Santa Cruz de Tenerife, Spain
Santa Cruz de Tenerife, Spain

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Abraldes J.G.,University of Barcelona | Villanueva C.,Autonomous University of Barcelona | Aracil C.,Hospital Universitario Arnau Of Vilanova | Turnes J.,Complejo Hospitalario Universitario Of Pontevedra | And 10 more authors.
Gastroenterology | Year: 2016

Background & Aims: The combination of β-blockers and band ligation is the standard approach to prevent variceal rebleeding, but bleeding recurs and mortality is high. The lipid-lowering drug simvastatin decreases portal pressure, improves hepatocellular function, and might reduce liver fibrosis. We assessed whether adding simvastatin to standard therapy could reduce rebleeding and death after variceal bleeding in patients with cirrhosis. Methods: We performed a multicenter, double-blind, parallel trial of 158 patients with cirrhosis receiving standard prophylaxis to prevent rebleeding (a β-blocker and band ligation) in Spain from October 2010 through October 2013. Within 10 days of bleeding, subjects were randomly assigned, but stratified by Child-Pugh class of A or B vs C, to groups given simvastatin (20 mg/d the first 15 days, 40 mg/d thereafter; n = 69) or placebo (n = 78). Patients were followed for as long as 24 months. The primary end point was a composite of rebleeding and death, and main secondary end points were the individual components of the composite (death and rebleeding). Results: The primary end point was met by 30 of 78 patients in the placebo group and 22 of 69 in the simvastatin group (P = .423). Seventeen patients in the placebo group died (22%) vs 6 patients in the simvastatin group (9%) (hazard ratio for adding simvastatin to therapy = 0.39; 95% confidence interval: 0.15-0.99; P = .030). Simvastatin did not increase survival of patients with Child-Pugh class C cirrhosis. Rebleeding occurred in 28% of patients in the placebo group and 25% in the simvastatin group (P = .583). Serious adverse events occurred in 53% of patients in the placebo group and 49% in the simvastatin group (P = .752); the percentages of serious adverse events related to therapy were 11% in the placebo group vs 8% in the in the simvastatin group (P = .599). Two patients in the simvastatin group, each with advanced liver disease, developed rhabdomyolysis. Conclusions: In a randomized controlled trial, addition of simvastatin to standard therapy did not reduce rebleeding, but was associated with a survival benefit for patients with Child-Pugh class A or B cirrhosis. Survival was not the primary end point of the study, so these results require validation. The incidence of rhabdomyolysis in patients receiving 40 mg/d simvastatin was higher than expected. European Clinical Trial Database ID: EUDRACT 2009-016500-24; ClinicalTrials.gov ID: NCT01095185. © 2016 AGA Institute.


Trinanes J.,University Hospital of the Canary Islands | Salido E.,University Hospital of the Canary Islands | Fernandez J.,University Hospital of the Canary Islands | Rufino M.,University Hospital of the Canary Islands | And 3 more authors.
Diabetes Care | Year: 2012

OBJECTIVE - Diabetes may accelerate atheromatosis in uremic patients. Our aim was to assess the influence of type 1 diabetes on the atheromatosis-related inflammation in patients with chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS - We analyzed the expression of proinflammatory cytokines and adhesion molecules in the inferior epigastric artery walls of type 1 diabetic patients with CKD (n = 22) and compared it with nondiabetic uremic patients (n = 92) at the time of kidney transplantation.Weevaluated the expression of interleukin (IL)-6, monocyte chemotractant protein (MCP)-1, vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule-1, and the activation of nuclear factor-κb p65 (NFkB-p65). Common carotid intima-media thickness (c-IMT) was determined by conventional echography. RESULTS - IL-6, MCP-1, and VCAM-1 proteins were elevated in type 1 diabetic patients compared with nondiabetic subjects (P < 0.05). The nuclear localization of NFkB-p65 was higher in type 1 diabetic patients (P < 0.01) and correlated with the levels of MCP-1 in this group (r = 0.726, P < 0.001). Arterial fibrosis correlated with IL-6 and MCP-1 levels (r = 0.411, P < 0.001 and r = 0.378, P = 0.001). A significant correlation was observed between VCAM-1 levels and both the degree of arterial narrowing and c-IMT. CONCLUSIONS - Type 1 diabetes produces a proinflammatory state in the arteries of endstage CKD patients, with increased levels of IL-6,MCP-1, and VCAM-1, aswell as a greater degree of p65 activation, which are associated with more severe vascular lesions and higher c-IMT. Although causality is not demonstrated, these findings support the major role of inflammation in type 1 diabetic patients with CKD. © 2012 by the American Diabetes Association.


