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Biomedical subjects

Jacob Rajfer

Publications and source records attributed to Jacob Rajfer.

At least 37 records · Page 2Linked to original sources
PubMed2005

Laparoscopic versus open renal procurement for pediatric recipients of living donor renal transplantation.

Despite reports demonstrating the safety of laparoscopic donor nephrectomy (LDN) for pediatric recipients of renal transplants, recent evidence has challenged using LDN for recipients 5 years of age or younger. We retrospectively reviewed the records of all pediatric recipients of living donor renal transplants from September 2000 through August 2004. We compared those who received allografts recovered by LDN (n = 34) with those recovered by open donor nephrectomy (ODN, n = 26). Outcomes of interest included operative complications, postoperative renal function, the incidence of delayed graft function or episodes of acute rejection and long-term graft function. Donor and recipient demographic data were similar for the LDN and ODN groups. Serum creatinine and calculated creatinine clearance were not significantly different between groups both in the early postoperative period and at long-term follow-up (p > 0.142). Rates of delayed graft function and acute rejection did not differ between groups. Among recipients aged 5 years old or younger stratified by donor technique (9 LDN, 5 ODN recipients), no difference was noted in graft outcomes both early and long-term (p > 0.079). At our center, pediatric LDN recipients have graft outcomes comparable to those of ODN recipients. At experienced centers, we recommend continued use of LDN for pediatric recipients of all ages.

Adolescent↗
PubMed2005

Carcinoid tumor of the kidney: case report and review of the literature.

Carcinoid tumors are low-grade malignant tumors that arise from neuroendocrine cells. Primary renal carcinoid tumors are extremely uncommon. They seem to be more indolent than renal cell carcinomas, although metastases to regional lymph nodes, liver, and bone have been described. The presence of metastases seems to indicate a more malignant course; however, even with metastases a patient might live for 3 or 4 years. Renal carcinoid tumors should be managed by radical or partial nephrectomy, and good outcomes have been obtained for organ-confined disease after radical excision. Conventional methods of imaging are inadequate for detecting smaller carcinoids, so somatostatin receptor scintigraphy should complement computed tomography and magnetic resonance imaging when searching for occult or metastatic disease. Close follow-up after surgery is necessary.

Case Reports↗
PubMed2004

Gene transfer of inducible nitric oxide synthase complementary DNA regresses the fibrotic plaque in an animal model of Peyronie's disease.

The goal of the present study was to investigate the antifibrotic role of inducible nitric oxide synthase (iNOS) in Peyronie's disease (PD) by determining whether a plasmid expressing iNOS (piNOS) injected into a PD-like plaque can induce regression of the plaque. A PD-like plaque was induced with fibrin in the penile tunica albuginea of mice and then injected with a luciferase-expressing plasmid (pLuc), either alone or with piNOS, following luciferase expression in vivo by bioluminescence imaging. Rats were treated with either piNOS, an empty control plasmid (pC), or saline. Other groups were treated with pC or piNOS, in the absence of fibrin. Tissue sections were stained for collagen, transforming growth factor (TGF) beta1, and plasminogen-activator inhibitor (PAI-1) as profibrotic factors; copper-zinc superoxide dismutase (CuZn SOD) as scavenger of reactive oxygen species (ROS); and nitrotyrosine to detect nitric oxide reaction with ROS. Quantitative image analysis was applied. Both iNOS and xanthine oxido-reductase (XOR; oxidative stress) were estimated by Western blot analysis. Luciferase reporter expression was restricted to the penis, peaked at 3 days after injection, but continued for at least 3 wk. In rats receiving piNOS, iNOS expression also peaked at 3 days, but expression decreased at the end of treatment, when a considerable reduction of plaque size occurred. Protein nitrotyrosine, XOR, and CuZn SOD increased, and TGFbeta1 and PAI-1 decreased. The piNOS gene transfer regressed the PD plaque and expression of profibrotic factors, supporting the view that endogenous iNOS induction in PD is defense mechanism by the tissue against fibrosis.

Animals↗
PubMed2004

Aging-related induction of inducible nitric oxide synthase is vasculo-protective to the arterial media.

