bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extent of lymph node dissection at nephrectomy affects cancer‐specific survival and metastatic progression in specific sub‐categories of patients with renal cell carcinoma (RCC)
Authors: Capitanio Umberto , Suardi Nazareno , Matloob Rayan , Roscigno Marco , Abdollah Firas , Di Trapani Ettore , Moschini Marco , Gallina Andrea , Salonia Andrea , Briganti Alberto , Montorsi Francesco , Bertini Roberto 
Published: October 2013

Objective
To test whether the number of lymph nodes removed affects cancer‐specific survival (CSS) or metastatic progression‐free survival (MPFS) in different renal cell carcinoma (RCC) scenarios.
Methods
We used Cox regression analyses to analyse the effect of the number of lymph nodes removed on CSS and MPFS in 1983 patients with RCC treated with nephrectomy.
To adjust for possible clinical and surgical selection bias, analyses were further adjusted for number of positive nodes, presence of metastases, age, performance status, T stage, tumour size and grade.
Results
The prevalence of lymph node invasion was 6.1%. The mean follow‐up period was 83.3 months.
Multivariable analyses showed that the number of nodes removed had an independent, protective effect on CSS in patients with pT2a–pT2b or pT3c–pT4 RCC (hazard ratio [HR] 0.91, P = 0.008 and HR 0.89, P < 0.001, respectively), in patients with bulky tumours (tumour size >10 cm, HR 0.97, P = 0.03) or when sarcomatoid features were found (HR 0.81, P = 0.006).
The removal of each additional lymph node was associated with a 3–19% increase in CSS.
When considering MPFS as an endpoint, the number of nodes removed had an independent, protective effect in the same patient categories.
Conclusions
When clinically indicated, the number of nodes removed affects CSS and MPFS in specific sub‐categories of patients with RCC.
Biology of AQP4 and Anti‐AQP4 Antibody: Therapeutic Implications for NMO
Authors: Verkman A. S. , Phuan Puay‐Wah , Asavapanumas Nithi , Tradtrantip Lukmanee 
Published: October 2013

AbstractThe water channel aquaporin‐4 (AQP4) is the target of the immunoglobulin G autoantibody (AQP4‐IgG) in neuromyelitis optica (NMO). AQP4 is expressed in foot processes of astrocytes throughout the central nervous system, as well as in skeletal muscle and epithelial cells in kidney, lung and gastrointestinal organs. Phenotype analysis of AQP4 knockout mice indicates the involvement of AQP4 in water movement into and out of the brain, astrocyte migration, glial scar formation and neuroexcitatory phenomena. AQP4 monomers form tetramers in membranes, which further aggregate to form supramolecular assemblies called orthogonal arrays of particles. AQP4‐IgG is pathogenic in NMO by a mechanism involving complement‐ and cell‐mediated astrocyte cytotoxicity, which produces an inflammatory response with oligodendrocyte injury and demyelination. AQP4 orthogonal arrays are crucial in NMO pathogenesis, as they increase AQP4‐IgG binding to AQP4 and greatly enhance complement‐dependent cytotoxicity. Novel NMO therapeutics are under development that target AQP4‐IgG or AQP4, including aquaporumab monoclonal antibodies and small molecules that block AQP4‐IgG binding to AQP4, and enzymatic inactivation strategies to neutralize AQP4‐IgG pathogenicity.
Clinical Spectrum and Treatment of Neuromyelitis Optica Spectrum Disorders: Evolution and Current Status
Authors: Sato Douglas Kazutoshi , Lana‐Peixoto Marco Aurelio , Fujihara Kazuo , de Seze Jerome 
Published: October 2013

