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Biomedical subjects

J T Grayhack

Publications and source records attributed to J T Grayhack.

At least 55 records · Page 3Linked to original sources
PubMed1985

The effect of testicular irradiation on established BPH in the dog: evidence of a non-steroidal testicular factor for BPH maintenance.

Irradiation of the testes of four to 13-year-old male beagles with benign prostatic hyperplasia (BPH) was undertaken to attempt to evaluate the possibility that the testes secrete a non-androgenic accessory sex gland-stimulating substance that may have a critical role in the development of BPH. Available evidence indicates that development of prostatic hyperplasia in dog and man is dependent on testicular secretions and that testes irradiation is unlikely to alter testosterone secretion appreciably but does produce profound effects on the seminiferous tubules. Thirteen non-irradiated and shoulder irradiated control and 16 beagles subjected to 1500 to 2200 rads single dose testis irradiation had pre-irradiation, interval post-irradiation and terminal caliper measurements of prostatic length, width and depth, prostatic and testicular biopsies, and determination of serum testosterone and estradiol levels. Four beagles survived in a group observed for 109 weeks post testis irradiation, 12 in a group observed for 51 and 10 in a group observed for 59 weeks. The wet weight of the prostate was determined at sacrifice. Ratios of the final/initial length and width and final actual/initial calculated weight of the prostate were significantly decreased in testis-irradiated as compared to control beagles. Histologic evaluation also demonstrated a significant difference in degree of prostatic stimulation in control and testis-irradiated groups. The serum testosterone and estradiol levels were not significantly different in the testis-irradiated and control beagles. These observations indicate that irradiation of the testes of beagles with BPH alters the size, weight and histology to suggest decreased stimulation of the prostate without producing an identifiable change in the serum levels of the steroid hormones studied. The data support the hypothesis that the testis of the aging beagle secretes a non-androgenic and probably non-steroidal prostatic stimulating substance which is affected by irradiation of the testis.

Animals↗
PubMed1985

Estimation of canine prostatic size by in vivo ultrasound and volumetric measurement.

Two methods for estimating the weight of the canine prostate gland in vivo were investigated. Twenty-six beagle dogs underwent transrectal and transabdominal ultrasound examination of the prostate, followed by careful, standardized caliper measurement of the prostate at surgical exploration. The prostate glands were then removed and weighed, and nomograms were constructed for use in future laboratory research. The validity of these nomograms for determining prostate weight in vivo was confirmed on evaluation of 6 additional dogs.

Animals↗
PubMed1984

Action of prolactin in regressing prostate: independent of action mediated by androgen receptors.

Hyperprolactinemia, achieved by grafting pituitaries under the renal capsule, has been shown to cause a delay in the rate of castration-induced prostatic regression in rats. The mechanism of this prolactin action is not established, although it has been suggested that the action of prolactin in the rat prostate is mediated through the action of androgen. To explore the possibility that a small amount of residual endogenous androgen present in the prostate at the time of castration acts synergistically with prolactin to cause this delay in prostatic regression, Flutamide has been used in the present study in an attempt to inhibit this residual androgen effect by blocking its interaction with androgen receptors. Two experiments were conducted. In experiment 1, daily sc injections of Flutamide (25 mg/kg) for 7 days to castrated rats supplemented with dihydrotestosterone-filled silastic tubing either 1 or 4 cm long completely suppressed both prostatic weight and protein content to the level that was normally observed in castrated rats receiving empty tubings. Furthermore, treatment of Flutamide to castrated rats did not cause an increase in prostatic weight and protein content over those of castrated rats treated with the vehicle only. These results indicate that Flutamide, at this dosage, is a potent antiandrogen and that the compound itself does not have any androgenic activity in the rat prostate. In experiment 2, adult male rats were castrated and received two female pituitaries grafted under the renal capsule. One week later, their serum prolactin levels increased from 20 +/- 3 ng/ml to 102 +/- 8 ng ml. This elevated level of serum prolactin was associated with a delay in the rate of prostatic regression. Administration of Flutamide, at a dose (25 mg/kg) which completely suppressed prostatic growth, failed to inhibit the delay in prostatic regression in castrated rats bearing the pituitary grafts. Since Flutamide inhibits the androgen action in the prostate by blocking the binding of intracellular dihydrotestosterone to androgen receptors, the failure of Flutamide to block the effect of prolactin suggests that the prolactin action in regressing prostates is not mediated by androgen receptors.

Animals↗
PubMed1984

Efficacy of polyglycolic acid (PGA) tubing stents in ureteroureterostomies.

