Showing papers on "Prostate published in 1976"

The induction of prostatic hypertrophy in the dog with androstanediol.

Abstract: The effects of androstanediol and estradiol on prostatic growth were investigated in castrate dogs. Estrogens along resulted in no significant change in prostatic weight, whereas androstanediol produced growth comparable to that in uncastrated controls. Androstanediol plus estradiol resulted in an even more striking increase in prostate growth. Approximately half the animals receiving androstanediol alone and all of those receiving androstanediol plus estradiol fulfill the weight and histological criteria for prostatic hypertrophy in the dog. Since both these steroid hormones are presumed to be normal secretory products of the testis, it is possible that they are involved in the pathogenesis of prostatic hypertrophy in the dog.

The use of alpha-adrenergic blockers in benign prostatic obstruction.

Abstract: There has been much interest in recent years in the role played by the adrenergic receptors in the urinary tract and a certain amount of work has been done in our department on this subject. Amongst other investigations we have studied the adrenergic receptors in the rat prostate (Raz, Zeigler and Caine, 1973) and subsequently in the human prostate (Caine, Raz and Zeigler, 1975). The latter was performed on tissue obtained from patients undergoing operations for benign prostatic obstruction, and separate studies were made of the receptors in the prostatic capsule, the enucleated “adenoma” and selected parts of the bladder neck and trigone. It was found that the prostatic capsule was extremely rich in α-adrenergic receptors, the prostatic adenoma moderately rich and the bladder neck region showed variable results, the maximal α-receptor response being in the region of the trigone. In the case of the rat prostate there was evidence of additional β-adrenergic activity but for practical purposes this was negligible in the human material. As a consequence of the above findings, and having regard to known clinical and pharmacological causative factors, it was suggested in those papers that certain cases of acute retention urine in patients with benign hypertrophy of the prostate may be due to sudden stimulation the α-adrenergic receptors, causing an increase in tone of the smooth muscle tissue in the prostate and prostatic capsule, hence resulting in an increase in the closure pressure on the urethra. Further consideration suggested that if this be the case, variations in a-adrenergic activity lesser degree might be responsible for at least some of the variations in the severity of the obstructive symptoms, which is so typical of many patients suffering from prostatic enlargement. As a corollary, if this hypothesis be true, one could anticipate a beneficial effect from the use α-adrenergic blocking agents in such patients with retention or obstructive symptoms. It was accordingly decided to carry out a trial of such agents, to see if they would be of help to these patients. During the course of the trial it soon became evident that the majority of the patients were deriving considerable benefit from the treatment and that they fell into a number of clinical groups, which will be discussed below. A few illustrative cases from the different groups will briefly described.

The prostatic antibacterial factor: identity and significance.

Abstract: Normal human prostaticfluid possesses pronounced antibacterial activity. This activity is absent or markedly diminished in the fluid of men with chronic bacterial prostatitis. Ion-probe and mass spectrographic analysis of this antibacterialfactor has shown it to be a zinc salt. ProstaticfEuid zinc levels in 15 men with chronic bacterial prostatitis averaged 50 pg. per milliliter (range 0 to 139 pg. per milliliter). The zinc level in the expressed prostate secretion (EPS) of49 control men averaged 448 pg. per milliliter (range 150 to 1,000 pg. per milliliter). There was no overlap in the range of zinc values between the two groups. The decrease in EPS zinc concentration in the patient population was not secondary to a decreased serum zinc level. Exogenous zinc given orally did not increase the EPS zinc level. The decrease in EPS zinc was not limited to infected prostaticfEuid cultures and may precede the entry of bacteria into the prostate. The data presented suggest that zinc may serve as an in vivo defense mechanism against prostatic invasion and subsequent urinary tract infections in men. Urinary tract infections occur more frequently in adult females than males. The reason for this dif- ference is unknown. In adult males the majority of urinary tract infections are secondary to an initial prostatic infection which later ascends to infect the bladder urine.' For several years, we and others have been investigating the biochemical properties of prostatic fluid and have dem- onstrated that the normal human, canine, and rat prostatic secretions possess pronounced an- tibacterial activity. 2-6 These observations have led to the purification and isolation of PAF (prostatic antibacterial factor) from prostatic fluid and se- men. 7 Positive identification of PAF by mass spec- troscopy and ion-probe analysis has confirmed that the bactericidal activity of PAF is directly related to the total zinc concentration of the fluid and no other antibacterial agent was identified. *This study was supported in part by Research Grant No. 5 ROl A110668, National Institute of Allergy and Infectious Disease, National Institutes of Health, U.S. Public Health Service. Studies involving patients with bacteriologi- cally documented chronic bacterial prostatitis demonstrated a marked diminution or total ab- sence of zinc in the EPS (expressed prostate se- cretion) of these patients as compared with nor- mal males. This suggests that the cation may serve as an in vivo antibacterial defense mechanism against prostatic and urinary tract infections in humans.

