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J Rajfer

Publications and source records attributed to J Rajfer.

At least 19 recordsLinked to original sources
PubMed1995

Treatment with finasteride following radical prostatectomy for prostate cancer.

OBJECTIVES: The objective of this study was to evaluate the effect of finasteride (10 mg/d) or placebo on serum prostate-specific antigen (PSA) and recurrence rates in men with detectable PSA levels after radical prostatectomy. METHODS: A total of 120 men, 48 to 89 years old, previously treated with radical prostatectomy for prostate cancer within the past 10 years, with serum PSA levels between 0.6 and 10.0 ng/mL, with no evidence of skeletal metastasis on bone scan, and with no previous androgen deprivation therapy, were treated with 10 mg finasteride or placebo in a double-blind fashion for 12 months. After the first year, all patients were treated with finasteride for an additional 12 months. Primary endpoints were serum PSA levels and recurrence rates defined as positive bone scan or positive biopsy. RESULTS: Patients treated with finasteride had a delayed increase in serum PSA compared with placebo of approximately 9 months in the first year and 14 months by the end of the second year. Patients with baseline PSA levels less then 1.0 ng/mL had no significant increase in serum PSA during the 2 years of treatment. Fewer recurrences were observed in the finasteride group, but these differences were not statistically significant. Finasteride was well tolerated, and side effects were balanced between treatment groups. CONCLUSIONS: The results of this study indicate that treatment with finasteride delays but does not prevent the rise in serum PSA observed in untreated patients with detectable PSA levels after radical prostatectomy. The reduction in local and distant recurrences in the finasteride group suggests that the effect on PSA reflects a direct effect on tumor growth without affecting the initial response to subsequent hormonal therapy. These data require confirmation by studies that are longer and larger, focused on demonstrating significant differences in progression rates and survival before the use of finasteride can be considered as an option for men with detectable PSA levels after radical prostatectomy.

Aged↗
PubMed1995

Effect of aging on nitric oxide-mediated penile erection in rats.

Aging is an important risk factor for impotence in men. Because nitric oxide (NO) appears to be the mediator of corpora cavernosal smooth muscle relaxation, we have examined in 5-, 20-, and 30-mo-old rats, designated "adult," "old," and "senescent," respectively, whether aging causes a decrease of erectile response that may correlate with lower NO synthase (NOS) in the penis. Electric field stimulation (EFS) of the cavernosal nerve showed that the maximum intracavernosal pressure (MIP) declined in the old and senescent rats to 80 and 51% of the adult value, respectively. A low systemic dose of the NOS inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME; 2 mg/kg), reduced the MIP by only 38% in the adult rats but decreased it in the old and senescent rats by 72 and 80%, respectively. In the absence of EFS, intracavernosal papaverine (phosphodiesterase inhibitor), or nitroglycerin (NO donor), caused a lower erectile response in the old and senescent rats compared with the adult animals (MIP: 41 and 14%, respectively; duration of the erection 46 and 21%, respectively). Tissue sections from old and senescent penises showed increasing degrees of sclerotic degeneration. In comparison with the adult rats, the penile soluble NOS activity per gram of tissue that is sensitive to L-NAME decreased significantly by 63% in the senescent rats but was elevated in the old rats. These results indicate that aging causes an erectile failure due to factors initially independent from an impairment of penile NO synthesis but which are compounded in the very old rats by the decrease of penile NOS activity.

Aging↗
PubMed1995

Reduction of penile nitric oxide synthase in diabetic BB/WORdp (type I) and BBZ/WORdp (type II) rats with erectile dysfunction.

