bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of cerebellar parallel fibers monitored in transgenic mice expressing a fluorescent Ca2+ indicator protein
Authors: Díez‐García Javier , Matsushita Shinichi , Mutoh Hiroki , Nakai Junichi , Ohkura Masamichi , Yokoyama Jennifer , Dimitrov Dimitar , Knöpfel Thomas 
Published: August 2005

AbstractGenetically encoded fluorescent Ca2+ indicator proteins (FCIPs) are promising tools to study Ca2+ signaling in large assemblies of nerve cells. Currently, there are few examples of stable transgenic mouse lines that functionally express such sensors in well‐defined neuronal cell populations. Here we report the generation and characterization of transgenic mice expressing an FCIP under the 5′ regulatory sequences of the Kv3.1 potassium channel promoter. In the cerebellar cortex, expression was restricted to granule cells. We first demonstrated reliable measurements of Ca2+ transients from beams of parallel fibers and compared the FCIP signals with intrinsic autofluorescence signals. We demonstrate that, in a transgenic line that exhibits a high expression level of the FCIP, autofluorescence signals are negligible and stimulation‐induced fluorescence transients represent FCIP signals. Using frontal cerebellar slices we imaged antidromic activation of granule cells following electrical stimulation of parallel fibers and orthodromic activation of beams of parallel fibers following electrical stimulation of granule cells. We found that paired pulse‐induced presynaptic Ca2+ transients of parallel fibers are not affected by blockade of N‐methyl‐d‐aspartate receptors.
Neurturin has multiple neurotrophic effects on adult rat sacral parasympathetic ganglion neurons
Authors: Wanigasekara Yewlan , Keast Janet R. 
Published: August 2005

AbstractNeurturin (NTN) is an important neurotrophic factor for parasympathetic neurons; however, no studies to date have investigated the signalling mechanisms downstream of GFRα2 and Ret activation underlying this neurotrophic support. This is particularly important for pelvic parasympathetic neurons, which are prone to injury during surgical procedures such as prostatectomy, and where there are no current therapies for axonal regeneration. To address this issue we have cultured dissociated adult rat pelvic ganglion neurons and also examined the structural changes in pelvic ganglion neurons after axotomy. Axotomised penile neurons deprived of target‐derived support had smaller somata than intact neurons. Studies of cultured adult pelvic ganglion neurons also demonstrated that NTN stimulated soma growth. Further experiments showed that NTN reduced the up‐regulation of tyrosine hydroxylase expression in cultured pelvic parasympathetic neurons. NTN stimulated the extension of neurites in cultured parasympathetic, but not sympathetic, pelvic ganglion neurons. Inhibition of phosphatidylinositol 3‐kinase prevented initiation of neurite outgrowth, whereas inhibition of the mitogen‐activated protein kinase and the Src family kinase pathways disrupted NTN‐stimulated microtubule assembly. Surprisingly, NTN did not activate the transcription factor cAMP‐response element binding protein (CREB), which is typically involved in neurotrophic signalling in sympathetic neurons. This is the first study to identify signalling pathways activated by NTN in adult parasympathetic neurons. Our results may lead to a better understanding of regenerative mechanisms in parasympathetic neurons, especially for those innervating urogenital organs. Our results also indicate that neurotrophic signalling in parasympathetic neurons is different from that in other types of peripheral neurons.
A perspective on protein profiling of blood
Authors: Katz Jonathan E. , Mallick Parag , Agus David B. 
Published: August 2005

Protein profiling of blood is going to lead to huge changes in the development of biomarkers and perhaps also in producing targets for the medical treatment of cancer. Experts in this field from Los Angeles have written an outstanding mini‐review about this topic.Renal cancer has been an area of interest to all of those involved in urological oncology, particularly from the point of view of adjuvant medical treatment either to prevent metastatic disease or to treat it. Authors from Los Angeles have produced a review of great interest on this subject.There are three other reviews on important issues. Authors from Paris have written about microsatellite instability and TCC of the upper urinary tract, and authors from Bristol have written a mini‐review about the options available when considering orthotopic bladder reconstruction. Finally, authors from Dublin have written about a significant problem in renal transplantation, delayed graft function.
Long‐term side‐effects of intermittent androgen suppression therapy in prostate cancer: results of a phase II study
Authors: Malone Shawn , Perry Gad , Segal Roanne , Dahrouge Simone , Crook Juanita 
Published: August 2005

