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Biomedical subjects

Jacob Rajfer

Publications and source records attributed to Jacob Rajfer.

54 records · Page 3Linked to original sources
PubMed2003

Quality of life, pain and return to normal activities following laparoscopic donor nephrectomy versus open mini-incision donor nephrectomy.

PURPOSE: We evaluated pain, convalescence and health related quality of life in patients undergoing laparoscopic and open mini-incision donor nephrectomy. MATERIALS AND METHODS: We compared the records of consecutive patients who underwent laparoscopic and mini-incision open donor nephrectomy from our donor nephrectomy data base in retrospective fashion using 2 questionnaires. The first questionnaire evaluated postoperative pain, return to functioning time and satisfaction. The second questionnaire was the RAND 36-Item Health Survey, version 2, a standardized and validated health survey quality of life assessment tool. Mean patient sex, age and followup were similar for the 2 groups. All data were analyzed using the 2-tailed t test for independent variables with commercially available statistical analysis software. RESULTS: Pain in the laparoscopic group was significantly less than in the mini-incision group at all followup time points (p <0.05). Statistically significant differences demonstrated that laparoscopy led to more rapid recovery time in certain categories, including walking, discontinuation of prescribed oral pain relievers, return to driving, and resumption of normal work and home daily activities. More subjective questions in the survey showed high levels of acceptance for the 2 procedures. Using the RAND 36-Item Health Survey, version 2 health related quality of life was significantly higher in the laparoscopy group in 3 domains that measure bodily pain, physical functioning and emotional role functioning. However, each group scored at or above age matched American averages in all domains. CONCLUSIONS: The laparoscopy group had significantly less postoperative pain and required less time to return to normal functional activities than the mini-incision group. In addition, the laparoscopic group showed significantly higher quality of life scores than the mini-incision group in 3 domains.

Activities of Daily Living↗
PubMed2003

Peyronie's Disease: A Review.

Peyronie's disease is an acquired benign condition without known systemic sequelae with presenting symptoms that include the presence of a plaque or induration of the penile shaft, penile curvature or deformity during erection, penile pain, and erectile dysfunction. This article reviews the natural history of the disease, discusses the disease's etiology (widely thought to involve minor penile trauma with subsequent aberrant wound healing), and outlines proper clinical evaluation of Peyronie's disease patients. Medical treatments can be systemic (colchicine, potassium aminobenzoate, vitamin E), intralesional (steroids, verapamil, collagenase, interferons), or topical. Surgical therapy for Peyronie's disease (plication, graft-based, and prosthetic techniques) should be reserved for the man who has failed conservative therapy and whose curvature, indentation, or erectile dysfunction precludes intercourse. Regardless of the surgical procedure, the patient should be made aware of the inherent risks of surgery.

Journal Article↗
PubMed2002

Ketorolac-based analgesia improves outcomes for living kidney donors.

BACKGROUND: To reduce the morbidity of living kidney donors we introduced ketorolac-based analgesia for patients undergoing open donor nephrectomy in August 1999. There are no prior reports on the use of ketorolac for patients undergoing donor nephrectomy. METHODS: We conducted a retrospective review of all 198 consecutive patients who underwent open living donor nephrectomy between January 1998 and July 2000 at our institution. We compared patients who underwent surgery before and after introduction of ketorolac-based analgesia. RESULTS: The introduction of ketorolac-based analgesia resulted in a reduction in length of postoperative stay from 3.7+/-0.1 to 3.1+/-0.1 days (P<0.001). Patients who underwent surgery after ketorolac introduction required 58% less narcotics (P<0.001), recalled having less postoperative pain, and stopped taking pain medications sooner than patients before routine ketorolac use. Moreover, these patients drank 38% more liquids on the first postoperative day (P<0.001) and were able to resume a regular diet sooner than patients who were not managed with ketorolac. Patients who received ketorolac had a slightly lower creatinine clearance on the second postoperative day relative to patients who did not (66 vs. 72% of preoperative calculated creatinine clearance, P=0.05). However at a minimum of 3 months postoperatively, creatinine clearance did not differ between the two groups (70 vs. 73%, P=0.92). There were no differences in the rates of complications between the two groups. CONCLUSIONS: The use of ketorolac to control postoperative pain for patients undergoing open donor nephrectomy reduced morbidity and was not associated with any effect on long-term renal function or increased risk of complications. This is the first study to demonstrate the safety of using ketorolac at the time of donor nephrectomy.

