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Biomedical subjects

R R Bahnson

Publications and source records attributed to R R Bahnson.

At least 55 records · Page 3Linked to original sources

Multiple renal neoplasms: a case of 3 histologically dissimilar primary tumors.

A 69-year-old woman who presented with bilateral renal masses and gross hematuria was found to have 3 different primary renal neoplasms. She first underwent left partial nephrectomy for an oncocytoma and subsequently right radical nephroureterectomy for transitional cell carcinoma of the pelvis. An incidental angiomyolipoma was found in the specimen. Deoxyribonucleic acid image analysis of all 3 tumors is presented.

Adenoma↗

DNA analysis of multiple synchronous renal cell carcinomas.

The authors used retrospective quantitative DNA analysis to study interrelationships between multiple synchronous renal cell carcinomas in seven patients. DNA content was determined by image analysis on Feulgen-stained nuclear smears prepared from multiple paraffin blocks from each tumor. Tumors were unilateral in four cases and bilateral in three. Ten tumors had homogeneous, and four heterogeneous DNA stemlines. Intertumoral heterogeneity in four cases suggested multifocal origin. Identical DNA aneuploid indices in bilateral tumors in one case suggested metastasis from a solitary origin. Abnormal DNA content and heterogeneous populations began to appear in the size range 2.0 to 5.0 cm. All tumors over 5.0 cm contained nondiploid populations. Although the interrelationships between these multiple synchronous neoplasms are not entirely clear, the DNA analysis suggests that the occurrence of nondiploid stemlines and heterogeneous DNA content may parallel both tumor growth and more aggressive behavior.

Adult↗

Neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin for locally advanced transitional cell carcinoma of the bladder.

Nine patients with locally advanced transitional cell carcinoma (TCC) of the bladder were treated with neoadjuvant methotrexate, vinblastine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (M-VAC) followed by radical cystoprostatectomy and modified pelvic lymphadenectomy. Five patients, including three with pelvic sidewall fixation, had clinical stage T4N0M0 tumors whereas the remaining patients had T3N0M0 tumors. All patients were pathologically restaged by a referee pathologist after surgery. The complete response rate was 22% and an additional 44% experienced a partial response. Neutropenia preventing a second cycle of M-VAC occurred in one patient. Downstaging of locally advanced TCC of the bladder was achieved in the majority of patients treated with neoadjuvant M-VAC.

Aged↗

Toxicity comparison of neoadjuvant versus adjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) in radical cystectomy patients.

A reduction in the toxicity of M-VAC chemotherapy has been postulated for patients who receive these drugs prior to radical cystectomy for muscle invasive bladder carcinoma. A review of the toxicity and patient dropout rates from a group of 9 patients who received neoadjuvant M-VAC was little different from 9 patients who were treated with M-VAC after radical cystectomy. This similarity suggests that preoperative M-VAC should not be favored on the basis of reduced patient morbidity.

Aged↗

In vitro and in vivo anti-tumor activity of recombinant mouse tumor necrosis factor (TNF) in a mouse bladder tumor (MBT-2).

Tumor necrosis factor (TNF) has confirmed anti-tumor activity. When used in combination with interferon gamma (IFNG) or chemotherapeutic drugs targeted at DNA topoisomerase II, synergistic cytotoxicity has been observed. Investigations of the anti-tumor activity of recombinant mouse TNF in a mouse bladder tumor model (MBT-2) were performed. The cytotoxicity of TNF and low dose actinomycin-D (AMD) against MBT-2 in vitro was examined alone and following preincubation with IFNG. The activity of TNF/AMD in vivo utilizing an intravesical implantation mode (MBT-2) was also evaluated. TNF alone had no cytotoxic effect in vitro. TNF/AMD was cytotoxic for MBT-2 growth in vitro. Maximum cytotoxicity (86%) occurred at one microgram./ml. TNF/one microgram./ml. AMD with 50% cytotoxicity at .64 micrograms./ml. TNF/one/microgram./ml. AMD. A two hour preincubation with IFNG markedly increased the cytotoxicity of TNF/AMD whereas longer incubations did not enhance cytotoxic activity. TNF alone and in combination with AMD did not significantly reduce the percentage of intravesical tumor outgrowth in vivo compared to controls. This study demonstrated that TNF/AMD exhibits cytotoxicity for MBT-2 cells in vitro but is ineffective in reducing implantation of intravesical tumors in vivo. The in vitro data suggest brief exposure of MBT-2 cells to IFNG augments the subsequent anti-tumor activity of TNF/AMD.

Administration, Intravesical↗

Early experience with the DuraPhase penile prosthesis.

