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Biomedical subjects

M C Benson

Publications and source records attributed to M C Benson.

At least 73 records · Page 4Linked to original sources

Analysis of continent versus standard urinary diversion.

The seemingly high complication and re-operation rates associated with continent urinary diversion have led some to criticize its morbidity and question its role in reconstructive urological surgery. We therefore reviewed our experience with all patients undergoing either continent or standard urinary diversion performed by 3 urological surgeons during a specified 3-year period. In 73 consecutive patients (22 continent urinary diversion, 51 standard urinary diversion), no significant difference was demonstrated with respect to the number of post-operative in-hospital days, complication rate, re-operation rate and operative mortality rate between the 2 groups. While those undergoing continent diversion were on average younger and healthier than their counterparts receiving standard diversion, stratification of patients in each group according to age and a pre-operative "fitness" score showed no significant difference in operative mortality or major morbidity between comparable patients in each group. The mean post-operative length of hospital stay was, however, 3 days shorter for the youngest and fittest patients receiving standard versus continent urinary diversion.

Adult↗

Detection of cellular proliferation during compensatory renal growth using flow cytometry.

Compensatory renal growth (CRG) consists of cellular enlargement and a small but consistent increase in DNA content. It has been assumed that the increase in total renal DNA content was due to new cell formation, however, the possibility of nuclear polyploidy remained an alternative explanation. To test the hypothesis whether cellular hyperplasia is the cause of the increase in DNA content during compensatory growth after renal deprivation, we performed cell cycle analysis using flow cytometry. Following unilateral nephrectomy, the amount of cortical cells in the S phase increased by 12% at 10 h while the number of cells in the G2M phase increased by 7% at 120 h. Medullary cells entering the S phase increased by 26% at 24 h and those in G2M increased by 12% at 168 h. DNA synthesis and replication occurs during CRG following unilateral nephrectomy as evidenced by an increase in cells entering both the S and G2M phases of the cell cycle. The increase in DNA content during CRG is a result of cellular proliferation and not polyploidy.

Animals↗

Urinary diversion.

The patient facing cystectomy now has the opportunity to select various forms of urinary diversion. Although not all of the newer techniques have stood the test of time, preliminary results indicate that these continent diversions should be considered safe and effective. These procedures definitely alter the patient's lifestyle, resulting in a significantly better adjustment to the need for bladder removal. With experience, these procedures can be performed with morbidity rates very similar to those encountered with ileal conduit diversion. As with any procedures, however, appropriate patient selection and surgical training are imperative.

Carcinoma, Transitional Cell↗

Flow cytometric determination of the multidrug resistant phenotype in transitional cell cancer of the bladder: implications and applications.

We detail our experience with a monoclonal antibody to detect the cell surface P-glycoprotein product of the multidrug resistance gene (MDR-1) in the human bladder. A total of 32 patients had 44 different specimens analyzed. The samples consisted of 8 normal bladders, 21 transitional cell carcinomas, 1 mucinous adenocarcinoma, 3 P-0 bladder wall specimens and 10 nonmalignant urothelial samples from cystectomies. P-glycoprotein was not detected in the normal adult or pediatric bladder. Bladder specimens from 3 children with a neurogenic bladder revealed enhanced expression (21%, 14% and 4% positivity). Transitional cell carcinoma usually demonstrates low expression at diagnosis (less than 6%), although 3 patients had enhanced initial expression (11%, 12% and 31%). Three patients treated with chemotherapy demonstrated 56%, 76% and 50% expression of MDR-1. Nonmalignant tissue from cystectomy specimens had low expression of MDR-1. The specificity of this system was confirmed with human bladder cell lines. The ability of flow cytometry to detect and quantify the expression of MDR-1 may allow for the early detection of chemotherapy resistance in patients with transitional cell carcinoma treated with systemic and intravesical therapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Flow cytometric analysis of localized adenocarcinoma of the prostate: the use of archival DNA analysis in conjunction with pathological grading to predict clinical outcome following radical retropubic prostatectomy.

Fifty-four specimens from patients undergoing radical prostatectomy for clinically confined prostate cancer between 1983 and 1987 were reviewed to determine the potential for flow cytometric (FCM) analysis of DNA ploidy and replication rate to predict disease recurrence. Each specimen was deparaffinized for FCM analysis and the pathology slides were reviewed by a single pathologist. FCM characteristics were correlated with pathological grade and stage, and both were correlated with disease status. In this series of patients, routine FCM analysis of DNA ploidy and replication rate failed to significantly enhance the ability of standard histopathological grading to predict disease recurrence in patients having clinically localized prostate cancer. Aneuploid tumors pathologically confined to the prostate did not appear to negatively affect prognosis.

