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Biomedical subjects

Daniel Gillen

Publications and source records attributed to Daniel Gillen.

5 recordsLinked to original sources
PubMed2006

Treatment of renal allograft polyoma BK virus infection with leflunomide.

BACKGROUND: Polyoma BK virus produces an aggressively destructive nephropathy in approximately 3% to 8% of renal allografts, is associated with graft loss within one year in 35% to 67% of those infected and there is no therapy of proven efficacy. Leflunomide is an immune suppressive drug with anti viral activity in vitro and in animals. METHODS: We treated twenty-six patients with biopsy proven NK virus nephropathy (BKN) with either leflunomide alone (n=17) or leflunomide plus a course of cidofovir (n=9) and followed them for six to forty months. Leflunomide was dosed to a targeted blood level of active metabolite, A77 1726, of 50 microg/ml to 100 microg/ml (150 microM to 300 microM). Response to treatment was gauged by serial determinations of viral load in blood and urine (PCR), serum creatinine, and repeat allograft biopsy. RESULTS: In the 22 patients consistently sustaining the targeted blood levels of active drug, blood and urine viral load levels uniformly decreased over time (P<.001). Mean serum creatinine levels stabilized over the first six months of treatment, and with 12 months or more of follow-up in 16 patients the mean serum creatinine has not changed significantly from base line. Four patients who did not consistently have blood levels of active drug (A77 1726) above 40 microg/ml did not clear the virus until these levels were attained or cidofovir was added. CONCLUSIONS: Leflunomide inhibits Polyoma virus replication in vitro and closely monitored leflunomide therapy with specifically targeted blood levels appears to be a safe and effective treatment for Polyoma BK nephropathy.

Aniline Compounds↗
PubMed2006

Risk of lymphoma after renal transplantation varies with time: an analysis of the United States Renal Data System.

BACKGROUND: Characterization of the incidence of posttransplant lymphoma over time may help guide the timing and intensity of posttransplant monitoring. We analyzed the United States Renal Data System to describe the occurrence of lymphoma following renal transplantation. METHODS: All end-stage renal disease patients placed on the transplant waiting list between January 1, 1990 and December 31, 1999 were considered. Survival analysis was used to estimate lymphoma risk in renal transplant patients. RESULTS: Of 89,260 eligible patients, a total of 556 lymphoma cases were identified with 357 in transplant patients. The overall rate of posttransplant lymphoma was 33.3/10,000 person-years in transplant patients. There was variation in the duration and magnitude of increased lymphoma risk by age. The highest rates of lymphoma were among transplanted patients in the first 12 months, after which the rate of lymphoma decreased. Among Caucasian transplant recipients less than 25 years of age, the adjusted relative risk of lymphoma ranged from 13.82 [95% CI: (3.96, 48.15)] within 6 months posttransplant to 3.46 [95% CI: (0.69, 17.44)] within months 30-36 posttransplant. Only patients under 25 years had a notably increased risk beyond the first 2 posttransplant years. The risk of lymphoma differed by race, with Caucasian patients at nearly double the risk of African-Americans. Gender was not associated with lymphoma incidence. CONCLUSIONS: We found and quantified a time-varying relationship between renal transplant and lymphoma risk. This information can be used in combination with knowledge of established risk factors to guide the schedule of posttransplant monitoring.

Adult↗
PubMed2004

Analysis of prostate-specific antigen rebound interval in patients with prostate cancer receiving hormonal therapy and external-beam radiation therapy.

The goal of this investigation is to characterize the clinical significance of the rebound interval (RI) after neoadjuvant short-course hormonal therapy (HT) and external-beam radiation therapy (RT), during which the prostate-specific antigen (PSA) may rise because of hormone withdrawal prior to full RT efficacy. The charts of 257 consecutive patients with localized prostate cancer who received short-course neoadjuvant HT and RT were reviewed. A piecewise-linear log PSA versus time curve was generated for each patient and averaged over the population to facilitate identification of the RI start and end dates. Existing definitions of biochemical failure--American Society for Therapeutic Radiology and Oncology (ASTRO), Vancouver and Houston--were applied, as were these same definitions modified to exclude failures during the RI. Sensitivity and specificity were analyzed, using no evidence (by digital rectal examination or radiology) of disease failure as the gold standard. The 5-year biochemical survival with different failure definitions were ASTRO versus ASTRO-modified: 81.6% versus 86.7%; Houston versus Houston-modified: 71.4% versus 76.7%; and Vancouver versus Vancouver-modified: 83.5% versus 85.6%. The sensitivity and specificity comparisons were ASTRO versus ASTRO-modified 58.3% versus 33.3%; 91.4% versus 94.3%, Vancouver versus Vancouver-modified: 50% versus 50%; 92.7% versus 95.5%, Houston versus Houston-modified: 100% versus 66.7%; 90.6% versus 92.2%. The RI after HT and RT is likely not merely an artifact of hormone withdrawal but is correlated with ultimate clinical outcome. Excluding RI failures can marginally improve specificity but may possibly have an unacceptable risk of lowering sensitivity. Further work is needed to design and validate definitions of failure, which account for the RI.

Aged↗
PubMed2003

Racial differences in early-onset renal disease among young adults: the coronary artery risk development in young adults (CARDIA) study.

Although 11 million people in the United States have chronic renal insufficiency, little is known about ethnic/racial disparities for early-onset renal impairment. This study sought to determine whether there is an independent association between race/ethnicity and early-onset renal impairment and to identify other risk factors that might account for observed disparities. All Coronary Artery Risk Development in Young Adults subjects in which serum creatinine was measured at the year 15 examination were identified (n = 3554), excluding those who were pregnant at year 15. Potential risk factors at study entry (ages 18 to 30 yr, 1985 to 1986) included age, weight, gender, race/ethnicity, glucose, uric acid, and systolic BP. Renal impairment was defined as creatinine > or =1.5 mg/dl for men and > or = 1.2 mg/dl for women at year 15 (ages 33 to 45 yr). Fifty-two (2.7%) women and 39 (2.4%) men had renal impairment at the year 15 examination. In bivariate analyses, the odds of renal impairment among black women was estimated to be 2.4-fold that of white women, and among black men, the odds of renal impairment were 9.0-fold that of white men. In multivariate analysis, the odds of an elevated creatinine among black women compared with white women reduced to a nonsignificant 1.5-fold, whereas among men, the odds of an elevated creatinine among blacks was 11.4-fold that of whites. Although adjustment for baseline glucose levels accounted for much of the association between ethnicity and elevated creatinine among women, adjustment for weight, systolic BP, uric acid, glucose, and socioeconomic status did not account for the association between ethnicity and renal impairment among men. The data suggest that there are ethnic differences in the development of early-onset renal dysfunction. Among women, these differences are modest and largely accounted for by differences in glucose levels early in adult life. Differences in race/ethnicity related risk of early-onset renal impairment are particularly large among men and are not accounted for by the metabolic or socioeconomic factors evaluated.

Adolescent↗