Erectile dysfunction occurs frequently in human diabetes, and it is sometimes associated with hypogonadism. These conditions also develop in a model of insulin-dependent (type I) diabetes, the BB/WORdp (diabetic prone) rat but have not yet been investigated in the model of insulin-resistant (type II) diabetes, the BBZ/WOR rat. It is also unknown whether diabetes-related impotence is due to reduced levels of the mediator of penile erection, nitric oxide, caused by a decrease of nitric oxide synthase (NOS) in the penis. To clarify these questions, groups (n = 5-6) of diabetic BB/WORdp (insulin-maintained) and BBZ/WOR rats were age-matched with diabetic-resistant BB/WORdr and non-diabetic BB/WORdp rats and submitted to determinations of serum glucose, testosterone, and penile reflexes (cups and flips). Erectile dysfunction was found in all of type I and in most of type II diabetic animals (glycemias of 25.0 and 31.1 mM), at the selected mean ages of 310 and 180 days old, respectively. This was evidenced by over 95% decreases of erectile reflexes in both types of diabetes and was accompanied by 75% reduction of serum testosterone. Soluble NOS activity was measured in penile tissue from the diabetic rats with impaired erectile reflexes and in the corresponding controls, by the (3H)-L-arginine/citrulline conversion assay. The neuronal NOS isoform (nNOS) content was determined by a semiquantitative western blot assay. Both types of diabetes showed a marked decrease of penile NOS activity (74 and 55%, respectively), and a lower reduction of penile nNOS content (47 and 33%, respectively). No endogenous NOS inhibitor was detected in the diabetic type I penile cytosol by cross-mixing NOS activity assays. Our data support a common etiology for erectile dysfunction present in rats with types I and II diabetes mellitus and suggest that the etiology is related to a decrease of penile NOS derived in part from serum androgen deficiency.

Animals↗
PubMed1995

Dihydrotestosterone is the active androgen in the maintenance of nitric oxide-mediated penile erection in the rat.

Androgens are essential for the expression of normal libido in the male, but their role in the maintenance of the erectile response in humans is controversial. It has been shown previously in the rat that castration induces 1) loss of penile reflexes; and 2) considerable reduction in the erectile response to electric field stimulation (EFS) of the cavernosal nerve. Both of these effects can be reversed by testosterone replacement. The current study was performed to determine whether these testosterone effects are mediated via its conversion to dihydrotestosterone (DHT), and to what extent the synthesis of the mediator of penile erection, nitric oxide, is affected by castration and androgen replacement. Five-month-old rats were either castrated or left intact. The orchiectomized rats were implanted with SILASTIC brand silicon tubing (Dow Corning) containing testosterone or DHT with or without daily injections of the 5 alpha-reductase inhibitor finasteride. After 7 days, rats were submitted to EFS and the intracavernosal pressure was recorded. Castration reduced the EFS-induced erectile response by 50% in comparison with intact rats and testosterone restored this decrease to normal. When finasteride was given to these testosterone-treated castrate rats, erectile response was not restored. DHT was as effective as testosterone in restoring response to EFS in castrates and this effect was not decreased by finasteride. Nitric oxide synthase activity in the penile cytosol was measured by the arginine-citrulline conversion and was found to correlate with the EFS determinations. These results show that DHT is the active androgen in the prevention of erectile failure seen in castrated rats, and suggest that this effect may be mediated, at least partially, by changes in nitric oxide synthase levels in the penis.

Amino Acid Oxidoreductases↗
PubMed1995

The effect of zanoterone, a steroidal androgen receptor antagonist, in men with benign prostatic hyperplasia. The Zanoterone Study Group.

PURPOSE: Zanoterone (100 to 800 mg.) versus placebo was studied in 463 patients with benign prostatic hyperplasia. MATERIALS AND METHODS: Study end points were maximum urinary flow rate, American Urological Association symptom index, prostate volume, prostate specific antigen and sex steroid concentrations after 6 months of treatment. RESULTS: Mean increases in maximum urinary flow rate were 2 to 3-fold over placebo, although only the 200 mg. group had significant results (1.7 ml. per second, p = 0.026). There were no statistically significant differences between the zanoterone and placebo groups in symptom index or prostate volume. Estradiol and testosterone concentrations, and the incidence of breast pain and gynecomastia increased significantly with zanoterone compared with placebo. Prostate specific antigen levels decreased significantly. CONCLUSION: Zanoterone did not demonstrate a favorable risk-to-benefit profile for the treatment of benign prostatic hyperplasia.

Aged↗
PubMed1994

New device for visual neodymium:YAG laser prostate ablation: acute and chronic canine evaluation.

