bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative effects of T‐type and L‐type Ca2+‐antagonists against noradrenaline‐induced contractions of human vas deferens
Authors: Amobi Nnaemeka , Guillebaud John , Smith Christopher H. 
Published: December 2009

OBJECTIVETo investigate the effects of the relatively selective T‐type Ca2+‐antagonists, mibefradil and flunarizine, and the L‐type Ca2+‐antagonist, nifedipine, on the contractions of longitudinal and circular muscles of human vas deferens, to elucidate the possible involvement of T‐type voltage‐gated Ca2+channels (VOCs) in the contractile function of the tissue.MATERIALS AND METHODSHuman vas deferens specimens from elective vasectomies were cut into strips of longitudinal muscle or transversely into rings of circular muscle. These were set up for tension recording and superfused with Krebs’ medium (36° C). Contractions were evoked by noradrenaline or high [K+]o(in the presence of the L‐type Ca2+agonist, FPL 64176) and the effects of Ca2+antagonists were determined.RESULTSNoradrenaline (0.1–100 µmol/L) evoked rhythmic and tonic contractions of longitudinal and circular muscles, which were potently inhibited by nifedipine (≤0.1 µmol/L). Mibefradil (1–10 µmol/L) inhibited the contractions but was comparatively more effective in longitudinal than circular muscle. Flunarizine was ineffective except against contractions to low concentrations of noradrenaline. The drugs’ potencies as antagonists of L‐type VOCs were determined against contractions to high K+ (120 mmol/L in the presence of FPL 64176, 1 µmol/L). The contractions in longitudinal and circular muscle had different times to peak and decline but were inhibited comparably by nifedipine (50% inhibitory concentration, IC50, longitudinal and circular muscle, ≈2 nmol/L) or by mibefradil (IC50longitudinal muscle, 1.1 µmol/L; circular muscle, 2.4 µmol/L) and were less sensitive to flunarizine (up to 30 µmol/L).CONCLUSIONThese results indicate that noradrenaline‐induced contractions of human vas deferens depend primarily on nifedipine‐sensitive L‐type VOCs, as opposed to mibefradil/flunarizine‐sensitive T‐type VOCs. The effects of mibefradil and flunarizine, at concentrations found to be effective against noradrenaline‐induced contractions, involve the blockade of L‐type VOCs. The modest differential effect of mibefradil in longitudinal and circular muscle is discussed in relation to factors that modulate activation and drug‐sensitivity of L‐type VOCs.
Management of urethral recurrence after orthotopic urinary diversion
Authors: Taylor Jennifer M. , Spiess Philippe E. , Kassouf Wassim , Munsell Mark F. , Kamat Ashish M. , Dinney Colin P.N. , Grossman H. Barton , Pisters Louis L. 
Published: December 2009

Study Type – Therapy (case series) Level of Evidence 4OBJECTIVETo evaluate our experience with urethral recurrences in patients treated by radical cystectomy(RC) and orthotopic neobladder urinary diversion for carcinoma of the bladder.PATIENTS AND METHODSWe retrospectively reviewed the records of patients treated with RC and orthotopic urinary diversion between January 1980 and July 2004.RESULTSIn all, 260 patients underwent RC with a Studer or Hautmann orthotopic urinary diversion; the median (range) follow‐up was 5.1 (0–15.6) years. Six patients (2.3%) developed local recurrence of urothelial cancer (UC) within the urethra after this treatment. The median (range) time to presentation with recurrence after RC was 2.4 (0.7–3.6) years for pT1‐4 UC. Recurrences were treated with various methods, including transurethral resection, urethrectomy with conversion of neobladder to continent catheterizable diversion, and chemotherapy. At the last follow‐up, four of these six patients were alive without disease, one was alive with disease, and one had died from disease.CONCLUSIONSIn our experience, local recurrences involving the urethra are infrequent. Complete surgical excision can provide a good outcome. Neoadjuvant chemotherapy should be considered for recurrences with adverse clinicopathological features.
Chronic inhibition of nitric‐oxide synthase induces hypertension and erectile dysfunction in the rat that is not reversed by sildenafil
Authors: Gur Serap , Kadowitz Philip J. , Gurkan Levent , Chandra Surabhi , DeWitt Sharon Y. , Harbin Andrew , Sikka Suresh C. , Agrawal Krishna C. , Hellstrom Wayne J.G. 
Published: December 2009