A retrospective review of the medical records of 26 consecutive patients who underwent surgical implantation of the DuraPhase penile prosthesis for erectile impotence was performed. In addition, telephone interviews were used to evaluate patient and partner satisfaction with the device. Average patient age was 61 years. The presumed etiology of erectile dysfunction was vascular in 19 patients, postoperative in 4 and neurogenic in 3. Followup averaged 5 months (range 1 to 15 months). Sixteen patients and partners with a minimum of 3 months of followup were evaluated for satisfaction with the device. On a scale of 1 to 10 the average patient score was 8.6 and the average partner score was 9. Our early experience with the DuraPhase penile prosthesis has been favorable. Surgical insertion is simple, and patient and partner satisfaction has been superior. The device functions easily, can be well concealed and has excellent axial rigidity for intercourse.

Adult↗

A phase IA trial of sequential administration recombinant DNA-produced interferons: combination recombinant interferon gamma and recombinant interferon alfa in patients with metastatic renal cell carcinoma.

This study investigated the effects of sequentially administered recombinant interferon gamma (rIFN gamma) and recombinant interferon alfa (rIFN alpha) in 36 patients with metastatic renal cell carcinoma (RCC). rIFN alpha was subcutaneously administered daily for 70 days at dosages that varied (2.5, 5, 10, and 20 x 10(6) U/m2) across four cohorts of patients. Within each cohort of patients receiving a given dose of rIFN alpha, three subsets of patients received either 30, 300, or 1,000 micrograms/m2 rIFN gamma. rIFN gamma was administered intravenously for 5 days every third week, 6 hours prior to administration of rIFN alpha. Dose-limiting toxicity (DLT) included constitutional symptoms, leukopenia, nephrotic syndrome with acute renal failure, hypotension associated with death, and congestive heart failure. DLT was related more often to the rIFN alpha dose level than to rIFN gamma dose level. Maximum-tolerated dose (MTD) was 10 x 10(6) U/m2 rIFN alpha and 1,000 micrograms/m2 rIFN gamma. Six patients failed to complete a minimum of 21 days of therapy due to toxicity or rapid progression of disease. Clinical responses were seen in eight of 30 assessable patients. Two patients experienced complete remission and have remained in complete remission 20+ and 22+ months. An additional six patients have shown partial responses for 4 to 18+ months. One patient in partial remission continues to show slow regression of pulmonary and liver lesions off therapy with rIFNs. Clinical responses have remained durable for patients with complete remissions and patients with partial remissions. The results of this study suggest that toxicities associated with combination rIFN therapy can be reduced by administering these agents sequentially as opposed to simultaneously.

Adolescent↗

Immunophenotypic markers in renal cell carcinoma.

UNLABELLED: We studied immunophenotypic and tumor cell markers in renal cell carcinoma (RCC) to determine if there are patterns of expression which may correlate with biologic behavior and response to therapy. Fourteen RCCs from 13 patients were stained by the immunoperoxidase technique using primary antibodies to Leu 4, Leu 14, Leu 2a, Leu 3a and b, lysozyme, dendritic reticulum cell (DRC), S-100, HLA-DR, epithelial membrane antigen (EMA) and beta-2-microglobulin (B2-MG). Staining was correlated with tumor stage, nuclear grade, histologic patterns, degree of cellular infiltrate, and clinical followup. Four RCCs were stage T1, four T2, five T3, and one T4. Most tumors were clear or granular cell type, with a solid or tubular growth pattern. The number of infiltrating lymphocytes and monocytes correlated with tumor grade and stage. Tumor-infiltrating lymphocytes (TILs) were predominantly Leu 3-positive (T-helper phenotype). B-cell markers were negative. Dendritic cells were rare. HLA-DR was present on endothelial cells in 11 tumors and on tumor cells in ten. HLA-DR expression increased with tumor grade. Tumor cells expressed EMA in 12 cases; B2-MG in four cases. Two patients, stages 3 and 4, died at 2 and 6 mo. CONCLUSIONS: (a) T-helper cells and monocytes infiltrate RCCs. Their numbers increase with tumor grade and stage. (b) HLA-DR expression by tumor cells tends to correlate with increasing stage and grade. (c) Dendritic cells are infrequent in RCCs.

Antigens, Differentiation↗

Toxicity of intravesical recombinant human tumor necrosis factor in cynomolgus monkeys.

