Search PubMed⌕ Search

Biomedical subjects

J Rajfer

Publications and source records attributed to J Rajfer.

At least 55 records · Page 3Linked to original sources
PubMed1997

MUSE therapy: preliminary clinical observations.

OBJECTIVES: Intracavernosal injection of vasodilating agents has been a mainstay in the treatment of erectile dysfunction. Recently, a transurethral delivery system (MUSE) for alprostadil (prostaglandin E1) was introduced as an alternative form of pharmacotherapy. METHODS: One hundred consecutive patients with erectile dysfunction were treated with MUSE in doses ranging from 125 to 1000 micrograms and their erections were observed in the clinical setting. All patients had previous intracavernosal injections of combination pharmacotherapy (papavarine, Regitine, and/or prostaglandin E1). RESULTS: Of these 100 patients that used MUSE, only 7% had well-sustained, rigid erections while 30% had full erections but with partial rigidity. The remaining 63% of patients did not achieve erections that they thought were adequate for penetration. Penile and/or perineal pain occurred in 24% of patients, 3% had a syncopal episode, and 3% experienced urethral bleeding. One patient had priapism that required drainage. Using intracavernosal injections, 49% had sustained rigid erections, 40% had full erections with partial rigidity, and 11% did not have a response satisfactory for penetration. CONCLUSIONS: These data suggest that intracavernosal injections appear to be more effective than MUSE in achieving a rigid erection in men with erectile dysfunction.

Adult↗
PubMed1997

Cloning of rat and human inducible penile nitric oxide synthase. Application for gene therapy of erectile dysfunction.

Erectile dysfunction is mainly due to the inability of the cavernosal smooth muscle of the penis to undergo complete relaxation. In the aging rat model, erectile dysfunction is accompanied by a reduction of penile smooth muscle compliance and, in very old animals, by a decrease in penile nitric oxide synthase (NOS), which is responsible for the synthesis of the mediator of penile erection, nitric oxide (NO). We have investigated whether the stimulation of penile NOS expression by local induction or gene therapy can mitigate erectile dysfunction in the aged rat. A mix of iNOS (inducible NOS) inducers was continuously delivered to the penises of 5- ("adult"), 20- ("old"), and 30- ("very old") mo-old rats for 3-6 days, and the erectile response to electrical field stimulation of the cavernosal nerve was measured. The erectile dysfunction observed in old and very old rats as compared to adult animals was ameliorated by treatment with iNOS inducers. Penile iNOS was detectable in the penis of these rats by Western blot, NADPH diaphorase, and NOS activity assays. Inducible NOS was inducible in vitro in both rat and human corpora cavernosal tissue and in rat penile smooth muscle cells (RPSMC), as shown by Western blots. However, NO synthesis in cavernosal tissue upon iNOS protein induction remained low, indicating that the increased NOS levels were under physiological control. The iNOS cDNA was cloned from induced RPSMC mRNA and generated by reverse transcriptase polymerase chain reaction (RT-PCR) from induced human penile smooth muscle cells and corporal tissue. The coding regions from both the rat (RPiNOS) and human (HPiNOS) penile iNOS showed several amino acid differences from their analogous isoform in nonpenile tissues. RPiNOS cDNA injected into the penis mitigated the aging-associated erectile dysfunction. The iNOS construct was detected in cavernosal tissue by PCR, and its expression by RT-PCR and Western blots. These results open the way for the possible use of NOS isoforms in the management of erectile dysfunction.

Aging↗
PubMed1997

Effects of long-term oral administration of L-arginine on the rat erectile response.

