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Biomedical subjects

J T Grayhack

Publications and source records attributed to J T Grayhack.

At least 19 recordsLinked to original sources
PubMed1992

Benign prostatic hyperplasia. The scope of the problem.

BACKGROUND: The prevalence and incidence of clinical problems secondary to and associated with benign prostatic hyperplasia (BPH) are of increasing concern as the population ages. METHODS: Selected published reports using anatomical and clinical criteria to identify BPH and its clinical sequelae were reviewed. RESULTS: The following observations seem to reflect the current state of knowledge: (1) BPH develops with increasing frequency as men age; (2) BPH causes significant pathologic changes in the urinary tract of some patients and symptoms in others; and (3) other identifiable or cryptic etiologic factors may be the predominant cause of identical voiding dysfunction in patients with BPH. CONCLUSION: Essential information about factors initiating and promoting development of BPH, the exact mechanisms by which BPH alters voiding mechanisms, and definitive diagnostic criteria to establish the role of BPH in clinical changes are lacking. Progress in these problem areas is essential to guide appropriate clinical management.

Adult↗
PubMed1992

A local direct effect of pituitary graft on growth of the lateral prostate in rats.

Prolactin and testosterone are synergistic in stimulating growth of the rat prostate. The lateral lobe is more sensitive to this synergism than the ventral and dorsal lobes. To investigate whether prolactin acts directly in the rat prostate or indirectly through another systemic mediator, anterior pituitary grafts (1 mm3) were implanted in the lateral prostate of castrated Sprague-Dawley rats in whom a 0.5 cm or 1.0 cm testosterone-filled silastic tubing was implanted subcutaneously at the same time. Rats were randomly assigned to receive either the pituitary or a muscle chip of similar size grafted beneath the fascia lateral to the lateral prostate. Twenty-one days later, serum prolactin levels were not elevated in pituitary-grafted animals and were not significantly different from those in muscle-grafted rats. The mean lateral prostate weight on the grafted side in pituitary-implanted rats with 1.0 cm testosterone tubing was 43% heavier than either that of the contralateral side or the corresponding weights in muscle-implanted rats. In pituitary-implanted rats with 0.5 cm testosterone tubing, the mean lateral prostate weight on the grafted side was 60% heavier than either that of the contralateral side or that of the corresponding weights in muscle-implanted rats. The weight of the ventral and dorsal lobes of the prostate was not significantly affected by the presence of pituitary grafts in one of the lateral lobes. The local effect of prolactin on the lateral prostate was further demonstrated by an overall decline in tissue concentrations of dihydrotestosterone in the grafted side. These results provided evidence to indicate that there was a direct effect of prolactin on growth of the lateral prostate in rats.

Animals↗
PubMed1992

Evidence for a non-androgenic role of testis and epididymis in androgen-supported growth of the rat ventral prostate.

A widely held view is that the role of testis in prostatic growth is through its ability to secrete androgen. Our earlier observation suggested a non-androgenic role for the testis, and perhaps the epididymis, in promoting growth of the ventral prostate in rats. The present study was conducted to evaluate the separate role of the testis and the epididymis in this phenomenon. In the first study, increasing quantities of silastic tubing filled with crystalline testosterone were implanted into adult Sprague-Dawley rats at the time of bilateral epididymo-orchiectomy or sham-operation. Twenty-eight days later, growth of the ventral prostate, as determined by fresh weight, DNA, and protein content, was significantly greater in sham-operated rats than in those receiving combined epididymo-orchiectomy, confirming our previous observation using dihydrotestosterone. In the second and third studies, rats were subjected to selective surgical procedures to evaluate the independent role of the testis and the epididymis. At the same time, 12 cm silastic tubing filled with testosterone or dihydrotestosterone were implanted subcutaneously into each of these animals for 28 days. Results indicated that the ventral prostate was significantly smaller in rats receiving the combined epididymo-orchiectomy than that of sham-operated controls. Simple orchiectomy or simple epididymectomy resulted in an increased weight of the ventral prostate between the two values obtained from the above two groups. Ligation of either the efferent duct or the vas deferens yielded ventral prostatic weights comparable to the androgen-treated, sham-operated controls. These results indicated that in order to achieve a maximal effect on androgen-supported growth of the ventral prostate, the presence of both the testis and the epididymis is required.