OBJECTIVETo assess the feasibility and tolerability of intermittent androgen suppression therapy (IAS) in prostate cancer.PATIENTS AND METHODSPatients with recurrent or metastic prostate cancer received cyclical periods of treatment with leuprolide acetate and nilutamide for 8 months, and rest periods. Cycles were repeated at progression until the treatment failed to achieve normal prostate‐specific antigen (PSA) levels. Patients were followed with PSA level, testosterone level, haemoglobin level, weight and bone mineral density evaluations. The median time to treatment failure, recovery from anaemia, or normalization of testosterone level was estimated by the Kaplan‐Meier method.RESULTSIn all, 95 patients received 245 cycles; the median duration of rest periods was 8 months and median time to treatment failure 47 months. Testosterone recovery during rest periods was documented in 117 (61%) of cycles. Anaemia was mild and reported in 33%, 44% and 67% of cycles 1, 2 and 3, respectively. Sexual function recovered during the rest periods in 47% of cycles. There was no significant overall change in body mass index at the end of the treatment period. Osteoporosis was documented in at least one site evaluated in 41 patients (37%).CONCLUSIONSIAS has the potential to reduce side‐effects, including recovery of haemoglobin level, return of sexual function and absence of weight gain at the end of the study period.
A lower dose of thalidomide is better than a high dose in metastatic renal cell carcinoma
Authors: Srinivas Sandy , Guardino Alice E. 
Published: August 2005

OBJECTIVETo conduct a dose‐finding trial using a single low dose and dose escalation of a higher dose of thalidomide in patients with metastatic renal cell carcinoma (RCC), and to evaluate the antineoplastic effectiveness of thalidomide as an anti‐angiogenic agent on RCC.PATIENTS AND METHODSThe 14 patients enrolled in the study had progressive measurable metastatic RCC and consented to participate. Patients were randomized to either a fixed low dose of 200 mg of thalidomide or to a high dose of 800 mg that was increased to a maximum dose of 1200 mg daily. Patients were evaluated for response after 8 weeks of therapy.RESULTSStable disease was achieved in six patients and was seen in both the low‐dose and high‐dose thalidomide groups. The median overall survival was 9 months. The low‐dose thalidomide regimen was better tolerated and patients survived longer than those on the high‐dose regimen (16 vs 6 months, P = 0.04)CONCLUSIONThe use of low‐dose thalidomide in patients with metastatic RCC was well tolerated and they survived for longer than those on the high‐dose regimen.
Epstein‐Barr virus infection in sarcomatoid renal cell carcinoma tissues
Authors: Kim Kwang Hee , Han Eun Mee , Lee Eung Seok , Park Hong Seok , Kim Insun , Kim Young‐Sik 
Published: August 2005

OBJECTIVETo determine whether Epstein‐Barr virus (EBV) infection is related to renal cell carcinoma (RCC) tissues.MATERIALS AND METHODSWe investigated EBV infection and its genotypes in 73 cases of different types of RCC and 18 of non‐neoplastic kidney. EBV infection and its genotypes were determined by EBV‐encoded RNAs in situ hybridization (EBER‐ISH) and polymerase chain reactions for EBV‐encoded nuclear antigen 1 (EBNA‐1) and EBNA‐3C. The immunophenotype and EBV status of the EBV‐infected cells were examined by double‐labelling of EBER‐ISH and/or immunohistochemistry for lymphoid cell markers, EBV proteins, and CD21.RESULTSEBER‐ISH signals were detected in five of 73 RCC tissues (6.8%), but in none of 18 non‐neoplastic kidneys. Interestingly, EBER‐ISH was positive only in five of the 10 sarcomatoid RCCs, and of these, four also showed amplification of EBNA‐1. EBV was located exclusively in the tumour‐infiltrating B lymphocytes of sarcomatoid RCCs. The genotype of EBV was determined as type 1. A few EBV‐infected B cells expressed BZLF1 (an EBV immediate‐early gene product) while none expressed EBNA‐2 or latent membrane protein 1. This indicates that the B cells are of EBV latency type I, often replicating EBV. EBV infection did not affect the survival rates of patients with sarcomatoid RCC (P = 0.635, Kaplan–Meier analysis, log‐rank test).CONCLUSIONEBV is present only in tumour‐infiltrating B lymphocytes of sarcomatoid RCCs. The present study suggests that sarcomatoid RCC modulates a function of EBV‐specific T cells controlling EBV replication, or stimulates differentiation of memory B cells into plasma cells.
A case‐control study of risk factors in men with chronic pelvic pain syndrome
Authors: Pontari Michel A. , McNaughton‐Collins Mary , O'Leary Michael P. , Calhoun Elizabeth A. , Jang Thomas , Kusek John W. , Landis J. Richard , Knauss Jill , Litwin Mark S. ,   The CPCRN Study Group
Published: August 2005