Study Type – Aetiology (case control) Level of Evidence 3bOBJECTIVETo evaluate the effect of N(G)‐nitro‐l‐arginine methyl ester (L‐NAME)‐induced hypertension (HT) on erectile function in the rat and determine if the phosphodiesterase (PDE)‐5 inhibitor, sildenafil, can reverse the effects of nitric oxide (NO) deficiency, as HT is a risk factor for erectile dysfunction (ED) and the NO synthase (NOS) inhibitor L‐NAME induces NO‐deficient HT.MATERIALS AND METHODSThirty‐six adult Sprague‐Dawley male rats were divided into three groups, i.e. a control, L‐NAME‐HT (40 mg/rat/day in the drinking water for 4 weeks), and sildenafil‐treated L‐NAME‐HT (1.5 mg/rat/day sildenafil, by oral gavage concomitantly with L‐NAME). The erectile response expressed as a ratio of intracavernosal pressure (ICP)/mean arterial pressure (MAP), evaluated after electrical stimulation of the right cavernous nerve. The isometric tension of corpus cavernosum smooth muscle (CCSM) was measured in organ‐bath experiments. NOS expression was determined immunohistochemically for neuronal (n)NOS and by Western blot analysis for endothelial (e) and inducible (i) NOS protein. cGMP levels were evaluated by enzyme‐linked immunosorbent assay.RESULTSThe erectile response was diminished in the HT group. Nitrergic and endothelium‐dependent relaxation was reduced, while the relaxation response to sodium nitroprusside and contractile response to phenylephrine were not altered in CCSM from L‐NAME‐treated rats. HT rats showed decreased expression of nNOS, whereas eNOS and iNOS protein expression was increased. Sildenafil partly restored endothelial and molecular changes in CCSM from HT rats, but did not reverse the decreased erectile response, even as cGMP levels returned to normal levels.CONCLUSIONSSildenafil treatment did not correct the ED in L‐NAME‐treated HT rats. Under sustained high blood pressure, up‐regulation of PDE5 expression failed to reverse the depletion of neuronal NO and/or impaired nNOS activity. However, endothelium‐dependent relaxation was restored. Drug targeting of neuronal dysfunction might delay the onset of ED in HT.
Chronic partial bladder outlet obstruction does not impair erectile function in male rats
Authors: Aldridge Nicholas , Kim Hyun Woo , Motamedi Amir , Rajasekaran Mahadevan 
Published: December 2009

OBJECTIVETo evaluate, in a well‐controlled study, the effect of surgically induced partial bladder outlet obstruction (PBOO) on male erectile function in a rat model.MATERIALS AND METHODSPBOO was created in 17 adult male Sprague‐Dawley rats by partial ligation of the proximal urethra. Sham‐operated and PBOO rats were evaluated for urodynamic and erectile function at 4–8 weeks after surgery. Erectile responses to electrical field stimulation (EFS) to the major pelvic ganglion, and to erectogenic agents (1,1‐diethyl‐2‐hydroxy‐2‐nitroso‐hydrazine, DEA‐NO, and Y‐27632) were evaluated and the area under the curve (AUC, a product of the intracavernous pressure and duration) was used to denote the erectile response.RESULTSExperimental PBOO in rats significantly increased the mean (sem) bladder weight, to 256 (25) mg in PBOO rats vs 123 (24) mg in sham controls, and the voiding frequency to 1.01 (0.1) voids/min vs 0.72 (0.14) voids/min in sham controls (P < 0.05). There was no significant difference between the erectile response to EFS, with a mean AUC in sham control rats at 1.5, 3.0 and 4.5 V of 2603 (372), 3200 (332) and 3357 (166), respectively, vs 2273 (183), 3794 (211) and 4177 (306) in PBOO rats (P > 0.05); or to the erectogenic agents, the AUC for DEA‐NO being 9000 (975) in PBOO rats vs 13 201 (2756) in sham controls, and the AUC for Y‐27 632 being 44 915 (2462) and 45 907 (7408), respectively (P > 0.05). There was greater immunoreactivity to RhoA in bladder and penile tissues of PBOO than control rats.CONCLUSIONPBOO does not affect erectile function in rats. Additional mechanisms or pathways might be involved in lower urinary tract symptom‐related erectile dysfunction in humans.
Lymph node mapping in patients with bladder cancer undergoing radical cystectomy and lymph node dissection to the level of the inferior mesenteric artery
Authors: Jensen Jørgen B. , Ulhøi Benedicte P. , Jensen Klaus M.‐E. 
Published: December 2009