Androgens↗
PubMed1991

Advanced prostatic carcinoma. Early versus late endocrine therapy.

Since the landmark observations of Huggins and Hodges in 1941, androgen deprivation has been the mainstay of treatment for advanced-stage prostate cancer. Although early, poorly controlled studies suggested enhanced survival with hormonal therapy, this view fell into disfavor as a result of the observations of the first and second VACURG studies. Recently, there has been a proliferation of experimental and clinical data supporting early androgen deprivation, including a reanalysis of the VACURG data, which suggests a survival advantage for younger patients with stage D disease and high-grade tumors who undergo androgen-ablative therapy at the time of diagnosis. The risk-benefit analysis presented in this review is strongly supportive of early hormonal therapy. Finally, long-term survival of patients with metastatic prostate cancer will require the development of novel treatment strategies effective against androgen-resistant tumor cells and their use in concert with early androgen deprivation.

Androgen Antagonists↗
PubMed1990

Non-androgenic role of testis in enhancing ventral prostate growth in rats.

This study was conducted to investigate whether the testis, aside from its ability to secrete androgen, is able to promote prostatic growth in rats. Increasing quantities of silastic capsules filled with crystalline dihydrotestosterone (DHT) were implanted subcutaneously into adult Sprague-Dawley rats at the time of bilateral epididymo-orchiectomy or sham operation on the testes. Control animals received empty capsules. Twenty-eight days later, the growth of the ventral prostate as measured by wet weight, DNA, and protein content per prostate was significantly greater in rats with intact testes than in orchiectomized rats. An overall increased growth was noted at all doses of exogenous DHT administered. Serum levels of luteinizing hormone in animals treated with DHT were undetectable. Serum levels of testosterone in intact rats treated with DHT were not significantly different from those in castrated rats. These observations suggest a non-androgenic role for the testis and, perhaps, epididymis in promoting prostatic growth in rats, and are consistent with the concept that a non-androgenic substance, produced from the testis and/or epididymis, is able to enhance prostate growth induced by androgen stimulation. The possibility that this phenomenon may play a role in the benign growth of the prostate observed in aging human males with decreased blood levels of androgen warrants consideration.

Analysis of Variance↗
PubMed1990

Elevated transferrin receptor content in human prostate cancer cell lines assessed in vitro and in vivo.

Transferrin receptors (TfR) were measured in benign and malignant prostatic cells by performing Scatchard analysis following the administration of 125I-transferrin. Established human prostate cancer cell lines (PC-3 and DU-145) as well as biologically aggressive variants (PC-3 ASC and PC-3 DES) were shown to possess significant levels of high affinity TfR when assessed in vitro. In contrast, TfR content was negligible in cultured stromal cell fractions derived from human benign prostatic hyperplasia (BPH) specimens. Scatchard analysis was also performed on in vivo derived prostatic tissues: tumors resulting from the subcutaneous xenografting of PC-3 ASC cells into athymic, nude mice and fresh BPH surgical specimens. These tissues were dissociated and their stromal and epithelial components separated. TfR were only detected in the epithelial component of both malignant and benign epithelial cells. PC-3 ASC tumor cells exhibited TfR levels comparable to their in vitro expression and these levels were 10-fold greater than in the BPH cells. These findings suggest that elevated TfRs may serve as another useful marker of the transformed phenotype within human prostate tumor systems.

Animals↗
PubMed1979

Ureterosigmoidostomy in rats: a model for the study of bladder tumour carcinogenesis and cocarcinogenesis.

