Using a rabbit model, the involvement of the L-arginine/nitric oxide pathway in penile erection was investigated. The mean basal intracavernous pressure was 21 cm H2O. Cavernous nerve stimulation (4-8 V, 20-30 Hz) increased the pressure to approximately 130 cm H2O. This response was highly reproducible and usually associated with full penile erection. The pressure increase could be quantified in terms of: (1) the slope of the initial, ascending part of the pressure increase; (2) delta P, which was defined as the maximal pressure obtained by the stimulation minus the basal pressure before the stimulation; (3) T90, which was defined as the time to reach 90 per cent of delta P. Intrapenile administration of the L-arginine/nitric oxide synthesis inhibitor NG-nitro-L-arginine had no effect on systemic arterial blood pressure. However, NG-nitro-L-arginine (0.22 and 2.19 mg), administered via the same route, abolished the erectile response induced by cavernous nerve stimulation; T90 increased and slope and delta P decreased significantly. NG-nitro-D-arginine (2.19), on the other hand, had no inhibitory effect. L-arginine (21.07 mg), given either directly or after NG-nitro-L-arginine had no consistent effect on the functional response to cavernous nerve stimulation. The results suggest that pharmacologically induced effects on intracavernous pressure in the rabbit can be described quantitatively, and that this model may be useful to study the mechanisms controlling penile erection in vivo. The pronounced inhibitory action of NG-nitro-L-arginine demonstrates the important role of the arginine/nitric oxide pathway in mediating relaxation of penile smooth muscles necessary for erection.
ObjectiveDespite having an organ confined tumor stage at the time of radical cystectomy, a certain number of bladder cancer patients will develop local or distant metastases over time. Currently there are no reliable serum markers for monitoring and evaluating risk profiles of urothelial cancers. Several studies suggest that detection of Circulating Tumor Cells (CTC) may correlate with disease status and prognosis at baseline and early in the treatment of cancers. The presence of CTCs in whole blood before and during radical cystectomy could provide further information on disease status, and could be used as an indicator to determine the need for adjuvant or even perioperative chemotherapy.MethodsFrom 03/2009 to 05/2009, five patients with histologically proven transitional cell carcinoma of the urinary bladder participated in this study. All patients were admitted to the hospital for radical cystectomy (rCx). A standard or extended lymph node dissection was performed in all cases. Preoperative CT or MRI scans revealed no distant or local metastases. Median age was 66.8 years (55-81 yrs). After obtaining informed consent from each patient, approximately 30 mL of peripheral blood was taken immediately before rCx and again during surgical removal of the urinary bladder from the patients' body. As additional parameters, operation time (OR) for surgical removal of the bladder and the amount of blood volume that was used for the detection of CTCs were recorded. Obtained blood samples were processed using the Cell-Search System (Veridex©) within 48 hours of collection. CTCs were identified and quantitated using the Cell-Search System, followed by re-evaluation of the provided results by specially trained and experienced personal. (CS, SH)ResultsCTCs were detected before and during surgical removal of the urinary bladder in one of five patients (20%). In the one patient positive for CTC, two CTCs were detected in the blood sample that was obtained before surgery (analyzed blood volume was 25 mL). There was one CTC detected in the blood sample that was obtained during surgical removal of the urinary bladder (analyzed blood volume was 27 mL). There was no rise in the amount of CTCs during surgical procedure. The final pathological report of this patient showed an advanced tumor stage (T3b, N0, R1). In the other patients, no CTCs were detected at all, neither before rCX nor right after surgical removal of the bladder. Pathological stage for these patients ranged from pT1m G3 -pT2b G3. None of these patients showed lymph node involvement. An average of 14.6 lymph nodes (5-40 LNs) were obtained. OR time to surgical removal of the urinary bladder ranged from 60 minutes to 150 minutes (mean 82 min.).ConclusionsAlthough only a very small group of patients was analyzed in this study, the presence of CTCs seems to be correlated with an advanced tumor stage. Therefore the detection of CTCs could be used for an optimized assessment of a patient's disease status in urothelial cancer. A further aim of this study was to assess whether...
Background Partial or radical cystectomy requires replacement of the urinary reservoir normally achieved by using small or large bowel segments. Our aim was to establish tissue engineering of an bioartificial bladder wall using primary cultures of porcine urothelial (pUC) and bladder smooth muscle cells (pSMC) to be reseeded on different acellular biological matrices. Methods Primary porcine cultures of pUC and pSMC were established from open bladder biopsy material 25 mm 2 in size. Acellular matrix was generated either from a) porcine bladder wall segments or b) tubular small intestinal submucosa with the still attached decellularized muscularis layer. Reseeding of these matrices with primary cells was done in a two-dimensional static model and in a three-dimensional rotating bioreactor perfused with cell culture medium for a period of 6 weeks. Results Prior to reseeding the cultured cells were characterized as pUC and pSMC by immunohistochemical staining with either anti-keratin 7 or anti-alpha actin. For both matrices a reseeded double layer cell system of pUC and pSMC could be identified after incubation in the described systems for 6 weeks. Conclusions Our results document successful generation of tissue engineered urinary bladder wall, which can be used in further large animal transplantation experiments.
Surgical removal continues to be the mainstay in the treatment of renal-cell carcinoma with neoplastic venous extension. The steady improvement of surgical and anesthesiological techniques and the introduction of complete circulatory arrest has dramatically improved the morbidity even of patients with extensive thrombi. If ultrasound or computerized tomography (CT) scanning suggests the presence of a venous extension in a patient with renal-cell carcinoma, cavography, magnetic resonance imaging (MRI), transesophageal color-coded ultrasound, and echocardiography may be needed to resolve the questions of cranial extension and vascular wall infiltration. Surgical stratification and, thus, classification of the venous extension depend on the potential need for complete circulatory arrest. Surgical removal is done en bloc for smaller venous extensions and in a two-step procedure (radical nephrectomy followed by thrombectomy) for more extensive thrombi. In patients with infiltration of the suprahepatic inferior vena cava, the hepatic veins or atrium, pending thrombotic embolism, or large masses of suprahepatic thrombotic material, the use of cardiopulmonary bypass and complete circulatory arrest is recommended.
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