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Biomedical subjects

Michael N Liebman

Publications and source records attributed to Michael N Liebman.

7 recordsLinked to original sources
PubMed2003

Mycophenolate mofetil versus azathioprine therapy is associated with a significant protection against long-term renal allograft function deterioration.

BACKGROUND: To evaluate the association of long-term continuous mycophenolate mofetil (MMF) versus azathioprine (AZA) therapy and renal allograft function, as measured by the slope of reciprocal creatinine, we analyzed 49,666 primary renal allograft recipients reported to the United States Renal Data System between October 31, 1988 and June 30, 1998. METHODS: The primary study endpoint was defined as a greater than 20% decrease below a 6-month baseline of 1/serum creatinine (SCr) (slope of reciprocal creatinine) at or beyond 1 year after transplantation. A secondary endpoint was defined as reaching an SCr value greater than 1.6 mg/dL. Univariate Kaplan-Meier analysis and multivariate Cox proportional hazard models were used to investigate the risk of reaching the study endpoints. Multivariate analyses were corrected for potential confounding covariates. RESULTS: According to the Cox proportional hazard model, 12-month continued therapy of MMF versus AZA was associated with a protective effect against declining renal function, as measured by the slope of reciprocal creatinine (relative risk [RR]=0.84, confidence interval 0.78-0.91, P<0.001). For 24-month continued therapy of MMF versus AZA, MMF was associated with a further decreased risk for a decline in renal function (RR=0.66, confidence interval=0.57-0.77, P<0.001). Furthermore, MMF was associated with a protective effect against reaching the SCr threshold of 1.6 mg/dL (RR=0.80, P<0.001) beyond 12 months posttransplantation. CONCLUSIONS: Continuous use of MMF versus AZA was associated with a protective effect against declining renal function beyond 1 year after transplantation. Further study is needed to confirm that continued MMF therapy is protective against long-term deterioration in renal function.

Adult↗
PubMed2003

Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer.

BACKGROUND: Although tumor-infiltrating T cells have been documented in ovarian carcinoma, a clear association with clinical outcome has not been established. METHODS: We performed immunohistochemical analysis of 186 frozen specimens from advanced-stage ovarian carcinomas to assess the distribution of tumor-infiltrating T cells and conducted outcome analyses. Molecular analyses were performed in some tumors by real-time polymerase chain reaction. RESULTS: CD3+ tumor-infiltrating T cells were detected within tumor-cell islets (intratumoral T cells) in 102 of the 186 tumors (54.8 percent); they were undetectable in 72 tumors (38.7 percent); the remaining 12 tumors (6.5 percent) could not be evaluated. There were significant differences in the distributions of progression-free survival and overall survival according to the presence or absence of intratumoral T cells (P<0.001 for both comparisons). The five-year overall survival rate was 38.0 percent among patients whose tumors contained T cells and 4.5 percent among patients whose tumors contained no T cells in islets. Significant differences in the distributions of progression-free survival and overall survival according to the presence or absence of intratumoral T cells (P<0.001 for both comparisons) were also seen among 74 patients with a complete clinical response after debulking and platinum-based chemotherapy: the five-year overall survival rate was 73.9 percent among patients whose tumors contained T cells and 11.9 percent among patients whose tumors contained no T cells in islets. The presence of intratumoral T cells independently correlated with delayed recurrence or delayed death in multivariate analysis and was associated with increased expression of interferon-gamma, interleukin-2, and lymphocyte-attracting chemokines within the tumor. The absence of intratumoral T cells was associated with increased levels of vascular endothelial growth factor. CONCLUSIONS: The presence of intratumoral T cells correlates with improved clinical outcome in advanced ovarian carcinoma.

Adult↗
PubMed2003

Long-term use of mycophenolate mofetil is associated with a reduction in the incidence and risk of late rejection.

To evaluate the association of long-term continuous (minimum 1 year) mycophenolate mofetil (MMF) vs. azathioprine (AZA) therapy with the incidence of late acute rejection, we analyzed 47 693 primary renal allograft recipients reported to the United States Renal Data System between 1988 and 1998. The primary study endpoint was acute rejection beyond 1 year after transplantation. Univariate Kaplan-Meier analysis and multivariate Cox proportional hazard models were used to investigate the risk of reaching the study endpoints. All multivariate analyses were corrected for potential confounding covariates. Mycophenolate mofetil was associated with a 65% decreased risk of developing late acute rejection as compared to AZA (RR = 0.35, CI 0.27-0.45, p < 0.001). The incidence of acute rejection episodes at 2 and 3 years post-transplantation was significantly lower in the MMF group (0.9% at 2 years, 1.1% at 3 years) than the AZA group (6.1% at 2 years, 9.3% at 3 years). In the primary vs. repeat late rejection analysis, MMF patients exhibited a decreased late acute rejection risk of 72% (RR = 0.28, p < 0.001) and 60%, respectively (RR = 0.40, p < 0.001). In African Americans, the late acute rejection risk was 70% lower in MMF patients than AZA patients (RR = 0.30, p < 0.001). Further study is indicated to determine the optimal duration of MMF therapy after renal allograft transplantation.

Black People↗
PubMed2002

Biomedical informatics: the future for drug development.

The problems that exist in drug development are well documented: the limited number of new chemical entities, increased cost of drug development, problems in clinical trials (Phase III), product launches that result in withdrawal, and pressure to reduce the cost of pharmaceuticals from the government. It appears that the promise of genomics has not yet reached its full potential to impact the process. This review identifies the need to develop and implement the area of biomedical informatics for increased success in drug development and healthcare in general.

Aging↗
PubMed2002

Opening Pandora's box: clinical data and the study of complex diseases.

Complex diseases have complex phenotypes, and proper diagnosis requires that the analysis take into account the patient's history and exposure to environmental factors, as well as genetic information. Signaling information is one aspect of a grander "biomedical informatics" approach advocated for a better understanding of a patient's medically relevant disease phenotype.

Disease Progression↗
PubMedDate not supplied

Modeling and simulation of pathways in menopause.

The analytical representation and simulation of complex molecular pathways can contribute to understanding and evaluating physiological as well as pathological processes. We are interested in modeling the processes of menopause to stratify women in terms of the genotypic and environmental components and their implications for development of individualized risk of postmenopausal disorders, e.g., breast and ovarian cancer, cardiovascular disease, and osteoporosis. We have initiated this study using the UltraSAN package to analyze the pathway associated with estrogen production. This model incorporates detailed information about the hormone factors affecting estrogen production, and the simulations carried out are based on published experimental data corresponding to hormone levels during the course of the normal female reproductive cycle. The agreement between the experimental data and the simulation is typically less than 2 ng/ml or 2 pg/ml respectively for progesterone and estradiol output. This approach further permits inclusion of information about an SNP observed in the gene coding for the enzyme aromatase as a model to study the impact of reduced enzymatic activity on hormone levels.

Climacteric↗