AbstractNeuromyelitis optica (NMO) is an inflammatory neurologic disease clinically characterized by severe optic neuritis (ON) and transverse myelitis (TM). The relationship between NMO and multiple sclerosis (MS) has long been a matter of debate. However, the discovery of an NMO‐specific autoantibody, NMO‐immunoglobulin G/aquaporin 4 (AQP4) antibody, has dramatically advanced our understanding of the disease, and the clinical, magnetic resonance imaging (MRI), optical coherence tomography, and laboratory examinations have clarified unique features of NMO that are distinct from MS. The term NMO spectrum disorders (NMOSD) incorporating spatially limited forms was introduced, as patients with recurrent or simultaneous bilateral ON or recurrent longitudinally extensive TM (LETM) alone are also often AQP4 antibody‐seropositive. Moreover, studies of seropositive cases have shown that more than half of them have brain lesions, some of which are unique to NMO, and can be the onset manifestation. Some clinical features of AQP4 antibody‐seronegative NMO differ from seropositive, but it remains unknown whether they are pathologically distinct. Immunosuppressive treatments are effective for acute attacks and prevention of relapses of NMOSD, and new molecularly targeted drugs are under investigation. Importantly, some disease modifying drugs for MS may exacerbate NMOSD, making early differential diagnosis of the two diseases crucial. We review the evolving clinical spectrum, the updated clinical, MRI, neuro‐ophthalmological and laboratory findings, and the current status of treatment in NMOSD.
Structure–activity relationships of the N‐terminus of calcitonin gene‐related peptide: key roles of alanine‐5 and threonine‐6 in receptor activation
Authors: Hay Debbie L , Harris Paul W R , Kowalczyk Renata , Brimble Margaret A , Rathbone Dan L , Barwell James , Conner Alex C , Poyner David R 
Published: October 2013

Background and PurposeThe N‐terminus of calcitonin gene‐related peptide (CGRP) is important for receptor activation, especially the disulphide‐bonded ring (residues 1–7). However, the roles of individual amino acids within this region have not been examined and so the molecular determinants of agonism are unknown. This study has examined the role of residues 1, 3–6 and 8–9, excluding Cys‐2 and Cys‐7.Experimental ApproachCGRP derivatives were substituted with either cysteine or alanine; further residues were introduced at position 6. Their affinity was measured by radioligand binding and their efficacy by measuring cAMP production in SK‐N‐MC cells and β‐arrestin 2 translocation in CHO‐K1 cells at the CGRP receptor.Key ResultsSubstitution of Ala‐5 by cysteine reduced affinity 270‐fold and reduced efficacy for production of cAMP in SK‐N‐MCs. Potency at β‐arrestin translocation was reduced by ninefold. Substitution of Thr‐6 by cysteine destroyed all measurable efficacy of both cAMP and β‐arrestin responses; substitution with either alanine or serine impaired potency. Substitutions at positions 1, 4, 8 and 9 resulted in approximately 10‐fold reductions in potency at both responses. Similar observations were made at a second CGRP‐activated receptor, the AMY1(a) receptor.Conclusions and ImplicationsAla‐5 and Thr‐6 are key determinants of agonist activity for CGRP. Ala‐5 is also very important for receptor binding. Residues outside of the 1–7 ring also contribute to agonist activity.
The opioid methadone induces a local anaesthetic‐like inhibition of the cardiacNa+channel,Nav1.5
Authors: Schulze V , Stoetzer C , O'Reilly A O , Eberhardt E , Foadi N , Ahrens J , Wegner F , Lampert A , de la Roche J , Leffler A 
Published: October 2013

Background and PurposeTreatment with methadone is associated with severe cardiac arrhythmias, a side effect that seems to result from an inhibition of cardiachERG K+channels. However, several other opioids are inhibitors of voltage‐gatedNa+channels. Considering the common assumption that an inhibition of the cardiacNa+channelNav1.5, is the primary mechanism for local anaesthetic (LA)‐induced cardiotoxicity, we hypothesized that methadone hasLA‐likeproperties leading to a modulation ofNav1.5 channels.Experimental ApproachThe whole‐cell patch clamp technique was applied to investigate the effects of methadone on wild‐type and mutant humanNav1.5 channels expressed inHEK293 cells. A homology model of human Nav1.5 channels was used to perform automated ligand‐docking studies.Key ResultsMethadone inhibitedNav1.5 channels in a state‐dependent manner, that is, tonic block was stronger with inactivated channels than with resting channels and a use‐dependent block at 10 Hz. Methadone induced a concentration‐dependent shift of the voltage dependency of both fast and slow inactivation towards more hyperpolarized potentials, and impaired recovery from fast and slow inactivation. TheLA‐insensitive mutantsN406KandF1760Aexhibited reduced tonic and use‐dependent block by methadone, and docking predictions positioned methadone in a cavity that was delimited by the residueF1760. Dextromethadone and levomethadone induced discrete stereo‐selective effects onNav1.5 channels.Conclusions and ImplicationsMethadone interacted with theLA‐binding site to inhibitNav1.5 channels. Our data suggest that these channels are a hitherto unrecognized molecular component contributing to cardiac arrhythmias induced by methadone.
Role of CXCR2 and TRPV1 in functional, inflammatory and behavioural changes in the rat model of cyclophosphamide‐induced haemorrhagic cystitis
Authors: Dornelles Fabiana N , Andrade Edinéia L , Campos Maria M , Calixto João B 
Published: October 2013

