Biomedical subjects

Rodney Dunn

Publications and source records attributed to Rodney Dunn.

7 recordsLinked to original sources

PubMed2005

Racial treatment trends in localized/regional prostate carcinoma: 1992-1999.

BACKGROUND: African-American men have a greater incidence of and mortality from prostate carcinoma compared with white men, and they are less likely to receive definitive therapy (radical prostatectomy or external beam radiation therapy). During the 1990s, the use of brachytherapy increased; however, its influence on racial and ethnic prostate carcinoma treatment trends remains unclear. The objective of this study was to describe treatment trends over the period 1992-1999 for localized/regional prostate carcinoma among white, Hispanic, and African-American men. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) registry data from 1992 through 1999, logistic regression models were used to determine whether the odds of receiving a specific treatment modality differed by racial and ethnic group and whether the differences changed over time when the models were adjusted for age, marital status, tumor grade, and SEER site (geography). RESULTS: The authors identified 142,340 men, including white men (81.6%), Hispanic men (6.4%), and African-American men (12.0%). Racial and ethnic differences in the rates of use of androgen-deprivation therapy/expectant management were noted; however, these differences appeared to lessen over time (P < 0.001). The rate of utilization of radical prostatectomy increased for Hispanic men, remained flat for African-American men, and decreased for white men. The utilization of brachytherapy and combination therapy increased for all three groups; however, the greatest increase in utilization was among white men. CONCLUSIONS: Further research will be required to determine the patient-level and provider-level variables that influence racial and ethnic treatment differences in localized/regional prostate cancer.

Black or African American↗

PubMed2005

The increasing incidence of newborn circumcision: data from the nationwide inpatient sample.

PURPOSE: Newborn circumcision is the most common surgical procedure in the United States, yet there are few contemporary data regarding circumcision rates or the factors that affect these rates. The goal of this study was to determine trends in the national rate of newborn circumcision between 1988 and 2000, and to evaluate patient and hospital factors associated with newborn circumcision. MATERIALS AND METHODS: The Nationwide Inpatient Sample provides information on 5 million to 7 million inpatient stays per year. Newborn male hospitalizations were selected, and those newborns who underwent circumcision were identified using International Classification of Disease-9 procedure codes. Weighted national estimates of circumcision rates were calculated, and patient and hospital characteristics were examined to identify factors associated with newborn circumcision. RESULTS: We identified 4,657,402 newborn male hospitalizations during a 13-year period. Circumcision rates increased significantly with time-48.3% of newborn males underwent circumcision in 1988 to 1991 vs 61.1% in 1997 to 2000 (p <0.0001). In multivariate regression analysis the odds of circumcision increased by 6.8% per year during the study period (p <0.0001). Patient characteristics associated with increased odds of circumcision in the multivariate model included private insurance (p <0.0001), higher socioeconomic status (p <0.0001), fewer co-morbid diagnoses (p <0.0001) and black race (p <0.0001). Hospital factors associated with increased odds of circumcision included Northeast or Midwest geographic region and rural location. CONCLUSIONS: There was a significant increase in the rate of newborn circumcision between 1988 and 2000. The increase may be related to increased recognition of the potential medical benefits of circumcision. However, the increase may also result in a higher incidence of surgical complications of circumcision.

Circumcision, Male↗

PubMed2003

Phase II trial of oral cyclophosphamide, prednisone, and diethylstilbestrol for androgen-independent prostate carcinoma.

BACKGROUND: The authors evaluated the combination of oral cyclophosphamide, oral prednisone, and diethylstilbestrol (DES) in patients with androgen-independent prostate carcinoma (AIPC). METHODS: Thirty-seven patients with prostate carcinoma refractory to androgen ablation who had undergone antiandrogen withdrawal (if previously treated with an antiandrogen) were enrolled in the current study. They were treated with oral cyclophosphamide 100 mg per day on Days 1-20, prednisone 10 mg per day continuously, and DES 1 mg continuously, on a 30-day cycle. Warfarin 1 mg per day was given as prophylaxis for thrombosis. Patient levels of prostate-specific antigen (PSA) were monitored on a monthly basis, with imaging studies every 3 months. Patients continued to receive therapy until disease progression or the occurrence of significant toxicity. The effect of therapy on the patient's quality of life was assessed using the Functional Assessment of Cancer Therapy-Prostate. RESULTS: Thirty-six patients were evaluable for response. Of the 36 patients, 15 (42%) had a 50% or greater decline in PSA levels from pretreatment levels and 1 patient (6%) with measurable disease had a partial response to therapy. The median duration of response was 4.5 months (range, 4-18 months). The overall median survival period was 16.4 months. The treatment was well tolerated, with only three patients removed from the study for toxicities associated with treatment. One patient, who had been treated for more than 24 months, developed acute leukemia. Quality of life evaluation in 17 patients showed a significant improvement in responders, whereas nonresponders had no deterioration while receiving therapy. CONCLUSIONS: Cyclophosphamide, prednisone, and DES represent a well tolerated, low-cost combination therapy with significant activity in the treatment of patients with AIPC.

