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To investigate outcomes of urothelial carcinoma of the bladder (UCB) patients treated with radical cystectomy (RC) according to the presence of circulating tumor cells (CTC) and the administration of adjuvant chemotherapy (AC). We prospectively enrolled 226 UCB patients treated with RC without neoadjuvant chemotherapy at our institution between 2007 and 2013. Blood samples were obtained from all patients preoperatively and analyzed for CTC using the CellSearch ® system. Platinum-based AC was administered in 50 patients (27.0%). Cox regression models evaluated the association of CTC with disease recurrence, cancer-specific and overall mortality according to AC administration. 185 patients were available for analyses. CTC were present in 41 patients (22.2%). Patients with presence of CTC received AC more frequently, compared to patients without CTC (p = 0.027). At a median follow-up of 31 months, the presence of CTC was associated with disease recurrence, cancer-specific and overall mortality (p-values < 0.001) in patients without AC administration. In patients who received AC, there was no difference in either endpoint between patients with or without presence of CTC. In multivariable analysis of patients without AC administration, the presence of CTC was an independent predictor for disease recurrence (HR: 4.9; p < 0.001), cancer-specific (HR: 4.2; p = 0.003) and overall mortality (HR: 4.2; p = 0.001). The CTC status may be implemented in decision-making regarding AC administration in UCB patients following RC. CTC measurement should be implemented in future UCB studies on systemic chemotherapy to validate our findings., (© 2016 UICC.)

Objectives: From previous data in animal models of cerebral ischemia, lipocalin-2 (LCN2), a protein related to neutrophil function and cellular iron homeostasis, is supposed to have a value as a biomarker in ischemic stroke patients. Therefore, we examined LCN2 expression in the ischemic brain in an animal model and measured plasma levels of LCN2 in ischemic stroke patients., Methods: In the mouse model of transient middle cerebral artery occlusion (tMCAO), LCN2 expression in the brain was analyzed by immunohistochemistry and correlated to cellular nonheme iron deposition up to 42 days after tMCAO. In human stroke patients, plasma levels of LCN2 were determined one week after ischemic stroke. In addition to established predictive parameters such as age, National Institutes of Health Stroke Scale and thrombolytic therapy, LCN2 was included into linear logistic regression modeling to predict clinical outcome at 90 days after stroke., Results: Immunohistochemistry revealed expression of LCN2 in the mouse brain already at one day following tMCAO, and the amount of LCN2 subsequently increased with a maximum at 2 weeks after tMCAO. Accumulation of cellular nonheme iron was detectable one week post tMCAO and continued to increase. In ischemic stroke patients, higher plasma levels of LCN2 were associated with a worse clinical outcome at 90 days and with the occurrence of post-stroke infections., Conclusions: LCN2 is expressed in the ischemic brain after temporary experimental ischemia and paralleled by the accumulation of cellular nonheme iron. Plasma levels of LCN2 measured in patients one week after ischemic stroke contribute to the prediction of clinical outcome at 90 days and reflect the systemic response to post-stroke infections.

Background and Purpose: Antibiotics disturbing microbiota are often used in treatment of poststroke infections. A bidirectional brain-gut microbiota axis was recently suggested as a modulator of nervous system diseases. We hypothesized that gut microbiota may be an important player in the course of stroke., Methods: We investigated the outcome of focal cerebral ischemia in C57BL/6J mice after an 8-week decontamination with quintuple broad-spectrum antibiotic cocktail. These microbiota-depleted animals were subjected to 60 minutes middle cerebral artery occlusion or sham operation. Infarct volume was measured using magnetic resonance imaging, and mice were monitored clinically throughout the whole experiment. At the end point, tissues were preserved for further analysis, comprising histology and immunologic investigations using flow cytometry., Results: We found significantly decreased survival in the middle cerebral artery occlusion microbiota-depleted mice when the antibiotic cocktail was stopped 3 days before surgery (compared with middle cerebral artery occlusion specific pathogen-free and sham-operated microbiota-depleted mice). Moreover, all microbiota-depleted animals in which antibiotic treatment was terminated developed severe acute colitis. This phenotype was rescued by continuous antibiotic treatment or colonization with specific pathogen-free microbiota before surgery. Further, infarct volumes on day one did not differ between any of the experimental groups., Conclusions: Conventional microbiota ensures intestinal protection in the mouse model of experimental stroke and prevents development of acute and severe colitis in microbiota-depleted mice not given antibiotic protection after cerebral ischemia. Our experiments raise the clinically important question as to whether microbial colonization or specific microbiota are crucial for stroke outcome., (© 2016 The Authors.)

Background: Stricture excision and posterior urethroplasty is the most common procedure after posttraumatic urethral strictures., Results: Re-strictures and fistulas are treated by repeat urethroplasty. Tension-free anastomosis is prerequisite for surgical success. Urinary incontinence after posttraumatic injuries is treated by an artificial urinary sphincter.

Purpose: To validate a German language version of the patient-reported outcome measurement (PROM) following urethral stricture surgery (USS) in a cohort of men undergoing one-stage buccal mucosa graft urethroplasty (BMGU) for urethral stricture. Furthermore, to explore the responsiveness of erectile function (EF) and urinary incontinence (UI) constructs in the context of this intervention., Methods: The USS-PROM captures voiding symptoms (ICIQ-MLUTS) and health-related quality of life (HRQoL) (EQ-5D). To evaluate EF and UI, the IIEF-5 and ICIQ-UI SF were included. Between March 2012 and April 2013, all patients undergoing BMGU at our institution were prospectively enrolled in this study. Psychometric assessment included internal consistency, test-retest reliability, criterion validity and responsiveness., Results: Ninety-three men completed the USS-PROM before and 3 months after surgery, with 40 (43 %) also completing the USS-PROM 6 months after surgery to assess reliability. Internal consistency: for the ICIQ-MLUTS, Cronbach's α was 0.83. The test-retest intraclass correlation coefficient was 0.94. There was a negative correlation between change in ICIQ-MLUTS total score and change in Q max (r = -0.40). All values exceeded our predefined thresholds. Significant improvements of voiding symptoms and HRQoL demonstrate responsiveness to change (all p values <0.001). While ICIQ-UI scores did not change (p > 0.05), IIEF-5 scores improved significantly (p = 0.048)., Conclusions: The German language USS-PROM shows similar psychometric properties to the English language version. This instrument can be improved by assessing EF by the use of IIEF-5. Further studies with larger patient cohorts are needed to evaluate the significance of measuring UI in urethroplasty patients.