Study Type – Therapy (case series) Level of Evidence 4OBJECTIVETo evaluate extended lymph node dissection (LND) as a nodal staging tool in the treatment of invasive carcinoma of the urinary bladder and to suggest a reasonable proximal limit of the dissection.PATIENTS AND METHODSIn all, 170 patients underwent radical cystectomy with extended LND up to the level of the inferior mesenteric artery. Specimens were evaluated as 13 separate packages from pre‐designated anatomical locations. The number of LNs and presence of positive LNs (LN+) at each location was prospectively registered.RESULTSThe median (range) number of LNs removed was 24 (6–62). In all, 25.3% of the patients had LN+. The median (range) number of LN+ was 2 (1–20). Advanced T‐stage was correlated with a higher risk of LN+ but not to the specific location of the LN+. Two patients had LN+ above the common iliac bifurcation with no LN+ more distally located within the pelvic region. All other patients with LN+ above the common iliac bifurcation had more distally located LN+. There were no skip lesions to LNs above the aortic bifurcation.CONCLUSIONSExtended LND above the common iliac bifurcation including the presacral area provides a more accurate LN staging compared with a standard pelvic LND. Extending the limits above the aortic bifurcation is not necessary from a staging perspective.
Efficacy, tolerability and safety of propiverine hydrochloride in comparison to oxybutynin in children with urge incontinence due to overactive bladder: Results of a multicentre observational cohort study
Authors: Alloussi Schahnaz , Mürtz Gerd , Braun Reinhard , Gerhardt Ulrich , Heinrich Martina , Hellmis Eva , Horn Werner , Marschall‐Kehrel Daniela , Niklas Kurt , Raabe Michael , Rößler Thomas , Seibt Beatrix , Siemer Stefan , Schultz‐Lampel Daniela , Walter Heiko , Wiedeking Burkhard , Alloussi Saladin , Bock Paul , Strugala Gerhard , Madersbacher Helmut 
Published: December 2009

Study Type – Therapy (observational cohort) Level of Evidence 2bOBJECTIVETo compare, in a retrospective observational cohort study, the efficacy, tolerability and safety of propiverine and oxybutynin in children with urge incontinence (UI) due to overactive bladder.PATIENTS AND METHODSMedical records were scrutinized for children with UI. As a primary efficacy outcome variable the achievement of continence after treatment with variable doses of propiverine or oxybutynin was assessed. Weekly UI episodes and daily voiding frequency were evaluated as secondary efficacy outcomes. Tolerability was evaluated by the rate of adverse events, adverse drug reactions caused by antimuscarinics and premature treatment termination.RESULTSAt 16 study centres, 621 children aged 5–14 years with UI due to overactive bladder were enrolled. After anticholinergic treatment (437 propiverine, 184 oxybutynin) continence was achieved in 61.6% and 58.7% of the patients after 186 and 259 days, respectively. There were clinically relevant improvements in voiding frequency across treatment groups. Daily doses of propiverine were markedly below the recommendations (0.54 vs 0.8 mg/kg body weight), daily doses of oxybutynin were according to the recommendations (0.31 vs 0.2–0.4 mg/kg body weight) at treatment initiation. There was a significantly more favourable tolerability to propiverine than oxybutynin for the overall rate of adverse events (3.9% vs 16.3%, odds ratio 4.813), adverse drug reactions caused by propiverine or oxybutynin (2.8% vs 9.2%) and premature treatment termination due to adverse drug reactions (1.6% vs 4.4%).CONCLUSIONPropiverine and oxybutynin are effective in children with UI due to overactive bladder. Sufficient treatment periods of at least 2, preferably 3–4, months are the crucial factors for a successful treatment. The tolerability profile of propiverine is better than for oxybutynin.
Treatment failure and clinical progression after salvage therapy in men with biochemical recurrence after radical prostatectomy: radiotherapy vs androgen deprivation
Authors: Song Cheryn , Kim Young Seok , Hong Jun Hyuk , Kim Choung‐Soo , Ahn Hanjong 
Published: December 2009