A modified Coffey I ureterosigmoidostomy has been developed in rats as a model of urinary diversion for studying bladder carcinogenesis and co-carcinogenesis. Diverted and sham-operated animals were killed at 1, 3 and 6 months. Excretory urograms revealed minimal hydroureteronephrosis in most diverted animals. Upper tract bacterial colonisation was 9 times more frequent in diverted animals. Approximately one-third of the diverted animals had focal cortical scarring; however, renal function was normal in all groups as assessed by serum creatinine and electrolytes. These studies indicate that ureterosigmoidostomy in rats is a satisfactory model of urinary diversion for studying carcinogenesis.

Animals↗
PubMed1979

Morbidity of pelvic lymphadenectomy.

A retrospective review of 100 patients undergoing pelvic lymphadenectomy alone or with additional surgery was done to assess the morbidity and to help identify factors contributing to a high wound morbidity. Major wound morbidity occurred in 8 per cent of patients, while 16 per cent had minor wound problems. Factors contributing to wound morbidity included urinary tract infection, altered metabolic states, and the use of wound drains. Other morbid events are tabulated.

Drainage↗
PubMed1979

Analysis of specific proteins in prostatic fluid for detecting prostatic malignancy.

In an attempt to identify an indicator(s) specifically associated with prostatic cancer prostatic fluid was collected by rectal massage from patients with prostatic cancer, prostatitis, benign prostatic hyperplasia and from those without recognized prostatic lesions in order to measure various immunoproteins. The proteins examined were IgG, IgA, IgM, complements C3 and C4, and transferrin. Prostatic fluid samples were subjected first to immunoelectrophoresis. Distinct differences in C3, C4 and transferrin concentrations were noted between patients with prostatic cancer and other patients. These proteins were stained heavily in the electrophoresis gels of fluid from cancer patients but were either missing or lightly stained in all other groups. These qualitative determinations were replaced subsequently by a quantitative measurement using the radial immunodiffusion technique. Results of the latter study confirmed the aforementioned observations and indicated that the levels of C3, C4 and transferrin in the prostatic fluid of cancer patients were elevated significantly when compared to all other patient groups. These observations indicate that the measurement of complements C3 and C4, and transferrin in the prostatic fluid may assist in the identification of patients with a high risk of prostatic cancer.

Body Fluids↗
PubMed1979

Acid phosphatase.

Acid phosphatase is a ubiquitous lysosomal enzyme that hydrolyses organic phosphates at an acid pH. Although the postpuberteral prostatic epithelial cell contains a uniquely high concentration of acid phosphatase, cellular components of bone, spleen, kidney, liver, intestine, and blood also contain this enzyme. The discovery that prostatic carcinoma cells often retain a high concentration of acid phosphatase characteristic of the normal postpubertal gland led to the recognition of the first clinically useful tumor marker. Recognition that the serum of patients with prostatic malignancy frequently contains an increased concentration of this enzyme has resulted in persistent efforts to identify the source, to accurately quantitate the level of serum acid phosphatase, and to determine the clinical significance of those levels. A variety of enzymatic and immunologic techniques have been employed to measure acid phosphatase. In the past, various substrates and inhibitors were utilized to increase specificity and sensitivity. Emphasis has now shifted to the development of radioimmunoassay and counterimmunoelectrophoresis in an attempt to enhance those parameters. Judgment of their efficacy awaits further testing and evaluation. The clinical significance of normal and abnormal serum acid phosphatase is constantly being reevaluated. In order to maximize the value of laboratory measurements, the clinical and pathologic status of the patient, the techniques employed in obtaining and storing the blood sample and the procedures used in analysis must be known and considered. Traditionally, the serum prostatic acid phosphatase has been thought to originate in the prostatic cancer cell and has been used to stage the disease. Until recently, elevated serum values have been accepted as an indication of extraprostatic disease, and were thought to rule out lesions confined to the prostate. The elevation of acid phosphatase levels in patients with disseminated disease or the failure of elevated levels to return to normal with treatment have been assumed to indicate a poor prognosis. However, unequivocal documentation of the validity of these statements is not available. Newer immunologic techniques for measuring acid phosphatase may significantly alter our current concept of its role as a tumor marker.

