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Biomedical subjects

Kris E Gaston

Publications and source records attributed to Kris E Gaston.

11 recordsLinked to original sources

The use of erythropoietin in patients undergoing radical prostatectomy: effects on hematocrit, transfusion rates and quality of life.

OBJECTIVE: It was the aim of this study to prospectively study the effects on hematocrit levels, transfusion rates and quality of life (QOL) indices in men preoperatively supplemented with recombinant erythropoietin (rEPO) undergoing radical prostatectomy for clinically localized prostate cancer. METHODS: Thirty men undergoing radical prostatectomy were randomized either to receive rEPO (n=25) or to serve as controls (n=25). Outcome measurements obtained preoperatively, as well as 10 days and 6 weeks postoperatively included serum hematocrit levels, transfusion rates and QOL indices (using SF-12 validated questionnaires). RESULTS: The rEPO group had a significant increase in preoperative hematocrit (median increase=4 points; p=0.002). Although there were no significant differences in hematocrit at 10 days, the rEPO had a significantly higher hematocrit value at 6 weeks (p=0.0086). No differences were observed in transfusions rates between groups (4% in each group). SF-12 mental and SF-12 physical scores were not different between the two groups at any time point. CONCLUSION: Preoperative administration of rEPO significantly increases preoperative and postoperative hematocrit levels. However, no differences were observed with regard to transfusion rates or postoperative QOL indices despite these higher hematocrit values.

Adult↗

Plasma cell (Zoon's) balanitis with concomitant HIV infection.

We report a case of the development of Zoon's balanitis in an African-American man with human immunodeficiency virus. Photographs of the clinical and pathological lesion are presented. To our knowledge, this has not been recently reported in urologic studies. The clinicopathologic correlation is discussed.

Adult↗

Rare cause of ureteral obstruction.

This report presents bilateral ureteral obstruction due to possible ureteritis in a bone marrow transplant patient with resurgence of BK virus after hemorrhagic cystitis. This is believed to be the first description of this type of ureteral obstruction. The presented case includes the management plan.

Adult↗

Hand-assisted laparoscopic nephrectomy: prospective evaluation of the learning curve.

PURPOSE: Laparoscopic nephrectomy (LN) has recently become an emerging standard for extirpative surgery of the kidney. LN has historically proven to have a steep learning curve with longer operative times until a surgeon gains adequate laparoscopic experience. Hand-assisted laparoscopic nephrectomy (HALN) is fast becoming a commonly used procedure to remove kidneys as it may have a reduced learning curve compared to standard LN. To date no prospective studies have evaluated the learning curve of HALN with regard to improvements in operative times and technical difficulty. We prospectively evaluated the learning curve for HALN in a residency training program as it compares to open nephrectomy. MATERIALS AND METHODS: HALN was performed in 30 consecutive patients for various indications. The senior urology resident functioned as the primary surgeon and the same attending surgeon was present throughout all cases. All participating residents had to have performed at least 15 open nephrectomies to serve as an internal, personal reference. Difficulty scores were obtained at the completion of the case from the resident surgeon comparing HALN to open nephrectomy, which ranged from 1 to 5. Operative times, estimated blood losses and lengths of stay were obtained at the time of surgery and hospitalization. RESULTS: Median difficulty score was equivalent to open nephrectomy for the first case but decreased significantly by case 4 (p = 0.0006). Median operative times decreased significantly from 178 minutes in the first cases to 85 minutes by case 6 (p = 0.0002). Estimated blood loss and length of hospitalization did not differ significantly. CONCLUSIONS: HALN has a relatively short learning curve reflected by the rapid decrease in difficulty scores and operative times by case 4. Similar results may be expected when training practicing urologists to perform HALN.

Adult↗

Racial differences in prostate androgen levels in men with clinically localized prostate cancer.

PURPOSE: We sought to determine whether there are racial differences in androgenic stimulation within the prostate tissue microenvironment. MATERIALS AND METHODS: Steroid hormones were extracted from snap frozen tissue obtained intraoperatively from radical prostatectomy specimens of 36 black and 59 white Americans. Testosterone, dihydrotestosterone (DHT), androstenedione (ASD), dehydroepiandrosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin (SHBG) and prostate specific antigen (PSA) were measured using radioimmunoassay. The Wilcoxon 2 group test was performed to compare clinical characteristics and tissue steroid levels between white and black Americans. Nonparametric rank ANOVA was used to consider race and other clinical factors in a multivariable way. RESULTS: Black and white American men were similar with respect to serum PSA, and pathological grade and stage. However, black men were younger (p = 0.01) and had a significantly higher body mass index (p = 0.02). Black and white men had similar testosterone and DHT. However, black men had higher ASD (p = 0.006) and SHBG (p = 0.009). Racial differences in ASD (p = 0.015) and SHBG (p = 0.008) persisted after controlling for age, body mass index, PSA, and pathological Gleason sum and stage. CONCLUSIONS: Tissue levels of testosterone and DHT did not differ by race. However, black men had higher tissue ASD and SHBG than white men. Higher tissue ASD did not result in a greater conversion of ASD to testosterone in the prostate of black men. Higher tissue SHBG may activate the androgen receptor through cyclic adenosine monophosphate dependent pathways.