Background and PurposeCyclophosphamide induces urotoxicity characterized by the development of cystitis, which involves bladder overactivity and inflammation. Here, we investigated the roles of chemokine receptor 2 (CXCR2) and transient receptor potential vanilloid 1 (TRPV1) channels in a rat model of cyclophosphamide‐induced cystitis.Experimental ApproachCystitis induced by cyclophosphamide in rats was assessed by gross morphology, histology and immunohistochemistry of bladder tissue. mRNA for CXCR2 and TRPV1 channels were measured by RT‐PCR. Nociceptive responses in paw and abdomen, along with cystometric measures were recorded.Key ResultsCyclophosphamide, i.p., induced pain behaviour, bladder inflammation and voiding dysfunction. The CXCR2 antagonist, SB225002, the TRPV1 channel antagonist, SB366791 or their combination reduced the mechanical hypersensitivity of paw and abdominal area and nociceptive behaviour after cyclophosphamide. Cyclophosphamide‐induced cystitis was characterized by haemorrhage, oedema, neutrophil infiltration and other inflammatory changes, which were markedly decreased by the antagonists. Up‐regulation of CXCR2 and TRPV1 mRNA in the bladder after cyclophosphamide was inhibited by SB225002, SB366791 or their combination. Expression of CXCR2 and TRPV1 channels was increased in the urothelium after cyclophosphamide. Bladder dysfunction was shown by increased number of non‐voiding contractions (NVCs) and bladder pressures and a reduction in bladder capacity (BC), voided volume (VV) and voiding efficiency (VE). SB225002 or its combination with SB366791 reduced bladder pressures, whereas SB225002, SB366791 or their combination increased BC, VV and VE, and also reduced the number of NVCs.Conclusions and ImplicationsCXCR2 and TRPV1 channels play important roles in cyclophosphamide‐induced cystitis in rats and could provide potential therapeutic targets for cystitis.
Unsymmetrical Oxovanadium Complexes Derived from Salicylaldehyde and Phenanthroline: Synthesis, DNA Interactions, and Antitumor Activities
Authors: Liao Xiangwen , Pan Weijian , He Rongwei , Guo Haiwei , Ying Peng , Lu Jiazheng 
Published: October 2013

Two unsymmetrical oxovanadium complexes incorporating salicylaldehyde derivate and phenanthroline [VO(DESAA)(phen)] (1), (DESAA = 4‐(diethylamino)salicylaldehyde anthranilic acid, phen = phenanthroline) and [VO(CLSAA)(phen)] (2), (CLSAA = 5‐chlorosalicylaldehyde anthranilic acid)] have been synthesized and characterized. The interactions of the complexes with CT‐DNA were studied using different techniques. Complexes 1 and 2 interact with CT‐DNA by intercalative modes and can efficiently cleave pBR322 DNA after light irradiation. The two complexes showed high cytotoxic activities against myeloma cell (Ag8.653) and gliomas cell (U251) lines. Interestingly, complex 1 exhibited greater antitumor efficiency, larger binding affinity with CT‐DNA, and better cleaving ability than those of complex 2. In addition, their antitumor mechanism has been analyzed by using cell cycle analysis, apoptosis, and Annexin V‐FITC/PI assay. The results showed that complex 1 can cause G2/M‐phase arrest of the cell cycle, exhibit a significantly induced apoptosis in Ag8.653 cells, and display typical morphological apoptotic characteristics. These complexes induced proliferative suppression of Ag8.653 cells via the induction of apoptosis.
Impact of subclinical haemorrhage on the pituitary gland in patients with pituitary adenomas
Authors: Kinoshita Yasuyuki , Tominaga Atsushi , Usui Satoshi , Arita Kazunori , Sugiyama Kazuhiko , Kurisu Kaoru 
Published: October 2013

