Post-transplant lymphoproliferative disorder mimicking a thrombotic microangiopathy.
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Adult↗
Biomedical subjects
Rafael Carrion
Publications and source records attributed to Rafael Carrion.
The effect of FK1706 on erectile function following bilateral cavernous nerve crush injury in a rat model.
PURPOSE: We investigated the neurotrophic effect of FK1706 on erectile recovery following bilateral cavernous nerve crush injury in a rat model. MATERIALS AND METHODS: A total of 28 male Sprague-Dawley rats were randomly divided into 4 equal groups. Seven animals underwent sham operation and subcutaneous vehicle injection, whereas 21 underwent bilateral cavernous nerve crush injury followed by vehicle injection alone, or by low (0.1 mg/kg) or high (1.0 mg/kg) dose FK1706 treatment. Injections were continued 5 days weekly for 8 weeks. Erectile function was then assessed by cavernous nerve electrostimulation and penile tissue was evaluated immunohistochemically. RESULTS: No erectile dysfunction was identified in the sham treated group (mean maximal intracavernous pressure +/- SEM 106.8 +/- 6.4 cm H(2)O), whereas nerve injury significantly decreased ICP to 17.9 +/- 7.0 cm H(2)O. FK1706 facilitated neural and erectile recovery in a concentration dependent manner with a mean ICP in the high dose FK treatment group of 80.1 +/- 7.8 cm H(2)O compared with 44.1 +/- 12.9 cm H(2)O in the low dose group. Similar stepwise findings were observed using mean area under the curve data. Sham treated animals showed regular axon sizes and shapes with homogenous GAP-43 and neurofilament staining, whereas injured axons showed irregular shapes, sizes and staining patterns. FK1706 treatment restored axon shape and staining patterns. Injury significantly decreased nicotinamide adenine dinucleotide phosphate staining and FK1706 treatment showed a nonsignificant trend toward increased staining. CONCLUSIONS: Bilateral cavernous nerve crush causes reproducible erectile dysfunction, consistent with prior experiments. High dose subcutaneous FK1706 therapy promotes significant neuroregeneration and erectile function recovery.
Animals↗
Crural ligation for primary erectile dysfunction: a case series.
PURPOSE: Some men with primary erectile dysfunction (ED) have maldevelopment of the crura of the penis. We report our experience with crural ligation for primary venous leakage ED in the last 5 years. MATERIALS AND METHODS: Between December 1998 and March 2004, 11 patients with primary ED underwent crural ligation surgery for congenital venous leakage. All patients were evaluated with pertinent history and physical examinations, color duplex ultrasound, nocturnal penile tumescence study with RigiScan, cavernosometry and cavernosography. Localized crural leakage was the pathognomonic feature in these patients. Surgery involved reflection of the dorsal and cavernous arteries and nerves off of the crura, followed by ligation of the 2 crura proximal to the entrance of the cavernous artery with umbilical tapes. Followup was performed by telephone interview or personal interview at the clinic. A retrospective preoperative and postoperative questionnaire, that is the abridged 5-item version of the 15-item International Index of Erectile Function, was given at the time of the interview. Statistical analysis was performed with the paired t test. RESULTS: Median patient age at surgery was 28 years (range 22 to 39) and mean followup after surgery was 34 months (range 6 to 58). Mean International Index of Erectile Function +/- SD preoperatively and postoperatively was 8.9 +/- 4.5 and 17.5 +/- 5.0, respectively. For questions 2, 3 and 5 mean postoperative scores were significantly better than postoperative scores (p <0.05). Marked improvement in erectile function was noted in 9 of our 11 patients. CONCLUSIONS: Penile venous surgery may not have a lasting result in men in whom venous leakage is due to systemic diseases or penile smooth muscle atrophy. However, in patients with a congenital venous leak abnormality of the crura ligation of the proximal crura with umbilical tapes seems to have a satisfactory, durable result.
Adult↗
Improving erectile function by silencing phosphodiesterase-5.