Adenocarcinoma↗

The flow cytometric analysis of undescended testes in children.

Flow cytometric analysis was performed on the testicular aspirates of 45 consecutive children with unilateral cryptorchidism undergoing elective orchiopexy or orchiectomy. Concomitant histological analysis was performed on the testicular tissue obtained from either biopsy or orchiectomy specimens. In all cases deoxyribonucleic acid histograms appeared to correspond with microscopic appearance. Histograms from prepubescent patients demonstrated 85 to 95% of cells in the diploid (2c) peak and less than 10% of cells in the tetraploid peak (4c), representing prepubertal testes without active spermatogenesis. Three distinct patterns of ploidy were identified in postpubertal children corresponding to the histological appearances of normal spermatogenesis, maturation arrest and the Sertoli-cell-only syndrome, respectively. In addition, we identified an aneuploid cell population in the specimen from 1 patient, suggesting that this testis may be at risk for future malignant degeneration. We conclude that flow cytometry of testicular aspirates is an easy and effective means of testicular evaluation, which may permit predictions regarding the fertility and malignant potential of undescended testes in postpubertal children.

Adolescent↗

Ureteral reconstruction and bypass: experience with ileal interposition, the Boari flap-psoas hitch and renal autotransplantation.

A total of 18 patients underwent an operation for extensive ureteral loss from 1980 to 1986. The indications included recurrent calculi, retroperitoneal fibrosis, surgical trauma and tumor. Of the patients 10 had construction of an ileal ureter (4 had bilateral reconstruction), 6 had creation of a psoas hitch with a Boari bladder tube and 2 were treated by autotransplantation. Mean duration of followup was 4.8 years. The procedure was successful in 17 patients. There were no apparent differences among the groups. Selection criteria and potential complications are discussed with regard to each technique. These procedures provide an excellent means for reconstruction of the urinary tract in patients who have failed other treatments.

Adult↗

Enhanced detection of bladder cancer using the epithelial surface marker epithelial membrane antigen: a preliminary report.

The flow cytometry (FCM) technique allows for the rapid quantitative analysis of the DNA content of individual cells. In a variety of genitourinary tumors, DNA ploidy has a significant impact upon prognosis and ultimate patient survival. In patients having transitional cell cancer (TCC) of the bladder, FCM of voided urine and bladder barbotage specimens is highly correlated with cytologic analysis in the detection of malignant cells. One problem with this technique has been decreased sensitivity in samples containing large numbers of inflammatory cells. To improve FCM detection of TCC in bladder wash specimens, we developed a technique using a monoclonal antibody (Mab) specific to human, epithelial membrane antigen (EMA). The EMA cell-surface marker enabled us to differentiate bladder epithelial cells from lymphocytes and cellular debris. In combination with DNA analysis using propidium iodide, the EMA Mab increased the sensitivity and specificity of FCM compared to conventional analysis using propidium iodide alone. We conclude that epithelial cell-surface antigen staining using both EMA Mab and DNA staining can increase the FCM detection of TCC in bladder wash specimens.

Aged↗

Flow cytometry in carcinoma of the prostate.

Flow cytometry is a quantitative cytologic technique with demonstrated utility in the assessment of prostate cancer as well as other tumors. The authors summarize current data on its use in disease detection and diagnosis, prognostic evaluation, and monitoring of response to therapy. They also project future developments.

Cell Separation↗

Gene activity during the early phase of androgen-stimulated rat prostate regrowth.