Comparison of androgen metabolites in benign prostatic hypertrophy (bph) and normal prostate

Abstract: 5 alpha-Dihydrotestosterone (DHT) and androstanediols (diols) have been measured in human prostate tissue. DHT levels in surgical specimens of prostate from 8 patients with BPH averaged 5.6 +/- 0.93 S.E. ng/g and were significantly greater than (P less than 0.01) values of 2.1 +/- 0.32 S.E. ng/g in 6 normal prostates obtained post-mortem from males less than 50 yrs old. Androstanediols averaged 2.3 +/- 0.35 S.E. ng/g in the BPH specimens compared to values of 10.2 +/- 2.4 S.E. ng/g in the normal prostates (P less than 0.01). This significantly higher (P less than 0.001) ratio of diols/DHT in the normal (5.1 +/- 0.93 S.E.) compared to the BPH prostate (0.45 +/- 0.08 S.E.) suggests that a decrease in 3-hydroxysteroid oxido-reductase, which converts DHT to diol, may be an important clue to the pathogenesis of BPH.

Androgen levels in the plasma and prostatic tissues of patients with benign hypertrophy and carcinoma of the prostate

Abstract: Specific radioimmunoassays for testosterone, dihydrotestosterone (DHT) and androstenedione were carried out to measure the concentrations of the three hormones in the plasma and prostatic tissue of ten patients with benign prostatic hypertrophy (BPH) and ten patients with carcinoma of the prostate. The results indicate that there are no significant differences between the peripheral plasma concentrations of testosterone, DHT and androstenedione in BPH [19.7 +/- 2.6, 2.6 +/- 0.9 AND 5.5 +/- 1.7 (S.E.M.) nmol/l respectively] and in carcinoma [16.9 +/- 2.8, 2.4 +/- 0.5, 4.4 +/- 1.1 nmol/l respectively], (in all cases P greater than 0.1). In contrast, the prostate tissue rations DHT: testosterone (3.59 +/- 0.55 for BPH and 0.66 +/- 0.09 for carcinoma) and androstenedione: testosterone (2.83 +/- 0.38 for BPH and 1.07 +/- 0.16 for carcinoma) are significantly less in carcinoma than in benign hypertrophy ( in all cases P less than 0.01). The accumulation of testosterone in the carcinoma, relative to values found in BPH tissue is, therefore, not associated with changes in the concentrations of androgens in the plasma pool but may be related to local factors and metabolic changes within the prostate.

The value of prophylactic antibiotics in transurethral prostatic resection: a controlled trial, with observations on the origin of postoperative infection.

Abstract: Prophylactic antibiotics significantly decrease the incidence of urinary tract infection following endoscopic prostate resection. They are ineffective in reducing the incidence of postoperative fevers, or in reducing the frequency of positive blood cultures during or after operation. A majority of prostate glands harbour colonies of potentially pathogenic organisms, and these are the commonest source of infection of the urinary tract following release by prostatic surgery.

Metal–androgen interrelationships in carcinoma and hyperplasia of the human prostate