PURPOSE: Nitric oxide (NO), the neurotransmitter responsible for mediating penile erection in the rat, is synthesized from L arginine by nitric oxide synthase (NOS) in a reaction blocked by L-NAME (N-omega-nitro-L-arginine methyl ester). To determine whether dietary supplementation of L-arginine can stimulate penile erection and whether ancillary pathways for penile erection may exist, a series of experiments were conducted in the Fischer 344 rat. MATERIALS AND METHODS: Adult male (5 month old) and aged (20 month old) rats were fed L-arginine (2.25%) and L-NAME (0.7%) dissolved in tap water for 8 weeks. Animals (n = 6) underwent electrical field stimulation (EFS) of the cavernosal nerve to induce erection and both maximal intracavernosal pressure (MIP) and mean arterial pressure (MAP, mm. Hg +/- SEM) were measured. Tissue and serum levels of L-arginine were measured by an automated amino acid analyzer. Penile eNOS (endothelial) and nNOS (neuronal) content were measured by western blot densitometry. Total penile NOS enzyme activity was measured by the L-arginine to L-citrulline conversion assay. RESULTS: The L-arginine fed animals demonstrated a significant increase in EFS-induced MIP when compared to the controls in both the adult (104 +/- 4 vs. 86 +/- 6, p = 0.04) and aged (87 +/- 5 vs. 66 +/- 4, p = 0.02) animals, without changes in MAP. L-NAME virtually abolished the MIP in adult rats (8 +/- 3, p < 0.0001), while increasing the MAP (186 +/- 8, p < 0.0001). Serum and penile tissue levels of L-arginine were increased by 64-148% in all groups compared to control animals. Penile eNOS and nNOS content remained unchanged in control and treated animals. Penile NOS activity was increased nearly 100% in the L-arginine treated groups vs. controls. CONCLUSIONS: Long-term oral administration of supra-physiologic doses of L-arginine improves the erectile response in the aging rat. We postulate that L-arginine in the penis may be a substrate-limiting factor for NOS activity and that L-arginine may up-regulate penile NOS activity but not its expression. The blockade of penile erection by EFS with L NAME suggests that if ancillary corporeal vasodilator mechanisms develop, a basal level of NO synthesis is still required for activation and relaxation of the corporeal smooth muscle. These data support the possible use of dietary supplements for treatment of erectile dysfunction.

Administration, Oral↗
PubMed1997

Adrenal control of erectile function and nitric oxide synthase in the rat penis.

Penile erection is a nitric oxide (NO)-mediated process that has been shown to be androgen dependent in rats. Castration reduces the activity of the penile enzyme involved in NO synthesis, nitric oxide synthase (NOS). To determine whether adrenal androgens and/or corticosteroids contribute to this control, the following groups of Fischer 344 adult male rats (n = 5-7) were studied: 1) intact, 2) castrated, 3) adrenalectomized alone, 4) castrated/adrenalectomized, 5) castrated/adrenalectomized with aldosterone (1.25 mg/kg, s.c.) and hydrocortisone (12 mg/kg, s.c.), 6) castrated/adrenalectomized with dihydrotestosterone (1.2-cm SILASTIC-brand tubing pellet; Dow Corning, Midland, MI), 7) castrated/adrenalectomized with dehydroepiandrosterone (2-cm tubing), 8) castrated/adrenalectomized with aldosterone (1.25 mg/kg, s.c.), and 9) castrated/adrenalectomized with hydrocortisone (12 mg/kg, s.c.). After 1 week, EFS was applied, and the maximal intracavernosal pressure (MIP) and mean arterial pressure (MAP) were recorded. The MIP/MAP ratio in the adrenalectomized group (0.37) was reduced to values found in the castrated group (0.40). The values in both groups were significantly less than those in intact controls (0.75). The most significant reduction in MIP/MAP was seen in the adrenalectomized/castrated group (0.16). Erectile response in animals submitted to adrenalectomy and castration was restored close to intact values with the administration of hydrocortisone and aldosterone (0.63). Similar results were obtained by the administration of either of the substances alone (0.56 and 0.67, respectively). Penile NOS activity assayed by the L-arginine/citrulline conversion was decreased by 55% in the castrated group compared with that in the intact group, but was not further reduced in the adrenalectomized/castrated or adrenalectomized groups. Penile neuronal NOS protein content, estimated by Western blot, was decreased only in the adrenalectomized/castrated animals (35%), and endothelial NOS content was not affected. These data suggest that the rat adrenal gland contributes to the maintenance of the erectile mechanism and may affect neuronal NOS content in the penis in the rat model. The possibility that hypotension may play a role in the erectile dysfunction observed in adrenalectomized rats cannot be discarded.

Adrenal Glands↗
PubMed1997

Helical CT angiography for examination of living renal donors.

