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J B Thrasher

Publications and source records attributed to J B Thrasher.

At least 37 records · Page 2Linked to original sources
PubMed1996

Insulin-like growth factor-binding protein-2 and -3 expression in benign human prostate epithelium, prostate intraepithelial neoplasia, and adenocarcinoma of the prostate.

Insulin-like growth factor (IGF)-binding proteins (IGFBPs) modulate the activity of IGFs. In vitro human prostate epithelial cells secrete IGFBP-2 and -3. In vivo IGFBP-2 is increased, and IGFBP-3 is decreased in the serum of patients with prostate cancer. Immunohistochemistry and in situ hybridization were performed to compare the expression of IGFBP-2 and -3 in vivo in prostate tissue containing benign epithelium, high grade prostate intraepithelial neoplasia (PIN), and adenocarcinoma. Immunoreactivity and messenger ribonucleic acid (mRNA) hybridization signals for IGFBP-2 and -3 were localized to epithelial cells. IGFBP-2 immunostaining intensity was significantly increased in PIN regions compared to that in normal epithelium and was further increased in malignant cells. IGFBP-2 mRNA was also significantly increased in PIN and cancer cells. IGFBP-3 immunoreactivity was significantly increased in PIN regions compared to normal epithelium; however, IGFBP-3 protein was significantly decreased in malignant cells. IGFBP-3 mRNA remained virtually unchanged in benign epithelium, PIN, and adenocarcinoma cells. These results demonstrate that increased IGFBP-2 protein in PIN and malignant cells is probably due to increased mRNA expression. However, levels of IGFBP-3 protein may be due to pre- and/or posttranslational mechanisms, including proteolysis. The changes in IGFBP-2 and -3 protein levels in prostatic tissue are in agreement with serum changes reported in patients with prostate cancer.

Adenocarcinoma↗
PubMed1996

The effect on the insulin-like growth factor system in human prostate epithelial cells of immortalization and transformation by simian virus-40 T antigen.

The insulin-like growth factor (IGF) system has been demonstrated to be important for proliferation and differentiation in tissues. This system has also been demonstrated to be an important regulator of the growth of normal prostate epithelium and has been implicated in the process of transformation to human epithelial prostate cancer. This study examined the function of the various components of the IGF system in benign prostate epithelium (BPE), simian virus-40 (SV40)-T antigen-immortalized prostate epithelial cells, P69SV40-T (P69), and two sublines generated from the parental line by serial passage through athymic mice: one tumorigenic (M2182) and one metastatic (M12). IGF-II messenger ribonucleic acid (mRNA) and protein were detected in BPE cells, and each of the three P69 cell lines. IGF-II protein levels were significantly higher in medium collected from the P69, M2182, and M12 cells than in BPE. Proliferation in response to IGF was P69 > BPE > M2182 > M12. The proliferative responses in the four cell types were paralleled by an increase in c-jun. In addition, as the cells became progressively more tumorigenic, the basal level of c-jun mRNA increased. IGF-binding protein-2 (IGFBP-2), -3, -4, -5, and -6 could be detected in the primary epithelial cell medium; however, as the cells became progressively more tumorigenic, there was a decrease in IGFBP-2, -3, -5, and -6 in the medium. The type 1 IGF receptor (IGFr) also decreased as the cells became more tumorigenic. The M12 cells had 80% fewer receptors than the P69 cells and 70% fewer than M2182 cells. There was no change in the Kd for IGF between the cell lines. Based on these data it would appear that the difference in proliferation between the BPE cells and P69s may be due to an increased concentration of inhibitory IGFBPs in the P69 medium. The decrease in proliferation seen in response to IGF in M2182 and M12 cells compared to the P69s would appear at least in part to be due to a decreased IGFr number. IGFr mRNA is represented by 11.0- and 7.0-kilobase bands in the BPE and P69 cells, but only by an 11.0-kilobase band in M2182 and M12 cells. These data indicate that there are significant changes that occur in the IGF system during the process of malignant transformation of the prostate epithelium. The changes described in the P69 cell system are similar to those seen in vivo and suggest that an intact IGF system may be important in maintaining a differentiated epithelial cell.

Animals↗
PubMed1996

Protein and messenger ribonucleic acid (mRNA) for the type 1 insulin-like growth factor (IGF) receptor is decreased and IGF-II mRNA is increased in human prostate carcinoma compared to benign prostate epithelium.