Pneumonia is the leading cause of death after acute spinal cord injury and is associated with poor neurological outcome. In contrast to the current understanding, attributing enhanced infection susceptibility solely to the patient's environment and motor dysfunction, we investigate whether a secondary functional neurogenic immune deficiency (spinal cord injury-induced immune deficiency syndrome, SCI-IDS) may account for the enhanced infection susceptibility. We applied a clinically relevant model of experimental induced pneumonia to investigate whether the systemic SCI-IDS is functional sufficient to cause pneumonia dependent on spinal cord injury lesion level and investigated whether findings are mirrored in a large prospective cohort study after human spinal cord injury. In a mouse model of inducible pneumonia, high thoracic lesions that interrupt sympathetic innervation to major immune organs, but not low thoracic lesions, significantly increased bacterial load in lungs. The ability to clear the bacterial load from the lung remained preserved in sham animals. Propagated immune susceptibility depended on injury of central pre-ganglionic but not peripheral postganglionic sympathetic innervation to the spleen. Thoracic spinal cord injury level was confirmed as an independent increased risk factor of pneumonia in patients after motor complete spinal cord injury (odds ratio = 1.35, P < 0.001) independently from mechanical ventilation and preserved sensory function by multiple regression analysis. We present evidence that spinal cord injury directly causes increased risk for bacterial infection in mice as well as in patients. Besides obvious motor and sensory paralysis, spinal cord injury also induces a functional SCI-IDS ('immune paralysis'), sufficient to propagate clinically relevant infection in an injury level dependent manner., (© The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Unlabelled: The present retrospective multicenter study analyzed the effect of perioperative blood transfusions (PBTs) on the outcomes in 285 patients with upper tract urothelial carcinoma who had undergone radical nephroureterectomy (RNU). We found that patients receiving PBTs had inferior survival compared with that of patients without PBTs. Future investigations should focus on optimization of preoperative hemoglobin levels, surgical accuracy, and anesthetic management of RNU., Background: Preoperative anemia is an independent predictor for unfavorable outcomes in patients with upper tract urothelial carcinoma (UTUC) who undergo radical nephroureterectomy (RNU). The effect of perioperative blood transfusion (PBT) on survival, however, has been insufficiently investigated. We investigated the impact of PBT on the outcomes of patients UTUC treated with RNU., Patients and Methods: We analyzed the data from 285 patients with UTUC who had undergone RNU at 3 German academic institutions. PBT administration was analyzed as a dichotomous variable (administered vs. not administered) and the number of PBT units as a continuous and categorical variable (0 vs. ≤ 2 vs. > 2). Cox regression models were used to analyze the impact of PBT on disease recurrence and survival., Results: A total of 81 patients (28.4%) had received a PBT with a median number of 2 U (interquartile range, 2-4). The administration of PBT was associated with advanced tumor stage, higher tumor grade, and preoperative anemia (P ≤ .049 for all). At a mean follow-up of 52 months, PBT and an increasing number of PBT units were significantly associated with inferior overall survival (P ≤ .025). On multivariable analyses adjusted for established UTUC outcome prognosticators, PBT was significantly associated with inferior overall survival (hazard ratio, 1.6; 95% confidence interval, 1.055-2.428; P = .027)., Conclusion: PBT is an independent risk factor for worse overall survival in patients with UTUC treated with RNU. Continued efforts are warranted to optimize patients' preoperative hemoglobin level, surgical accuracy, and anesthetic management of RNU to reduce the necessity for PBTs., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background and Purpose: Temporary immunosuppression has been identified as a major risk factor for the development of pneumonia after acute central nervous system injury. Although overactivation of the sympathetic nervous system was previously shown to mediate suppression of systemic cellular immune responses after stroke, the role of the parasympathetic cholinergic anti-inflammatory pathway in the antibacterial defense in lung remains largely elusive., Methods: The middle cerebral artery occlusion model in mice was used to examine the influence of the parasympathetic nervous system on poststroke immunosuppression. We used heart rate variability measurement by telemetry, vagotomy, α7 nicotinic acetylcholine receptor-deficient mice, and parasympathomimetics (nicotine, PNU282987) to measure and modulate parasympathetic activity., Results: Here, we demonstrate a rapidly increased parasympathetic activity in mice after experimental stroke. Inhibition of cholinergic signaling by either vagotomy or by using α7 nicotinic acetylcholine receptor-deficient mice reversed pulmonary immune hyporesponsiveness and prevented pneumonia after stroke. In vivo and ex vivo studies on the role of α7 nicotinic acetylcholine receptor on different lung cells using bone marrow chimeric mice and isolated primary cells indicated that not only macrophages but also alveolar epithelial cells are a major cellular target of cholinergic anti-inflammatory signaling in the lung., Conclusions: Thus, cholinergic pathways play a pivotal role in the development of pulmonary infections after acute central nervous system injury., (© 2015 American Heart Association, Inc.)

Purpose: To investigate the impact of the AB0 and the Rhesus blood group system on outcomes of urothelial carcinoma of the bladder (UCB) patients treated with radical cystectomy (RC)., Methods: We included 511 UCB patients treated with RC without neoadjuvant chemotherapy from 1996 to 2011 at our institution. Cox and logistic regression models assessed the association of the AB0 blood group antigen and Rhesus factor expression with tumor biologic features and outcomes, respectively., Results: In total, 216 patients (42.3 %) had the blood group antigen A0, 73 patients (14.3 %) the antigen B0, 33 patients (6.4 %) the antigen AB and 189 patients (37.0 %) the antigen 00. In addition, 414 patients (81.0 %) were Rhesus factor positive. The AB0 blood group antigen expression was associated with a higher tumor grade (p = 0.003). In contrast, the Rhesus factor was not associated with any clinicopathologic characteristics. Neither the AB0 blood group antigens nor the Rhesus factor was associated with survival. In a sensitivity analysis of patients receiving adjuvant chemotherapy, however, the blood group antigen AB expression was associated with reduced cancer-specific and overall survival., Conclusion: The AB0 blood group antigens and the Rhesus factor are not associated with survival. Although the AB0 blood groups and the Rhesus factor are analyzed in every patient treated with RC, they do not represent appropriate biomarkers for UCB outcome prognostication. The association of the AB0 blood group antigens with response to adjuvant chemotherapy requires further validation.

Purpose: To determine the success rate of direct vision internal urethrotomy (DVIU) in the treatment of short stricture recurrence after buccal mucosa graft urethroplasty (BMGU)., Methods: Patients who underwent DVIU for the treatment of short, "veil-like" recurrent urethral strictures (<1 cm) after BMGU between October 2009 and 2013 were retrospectively identified within our urethroplasty database. Stricture recurrence was defined as maximum flow rate (Q max) <15 ml/s and a consecutively verified stricture in a combined retro- and antegrade voiding cystography or cystoscopy at a follow-up visit. The success rate of DVIU was assessed by Kaplan-Meier analysis. Univariable Cox regression analyses evaluated risk factors for stricture recurrence following DVIU., Results: Forty-three patients underwent DVIU for short stricture recurrence after BMGU for bulbar (81.3 %), penile (14.0 %) and membranous (4.7 %) strictures. Relapse had occurred proximally to the buccal mucosa graft in 28 (65.1 %) and distally in 12 (27.9 %) patients, respectively. At a mean follow-up of 11.7 (±9.7) months, stricture recurrence was observed in 48.8 % of our patients. Stricture recurrence was significantly associated with weak urinary stream (9.3 ml/s vs. no recurrence 19.5 ml/s) and patient dissatisfaction (66.7 % vs. no recurrence 18.1 %; both p < 0.001). The overall success rate was 60.5 % 15 months after DVIU. The main limitations of this study are its retrospective design, the small sample size and the short follow-up., Conclusions: DVIU after BMGU showed a moderate success rate and therefore might be a viable treatment option in selected patients with very short strictures after BMGU. However, longer follow-up is warranted to prove long-term effectiveness.