Parra-Blanco A.,University Hospital of the Canary Islands | Parra-Blanco A.,University of Oviedo | Nicolas D.,University Hospital of the Canary Islands | Arnau M.R.,University of La Laguna | And 3 more authors.
Gastrointestinal Endoscopy | Year: 2011

Background: Endoscopic submucosal dissection (ESD) is the standard of care for treating gastric intramucosal neoplasias in Japan. However, it is seldom performed in Western countries, mainly because it is technically very challenging. Several traction methods have been proposed to facilitate submucosal dissection, but they are usually not widely available or are difficult to apply. Objective: Our main aim was to evaluate the feasibility of a new method, the clip-band technique, for improving the visualization of the submucosal layer during ESD. Design: Observational, experimental, feasibility study conducted in a porcine model. Setting: University Hospital of the Canary Islands, Research Animal Laboratory. Patients: Animal study. Interventions: After completion of the circumferential cutting, a clip-band traction system was applied. Main Outcome Measurements: Efficacy and safety of the clip-band technique. Results: Eighteen ESDs performed in live domestic pigs were completed without any serious complications. The mean specimen size was 35.38 ± 12.17 mm, the mean cutting time was 13.06 ± 10.52 minutes, and the mean dissection time was 16.67 ± 9.01 minutes. Limitations: The clip-band technique was not compared with the standard ESD technique. Conclusions: This initial study shows that the clip-band traction technique is feasible and that it permits safe, effective, and relatively inexpensive gastric ESD. © 2011 American Society for Gastrointestinal Endoscopy.


Wagg A.,University of Alberta | Cardozo L.,King's College London | Nitti V.W.,NYU Langone Medical Center | Castro-Diaz D.,University Hospital of the Canary Islands | And 4 more authors.
Age and Ageing | Year: 2014

Introduction: mirabegron is a β3-adrenoceptor agonist developed for the treatment of symptoms of overactive bladder (OAB). As the prevalence of OAB increases with age, a prospective subanalysis of individual and pooled efficacy and tolerability data from three 12-week, randomised, Phase III trials, and of tolerability data from a 1-year safety trial were conducted in order to evaluate the efficacy and tolerability of mirabegron in subgroups of patients aged ≥65 and ≥75 years. Methods: primary efficacy outcomes were change from baseline to final visit in the mean number of incontinence episodes/24 h and the mean number of micturitions/24 h. Tolerability was assessed by the incidence of treatment-emergent adverse events (TEAEs). Results: over 12 weeks mirabegron 25 mg and 50 mg once-daily reduced the mean numbers of incontinence episodes and micturitions/24 h from baseline to final visit in patients aged ≥65 and ≥75 years. Mirabegron was well tolerated: in both age groups, hypertension and urinary tract infection were among the most common TEAEs over 12 weeks and 1 year. The incidence of dry mouth, a typical anticholinergic TEAE, was up to sixfold higher among the older patients randomised to tolterodine than any dose of mirabegron. Conclusions: these analyses have demonstrated the efficacy of mirabegron over 12 weeks and the tolerability of mirabegron over 12 weeks and 1 year in OAB patients aged ≥65 and ≥75 years, supporting mirabegron as a therapeutic option in older patients with OAB. © The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved.