Insulin-like growth factors (IGFs) and the type 1 IGF receptor (IGF-R) are involved in normal growth and development of the human prostate. Changes in levels of IGF-R and IGFs have been shown for several malignancies. Immunohistochemistry and in situ hybridization were performed to compare the expression of IGF-R and IGF-II in vivo in prostate tissue containing benign epithelium, high grade prostate intraepithelial neoplasia (PIN), and adenocarcinoma. Messenger ribonucleic acid (mRNA) hybridization signals and immunoreactivity for IGF-R were localized primarily to epithelial cells, with less signal in stroma. IGF-R mRNA was significantly decreased by 42% in PIN and 35% in cancer cells compared to that in benign epithelium (P < 0.0001). IGF-R immunostaining was significantly decreased by 32% in PIN and by 42% in malignant epithelium compared to that in benign epithelium (P < 0.004). IGF-II mRNA was also localized primarily to epithelial cells. IGF-II mRNA was significantly increased by 30% in adenocarcinoma compared to that in benign epithelium (P < 0.03). Immunoreactivity for IGF-II was localized to both stroma and epithelium. Protein levels for IGF-II were not significantly increased in cancer cells compared to those in benign epithelium. The decrease in the type 1 IGF receptor and increase in IGF-II mRNA may affect prostate cancer proliferation and differentiation.

Adenocarcinoma↗
PubMed1996

Insulin-like growth factor-binding proteins (IGFBP)-4, -5, and -6 in the benign and malignant human prostate: IGFBP-5 messenger ribonucleic acid localization differs from IGFBP-5 protein localization.

Insulin-like growth factor (IGF)-binding proteins (IGFBPs) modulate the actions of IGF. We have previously reported that IGFBP-2 messenger ribonucleic acid (mRNA) and protein are increased, and IGFBP-3 protein decreased in malignant prostate epithelium compared to benign epithelium. In this study, we examined the other IGFBPs secreted by prostate cells in vitro, namely IGFBP-4, -5, and 6. Immunoreactivity and mRNA signals for IGFBP-4 and -6 were localized to epithelial cells, with less signal in stroma. IGFBP-4 immunostaining and hybridization signal were significantly increased in prostate adenocarcinoma compared to those in benign epithelium. Immunostaining for IGFBP-5 was localized to the epithelium and stroma. IGFBP-5 immunoreactivity was significantly increased in malignant compared to benign epithelium. IGFBP-5 mRNA signal was not localized to epithelial cells; rather, the signal was over stromal cells surrounding the acinar structures. These cells are thought to be fibroblasts. We show that IGFBP-4 mRNA and protein and IGFBP-5 protein are increased in malignant epithelium compared to benign epithelium, that IGFBP-6 is present in benign and malignant epithelium, and that there is differential localization of IGFBP-5 mRNA and protein in prostate tissue. IGFBP-5 that is made by fibroblasts appears to be sequestered by epithelial cells. IGFBP-5 may, therefore, be a factor in cellular interactions between stromal and epithelial cells that are of fundamental importance for normal prostatic development and function.

Aged↗
PubMed1996

Immunohistochemical localization of insulin-like growth factor binding proteins 2 and 3 in prostate tissue: clinical correlations.

PURPOSE: The insulin-like growth factor system has recently been shown to have important mitogenic effects in the prostate. The system consists of 2 ligands: insulin-like growth factor types 1 and 2, which are potent mitogens for prostate cell growth, and 6 insulin-like growth factor binding proteins that modify the activity of these growth factors. Recently, changes in serum levels of insulin-like growth factor binding proteins 2 and 3 have been identified in prostate cancer patients but in vivo studies of these changes have not been previously reported. MATERIALS AND METHODS: We performed immunohistochemical staining for insulin-like growth factor binding proteins 2 and 3 in areas of benign disease, prostatic intraepithelial neoplasia, and cancer from specimens obtained from 24 patients who underwent prostatectomy to determine changes in the quantity of these proteins with progression from the benign through the premalignant and into the malignant states. Quantification of the differences noted in the amount of insulin-like growth factor binding proteins 2 and 3 found in each of the 3 tissue types was then correlated with serum and tissue prostate specific antigen levels, pathological stage and grade of the tumors. RESULTS: Our data indicate that as human prostate tissue progresses from the benign to the malignant state, insulin-like growth factor binding protein 2 immunoreactivity in the prostatic luminal epithelial cells increases and that of insulin-like growth factor binding protein 3 decreases. Quantification of the differences noted in binding proteins 2 and 3 among all 3 tissue types was statistically significant. However, no correlation was noted between the stage or grade of prostate carcinoma and insulin-like growth factor binding protein 2 or 3 immuno-staining intensity. Additionally, no significant correlation was found between serum or tissue levels of prostate specific antigen and insulin-like growth factor binding protein 2 or 3 immunoreactivity. CONCLUSIONS: Our data suggest that significant changes in the insulin-like growth factor system occur with malignant transformation in the prostate. It is hoped that this system may eventually result in a better serum or tissue (from prostate biopsy) marker of malignant transformation, and/or represent a target for early therapeutic intervention to alter the growth and development of prostate cancer.