Six groups of two cynomolgus monkeys were treated with escalating intravesicular doses of recombinant human tumor necrosis factor (rHuTNF) for a 6 week interval. The doses of rHuTNF ranged from 10 ng to 1 mg and were instilled weekly. Two monkeys had instillation of saline only and served as controls. The monkeys were weighed and temperatures determined before, immediately after, and 2 days following each treatment. Cystoscopic examination was performed 2 days after each treatment and blood samples were obtained. At the conclusion of the study, animals were killed and necropsy was performed. There was no observable toxicity from treatment with rHuTNF. There was no difference between treated and control monkeys with respect to temperature, weight, or blood measurements. No drug-induced alteration in bladder morphology was found by either cystoscopic or microscopic pathologic examination.

Administration, Intravesical↗

Catecholamine excess: probable cause of postoperative tachycardia following retroperitoneal lymph node dissection (RPLND) for testicular carcinoma.

Review of the postoperative course of seven patients who underwent retroperitoneal lymph node dissection (RPLND) for staging of testicular carcinoma revealed an unexplained tachycardia that was persistent for several days. Postoperative catecholamine determinations from three subsequent patients subjected to RPLND revealed dramatic increases in epinephrine, norepinephrine, dopamine, and total catecholamines. Since cardiac acceleration is mediated almost exclusively by sympathetic stimulation, this finding may explain the postoperative tachycardia observed in these patients.

Adolescent↗

Incidence and prognostic significance of lymphatic and vascular invasion in radical prostatectomy specimens.

A review of 55 radical prostatectomy specimens from patients with clinically localized carcinoma of the prostate was performed. Blinded review of slides was performed by a single pathologist and urologist. Criteria for invasion were encroachment by tumor of the lymphatic or vascular lumen and evidence of reaction around or in the lymphatic or vascular channel. Notation was made of the degree and location of lymphatic and vascular invasion. All patients had a minimum of 5 years of follow-up. Twenty-one of 55 (38%) patients either had lymphatic or vascular invasion, and seven (13%) had both findings. In the majority of these patients the degree of invasion was rare (71%), while multifocal (19%) and diffuse (10%) involvement were seen less frequently. Nine patients experienced either progression of their tumors or death from disease. Those patients with evidence of lymphatic or vascular invasion had a fourfold greater incidence of progression and or death. However, the presence of lymphatic or vascular invasion was clearly related to both tumor grade and stage, and multivariate statistical analysis demonstrated that its prognostic significance was dependent upon tumor grade.

Carcinoma↗

Ultrasonography and diagnosis of pediatric genitourinary rhabdomyosarcoma.

Rhabdomyosarcoma is the most common tumor of the lower genitourinary tract in children during their first two decades of life. Four patients with genitourinary rhabdomyosarcoma are presented, with ultrasonographic and radiographic findings. The utility of ultrasound in the diagnosis of this pediatric tumor is emphasized.

Child↗

Pharmacological modulators of DNA-interactive antitumor drugs.

The poor therapeutic index and limited efficacy of current cancer chemotherapeutic agents represent an important pharmacological problem. Although there has been a significant increase in our understanding of the mechanisms by which anticancer drugs kill mammalian cells, identification of new, effective anticancer agents during the last decade has been exceeding slow. Thus, attention has focused on understanding the causes of drug resistance and on either sensitizing tumor cells to existing anticancer agents using what could be called 'chemoenhancers', or protecting non-malignant tissues against serious untoward effects using 'chemoprotectors'. John Lazo and Robert Bahnson review recent strategies attempting to modulate the activity of antineoplastic drugs.

Antineoplastic Agents↗

Clinical use of prostate specific antigen in patients with prostate cancer.

The clinical use of prostate specific antigen as a screening test for prostate cancer, as a preoperative determinant for staging of prostate cancer and to monitor response to therapy in prostatic cancer patients was evaluated in 168 men with benign prostatic hyperplasia and 231 men with prostate cancer. Only 3% of the men with benign prostatic hyperplasia had prostate specific antigen levels greater than 10 ng. per ml. compared to 44% of the men with proved prostate cancer. Preoperative prostate specific antigen levels increased with higher clinical stages of prostate cancer but there was substantial overlap among stages. Among patients with stage A1 prostate cancer who were followed expectantly none had an elevated prostate specific antigen value or metastatic disease during a followup of 15 to 120 months. After radical prostatectomy serum prostate specific antigen values decreased to undetectable levels (less than 0.6 ng. per ml.) in 89% of the patients with organ-confined disease, in 87% of those with microscopically positive margins only but in only 34% with seminal vesicles or lymph node involvement. Failure of the prostate specific antigen levels to decrease to the undetectable range after radical prostatectomy was associated with a greater likelihood of subsequent tumor recurrence. Only 3 of 18 patients (17%) treated with definitive radiation therapy had post-irradiation prostate specific antigen values of less than 0.6 ng. per ml., while in 39% the prostate specific antigens values remained greater than 4 ng. per ml. and in 4 of 18 (22%) the values were greater than 10 ng. per ml. Of patients with previously untreated stage D2 prostate cancer the mean pre-treatment prostate specific antigen value was 63.7 ng. per ml. compared to a post-hormonal therapy mean value of 31.1 ng. per ml. Of 32 patients treated with hormonal therapy 14 had stable disease, including 13 with prostate specific antigen levels of less than 10 ng. per ml. In contrast, 18 patients had progressive disease, of whom 16 had prostate specific antigen levels of more than 10 ng. per ml. We conclude that the serum prostate specific antigen assay is most useful clinically to monitor the response to therapy of prostate cancer patients.

