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Biomedical subjects

W R Fair

Publications and source records attributed to W R Fair.

At least 235 records · Page 13Linked to original sources

The pharmacokinetics of antibiotic diffusion in chronic bacterial prostatitis.

Historically chronic bacterial prostatitis in the male human has been relatively resistant to antimicrobial chemotherapy. The pharmacokinetic theory of drug diffusion into the prostate is reviewed. A brief description of the various canine models utilized to quantitate antimicrobial drug diffusion is presented. Specific data concerning the diffusion of various antimicrobial agents are abstracted followed by a brief discussion of mechanistic explanations for the success or failure of drug therapy.

Aminoglycosides↗

Copenhagen rat prostatic tumor ornithine decarboxylase activity (ODC) and the effect of the ODC inhibitor alpha-difluoromethylornithine.

The R3327MAT-Lu tumor is a rapidly growing anaplastic derivative of the Dunning R3327 prostatic adenocarcinoma. We have found the ornithine decarboxylase (ODC) activity of this tumor to be as sensitive to inhibition by alpha-difluoromethylornithine (DFMO) as normal rat prostate. The same was true for all the other R3327 tumor derivatives we studied. The in vivo inhibition of ODC by DFMO allowed increased uptake of exogenously administered putrescine by the R3327AT tumor. Further, DFMO was inhibitory to the growth of the R3327MAT-Lu both in vitro and in vivo.

Animals↗

Clinical value of sensitivity determinations in treating urinary tract infections.

The results of bacterial susceptibility testing in 2,413 urine specimens obtained from patients with urinary tract infections indicated that in a high percentage clinical response could be predicted without the need for antimicrobial sensitivity testing. Simply identifying the infecting organism will provide the clinician with enough information to treat most urinary tract infections intelligently. The relative effectiveness of antimicrobial agents to enable the proper selection of therapy in patients with urinary tract infections is discussed.

Anti-Bacterial Agents↗

Prostatic cancer, acid phosphatase, creatine kinase-BB and race: a prospective study.

To examine the effectiveness of prostatic acid phosphatase and creatine kinase-BB determinations in detecting prostatic cancer serum from 594 men more than 40 years was assayed for prostatic acid phosphatase with the thymolphthalein monophosphate substrate and a radioimmunoassay kit. Creatine kinase-BB levels also were measured with a radioimmunoassay kit. Patients with benign prostatic hyperplasia had higher prostatic acid phosphatase levels than normal controls. Accordingly, to avoid a high incidence of false positives in patients with benign prostatic hyperplasia the 92.5 percentile level of the patients with benign prostatic hyperplasia (3.9 ng./ml.) was chosen as the upper limit of normal. With this critical value elevated prostatic acid phosphatase levels were observed in 6 per cent of the patients with clinical stage A disease, 8 per cent with stage B, 35 pr cent with stage C and 68 per cent with stage D. The radioimmunoassay was no more effective than the enzymatic assay in detecting prostatic cancer. A correlation between prostatic acid phosphatase levels and patient race was observed, with 80 per cent of the black patients with extracapsular prostatic cancer having elevated prostatic acid phosphatase levels compared to 34 per cent of the white patients with similar stage disease. Creatine kinase-BB was elevated only in patients with advanced disease and was of little value in the diagnosis of prostatic cancer.

Acid Phosphatase↗

Internal urethrotomy without a catheter: use of a urethral stent.

A method is presented that permits prolonged urethral stenting following an internal urethrotomy without the need of an indwelling Foley catheter. During this technique a 22F silicone catheter is inserted into the distended bladder, the balloon is left deflated and the catheter is advanced until the drainage hole is beyond the sphincter and no fluid drains through the catheter. At this point the catheter is cut flush with and sutured to the urethral meatus using 2 nylon sutures. The patient then is continent, able to void through the catheter lumen and has the advantage of a urethral stent without requiring catheter drainage. Of 21 patients 19 had good to excellent results 1 to 4 years after internal urethrotomy. Patient acceptance uniformly has been excellent and enthusiastic.

Catheters, Indwelling↗

Grading errors in prostatic needle biopsies: relation to the accuracy of tumor grade in predicting pelvic lymph node metastases.

To examine how accurately needle biopsies reflect the true histologic grade of prostatic cancers the histologic grade of needle biopsy specimens was compared to that of the radical prostatectomy specimen in 66 consecutive patients. Needle biopsies were given a lower grade than the prostatectomy specimen in 21 patients (33 per cent) and a higher grade in 5 patients (8 per cent). To examine how accurately the tumor grade of needle biopsy specimens predicts lymph node metastases in patients with clinical stage B prostatic cancer the needle biopsy grade was compared to lymph node metastases in 78 consecutive patients who underwent staging pelvic lymphadenectomy. Thirteen per cent of the patients with well differentiated cancer, 50 per cent with moderately differentiated cancer and 64 per cent with poorly differentiated cancer had pelvic lymph node metastases. In most cases grading errors did not influence the capacity of needle biopsies to predict nodal involvement. We conclude that although prostatic needle biopsies are associated with significant errors in grading they do provide valuable information about the predominant histologic pattern, which reflects the biologic potential of the tumor.

Biopsy, Needle↗

Treatment of a metastatic prostate derived tumor with surgery and chemotherapy.

The R3327/MAT-Lu tumor is a metastasizing variant of the Dunning R3327 Copenhagen rat prostatic carcinoma which, when implanted subcutaneously in the flank or intramuscularly in the hind leg, invariably metastasizes to the lungs. We examined treatment with either single dose chemotherapy, surgical excision of the primary tumor, or a combination of tumor excision and postoperative single dose chemotherapy. All 3 regimens significantly reduced the number of lung metastases; however, only the combination of tumor excision, followed by postoperative chemotherapy substantially prolonged survival and produced cures.