Humans↗
PubMed1996

New use of Foley catheter for precise vesicourethral anastomosis during radical retropubic prostatectomy.

PURPOSE: We describe a new method of using a Foley catheter to assist vesicourethral anastomosis during radical retropubic prostatectomy. MATERIALS AND METHODS: A total of 81 patients underwent radical retropubic prostatectomy with this technique. Followup ranged from 4 to 48 months. Peri-catheter urethrograms were performed at 3 weeks. Patients were evaluated specifically for bladder neck contracture, urinary continence and prolonged catheterization. RESULTS: Bladder neck contracture, occurred in 4.9% of the patients and 87.6% were completely continent of urine. Only 1 patient required extended postoperative catheterization. CONCLUSIONS: Use of a Foley catheter for vesicourethral anastomosis is consistent and simple, and provided good surgical results in our experience.

Anastomosis, Surgical↗
PubMed1996

A randomized prospective comparison of antibiotic tissue levels in the corpora cavernosa of patients undergoing penile prosthesis implantation using gentamicin plus cefazolin versus an oral fluoroquinolone for prophylaxis.

PURPOSE: We performed a prospective randomized trial comparing the efficacy, safety and cost of parenteral antibiotics and oral fluoroquinolones for prophylaxis in penile prosthesis surgery. MATERIALS AND METHODS: We prospectively randomized 20 consecutive patients undergoing penile prosthesis surgery to receive ofloxacin orally or gentamicin and cefazolin parenterally followed by cephradine orally. Intraoperatively corpora cavernosa tissue and simultaneous peripheral serum samples were evaluated for antibiotic levels. Median followup was 16 months (range 8 to 21, mean 15.35). RESULTS: There were no implant losses or reoperations and complications were comparable in the 2 groups. The difference in mean serum-to-tissue ratios of ofloxacin versus the combination of cefazolin and gentamicin was statistically significant (p < 0.03). The minimum inhibitory concentrations of ofloxacin met or exceeded those of the 2 most common offending organisms, Staphylococcus epidermidis and Escherichia coli, in 80% of patients, which was comparable to the results of the parenteral regimen. Cost savings of the medications alone were more than $250,000 in the ofloxacin group. By eliminating a hospital stay of the 25,000 cases of penile prosthesis placement in the United States yearly a total cost savings of more than $36 million would be realized. CONCLUSIONS: When oral ofloxacin is given for prophylaxis in penile implant surgery, the procedure may be performed on an outpatient basis and health care dollars are saved.

Administration, Oral↗
PubMed1994

Clinical variables which serve as predictors of cancer-specific survival among patients treated with radical cystectomy for transitional cell carcinoma of the bladder and prostate.

BACKGROUND: Studies have demonstrated conclusively that the stage and grade of transitional cell tumors at presentation are major determinants of survival for those with the disease in the bladder and prostate. The authors initiated a review of 531 patients with transitional cell carcinoma of the bladder and prostate treated with radical cystectomy between 1969 and 1990 to identify other clinical features predictive of cancer-specific survival. MATERIALS AND METHODS: Inpatient and clinical medical records were analyzed for age, race, gender, clinical T stage, medical history, and presenting symptoms and signs, and admission laboratory values were correlated with the patient's cancer-specific outcome. Both univariate and multivariate analyses of the various clinical factors were performed to identify variables predictive of cancer-specific survival. RESULTS: Univariate analysis indicated that clinical T classification, preoperative hemoglobin, tumor grade, irritative voiding symptoms, age, preoperative creatinine, obstructive hydronephrosis on preoperative excretory urography, a history of bladder tumors or nephrouretectomy for transitional cell cancer, prior urinary tract infections, prior pelvic irradiation, and obstructive symptoms were all predictive of poor cancer-specific survival. Multivariate analysis demonstrated that higher clinical T classification (T2, T3a, T3b, T4 versus Ta, Tis, T1) (P < 0.001), increasing age (< 65 years versus > or = 65 years) (P < 0.001), the presence of irritative voiding symptoms (P = 0.01), higher tumor grade, lower preoperative hemoglobin level (< or = 12 gm/dl versus > 12 gm/dl) (P < 0.001), higher preoperative creatinine level (> or = 1.5 mg/dl versus < 1.5 mg/dl) (P = 0.002), a history of nephroureterectomy for transitional cell cancer (P = 0.016), and a history of pelvic irradiation (P = 0.002) were all predictive of poor cancer-specific survival. CONCLUSIONS: Although clinical T classification and tumor grade remain the best predictors of survival in patients with transitional cell carcinoma of the bladder or prostate, clinical variables such as age, preoperative creatinine and hemoglobin levels, a history of nephroureterectomy or pelvic irradiation, and irritative voiding symptoms at presentation may provide additional prognostic information independent of tumor grade and stage.

