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Biomedical subjects

P C Walsh

Publications and source records attributed to P C Walsh.

At least 19 recordsLinked to original sources
PubMed1992

The effect of finasteride in men with benign prostatic hyperplasia. The Finasteride Study Group.

BACKGROUND: Benign prostatic hyperplasia is a progressive, androgen-dependent disease resulting in enlargement of the prostate gland and urinary obstruction. Preventing the conversion of testosterone to its tissue-active form, dihydrotestosterone, by inhibiting the enzyme 5 alpha-reductase could decrease the action of androgens in their target tissues; in the prostate the result might be a decrease in prostatic hyperplasia and therefore in symptoms of urinary obstruction. METHODS: In a double-blind study, we evaluated the effect of two doses of finasteride (1 mg and 5 mg) and placebo, each given once daily for 12 months, in 895 men with prostatic hyperplasia. Urinary symptoms, urinary flow, prostatic volume, and serum concentrations of dihydrotestosterone and prostate-specific antigen were determined periodically during the treatment period. RESULTS: As compared with the men in the placebo group, the men treated with 5 mg of finasteride per day had a significant decrease in total urinary-symptom scores (P less than 0.001), an increase of 1.6 ml per second (22 percent, P less than 0.001) in the maximal urinary-flow rate, and a 19 percent decrease in prostatic volume (P less than 0.001). The men treated with 1 mg of finasteride per day did not have a significant decrease in total urinary-symptom scores, but had an increase of 1.4 ml per second (23 percent) in the maximal urinary-flow rate, and an 18 percent decrease in prostatic volume. The men given placebo had no changes in total urinary-symptom scores, an increase of 0.2 ml per second (8 percent) in the maximal urinary-flow rate, and a 3 percent decrease in prostatic volume. The frequency of adverse effects in the three groups was similar, except for a higher incidence of decreased libido, impotence, and ejaculatory disorders in the finasteride-treated groups. CONCLUSIONS: The treatment of benign prostatic hyperplasia with 5 mg of finasteride per day results in a significant decrease in symptoms of obstruction, an increase in urinary flow, and a decrease in prostatic volume, but at a slightly increased risk of sexual dysfunction.

5-alpha Reductase Inhibitors↗
PubMed1992

Estimation of prostatic growth using serial prostate-specific antigen measurements in men with and without prostate disease.

Prostate growth curves were estimated from serial prostate-specific antigen (PSA) measurements on frozen sera in three groups of men: (a) 16 men with no prostatic disease by urological history and examination; (b) 20 men with a histological diagnosis of benign prostatic hyperplasia (BPH) who had undergone simple prostatectomy; and (c) 18 men with a histological diagnosis of prostate cancer. The median number of repeated PSA measurements over an 8- to 26-yr period prior to histological diagnosis or exclusion of prostate disease was eight and 11 for noncancer and cancer subjects, respectively. Predicted rates of change in PSA (PSA velocity) were linear and curvilinear for control and BPH subjects, respectively. Subjects with cancer demonstrated both a linear and an exponential phase of PSA velocity. Based on time to double PSA, we estimated the epithelial doubling time for men without prostate disease to range from 54 +/- 13 yr at age 40 to 84 +/- 13 yr at age 70. For men with BPH, doubling times ranged from 2 +/- 13 yr at age 40 to 17 +/- 5 yr at age 85. Subjects with local/regional and advanced/metastatic cancer had similar PSA doubling times of 2.4 +/- 0.6 yr and 1.8 +/- 0.2 yr, respectively. These data are consistent with what is known about prostatic growth with age in men without prostate disease and BPH, and the kinetics of prostate cancer growth. Estimates of prostatic growth rate from changes in PSA may be useful clinically in management of men with prostate disease.

Aged↗
PubMed1992

Mendelian inheritance of familial prostate cancer.

Previous studies have demonstrated familial clustering of prostate cancer. To define the nature of this familial aggregation and to assess whether Mendelian inheritance can explain prostate cancer clustering, proportional hazards and segregation analyses were performed on 691 families ascertained through a single prostate cancer proband. The proportional hazards analyses revealed that two factors, early age at onset of disease in the proband and multiple affected family members, were important determinants of risk of prostate cancer in these families. Furthermore, segregation analyses revealed that this clustering can be best explained by autosomal dominant inheritance of a rare (q = 0.0030) high-risk allele leading to an early onset of prostate cancer. The estimated cumulative risk of prostate cancer for carriers revealed that the allele was highly penetrant: by age 85, 88% of carriers compared to only 5% of noncarriers are projected to be affected with prostate cancer. The best fitting autosomal dominant model further suggested that this inherited form of prostate cancer accounts for a significant proportion of early onset disease but overall is responsible for a small proportion of prostate cancer occurrence (9% by age 85). These data provide evidence that prostate cancer is inherited in Mendelian fashion in a subset of families and provide a foundation for gene mapping studies of heritable prostate cancer. Characterization of genes involved in inherited prostate cancer could provide important insight into the development of this disease in general.