Adult↗
PubMed2002

Gene expression profiles in the Peyronie's disease plaque.

OBJECTIVES: To provide molecular insight into the pathophysiology of Peyronie's disease (PD), a preliminary profile of differential gene expression between the PD plaque and control tunica albuginea was obtained with DNA microarrays. METHODS: Seven PD plaques and five control tunica albugineas were studied. cDNA specimens were prepared from RNA isolated from one calcified PD plaque and one control tissue and hybridized with the Clontech Atlas 1.2 Array. Another set of plaque and control RNA samples was hybridized with the Affymetrix GeneChip. Relative changes of greater than 2.0 defined up-regulation and down-regulation, respectively. RNA from the remaining tissues was used to determine, by reverse transcriptase-polymerase chain reaction and Western blot analysis, the expression of selected individual genes. RESULTS: Some of up-regulated genes in the PD plaque detected by the Clontech assay were pleiotrophin, monocyte chemotactic protein 1, and early growth response protein, which are involved in osteoblast recruitment, inflammation, and fibroblast proliferation, respectively. Ubiquitin and Id-2, which are involved in tissue remodeling, were down-regulated. The Affymetrix DNA chips identified the up-regulation of elastase (involved in elastic fiber degradation) and the myofibroblast markers alpha and gamma-smooth muscle actin, desmin, and others, as well as the down-regulation of collagenase IV and transforming growth factor-beta modulators. Four of the five genes selected for reverse transcriptase-polymerase chain reaction and Western blotting confirmed the DNA microarray results. CONCLUSIONS: In the PD tissue, the genes involved in collagen synthesis, myofibroblast differentiation, tissue remodeling, inflammation, ossification, and proteolysis are up-regulated, and the genes that inhibit some of these processes and collagenase are down-regulated.

Carrier Proteins↗
PubMed2002

Effect of ketorolac on renal function after donor nephrectomy.

OBJECTIVES: To evaluate the safety of ketorolac, a nonsteroidal anti-inflammatory drug, that is being used more frequently for postoperative analgesia, we performed a detailed analysis of healthy patients undergoing open donor nephrectomy. METHODS: We conducted a retrospective review of 198 consecutive patients who underwent open living donor nephrectomy between January 1998 and July 2000. We compared patients who were and were not given ketorolac. Regression analysis was used to determine whether any significant interactions were present between ketorolac and donor age, sex, weight, estimated surgical blood loss, or operative time in terms of its effect on renal function. Creatinine clearance was calculated by the Gault-Cockcroft equation. RESULTS: Among the 83 patients given ketorolac, the mean amount received was 200 mg (range 30 to 360, median 210). No differences were found in the preoperative creatinine clearance between patients who did (118 +/- 29 mL/min) or did not (118 +/- 27 mL/min, P = 0.89) receive ketorolac. Patients who received ketorolac had a slightly lower creatinine clearance on the second postoperative day relative to patients who did not receive ketorolac (66% versus 72% of preoperative calculated creatinine clearance, P = 0.05). However, at a minimum of 3 months postoperatively, the creatinine clearance did not differ between the two groups (70% versus 73%, P = 0.92). Among patients who received ketorolac, no significant association was found between the amount received and renal function at any point tested. In the regression analysis, no significant interactions were found between ketorolac and the clinical variables of age, sex, weight, estimated surgical blood loss, or operative time. Moreover, in an analysis of only the patients who received ketorolac, no significant interactions were found between the amount of ketorolac received and the clinical variables of age, sex, weight, estimated surgical blood loss, or operative time. CONCLUSIONS: Ketorolac use was not associated with any long-term impairment in renal function when used during the first 2 postoperative days in healthy patients undergoing open donor nephrectomy. Moreover, in the range administered, no subset of patients or maximal ketorolac dose was identified at which ketorolac use was not safe.