OBJECTIVE: Aging associated erectile dysfunction (ED) is primarily caused by the reduction in smooth muscle cells (SMC) and an increase in collagen within the corpora cavernosa, assumed to result from an increase in reactive oxygen species (ROS). This is accompanied by the expression of inducible nitric oxide synthase (iNOS) to produce nitric oxide that scavenges ROS and inhibits collagen deposition. We investigated whether with aging similar processes occur within the arterial media SMC that share some common physiological functions with the cavernosal SMC. METHODS: Aged (22-24 months) male Brown Norway rats received water with or without an inhibitor of iNOS activity (L-N-(iminoethyl)-lysine acetate [L-NIL], 0.1 g/l), for 3 weeks. Young (3 months) untreated rats were used as control (n=5 per group). Tissue sections from the penis, abdominal aorta, femoral and brachial arteries were stained for collagen, SMC, iNOS, ROS plasminogen activator inhibitor (PAI) and apoptosis, and evaluated by quantitative image analysis. ROS were also determined in fresh tissue and whole blood by the GSH/GSSG ratio. RESULTS: It was observed that most aging-induced changes in the media of the arterial tree from the aorta to the resistance arteries in the penis are similar to what occurs in the corpora cavernosa, i.e. a decrease in the SMC/collagen ratio and an increase in ROS and iNOS, and specifically in the case of the resistance arteries, an increase in SMC apoptosis and PAI. iNOS inhibition by L-NIL further increased ROS and decreased the SMC/collagen ratio in the media. CONCLUSIONS: These observations suggest that ED and arteriosclerosis in the aging male may share a common etiology, and that the expression of iNOS by the SMC is an attempt to counteract this fibrosis.

Aging↗
PubMed2004

New discoveries in the basic science understanding of Peyronie's disease.

Peyronie's disease is an acquired benign condition representing localized fibrosis of the penis. The disease is caused by microvascular trauma to the penis, with subsequent fibrin deposition resulting in aberrant wound healing and possibly other etiologies. Histopathologic studies of the Peyronie's plaque have demonstrated the role of transforming growth factor-beta 1 in the pathologic development of penile plaque. Animal models have been developed to test pathophysiology and therapeutics. The role of inducible nitric oxide synthase and nitric oxide has been established to limit and counteract fibrosis. Differential gene expression studies have identified candidate up-regulated or down-regulated genes that are involved in the pathophysiology of Peyronie's disease.

Animals↗
PubMed2004

A multicenter, randomized, double-blind, crossover study to evaluate patient preference between tadalafil and sildenafil.

PURPOSE: To assess patient preference for erectile dysfunction treatment between either sildenafil or tadalafil, each administered with their respective dosing instructions, and to evaluate preference for either sildenafil or tadalafil dosing instructions during tadalafil therapy. METHODS: We conducted a randomized, double-blind, crossover study consisting of four treatment arms. Because the dosing instructions for sildenafil and tadalafil are different, a unique methodology using sham placebo arms was employed to maintain the blind. To assess drug preference, 219 patients were randomized to either sildenafil 50 mg or tadalafil 20 mg, with dosing instructions reflecting their respective product profiles. To assess dosing instruction preference during tadalafil therapy, 46 patients were randomized to tadalafil 20 mg with either tadalafil or sildenafil dosing instructions. After 12 weeks, patients were crossed-over. After 4 weeks of each treatment, all patients following sildenafil dosing instructions were offered the opportunity for an upward dose titration. In a double-blind fashion, all patients who requested an upward titration received additional capsules. To mimic the pattern of dose usage observed in clinical practice, the number of patients who received additional double-blind active medication was limited to 35% of patients taking sildenafil in each treatment period in each country. Following the crossover treatment period, patients chose their preferred double-blind treatment with dosing instructions to receive in the 12-week extension period. RESULTS: In the drug preference assessment, 132 of 181 (73%) evaluable patients chose to receive tadalafil (p < 0.001) during the extension period. In the dosing instruction preference assessment, 24 of 36 (67%) evaluable patients preferred tadalafil with tadalafil dosing instructions (p = 0.046). Sildenafil and tadalafil were well tolerated. CONCLUSIONS: In the doses utilized in this study, 73% of patients preferred tadalafil with tadalafil dosing instructions for the treatment of their erectile dysfunction over sildenafil with sildenafil dosing instructions. During tadalafil therapy, 67% of patients preferred tadalafil dosing instructions over sildenafil dosing instructions.

Adult↗
PubMed2004

Current treatment options for penile fractures.

