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Biomedical subjects

W R Fair

Publications and source records attributed to W R Fair.

At least 217 records · Page 12Linked to original sources

Selection of testicular tumor patients for omission of retroperitoneal lymph node dissection.

Excluding patients with bulky stages II or III disease, 73 patients with nonseminomatous germ cell testicular tumors were evaluated between September 1979 and April 1983 for a protocol omitting retroperitoneal lymph node dissection. Patient eligibility required clinical stage I (T1 category) disease based upon normal post-orchiectomy serum tumor markers (alpha-fetoprotein, human chorionic gonadotropin and lactic dehydrogenase), chest x-ray, ipsilateral lymphangiography, and a computerized tomography scan of the abdomen and pelvis. Of the 73 patients 10 (14 per cent) were entered and followed for more than 2 years (3 had relapse within 7 months but were salvaged with retroperitoneal lymph node dissection and chemotherapy). Analysis of failures showed embryonal carcinoma in all 3 patients, with vascular invasion in the primary tumor in 1 and undetected spermatic cord involvement in 1, while 1 had a slower than expected decrease to normal of an elevated human chorionic gonadotropin level after orchiectomy. There were 63 patients (86 per cent) excluded from the protocol for various reasons: 2 (3 per cent) refused treatment, 16 (25 per cent) had suspicious or positive lymphangiography, 22 (40 per cent) had a positive CT scan, 6 (9 per cent) had elevated tumor markers, 3 (5 per cent) were less than 15 or more than 15 or more than 40 years old, 8 (13 per cent) had had a prior orchiopexy or scrotal violation, 4 (6 per cent) had extension to the spermatic cord and 2 (3 per cent) were unavailable for monthly followup. These 63 patients underwent retroperitoneal lymph node dissection, and 36 (57 per cent) had negative and 27 (43 per cent) had positive nodes (8 had stage N1, 10 stage N2A, 6 stage N2B and 3 stage N3 disease). Average interval from orchiectomy to final staging was 6 weeks. The results suggest that assessment of local tumor extent and potential sites of metastases via all available means are necessary in an effort to reduce the risk of tumor recurrence in patients who are followed expectantly.

Adolescent↗

High energy shock waves suppress tumor growth in vitro and in vivo.

Exposure of the Dunning R3327AT-3 rat prostatic carcinoma and SK-Mel-28 human melanoma, in vitro, to high energy shock waves resulted in a reduction in cell viability as determined by trypan blue exclusion and a decrease in the number of colonies formed in a clonogenic assay. Flow cytometric determination of DNA content in R3327AT-3 cells treated in vitro indicated a selective diminution of cells in the G2 and M phases of the cell cycle. When R3327AT-3 cells exposed to high energy shock waves were subsequently injected into rats, or tumor bearing animals were treated by high energy shock waves targeted at the tumor, a delay in tumor growth was observed. These observations indicate that high energy shock waves are cytotoxic to tumor cells in vitro and in vivo. Additional research into the possible use of high energy shock waves in the non-invasive destruction of animal and human tumors is warranted.

Animals↗

Regression of metastatic renal cell carcinoma: a case report and literature review.

The literature provides few examples of regression of documented metastatic renal cell carcinoma. We report a case of cytologically documented pulmonary metastases from a renal cell carcinoma, which resolved following nephrectomy and hormonal therapy. The patient has been followed for 6 years without evidence of recurrence.

Adenocarcinoma↗

Human renal cell carcinoma xenograft: morphology, growth and chemosensitivities.

A primary human renal clear cell carcinoma has been developed as a xenograft (JDF-1). Passage 7 of the JDF-1 tumor retained the microscopic morphology of the primary tumor, electron micrographs have confirmed its epithelial characteristics and karyotyping of a subsequent passage has proved it is not a murine hybrid. Immunoperoxidase studies using a panel of murine monoclonal antibodies demonstrate an antigenic phenotype specific for human renal cancer. In vitro chemosensitivities of the JDF-1 tumor were determined by the double-layer soft-agar clonogenic assay method. JDF-1 showed no significant sensitivities to several standard chemotherapeutic agents, but alpha-2-interferon and difluoromethylornithine in combination synergistically inhibited its growth by 74 per cent.