This canine study (n = 6) evaluated the acute and chronic effects of Nd:YAG laser prostatectomy using a Prolase II fiber. The Prolase II device consists of a 1,000 microns quartz fiber which directs a cone of Nd:YAG laser energy, at 45 degrees to the axis of the fiber, into the prostatic urethra under direct visual guidance [visual laser ablation of prostate, (VLAP)]. Under visual guidance and saline irrigation, 60 seconds of 60 watts of laser power was delivered at 3, 6, 9, and 12 o'clock positions (14,400 J). One canine was instrumented but received no laser energy (control). One prostate was harvested acutely. The remaining four laser-treated dogs were evaluated at 6 to 16 weeks. The histopathology of acute laser effects shows areas of necrosis with loss of glandular structures and stromal edema. Surrounding this area was a zone of degenerative glandular structures extending up to 12.6 mm into the prostate. Two of the four dogs developed urinary retention at 6.5 and 9 weeks. On examination, both were found to have fibrotic strictures at the distal prostatic urethra with markedly dilated proximal prostatic urethral lumens (1.98 and 2.8 cm). Two other dogs showed no signs of urinary retention at sacrifice. Histopathology, both the 6 and 16 week laser-treated animals without urinary retention demonstrated dilated prostatic urethras with maximum cross-sectional diameters of 1.52 and 1.50 cm, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to nonadrenergic, noncholinergic neurotransmission.

BACKGROUND: Nitric oxide has been identified as an endothelium-derived relaxing factor in blood vessels. We tried to determine whether it is involved in the relaxation of the corpus cavernosum that allows penile erection. The relaxation of this smooth muscle is known to occur in response to stimulation by nonadrenergic, noncholinergic neurons. METHODS: We studied strips of corpus cavernosum tissue obtained from 21 men in whom penile prostheses were inserted because of impotence. The mounted smooth-muscle specimens were pretreated with guanethidine and atropine and submaximally contracted with phenylephrine. We then studied the smooth-muscle relaxant responses to stimulation by an electrical field and to nitric oxide. RESULTS: Electrical-field stimulation caused a marked, transient, frequency-dependent relaxation of the corpus cavernosum that was inhibited in the presence of N-nitro-L-arginine and N-amino-L-arginine, which selectively inhibit the biosynthesis of nitric oxide from L-arginine. The addition of excess L-arginine, but not D-arginine, largely reversed these inhibitory effects. The specific liberation of nitric oxide (by S-nitroso-N-acetylpenicillamine) caused rapid, complete, and concentration-dependent relaxation of the corpus cavernosum. The relaxation caused by either electrical stimulation or nitric oxide was enhanced by a selective inhibitor of cyclic guanosine monophosphate (GMP) phosphodiesterase (M&B 22,948). Relaxation was inhibited by methylene blue, which inhibits cyclic GMP synthesis. CONCLUSIONS: Our findings support the hypothesis that nitric oxide is involved in the nonadrenergic, noncholinergic neurotransmission that leads to the smooth-muscle relaxation in the corpus cavernosum that permits penile erection. Defects in this pathway may cause some forms of impotence.

Adult↗
PubMed1992

Variability of venous anatomy of rat testis: application to experimental testicular surgery.

The venous drainage of the testis of the laboratory rat was observed in 31 animals. The right testicular (internal spermatic) vein drained directly into the right common iliac vein in 77.4%, and into the inferior vena cava in 22.6% of the animals. The left testicular vein drained into the left common iliac vein in all animals, but in 90.3% there was also an accessory branch of the testicular vein draining into the left renal vein. These observations suggest that in the rat the exact anatomy of the venous drainage of each testis should be identified prior to undertaking any surgical procedure on the testis where the venous vasculature plays a major role such as testicular transplantation or the creation of an experimental varicocele.

Animals↗
PubMed1992

Identification of motile sperm in caput epididymis. Intraoperative observations and clinical correlations.

This retrospective review of patients who underwent vasoepididymostomy demonstrates that motile sperm may be identified in the most proximal portion of the epididymis, and implies that induction of sperm motility may be independent of transit through the epididymis. Although further studies are needed, the data imply that it may not be necessary to identify motile sperm in the epididymal fluid to achieve a successful vasoepididymostomy.

Adult↗
PubMed1992

Effects of multiple injections of HCG on testis blood flow.