News Article | November 15, 2016
Site: www.sciencemag.org

BARCELONA, SPAIN—Two major airlines have stopped transporting laboratory animals from mainland Spain to the Canary Islands, an archipelago in the Atlantic Ocean. Their move has put research projects on the islands on hold and has left scientists and politicians scrambling for solutions. The ban is particularly problematic for researchers who need transgenic mice, which are often ordered from specialized labs. The issue may soon be debated in the Spanish parliament; some members want the federal government in Madrid to force the companies to lift their ban, according to a story in Spanish newspaper El País last week. At the request of the Canarian government, the Spanish civil aviation authority has been negotiating a possible solution with various airlines, local newspaper Diario de Avisos reports. Air Europa stopped transporting research animals last year, without providing an explanation. Iberia, Spain's national airline, followed suit in March, citing international regulations and safety issues, including the possibility that mice might escape and damage the aircraft. But regulations don't preclude animal shipments, and damage from escaped rodents "has never been reported in the history of aviation,” says a spokesperson for the European Animal Research Association (EARA) in London. EARA suspects the companies have given in to pressure from animal rights activists. Both Air Europa and Iberia continue to fly pets, including some rodent species. The issue was brought to the media's attention recently by Javier Castro Hernández, a postdoc in rheumatology at the University Hospital of the Canary Islands on Tenerife. Castro had ordered 29 knockout mice from Charles River Laboratories, headquartered in Wilmington, Massachusetts, but the animals have been stranded at an animal facility in Madrid since late September, which costs money and is delaying research, Castro says. Canarian researchers say some 30 other biomedical research projects at the islands' two universities and at university hospitals will be affected as well. Researchers who need transgenic mice from overseas have put their plans on hold, says Teresa Giraldez, who studies the role of ion channels in neurological diseases at the University of La Laguna on Tenerife. "We cannot take the risk that [the animals] get stuck in Madrid,” says Giraldez, who calls the situation “very worrisome.” Without access to transgenic mice, Castro says he's "competing at a disadvantage" with mainland Spain. In recent years, animal rights groups have pressured the few airlines that still transported nonhuman primates for research into ending their service. Many companies, including British Airways, which merged with Iberia in 2011, have gone further and have halted shipments of all research animals; so have some ferry companies. Several scientific associations have expressed support for Air France, which is continuing to ship laboratory animals all over the world. An Iberia spokesperson says Canarian researchers still have other transport options, but researchers have been struggling to find a suitable alternative. The only solution that Castro and his institution could find for his mice is road transport to Lisbon, followed by a flight on Canarian airline Binter. But the long journey would create extra stress for the animals and drive up costs, says Castro, who's hopeful that Spain's civil aviation authority will negotiate a solution. Using a ferry for the more than 1200-kilometer trip across the Atlantic is logistically complex, Giraldez says. Nuno Franco, who studies laboratory animal welfare and ethics at the University of Porto in Portugal, calls the ban "poorly justified" and "damaging" to science. “Canarian scientists, their institutions, and science itself are being [held] hostage," Franco says. “The issue goes beyond whether we should do animal research or not,” Giraldez says. Regulations across Spain are the same, she says, so "you can't have discrimination of this type” between regions.


Cages containing Javier Castro Hernández's transgenic mice after their arrival on Gran Canaria. The animals had been held up in Madrid for months. BARCELONA, SPAIN—Twenty-nine transgenic mice that two Spanish airlines had refused to transport hitched a ride to the Canary Islands on a military plane Friday and are now at their final destination, the University of La Laguna on Tenerife in Spain. The mice, bred in the United States, had been stranded in Madrid for 2 months because Iberia and Air Europa have stopped shipping laboratory animals. The military aircraft left Madrid early Friday morning and flew the mice to the Gando Air Base on Gran Canaria. From there, a shipping company ferried the animals in a 90-minute sea journey to the island of Tenerife, where they were delivered at the only animal facility on the island at 5:30 p.m. local time. The university had negotiated the solution with the military. “We feel relieved after these 2 months, which have been very stressful,” says Javier Castro Hernández, a postdoc at the University Hospital of the Canary Islands who had ordered the animals and who recently sounded the alarm about the airlines' decision. Castro says he looks forward to continuing his research project. But a permanent solution must still be found, Castro Hernández says. The University of La Laguna and the Spanish civil aviation authority are still trying to work out a deal with various carriers. But “the airlines continue to delay giving their answer,” Castro says. “So … the blockade still persists for now.”