Androgenic steroids regulate the proliferation rate of normal and malignant prostate cells. In order to investigate the molecular basis of this control, we utilized Northern and Western blot techniques to measure changes in the expression of individual genes during the early phase of prostate regrowth. Vestigial ventral prostate glands of 7-day castrated rats showed increased numbers of replicating cells within 12 h of continuous pharmacological testosterone replacement as demonstrated by flow cytometric procedures. The period prior to the onset of proliferative enhancement was accompanied by the sequential induction of a variety of transcripts encoding gene products often associated with cell growth. Within 1 h of treatment, mature mRNA transcripts for c-fos were induced 6-fold, returning to control levels by 2 h. Other genes showed transiently elevated transcript levels after 2 h (c-Ha-ras, c-Ki-ras) or after 8 h (c-myc,c-myb, beta-actin, and Mr 70,000 heat shock protein) of testosterone replacement. Expression of the polypeptide encoded by c-Ha-ras was coordinately enhanced (2-fold) during this period, but not to the levels of the transcript (20-fold induction). Transcripts encoding basic fibroblast growth factor were increased 16 h and later, subsequent to the earlier enhancement in the proliferation rate. By placing these genes in a defined temporal order with regard to their expression in response to testosterone, we have constructed a map of gene activity during early prostate regrowth. This map shows a number of genes, the products of which might participate in the mechanism by which androgens induce mitogenesis of prostate cells.

Animals↗

Long-term follow-up in patients treated with methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) for transitional cell carcinoma of urinary bladder: cause for concern.

Twenty-one patients with high-stage transitional cell carcinoma (TCC) of the bladder were treated with a combination of methotrexate, vinblastine, doxorubicin (Adriamycin), and cisplatin (M-VAC). There was a minimum follow-up of thirty-six months (range 36-45) in all patients. Patients were divided into three groups: 10 patients with recurrent TCC post radical cystectomy, 6 patients staged as T3/T4 or N1 treated in a neo-adjuvant setting, and 5 patients who received adjuvant M-VAC four weeks post radical cystectomy. The overall initial response rate in patients with measurable disease was 68 percent (11 of 14), complete response rate 31 percent, and partial response rate 37 percent. There was no response in 31 percent. The durability of response in this series was very disappointing with all complete responders having recurrence of disease, with duration of responses ranging from eight to twenty-one months. Of the 5 patients who received M-VAC as adjunctive therapy, only 1 remains disease-free; the other 4 patients experienced disease progression four to seventeen months postoperative, and all have died. There was one drug-associated death due to nadir sepsis, and myelosuppression occurred in 12 patients. While M-VAC seems to be the best protocol currently available, the real durability of response is most disappointing.

Aged↗

Calcium channel antagonists delay regression of androgen-dependent tissues and suppress gene activity associated with cell death.

Androgen deprivation subsequent to castration of an adult male rat results in the regression of sexual accessory tissues. Regression of these tissues involves the massive death of androgen-dependent cells. Using the rat ventral prostate gland as a model to study androgen-programed cell death, we have characterized a series of molecular events that accompany its regression. This analysis has shown that there was a sequential induction of specific gene transcripts in the ventral prostate gland following castration. The first event in this cascade was an abrupt induction of transcripts encoding c-fos. Since c-fos expression has been linked to perturbations in intracellular Ca2+ levels, we investigated whether membrane-mediated Ca2+ flux might be an early physiological step involved in the death of prostatic cells. To test this, rats were treated simultaneously upon castration with either verapamil or nifedipine, two different calcium channel antagonist drugs. Compared to the ventral prostate glands of untreated castrated rats, the glands of the calcium channel antagonist-treated rats showed a significant delay in all parameters associated with regression (loss of wet weight and DNA content and delay in histological changes associated with prostatic regression). The seminal vesicle glands of treated rats also showed signs of delayed regression. Furthermore, calcium channel antagonists suppressed the induction of transcripts encoding both c-fos and testosterone-repressed prostate message-2 (TRPM-2), a gene expressed exclusively by dying cells, during the first 62 hr following castration. These findings further support a role for calcium ion influx in the pathway leading to hormonally programed prostate cell death, and suggest the intriguing possibility that modulation of this activity can alter the process by which cells die.

Androgens↗

A report of cytomegalovirus cystitis and a review of other genitourinary manifestations of the acquired immune deficiency syndrome.

We report a case of symptomatic cytomegalovirus cystitis associated with the acquired immune deficiency syndrome related complex. The diagnosis of the acquired immune deficiency syndrome was established by bladder biopsy. The hematuria resolved after systemic acyclovir therapy. The other known urological manifestations of the acquired immune deficiency syndrome are discussed.

Acquired Immunodeficiency Syndrome↗

Fine-needle aspiration of the prostate.

Fine-needle aspiration biopsy of the prostate has been used for over 20 years as the prostate biopsy technique of choice throughout much of Europe. However, this technique has only recently gained acceptance in the United States. There is now an enlarging body of data confirming that fine-needle aspiration can be viewed as a safe, accurate, and reliable means for detection and diagnosis of prostate cancer. This review summarizes the European and United States experience with fine-needle aspiration and supports the utility of this biopsy technique as an important addition to the urologist's diagnostic armamentarium.