Polyglycolic acid (PGA) tube stented, silastic stented and non-stented anastomoses were compared in 18 ureteroureterostomies performed in 13 dogs. Urinalysis, urine culture, BUN and serum creatinine and intravenous pyelograms were done periodically from 1 day to 6 months postoperatively and ureteral dynamics were performed at 6 months. Normal intravenous pyelograms were observed following 10 of 11 PGA stented, 3 of 4 silastic stented and 2 of 3 unstented anastomoses. PGA stents prevented extravasation and dissolved within 7 days without stone formation. Urodynamic and histopathologic studies revealed no significant differences among the 3 groups. The data suggest that PGA stents are as effective as silastic stents and do not require additional procedures for removal.

Animals↗
PubMed1984

Correlation of ABH antigenicity and urine cytology results in transitional cell carcinoma of bladder.

Loss of ABH antigens from the cell surface of transitional cell carcinoma of the bladder has been proposed as an indicator of increased cellular dedifferentiation and the tendency toward invasive recurrence. An attempt was made to correlate the urinary cytology and the ABH antigen status of 57 patients with histologically confirmed bladder tumors and 28 with only dysplasia on biopsy. A review of the results of surface antigenicity studies and the preoperative urine cytologies showed no significant difference in the diagnostic sensitivity of cytology between comparable antigen negative and positive groups.

ABO Blood-Group System↗
PubMed1984

The accuracy of diagnostic biopsy specimens in predicting tumor grades by Gleason's classification of radical prostatectomy specimens.

We reviewed the tissue histology of 115 patients with clinically localized carcinoma to determine the correlation between tumor grades in the biopsy and the prostatectomy specimen. Gleason's primary and secondary pattern score systems were used, and each specimen was graded on a scale of 2 to 10 by a referee pathologist in a blind fashion. If the difference in the summed primary and secondary grades in the 2 specimens was no more than 1 grade, the discrepancy was regarded as insignificant. In all but 32 cases initial diagnostic biopsy specimens predicted accurately the final prostatectomy specimen score. The discrepancy was 3 grades in 7 cases and 2 grades in 25 cases. As a result, the lesions in 19 cases were changed from a well differentiated (2 to 4), a moderately differentiated (5 to 7) or a poorly differentiated (8 to 10) lesion to another of these categories. The lesions were upgraded from a well differentiated to a moderately differentiated category in 9 cases and from a moderately to a poorly differentiated category in 4 cases. The lesions were downgraded from a moderately differentiated to a well differentiated category in 6 cases. In 13 other cases the discrepancy was 2 but the lesion remained within the moderately differentiated group. Although in 19 cases the cancerous tissue occupied less than 10 per cent of the biopsy specimen, accurate prediction could be made in 16. The results indicate that diagnostic biopsy specimens will predict the grade of the primary tumor in a majority (72 per cent) but not all of the cases.

Aged↗
PubMed1984

Adjuvant doxorubicin hydrochloride and radiation in stage D bladder cancer: a preliminary report.

The prognosis of patients with stage D bladder cancer is dismal. This report expands the results of our efforts to modify the clinical course of such patients by administration of doxorubicin hydrochloride sandwiched around pelvic radiation. Pathologic stage D bladder cancer was recognized in 19 patients by evaluation of tissue obtained by radical cystectomy and pelvic lymphadenectomy (8), pelvic lymph node dissection (5) or biopsies (3), ileal conduit and pelvic lymph node biopsy (1), or transurethral biopsy of the bladder and prostate (2). Treatment of these patients with doxorubicin hydrochloride before and after radiation was initiated 3 to 4 weeks postoperatively. The treatment regimen consisted of 1) 60 mg. per M.2 doxorubicin intravenously every 3 weeks for 3 cycles, 2) 5,000 rad external radiation to the entire pelvis in 5 to 6 weeks and 3) doxorubicin for 5 cycles. The observed survival rates were 37 per cent at 3 years and 28 per cent at 5 years. The median survival time was 16 months. Five patients had no evidence of disease 13 to 63 months postoperatively. One patient underwent salvage cystectomy for recurrent bladder carcinoma at 33 months and had no evidence of disease at 74 months. One patient was alive with recurrent disease at 13 months. Three patients who died did not complete the protocol owing to metastatic disease, 8 lived 6 to 52 months without recognized disease and died of metastases, and 1 died of a second primary. The extent of surgical excision was not associated significantly with survival. Of 8 patients treated with radical cystectomy 7 suffered a significant obstruction of the small bowel that required decompression or bypass surgery and all 7 recovered completely. These preliminary observations indicate encouraging results with a high but manageable morbidity for this regimen.