Acid Phosphatase↗
PubMed1979

Partial inhibition of castration-induced involution in rat prostate by chloroquine. A preliminary observation.

The effect of chloroquine phosphate, a membrane stabilizing agent, on castration-induced involution in the prostate was investigated in adult Sprague-Dawley rats. Chloroquine phosphate (75 mg per kg of body weight) was administered daily by gastric tube on 4 consecutive days beginning 1 day before castration. Control rats received water. All animals were sacrificed 7 days after castration and the ventral prostates were analyzed. The chloroquine group had a mean prostatic weight 17 per cent greater than that of the water-fed control group (P less than 0.01) despite a modest loss in body weight. The activity of cathepsin D, a lysosomal enzyme, in the prostate of treated rats was double that measured in control rats. Histologically, prostates from chloroquine treated rats contained more lysosomal particles that were larger than those from control rats. Serum testosterone reached castrate levels in both groups of animals within 24 hr of castration. These results indicate that it is possible to reduce the rate of prostatic regression by chloroquine, although at a small magnitude, probably through the action of membrane stabilization.

Animals↗
PubMed1978

Palliative urinary diversion for malignant ureteral obstruction.

An analysis of 62 palliative urinary diversions for malignant ureteral obstruction is presented. The average postoperative survival was 187 days. Cell type, duration of known disease, tumor grade and stage, renal function and previous therapy did not strongly influence survival. Renal function returned to normal in 64 per cent of the azotemic patients. Morbidity and mortality rates were high, largely because of underlying disease and adjuvant therapy . Nearly two-thirds of the patients left the hospital and this group subsequently spent 84 per cent of their remaining survival time at home. A criterion is presented for patient selection and suggestions are made for the selection of an operative procedure.

Abdominal Neoplasms↗
PubMed1978

Ureterolymphatic backflow.

A case is reported of apparent radiologic demonstration of a communication between a completely obstructed distal ureter and its draining lymphatics in a patient with invasive bladder tumor involving the ureteral orifice.

Aged↗
PubMed1978

Effect of 2-bromo-alpha-ergocryptine (CB-154) on estrogen induced growth of the rat prostate.

Castrate male Sprague-Dawley rats were treated with either testosterone; testosterone and estradiol; testosterone, estradiol and 2-Bromo-alpha-Ergocryptine (CB-154), an inhibitor of prolactin secretion; or testosterone and CB-154. Estradiol potentiated testosterone-induced growth of the dorsal, lateral, and ventral prostate and this effect was not counteracted by CB-154. Estradiol only induced hypertrophy of the dorsal and ventral prostate, however, hyperplastic changes occurred in the lateral prostate.

Animals↗
PubMed1978

Elevated rate of 3H-uridine incorporation in regressing rat ventral prostate.

Ventral prostates from adult Sprague-Dawley rats were removed at intervals during the first 2 weeks postcastration. Incubation of tissue with 3H-uridine and 3H-leucine was performed to determine the incorporation rate of radioactivity into the RNA and protein fractions respectively. Prostatic wet weight and 3H-leucine incorporation rate into prostate protein diminished postcastration, whereas 3H-uridine incorporation rate remained relatively high. The data suggest that RNA synthesis is relatively active in comparison with other parameters during regression.

Animals↗
PubMed1978

Partial inhibition of castration induced ventral prostate regression with actinomycin D and cycloheximide.

Sprague Dawley male rats were injected subcutaneously with either actinomycin D or cycloheximide in saline immediately after castration. Control animals received saline only. Treatment was repeated daily for 4 subsequent days, and 24 hr after the last injection rats were sacrificed by decapitation. Ventral prostates were dissected and weighed. Actinomycin D and cycloheximide administration significantly reduced the rate of prostatic weight loss in castrated rats; serum testosterone levels in the control and drug treated animals were comparable. Histologic studies of the prostates indicated that drug treated animals had more active epithelial cells than saline injected controls. These results indicate that the rate of prostatic regression induced by castration can be modified by drugs such as actinomycin D and cycloheximide.

Adrenal Cortex Hormones↗