Purpose: We evaluated stricture-free survival and functional outcomes of buccal mucosa graft urethroplasty in patients with urethral stricture disease after radiotherapy., Materials and Methods: We reviewed our urethroplasty database for patients with a radiotherapy history who underwent buccal mucosa graft urethroplasty between January 2009 and October 2013. We reviewed patient charts and the institutional, standardized, nonvalidated questionnaires administered to each patient postoperatively. Study end points included 1) the success rate, 2) continence status, 3) erectile function and 4) patient satisfaction postoperatively. Success was defined as stricture-free survival., Results: Of 38 men included in the study prostate cancer was the most common indication for radiotherapy in 35 (92.1%). External beam radiotherapy was performed in 24 cases (64.9%), brachytherapy was done in 8 (21.6%) and a combination of the 2 treatments was performed in 6 (13.5%). Strictures were in the bulbar/bulbomembranous urethra and had a median length of 3.0 cm (range 1.0 to 8.0). The overall success rate was 71.1% at a median followup of 26.5 months (range 1.0 to 50.0). Median time to stricture recurrence was 17.0 months (range 3.0 to 44.0). De novo urinary incontinence was observed in 4 patients (10.5%). Erectile function remained mostly unchanged compared to preoperative status. Study limitations include the small sample size and the lack of validated questionnaires., Conclusions: At short-term to mid-term followup the success rate of ventral onlay buccal mucosa graft urethroplasty in patients with radiotherapy history seems acceptable. However, patients must be counseled about the increased risk of urinary incontinence. Longer followup is warranted to address long-term outcomes., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Ureteral reconstruction is still a sophisticated approach. Because of an increase in endoscopic procedures for kidney and ureteral stone treatment, radiation therapy and pelvic surgery, ureteral strictures are more frequently observed. Short proximal and distal strictures can be reconstructed by using the renal pelvis or urinary bladder. New techniques are needed for reconstruction of long strictures as well as those located in the middle ureter., Recent Findings: This article summarizes very recent studies from 2014, investigating new techniques and their functional outcome of procedures for ureteral reconstruction. In an open reconstruction, some new techniques to reconstruct full-length ureter defects using bladder flaps or by intestinal onlay techniques were described. In addition, laparoscopic and robotic reconstruction methods as well as single site procedures demonstrated feasibility. Visualizing the ureter using near-infrared fluorescence techniques for prevention of ureteral injuries is also a new aspect. Future targets focus on the development of artificial transplants by tissue engineering for ureteral reconstruction., Summary: Novel open and minimally invasive techniques for reconstruction of full-length and middle ureter strictures demonstrated feasibility in the past year. Although reasonable outcomes were reported, current results are significantly compromised by short-term follow-up. To date, artificial transplants remain experimental.

Objective: To evaluate the influence of tumor diameter and tumor necrosis on oncologic outcomes in patients with urothelial carcinoma of the bladder treated with radical cystectomy (RC)., Materials and Methods: We treated 517 consecutive patients with urothelial carcinoma of the bladder treated with RC without neoadjuvant chemotherapy at our institution between 1996 and 2011. All RC specimens were meticulously re-reviewed for the largest residual tumor diameter and for the presence and extent of tumor necrosis. Cox regression models evaluated the association with disease recurrence and cancer-specific survival., Results: At RC, 155 patients (30.0%) had a residual tumor diameter ≥3 cm and tumor necrosis was present in 156 patients (30.2%). Tumor diameter and necrosis were significantly correlated (P <.001). Both a tumor diameter ≥3 cm and the presence of tumor necrosis were associated with an older age, advanced tumor stage, higher tumor grade, lymph node metastasis, positive surgical margin status, lymphovascular invasion, and administration of adjuvant chemotherapy (P values ≤.009). A tumor diameter ≥3 cm and the presence of tumor necrosis were associated with disease recurrence and cancer-specific mortality in Kaplan-Meier analyses, respectively (pairwise P values <.001). In addition, a tumor diameter ≥3 cm was an independent predictor of cancer-specific mortality in multivariate analysis that adjusted for standard clinicopathologic features., Conclusion: Tumor diameter and necrosis are closely correlated and associated with aggressive tumor features and inferior oncologic outcomes. A residual tumor diameter ≥3 cm is an independent predictor of cancer-specific mortality. This additional information should be considered to be reported in every pathology report for consideration in patient counseling and treatment decision making. In addition, these results underscore the importance of a thorough transurethral resection of the bladder tumor before RC., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Systemic chemotherapy is the standard treatment of advanced and metastatic urothelial carcinoma of the bladder (UCB). Unfortunately, systemic chemotherapy is ineffective in a significant number of patients, while side effects occur frequently. Detailed molecular-genetic investigations revealed a broad heterogeneity of underlying genomic mutations in UCB and led to the detection of cancer-specific therapeutic targets. These findings may allow a more tailored and individualized patient-based therapy, focusing on specific genomic variations, which may cause chemo-resistance in patients progressing or relapsing after standard chemotherapy. Targeted therapies hold the potential to be more effective in inhibiting cancer cell growth and progression, as well as to cause fewer side effects. While targeted therapies have been successfully established in the treatment of various malignancies including renal cell carcinoma, the clinical impact of these modern treatment strategies still remains unsettled for UCB. In this review, we comprehensively summarize the most current and relevant findings on targeted therapy in advanced and metastatic UCB, elucidating chances and limitations and discussing future perspectives.

Posterior urethroplasty is the most common strategy for the treatment of post-traumatic urethral injuries. Especially in younger patients, post-traumatic injuries are a common reason for urethral strictures caused by road traffic accidents, with pelvic fracture or direct trauma to the perineum. In many cases early endoscopic realignment is the first attempt to restore the junction between proximal and distal urethra, but in some cases primary realignment is not possible or not enough to treat the urethral injury. In these cases suprapubic cystostomy alone and delayed repair by stricture excision and posterior urethroplasty is an alternative procedure to minimise the risk of stricture recurrence.

Background: Toll-like receptors (TLR) constitute a highly conserved class of receptors through which the innate immune system responds to both pathogen- and host-derived factors. Although TLRs are involved in a wide range of central nervous system (CNS) disorders including neurodegenerative diseases, the molecular events leading from CNS injury to activation of these innate immune receptors remain elusive. The stress protein heat shock protein 60 (HSP60) released from injured cells is considered an endogenous danger signal of the immune system. In this context, the main objective of the present study was to investigate the impact of extracellular HSP60 on the brain in vivo., Results: We show here that HSP60 injected intrathecally causes neuronal and oligodendrocyte injury in the CNS in vivo through TLR4-dependent signaling. Intrathecal HSP60 results in neuronal cell death, axonal injury, loss of oligodendrocytes, and demyelination in the cerebral cortex of wild-type mice. In contrast both mice lacking TLR4 and the TLR adaptor molecule MyD88 are protected against deleterious effects induced by HSP60. In contrast to the exogenous TLR4 ligand, lipopolysaccharide, intrathecal HSP60 does not induce such a considerable inflammatory response in the brain. In the CNS, endogenous HSP60 is predominantly expressed in neurons and released during brain injury, since the cerebrospinal fluid (CSF) from animals of a mouse stroke model contains elevated levels of this stress protein compared to the CSF of sham-operated mice., Conclusions: Our data show a direct toxic effect of HSP60 towards neurons and oligodendrocytes in the CNS. The fact that these harmful effects involve TLR4 and MyD88 confirms a molecular pathway mediated by the release of endogenous TLR ligands from injured CNS cells common to many forms of brain diseases that bi-directionally links CNS injury and activation of the innate immune system to neurodegeneration and demyelination in vivo.