In the section on the lower urinary tract this month there are several papers of general interest. First, authors from the USA present a case‐control study of risk factors in men with chronic pelvic pain syndrome. There are also papers presenting important data on alfuzosin, dutasteride, and tamsulosin versus naftopidil, respectively. In addition, the use of thermo‐expandable prostate stents is further explored by authors from the UK and Denmark. Finally, authors from Austria describe the use of a new minimally invasive device in the treatment of incontinence after prostatectomy.OBJECTIVETo compare the demographic, behavioural, clinical and medical history characteristics of men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and asymptomatic controls, to identify characteristics that might be associated with this syndrome.PATIENTS AND METHODSSelf‐administered epidemiological questionnaires were completed by 463 men with CP/CPPS and 121 asymptomatic age‐matched controls. We compared the prevalence of possible risk factors between men with CP/CPPS and controls, using generalized Mantel‐Haenszel tests, and developed multivariate predictive models using logistic regression methods, adjusting for clustering by clinical centre within both methods.RESULTSCompared to controls, men with CP/CPPS reported a significantly greater lifetime prevalence of nonspecific urethritis (12% vs 4%, P = 0.008), cardiovascular disease (11% vs 2%, P = 0.004), neurological disease (41% vs 14%, P < 0.001), psychiatric conditions (29% vs 11%, P < 0.001), and haematopoietic, lymphatic or infectious disease (41% vs 20%, P < 0.001).CONCLUSIONA wide range of self‐reported medical conditions was associated with CP/CPPS. Further studies are necessary to determine whether they play a role in the pathogenesis of CP/CPPS.
The economic impact of using alfuzosin 10 mg once daily in the management of acute urinary retention in the UK: a 6‐month analysis
Authors: Annemans Lieven , Cleemput Irina , Lamotte Mark , McNeill Alan , Hargreave Timothy 
Published: August 2005

OBJECTIVETo calculate the economic consequences of using alfuzosin 10 mg once daily for managing acute urinary retention (AUR) related to benign prostatic hyperplasia (BPH).METHODSWe examined whether alfuzosin use during hospitalization for AUR and for 6 months after a successful trial without catheter (TWOC) is cost effective compared to placebo and immediate prostatectomy, from the perspective of patients managed in the National Health Service (NHS) in the UK. A decision‐analysis model was developed to estimate the costs of various treatment options within the first 6 months after a first episode of AUR. Clinical data were obtained from a large randomized clinical trial comparing alfuzosin 10 mg with placebo, and from published reports. Cost data were obtained from both NHS and resource‐use data gathered during the clinical trial. A Monte Carlo analysis, allowing variability in all uncertain variables of the model, was used to calculate the uncertainty surrounding the results.RESULTSTreating patients with alfuzosin during initial hospitalization for AUR and in the first 6 months after a successful TWOC generates a cost‐saving of £349 relative to placebo. Savings related to immediate prostatectomy were £892; both savings were significant (P < 0.05). Alfuzosin treatment was associated with a lower rate of prostatectomy after discharge from hospital after a successful TWOC.CONCLUSIONTreatment with alfuzosin 10 mg once daily before and after a successful TWOC has both clinical and economic benefits. It decreases the need for emergency surgery for BPH and reduces treatment costs in the first 6 months.
Pelvic floor exercises for erectile dysfunction
Authors: Dorey Grace , Speakman Mark J. , Feneley Roger C.L. , Swinkels Annette , Dunn Christopher D.R. 
Published: August 2005

