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Lluch P.,Hospital Clinico Universitario Valencia | Segarra G.,University of Valencia | Medina P.,University of Valencia
World Journal of Gastroenterology | Year: 2015

Cirrhosis is associated with marked abnormalities in the circulatory function that involve a reduction in systemic vascular resistance. An important cause of this vasodilatation is the increased production or activity of nitric oxide (NO) in the splanchnic circulation. During portal hypertension and cirrhosis an increased endothelial NO synthase (eNOS) activity is demonstrated in splanchnic vessels. In contrast, the activity of eNOS in the cirrhotic liver is decreased, which suggests a different regulation of eNOS in the liver and in the splanchnic vessels. Asymmetric dimethylarginine (ADMA) is an endogenous NO inhibitor and higher plasma levels of ADMA are related to increased cardiovascular risk in both the general population and among patients with cirrhosis. It has been demonstrated that the liver is a key player in the metabolism of ADMA. This observation was further supported by investigations in human patients, showing a close correlation between ADMA plasma levels and the degree of hepatic dysfunction. ADMA is degraded to citrulline and dimethylamine by dimethylarginine dimethylaminohydrolases (DDAHs). DDAHs are expressed as type 1 and 2 isoforms and are widely distributed in various organs and tissues, including the liver. In this review, we discuss experimental and clinical data that document the effects of dimethylarginines on vascular function in cirrhosis. Our increasing understanding of the routes of synthesis and metabolism of methylarginines is beginning to provide insights into novel mechanisms of liver disease and allowing us to identify potential therapeutic opportunities. © The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.

Villanueva V.,Polytechnic University of Valencia | Lopez-Gomariz E.,Hospital Lluis Alcanyis Xativa | Lopez-Trigo J.,Consorcio Hospital General Universitario Valencia | Palau J.,Polytechnic University of Valencia | And 4 more authors.
Epilepsy and Behavior | Year: 2012

There has been little long-term success with polytherapy for patients with refractory partial-onset epilepsy. The rational combination of antiepileptic drugs based on their mechanism of action may help improve treatment efficacy and tolerability. Lacosamide, a novel sodium channel blocker (SCB), was investigated in 158 patients with partial-onset epilepsy in the prospective, multicenter, observational, RELACOVA cohort study conducted in Spain. After 12. months' treatment with lacosamide, 47% of patients were responders (≥ 50% reduction in seizure frequency) and 24% were seizure free. Lacosamide was well tolerated; dizziness was the most frequent adverse event. Efficacy was better (responder rate, 65% vs 38%; seizure free rate, 35% vs 17%) and there was a lower adverse event rate (33% vs 58%) in patients receiving non-SCBs (n = 49) versus those receiving SCBs (n = 104) as concomitant therapy at baseline. Further investigation of lacosamide combination therapy is warranted. © 2012 Elsevier Inc.

Perez-Fidalgo J.A.,Hospital Clinico Universitario Valencia | Eroles P.,University of Valencia | Ferrer J.,Research Institute INCLIVA | Bosch A.,Hospital Clinico Universitario Valencia | And 5 more authors.
Breast | Year: 2013

Purpose: Whether or not to biopsy the metastasis in recurrent breast cancer has become mired in controversy. Several studies have shown an important discordance of the immunohistochemical (IHC) determinations for ER, PR and HER2 between primary (PT) and recurrent tumors (RT). Yet it remains unknown within this what impact technical issues have. The aim of our study was to assess whether technical variability might have an impact on the concordance between PT and RT. Methods: IHC determinations in paired biopsies from PT and RT were compared under routine vs study conditions. In the former, pathological analysis reproduced the conditions used in the routine of a University Pathology Department. In the latter, in a technical bias-minimizing manner, samples were re-assessed at the same timing and by two independent observers. Results: 128 paired biopsies from 64 patients were analyzed under both conditions. Concordance under routine vs study conditions for ER was 66% vs 93.4% ( p=0.001), for PR 58.7% vs 80.3% ( p=0.064) and for HER2 86.8% vs 96.8% ( p=0.25). Kappa index under routine versus study conditions for ER was 0.27 vs 0.79 ( p=0.002), for PR 0.26 vs 0.39 ( p=0.47) and for HER2 0.67 vs 0.9 ( p=0.14). Conclusions: Although discordance rate between PT and RT decreased under conditions minimizing technical issues, some discordant cases appeared not to be subjected to this confounding factor. Either for clinical practice or for future studies reassessment of PT in recurrent breast cancer should be encouraged. © 2013 Elsevier Ltd.

Rovira Soriano L.,Hospital Clinico Universitario Valencia | Belda Nacher J.,Hospital Clinico Universitario Valencia
Trends in Anaesthesia and Critical Care | Year: 2013

Morbidly obese patients are at increased risk of respiratory complications, appropriate management of these patients prevents perioperative respiratory complications. Some aspects of respiratory physiology, posture, ventilatory management including mechanical ventilation and Non-invasive ventilation (NIV), drugs related to respiratory function, and chest physiotherapy will be reviewed to manage these patients properly. © 2012 Elsevier Ltd.

Merlos P.,Hospital Clinico Universitario Valencia | Nunez J.,Hospital Clinico Universitario Valencia | Sanchis J.,Hospital Clinico Universitario Valencia | Minana G.,Hospital Clinico Universitario Valencia | And 7 more authors.
European Journal of Internal Medicine | Year: 2013

Background Prognostic implications of echocardiographic assessment of pulmonary hypertension (PH) in non-selected patients hospitalized for acute heart failure (AHF) are not clearly defined. The aim of this study was to evaluate the association between echocardiography-derived PH in AHF and 1-year all-cause mortality. Methods We prospectively included 1210 consecutive patients admitted for AHF. Patients with significant heart valve disease were excluded. Pulmonary arterial systolic pressure (PASP) was estimated using transthoracic echocardiography during hospitalization (mean time after admission 96 ± 24 h). Patients were categorized as follows: non-measurable, normal PASP (PASP ≤ 35 mm Hg), mild (PASP 36-45 mm Hg), moderate (PASP 46-60 mm Hg) and severe PH (PASP > 60 mm Hg). The independent association between PASP and 1-year mortality was assessed with Cox regression analysis. Results At 1-year follow-up, 232 (19.2%) deaths were registered. PASP was measured in 502 (41.6%) patients with a median of 46 [38-55] mm Hg. The distribution of population was: 708 (58.5%), 76 (6.3%), 147 (12.1%), 190 (15.7%) and 89 (7.4%) for non-measurable, normal PASP, mild, moderate and severe PH, respectively. One-year mortality was lower for patients with normal PASP (1.32 per 10 person-years), intermediate for patients with non-measurable, mild and moderate PH (2.48, 2.46 and 2.62 per 10 persons-year, respectively) and higher for those with severe PH (4.89 per 10 person-years). After multivariate adjustment, only patients with PASP > 60 mm Hg displayed significant adjusted increase in the risk of 1-year all-cause mortality, compared to patients with normal PASP (HR = 2.56; CI 95%: 1.05-6.22, p = 0.038). Conclusions In AHF, severe pulmonary hypertension derived by echocardiography is an independent predictor of 1-year-mortality. © 2013 European Federation of Internal Medicine.

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