SummaryObjectiveAdvanced magnetic resonance imaging (MRI) and optical instruments for surgery frequently demonstrate subclinical haemorrhage in pituitary adenomas; however, the effects of subclinical haemorrhage on pituitary glands remain unclear. We sought to clarify the pituitary function in patients with subclinical pituitary adenoma haemorrhage (SPAH).Design/PatientsBetween January 2006 and December 2012, we retrospectively reviewed 328 consecutive patients who underwent surgery for pituitary adenoma. SPAH was defined as an intratumoral haemorrhage based on both 3 tesla MRI and operative findings, with no clinical symptoms of acute pituitary adenoma apoplexy. The pituitary dysfunction assessed using pre‐ and postoperative provocative tests was investigated in patients categorized into three groups: nonapoplectic adenoma, adenoma with SPAH and adenoma with clinical apoplexy.MeasurementsThe main outcome measure was the incidence of pituitary dysfunction.ResultsThe overall incidence of nonapoplectic adenomas, adenomas with SPAH and adenomas with clinical apoplexy was 82·3%, 14·3% and 3·4%, respectively. Clinical pituitary apoplexy frequently occurred in male patients with large nonfunctioning adenomas, causing pituitary dysfunction. Contrastingly, the incidence of SPAH was significantly higher in the patients with prolactinoma (P = 0·0260), including those with relatively small adenomas (P = 0·0007). No medications, such as dopamine agonists or somatostatin analogues, were observed to affect the occurrence of SPAH. No deterioration of the pituitary function was observed in the SPAH patients in comparison with the patients with nonapoplectic adenoma, and the size of the haematoma occupying the pituitary adenoma did not exhibit any relationships with the deterioration of the pituitary function. Furthermore, SPAH caused no deterioration of the pituitary function after a surgery based on the postoperative provocation tests.ConclusionsSubclinical pituitary adenoma haemorrhage does not cause any added dysfunction in pituitary glands. Signs of haemorrhage in pituitary adenomas do not necessitate immediate tumour decompression surgery, if there are no symptoms of acute haemorrhage.
Combining Statins with Tissue Plasminogen Activator Treatment After Experimental and Human Stroke: A Safety Study on Hemorrhagic Transformation
Authors: Campos Mireia , García‐Bonilla Lidia , Hernández‐Guillamon Mar , Barceló Verónica , Morancho Anna , Quintana Manolo , Rubiera Marta , Rosell Anna , Montaner Joan 
Published: October 2013

SummaryAimsStatins may afford neuroprotection against ischemic injury, but it remains controversial whether combined treatment with tissue plasminogen activator (tPA) after stroke increases the risk of hemorrhagic transformation (HT), the major tPA‐related complication. We evaluated the safety of combining statin with tPA administration during the acute phase of both experimental and human stroke.MethodsThe occurrence and severity of HT, infarct volume, and neurological outcome were evaluated in spontaneous hypertensive rats (SHR) subjected to embolic middle cerebral arterial occlusion (MCAO), which received vehicle or simvastatin (20 mg/kg), 15 min after ischemia and tPA (9 mg/kg) 3 h after ischemia. Additionally, HT rate was evaluated in stroke patients who were treated with tPA (0.9 mg/kg) within 3 h after symptom onset, considering whether or not were under statins treatment when the stroke occurred.ResultsIn the experimental study, no differences in HT rates and severity were found between treatment groups, neither regarding mortality, neurological deficit, infarct volume, or metalloproteinases (MMPs) brain content. In the clinical study, HT rates and hemorrhage type were similar in stroke patients who were or not under statins treatment.ConclusionThis study consistently confirms that the use of statins does not increase HT rates and severity when is combined with tPA administration.
Impact of slow transit constipation on the outcome of laparoscopic ventral rectopexy for obstructed defaecation associated with high grade internal rectal prolapse
Authors: Gosselink M. P. , Adusumilli S. , Harmston C. , Wijffels N. A. , Jones O. M. , Cunningham C. , Lindsey I. 
Published: October 2013