Abstract: Studies were undertaken to examine the endogenous concentrations of zinc testosterone and 5alpha-dihydrotestosterone (DHT) within the hypertrophic and neoplastic human prostate. The reported high incidence of carcinoma with cadmium prompted exploration of concentrations of cadmium in both types of prostatic tissue. Prostatic tissue was obtained from 23 patients aged 58-87 years with benign prostatic hypertrophy (BPH) and 9 patients aged 64-91 years with carcinoma of the prostate. None was receiving any form of hormonal therapy. For controls normal prostate tissue was obtained at autopsy from 9 men aged 25-58 years. Chemical methods employed are described. Zinc and cadmium concentrations were compared with the histological appearance of an adjacent serial section. There was no correlation between the concentrations of zinc or cadmium in either type of tissue (p greater than .1) despite the histological differences. Similar concentrations of zinc in both normal and BPH tissues were found. However in carcinoma tissue a marked decrease in zinc was found. The cadmium levels in BHT tissue were higher than those found in normal tissue and markedly increased in carcinomatous tissue. The concentrations of DHT in benign hypertrophy tissue and of testosterone and DHT in carcinoma tissues were inversely proportional to the levels of zinc in abnormal tissue. The DHT levels in both tissues were proportional to the cadmium concentrations.

"Endometrial" adenocarcinoma of the prostate: a distinctive tumor of probable prostatic duct origin.

Abstract: A so-called “endometrial” adenocarcinoma of the prostate has been studied by light and electron microscopy, and by histochemical techniques. The previously proposed utricular origin and estrogen dependence of such tumors is questioned. Strong acid phosphatase staining, and the ultrastructural demonstration of multivacuolated, lipid, and lysosome-containing tumor cells, suggest a prostatic ductal origin for this type of carcinoma despite the histologic similarity to carcinoma of the endometrium.

Physical and chemical determinations of prostatic secretion in benign hyperplasia, prostatitis, and adenocarcinoma.

Abstract: With a view to detecting early biochemical changes in diseased prostate glands, polyamines, zinc, cholesterol, and physical measurements of pH and specific gravity were determined in expressed prostatic secretion. The pH of prostatic secretion from normal men was found to be higher than previously reported in the literature. The other measured substances and specific gravity were found to be decreased in prostatitis whereas the specific gravity was markedly elevated in those patients with adenocarcinoma. Clarification of physicochemical studies on prostate secretion may lead to a system of better monitoring the course of prostate disease.

Effect of Megestrol Acetate (Megace®) on Steroid Metabolism and Steroid-Protein Binding in the Human Prostate

Abstract: Megestrol acetate (Megace), an antiandrogen, was administered in a dosage of 80 mg daily to 6 patients with benign prostatic hypertrophy (BPH) for 4 to 25 days prior to transurethral resection of the prostate (TURP). Surgical tissue from drug-treated patients was compared to untreated controls in regard to: 1) the enzymatic reduction of testosterone (T) and dihydrotestosterone (DHT); 2) DHT binding to a cytosol receptor protein; 3) tissue levels of endogenous dihydrotestosterone and androstanediols (diols). When minced prostate was incubated with 3H-T and 14C-androstenedione for 1 h at 37 C, prostate 5alpha-reductase activity, measured as reduced products formed from substrate, decreased to 31% and 39%, respectively, of the control values. Prostate 3-oxido-reductase enzyme activity, measured as diols formed from 3H-DHT, was decreased to neglible values in Megace-treated patients compared to an 8.7% conversion to diols in controls. No 3H-DHT binding to a cytosol receptor protein could be demonstrated in 4 out of 5 prostates from Megace-treated patients, whereas the presence of such a receptor was noted in 14 out of 17 untreated controls. Endogenous DHT levels in Megace-treated patients averaged 1.1 ng/g (SE = 0.26), significantly less than the average of 3.9 ng/g (SE = 0.49) found in controls (P less than 0.001). No significant difference was noted in endogenous diols. In addition to these effects on tissue, Megace significantly decreased plasma levels of T, LH, and FSH at the end of the 4- to 25-day period; plasma prolactin levels did not change. Continued studies of Megace for the possible treatment of benign prostatic hypertrophy may be warranted since the drug appears to block several important biochemical steps which mediate the effects of androgen on the human prostate.

The autonomic innervation of the human prostate. Histochemistry of acetylcholinesterase in the normal and pathologic states.

Abstract: The pattern of innervation of fibres containing AchE was examined by histochemical methods in fresh frozen sections of normal adult prostate, benign nodular hyperplasia, carcinoma of the prostate and the prepubertal prostate. Significant differences between the four groups investigated have been found.

Androgen of the human prostate.