Adult↗
PubMed1994

Expanding indications for conservative renal surgery in renal cell carcinoma.

OBJECTIVE: To more clearly define the selection criteria for conservative renal surgery in renal cell carcinoma. METHOD: The survival experience of 42 patients who underwent in situ partial nephrectomy (21), enucleation (18), or both (3) over an eighteen-year period was examined. The presence or a history of contralateral cancer, type of surgery, gender, grade, diameter of tumor, age at diagnosis, presenting symptoms, positive surgical margins, smoking history, and stage were examined with regard to prognostic significance. RESULTS: The five-year cancer-specific survival rates were 100 percent for those patients undergoing partial nephrectomy and 84 percent for those undergoing enucleation. The local recurrence rate was 4.8 percent (2/42) for the group, with both recurrences occurring in patients with von Hippel-Lindau disease. The mean diameter of tumor resected was 4.2 cm. Those patients found to have a positive surgical margin (6) had a significantly shorter disease-specific survival than those who did not (37) (p = 0.004), and those with a smoking history (23) had a significantly shorter survival than non-smokers (19) (p = 0.038). CONCLUSIONS: We conclude that both partial nephrectomy and enucleation are acceptable approaches to renal cell carcinoma in select cases, with survival rates that closely approximate those found in radical nephrectomy series. Renal carcinomas that are peripherally located and small in diameter (< or = 5 cm) are most appropriate for these procedures, and given the excellent results noted to date, the expanded use of these approaches to include very young patients and those with any disease process that may affect renal function is warranted. A positive surgical margin is an ominous pathologic finding and should be avoided by frozen section biopsy at surgery or possibly intraoperative ultrasonography. Additionally, smokers with renal cell carcinoma have a poorer disease-specific survival than non-smokers, further questioning a carcinogenic etiology in this disease.

Carcinoma, Renal Cell↗
PubMed1994

Compartment syndrome: an unusual complication of the lithotomy position.

The compartment syndrome is a rare complication of surgery in the lithotomy position, but one that may result in neurovascular damage and permanent disability. Herein, we present a case of bilateral three-compartment syndrome following urethroplasty in the dorsolithotomy position, with review of the literature and discussion of the causes and possible means to prevent this complication.

Adult↗
PubMed1994

Granulocytic sarcoma presenting as a diffuse renal mass before hematological manifestations of acute myelogenous leukemia.

Granulocytic sarcoma is a rare tumor composed of granulocytic precursor cells. The most common sites of involvement include the bones, soft tissue, lymph nodes and skin. Granulocytic sarcoma usually develops as a delayed manifestation of the disease process in patients with known acute myelogenous leukemia. To our knowledge we report the first case of renal granulocytic sarcoma presenting as the first sign of acute myelogenous leukemia. Computerized tomography and magnetic resonance imaging revealed diffuse nonspecific global tumor infiltration of the kidney and ureter. Renal granulocytic sarcoma was diagnosed on open renal biopsy and acute myelogenous leukemia on bone marrow biopsy. There has been partial response to combination chemotherapy. Renal granulocytic sarcoma may diffusely involve the kidney as the only manifestation of acute myelogenous leukemia and it should be included in the differential diagnosis of the many disease entities with global renal involvement since initial treatment is combination chemotherapy.

Diagnosis, Differential↗
PubMed1994

Does of stage pT0 cystectomy specimen confer a survival advantage in patients with minimally invasive bladder cancer?