Background: To evaluate the effect of variant histology and its extent on oncological outcomes in patients with urothelial carcinoma of the bladder (UCB) who are treated with radical cystectomy., Material and Methods: Data from 485 patients with UCB who were treated with radical cystectomy without neoadjuvant chemotherapy at a single academic center between 1996 and 2011 were collected retrospectively. All pathologic specimens were meticulously re-reviewed for the presence and extent of variant UCB histologies. Cox regression models were used to evaluate the association with disease recurrence and cancer-specific survival., Results: Variant histology was present in 96 patients (19.8%), with squamous cell differentiation (12.6%) being most common. In patients with variant histology, the median and mean extent was 70% and 60%, respectively. Variant histology was associated with female sex, advanced tumor stage, less presence of concomitant carcinoma in situ, and administration of adjuvant chemotherapy (P ≤ 0.001). The presence of variant histology and non-squamous cell differentiation was associated with cancer-specific mortality (pairwise P ≤ 0.02). Moreover, non-squamous cell differentiation was associated with disease recurrence (P = 0.002). The presence of variant histology, non-squamous cell differentiation, and the extent of variant histology were associated with cancer-specific mortality in univariable but not in multivariable analyses., Conclusions: The presence of variant histology, particularly non-squamous cell differentiation, and its extent are associated with inferior survival. However, they are not independent predictors of outcomes. The association of variant histology with established predictors of aggressive tumor biology is likely impairing oncological outcomes and thus has to be considered in clinical decision making., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background and Purpose: Muscle wasting is a common complication accompanying stroke. Although it is known to impair poststroke recovery, the mechanisms of subacute catabolism after stroke have not been investigated in detail. The aim of this study is to investigate mechanisms of local and systemic catabolism and muscle wasting (sarcopenia) in a model of ischemic stroke systematically., Methods: Changes in body composition and catabolic activation in muscle tissue were studied in a mouse model of acute cerebral ischemia (temporal occlusion of the middle cerebral artery). Tissue wasting (nuclear magnetic resonance spectroscopy), tissue catabolism (caspases-3 and -6, myostatin), and proteasome activity were assessed. Food intake, activity levels, and energy expenditure were assessed, and putative mechanisms of postischemic wasting were tested with appropriate interventions., Results: Severe weight loss in stroke animals (day 3: weight loss, -21.7%) encompassed wasting of muscle (-12%; skeletal and myocardium) and fat tissue (-27%). Catabolic signaling and proteasome activity were higher in stroke animals in the contralateral and in the ipsilateral leg. Cerebral infarct severity correlated with catabolic activity only in the contralateral leg but not in the ipsilateral leg. Lower energy expenditure in stroke animals together with normal food intake and activity levels suggests compensatory mechanisms to regain weight. Interventions (high caloric feeding, β-receptor blockade, and antibiotic treatment) failed to prevent proteolytic activation and muscle wasting., Conclusions: Catabolic pathways of muscle tissue are activated after stroke. Impaired feeding, sympathetic overactivation, or infection cannot fully explain this catabolic activation. Wasting of the target muscle of the disrupted innervation correlated to severity of brain injury. Our data indicate the presence of a stroke-specific sarcopenia., (© 2014 American Heart Association, Inc.)

Purpose: Histopathological changes in buccal mucosa transplants after engraftment to the urethra and exposure to urine remain nebulous. We investigated histopathological changes in buccal mucosa transplants integrated into the urethra in humans., Materials and Methods: We prospectively evaluated 22 patients with recurrent urethral stricture after buccal mucosa urethroplasty between November 2012 and October 2013. All patients underwent repeat buccal mucosa urethroplasty performed by a single surgeon. Intraoperatively we harvested a sample of the integrated buccal mucosa transplant previously engrafted to the urethra, a sample of healthy urethra, a sample of freshly harvested buccal mucosa from the contralateral inner cheek and a sample of fibrotic tissue from the area of the current stricture. A dedicated uropathologist performed meticulous histopathological examination of all tissue samples using hematoxylin and eosin staining. Preoperative clinical data were also collected on all patients., Results: The mean interval from previous to current buccal mucosa urethroplasty was 22.2 months (range 4.1 to 76.0). Mean stricture length at repeat urethroplasty was 52.7 mm (range 30.0 to 70.0). Histopathological characteristics of the integrated buccal mucosa transplants were completely preserved in all patients, consisting of thick sheets of stratified nonkeratinized squamous epithelium with a stratum spinosum. Transplants were not partially or entirely overgrown with urothelium., Conclusions: Buccal mucosa transplants retain their histopathological characteristics and are not overgrown with urothelium after urethral engraftment and urine exposure in humans. These findings may explain the superiority of buccal mucosa transplants on the outcome of substitution urethroplasty compared to that of other materials., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Lung diseases, including pneumonia and asthma, are among the most prevalent human disorders, and murine models have been established to investigate their pathobiology and develop novel treatment approaches. Whereas bronchoscopy is valuable for diagnostic and therapeutic procedures in patients, no equivalent for small rodents has been established. Here, we introduce a miniaturized video-bronchoscopy system offering new opportunities in experimental lung research. With an outer diameter of 0.75 mm, it is possible to advance the optics into the main bronchi of mice. An irrigation channel allows bronchoalveolar lavage and unilateral application of substances to one lung. Even a unilateral infection is possible, enabling researchers to use the contralateral lung as internal control.

Background: In an earlier study we demonstrated the feasibility to create tissue engineered venous scaffolds in vitro and in vivo. In this study we investigated the use of tissue engineered constructs for ureteral replacement in a long term orthotopic minipig model. In many different projects well functional ureretal tissue was established using tissue engineering in animals with short-time follow up (12 weeks). Therefore urothelial cells were harvested from the bladder, cultured, expanded in vitro, labelled with fluorescence and seeded onto the autologous veins, which were harvested from animals during a second surgery. Three days after cell seeding the right ureter was replaced with the cell-seeded matrices in six animals, while further 6 animals received an unseeded vein for ureteral replacement. The animals were sacrificed 12, 24, and 48 weeks after implantation. Gross examination, intravenous pyelogram (IVP), H&E staining, Trichrome Masson's Staining, and immunohistochemistry with pancytokeratin AE1/AE3, smooth muscle alpha actin, and von Willebrand factor were performed in retrieved specimens., Results: The IVP and gross examination demonstrated that no animals with tissue engineered ureters and all animals of the control group presented with hydronephrosis after 12 weeks. In the 24-week group, one tissue engineered and one unseeded vein revealed hydronephrosis. After 48 weeks all tissue engineered animals and none of the control group showed hydronephrosis on the treated side. Histochemistry and immunohistochemistry revealed a multilayer of urothelial cells attached to the seeded venous grafts., Conclusions: Venous grafts may be a potential source for ureteral reconstruction. The results of so far published ureteral tissue engineering projects reveal data up to 12 weeks after implantation. Even if the animal numbers of this study are small, there is an increasing rate of hydronephrosis revealing failure of ureteral tissue engineering with autologous matrices in time points longer than 3 months after implantation. Further investigations have to prove adequate clinical outcome and appropriate functional long-term results.