Administration, Oral↗

PubMed2003

Glycogen synthase kinase-3 regulates mouse oocyte homologue segregation.

Intracellular regulation of oocyte meiosis is not completely understood. However, reversible phosphorylation, which involves serine/threonine protein kinases and phosphatases (PP), is an important mediator. Glycogen synthase kinase-3 (GSK-3) is a highly conserved serine/threonine protein kinase. Currently no reports exist on presence or function of GSK-3 in mammalian oocytes. The aim of this study was to determine GSK-3 presence/absence, transcript and protein expression, intracellular protein distribution, and to investigate the functional importance of GSK-3 in mouse oocyte meiosis. Germinal vesicle-intact (GVI) oocytes contained both GSK-3 transcript and protein. Although GSK-3 beta-isoform is the only transcript identifiable in GVI oocytes, both alpha- and beta-isoforms were recognized by Western blot analysis. In growing, meiotic-incompetent oocytes GSK-3 was present, diffusely located throughout the cytoplasm and absent in the nucleus, whereas in meiotic-competent oocytes this cytoplasmic GSK-3 displays a predominant peri-oolemma staining. Treatment of mouse GVI oocytes with lithium chloride (LiCl), which inhibits both inositol monophosphatase (IMPase) and GSK-3, had no significant influence on oocyte viability, morphology, or development to metaphase II (MII). However, LiCl caused abnormal spindle formation and significantly increased incidence of abnormal homologue segregation during the first meiotic division. L690,330, which is a specific IMPase inhibitor, had no significant effect on oocyte viability, morphology, MII development, or homologue segregation. This is the first report of GSK-3 in mammalian oocytes. LiCl inhibition of mouse oocyte GSK-3 modified organization of microtubules and/or function of meiotic spindles thus compromising segregation of condensed bivalent chromosomes.

Animals↗

PubMed2003

Specific inhibition of mouse oocyte nuclear protein phosphatase-1 stimulates germinal vesicle breakdown.

Okadaic acid (OA)-induced germinal vesicle breakdown (GVBD) and localization of protein phosphatase-1 (PP1) in oocyte nuclei are suggestive of PP1's role in regulating oocyte GVBD. To explore this possibility, we microinjected protein phosphatase (PP) inhibitors OA, anti-PP1 antibody (anti-PP1), PP1 inhibitor I2, and anti-PP2A antibody (anti-PP2A) into nuclei of roscovitine (ROSC)-arrested mouse oocytes. Oocytes were also injected with recombinant PP1 in the absence of ROSC. Oocytes were assessed for GVBD and metaphase II (MII) development at 2 and 18 hr post-injection. Data were analyzed using Cochran-Mantel-Haenszel Statistics adjusted for time. Microinjection of OA significantly enhanced GVBD in comparison to controls at 2 and 18 hr (P < 0.01), yet had no effect on MII development. Similarly, microinjection of anti-PP1 resulted in significantly higher levels of GVBD compared to controls at 2 and 18 hr (P < 0.01). Interestingly, anti-PP1 microinjection also tended to enhance MII development at 18 hr in comparison to controls (P < 0.09). Microinjection of I2, anti-PP2A, and PP1 had no effect on GVBD or MII development. If reduction of PP1 activity was important for GVBD, one would anticipate an endogenous means of regulating PP1 activity at this developmental stage. In somatic cells, phosphorylation of PP1 at Thr320 causes PP1 inactivation. Germinal vesicle-intact oocytes did not contain phosphorylated PP1, as determined using a specific Thr320-Phospho-PP1 antibody, Western blot analysis, and confocal immunocytochemistry. At or around the time of GVBD, oocyte PP1 became phosphorylated at Thr320, which remained phosphorylated through MII development. These data indicate that inhibition of intra-nuclear PP1, through specific antibody neutralization, mimics OA-stimulated GVBD, providing the first direct evidence that nuclear PP1 is involved in regulation of oocyte nuclear membrane integrity. In addition, phosphorylation of PP1 occurs at/or around GVBD indicating that inactivation of PP1 is an important intracellular event in regulation of nuclear envelope dissolution at GVBD.