Aged↗

Mitogenic factors in prostatic tissue and expressed prostatic secretion.

Expressed prostatic secretions and extracts of benign prostatic hyperplasia tissue contain a polypeptide growth factor(s) that stimulates the uptake of tritium-labeled thymidine by cultured 3T3 fibroblasts. Mitogenic activity was present in expressed prostatic secretions and extracts of benign prostatic hyperplasia tissue. The apparent molecular weights of the mitogenic fractions were estimated to be 300,000, 150,000 and 60,000 daltons for prostatic tissue extracts, and 30,000 daltons for expressed prostatic secretions. Bioassays yielded a mean of 27 units of mitogenic activity per mg. protein in expressed prostatic secretions obtained from men with normal and enlarged prostate glands. There was no difference in bioassayable mitogenic activity in the expressed prostatic secretions from normal and benign prostatic hyperplasia samples but gel filtration studies revealed a high molecular weight component present only in samples from men with prostatic enlargement. A dialyzable low molecular weight inhibitor of fibroblast growth was found in the prostatic tissues and expressed prostatic secretions. We report the characterization studies and discuss the possible roles of growth factors in the pathogenesis of benign prostatic hyperplasia.

Cells, Cultured↗

Endoscopic bladder neck suspension for stress urinary incontinence.

Endoscopic vesicourethral suspension is an acceptable procedure for the treatment of true stress urinary incontinence, and is associated with a high success rate and little morbidity. Endoscopic vesical neck suspension was performed in 60 patients, with cure of the incontinence in 49 (82 per cent). A higher success rate was achieved in patients without a prior hysterectomy and/or surgical procedure to correct incontinence. Abnormalities on urodynamic testing may be somewhat suggestive of outcome. However, these studies cannot be used to predict success or failure.

Adult↗

Prophylactic antibiotics and Foley catheter use in transperineal needle biopsy of the prostate.

We studied retrospectively 162 patients undergoing transperineal needle biopsy of the prostate. All patients had urine cultures before biopsy. Patients were divided into 4 groups: group 1--no antibiotics (44), group 2--antibiotics before and after biopsy (69), group 3--antibiotics after biopsy only (42) and group 4--antibiotics before biopsy only (7). Groups were similar in average age (65 years) and pathologic diagnosis (prostatic cancer in 28 per cent and a benign prostate in 72 per cent). Of the 162 patients 4 (2.5 per cent) had positive urine cultures preoperatively. Post-biopsy urine cultures were obtained in 86 patients and 2 (2 per cent) were positive. Only 12 patients (11 per cent) required catheters for postoperative urinary retention. Complications occurred in 9 patients (5.5 per cent): 7 (4.3 per cent) had febrile episodes, 1(0.6 per cent) had a documented postoperative urinary tract infection and 1(0.6 per cent) sustained a large pelvic hematoma. No statistically significant difference could be found among the 4 groups in regard to complication rate. This study demonstrates no advantage to the routine use of antibiotics or Foley catheters in transperineal needle biopsy of the prostate, provided the urine is sterile before biopsy. Cost analysis of these data demonstrates a considerable savings when routine antibiotics and Foley catheters are not used.

Aged↗

Differential effect of alpha-difluoromethylornithine on the in vivo uptake of 14C-labeled polyamines and methylglyoxal bis(guanylhydrazone) by a rat prostate-derived tumor.