Objective: Comorbidity and performance indices (CPIs) are useful tools to evaluate patient's risk of comorbidities and thus may guide clinical decision making regarding surgery or multimodal therapy approaches. Hence, the aim of the current study was to assess the predictive capacity of CPIs comprising the American Society of Anaesthesiologists (ASA)-score, the Charlson comorbidity index (CCI), the age-adjusted CCI (ACCI), and the Eastern Cooperative Oncology Group performance status (ECOG-PS) in patients with upper tract urothelial carcinoma (UTUC) who were treated with radical nephroureterectomy (RNU)., Methods and Materials: A total of 242 patients with UTUC underwent RNU without neoadjuvant chemotherapy between 1992 and 2012 at 3 German academic centers. Patients were stratified according to the pre-RNU CPIs dichotomized as ASA 1/2 vs .≥ 3, CCI 0 to 2 vs. > 2, ACCI 0 to 5 vs. > 5, and ECOG-PS 0 to 1 vs. > 1. We assessed the associations of CPIs with clinicopathologic features, as well as the prognostic effect on recurrence-free survival, cancer-specific survival (CSS), overall survival, and cancer-independent mortality (CIM), using univariable and multivariable Cox regression analyses., Results: Sixty-two patients (25.6%) had an ASA-score ≥ 3, 71 patients (29.3%) a CCI>2, 50 patients (20.7%) an ACCI > 5, and 122 (50.4%) patients an ECOG-PS > 1. The ASA-score (P = 0.001), CCI (P = 0.029), and the ECOG-PS (P < 0.001) were significantly associated with age. In addition, the ECOG-PS was associated with pelvicalyceal tumors (P = 0.012), and the CCI with preoperative hydronephrosis (P = 0.026). The median follow-up was 30 months. In Kaplan-Meier analyses, ACCI > 5 (P ≤ 0.025) and ECOG-PS > 1 (P ≤ 0.042) were associated with recurrence-free survival, CSS, and overall survival, and ASA-score ≥ 3 (P = 0.011) and ACCI > 5 (P = 0.006) with CIM. In multivariable analysis that adjusted for standard clinicopathologic parameters, an ECOG-PS > 1 was an independent predictor for CSS (hazard ratio = 1.89, P = 0.019), and an ASA-score ≥ 3 (hazard ratio = 1.86, P = 0.026) was a predictor for CIM., Conclusion: CPIs are easy assessable predictors for outcome in patients with UTUC who were treated with RNU. CPIs have carefully to be taken into account in patient counseling regarding operative decision making and multimodal treatment., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Hypospadias is the most common congenital abnormality of the lower urinary tract affecting one of 300 male newborns. More than 300 different surgical hypospadias repair techniques have been described. Currently, tubularized incised plate and meatal advancement and glansplasty integrated repair are the preferred techniques for distal hypospadias, whereas two-staged procedures are most frequently used in proximal forms. Success rates are high in the hands of dedicated surgeons, although studies on long-term results are sparse. The most frequent complications of hypospadias repairs include urethrocutaneous fistulas, meatal stenosis, and urethral strictures. Urological follow-up into puberty is warranted, as well as further studies with standardized reporting of long-term results and complications.

In 2008, urothelial carcinoma of the bladder (UCB) was the 8th most common cause of death in Germany. An increasing body of evidence suggests differences in the presentation and prognosis of UCB between genders. Large population-based and multi-institutional studies have found a higher incidence of UCB in men, while women treated with radical cystectomy (RC) have shown unfavorable outcomes compared to their male counterparts. Indeed, it is important to note that UCB incidence and outcomes have regional and country-specific variability. These distinct country and gender-specific differences must be considered in patient counseling, treatment decisions, and UCB management. This review summarizes the contemporary literature regarding the impact of gender on UCB outcomes, focusing on patients treated with RC in Germany. We evaluated the most current literature regarding gender-specific differences in UCB incidence, treatment patterns, and oncological outcomes, including pathological stage distribution and survival.

Circulating tumor cells (CTC) play a crucial role in the natural history of several malignancies and, thus, are the subject of intense research efforts. This review summarizes the most contemporary literature data regarding detection of CTC and their impact on the oncological prognosis of patients with urothelial carcinoma of the bladder (UCB). Despite the availability of different methods for CTC detection and isolation in the peripheral blood, the standardized and Food and Drug Administration-approved CellSearch® assay is currently the most commonly used system for CTC detection. The majority of studies did not find any association between presence of CTC and clinicopathologic features. However, CTC have been demonstrated to represent a strong, independent predictor for unfavorable oncological outcomes in UCB. Since the peripheral blood is an easily accessible source, CTC represent a promising biomarker to effectively monitor early disease progression and therapy response in the near future. CTC hold the potential to individualize patient counseling regarding the optimal timing of radical surgery or bladder-sparing treatment as well as multimodal therapies.

Objective: To evaluate the outcome of holmium laser enucleation of the prostate (HoLEP) in the known presence of prostate cancer (PCa) and concomitant lower urinary tract symptoms (LUTS)., Patients and Methods: We retrospectively identified 62 patients who underwent HoLEP for LUTS in the known presence of PCa at our center. Perioperative data were assessed including complications, functional outcomes, and quality of life (QoL). Giving respect to different disease characteristics, patients were stratified according to treatment strategy setting into palliative (I), radiation (II), and surveillance (III) groups and compared accordingly., Results: Median follow-up (FU) of the entire study cohort was 27 months (range 2-65 mos). Medians of functional parameters (International Prostate Symptom Score): 18.5 vs 4.5, QoL: 4 vs 1, maximal flow rate: 9.0 vs 18.8 mL/s and residual urine: 100 vs 0 mL, all P<0.05) improved significantly in all groups. Perioperative complications were low and without any statistically significant difference between the groups. Postoperatively, voiding was successful in 90.3% of all patients; at last FU, 17% had some degree of urinary incontinence. Treatment strategy groups showed comparable functional outcomes after HoLEP., Conclusion: In the presence of PCa and LUTS, HoLEP represents a feasible, safe, and effective treatment option for patients unfit or without indication for radical prostatectomy. This applies as well in a palliative situation of advanced, obstructive PCa as for patients with LUTS who are scheduled for radiation therapy or surveillance in presumably indolent disease.

Despite advances in the surgical and medical treatment for urothelial carcinoma of the bladder (UCB), there have only been limited improvements in disease-specific mortality rates over the past decades. Lymph node dissection (LND) during radical cystectomy is an integral part of the treatment for muscle-invasive and high-risk UCB. LND may detect and remove lymph node (LN) metastasis and thus guide patient counseling and decision making regarding additional treatment decisions. In addition, LND may improve survival in patients both with and without LN metastasis. In this non-systematic review article, we discuss benefits and risks of LND, the role of limited versus extended LND and the dilemma of preoperative LN staging.