AbstractAimLimited literature exists on whether slow colonic transit adversely influences the results of outlet obstruction surgery. We compared the functional results of laparoscopic ventral rectopexy (LVR) for obstructed defaecation secondary to high grade internal rectal prolapse in patients with normal and slow colonic transit.MethodConsecutive patients suffering from obstructed defaecation associated with an internal rectal prolapse, who underwent an LVR between 2007 and 2011, were identified from a prospective database. All patients underwent preoperative defaecating proctography, anorectal manometry and colonic transit studies. Symptoms were assessed preoperatively and at 12 months after operation using a standardized questionnaire incorporating the Patient Assessment of Constipation Symptoms (PAC‐SYM) questionnaire, the Fecal Incontinence Severity Index (FISI), the Patient Assessment of Constipation Quality of Life (PAC‐QOL) scale and the Gastrointestinal Quality of Life Index (GIQLI).ResultsIn all, 151 patients underwent LVR, 109 with normal and 42 with slow colonic transit. Preoperatively there was no significant difference between the two groups in age, sex, PAC‐SYM score or FISI score. The PAC‐SYM and FISI scores were significantly reduced in both groups at 12 months (P < 0.001). When comparing the change from baseline of PAC‐SYM between patients with and without slow transit constipation, a significant difference was observed (P = 0.030) with changes of 58% and 40%. Quality of life (GIQLI and PAC‐QOL) was equally improved in both groups. Quality of life improvement was less in patients with right colonic stasis.ConclusionSlow colonic transit has no adverse impact on function and quality of life after LVR for obstructed defaecation due to high grade internal rectal prolapse.
Integrating Cognitive Process and Descriptive Models of Attitudes and Preferences
Authors: Hawkins Guy E. , Marley A.A.J. , Heathcote Andrew , Flynn Terry N. , Louviere Jordan J. , Brown Scott D. 
Published: October 2013

AbstractDiscrete choice experiments—selecting the best and/or worst from a set of options—are increasingly used to provide more efficient and valid measurement of attitudes or preferences than conventional methods such as Likert scales. Discrete choice data have traditionally been analyzed with random utility models that have good measurement properties but provide limited insight into cognitive processes. We extend a well‐established cognitive model, which has successfully explained both choices and response times for simple decision tasks, to complex, multi‐attribute discrete choice data. The fits, and parameters, of the extended model for two sets of choice data (involving patient preferences for dermatology appointments, and consumer attitudes toward mobile phones) agree with those of standard choice models. The extended model also accounts for choice and response time data in a perceptual judgment task designed in a manner analogous to best–worst discrete choice experiments. We conclude that several research fields might benefit from discrete choice experiments, and that the particular accumulator‐based models of decision making used in response time research can also provide process‐level instantiations for random utility models.
Immunosuppression after renal allograft failure: a survey of US practices
Authors: Bayliss George P. , Gohh Reginald Y. , Morrissey Paul E. , Rodrigue James R. , Mandelbrot Didier A. 
Published: October 2013

AbstractBackgroundLittle data exist to guide the management of immunosuppression after renal graft failure. More aggressive tapering of immunosuppressive medications may reduce the risk of infection, but may increase the risk of rejection and sensitization.MethodsTo document current practices in the US, we emailed a questionnaire to medical and surgical transplant directors as identified by the United Network for Organ Sharing (UNOS).ResultsEmails were sent to 221 programs, of which 93 (42.1%) responded. About 24.7% of respondents reported adjusting immunosuppression according to a standard protocol; 75.3% said practices are physician dependent. The majority said that 80 or 100% of patients are off all immunosuppression one yr after returning to dialysis. The most important factors cited in deciding whether to stop immunosuppression were plans to retransplant (40.2%) and signs and symptoms of rejection (37.0%). When asked which immunosuppressive medications are continued indefinitely, 21.5% responded prednisone and 71.0% said none. Respondents most commonly said they performed graft nephrectomy only if there are signs and symptoms of rejection (47.3%) or if signs and symptoms of rejection fail to respond to steroids (34.4%).ConclusionsIn the absence of good data to guide decisions on immunosuppression in patients with failed allografts, practices in the US vary greatly. More data are needed to determine which policies lead to the best outcomes.
Allotransplanting donor kidneys after resection of a small renal cancer or contralateral healthy kidneys from cadaveric donors with unilateral renal cancer: a systematic review
Authors: Yu Nengwang , Fu Shuai , Fu Zhihou , Meng Jianzhong , Xu Zhonghua , Wang Baocheng , Zhang Aimin 
Published: October 2013

AbstractThis systematic review summarizes evidence on allotransplantation of donor kidneys after resection of a small renal cancer or contralateral healthy kidneys from cadaveric donors with unilateral renal cancer. Eligible studies were identified by screening four bibliographic databases, contacting key authors, and analyzing the bibliographies of included studies. Two reviewers independently assessed the reports for inclusion and extracted data, which were summarized as a narrative review. In the 20 case report or case series studies included in the analysis, there were 97 documented cases of donor kidney transplantation after resection of small renal cancer without pathologically confirmed recurrence, whereas 22 cases used contralateral healthy kidneys from cadaveric donors with unilateral renal cancer with one case of cancer recurrence. These results suggest that the use of donor kidneys after resection of small renal cancer is associated with a relatively low cancer recurrence rate.