The diagnosis of "penile fracture" describes the traumatic rupture of the tunica albuginea of an erect penis. Penile fractures typically occur when the engorged penile corpora are forced to buckle and literally "pop" under the pressure of a blunt sexual trauma. Patients typically describe immediate detumescence, severe pain, and swelling as a result of the injury. Prompt surgical exploration and corporal repair is the most efficacious therapy. Although a majority of cases can be diagnosed from the history and physical examination alone, radiographic studies, including retrograde urethrography and corporal cavernosography can aid in the diagnosis of unusual cases.

Journal Article↗
PubMed2004

The role of serum testosterone testing: routine hormone analysis is an essential part of the initial screening of men with erectile dysfunction.

As oral phosphodiesterase-5 inhibitor therapy has become the first-line treatment of erectile dysfunction (ED), common approaches in the evaluation of ED have been largely abandoned. Not only is routine hormone analysis no longer widely recommended, but most specialists perform serum testosterone level testing only in the most complex cases of ED. This article explores the rationale for including serum testosterone analysis as part of the initial screening of patients with ED. The use of routine serum testosterone testing is advocated for its efficacy in the diagnosis and treatment of hypogonadism and pituitary disorders associated with ED.

Journal Article↗
PubMed2004

Rising PSA during Testosterone Replacement Therapy.

Although testosterone replacement therapy (TRT) is indicated for the management of symptomatic hypogonadism, there is still controversy over whether TRT should be administered to middle-aged men for the clinical manifestations of andropause, regardless of whether the serum testosterone levels are depressed or not. Side effects of TRT may include fluid retention, gynecomastia, polycythemia, and exacerbation of existing prostate cancer. As a result, patients on TRT require meticulous surveillance including regular digital rectal examination and serum prostate-specific antigen (PSA) testing. Herein, we present the case of a middle-aged man with andropause and a rising PSA on TRT.

Case Reports↗
PubMed2003

Penile neuronal nitric oxide synthase and its regulatory proteins are present in hypothalamic and spinal cord regions involved in the control of penile erection.

Control of penile erection requires the coordination of the hypothalamus and the L6-S1 region of the spinal cord. Erection requires the activation of neuronal nitric oxide synthase (nNOS), which is tightly regulated. Because variants of nNOS (penile nNOS: PnNOS) and the N-methyl-D-aspartate receptor (truncated NMDAR subunit 1: NMDAR1-T) as well as protein inhibitor of NOS (PIN) have all been located in the pelvic ganglia and penile nerves, this work aims to determine whether these proteins are also present in the hypothalamus. It was found that PnNOS, the brain-type nNOS, and PIN, were expressed in the hypothalamus. In contrast, NMDAR1-T was expressed only in the penis, whereas the brain-type NMDAR1 was present in the brain and sacral spinal cord and not in the penis. PnNOS was found in the media preoptic area, posterior magnocellular, and the parvocellular regions of the paraventricular nucleus, supraoptic nucleus, septohypothalamic nucleus, medial septum, cortex, and in some of the nNOS staining neurons throughout the brain. It was absent in the organum vasculosum of the lamina terminalis. PIN staining was present in neurons of the medial preoptic area, paraventricular nucleus, medial septum, and cortex, but not in the supraoptic nucleus, septohypothalamic nucleus, or organum vasculosum of the lamina terminalis. Colocalization between PnNOS and PIN was found in the medial preoptic area, medial septum, and cortex, and less in the paraventricular nucleus. PnNOS and oxytocin were colocalized in the paraventricular nucleus and supraoptic nucleus. In hypothalamic extracts, recombinant PIN-GST protein bound to PnNOS in the extracts and partially inhibited NOS activity. These results indicate that both nNOS variants, and their respective regulatory proteins are present and colocalize in the hypothalamic and spinal cord regions involved in penile erection.

Animals↗
PubMed2003

L-arginine and phosphodiesterase (PDE) inhibitors counteract fibrosis in the Peyronie's fibrotic plaque and related fibroblast cultures.