Study Type – Therapy (case series) Level of Evidence 4OBJECTIVETo compare the outcomes between salvage radiotherapy (RT) and androgen‐deprivation therapy (ADT), to investigate factors determining clinical progression (CP) in men with prostate cancer.PATIENTS AND METHODSThe study comprised 121 patients with biochemical recurrence while on follow‐up by prostate‐specific antigen (PSA) measurement, without adjuvant therapy after radical prostatectomy, received RT (45) or ADT (76). Failure after salvage therapy was defined as a PSA level of >0.2 ng/mL. Clinical, pathological and treatment factors were analysed.RESULTSThe clinicopathological characteristics were similar between the RT and ADT groups except that men in the RT group were younger (61.4 vs 65.4 years). After ADT, salvage failed in 10 (13%) after a mean (sd) of 18.5 (4.5) months of treatment, and 6.7 months after salvage failed all patients progressed clinically. After RT, salvage failed in 22 (49%) after 30.7 (5.2) months of response. Upon RT failure, all patients received ADT, after which in three (14%) patients the treatment failed again after 20.1 months of treatment and progressed to CP after 6.5 months, while in the remaining 19 (86%) patients the PSA level remained undetectable for 37.6 (7.7) months. On multivariate analysis, pathological stage (≥T3b) and Gleason grade 5 disease were independently prognostic of CP.CONCLUSIONSalvage RT alone and combined with subsequent ADT provided PSA control in most patients, significantly increasing CP‐free survival compared with initial ADT. Patients with a short PSA doubling time (<3 months) are at high risk of failed salvage treatment after RT, and initial ADT might be considered. Regardless of salvage method, advanced pathological stage and Gleason grade 5 were factors prognostic of CP.
The effect of gender on response to bacillus Calmette‐Guérin therapy for patients with non‐muscle‐invasive urothelial carcinoma of the bladder
Authors: Boorjian Stephen A. , Zhu Fang , Herr Harry W. 
Published: December 2009

Study Type – Therapy (case series) Level of Evidence 4OBJECTIVETo determine the influence of gender on the outcome of patients with high‐risk non‐muscle‐invasive bladder cancer treated with intravesical bacille Calmette‐Guérin (BCG) therapy, as the role of hormone status in the pathogenesis of urothelial carcinoma and the response to treatment remains subject to debate.PATIENTS AND METHODSWe reviewed 1021 consecutive patients (756 men and 265 women) who were treated with induction BCG between 1978 and 2006 for multiple or recurrent high‐grade Ta, T1, and/or carcinoma in situ (CIS) bladder cancer. All patients had ≥5 years of follow‐up. The endpoints of initial response to BCG and the time to disease recurrence and progression were correlated with gender using Kaplan‐Meier methods and multivariate Cox regression models.RESULTSMen were significantly more likely to present with high grade (P = 0.003) tumours and with CIS (P < 0.001), while age and clinical stage at presentation were similar between men and women. There was no significant difference in the initial response to BCG by gender, as 593/756 (78.4%) men and 219/265 (82.6%) women had no evidence of disease at 6 months after BCG treatment (P = 0.14). The median time to recurrence after BCG therapy was also similar for men and women (20 vs 21 months, P = 0.51). Likewise, there was no evidence of a significant association between gender and the risk of disease progression after BCG therapy, such that the 5‐year estimated freedom from progression was 77% and 82%, respectively, for men and women (P = 0.08). Moreover, on a multivariate analysis controlling for patient age and tumour stage, grade and CIS, gender was not associated with the risk of recurrence (hazard ratio 0.94, 95% confidence interval 0.79–1.11; P = 0.44) or progression (1.18, 0.85–1.63; P = 0.33) after BCG. When the outcomes for women treated with BCG were stratified by age <50 years (the median age of menopause in the USA) vs ≥50 years, again there were no differences in the risk of tumour recurrence (P = 0.95) or progression (P = 0.35).CONCLUSIONThese data suggest that the outcomes of men and women with high risk non‐muscle‐invasive urothelial carcinoma treated with BCG are similar. As such, further studies are required to determine the clinical relevance of preclinical evidence that has suggested a potential role for sex steroids in the pathophysiology of bladder cancer.
Predicting individual outcomes after radical cystectomy: an external validation of current nomograms
Authors: Zaak Dirk , Burger Maximilian , Otto Wolfgang , Bastian Patrick J. , Denzinger Stefan , Stief Christian G. , Buchner Hannes , Hartmann Arndt , Wieland Wolf F. , Shariat Shahrokh F. , Fritsche Hans‐Martin 
Published: December 2009