Adult↗
PubMed1992

The value of serum enzymatic acid phosphatase in the staging of localized prostate cancer.

With the development of reliable assays for the measurement of prostate specific antigen (PSA), the use of serum enzymatic acid phosphatase in the staging of disease before radical prostatectomy has been called into question. We evaluated 460 consecutive men who were referred to our institution as candidates for radical prostatectomy. Staging evaluation included digital rectal examination, serum measurements of enzymatic acid phosphatase and PSA, bone scans and, in patients in whom advanced clinical stage was anticipated, computerized tomography, magnetic resonance imaging or transrectal ultrasonography. Of the 460 men 21 (4.6%) had elevations of serum enzymatic acid phosphatase. All 19 men with elevations who were fully evaluated proved to have either positive bone scans, extraprostatic extension of disease, PSA greater than 100 ng./ml., positive lymph nodes or positive seminal vesicles. However, in 17 of the 21 men (81%) with elevated serum enzymatic acid phosphatase advanced disease was detected by either abnormal digital rectal examination or PSA alone. Thus, serum enzymatic acid phosphatase provided unique information in only 4 of the entire study population (0.9%). Recognizing this low yield of unique information, we believe that measurements of serum enzymatic acid phosphatase are no longer mandatory before radical prostatectomy but may provide important confirmatory information in patients in whom advanced disease is suspected.

Acid Phosphatase↗
PubMed1992

The management of rectal injury during radical retropubic prostatectomy.

From May 1982 through March 1991, 10 rectal injuries were identified in 1,000 men who underwent radical retropubic prostatectomy for clinically localized adenocarcinoma. All rectal injuries occurred in nonirradiated patients. Of these patients 9 were identified during surgery and 1 was diagnosed on postoperative day 2. The 9 patients in whom the injury was recognized at operation underwent successful primary closure without a diverting colostomy. The patient who underwent delayed closure was treated with a temporary diverting colostomy. As a preoperative routine, all patients received a Fleet enema without preoperative antibiotics. In all patients the rectal injury was closed in 2 layers, the anal sphincter was dilated, and a pedicle of omentum was mobilized through a small opening in the peritoneum and placed through the rectovesical cul-de-sac to cover the suture line. All patients received 7 to 14 days of broad-spectrum antibiotics. Postoperatively, no patient had a wound infection, pelvic abscess or urethrorectal fistula. Overall hospital stay was increased by an average of 2 days. Rectal injuries recognized during surgery in previously nonirradiated patients undergoing radical retropubic prostatectomy can be managed successfully with primary closure alone, avoiding the morbidity of a diverting colostomy.

Adenocarcinoma↗
PubMed1992

Prostate cancer recurrence in radical surgery patients receiving autologous or homologous blood.

An evaluation of the effects of blood transfusion on recurrence and survival after radical surgery for prostate cancer was performed. Between 1982 and 1986, 315 consecutive patients underwent radical retropubic prostatectomy by a single surgeon; of 309 patients for whom transfusion data were available, 94 received homologous blood (Group I) and 215 received autologous blood or no blood (Group II). At the time of surgery, there were no differences between Group I and Group II with respect to age, preoperative cancer stage, preoperative histologic grade (Gleason grade), prostatic acid phosphatase score, and preoperative potency. At discharge, the groups were similar in the status of neurovascular bundles, capsular involvement, seminal vesicle involvement, lymph node involvement, postoperative Gleason grade, and postoperative potency. No adjuvant hormone therapy or radiation therapy was administered until tumor recurrence. The patients were followed annually by physical examinations and measurements of prostate-specific antigen. Cancer recurrence was detected in 23 (24.5%) Group I patients and 49 (22.7%) Group II patients. These proportions were not significantly different in univariate or multivariate analysis, and the time to recurrence curves overlapped. It is concluded that homologous blood transfusions are not associated with more rapid tumor recurrence or death after radical surgery for prostate cancer than is seen with autologous transfusions. These results differ from previous reports, which suggested that transfusions may cause recurrence of cancer in patients with colorectal or prostate cancer because of the immunosuppressive effects of blood transfusions.