Aged↗

Racial differences in androgen receptor protein expression in men with clinically localized prostate cancer.

PURPOSE: Black American men experience disproportionate mortality from prostate cancer (CaP) compared with white American men. Differences in outcome may stem from differences within the androgen axis. Since serum testosterone levels appear to be similar by race in men with CaP, we measured and compared androgen receptor (AR) protein expression in malignant and benign prostate tissue from black and white men who underwent radical prostatectomy for clinically localized CaP. MATERIALS AND METHODS: Archived radical prostatectomy specimens obtained from 25 white and 25 black men had AR protein antigen retrieved and immunostained. AR protein expression from CaP and benign tissue was assessed by 2 methods. Automated digital color video image analysis was used to measure the percent area immunostained for AR protein and the intensity of expression (mean optical density). Visual scoring was performed to compare results with automated values. RESULTS: In black compared with white men malignant nuclei were 27% more likely to immunostain for AR (p = 0.005) and in immunopositive nuclei AR protein expression was 81% greater (p = 0.002). Visual scoring of malignant nuclei revealed that AR immunostaining was significantly increased in black vs white men (171 +/- 40 vs 149 +/- 37, p = 0.048). In immunopositive benign nuclei AR protein expression was 22% greater in black than in white men (p = 0.027). Visual scoring of benign nuclei revealed 20% increased immunostaining in black vs white men, although this difference did not attain statistical significance (p = 0.065). Racial differences in AR protein expression were not explained by age, pathological grade or stage, although serum prostate specific antigen levels were higher in black men (9.7 +/- 7.5 vs 15.5 +/- 12.2 ng/ml, p = 0.049). CONCLUSIONS: AR protein expression was 22% higher in the benign prostate and 81% higher in the CaP of black African compared with white men. CaP may occur at a younger age and progress more rapidly in black than in white men due to racial differences in androgenic stimulation of the prostate.

Aged↗

Mutational analysis of the androgen receptor using laser capture microdissection and direct sequencing.

Molecular analysis of prostate cancer specimens is complicated by tumor heterogeneity and admixture of malignant cells with benign epithelium, stroma and inflammatory cells. Laser Capture Microdissection allows procurement of selected groups of cells from specific areas of tissue sections. We have used Laser Capture Microdissection to obtain pure samples of malignant prostate epithelial cells from frozen radical prostatectomy specimens. Methods for DNA extraction, androgen receptor amplification and exon sequencing have been optimized. These methods should be adaptable for molecular analysis of DNA, RNA and protein from other complex tissues.

DNA Mutational Analysis↗

A novel method for the analysis of the androgen receptor.

The role of the androgen receptor in the regulation of prostate cancer development and progression has been a focus of intense research. Until recent years, the level of expression of the androgen receptor protein was described qualitatively. Immunohistochemical parameters have been established that show a linear relationship between androgen receptor expression and immunostaining. Intensity of immunostaining can be accurately measured using computer-assisted color video image analysis. Studies of progression and treatment of prostate cancer will benefit from the ability to quantitatively measure androgen receptor expression.

Animals↗

Pharmacotherapy for biochemical recurrences after therapy for localised prostate cancer.

Prostate-specific antigen (PSA) has revolutionised screening for and monitoring of prostate cancer (CaP). Currently, most men failing potentially curative CaP therapies develop biochemical evidence of recurrent disease (defined by detectable PSA levels) long before the onset of clinical symptoms. Androgen deprivation therapy (ADT) remains the gold standard for the treatment of metastatic CaP. Conventional ADT is orchiectomy or luteinising hormone-releasing hormone agonists. ADT is most commonly associated with side effects such as erectile dysfunction, decreased libido, gynecomastia and osteoporosis. Intermittent ADT or oral anti-androgens may limit the side effects associated with ADT while retaining efficacy. Although widely studied, the optimal timing to begin ADT remains an important and unanswered question. Future advances in gene therapy and immunotherapy hold the greatest promise to provide effective treatments against recurrent CaP while minimising morbidity.

Androgen Antagonists↗