Acid Phosphatase↗

Differences in values obtained with 2 assays of prostate specific antigen.

Several different assays for prostate specific antigen have become available for use in clinical laboratories. We compared the 2 most widely used assays, the Tandem-R and the Pros-Check prostate specific antigen assays, to determine if different assays yield comparable results. We analyzed 70 serum specimens from patients with suspected or known prostatic carcinoma by both assays. Results from the assays showed close linear correlation (r equals 0.988) but the Pros-Check assay yielded values 1.85 times those of the Tandem-R test. The proportional bias between assays is owing to differences in the values assigned to calibration standards in the assays, and it demonstrates a need for improved standardization of prostate specific antigen assays. Important consequences of the bias between assays are that different normal ranges apply and that values from the 2 assays cannot be compared directly.

Antigens, Neoplasm↗

Papaverine testing of impotent patients following nerve-sparing radical prostatectomy.

To investigate the etiology of impotence following nerve-sparing radical retropubic prostatectomy we performed papaverine testing on 23 patients who did not regain erections sufficient for vaginal penetration. Intervals from surgery to testing ranged from 3 to 30 months, with an average of 9 months. All patients achieved some degree of tumescence. In response to intracavernous papaverine injection only 1 patient (5 per cent) obtained an erection equivalent to the preoperative state. Of 18 patients who were fully potent preoperatively 8 (44 per cent) achieved an erection less than normal but judged to be sufficient for intercourse by the examining physician. Twelve patients, including 2 who were not fully potent preoperatively, had erections of poor quality insufficient for vaginal penetration. The results suggest that in most of these patients postoperative erectile dysfunction is predominantly vasculogenic in origin. Thus, factors other than injury to the neurovascular bundles may be responsible for postoperative impotence.

Erectile Dysfunction↗

Inhibition of mouse bladder tumor proliferation by alpha difluoromethylornithine and interferon in vitro and in vivo.

Previous studies have reported that alpha difluoromethylornithine (DFMO), an enzyme-activated, irreversible inhibitor of ornithine decarboxylase (ODC), has anti-tumor activity in several tumor systems. Recently, investigations have revealed that combinations of DFMO and Interferon (IFN) are synergistic in inhibiting tumor cell growth. We tested the effects of DFMO and IFN alpha, beta alone and in combination on the growth of mouse bladder tumor (MBT-2) cells both in vitro and in vivo. MBT-2 cells were incubated for 72 hours in 96 well microtiter plates with DFMO, IFN alpha, beta and combinations of both agents and percentage inhibition was calculated. In vivo studies utilized the intravesical implantation method as well as subcutaneous implantation. DFMO was administered as a 1% solution in the drinking water. IFN alpha, beta was given bi-weekly by intravesical administration. DFMO effectively inhibited MBT-2 growth in vitro. The ID50 was 0.08 mM and peak inhibitory activity was reached at concentrations of 0.16 mM and remained constant with concentrations of up to 10 mM. IFN alpha, beta also inhibited the in vitro proliferation of MBT-2 with maximum inhibition (46%) at 2,000 U/ml. Combinations of DFMO and IFN alpha, beta showed increased anti-proliferative activity. The degree of enhancement varied with synergism, additivity, or sub-additivity at varying drug concentrations. In vivo, DFMO significantly retarded the growth of tumors implanted subcutaneously (p less than .05) and significantly delayed the outgrowth of tumors implanted intravesically (p less than .01). IFN alpha, beta alone was ineffective in vivo and produced no additive effect in vivo when used in combination with DFMO. Results of our investigation show that DFMO inhibits proliferation of MBT-2 cells in vitro and exhibits a similar effect in vivo against subcutaneous and intravesical tumor implants. IFN alpha, beta alone demonstrated anti-proliferative activity in vitro but did not affect MBT-2 growth in vivo. Although the combination of DFMO and IFN alpha, beta exhibited enhanced activity in vitro, no enhancement was observed with combination therapy in vivo.

Animals↗