Biopsy, Needle↗

Application of flow cytometry and automated image analysis to the study of prostate cancer.

Flow cytometry and image analysis are complementary quantitative cytologic techniques that have demonstrated utility in the assessment and analysis of prostate cancer and other urologic and nonurologic tumors. This review is intended to assess the current state of the art and to project future directions and applications of these modalities in the pathologic assessment of prostate cancer. Special attention is directed toward the topics of prostate cancer detection and diagnosis, determination of patient prognosis, and the monitoring of patient response to therapy. We recommend that 1) flow cytometry and image analysis be used to determine pathologic parameters that will help in predicting poor patient prognosis and 2) quantitative cytologic determinations of DNA content be included in clinical trials so that their ultimate role in monitoring patient response to therapy can be determined. This knowledge will allow the development of protocols designed to test the value of earlier institution of multimodal therapy in high-risk populations.

Flow Cytometry↗

Enhanced expression of the c-myc protooncogene in high-grade human prostate cancers.

We examined a series of 29 surgical specimens of benign and malignant human prostate tissue for the expression of both the cHa-ras and c-myc protooncogenes. Northern blots were prepared using polyadenylated mRNA extracted from nine prostatic adenocarcinomas, 19 benign hypertrophied prostates (BPH) and one normal prostate. When the Northern blots were hybridized to a probe for cHa-ras, only one specimen of BPH showed an appreciable amount of the 1.2-kb transcript homologous to cHa-ras. Upon reprobing these blots with c-myc, six cancers showed a considerable amount of a 2.4-kb transcript homologous to c-myc. Three other cancers and all the benign tissue showed little or no detectable 2.4-kb c-myc transcript. On retrospective analysis, the cancers with elevated c-myc transcripts were found to have a Gleason score of 5 and above (poorly differentiated tumors), while the cancers with little or no c-myc transcripts were all of Gleason score 4 and lower. Finally, we compared our ability to detect c-myc transcripts in mRNA extracted from a surgically derived prostate tumor with mRNA extracted from the same tumor subject to a sham electrocautery procedure, as would occur during transurethral resection. The electrocautery procedure decreased both the intensity and the integrity of the c-myc signal in mRNA from the tumor. Thus, our exclusive use of surgically derived prostate tumors may be the reason we are able to detect an elevation in the expression of c-myc mRNA in high-grade tumors.

Adenocarcinoma↗

Urologic manifestations of AIDS.

A retrospective analysis of 60 patients with Acquired Immune Deficiency Syndrome (AIDS) seen between 1981-1985 was performed to determine the genitourinary manifestations of this disease. Twenty-two per cent were found to have significant proteinuria, while 7 per cent had nephrotic syndrome which was associated with an extremely rapid demise. Renal insufficiency occurred in 27 per cent and renal biopsy results, when abnormal, revealed focal and segmental glomerulosclerosis. Pyuria was found in 52 per cent of patients, and urinary tract infections occurred in 20 per cent. Atypical pathogens including Candida, Salmonella, Acinetobacter calcoaticus, and cytomegalovirus were encountered.

Acquired Immunodeficiency Syndrome↗

Prognostic variables in patients with transitional cell carcinoma of the renal pelvis and proximal ureter.

Recent technological advances in urological endoscopic surgery of the renal pelvis and proximal ureter via ureteroscopy or percutaneous nephroscopy have made it possible to consider parenchymal-sparing procedures in patients with transitional cell carcinoma. To define the role of these procedures in the management of renal pelvic or proximal ureteral transitional cell carcinoma we analyzed retrospectively 31 patients who underwent nephroureterectomy for transitional cell carcinoma of the renal pelvis and/or proximal ureter. High grade upper urinary tract transitional cell carcinoma and a history of metachronous or synchronous bladder transitional cell carcinoma were independent adverse prognostic factors. However, patients with low grade upper urinary tract transitional cell carcinoma and no evidence of a urothelial field change had a 100 per cent 5-year survival rate. It would appear that parenchymal-sparing endoscopic techniques should be regarded with caution in patients with either high grade transitional cell carcinoma of the renal pelvis and proximal ureter or a history of bladder cancer.

Adolescent↗