Background: We assessed the association of serine protease inhibitor Kazal type I (SPINK1) expression with clinicopathologic outcomes in urothelial carcinoma of the bladder (UCB) patients treated with radical cystectomy (RC)., Materials and Methods: Tissue microarrays comprising 438 consecutive UCB patients treated with RC between 1988 and 2003 and 62 cases of normal urothelium controls were evaluated for SPINK1 protein expression by immunohistochemistry (IHC). Semiquantitative evaluation was performed by 2 pathologists blinded to clinical outcomes (loss of expression: <50% cells or intensity 0-2)., Results: In normal urothelium, SPINK1 expression was noted in umbrella cells of 32 of 62 controls (52%); 254 RC patients (57.9%) exhibited loss of SPINK1 expression. Loss of SPINK1 expression was significantly associated with higher pathologic stages (P = 0.002) and presence of lymph node metastasis (P = 0.04). At a median follow-up of 130 months (IQR: 98.4), loss of SPINK1 expression was associated with an increased risk of disease recurrence (P = 0.02) and cancer-specific mortality (P = 0.03). On multivariable analysis that adjusted for the effects of standard clinicopathologic parameters, SPINK1 was not an independent predictor of disease recurrence (P = 0.09) or cancer-specific mortality (P = 0.12)., Conclusions: Over half of UCB patients treated with RC exhibit loss of SPINK1 expression. Loss of SPINK1 correlates with features of biologically aggressive UCB. Although SPINK1 expression did not have independent prognostic value in RC patients, it may serve as a biomarker for tumor staging and may be useful as an adjunct in clinical decision-making., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background and Purpose: Only few comparative reports about different urethroplasties have been published, addressing success rate (SR), adverse events (AE), and quality of life (QoL). Our purpose was to evaluate SR, AE, and QoL in a contemporary cohort of patients undergoing urethroplasty in the short-term follow-up (FU)., Patients and Methods: Between December 2008 and June 2010, 205 patients underwent urethroplasty for anterior urethral strictures at our institution. A standardized questionnaire was sent to all patients. The primary end point was SR. Secondary end points were AE and QoL. To assess the risk of SR, the Kaplan-Meier method and log-rank test were used. To assess risk factors for urethral stricture recurrence (SRec), univariable Cox regression analysis was used., Results: Overall, 140 (68%) patients responded to our questionnaire and were used for analysis. Of these 9%, 85%, and 6% were treated by excision and primary anastomosis (EPA), buccal mucosa graft urethroplasty (BMGU), and mesh graft urethroplasty (MGU), respectively. At 10 months of FU, SR was 87.5%. SRs of EPA, BMGU, and MGU were 100% (n=13/13), 85.7% (n=102/119), and 87.5% (n=7/8), with no significant differences between the groups. In univariable analysis, ≥ 2 vs 1 previous urethroplasties showed a trend toward a reduced SR (hazard risk 2.95; P=0.057). Streaking the urethra (P=0.024) and penile curvature (P=0.026) were significantly more often associated with MGU compared with EPA and BMGU. Postoperative total median (mean) scores were 3.5 (4.8) for the International Consultation on Incontinence Questionnaire Male lower urinary tract symptoms, 15 (15.2) for the International Index of Erectile Function, and 80 (73) for EuroQol visual analogue score; there was no difference between urethroplasty types., Conclusion: In the short-term FU, urethroplasty demonstrates an excellent SR. Specific SRs of EPA, BMGU, and MGU seem comparable. Despite significant differences in AE, patient reported QoL is high with no difference between the applied techniques.

Stroke patients are prone to life-threatening bacterial pneumonia. Previous experimental stroke studies have demonstrated that preventive antibiotic treatment (PAT) improves outcome compared with placebo treatment, which however does not model the clinical setting properly. Here we investigate whether PAT is superior to the current clinical 'gold standard' for treating poststroke infections. Therefore, we modeled stroke care according to the current stroke guidelines recommending early antibiotic treatment after diagnosing infections. To reliably diagnose pneumonia in living mice, we established a general health score and a magnetic resonance imaging protocol for radiologic confirmation. Compared with standard treatment after diagnosis by these methods, PAT not only abolished pneumonia successfully but also improved general medical outcome. Both, preventive and standard antibiotic treatment using enrofloxacin improved survival in a similar way compared with placebo treatment. However, in contrast to standard treatment, only PAT improved functional outcome assessed by gait analysis. In conclusion, standard and preventive treatment approach reduced poststroke mortality, however at the cost of a worse neurologic outcome compared with preventive approach. These data support the concept of PAT for treating patients at risk for poststroke infections and warrant phase III trials to prove this concept in clinical setting.

Buccal mucosa is the ideal material for urethral reconstruction because it is easy to harvest, is accustomed to permanent moisture and can be used at any location in the urethra. Stricture length and local conditions of the urethra have to be considered to decide which technique is required to reconstruct the urethra. Open urethroplasty with buccal mucosa has a success rate over 85% and should be used after unsuccessful internal urethrotomy and primarily in longer strictures.

Despite its limited regenerative capacity, the central nervous system (CNS) shares more repair mechanisms with peripheral tissues than previously recognized. Scar formation is a ubiquitous healing mechanism aimed at patching tissue defects via the generation of fibrous extracellular matrix (ECM). This process, orchestrated by stromal cells, can unfavorably affect the capacity of tissues to restore function. Vascular mural cells have been found to contribute to scarring after spinal cord injury. In the case of stroke, little is known about the responses of pericytes (PCs) and stromal cells. Here, we show that capillary PCs are rapidly lost after cerebral ischemia in both experimental and human stroke. Coincident with this loss is a massive proliferation of resident platelet-derived growth factor receptor beta (PDGFRβ)(+) and CD105(+) stromal cells, which originate from the neurovascular unit and deposit ECM in the ischemic mouse brain. The presence of PDGFRβ(+) stromal cells demarcates a fibrotic, contracted, and macrophage-laden lesion core from the rim of hypertrophic astroglia in both experimental and human stroke. We suggest that a previously unrecognized population of CNS-resident stromal cells drives a dynamic process of scarring after cerebral ischemia, which appears distinct from the glial scar and represents a novel target for regenerative stroke therapies.

Local and peripheral immune responses are activated after ischemic stroke. In our present study, we investigated the temporal distribution, location, induction, and function of regulatory T cells (Tregs) and the possible involvement of microglia, macrophages, and dendritic cells after middle cerebral artery occlusion (MCAO). C57BL/6J and Foxp3(EGFP) transgenic mice were subjected to 30 minutes MCAO. On days 7, 14, and 30 after MCAO, Tregs and antigen presenting cells were analyzed using fluorescence activated cell sorting multicolor staining and immunohistochemistry. A strong accumulation of Tregs was observed on days 14 and 30 in the ischemic hemisphere accompanied by the elevated presence and activation of microglia. Dendritic cells and macrophages were found on each analyzed day. About 60% of Foxp3(+) Tregs in ischemic hemispheres were positive for the proliferation marker Ki-67 on days 7 and 14 after MCAO. The transfer of naive CD4(+) cells depleted of Foxp3(+) Tregs into RAG1(-/-) mice 1 day before MCAO did not lead to a de novo generation of Tregs 14 days after surgery. After depletion of CD25(+) Tregs, no changes regarding neurologic outcome were detected. The sustained presence of Tregs in the brain after MCAO indicates a long-lasting immunological alteration and involvement of brain cells in immunoregulatory mechanisms.