Inducible nitric oxide synthase (iNOS) is expressed in both the fibrotic plaque of Peyronie's disease (PD) in the human, and in the PD-like plaque elicited by injection of TGFbeta1 into the penile tunica albuginea (TA) of the rat. Long-term inhibition of iNOS activity, presumably by blocking nitric oxide (NO)- and cGMP-mediated effects triggered by iNOS expression, exacerbates tissue fibrosis through an increase in: (a) collagen synthesis, (b) levels of reactive oxygen species (ROS), and (c) the differentiation of fibroblasts into myofibroblasts. We have now investigated whether: (a) phosphodiesterase (PDE) isoforms, that regulate the interplay of cGMP and cAMP pathways, are expressed in both the human and rat TA; and (b) L-arginine, that stimulates NOS activity and hence NO synthesis, and PDE inhibitors, that increase the levels of cGMP and/or cAMP, can inhibit collagen synthesis and induce fibroblast/myofibroblast apoptosis, thus acting as antifibrotic agents. We have found by immunohistochemistry, RT/PCR, and Western blot that PDE5A-3 and PDE4A, B, and D variants are indeed expressed in human and rat normal TA and PD plaque tissue, as well as in their respective fibroblast cultures. As expected, in the PD fibroblast cultures, pentoxifylline (non-specific cAMP-PDE inhibitor) increased cAMP levels without affecting cGMP levels, whereas sildenafil (PDE5A inhibitor) raised cGMP levels. Both agents and L-arginine reduced the expression of collagen I (but not collagen III) and the myofibroblast marker, alpha-smooth muscle actin, as determined by immunocytochemistry and quantitative image analysis. These effects were mimicked by incubation with 8-Br-cGMP, which in addition increased apoptosis, as measured by TUNEL. When L-arginine (2.25 g/kg/day), pentoxifylline (10 mg/kg/day), or sildenafil (10 mg/kg/day) was given individually in the drinking water for 45 days to rats with a PD-like plaque induced by TGF beta1, each treatment resulted in a 80-95% reduction in both plaque size and in the collagen/fibroblast ratio, as determined by Masson trichrome staining. Both sildenafil and pentoxiphylline stimulated fibroblast apoptosis within the TA. Our results support the hypothesis that the increase in NO and/or cGMP/cAMP levels by long-term administration of nitrergic agents or inhibitors of PDE, may be effective in reversing the fibrosis of PD, and more speculatively, other fibrotic conditions.

Animals↗
PubMed2003

Incidence and severity of sexual adverse experiences in finasteride and placebo-treated men with benign prostatic hyperplasia.

OBJECTIVES: To evaluate the incidence and resolution of sexual adverse experiences (AEs) in men with benign prostatic hyperplasia treated with finasteride 5 mg compared with placebo. METHODS: The Proscar Long-term Efficacy and Safety Study (PLESS) was a 4-year, randomized, double-blind, placebo-controlled trial assessing the efficacy and safety of finasteride 5 mg in 3040 men, aged 45 to 78 years, with symptomatic benign prostatic hyperplasia, enlarged prostates, and no evidence of prostate cancer. Patients completed a questionnaire at screening regarding their history of sexual dysfunction. During treatment, spontaneously self-reported sexual AEs were recorded. RESULTS: At screening, 46% of patients in each treatment group reported some history of sexual dysfunction. During year 1 of the study, 15% of finasteride-treated patients and 7% of placebo-treated patients had sexual AEs that were considered drug related by the investigator (P <0.001). During years 2 to 4, no between-group difference was noted in the incidence of new sexual AEs (7% in each group). The drug-related sexual AE profile for finasteride was similar for men with or without a history of sexual dysfunction. Sexual AEs resolved while continuing therapy in 12% of finasteride patients and 19% of placebo patients. Only 4% of finasteride and 2% of placebo patients discontinued the study because of sexual AEs. In men who discontinued with a sexual AE, 50% and 41% experienced resolution of their sexual AE after discontinuing finasteride or placebo therapy, respectively. CONCLUSIONS: Compared with placebo, men treated with finasteride experienced new drug-related sexual AEs with an increased incidence only during the first year of therapy.

Aged↗
PubMed2003

Peyronie's disease: a review.

PURPOSE: We provide a current review of Peyronie's disease. MATERIALS AND METHODS: We reviewed the world peer reviewed literature on the pathology, pathogenesis, diagnosis and treatment of Peyronie's disease. RESULTS: The incidence of Peyronie's disease has continuously increased during the last 30 years. However, fewer patients need prosthesis surgery as the sole treatment option because of earlier diagnosis, improved medical therapy, refinement in surgical technique and better understanding of the basic sciences of the disease. CONCLUSIONS: Currently patients with Peyronie's disease have had improvements in prognosis and experienced an expansion of the available therapeutic options.

Cell Differentiation↗