Abstract: The relationship between the concentrations of total and apparent free testosterone in the plasma and the levels of testosterone (T), dihydrotestosterone (DHT) and 5 alpha-androstan-3-alpha, 17 beta-diol (DIOL) in 13 benign hypertrophic and 6 car-cinomatous prostates was studied. The androgen concentration within both types of glands was nearly 4-fold that in the blood but bore no direct relationship to the blood level. About 75% of the androgen in the tissue was DHT. The most striking finding was that, in spite of a 25.5% less concentrated pool of apparent free testosterone in the blood, the level of T and its metabolites in the cancer tissue was 29% above that in the samples of benign hypertrophic prostate.

Localized advanced carcinoma of the prostate: Radiation therapy versus hormonal therapy

Abstract: Since 1967, 26 patients with prostatic cancer T 3,4 N X M o have been treated by castration and estrogens; 30 patients received additional radiotherapy, 30 patients were submitted to radiotherapy only. Four year survival was best if radiotherapy only was the initial treatment though hormone treatment might be necessary during follow-up period. A low degree of differentiation of the growth worsens prognosis significantly. Irradiation complications can be reduced to an acceptable percentage. Transrectal prostatic needle aspiration in order to assess the presence of an estrogen effect—or its disappearance and at the same time reappearance of cancer cells—might be a useful tool in predicting failure of hormone treatment and in indicating local radiotherapy as a second attempt of "curative" treatment.

Therapeutic trial of aniline mustard in patients with advanced cancer. Comparison of therapeutic response with cytochemical assessment of tumor cell beta-glucuronidase activity.

Abstract: Seventy-eight patients with advanced cancer received an adequate therapeutic trial with aniline mustard (NSC 18429). Significant anticancer activity with clinical benefit was demonstrated in five patients with cancer of the prostate and one patient with renal cancer. beta-glucuronidase levels in aspirate and imprint preparations of tumor cells were assessed by a timed cytochemical technique. A partial correlation appeared to exist between very intense glucuronidase staining and tumor regression in prostate and kidney lesions; however, these high levels were observed only rarely. Sequential observations in two patients demonstrated loss of enzymatic activity concomitant with development of clinical relapse.

Factors influencing prognosis in the radiotherapeutic management of carcinoma of the prostate

Abstract: A total of 96 patients with adenocarcinoma of the prostate were irradiated with the intent to control the disease locally by two dissimilar techniques: pelvic irradiation with a prostatic boost vs pelvic and para-aortic irradiation with prostatic boost. Survival and local control of disease appeared to be enhanced by the use of adjuvant hormonal therapy. Advancing extent of disease, locally and distally, and the presence of disease within the lymph nodes affected prognosis adversely.

Impotence therapy and cancer of the prostate

Abstract: Prostate cancer developed in two male patients being treated with fluoxymesterone for erectile impotence. It is suggested that the current increased interest in and therapy for sexual dysfunction be accompanied by an awareness of a possible causal relationship between exogenous androgens and prostrate cancer.

Influence of Purified Plasma Proteins on Testosterone Uptake and Metabolism by Normal and Hyperplastic Human Prostate in “Constant-Flow Organ Culture”

Abstract: Surgical samples of human prostate were explanted and submitted to constant-flow organ culture. The medium contained 3H-testosterone 50 nM, and except for controls, increasing concentrations of human serum albumin (HSA)1 or human sex-steroid-binding plasma protein (SBP). At steady state, the explants were washed and homogenized, and the total radioactivity, radioactive testosterone, androstanolone (17β-hydroxyandrostan-3-one), androstane-3α, 17β-diol, and androstane-3β,17β-diol were determined after the addition of the corresponding internal 14C standards. From these data, testosterone uptake and metabolism were quantitated. The concentration of unbound testosterone in protein-supplemented culture media was measured separately by equilibrium dialysis. In control supervisions without protein, the tissue concentration of total radioactive steroids was equivalent to 182 ± 18 (mean ± SEM) pmoles/g of prostate. Androstanolone represented about 2β, testosterone 1/10, and the two androstanediols togethe...

A study of concentrations of trimethoprim-sulphamethoxazole in the human prostate gland.