Controversy exists regarding the clinical significance of a pathological stage T0 (pT0) specimen found at cystectomy or after repeat transurethral resection for transitional cell carcinoma of the bladder. Many investigators cite this subpopulation of patients as a reason to consider more conservative management, based on the premise that the patient may have benefited from the original transurethral resection. However, we questioned whether outcome would be improved in stage pT0 cancer patients or whether outcome in stage pT0 cases would parallel that noted when the original stage was equivalent to the final pathological stage. To test this hypothesis, we examined the survival advantage occasioned by a stage pT0 finding in 66 of 433 patients who underwent radical cystectomy for transitional cell carcinoma of the bladder. Of the 433 patients studied 54 had clinical stage Tis or Ta, 166 clinical stage T1 and 213 clinical stage T2 disease. Within each of the 3 clinical groups (clinical stage Tis/Ta, clinical stage T1 and clinical stage T2) Kaplan-Meier survival projections were generated comparing patients with stage pT0 disease to those whose pathological stage was identical to the original clinical stage. Among the 54 clinical stage Tis/Ta cancer patients 11 with stage pT0 and 24 with stage pTis/pTa had survival projections of 90% of 5 years. Of 166 patients with clinical stage T1 disease 32 with stage pT0 and 78 with stage pT1 tumor had survival projections of 75% at 5 years. Among 213 patients with clinical stage T2 cancer 23 with stage pT0 and 71 with stage pT2 disease had survival projections of 68% at 5 years. The data suggest that a stage pT0 cystectomy specimen does not confer a survival advantage over that noted from the initiating population in which the final pathological stage and initial clinical stage are equivalent. A patient with a stage pT0 specimen functions, by survival analysis, in a manner similar to one with the stated clinical stage.

Adult↗
PubMed1994

Radical cystectomy for stages Ta, Tis and T1 transitional cell carcinoma of the bladder.

Between January 1969 and January 1990, 531 patients underwent bilateral pelvic lymph node dissection and radical cystectomy for the management of transitional cell carcinoma of the bladder. Of these procedures 220 were performed for clinical stage Ta (31 patients), Tis (23) or T1 (166) disease, which was either high grade or recalcitrant to transurethral resection and/or intravesical chemotherapy. This subgroup of patients was studied to evaluate the outcome of recurrent or chemotherapy resistant superficial transitional cell carcinoma of the bladder after radical cystectomy. The operative mortality rate for the group was 2.3% and the overall complication rate was 20.4%. The pelvic recurrence rate was 5.9%. The 5-year cancer-specific survival rates for patients with pathological stage Ta (11), Tis (19), T0 (43) and T1 (91) disease were 88%, 100%, 80% and 76%, respectively. The 10-year cancer-specific survival rates were 75%, 92%, 66% and 62%, respectively. A total of 74 patients received preoperative radiation therapy (2,000 rad) but they had no better 5-year cancer-specific survival rates than did nonirradiated patients. Transurethral resection and/or preoperative radiation therapy resulted in a pathological status of T0 in 43 patients but this did not confer a survival advantage. Although bladder preservation is preferable, low operative mortality and pelvic recurrence rates, as well as new methods of continent urinary diversion continue to make radical cystectomy the definitive form of therapy for patients with superficial disease recalcitrant to transurethral therapy.

Adult↗
PubMed1994

Effect of terfenadine on urination.

Anticholinergic side effects of commonly used antihistamines are known to aggravate voiding difficulties in older men with benign prostatic hypertrophy. Newer antihistamines, such as terfenadine (Seldane), with less anticholinergic side effects may not have such an effect on voiding. We performed a randomized, double-blind, placebo-controlled, crossover study in eight normal male volunteers (phase I) and in 11 patients with documented benign prostatic hypertrophy (phase II) to study the effect of terfenadine on voiding. Subjects received either 60 mg of terfenadine or an identical placebo twice daily for 1 week each. After a 1-week washout period, they were crossed over to receive the other drug. Evaluation took place on days 0, 7, 14, and 21. Prick skin testing was performed with serial threefold dilutions of histamine to assess efficacy and degree of compliance. Uroflowmetry and urinary symptom assessment were also done. In phase I, after 1 week of terfenadine, mean skin test suppression was 83.8% compared with -0.5% with placebo (P < .01). Urinary peak flow increased 10.4% on terfenadine and 9.7% on placebo (P = NS). In phase II, the mean prick skin test suppression was 87.8% compared with 12.0% for placebo (P < .002). Urinary peak flow was decreased 0.1% from baseline on terfenadine and increased by 18.7% for placebo (P = NS). None of the subjects noted alterations in voiding symptom scores. We conclude that the commonly recommended dose of terfenadine does not significantly alter voiding characteristics in normal men or in patients with documented benign prostatic hypertrophy.

Adult↗