Adult↗
PubMed2002

Effect of nitric oxide on the differentiation of fibroblasts into myofibroblasts in the Peyronie's fibrotic plaque and in its rat model.

The myofibroblast shares phenotypic features of both fibroblasts and smooth muscle cells. It plays a critical role in collagen deposition and wound healing and disappears by apoptosis when the wound is closed. Its abnormal persistence leads to hypertrophic scar formation and other fibrotic conditions. Myofibroblasts are present in the fibrotic plaque of the tunica albuginea (TA) of the penis in men with Peyronie's disease (PD), a localized fibrosis that is accompanied by a spontaneous induction of the inducible nitric oxide synthase (iNOS), also observed in the TGFbeta1-elicited, PD-like lesion in the rat model. iNOS expression counteracts fibrosis, by producing nitric oxide (NO) that reduces collagen deposition in part by neutralization of profibrotic reactive oxygen species. In this study we investigated whether fibroblast differentiation into myofibroblasts is enhanced in the human and rat PD-like plaque and in cultures of human tissue fibroblasts. We also examined whether NO reduces this cell differentiation and collagen synthesis. The myofibroblast content in the fibroblast population was measured by quantitative immunohistochemistry as the ratio between alpha-smooth muscle actin (ASMA; myofibroblast marker) and vimentin (general fibroblast marker) levels. We found that myofibroblast content was considerably increased in the human and TGFbeta1-induced rat plaques as compared to control TA. Inhibition of iNOS activity by chronic administration of L-iminoethyl-L-lysine to rats with TGFbeta1-induced TA lesion increased myofibroblast abundance and collagen I synthesis measured in plaque and TA homogenates from animals injected with a collagen I promoter construct driving the expression of beta-galactosidase. Fibroblast differentiation into myofibroblasts occurred with passage in the cell cultures from the human PD plaque, but was minimal in cultures from the TA. Induction of iNOS in PD and TA cultures with a cytokine cocktail and a NO donor, S-nitroso-N-acetyl penicillamine (SNAP), was detected by immunohistochemistry. Both treatments reduced the total number of cells and the number of ASMA positive cells, whereas only SNAP decreased collagen I immunostaining. These results support the hypotheses that myofibroblasts play a role in the development of the PD plaque and that the antifibrotic effects of NO may be mediated at least in part by the reduction of myofibroblast abundance and lead to a reduction in collagen I synthesis.

Actins↗
PubMed2002

Gene therapy of erectile dysfunction in the rat with penile neuronal nitric oxide synthase.

Gene transfer to the penile corpora cavernosa of constructs of the inducible and endothelial nitric oxide synthase (NOS) cDNAs ameliorates erectile dysfunction in aged rats. In this study, we investigated whether the neuronal NOS (nNOS) variant responsible for erection, penile nNOS (PnNOS), can exert a similar effect, and whether the combination of electroporation with a helper-dependent adenovirus (AdV) improves gene transfer. PnNOS and beta-galactosidase cDNAs were cloned in plasmid (pCMV-PnNOS; pCMV-beta-gal) and "gutless" AdV (AdV-CMV-PnNOS; AdV-CMV-beta-gal) vectors, and injected into the penis of adult (beta-gal) or aged (PnNOS) rats, with or without electroporation. Penile erection was measured at different times after PnNOS cDNA injection, by electrical field stimulation of the cavernosal nerve. The expression of beta-galactosidase or PnNOS was estimated in penile tissue by either histochemistry and luminometry or Western blot, and the effects of AdV-CMV-PnNOS on mRNA expression were examined by a DNA microarray. We found that electroporation increased pCMV-beta-gal uptake, and its expression was detectable at 56 days. In the aged rats treated with pCMV-PnNOS and electroporation, the maximal intracavernosal:mean arterial pressure ratios were elevated for 11 and 18 days when compared with those in controls. Electroporation intensified penile uptake of as few as 10(6) viral particles (vp) of AdV-CMV-beta-gal, and with 10(7) vp beta-galactosidase was still detectable at 60 days. Electroporated AdV-CMV-PnNOS (10(7) vp) was effective at 18 days in stimulating the erection of aged rats, without inducing the expression of cytotoxic genes. In conclusion, intracavernosal gene therapy with PnNOS cDNA corrected the aging-related erectile dysfunction for at least 18 days when given by electroporation in a helper-dependent AdV at low viral loads.