In attempting to determine whether or not multiple injections of human chorionic gonadotropin (hCG) augment testis blood flow, adult male rats were injected with three doses of 10 IU of hCG every other day and testis blood flow was determined on day 5, the day of the final injection. Testis blood flow (mL/100 g testis tissue/min +/- SEM) as measured by the 133Xe washout method increased from 10.8 +/- 1.3 to 20.4 +/- 4.5 (p less than 0.05) after the three doses of hCG. These observations suggest that multiple injections of hCG appear to have the same effect as a single dose of hCG in increasing testis blood flow. This supports the hypothesis that hCG should be administered to all patients undergoing orchiopexy in the hope that the increased perfusion of the gonad will make it less susceptible to ischemia during the surgical procedure.

Animals↗
PubMed1992

Laparoscopic occlusion of testicular veins for clinical varicocele.

Surgery via the laparoscope is now a reliable and cost-effective alternative to some open surgical procedures. Advances in videoendoscopy, incorporating optical magnification combined with the development of instruments with which to dissect, ligate, and transect blood vessels provide the urologist the opportunity to surgically correct a varicocele. In the outpatient setting, 4 patients (14-26 years of age) underwent laparoscopic ligation of the left internal spermatic veins for painful left varicocele. Carbon dioxide pneumoperitoneum was obtained using a Veress needle. A 10-mm laparoscope was placed intraperitoneally through a cannula inserted in the infraumbilical border. Utilizing two additional endosurgical ports (5 mm and 10 mm) through which 5-mm dissecting instruments and vaso-occlusive endoclips were placed, three veins were individually isolated and ligated in each of the 4 patients. In all 4 patients, the left testicular artery was visualized and preserved. There was no blood loss or other intraoperative complication. In each patient the varicocele was successfully corrected. Analgesic medication was not required postoperatively. We conclude that laparoscopic ligation of the internal spermatic veins is a safe and effective way of treating a varicocele without immediate postoperative sequelae. Long-term follow-up is necessary to determine the place of the endoscopic approach.

Adolescent↗
PubMed1992

Nitric oxide is a potent relaxant of human and rabbit corpus cavernosum.

Nitric oxide (NO) caused a potent, marked, and transient relaxation of precontracted strips of corpus cavernosum isolated from humans and rabbits. The relaxation response elicited by NO was very similar to the relaxation evoked by electrical field stimulation via the nonadrenergic-noncholinergic pathway. Sodium nitroprusside, nitroglycerin, and S-nitroso-N-acetylpenicillamine, which are nitrovasodilators known to generate NO, also caused marked concentration-dependent relaxation of corpus cavernosum. Relaxant responses to NO were enhanced by the cyclic GMP phosphodiesterase inhibitor M&B 22,948 and inhibited by oxyhemoglobin. Similarly, relaxation of corpus cavernosum in response to electrical field stimulation or acetylcholine was enhanced by M&B 22,948 and inhibited by oxyhemoglobin. NO stimulated cyclic GMP formation in corpus cavernosum and a close positive correlation was found between the magnitudes of relaxation and cyclic GMP formation. The data suggest that NO-elicited activation of guanylate cyclase and cyclic GMP formation represents the signal transduction mechanism responsible for relaxation and nonadrenergic-noncholinergic-mediated penile erection. These observations indicate that NO is a potent relaxant of human and rabbit corpus cavernosum and support our hypothesis that endogenous NO is the principal mediator of penile erection caused by nonadrenergic-noncholinergic stimulation.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1991

Noninvasive radiological diagnosis of renal vein thrombosis in renal transplantation.

Thrombosis of the allograft renal vein is a rare complication of renal transplantation. Of 557 consecutive renal transplants performed between January 1, 1985 and November 30, 1989, 3 cases occurred for an over-all incidence of 0.4%. In 2 cases the diagnosis was made preoperatively with renal scintigraphy and duplex Doppler sonography. No graft was salvaged, despite timely diagnosis in 2 patients. We conclude that the diagnosis of renal vein thrombosis in the renal allograft recipient should be suspected clinically and by the radiographic findings of absent perfusion on renal scintigraphy, and the detection of an arterial signal, albeit abnormal, on duplex Doppler sonography. When diagnosed, nephrectomy appears to be the only treatment.

Adult↗
PubMed1991

Effect of 5-alpha-reductase inhibitor, 4-MAPC, on testicular descent in male rat.