Upper urinary tract urothelial carcinoma (UTUC) is an uncommon but potentially lethal disease. Accurate risk stratification remains a challenge owing to the difficulty of clinical staging. Identification of risk factors may lead to individualized treatment and patient counselling and holds the potential to improve outcome. A non-systematic PubMed/Medline literature research was performed to identify and summarize clinical and pathological risk factors and urine-based markers which are associated with clinical outcome. Although knowledge of potential prognostic factors has improved over the last 5 years the overall evidence on UTUC risk factors remains limited and prospective, randomized trials are still missing. Radical nephroureterectomy is currently standard treatment for high-grade and muscle invasive UTUC. Several clinical and pathological factors (e.g. stage, grade, age, hydronephrosis, lymphovascular invasion, tumor necrosis and architecture, delay between diagnosis and surgery) were identified to be associated with outcome. Urinary cytology and fluorescence in-situ hybridization are the most commonly used urinary markers. Prospective randomized controlled trials are urgently needed to identify new risk factors and assess the efficacy. The incorporation of such prognosticators into multivariable prediction models may help to guide decision-making with regard to type of treatment, performance of lymphadenectomy and consideration of neoadjuvant or adjuvant systemic therapy.

In the vast majority of cases the terminal ileum is used for incontinent or continent bladder substitution. However, in irradiated patients the use of ileum segments or the ileocecal reservoir is associated with an increased risk of early and late complications. For this reason these patients should be treated with a transverse conduit or pouch as the method of choice if urinary diversion is indicated. The superior outcome of this high urinary diversion is due to the use of non-irradiated segments of the colon and ureter. The lack of experience in large bowel surgery by today's urologists should be compensated by training or referral of these high risk patients to a specialized center.

Ameliorating stroke induced neurological deficits is one of the most important goals of stroke therapy. In order to improve stroke outcome, novel treatment approaches as well as animal stroke models predictive for the clinical setting are of urgent need. One of the main obstacles in experimental stroke research is measuring long-term outcome, in particular in mouse models of stroke. On the other hand, assessing functional deficits in animal models of stroke is critical to improve the prediction of preclinical findings. Automated gait analysis provides a sensitive tool to examine locomotion and limb coordination in small rodents. Comparing mice before and 10 days after experimental stroke (60 min MCAo) we observed a significant decrease in maximum contact area, stride length and swing speed in the hind limbs, especially the contralateral one. Mice showed a disturbed interlimb coordination represented by changes in regularity index and phase dispersion. To assess whether gait analysis is applicable to assess improvements by neuroprotective compounds, we applied a model calculation and approached common statistical problems. In conclusion, gait analysis is a promising tool to assess mid- to long-term outcome in experimental stroke research., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Two IgM monoclonal antibodies (MAbs), Y6F5 and Y13F9, were selected during a screening of clones obtained immunising BALB/c mice with purified envelop proteins of the A/Sydney/5/97 (H3N2) IVR108 influenza strain. These MAbs recognised avian glycans on the haemagglutinin (HA) of the virus. This broad recognition allowed these MAbs to be used as enzyme-labelled secondary antibody reagents in a strain specific enzyme-linked immunosorbent assay (ELISA) in combination with a capture MAb that recognised and allowed the quantitation of the strain specific HA protein present in an egg-produced influenza vaccine. Advantage was taken of these MAbs to develop a universal ELISA in which the MAbs were used both as capture antibody and as enzyme-labelled secondary antibody to detect and quantify the HA protein of any egg-derived influenza vaccine. These avian-glycan specific IgM MAbs may prove to be particularly useful for determining the HA concentration in monovalent egg-derived pandemic influenza vaccines, in which the HA concentration may be lower than 5μg/ml. The HA detection limit in the ELISA assays developed in this study was 1.9μg/ml, as opposed to the 5μg/ml quantitation limit generally accepted for the standard single-radial-immunodiffusion (SRID) assay, the approved technique for quantifying HA content in influenza vaccines. These ELISAs can also be used to quantify influenza HA formulated with emulsion-based or mineral salt adjuvants that could interfere with HA measurement by the SRID assay., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: A key prerequisite for urinary continence after radical prostatectomy (RP) is the functional length of the urethral sphincter and the stabilisation of its anatomic position within the pelvic floor., Objective: We describe our modified surgical technique for full functional-length urethra (FFLU) preservation during RP., Design, Setting, and Participants: We analysed 691 consecutive patients who underwent RP over a 12-mo period (285 without and 406 with the FFLU technique)., Surgical Procedure: The full functional urethra length was preserved by performing an individualised apical preparation strictly along anatomic landmarks, respecting the individual length of the intraprostatically located proportion of the urethral sphincter. Anatomic fixation of the sphincter was reached by a thorough preservation of the pelvic floor and anatomic restoration of the Mueller's ligaments., Measurements: Continence rates were assessed at 7 d and 12 mo after removal of the catheter. Continence was defined as the use of no pads and no urinary leakage., Results and Limitations: The continence rates were 50.1% and 30.9% 1 wk after catheter removal (p < 0.0001) and 96.9% and 94.7% (p=0.59) at 12 mo after surgery in patients operated on with the FFLU technique versus the non-FFLU technique. In multivariate regression analysis, only the surgical technique correlated significantly with the continence status 1 wk after catheter removal. Neither the overall positive surgical margin rates nor the number of positive margins at the urethral resection border differed significantly between the FFLU and non-FFLU groups (13.6% and 0.5% vs 14.9% and 1.3%, respectively). Although the patients' baseline characteristics were similar in the two surgical groups, the patients were not preoperatively randomised, and the number of patients in the groups was asymmetric., Conclusions: The combination of an FFLU preparation and improved preservation of the anatomic fixation of the urethral sphincter complex resulted in significantly increased early urinary continence results., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Foot-and-mouth disease virus (FMDV), one of the most dangerous viruses affecting cloven-hoofed animals, comprises seven serotypes that do not mutually cross-protect, with a total of about 80 subtypes. The Middle East is an FMD-endemic region, with repeated FMD outbreaks and In spite of its compulsory vaccination policy in Israel, outbreaks occur repeatedly. In order to compare the Israeli isolates, the complete viral VP1 genes of representative viruses isolated during the major outbreaks from 1989 to 2007 were sequenced and subjected to phylogenetic analysis, which showed that each outbreak was initiated by introduction of a new virus lineage and not by endemic and resident viruses. The differences between the nucleotide sequences of the viruses from the various outbreaks were too big to fit a model of outbreaks caused by endemic virus. Based on this approach, it was revealed that the 2002 outbreak was originated by viruses that circulated in the Arabian peninsula in 1997-1998., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Stroke is among the most frequent causes of death and adult disability, especially in highly developed countries. However, treatment options to date are very limited. To meet the need for novel therapeutic approaches, experimental stroke research frequently employs rodent models of focal cerebral ischaemia. Most researchers use permanent or transient occlusion of the middle cerebral artery (MCA) in mice or rats. Proximal occlusion of the middle cerebral artery (MCA) via the intraluminal suture technique (so called filament or suture model) is probably the most frequently used model in experimental stroke research. The intraluminal MCAO model offers the advantage of inducing reproducible transient or permanent ischaemia of the MCA territory in a relatively non-invasive manner. Intraluminal approaches interrupt the blood flow of the entire territory of this artery. Filament occlusion thus arrests flow proximal to the lenticulo-striate arteries, which supply the basal ganglia. Filament occlusion of the MCA results in reproducible lesions in the cortex and striatum and can be either permanent or transient. In contrast, models inducing distal (to the branching of the lenticulo-striate arteries) MCA occlusion typically spare the striatum and primarily involve the neocortex. In addition these models do require craniectomy. In the model demonstrated in this article, a silicon coated filament is introduced into the common carotid artery and advanced along the internal carotid artery into the Circle of Willis, where it blocks the origin of the middle cerebral artery. In patients, occlusions of the middle cerebral artery are among the most common causes of ischaemic stroke. Since varying ischemic intervals can be chosen freely in this model depending on the time point of reperfusion, ischaemic lesions with varying degrees of severity can be produced. Reperfusion by removal of the occluding filament at least partially models the restoration of blood flow after spontaneous or therapeutic (tPA) lysis of a thromboembolic clot in humans. In this video we will present the basic technique as well as the major pitfalls and confounders which may limit the predictive value of this model.