Herschorn S.,University of Toronto | Barkin J.,University of Toronto | Castro-Diaz D.,University Hospital of the Canary Islands | Frankel J.M.,Seattle Urology Research Center | And 6 more authors.
Urology | Year: 2013

Objective: To assess the efficacy and tolerability of mirabegron 25 mg and 50 mg once-daily vs placebo in patients with overactive bladder (OAB). Materials and Methods: Patients ≥18 years with OAB symptoms were recruited to a 2-week, single-blind, placebo run-in. Those with ≥8 micturitions per 24 hours and ≥3 urgency episodes were randomized 1:1:1 to once-daily mirabegron 25 mg or 50 mg, or placebo for 12 weeks. Primary endpoints were changes to final visit in mean number of incontinence episodes and micturitions per 24 hours. Key secondary endpoints were changes to final visit in mean volume voided or micturition, change to week 4 in mean number of incontinence episodes and micturitions per 24 hours, changes to final visit in mean level of urgency, number of urgency incontinence episodes, and urgency (grade 3 or 4) episodes per 24 hours. Patient-reported outcomes were assessed using the OAB-questionnaire, Patient Perception of Bladder Condition, and Treatment-Satisfaction-Visual Analog Scale. Results: Both mirabegron groups demonstrated statistically significant improvements in coprimary endpoints vs placebo. Mirabegron 50 mg demonstrated significantly greater improvements vs placebo in the following: change to final visit in mean volume voided per micturition and change to week 4 in mean number of incontinence episodes per 24 hours. Statistically significant improvements vs placebo were demonstrated by mirabegron 50 mg in all patient-reported outcome scales with no increase in the incidence of treatment-emergent adverse events vs placebo. Conclusion: Mirabegron 25 mg and 50 mg were associated with significant improvements in efficacy measures of incontinence episodes and micturition frequency. Mirabegron was well tolerated vs placebo. © 2013 Elsevier Inc. All Rights Reserved.


Groen J.,Erasmus Medical Center | Pannek J.,Swiss Paraplegic Center | Castro Diaz D.,University Hospital of the Canary Islands | Del Popolo G.,University of Florence | And 7 more authors.
European Urology | Year: 2016

Context Most patients with neuro-urological disorders require life-long medical care. The European Association of Urology (EAU) regularly updates guidelines for the diagnosis and treatment of these patients. Objective To provide a summary of the 2015 updated EAU Guidelines on Neuro-Urology. Evidence acquisition Structured literature searches in several databases were carried out to update the 2014 guidelines. Levels of evidence and grades of recommendation were assigned where possible. Evidence synthesis Neurological disorders often cause urinary tract, sexual, and bowel dysfunction. Most neuro-urological patients need life-long care for optimal life expectancy and quality of life. Timely diagnosis and treatment are essential to prevent upper and lower urinary tract deterioration. Clinical assessment should be comprehensive and usually includes a urodynamic investigation. The neuro-urological management must be tailored to the needs of the individual patient and may require a multidisciplinary approach. Sexuality and fertility issues should not be ignored. Numerous conservative and noninvasive possibilities of management are available and should be considered before a surgical approach is chosen. Neuro-urological patients require life-long follow-up and particular attention has to be paid to this aspect of management. Conclusions The current EAU Guidelines on Neuro-Urology provide an up-to-date overview of the available evidence for adequate diagnosis, treatment, and follow-up of neuro-urological patients. Patient summary Patients with a neurological disorder often suffer from urinary tract, sexual, and bowel dysfunction and life-long care is usually necessary. The update of the EAU Guidelines on Neuro-Urology, summarized in this paper, enables caregivers to provide optimal support to neuro-urological patients. Conservative, noninvasive, or minimally invasive approaches are often possible. © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.