Testicular descent has been reported to be a dihydrotestosterone (DHT) dependent event. To further elucidate the role of DHT in the process of testicular descent, a group of rats were treated with the 5-alpha reductase inhibitor, 4-MAPC, from birth to day 28 of age and the incidence of testicular descent as well as ventral prostate weight was noted at day 29 of age. It was determined that in the doses used, 4-MAPC failed to prevent testicular descent. Because 4-MAPC inhibited ventral prostate weight by only 53% (as compared to a 75% inhibition by castration), the failure of the 4-MAPC to prevent testicular descent could be due to its inability to completely inhibit tissue 5-alpha reductase activity. The results of this study do not mitigate against the role of other nonhormonal factors working in tandem with DHT in the induction of testicular descent in this animal model.

5-alpha Reductase Inhibitors↗
PubMed1991

Effect of the antiandrogen, WIN 49,596, on the descent of the testis in the male rat.

Testicular descent in the male rat is believed to be an androgen dependent event with dihydrotestosterone the most likely active androgen. To provide further insight into the endocrinology of this important physiological event, we treated male rats with the antiandrogen, WIN 49596 (50 mg./kg./day), from day 1 to day 27 of age and evaluated its effect on the post-natal androgen-dependent events in this animal model. It was determined that while treatment with WIN inhibited the weights of the ventral prostate, seminal vesicles and penis when compared to those seen in castrate animals, the drug only caused a 19% (3/16) inhibition in the descent of the testes when compared to the control group (0/16; p = 0.112). These data together with those previously obtained in animals exposed to selective inhibitors of the 5-alpha reductase enzyme suggest that other factors possibly working in tandem with androgens play a predominant role in testicular descent in the rat.

5-alpha Reductase Inhibitors↗
PubMed1991

Expression of the androgen receptor gene in rat penile tissue and cells during sexual maturation.

The cessation of rat and human penile growth at completion of sexual maturation appears to be related to a tissue-specific decrease in the number of androgen receptors (AR) in the penis. To find out whether this is due to either transcriptional or translational regulation of the AR gene, we determined the levels of AR mRNA by Northern blots in the corpora cavernosa from groups of 16-, 19-, 22-, 27-, 52-, and 90-day-old rats. The AR mRNA rapidly decreases with age and is nearly undetectable in the 52- and 90-day-old rats, paralleling the decline in AR number. The persistence of a low amount of AR mRNA in the adult penis was confirmed by reverse transcription/polymerase chain reaction amplification of total RNA, and its level was estimated by a semiquantitative modification of this procedure at less than 1/25th of that found in the youngest rats. Smooth muscle cells derived from the 16- and 90-day-old corpora cavernosa express in the AR gene in vitro in approximately the same levels, suggesting that there are factors in culture that up-regulate the AR mRNA. Our results are compatible with the assumption that the age-dependent decrease in AR in the rat penis is due to transcriptional regulation, although they do not exclude the less likely alternative of a selective effect on AR mRNA stability and support the use of this model for studying tissue-specific factors controlling the developmental expression of the AR gene.

Animals↗
PubMed1990

Nitric oxide and cyclic GMP formation upon electrical field stimulation cause relaxation of corpus cavernosum smooth muscle.

In the presence of functional adrenergic and cholinergic blockade, electrical field stimulation relaxes corpus cavernosum smooth muscle by unknown mechanisms. We report here that electrical field stimulation of isolated strips of rabbit corpus cavernosum promotes the endogenous formation and release of nitric oxide (NO), nitrite, and cyclic GMP. Corporal smooth muscle relaxation in response to electrical field stimulation, in the presence of guanethidine and atropine, was abolished by tetrodotoxin and potassium-induced depolarization, and was markedly inhibited by NG-nitro-L-arginine, NG-amino-L-arginine, oxyhemoglobin, and methylene blue, but was unaffected by indomethacin. The inhibitory effects of NG-substituted analogs of L-arginine were nearly completely reversed by addition of excess L-arginine but not D-arginine. Corporal smooth muscle relaxation elicited by electrical field stimulation was accompanied by rapid and marked increases in tissue levels of nitrite and cyclic GMP, and all responses were nearly abolished by NG-nitro-L-arginine. These observations indicate that penile erection may be mediated by NO generated in response to nonadrenergic-noncholinergic neurotransmission.

Animals↗