OBJECTIVE: This prospective study was intended to determine if helical CT arteriography plus conventional radiography is sufficiently accurate to replace and less costly than excretory urography and conventional renal arteriography, the techniques currently used to examine living renal donors. SUBJECTS AND METHODS: Patients underwent CT arteriography with a helical CT scanner. Conventional radiographs were obtained during the pyelographic phase to evaluate the urothelium. Findings on CT arteriograms were compared with findings on conventional arteriograms and at surgery. RESULTS: Of 57 patients who underwent CT arteriography, 46 also underwent conventional arteriography and 40 underwent surgery. For those 46 patients, we found agreement between results of CT arteriography and conventional arteriography in 89% of kidneys. For those 40 patients, we found agreement between results of CT arteriography and findings at surgery in 90% of kidneys and agreement between results of conventional arteriography and findings at surgery in 87% of kidneys. Of the 57 patients, six (11%) had findings on CT angiograms that precluded further consideration for donation. CONCLUSION: Eight to ten percent of renal arteries are not seen on renal arteriograms when compared with findings at surgery. Our results indicate that CT arteriography is as accurate as conventional arteriography at revealing the number of vessels that perfuse and drain the kidneys and can replace conventional arteriography. Use of CT angiography plus conventional radiography instead of excretory urography and conventional arteriography can result in a 35-50% reduction in cost of the imaging studies in potential renal donors.

Adult↗
PubMed1997

Effect of long-term passive smoking on erectile function and penile nitric oxide synthase in the rat.

PURPOSE: Given that smoking is a risk factor for erectile dysfunction, this study aimed to determine, in a rat model, whether long-term exposure to cigarette smoke impairs nitric oxide (NO)-dependent erectile function and reduces penile nitric oxide synthase (NOS), and if these changes are accompanied with effects on the systemic blood pressure. MATERIALS AND METHODS: Adult (5 month) and old (20 month) rats were exposed to daily passive smoking for 8 wks. Three days after the conclusion of exposure, half of the animals were submitted to electrical field stimulation (EFS) of the cavernosal nerve and the maximum intracavernosal pressure (MIP) and mean arterial pressure (MAP) were determined and expressed as mm. Hg. On the other half of the animals, NOS activity in the penile cytosol was measured by the arginine/citrulline assay, and neuronal NOS (nNOS) and endothelial NOS (eNOS) contents were estimated by western blot and densitometry. RESULTS: When compared to controls, the smoking rats had a higher MAP in both the adult (115 vs 162) and old (113 vs 140) rats, but surprisingly the MIP also increased, from 78 to 111 (adult rats) and from 59 to 83 (old rats). Smoking reduced penile NOS activity by 73% (adult rats), and 62% (old rats), and nNOS content by 43% and 50%, respectively. In contrast, eNOS was not affected. Nitrite release, in vitro, by cavernosa slices or in rat penile smooth muscle cells (RPSMC) was not inhibited by nicotine or cotinine. CONCLUSION: These results indicate that chronic smoking in the rat leads to age-independent moderate hypertension and considerable decreases in penile NOS activity and nNOS content, that are not reflected in a reduction of the erectile response to EFS or accompanied by a decrease in penile eNOS.

Age Factors↗
PubMed1997

Improved survival of en bloc renal allografts from pediatric donors.

PURPOSE: We developed a technical and immunological protocol to increase survival of renal transplants from pediatric donors. MATERIALS AND METHODS: En bloc kidneys (22) were procured from donors weighing 2 to 14 kg. (1 to 60 months old) and transplanted into adult recipients. In group 1 (12 patients) sequential therapy was used for kidneys with more than 35 hours of cold storage and immediate triple therapy (cyclosporine, azathioprine and prednisone) was used for those with less than 35 hours of cold storage. In group 2 (10 patients) OKT3 induction therapy was used. Mean followup was 4.7 years. RESULTS: Mean blood pressure at 1 and 4 years was not significantly different between the groups. Mean serum creatinine was not significantly different between the groups at 1 year but it was significantly less in group 2 at 4 years (1.9 +/- 1.0 versus 1.2 +/- 0.24 mg./dl., p <0.05). At 1 year of followup the complication rate was 75% in 9 of 12 patients in group 1, including 4 infections or leaks (2 lost), 6 rejections (3 lost) and 3 cases of thrombosis or hemorrhage, and 20% (p <0.01) in group 2 (1 patient had the hemolytic uremic syndrome leading to graft loss). Graft survival was significantly greater in group 2 at all 4 years of followup (p = 0.05). CONCLUSIONS: The success of pediatric en bloc renal transplantation can be enhanced by induction therapy in healthy recipients.

Child, Preschool↗
PubMed1996

Cloning of a novel neuronal nitric oxide synthase expressed in penis and lower urinary tract.