Ibanez M.,University of Oviedo | Parra-Blanco A.,University of Oviedo | Zaballa P.,University of Oviedo | Jimenez A.,University Hospital of the Canary Islands | And 4 more authors.
Diseases of the Colon and Rectum | Year: 2011

BACKGROUND: No consensus exists regarding the optimal bowel preparation regimen for patients with poor bowel cleansing at a previous colonoscopy. OBJECTIVE: We investigated the usefulness of an intensive cleansing regimen for repeat colonoscopy after previous failure of bowel preparation. DESIGN AND SETTING: A prospective observational study was performed in patients undergoing colonoscopy at a university-based, tertiary referral hospital. PATIENTS AND INTERVENTION: Outpatients with inadequate preparation at an index colonoscopy were offered a repeat colonoscopy and instructed to follow an intensive preparation regimen consisting of a low-fiber diet for 72 hours, liquid diet for 24 hours, bisacodyl (10 mg) in the evening of the day before the colonoscopy, and a split dose of polyethylene glycol (1.5 L in the evening before and 1.5 L in the morning on the day of the colonoscopy). MAIN OUTCOME MEASURES: The adequacy of bowel cleansing was assessed according to the Boston Bowel Preparation Scale (0 or 1 on any colon segment = inadequate bowel preparation). Procedural variables, detection rates for polyps and adenomas, compliance, and tolerability of the regimen were assessed. Satisfaction with the regimen was assessed with a 10-point visual analog scale. RESULTS: Of 83 patients with inadequate bowel preparation at colonoscopy, 51 underwent a second colonoscopy and were analyzed; 46 patients (90.2%) had adequate bowel cleansing at the second colonoscopy, with a mean (SD) total Boston Bowel Preparation Scale score of 7.43 (1.5) and scores of 2.31 (0.6) for the right colon, 2.49 (0.6) for the transverse colon, and 2.63 (0.6) for the left colon. Polyps, flat lesions, or flat lesions proximal to the splenic flexure were found in significantly more patients at the second colonoscopy than at the index colonoscopy. The global satisfaction score was 6.6 (2.7). LIMITATIONS: The study was limited because of its open observational design, possible patient learning effect for bowel preparation at the repeat colonoscopy, and the inclusion of only outpatients. CONCLUSIONS: An intensive regimen consisting of a lowfiber diet, bisacodyl, and a split dose of polyethylene glycol can achieve good colon preparation with an improved detection rate for polyps and adenomas in most patients who have had poor bowel cleansing at a previous colonoscopy. ©The ASCRS 2011.


Hernandez-Guerra M.,University Hospital of the Canary Islands | de Ganzo Z.A.,University Hospital of the Canary Islands | Gonzalez-Mendez Y.,University Hospital of the Canary Islands | Salido E.,University Hospital of the Canary Islands | And 5 more authors.
Hepatology | Year: 2013

Chronic intermittent hypoxia (CIH) occurs with obstructive sleep apnea syndrome (OSAS) and provokes systemic endothelial dysfunction, which is associated with oxidative stress and low nitric oxide (NO) bioavailability. Cirrhotic livers exhibit intrahepatic endothelial dysfunction, which is characterized by an impaired endothelium-dependent response to vasodilators and hyperresponse to vasoconstrictors. We hypothesized that CIH may also contribute to intrahepatic endothelial dysfunction in cirrhosis. Normal and cirrhotic rats were exposed for 14 days to repetitive cycles of CIH mimicking OSAS in humans, or caged with room air (handled controls [HC]). Hepatic endothelial function was assessed in isolated and perfused rat livers by dose-response curves to acetylcholine (ACh) and methoxamine (Mtx). In a group of cirrhotic rats, in vivo systemic and hepatic hemodynamic parameters were evaluated at baseline and after volume expansion. In addition, liver samples were obtained to assess endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS), NO bioavailability, and nitrotyrosinated proteins as a marker of oxidative stress. Cirrhotic rats exposed to CIH exhibited an attenuated vasodilatory response to ACh and hyperresponse to Mtx compared with HC rats. During volume expansion, similar portal pressure increases were observed in CIH and HC rats, although the mean arterial pressure increase was lower after CIH. These functional responses were associated with the presence of increased hepatic oxidative stress without changes in p-eNOS after CIH exposure. In normal rats, no hemodynamic changes were found. Conclusion: CIH exacerbates intrahepatic endothelial dysfunction in cirrhotic rats, which is associated with increased oxidative stress that may reduce NO bioavailability. Clinical studies are needed to assess whether OSAS contributes to endothelial impairment in human patients with cirrhosis. © 2012 American Association for the Study of Liver Diseases.

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