Animals↗

Difluoromethylornithine enhancement of putrescine uptake into the prostate: concise communication.

We studied the effect of alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, on putrescine uptake by the rat prostate. Using C-14 putrescine, we found a several-fold increase in uptake by both the dorsal and ventral prostates of DFMO-pretreated intact animals, compared with untreated controls. When previously castrated animals were treated with a combination of testosterone and DFMO, the prostatic uptake of exogenously administered C-14 putrescine increased more than tenfold. Under these conditions, DFMO enhanced the uptake by the prostate to a greater extent than by any other tissue studies.

Animals↗

Inhibition of the R3327MAT-Lu prostatic tumor by diethylstilbestrol and 1,2-bis(3,5-dioxopiperazin-1-yl)propane.

We have previously described the inhibitory effects of diethylstilbestrol on the growth of the androgen-independent, anaplastic Copenhagen rat prostatic tumor, R3327AT, which has a low metastatic potential. We have now selected a variant of the R3327AT tumor that metastasizes exclusively to the lungs, and we have designated it the R3327MAT-Lu. In a dose-response protocol, diethylstilbestrol was inhibitory to the primary R3327MAT-Lu tumor, thereby also inhibiting the formation of lung metastases. Inhibition was also observed in this model tumor by the chemotherapeutic agent 1,2-bis(3,5-dioxopiperazin-1-yl)propane.

Animals↗

Selective binding of zinc ions to heparin rather than to other glycosaminoglycans.

The relative binding affinity of Zn2+ to several glycosaminoglycans was determined by gel-filtration chromatography. Binding was observed only between Zn2+ and heparin. No binding was observed between Zn2+ and chondroitin 4-sulphate, chondroitin 6-sulphate, dermatan sulphate of hyaluronic acid. All of the glycosaminoglycans contained carboxy groups, but only heparin bound Zn2+. This observation suggests that, contrary to a previously proposed hypothesis, simple electrostatic interactions between the negatively charged carboxy groups of the glycosaminoglycans and the positively charged Zn2+ cannot explain the observed binding.

Chondroitin Sulfates↗

Effect of surgery and adjuvant chemotherapy on the R3327 MAT-Ly Lu tumor.

The R3327 MAT-Ly Lu is a prostate derived, anaplastic, hormone independent carcinoma. It spreads primarily to regional lymph nodes, followed by lung metastases. Combination therapy with surgery (tumor removal with or without regional lymphadenectomy) and chemotherapy (ICRF-159) was more effective treatment than either one alone. Primary tumor excision plus lymphadenectomy appeared to reduce the number of pulmonary metastases.

Animals↗

Aminoguanidine reversal of the inhibitory effects of ornithine analogs on the in vitro clonogenic survival of the R3327AT prostate-derived tumor.

In in vitro studies with the Copenhagen rat prostate-derived tumor cell lines, the activity of ornithine decarboxylase (ODC) of these lines were as sensitive to inhibition by alpha-difluoromethylornithine (alpha-DFMO) as normal prostatic tissue. The in vitro growth of the tumor in calf serum was inhibited by ODC inhibitors alpha-methylornithine and alpha-difluoromethylornithine. This inhibition was partially reversed by the diamine oxidase inhibitor aminoguanidine. Further, alpha-DFMO was not inhibitory to the growth of these cells in sera which lacked diamine oxidase activity, but was inhibitory when diamine oxidase was added.

Amine Oxidase (Copper-Containing)↗

End-to-end transureteroureterostomy: a report of 2 cases.

We report on 2 patients with extensive unilateral ureteral lesions and defunctionalized contralateral ureters who were treated by end-to-end transureteroureterostomy. Favorable results were achieved in both cases. Prolonged periods of ureteral non-function do not appear to be a contradiction to this procedure.

Carcinoma, Transitional Cell↗

Antibacterial substances in prostatic fluid.

We have identified the "prostatic antibacterial factor," responsible for the antibacterial activity of normal prostatic fluid as free zinc. It appears as if the bactericidal activity of the EPS is related to the amount of zinc present in the fluid and may play a role in the natural resistance of the male urinary tract to infection. In addition, the determination of the zinc content of the expressed prostatic secretion may be a useful test in diagnosing patients with chronic bacterial prostatitis or those who are likely to be susceptible to prostatitis. The factors responsible for the marked decrease of zinc in the prostatic fluid of patients with bacterial prostatitis and methods of altering the zinc level in the fluid as a possible means of eradicating chronic bacterial prostatitis or increasing the resistance of the patient to the disease are important questions requiring further study.

Animals↗

Three-day treatment of urinary tract infections.

There is little rationale to support the currently accepted 10 to 14-day treatment period for urinary tract infection. To assess the cure rate in patients given 3 days compared to the standard 10-day period of antimicrobial therapy a prospective trial was designed to test the over-all effectiveness of each treatment. Sixty patients were randomized to either penicillin-G or trimethoprim-sulfameth-oxazole for either 3 or 10 days. Urine and external vaginal cultures were done before therapy was instituted, at day 3 while on therapy and 7 days after the completion of treatment. The over-all cure rate in the short-term treatment group was 86 per cent and in the long-term treatment group it was 88 per cent. Patients receiving trimethoprim-sulfamethoxazole had a much better response to clearance of the pathogenic bacteria from the external vagina but this did not correlate with clearance of the bladder bacteriuria. Bacterial sensitivities on the external vaginal cultures suggest that in some patients 10 days of therapy actually may aid in the development of bacterial resistance noted in subsequent bladder infections. Finally, a cost-benefit analysis revealed that the use of a 3-day regimen as standard treatment for urinary tract infections would result in a savings to our patients conservatively estimated at $62,000,000 yearly.

Adolescent↗