The neuronal nitric oxide synthase (nNOS) is the main NOS isoform in the urogenital tract catalyzing the synthesis of nitric oxide, the mediator of penile erection and presumably an important factor in the control of urinary voiding. We have cloned from the rat penile corpora cavernosa a cDNA coding for a novel nNOS differing from the cerebellar nNOS by the presence of a 102 nucleotides stretch and other features. This new species is the only nNOS mRNA expressed in the rat penis, urethra, prostate, and skeletal muscle, coexists with the cerebellar nNOS in the pelvic plexus and bladder, and is detectable in the cerebellum. The novel insert is present in human penile RNA and is transcribed from intron 16. The features and distribution of the penile nNOS suggest that it is may be regulated differentially from the cerebellar nNOS.

Amino Acid Sequence↗
PubMed1996

Androgens are not major down-regulators of androgen receptor levels during growth of the immature rat penis .

This study was undertaken to investigate the prevalent hypothesis that androgens are responsible for the organ-specific down-regulation of penile androgen receptors (ARs) and decline of penile growth in the rat during sexual maturation. Sexually immature male rats (21 days old) were castrated and treated for 3 days ("short-term"), with high doses of: (a) testosterone and the alpha-reductase inhibitor finasteride (T/F); (b) dihydrotestosterone (DHT); or (c) finasteride alone (F). Intact and castrate controls received vehicle only. PolyA + RNA was analysed by Northern blot hybridization and ARs were estimated in the penis and ventral prostates by (3-H)R-1881 binding in the cytosol. Short-term castration, with or without F, increased penile AR mRNA, whereas high doses of T/F and DHT reduced it considerably. Although penile cytosol AR concentration in the control castrates, with or without F, paralleled the AR mRNA rise, treatment with androgens left cytosol AR content per organ and AR concentration above those of the intact rat penis despite the drop in AR mRNA. A "long-term" treatment (10 days) on 19-day-old rats with either medium or high doses of T/F and DHT also failed to down-regulate penile cytosol ARs below the intact controls. Western blot analysis of penile cytosol AR levels confirmed these results. Block of pituitary FSH and LH release by a GnRH antagonist in castrates receiving T/F or DHT at high doses did not modify the response. In the case of intact rats, high doses of T/F or DHT actually increased penile cytosol AR content. No difference was observed between T/F and DHT effects. In contrast to what occurs during sexual maturation, the prostate ARs and growth rate responded to all treatments in a similar way to what was observed in the penis. Our results suggest that increases in serum T or DHT are not major factors in the physiological down-regulation of ARs and androgen-dependent growth in the rat corpora cavernosa.

Androgens↗
PubMed1996

Androgen and pituitary control of penile nitric oxide synthase and erectile function in the rat.

Castration of adult male rats reduces by half the penile erectile response to electrical field stimulation (EFS) of the cavernosal nerve, and the activity of penile nitric oxide synthase (NOS). Both changes are prevented by androgen administration. We have now investigated whether other strategies of androgen ablation or competition may act as stronger inhibitors, and, if so, whether the stronger inhibition is due to the depletion of penile NOS content. Rats were castrated or left intact and were treated daily as follows: 1) intact, with the antiandrogen flutamide (25 mg/kg/day, i.p.); 2) castrated, with similar treatment; 3) castrated, with 17 beta-estradiol 3-benzoate (estradiol; via silastic tubing, s.c.). Additional groups of intact rats received injections of a GnRH antagonist (GnRHA, 1.25 mg/kg, s.c.), or were hypophysectomized and left untreated. Controls were untreated intact and castrated animals. After 7 days, rats were subjected to EFS, and the ratios between maximal intracavernosal pressure (MIP) and mean arterial pressure (MAP) were measured. Penile NOS activity and the contents of neuronal NOS (nNOS) and endothelial NOS (eNOS) were determined. Castration reduced the MIP:MAP ratio and penile NOS activity. Androgen receptor blockade with flutamide induced a similar response in intact rats. When flutamide treatment was combined with castration, the erectile response was nearly abolished, but NOS activity was not decreased below the values in castrated rats. Estradiol given to castrated rats and hypophysectomy or GnRHA treatment in intact rats diminished the erectile response below the level in castrated animals. In hypophysectomized rats, penile NOS activity fell below levels in castrated animals. contents of nNOS and eNOS were not significantly reduced by any treatment. These data suggest that penile erection in the rat is completely dependent on androgens, presumably because of their role in the maintenance of penile NOS activity and of other ancillary factors. However, only the complete blockade of residual androgen effects at the tissue level or a total androgen depletion can abolish the erectile response.