Study Type – Prognosis (outcomes research) Level of Evidence 2cOBJECTIVETo determine whether published nomograms, i.e. The International Bladder Cancer Nomogram Consortium (IBCNC) and the Bladder Cancer Research Consortium (BCRC) statistical models for predicting disease recurrence and survival of patients after radical cystectomy, are feasible for routine use in intermediate‐volume institutions in Europe, as although these nomograms had high accuracy by internal validation tests, they stem from high‐volume centres and have not been validated elsewhere and thus their general applicability remains unproven.PATIENTS AND METHODSWe externally validated the published nomograms. Information about treatments, pathological details, and recurrence and survival status was retrospectively collected from 246 patients. The expected survival according to the nomograms was calculated. The predictive accuracy of the proposed models was calculated by Harrell’s concordance indices. To assess the independent prognostic value of the variables proposed by IBCNC and BCRC, stepwise multivariable Cox regressions based on Akaike’s Information Criterion (AIC) for the different endpoints were used. A best model for prediction was created on the basis of our data.RESULTSThe IBCNC and the BCRC nomograms showed an improvement in the predictive accuracy of recurrence, all‐cause and bladder‐cancer‐specific survival after radical cystectomy of up to 4% compared to Tumour‐Node‐Metastasis stage‐based predictions. According to the calculated AIC values for the different models, all nomograms performed better than the TNM classification.CONCLUSIONSThe BCRC and IBCNC nomograms provided accurate predictions when they were applied to an external cohort of patients from low‐ to intermediate‐volume centres. The prediction of recurrence and survival based on the addressed nomograms is better than TNM stage‐based prediction. The application of such nomograms can be supported on a sound basis, but further amendments are warranted.
Renal medullary carcinoma: molecular, pathological and clinical evidence for treatment with topoisomerase‐inhibiting therapy
Authors: Schaeffer Edward M. , Guzzo Thomas J. , Furge Kyle A. , Netto George , Westphal Michael , Dykema Karl , Yang Ximing , Zhou Ming , Teh Bin Tean , Pavlovich Christian P. 
Published: December 2009

Study Type – Aetiology (case series) Level of Evidence 4OBJECTIVETo present the molecular rationale and potential clinical benefit of topoisomerase II (TopoII)‐inhibiting therapy for renal medullary carcinoma (RMC), a rare but extremely lethal form of kidney cancer that classically afflicts young men with sickle‐cell trait. The current therapeutic approach with these aggressive tumours is radical nephrectomy followed by systemic chemotherapy, but the prognosis remains dismal.MATERIALS AND METHODSThe whole‐genome expression was analysed in four RMC tumours. We also report a case of metastatic RMC in which a complete response was achieved for 9 months using a TopoII‐inhibiting therapy.RESULTSExpanded whole‐genome expression analysis showed increases of TopoII in all cases. There was also overall deregulation of DNA remodelling and repair, and an ontological association between RMC and urothelial carcinoma. Using a TopoII‐inhibiting agent, there was a complete response for 9 months in a patient with metastatic RMC.CONCLUSIONThis report provides molecular evidence for the rational use of TopoII inhibitors in the treatment of RMC.
Creole Materialities: Archaeological Explorations of Hybridized Realities on a North American Plantation
Authors: MROZOWSKI STEPHEN A. 
Published: December 2009

AbstractThis paper explores the hybridized realities of European, Native American and Afro‐Caribbean/Afro‐American residents of Sylvester Manor, New York and Constant Plantation, Barbados during the seventeenth century. It draws on archaeological and landscape evidence from two plantations that were owned and operated by different members of the same family during the seventeenth century. One of plantations, known as Sylvester Manor, encompassed all 8,000 acres of Shelter Island, New York. It was established in 1652 primarily to help in the provisioning of two large sugar plantations on Barbados, Constant and Carmichael plantations. Sylvester Manor was operated by Nathaniel Sylvester; an Englishman who spent the first twenty years of life living in Amsterdam where his father was a merchant. Constant and Carmichael plantations were operated by his brother Constant Sylvester. Both the Barbados and New York plantations relied upon a labor force of enslaved Afro‐Caribbean's. Archaeological evidence from Sylvester Manor has also revealed that Native American laborers played a prominent role in the daily activities of this northern plantation. Material and landscape evidence reveal the construction of hybridized identities that in the case of Barbados, are still part of the fabric of a postcolonial reality. Evidence from Sylvester Manor provides detailed insights into the construction of hybridized identities under the exigencies of a plantation economy whose global connections are dramatically visible in the archaeological record.
Redeeming the “Character of the Creoles”: Whiteness, Gender and Creolization in Pre‐Revolutionary Saint Domingue
Authors: FABELLA YVONNE 
Published: December 2009

AbstractThis article examines the political significance of white creolization in pre‐revolutionary French Saint Domingue. Eighteenth‐century Europeans tended to view white creoles as having physically, morally, and culturally degenerated due to the tropical climate, the monotony of plantation life, and their interaction with enslaved and free people of color. Yet elite white colonists in Saint Domingue claimed that white creoles possessed certain positive traits due to their new world birth, traits that rendered them physically stronger and potentially more virtuous than the French. Focusing on little‐known publications authored by the white creole Moreau de Saint‐Méry, this article highlights the deployment of gendered notions of virtue and noble savagery in debates over white creolization. Moreau's claims, when placed in the context of a conflict between local colonial magistrates and the French Colonial Ministry, challenge interpretations of white creolization as an undesirable, subversive side‐effect of colonial slavery. Rather, white colonial men claimed that white colonists knew best how to ensure the obedience of the enslaved precisely because of their creolization.