Associate EditorMichael G. WyllieEditorial BoardIan Eardley, UKJean Fourcroy, USASidney Glina, BrazilJulia Heiman, USAChris McMahon, AustraliaBob Millar, UKAlvaro Morales, CanadaMichael Perelman, USAMarcel Waldinger, NetherlandsOBJECTIVETo examine the role of pelvic floor exercises as a way of restoring erectile function in men with erectile dysfunction.PATIENTS AND METHODSIn all, 55 men aged > 20 years who had experienced erectile dysfunction for ≥ 6 months were recruited for a randomized controlled study with a cross‐over arm. The men were treated with either pelvic floor muscle exercises (taught by a physiotherapist) with biofeedback and lifestyle changes (intervention group) or they were advised on lifestyle changes only (control group). Control patients who did not respond after 3 months were treated with the intervention. All men were given home exercises for a further 3 months. Outcomes were measured using the International Index of Erectile Function (IIEF), anal pressure measurements and independent (blinded) assessments.RESULTSAfter 3 months, the erectile function of men in the intervention group was significantly better than in the control group (P < 0.001). Control patients who were given the intervention also significantly improved 3 months later (P < 0.001). After 6 months, blind assessment showed that 40% of men had regained normal erectile function, 35.5% improved but 24.5% failed to improve.CONCLUSIONThis study suggests that pelvic floor exercises should be considered as a first‐line approach for men seeking long‐term resolution of their erectile dysfunction.
Partial nephrectomy with perfusion cooling for imperative indications: a 24‐year experience
Authors: Steffens Joachim , Humke Ulrich , Ziegler Manfred , Siemer Stefan 
Published: August 2005

OBJECTIVETo report our 24‐year experience with open nephron‐sparing surgery for renal tumours, using cold ischaemia achieved by renal artery perfusion, as partial nephrectomy for imperative indications is a surgical challenge.PATIENTS AND METHODSFrom 1980 to 2004, open partial nephrectomy was performed in 717 patients; of these, 65 (9.1%) with a solitary kidney, synchronous bilateral tumours or renal failure in the opposite kidney (imperative indication) had surgery under cold ischaemia, achieved by continuous perfusion of Ringer's lactate at 4 °C through the renal artery, which was clamped and cannulated. The tumour was resected in a bloodless field, with biopsies taken from the tumour bed. Focusing on patients with an imperative indication and cold perfusion, we report our perfusion technique, and the ischaemia time, complication rate and cancer‐specific survival rate of these patients.RESULTSThe mean (sd, range) operative duration was 132 (103, 91–252) min and ischaemia time 49 (37, 31–71) min. The most common complications were postoperative haemorrhage in 19%, urinary fistula in 8% and acute renal failure in 6% of patients. There were no specific complications related to the perfusion technique (renal artery stenosis, renal artery or vein thrombosis). The mean (sd, range) long‐term follow‐up of 95 (71, 4.3–231) months showed increased but constant creatinine values (95 µmol/L before, 182 µmol/L after surgery; P < 0.05) with no need for long‐term dialysis. The tumour‐specific survival rate was 94%, 76% and 76% after 1, 5 and 10 years, respectively.CONCLUSIONSPartial nephrectomy under cold ischaemia remains reserved for selected patients with renal tumours with an imperative indication. The technique provides excellent intraoperative visibility in an absolutely bloodless field, allows surgery with no pressure of time, and makes ex vivo workbench surgery with autotransplantation unnecessary. Perfusion cooling allows good tumour‐specific long‐term results, with stable residual kidney function sufficient to prevent dialysis.
Combined low‐dose imatinib mesylate and paclitaxel lack synergy in an experimental model of extra‐osseous hormone‐refractory prostate cancer
Authors: Corcoran Niall M. , Costello Anthony J. 
Published: August 2005