Adenoviridae↗
PubMed2002

Gene therapy of erectile dysfunction in the rat with penile neuronal nitric oxide synthase.

Gene transfer to the penile corpora cavernosa of constructs of the inducible and endothelial nitric oxide synthase (NOS) cDNAs ameliorates erectile dysfunction in aged rats. In this study, we investigated whether the neuronal NOS (nNOS) variant responsible for erection, penile nNOS (PnNOS), can exert a similar effect, and whether the combination of electroporation with a helper-dependent adenovirus (AdV) improves gene transfer. PnNOS and beta-galactosidase cDNAs were cloned in plasmid (pCMV-PnNOS; pCMV-beta-gal) and "gutless" AdV (AdV-CMV-PnNOS; AdV-CMV-beta-gal) vectors, and injected into the penis of adult (beta-gal) or aged (PnNOS) rats, with or without electroporation. Penile erection was measured at different times after PnNOS cDNA injection, by electrical field stimulation of the cavernosal nerve. The expression of beta-galactosidase or PnNOS was estimated in penile tissue by either histochemistry and luminometry or Western blot, and the effects of AdV-CMV-PnNOS on mRNA expression were examined by a DNA microarray. We found that electroporation increased pCMV-beta-gal uptake, and its expression was detectable at 56 days. In the aged rats treated with pCMV-PnNOS and electroporation, the maximal intracavernosal:mean arterial pressure ratios were elevated for 11 and 18 days when compared with those in controls. Electroporation intensified penile uptake of as few as 10(6) viral particles (vp) of AdV-CMV-beta-gal, and with 10(7) vp beta-galactosidase was still detectable at 60 days. Electroporated AdV-CMV-PnNOS (10(7) vp) was effective at 18 days in stimulating the erection of aged rats, without inducing the expression of cytotoxic genes. In conclusion, intracavernosal gene therapy with PnNOS cDNA corrected the aging-related erectile dysfunction for at least 18 days when given by electroporation in a helper-dependent AdV at low viral loads.

Adenoviridae↗
PubMed2002

Kidney transplantation at UCLA.

The demand for renal transplantation continues to increase. Combined organ transplantation currently accounts for approximately 10% of the kidney transplants at UCLA. As the demand for renal transplantation has increased, living kidney donation has become more common and achieves excellent results. Thirty-five percent of the 1,307 renal transplants at UCLA during the past 5 years were from living donors. The donor morbidity has been reduced with improvements in postoperative analgesia and laparoscopic nephrectomy techniques. Management of the patients waiting for cadaveric renal transplantation is becoming increasingly complex, since this population now exceeds 1,000 patients and the median waiting time is approaching 5 years. Improved immunosuppressive, antibiotic, and antiviral medications have significantly reduced the rate of acute rejection and serious infections. As long-term graft survival improves, the side effect profiles of newer medications are increasingly important. The one- and 3-year graft survival rates during the past 5 years were 98% and 90% for adult recipients of living donor kidneys and were 91% and 82% for recipients of cadaveric grafts, respectively. The results for pediatric transplants were 100% and 97% for living donor kidneys and 97% and 85% for cadaveric grafts at one and 3 years, respectively. We are pleased with our excellent results and the manner in which our program has responded to changes in the organ transplant environment.