Androgen Antagonists↗
PubMed1996

Cavernosal nerve stimulation in the rat reverses castration-induced decrease in penile NOS activity.

Castration in the rat reduces both the erectile response and penile nitric oxide synthase (NOS) activity, and these effects are prevented by androgen administration. In this study we determined that the decrease of penile NOS in the castrated rat is due to NOS enzyme inhibition rather than to a reduction of its content and that this inhibition may be reversed. Adult rats were either castrated or left intact, and, after 1 wk, electrical field stimulation (EFS) was applied to the cavernosal nerve and the penises were excised either at the peak of erection or after detumescence. Penile NOS activity in the non-EFS castrates decreased by 70% as compared with the intact non-EFS-treated controls, but neuronal NOS content remained unaffected despite changes in regional distribution. NOS activity in the castrated penis was restored to normal values by EFS at the peak of stimulation, and then decreased on detumescence. This was in contrast to the intact controls in which EFS did not stimulate penile NOS activity. These data indicate that androgen depletion in the rat reduces penile NOS activity rather than NOS content and that this enzyme inhibition is reversed by cavernosal nerve stimulation.

Animals↗
PubMed1996

Extracorporeal methods of vascular control for difficult IVC procedures.

Surgical procedures in the juxtaheptic and intrapericardial inferior vena cava (IVC) are difficult because of the complexity of achieving vascular control in the area. We describe 10 patients with a variety of pathologies in this region who underwent venovenous bypass (VVB) or cardiopulmonary bypass with hypothermic circulatory arrest (CBCA). Renal cell carcinoma with IVC extension was present in three patients (with tumor extension into the right atrium in two), adrenal adenocarcinoma in one, septic IVC thrombus in one, and blunt IVC/hepatic trauma in five. Those patients without atrial involvement underwent VVB with a mean bypass time of 40 minutes (range 12-144). Those patients with tumor extension into the right atrium underwent CBCA with systemic hypothermia to 18(0)C, total body exsanguination for a bloodless field, and removal of the tumor by cavotomy and right atriotomy. The mean bypass, aortic cross-clamp, and circulatory arrest times were 152, 92, and 36 minutes, respectively. Eight of the 10 patients did well and went home within 4 weeks of surgery. Two patients died, one from metabolic sequelae of exsanguinating IVC injury (VVB) and one from sepsis 2 weeks postoperatively (CBCA).

Adult↗
PubMed1996

Modified venovenous bypass technique for resection of renal and adrenal carcinomas with involvement of the inferior vena cava.

Peripheric tumours with extension into the inferior vena cava pose difficult management problems. Venovenous bypass using a centrifugal pump to decompress the inferior vena cava may be useful adjunct during vascular isolation of the tumour. We have modified the technique by adding portal decompression to avoid visceral accumulation of toxic metabolites. We have used this technique in two patients who had intracaval extension of tumours, one renal and one adrenal carcinoma.

Adenocarcinoma↗
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

Restoration of normal adult penile erectile response in aged rats by long-term treatment with androgens.

In order to determine whether the aging-related impairment of penile erection can be corrected by exogenous androgens, 20-mo-old ("old") rats received implants of Silastic tubing containing either testosterone (T) or dihydrotestosterone (DHT). Untreated aged-matched rats were used as reference controls, and values were compared with those obtained previously for 5-mo old ("adult") rats. After 45 days, groups of six rats were submitted to electrical field stimulation of the cavernosal nerve (EFS), and the intracavernosal pressure and mean arterial pressure (MAP) were recorded. Compared to the untreated old rats, the old animals receiving either T or DHT showed a similar and significant (p < 0.01) increase (56%) in the maximal intracavernosal pressure (MIP) to a level slightly above that of the untreated adult rats. The response was sensitive to the nitric oxide synthase (NOS) inhibitor Nw-nitro-L-arginine methyl ester (L-NAME). The MIP:MAP ratio in the treated animals was nearly double that found in the old untreated controls. Penile NOS activity was measured by the [3H]L-arginine-citrulline conversion, and neuronal NOS (nNOS) levels were estimated by a semiquantitative Western blot assay with antibodies against human nNOS. No significant variations were observed in either NOS levels or NOS activity between the treated and untreated old rats. These results suggest that aging-related erectile dysfunction in the intact rat may be responsive to androgen therapy and that this correction is not associated with an increase in the basal levels of penile NOS, in contrast to what occurs in castrated rats.

Aging↗