Antigens, Neoplasm↗
PubMed1979

A microassay for the measurement of androgen receptors in human prostatic tissue.

A microassay utilizing R 1881 (methyltrienolone) has been developed for the measurement of androgen receptor sites in the cytosol and nuclear extract of human prostatic tissue. Binding of R 1881 to the progesterone binding molecule in cytosol was eliminated by the addition of triamcinolone acetonide. Utilizing a six tube, single point assay, the number of binding sites estimated in nuclear extract averaged 95% of the number measured by a full 7 point Scatchard analysis; the number estimated by the microassay in cytosol averaged 91%. When the single point assay was applied to needle biopsy specimens (200 mg of tissue), the estimated number of binding sites in nuclei averageed 83% of the number measured in bulk tissue (2 grams) utilizing a 7 point Scatchard analysis; the number in cytosol estimated by the microassay on needle biopsy specimens averaged 73%. It is hoped that this technique may be useful in correlating receptor content with hormonal responsiveness in men with metastatic carcinoma of the prostate.

Binding, Competitive↗
PubMed1979

Androgen, estrogen and progesterone receptors of the R3327H Copenhagen rat prostatic tumor.

Sucrose density gradient analysis of the R3327H tumor cytosol demonstrated the presence of both androgen and estrogen binding proteins. Competitive binding analysis with 17 beta-estradiol, 5 alpha-dihydrotestosterone, R1881, cyproterone acetate, and cortisol was consistent with the presence of 2 different binding sites for androgens and estrogens. Scatchard binding analysis was performed in the dorsal-lateral prostate as well as the R3327H tumor from normal Copenhagen rats. High affinity receptors for androgen and estrogen but not progesterone were found. However, in R3327H tumors relapsing following castration, the presence of high affinity receptors for progesterone were readily detectable.

Animals↗
PubMed1979

Renovascular hypertension: comparison of medical and surgical therapy.

1. Results of medical and surgical therapy were compared in 28 patients with hypertension and unilateral renovascular ischaemia. 2. Renal function remained normal in both groups throughout the study period. After 6 months of follow-up systolic and diastolic blood pressures were significantly lower in the surgically treated patients. After 12 months of follow-up there was no significant difference between the two groups in diastolic blood pressure and after 24 months of follow-up there was no significant difference between the two groups in either systolic or diastolic blood pressure. 3. Sixty per cent of surgically treated patients were cured 6 months after operation, but only 40% remained cured after 24 months of follow-up. 4. All patients cured at 6 months who subsequently required antihypertensive medication had arteriosclerotic renovascular disease.

Blood Pressure↗
PubMed1979

Comparison of spontaneous and experimentally induced canine prostatic hyperplasia.

Spontaneous prostatic hyperplasia in the beagle appears to progress with age from a glandular to a cystic histological appearance. Prostatic hyperplasia can be induced in young beagles with intact testes by treatment for 4 mo with either dihydrotestosterone or 5 alpha-androstane-3 alpha, 17 beta-diol, alone, or with either of these steroids in combination with 17 beta-estradiol. In contrast, the induction of prostatic hyperplasia in young castrated beagles, in which the gland had been allowed to involute for 1 mo, requires the administration of both 17 beta-estradiol and either 5 alpha-androstane-3 alpha, 17 beta-diol or dihydrotestosterone. Testosterone and 17 beta-estradiol, either singly or in combination, did not produce the hyperplastic condition in intact or castrated beagles. The experimentally induced prostatic hyperplasia is identical in pathology to the glandular hyperplasia that occurs naturally in the aging dog with intact testes. However, cystic hyperplasia was not produced by any of the treatments tested in young animals.

Androstane-3,17-diol↗
PubMed1979

Long-term survival after hormonal therapy for stage D prostatic cancer.

Hormonal therapy occasionally produces long-term survival of men with metastatic carcinoma of the prostate. To identify which patients will benefit for long intervals a retrospective analysis was done on 56 men with stage D carcinoma of the prostate treated between 1963 and 1968. Of this group 5 patients lived longer than 10 years. We were unable to identify clinical or pathologic characteristics that would have indicated which patients would have done well.

Adenocarcinoma↗