Adult↗
PubMed2002

Paraneoplastic syndromes in urologic malignancy: the many faces of renal cell carcinoma.

Renal cell carcinoma is unique among the genitourinary malignancies in that close to one third of affected patients show signs and symptoms of a paraneoplastic syndrome. The paraneoplastic syndromes associated with renal cell carcinoma range from those manifesting in constitutional symptoms (ie, fever, cachexia, and weight loss) to those that result in specific metabolic and biochemical abnormalities (ie, hypercalcemia, nonmetastatic hepatic dysfunction, amyloidosis, etc). The presence of a paraneoplastic syndrome in a patient with renal cell carcinoma is neither a marker of metastatic disease nor necessarily indicative of a poor prognosis. The importance of understanding the pathophysiology and biology behind the many paraneoplastic syndromes associated with renal cell carcinoma lies in the fact that the presence of these protean symptoms may be the initial presentation of either primary or recurrent disease. In this review, we will describe the proposed mechanisms of action of the many paraneoplastic syndromes associated with renal cell carcinoma as well as outline the clinical evaluation and treatment options currently available for these noteworthy disorders.

Journal Article↗
PubMed2002

Future strategies for treating erectile dysfunction.

Erectile dysfunction affects over half of all men between 50 and 70 years of age, and by the age of 40, about 40% of men may suffer from some form of erectile dysfunction. Many disease states, such as diabetes, hypertension, depression, and vascular disease, are associated with the condition, which may occur many years prior to the onset of these disorders. The phenomenal success of sildenafil in improving erections in men with erectile dysfunction is due to the fact that the drug, as a phosphodiesterase inhibitor, improves the relaxation of smooth muscle cells, which become dysfunctional with the aging process. However, not everyone responds to this medication, mainly because the efficacy of the drug is directly dependent on the release of nitric oxide from the nerve terminals of the cavernosal nerve, and this may become defective with aging/certain disease states. The goal of gene therapy for organic impotence is to allow the patient to sustain physiologically elicited erections without resorting to pharmacological treatment immediately prior to the sexual act. Experimental efforts in gene therapy for erectile dysfunction are likely to continue intensively in a series of directions, some specific to the nature of the selected gene to be manipulated or the physiology of the corpora cavernosa itself, and others extrapolatable from the advancement of gene therapy in general.

Journal Article↗
PubMedDate not supplied

Therapy of erectile dysfunction: potential future treatments.

Current research on the development of new medical treatments of erectile dysfunction (ED) fall essentially into two main types of approaches: (1) the traditional strategy based on compounds acting to induce an erection on demand, without modifying the underlying pathologic alterations that lead to ED; and (2) more novel agents not inducing an erectile response but aiming for a long-term correction of either the defect in cavernosal tissue integrity responsible for functional impairment, or the impairment per se of the cavernosal tissue function. In the first approach, new phosphodiesterase inhibitors (either more potent and specific than the clinically available ones or harboring nitric oxide-releasing structures), soluble guanylate cyclase activators, Rho kinase inhibitors, as well as centrally active agents stimulating hypothalamic dopamine or melanocortin receptors, combinations of different types of drugs, and new facilitators of tissue uptake of active agents, are being investigated and some may soon be applied clinically. In the second approach, the first type of correction comprises regulators of endogenous cell number and integrity and extracellular matrix turnover (inhibitors of apoptosis and fibrosis, neurotrophic and angiogenic factors), testosterone, and tissue and cell explants (nerve and smooth muscle grafting, adult pluripotent cells), whereas the second includes in vivo gene therapy with different genes and vectors, and ex vivo gene therapy, combining gene transfer with stem cell implants. This second approach requires extensive laboratory research prior to clinical translation but may provide a means to cure ED. The current status and future directions of these strategies are discussed.

Androgens↗