There are numerous procedures available for surgical management of a urethral stricture. Establishing the correct indication for performing a specific surgical method requires a great deal of experience. Nonetheless, postoperative complications are never avoidable. Secondary intervention after an unsuccessful primary operation poses particular challenges to the surgeon. This article provides an overview of the open surgical techniques currently employed. It also highlights factors that should be considered to minimize postoperative complications. The concluding discussion describes the individual surgical procedures suitable for revision surgery depending on the previous approach.

Infectious diseases are the most common medical complication after cerebral ischemia, inpairing both the neurological and the general medical outcome. The most frequent infectious complications are bacterial pneumonia and urinary tract infections. There is a growing body of evidence that a secondary immunosuppressive state accounts for the increased risk of infection following stroke. Infections do not only have an important impact on outcome after stroke but also are known risk factors for stroke. Thus, suitable models for investigating the relation between infections and stroke are urgently needed. Elucidating the underlying mechanisms might facilitate the development of new therapeutic strategies and improve patient outcome. Here we present recent insights into the relationship between infections and stroke, based on experimental models of post-stroke infection. In addition we give a brief overview of models that explore the impact on stroke of preceding infections.

High-flow priapism caused by a pathological arterial influx to the cavernous bodies was first described by F.B. Burt in 1960. The pathophysiological differentiation of high- and low-flow priapism was developed in 1983. The development of diagnostic tools for differentiation of different forms of priapism and the progress in the therapy of high-flow priapism from arterial ligation to supraselective embolization is presented.

High flow priapism is mainly caused by traumatic arteriocavernous fistulas. The standard therapy is a transcatheter embolization of the fistula. This study analyzes the combined approach of arteriography and color Doppler ultrasound during the embolization procedure. During the arteriography procedure, a perineal color Doppler ultrasound examination of the fistula was performed to achieve an optimal positioning of the catheter tip in the fistula with a minimum of radiation exposure. To visualize the correct localization, ultrasound contrast medium or saline solution was injected through the catheter. The flow-pattern of the contrast medium allowed evaluation of the successful occlusion of the fistula and preservation of the unaffected penile arteries. In six patients (unilateral fistula: three, bilateral fistulas: three) with a posttraumatic high-flow priapism, this technique was performed for embolization of the fistulas. A total of nine embolization sessions were performed. Only one case required a second session due to dislocation of a microcoil. In all cases, the priapism disappeared immediately after the final session while erectile function was restored within 4 weeks after embolization. The combined approach of x-ray and ultrasound imaging facilitates the supraselective embolization of the arteriocavernous fistula, leading to an optimal success rate, while reducing the radiation exposure and the applied dose of contrast medium.

Poppy seeds contain morphine in different amounts. Reported concentrations are up to 294 mg morphine/kg poppy seeds. Since penalties based on Street Traffic Law (parapgraph 24a StVG) in Germany (administrative offence) require definitive proof of morphine in blood samples, and the "Grenzwertkommission" in consultation with the Ministry of Transportation recommended a threshold of free morphine of 10 ng/mL, the question arose whether the consumption of poppy seeds can lead to a blood concentrations equal or higher than 10 ng/mL of free morphine. Therefore, five volunteers ate poppy seed products (50 mg morphine/kg poppy seeds). In urine, all on-site tests were enzyme immunologically positive for opiates and were positive to morphine by GC/MS. All the blood samples were negative to morphine by EIA and to free morphine by GC/MS. However, after hydrolysis, morphine was detected by GC/MS in all cases. Accordingly, in Germany, penalties based on parapgraph 24a StVG are not likely to cause road users any concerns should they have consumed poppy seeds. Driver Licensing Authorities, however, should be advised of this problem to avoid unjustified legal measures.

HIV gp41(24-157) unfolds cooperatively over the pH range of 1.0-4.0 with T(m) values of > 100 degrees C. At pH 2.8, protein unfolding was 80% reversible and the DeltaH(vH)/DeltaH(cal) ratio of 3.7 is indicative of gp41 being trimeric. No evidence for a monomer-trimer equilibrium in the concentration range of 0.3-36 micro m was obtained by DSC and tryptophan fluorescence. Glycosylation of gp41 was found to have only a marginal impact on the thermal stability. Reduction of the disulfide bond or mutation of both cysteine residues had only a marginal impact on protein stability. There was no cooperative unfolding event in the DSC thermogram of gp160 in NaCl/P(i), pH 7.4, over a temperature range of 8-129 degrees C. When the pH was lowered to 5.5-3.4, a single unfolding event at around 120 degrees C was noted, and three unfolding events at 93.3, 106.4 and 111.8 degrees C were observed at pH 2.8. Differences between gp41 and gp160, and hyperthermostable proteins from thermophile organisms are discussed. A series of gp41 mutants containing single, double, triple or quadruple point mutations were analysed by DSC and CD. The impact of mutations on the protein structure, in the context of generating a gp41 based vaccine antigen that resembles a fusion intermediate state, is discussed. A gp41 mutant, in which three hydrophobic amino acids in the gp41 loop were replaced with charged residues, showed an increased solubility at neutral pH.

The purpose of this study was to evaluate the diagnostic value of 3-D ultrasound with surface rendering in stones located in different parts of the urinary tract. A total of 55 patients with urinary stones were examined by transabdominal 3-D ultrasound (US) with surface rendering of the stone. In calculi of the prevesical ureter, bladder and prostatic urethra, transrectal 3-D endosonography was performed as well. The radiographic shape and the chemical analysis of the stone were correlated to the sonographic findings. The localization of the stone was: renal 23, ureteral 26, vesical 5 and urethral 1. All stones could be identified by 3-D US. Surface rendering produced useful results in stones > 2 cm with a 3.5-MHz transabdominal scanning probe, and in all stones that were accessible with a 7.5-MHz transrectal scanning probe. In stones < 1 cm, endoUS with surface rendering provides more information on the structure of the stone than plain radiography, but there is no correlation between surface and chemical analysis.