Abstract: The ability of trimethoprim (TMP) and sulphamethoxazole (SMX) components of co-trimoxazole to penetrate the human prostate gland was investigated. After a single 4-tablet dose TMP was evenly distributed between prostate and plasma, whereas SMX was mainly associated with plasma. Following a week's therapy significant accumulation of TMP was seen in the prostate relative to plasma whereas SMX although still associated with plasma had increased drug levels in prostate compared with the single dose study. It is concluded that co-trimoxazole produces effective antibacterial levels in the human prostate and has indications in the treatment of prostatitis.

Sarcoma of the prostate.

Abstract: The experience at the University of Iowa Hospitals with 12 patients having sarcoma of the prostate is described. Although the total number of patients is small, two distinct groups can be identified. The infants, children, and young adults presenting with this malignancy had a very poor survival regardless of the therapy administered. However, the older men have generally done well, surviving several years following therapy for the relief of lower urinary tract obstruction. The longest surviving patient was treated by transurethral prostectomy followed by transperineal instillation of radioactive gold. A program of combination therapy utilizing surgery, external irradiation, and triple chemotherapy is suggested for use in children and young adults with prostatic sarcoma.

Nonsurgical treatment of human benign prostatic hyperplasia.

Abstract: Publisher Summary This chapter elaborates the nonsurgical treatment of human benign prostatic hyperplasia (BPH). Benign nodular hyperplasia of the prostate is the most common neoplastic growth in man. The results of surgical treatment for BPH are good with a low mortality, a modest number of complications, obtainment of a good functional result and with little effect on potentia. The incidence of BPH in 100 men over 45 years of age who had received testosterone propionate in the treatment of either angina pectoris or the male climacterium with the incidence in 100 age-matched controls is compared. Testosterone propionate had been administered to these patients intramuscularly in doses of 25–75 mg per week for periods varying from 3 months to 4 years. Twenty-seven treated patients showed prostatic hypertrophy, but 34 control subjects also had an enlarged prostate. It is found that when estrogen therapy was combined with the 3α-androstanediol treatment, the prostates were even larger, and the glands developed additional stromal components, which more closely resembled the type of BPH observed in humans.

Evaluation of cellular immunologic responsiveness in the clinical management of patients with prostatic cancer. III. Inhibition of leucocyte migration.

Abstract: Host cellular responsiveness to tumour was evaluted in 37 patients with varying degrees of clinically active and inactive adenocarcinoma of the prostate by direct inhibition of leucocyte migration (ILM) employing saline extracts of pooled allogeneic normal, benign and malignant prostatic tissue as a source of antigen. The majority of these patients had received or were receiving conventional therapy at the time of evaluation. 13 (35%) prostatic cancer patients possessed clinically significant specific reactivity to malignant prostatic tissue, whereas only 1 (8%), of 13 control patients (11 healthy adults and 2 patients with carcinoma other than of the prostate: bladder and penis) possessed comparable reactivity. While the wide range of specific reactivity observed overall, including 'stimulation' of migration, compared with the mean percent ILM was very large, the SD of the mean specific percent ILM in the 13 prostatic cancer patients possessing clinically significant specific reactivity to malignant prostatic tissue, was most respectable. Since all reactions were allogeneic, these results indicated that prostatic cancer patients possessed cell-mediated immunity to presumably common prostatic tumour-associated antigens. Further evaluation disclosed that the incidence of patients possessing clinically significant reactivity to malignant tissue was almost identical regardless of the patient's stage of malignancy, histological grade of tumour, or clinical status. The degree of sensitization of clinically significant reactivity to malignant tissue was, however, greater in patients with localized disease, low grade tumour, and clinically inactive disease, than in patients with advanced disease, high-grade tumour, and clinically active disease. Evaluation of the possible correlation of specific reactivity to malignant prostatic tissue as a prognostic index of subsequent clinical responsiveness revealed a positive correlation with the degree of sensitization in 3 (43%) of 7 patients available for routine follow-up. Correlation in four patients was questionable due to the observations of 'stimulation' of migration rather than inhibition. While providing initial preliminary evidence of the presence of cell-mediated anti-tumour immunity in patients with prostatic cancer and promise of a possible prognostic index, the wide range in the variability of cellular responsiveness and the failure to identify clinically significant reactivity to malignant prostatic tissue in the majority (65%) of the patients evaluated, raises concern as to whether ILM employing saline extracts will provide the necessary in vitro assay of cellular responsivenss for the evaluation of prostatic cancer patients.