PURPOSE: We investigated whether phosphodiesterase-5 (PDE5) can be down-regulated by a specific small interfering RNA (siRNA) and whether this would improve erectile function. MATERIALS AND METHODS: A PDE5 siRNA encoding oligonucleotide was inserted into pSUPER-retro vector, resulting in the siRNA expressing construct, pPDE5-silencer. The construct was packaged into oncoretroviral particles and then transduced into rat cavernous smooth muscle cells (CSMCs). Cells were examined for PDE5 expression by reverse transcriptase-polymerase chain reaction, Western blotting and immunofluorescence microscopy. Cells were then treated with 10 microM sodium nitroprusside (SNP) and examined for cyclic guanosine monophosphate (cGMP) at 0, 10, 30, 60 and 240 minutes. The siRNA expressing cassette was transferred from the oncoretrovirus to lentivirus, which was then injected into rat penises. Three months later erectile function was examined by electrostimulation and PDE5 expression in cavernous smooth muscle was determined by immunohistochemistry. RESULTS: CSMCs transfected with pPDE5-silencer (CSMC plus siRNA) showed an 88.2% decrease in PDE5 compared with CSMCs transfected with control vector (CSMCs plus vector). Within 10 minutes of SNP treatment cells (CSMCs, CSMCs plus vector and CSMCs plus siRNA) showed similar sharp increases in cGMP. However, while cGMP levels in CSMCs and CSMCs plus vector returned to almost baseline in 1 hour, the cGMP level in CSMCs plus siRNA remained high even 4 hours after SNP treatment. Rats injected with the siRNA expressing lentivirus showed increased electrostimulated erectile function, as measured by peak intracorporeal pressure and the intracorporeal pressure increase, compared with rats injected with control lentivirus. PDE5 expression was decreased in the siRNA treated cavernous smooth muscle. CONCLUSIONS: PDE5 expression could be decreased by siRNA, resulting in prolonged cGMP accumulation and improved erection.
3',5'-Cyclic-GMP Phosphodiesterases↗
The effect of neural embryonic stem cell therapy in a rat model of cavernosal nerve injury.
OBJECTIVE: To isolate embryonic stem cells that have differentiated along the neuronal cell line, and to assess whether injecting these neural stem cells into the corpus cavernosum influences cavernosal nerve regeneration and functional status. MATERIALS AND METHODS: Embryonic neural stem cells were obtained; 26 male Sprague-Dawley rats were divided into four groups: five had a sham operation; eight (controls) had a bilateral cavernosal nerve crush and injection of culture medium into the corpora cavernosa; four had an injection of neural embryonic stem (NES) cells into the major pelvic ganglion (MPG); and nine had bilateral cavernosal nerve crush and injection of NES cells into the corpora cavernosa. Erectile response was assessed by cavernosal nerve electrostimulation at 3 months, and penile tissue samples were evaluated histochemically for nitric oxide synthase (NOS)-containing fibres, tyrosine hydroxylase and neurofilament staining. RESULTS: The groups injected with NES cells into the MPG and corpora cavernosa had significantly higher intracavernosal pressures than the control group. Immunohistochemical staining also revealed differences in the quality of the NOS-containing nerve fibres. Neurofilament staining was significantly better in the experimental groups injected with NES cells. CONCLUSION: We were able to isolate embryonic stem cells that had differentiated along the neural cell line and, using these NES cells intracavernosally, showed improved erectile function in a rat model of neurogenic impotence.
Animals↗
p53/MDM2 Pathway Aberrations in Parathyroid Tumors: p21(WAF-1) and MDM2 Are Frequently Overexpressed in Parathyroid Adenomas.