Aged↗
PubMed1984

Biochemical markers in prostatic cancer.

The status of the biochemical markers explored for use in patients with carcinoma of the prostate is reviewed. No unique marker has been identified. However, a variety of substances, primarily enzymes and specific proteins, found in the serum, urine, and prostatic fluid, have been evaluated. Their main value remains in the staging of disease and the monitoring of response to therapy.

Acid Phosphatase↗
PubMed1984

Systematic characterization of human prostatic fluid proteins with two-dimensional electrophoresis.

We present a systematic analysis of human prostatic fluid with two-dimensional gel electrophoresis (the ISO-DALT system) and a characterization of normal and disease-related protein patterns. A reference map for prostatic fluid proteins was established by analysis of pooled prostatic fluids from 80 men (age less than or equal to 50 years) without prostatic lesions. Proteins in prostatic fluid that share immunogenicity with serum proteins were identified by use of antibody to whole human-serum protein in an affinity-column fractionation of a reference pool and differential analysis of the absorbed (serum components) and unabsorbed (non-serum components) fractions. Individual prostatic fluids from 30 patients (eight with prostatic cancer, 10 with prostatitis and benign prostatic hyperplasia, six with benign prostatic hyperplasia alone, and six with asymptomatic chronic prostatitis) were scored qualitatively with respect to the presence or absence of 57 major prostatic fluid proteins. Statistically significant, disease-correlated alterations were observed for at least eight of the proteins so scored.

Blood Proteins↗
PubMed1983

Prognostic significance of tumor grade and stage in the patient with carcinoma of the prostate.

Available English language articles relating the grade, stage, and grade-stage of carcinoma of the prostate to evidence of tumor progression and survival in untreated and treated patients have been reviewed. Observations of the extremes of the spectrum of biological behavior of carcinoma of the prostate have been emphasized; for example, tumor progression, never or always; survival, never or always. The reported experiences indicated the following; namely, 1) reproducible biologically meaningful grading is achievable; however, grade cannot be utilized as a reliable indicator of stage; 2) accurate staging provides information that correlates with tumor progression and survival in groups of patients. However, unexpectedly prolonged or abbreviated progression-free survivals occur frequently enough in every stage, except perhaps patients with clinically unsuspected focal carcinoma, to indicate that the natural history and treatment response of individuals grouped by stage is far from homogeneous; 3) appropriate use of carefully obtained grade and stage information together maximizes the accuracy of prognostic attempts and is necessary to evaluate treatment results. At the present time, assessment and consideration of the grade and stage of carcinoma of the prostate is essential to formulate prognosis and advise and evaluate treatment in patients with this disease.

Adenocarcinoma↗
PubMed1983

The effect of CIS hydroxyproline on ventral prostatic growth in rats.

Changes in prostatic collagen were measured in Sprague-Dawley rats to gain further insight into the relationship between this stromal component and androgen mediated prostatic growth. Regulation of prostatic collagen by other endocrine factors was also studied. Collagen content per prostate was estimated by determination of tissue levels of hydroxyproline. The 1st experiment examined changes in the content of hydroxyproline in the prostate during pre- and post-pubertal growth with the use of rats between 21 and 80 days of age. As the animals grew, their prostatic weights and hydroxyproline contents increased in a parallel fashion (correlation coefficient R = 0.977, p less than 0.01). In the 2nd experiment, rats were castrated for a period up to 28 days. The hydroxyproline content in the prostate did not change significantly by castration despite a marked decrease in prostatic weights. Results of the 3rd experiment indicated that castration-hypophysectomy or castration-hypophysectomy plus estrogen treatment did not significantly change the content of prostatic hydroxyproline from that in the untreated intact animals. The 4th experiment studied the effect of the collagen synthesis inhibitor, cis-4-hydroxyproline, on prostatic growth. Subcutaneous injection of cis-4-hydroxyproline to castrated testosterone treated rats caused a significantly slower increase in total ventral prostatic weights and contents of protein, DNA and hydroxyproline than those of saline treated controls. This inhibition in prostatic growth is unlikely to be related to any antiandrogenic effect of cis hydroxyproline as the protein/DNA ratio in the prostate was the same for both saline and cis-4-hydroxyproline treated groups. Electron microscopic studies revealed that cis-4-hydroxyproline treatment resulted in a derangement of the basement membrane in the ventral prostate. The above results suggest that collagen plays an important role in limiting prostatic growth since inhibition of collagen synthesis by cis-4-hydroxyproline retarded the testosterone induced increase in prostatic weight, DNA, protein and hydroxyproline content in the prostate of rats.