Animals↗

PubMed2002

Insulin-like growth factor-1, insulin-like growth factor binding protein-3, and body mass index: clinical correlates of prostate volume among Black men.

OBJECTIVES: To examine the relationship between insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), and body mass index and prostate volume, as a surrogate marker for benign prostatic hyperplasia, in a community-based sample of black men. Epidemiologic studies examining the role of IGF-1 and IGFBP-3 suggest that increased levels of serum IGF-1 and decreased levels of serum IGFBP-3 are associated with an increased risk of prostate cancer. Few studies have examined these factors with respect to benign prostatic hyperplasia, and these have been limited to white men. METHODS: The study population consisted of a sample of 364 black men, 40 to 79 years of age, residing in Genesee County, Michigan. Men with prostate cancer or prior prostate surgery were excluded. All subjects completed a clinical examination, which included a complete urologic examination with transrectal ultrasonography, anthropometric measurements, and serum assays for IGF-1 and IGFBP-3. RESULTS: Multivariable regression models demonstrated that prostate volume increased with increasing age (P <0.0001) and body mass index (P = 0.03). IGFBP-3 rather than IGF-1 was positively associated with increasing prostate volume (P = 0.003). CONCLUSIONS: This is the largest study describing the relationships between IGF-1, IGFBP-3, and body mass index and prostate volume, and the only study in black men. Although earlier studies demonstrated an association between IGF-1 and prostate cancer risk, our findings indicate that IGFBP-3 is more relevant for prostate enlargement, suggesting that IGF-1 and IGFBP-3 may play different pathophysiologic roles in benign and malignant prostatic conditions.

Aged↗

PubMed2002

Tissue microarray sampling strategy for prostate cancer biomarker analysis.

High-density tissue microarrays (TMA) are useful for profiling protein expression in a large number of samples but their use for clinical biomarker studies may be limited in heterogeneous tumors like prostate cancer. In this study, the optimization and validation of a tumor sampling strategy for a prostate cancer outcomes TMA is performed. Prostate cancer proliferation determined by Ki-67 immunohistochemistry was tested. Ten replicate measurements of proliferation using digital image analysis (CAS200, Bacus Labs, Lombard, IL, USA) were made on 10 regions of prostate cancer from a standard glass slide. Five matching tissue microarray sample cores (0.6 mm diameter) were sampled from each of the 10 regions in the parallel study. A bootstrap resampling analysis was used to statistically simulate all possible permutations of TMA sample number per region or sample. Statistical analysis compared TMA samples with Ki-67 expression in standard pathology immunohistochemistry slides. The optimal sampling for TMA cores was reached at 3 as fewer TMA samples significantly increased Ki-67 variability and a larger number did not significantly improve accuracy. To validate these results, a prostate cancer outcomes tissue microarray containing 10 replicate tumor samples from 88 cases was constructed. Similar to the initial study, 1 to 10 randomly selected cores were used to evaluate the Ki-67 expression for each case, computing the 90th percentile of the expression from all samples used in each model. Using this value, a Cox proportional hazards analysis was performed to determine predictors of time until prostate-specific antigen (PSA) recurrence after radical prostatectomy for clinically localized prostate cancer. Examination of multiple models demonstrated that 4 cores was optimal. Using a model with 4 cores, a Cox regression model demonstrated that Ki-67 expression, preoperative PSA, and surgical margin status predicted time to PSA recurrence with hazard ratios of 1.49 (95% confidence interval [CI] 1.01-2.20, p = 0.047), 2.36 (95% CI 1.15-4.85, p = 0.020), and 9.04 (95% CI 2.42-33.81, p = 0.001), respectively. Models with 3 cores to determine Ki-67 expression were also found to predict outcome. In summary, 3 cores were required to optimally represent Ki-67 expression with respect to the standard tumor slide. Three to 4 cores gave the optimal predictive value in a prostate cancer outcomes array. Sampling strategies with fewer than 3 cores may not accurately represent tumor protein expression. Conversely, more than 4 cores will not add significant information. This prostate cancer outcomes array should be useful in evaluating other putative prostate cancer biomarkers.

Biomarkers↗