The uptake of exogenously administered radiolabeled polyamines by a rat prostate-derived tumor line, the Dunning R3327 MAT-Lu, and various normal tissues was studied. Pretreatment of tumor cells in vitro with alpha-difluoromethylornithine (DFMO), a polyamine synthesis inhibitor, resulted in a markedly enhanced uptake of both [14C]putrescine and [14 C]spermidine. The in vitro uptake of [14C]putrescine by these cells was effectively inhibited by unlabeled spermine, spermidine, 1,8-diaminooctane, 1,7-diaminoheptane, 1,6-diaminohexane, 1,5-diaminopentane, 1,4-diaminopentane, and 1,4-diaminobutane, but less effectively by 1,4-diamino-2,3-butene and 1,4-diamino-2,3-butyne. The diamines, 1,3-diaminopropane and 1,2-diaminoethane, were ineffective in inhibiting [14C]putrescine uptake in vitro into the R3327 MAT-Lu cell line. When tumor-bearing animals were pretreated with DFMO or with DFMO and 5-alpha-dihydrotestosterone propionate, the tumor and prostate uptake of [14C]putrescine and [14C]-cadaverine was enhanced but not substantially increased in other tissues. In contrast to the in vitro results, spermidine and spermine were not enhanced substantially by DFMO pretreatment into any tissue, and their uptake into the tumor actually decreased. Ethylenediamine, which does not utilize the polyamine transport system, did not have its uptake increased into any tissue following DFMO pretreatment. The chemotherapeutic agent, methylglyoxal bis(guanylhydrazone), which utilizes the polyamine transport system for uptake into cells, exhibited uptake behavior different from that of the polyamines. Thus, methylglyoxal bis(guanylhydrazone) uptake into the tumor was not significantly increased or decreased by DFMO or by DFMO + 5-alpha-dihydrotestosterone propionate pretreatment, and only the ventral, but not the dorsal-lateral, lobe of the prostate showed increased uptake of methylglyoxal bis(guanylhydrazone) following DFMO + 5-alpha-dihydrotestosterone propionate pretreatment.

Animals↗

Evidence against a zinc binding peptide in pilocarpine-stimulated canine prostatic secretions.

Pilocarpine-stimulated canine prostatic secretions were subjected to gel filtration chromatography over Sephadex G-100 and Bio Gel P-4. Free zinc and the zinc in pilocarpine-stimulated canine prostatic secretions were observed to elute in the same fractions from the Sephadex G-100 column. In addition, Sephadex G-100 chromatography could not resolve free zinc from the small peptide bacitracin. However, a column packed with Bio Gel P-4 could resolve free zinc and bacitracin. When pilocarpine-stimulated canine prostatic secretions were chromatographed over the Bio Gel P-4 column, the major portion of the zinc eluted in the same fractions as did free zinc. No zinc was observed in the fractions where the small peptide bacitracin was found to elute. These results indicate that contrary to a previous report, zinc in pilocarpine-stimulated canine prostatic secretions was not bound to an eight amino acid peptide, but, rather, behaved chromatographically like free zinc.

Animals↗

Renal cell carcinoma and the clonogenic assay.

The clonogenic assay is an in vitro chemosensitivity test performed on tumor specimens and has had limited success in predicting or confirming patient response to chemotherapy. We investigated this assay system, using a 1-hour method, in 37 renal cell carcinoma specimens to determine its clinical usefulness. These specimens also were graded independently by a pathologist with respect to cell type, mitotic figures and degree of differentiation. Only 22 specimens formed at least 50 colonies per 500,000 cells plated and few specimens displayed any chemosensitivities. Marked variations of colony counts among duplicate controls or drug-treated samples demonstrated further the unreliability of the assay. Of several factors responsible for the poor performance of the assay the 2 outstanding problems were losses of clear cells in variable amounts (unique to renal cell carcinoma), and the inability to generate and maintain single cell suspensions. Pathologic correlations confirmed that predominantly clear cell carcinomas did not form colonies as well as granular cell carcinomas. Owing to these problems in its present form the clonogenic assay is not useful clinically and is unsuited particularly for renal cell carcinoma.

Adenocarcinoma↗

Lack of value of radioimmunoassay for prostatic acid phosphatase as a screening test for prostatic cancer in patients with obstructive prostatic hyperplasia.

We examined the incidence of prostatic cancer in patients with an elevated radioimmunoassay for prostatic acid phosphatase and clinical benign prostatic hyperplasia on digital rectal examination. Of 295 patients screened with prostatic acid phosphatase tests 17 fulfilled the criteria of having an elevated prostatic acid phosphatase, clinically benign prostate and histological examination of the prostatectomy specimen. None of the 17 patients had histological evidence of prostatic cancer. The results confirm the predictions of mathematical models that prostatic acid phosphatase is of no practical value as a screening test for prostatic cancer in patients with clinical benign prostatic hyperplasia.

Acid Phosphatase↗