Animals↗
PubMed1982

Treatment of stage D bladder cancer with adjuvant doxorubicin hydrochloride and radiation.

pathologic Stage D bladder cancer was recognized in 16 patients by evaluation tissue obtained by radical cystectomy and pelvic lymphadenectomy (7), pelvic lymph node dissection (3) or biopsies (3), ileal conduit and pelvic lymph node biopsy (1), or transurethral biopsy of the bladder and prostate (2). Treatment of these patients with radiation preceded and followed by doxorubicin hydrochloride (Adriamycin) was initiated three to four weeks postoperatively. The treatment regimen consisted of the following: (1) doxorubicin 60 mg/M2 intravenously every three weeks for three cycles; (2) 5,000 rad external radiation to the whole pelvis in five to six weeks; and (3) doxorubicin for five cycles. The mean survival was twenty-three months. The survival rate was as follows: one year, 10 of 15 patients at risk; two years, 6 of 11; three years, 5 of 9; four years, 1 of 4; and five years, 0 of 2. Ten patients died six to thirty-six months (mean 13.6) postoperatively. In 6 of the patients significant obstruction of small bowel developed. These preliminary observations indicate encouraging therapeutic results with an acceptable morbidity for this regimen.

Aged↗
PubMed1982

Delay of castration induced regression in rat prostate by pituitary homografts.

Although prolactin has a synergistic effect with testosterone in stimulating growth of the lateral lobe of the rat prostate, the role of prolactin in the absence of testosterone has not been well established. We studied the effect of prolactin on the rate of prostatic regression induced by castration in mature Sprague-Dawley rats. Anterior pituitaries from female rats were transplanted under the renal capsule in all rats. Castration and unilateral nephrectomy were carried out 1 week later. Half of the animals had the normal, non-grafted kidney removed and another half had the kidney bearing the pituitary grafts excised. Rats were sacrificed on days 0, 7, 10 and 14 and 3 lobes of the prostate were dissected separately. The lateral lobe showed a marked decrease in the rate of regression in the pituitary graft-bearing rats. In control animals, the relative weight of the lateral lobe on days 7, 10 and 14 was 38 +/- 2 per cent (mean +/- SE), 33 +/- 2 per cent and 26 +/- 2 per cent of the day 0 value, respectively; the respective relative weight in animals carrying pituitary grafts was 67 +/- 4 per cent, 51 +/- 5 per cent, and 38 +/- 3 per cent of the day 0 value. The difference in the weight of the lateral lobe between the 2 groups was significant on days 7 (p less than 0.001) and 10 (p less than 0.05) and was not significant on day 14. There was no difference in the mean body weight in graft bearing and non-graft bearing animals. Bilateral adrenalectomy at the time of castration did not influence the rate of prostatic regression in either group. Furthermore, pituitaries implanted in rats castrated for 3 weeks had no stimulatory effect of the prostates. These results indicate that increased endogenous prolactin, in the absence of testicular and adrenal secretion, delays the castration-induced regression of the lateral lobe of the prostate of Sprague-Dawley rats.

Adrenal Glands↗
PubMed1982

Activities of cathepsin D in rat prostate during castration induced involution.

The possibility that an intracellular proteolytic process is activated during castration induced prostatic regression warrants consideration and investigation. We investigated the activities of cathepsin D, a lysosomal proteolytic enzyme, in the prostate of rats at different intervals following castration. The enzyme activity was noted to increase during the period of rapid prostatic involution. Administration of exogenous testosterone in varying doses to castrated rats prevented or retarded prostatic weight loss as well as the increase in cathepsin D activity in a dose related manner. Administration of actinomycin D to castrated rats also retarded ventral prostate regression and decreased cathepsin D activity. These observations suggest that cathepsin D is actively synthesized in the regressing prostate and that the enzyme may play an important role in castration induced prostatic regression.

Androgens↗
PubMed1981

Extensive suprapubic vesicocutaneous fistula following trauma.

There are few reports on extensive suprapubic vesicocutaneous fistulas. We report the problems encountered in the closure of these fistulas following lower abdominal trauma. Two patients are described in whom the trauma produced extensive loss of skin, fascia and muscle, leaving the bladder exposed and open. Despite several attempts at bladder closure the bladder repair always failed and the fistula remained open. It was necessary to cover the subsequent bladder closure with overlying muscle, fascia and skin to obtain a successful closure. The techniques of closure are explained.

Abdominal Injuries↗