverse effects unrelated to age included short-term nausea in 4/28 women, and skin irritation at the patch sites in 20/28 women. Vaginal bleeding was of shorter duration, but breast tenderness was more common in older women. Further studies of long-term tERT effects in elderly women are indicated.
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