Parathyroid adenomas (PTAs) are the main cause of primary hyperparathyroidism. Cell cycle regulation in normal parathyroid tissue (NPT) and PTA remains largely unknown. We have systematically explored several components involved in the p53/MDM2/p19(ARF) pathway in PTA and compared the results were with NPT. Forty-six PTA and 12 NPT were immunostained with anti-p21(WAF-1), MDM2, p53, and p27(KP1) antibodies. The slides were processed by cytometry and the results were statistically analyzed using nonparametric methods (Mann-Whitney test). p2l(WAF-1) and MDM2 expression were significantly higher in PTA compared with NPT (p < 0.05). The opposite results were found for p27(KIP1) (p< 0.05). Occasional p53 staining was found in some PTA, albeit no significant difference was found in comparison with NPT. In conclusion, MDM2 and p2l(WAF-1) are the proteins more overexpressed in PTA. These findings are surprising taking into account the benign nature of PTA, making them suitable candidates for further molecular analysis.
Journal Article↗
Analysis of the Cycilin D1/p16/pRb Pathway in Parathyroid Adenomas.
Cyclin D1/p16/pRb pathway controlling G1-S cell cycle checkpoint is frequently altered in human tumors. Currently, scarce data are available for parathyroid tumors. We have studied 46 parathyroid adenomas (PTAs) and 12 normal parathyroid glands (PTGs) by immunohistochemistry with cyclin D1 (CD1), p16, pRb, and Ki-67 antibodies. We observed CD1 expression in 89%, p16 in 70%, and pRb in 100% of PTAs. Statistically significant differences with normal PTGs were found only concerning p16 expression (p <0.05). Proliferating rate (Ki-67) was always low, although significantly higher than in normal PTGs. Our findings demonstrate the presence of alterations in the CD1/p16/pRb pathway in PTAs, consisting in p16 overexpression apparently unrelated to pRb downregulation. On the other hand, we did not find significant differences in CD1 expression between PTAs and normal PTGs, suggesting CD1 overexpression could be a physiological event in parathyroid tissue.
Journal Article↗
Caveolin expression in adult renal tumors.
Histopathological criteria are usually sufficient for the accurate distinction of benign form malignant renal tumors. A minority of cases however, poses a vexing diagnostic dilemma. Recent studies suggest that caveolin, a scaffolding cell membrane protein may prove helpful in predicting the behavior of these neoplasms. We analyzed a series of 40 renal tumors of which 7 were clear cell and 6 granular Renal Cell Carcinomas (RCC), 10 cases of Papillary Carcinoma (PCC), 4 cases of Chromophobe Renal cell carcinomas (CRCR), 11 cases of Oncocytomas (OC) and 2 cases of Collecting Duct Carcinomas (CDC). The distribution of immunoreactivity was analyzed by quantifying caveolin cell membrane staining in each case. There was a statistically significant difference in the expression of caveolin-1 between oncocytoma with a mean labeling index of 91.7 and the cases of malignant renal tumors with a mean labeling index of 26.9 for RCC, 24 for CDC, 21 for CRCR, and 19.2 for PCC. The results suggest an association between loss of caveolin expression among malignant renal tumors that might be useful in distinguishing oncocytoma from malignant renal tumors and possibly implicates this peptide in their pathogenesis.
Adenocarcinoma, Clear Cell↗
Surgical management of bladder carcinoma.
BACKGROUND: Despite advances in medical oncology, radiation therapy, and molecular and cell biology, the mainstay in the management of bladder cancer continues to be surgery. METHODS: The authors reviewed the literature regarding the endoscopic diagnosis and management of bladder cancer as well the role of partial and radical cystectomy. RESULTS: Cystoscopy and transurethral resection are required to diagnose and stage bladder cancer. The indications for random bladder biopsies, prostatic urethral biopsy, and re-resection of the tumor bed are examined. The results and complications of endoscopic resection in the management of Ta, T1, and T2 or greater bladder cancer are reported. The roles of partial cystectomy, radical cystectomy, extent of lymphadenectomy, and indications for urethrectomy are also examined. The results and complications of radical cystectomy for the management of T2, T3, T4, and N+ bladder cancer are reported. CONCLUSIONS: Surgery remains a critical element in the management of bladder cancer. Improvements in surgical technique, urinary reconstruction, and multimodal therapy continue to improve the prognosis and quality of life of patients with transitional cell cancer of the bladder.
Cystectomy↗