OBJECTIVETo determine the efficacy of low‐dose imatinib mesylate (STI571) alone or combined with a taxane (paclitaxel) in inhibiting the growth of experimental extra‐osseous hormone‐refractory prostrate cancer.MATERIALS AND METHODSOrthotopic PC3 prostate tumours were established in male severe combined‐immunodeficient mice; on day 3 the mice were randomly assigned to one of four groups: paclitaxel 10 mg/kg intraperitoneally once a week; STI571 50 mg/kg once a day for 6/7 weekdays; combined paclitaxel and STI571; and vehicle‐treated controls. On day 40, the primary prostate tumour and metastatic lymphadenopathy were removed and measured. Effects were correlated with tumour cell proliferation and microvessel density.RESULTSPaclitaxel reduced the mean tumour weight and volume by 21.3% (not significant) and 73.7% (P < 0.05), respectively, compared to controls, and reduced the number of lymph node metastases by 49.1% (P < 0.05) and mean lymph node size by 13.5% (not significant). Adding low‐dose STI571 had a small additive effect on tumour weight and the incidence of lymph node metastases, but this was not significant compared to paclitaxel alone. STI571 alone did not inhibit tumour progression. Antitumour effects were associated with parallel changes in tumour cell proliferation with no significant changes in neo‐angiogenesis.CONCLUSIONCombined low‐dose STI571 and paclitaxel had little synergy in this experimental model. Low‐dose STI571 monotherapy was not effective in extra‐osseous disease, apparently due to a site‐specific failure to up‐regulate β‐platelet‐derived growth factor receptor expression in prostate cancer cells and associated tumour stroma.
Property and Agri‐Environmental Legislation Europe
Authors: Sikor Thomas 
Published: August 2005

AbstractGovernments across Central and Eastern Europe have enacted agri‐environmental legislation over the past decade. This paper explores how the legislation has played out in practice, using property as an analytical lens to examine the social dynamics surrounding agri‐environmental problems. The analysis proceeds by way of three case studies on irrigation management in Bulgaria, biodiversity conservation in the Czech Republic, and the preservation of open space in Poland. The findings highlight the discrepancy between the legal rights accorded to land owners and their rights‐in‐practice. Land owners contest the constraints imposed by agri‐environmental legislation through strategies ranging from avoidance to open violation. They also counter the goal of environmental protection by invoking competing social values. The material and symbolic contestations form new sets of regulations blurring the boundary between public oversight and private rights delineated in agri‐environmental legislation.
Pre‐accession Europeanisation: The Strategic Realignment of the Environmental Policy Systems of Lithuania, Poland and Slovakia towards Agricultural Pollution in Preparation for EU Membership
Authors: Gorton Matthew , Lowe Philip , Zellei Anett 
Published: August 2005

AbstractThe divergent responses of three CEECs ‐ Lithuania, Poland and Slovakia ‐ to the common evolution of problems of agriculturally induced water pollution into matters of international concern is analysed from the end of their communist regimes to accession to the European Union (EU) in 2004. The early years of transition were characterised by an emerging international socialisation of domestic elites with Western academics and policy networks. These networks presented opportunities for norm entrepreneurs, who sought to draw attention to the problem of agriculturally induced water pollution and realign domestic policy. The success of these norm entrepreneurs depended on the positions they held in elite networks, their state's geo‐political concerns and desires for international legitimacy, and the degree to which productionist interests were entrenched in agricultural ministries. In contrast, the late 1990s and early 2000s were dominated by preparations for EU membership, particularly adoption of the acquis communautaire. While the CEECs had no option but to transpose EU directives into domestic legislation, the nature of directives has meant that they have had considerable leeway in terms of the administrative solutions chosen. This is illustrated by the Nitrates Directive; the three countries studied have adopted markedly different responses and sought expertise from established Member States that closely matched their own outlook. Arguments that the CEECs are en masse environmental laggards or merely passive players in the process of Europeanisation are rejected.
Broad Outcome Measures May Underestimate Effectiveness: An Instrument Comparison Study
Authors: Lee William , Jones Lynne , Goodman Robert , Heyman Isobel 
Published: August 2005

Background:  Outcome measures are routinely used in child and adolescent mental health services to demonstrate the effectiveness or otherwise of interventions.Methods:  We followed up a consecutive sample from a large teaching hospital's Obsessive Compulsive Disorder (OCD) service for young people, comparing improvements using instruments of differing broadness.Results:  The effect size of improvement decreased as the breadth of the questionnaire increased.Conclusion:  Specialist clinics are recommended to use two questionnaires: a broad one to facilitate comparability with other clinics, and a narrow one to maximise power to detect significant changes.