Balloon-Expandable Pulmonary Valves for Patched or Native Right Ventricular Outflow Tracts.

The implantation of percutaneous balloon expandable valves in native or patched right ventricular outflow tracts (nRVOT) is a challenging technique due to the diversity of anatomies and shapes, the large sizes, and the distensibility of the nRVOT, for which specific techniques have been developed. We present a single center experience with balloon expandable percutaneous pulmonary valves in nRVOT, describing the techniques used, complications observed, and a short-mid term follow-up.. This is a single center descriptive study of patients who underwent a percutaneous pulmonary valve implantation in a nRVOT with a balloon expandable pulmonary valve in our center between September 2012 and June 2022.. We implanted successfully 45 valves in 46 patients (20 Sapien and 25 Melody). Tetralogy of Fallot or pulmonary atresia with VSD were the main congenital heart disease (n = 32). All were pre-stented, 18 in a one step procedure. We used a Dryseal sheath in 13/21 Sapien. In 6 patients we used the anchoring technique, 5 with a very large nRVOT and one pyramidal nRVOT. In the 3.5 year follow-up 7 patients developed endocarditis and 3 required a valve redilation, no fractures were observed. PPVI of native RVOT with balloon expandable valves is feasible in a number of selected anatomies, including large or pyramidal nRVOT, using specific techniques, (presenting, LPA anchoring).

Sticholysin II shows similar immunostimulatory properties to LLO stimulating dendritic cells and MHC-I restricted T cell responses of heterologous antigen.

Induction of CD8+ T cell responses against tumor cells and intracellular pathogens is an important goal of modern vaccinology. One approach of translational interest is the use of liposomes encapsulating pore-forming proteins (PFPs), such as Listeriolysin O (LLO), which has shown efficacy at priming strong and sustained CD8+ T cell responses. Recently, we have demonstrated that Sticholysin II (StII), a PFP from the sea anemone Stichodactyla helianthus, co-encapsulated into liposomes with ovalbumin (OVA) was able to stimulate, antigen presenting cells, antigen-specific CD8+ T cells and anti-tumor activity in mice. In the present study, we aimed to compare StII and LLO in terms of their abilities to stimulate dendritic cells and to induce major histocompatibility complex (MHC) class I restricted T cell responses against OVA. Interestingly, StII exhibited similar abilities to LLO in vitro of inducing dendritic cells maturation, as measured by increased expression of CD40, CD80, CD86 and MHC-class II molecules, and of stimulating OVA cross-presentation to a CD8+ T cell line. Remarkably, using an ex vivo Enzyme-Linked ImmunoSpot Assay (ELISPOT) to monitor gamma interferon (INF-γ) producing effector memory CD8+ T cells, liposomal formulations containing either StII or LLO induced comparable frequencies of OVA-specific INF-γ producing CD8+ T cells in mice that were sustained in time. However, StII-containing liposomes stimulated antigen-specific memory CD8+ T cells with a higher potential to secrete IFN-γ than liposomes encapsulating LLO. This StII immunostimulatory property further supports its use for the rational design of T cell vaccines against cancers and intracellular pathogens. In summary, this study indicates that StII has immunostimulatory properties similar to LLO, despite being evolutionarily distant PFPs.

[Role of omega-3 fatty acids in cardiovascular disease prevention]. / Papel de los ácidos grasos omega-3 en la prevención de enfermedades cardiovasculares.

Fatty acids, in addition to its known energy value and its structural function, have other beneficial properties. In particular, the polyunsaturated fatty acids omega-3 acting on the cardiovascular apparatus through many channels exerting a protective effect against cardiovascular risk. The benefits associated with the reduction in cardiac mortality and sudden death particular, are related to the incorporation of EPA and DHA in phospholipid membrane of cardiomyocytes. An index is established that relates the percentage of EPA + DHA of total fatty acids in erythrocytes and risk of death from cardiovascular disease may layering in different degrees. Therefore, the primary source of fatty fish w-3 PUFA, behaves like a reference food in cardiosaludables diets.

Los ácidos grasos, además de su conocido valor energético y su función estructural, presentan otro tipo de propiedades beneficiosas. En concreto, los ácidos grasos poliinsaturados omega-3 actúan sobre el aparato cardiovascular a través de multitud de vías ejerciendo un efecto protector frente al riesgo cardiovascular. Los beneficios asociados a la reducción de la mortalidad cardiaca y en concreto la muerte súbita, están relacionados con la incorporación de EPA y DHA en los fosfolípidos de la membrana de los cardiomiocitos. Se ha establecido un índice que relaciona el porcentaje de EPA+DHA del total de ácidos grasos en los eritrocitos y riesgo de muerte por enfermedad cardiovascular pudiendo estratificarlo en diferentes grados. Por lo tanto, el pescado graso principal fuente de AGPI w-3, se comporta como alimento de referencia en las dietas cardiosaludables.

[Lipid profile analysis of two species of hake "merluccius capensis and merluccius paradoxus" and its contribution to cardiovascular disease prevention]. / Análisis del perfil lipídico de dos especies de merluza "Merluccius capensis y Merluccius paradoxus" y su aportación a la prevención de enfermedades cardiovasculares.

INTRODUCTION: In recent years it has been shown that omega-3 PUFAs have multiple cardiovascular protective effects. Currently, fish is the main and most important source of Omega-3 fatty acids. OBJECTIVE: To analyze the fatty acid composition in two species of hake, its content of omega-3 fatty acids and study their contribution to the prevention of cardiovascular diseases. MATERIAL AND METHODS: We analyzed samples of two species of hake (Merluccius capensis and Merluccius paradoxus) in its natural state and frozen, cooked by microwave and boiled samples. We have studied the moisture content, lipid content and analysis, identification and composition of fatty acids. RESULTS: It was observed that the content of w-3 PUFA was higher than the w-6 PUFA. The omega-3 fatty acids DHA and EPA were the most representative of the omega-3 family, highlighting the DHA content in all samples analyzed. It has also demonstrated the safety of the cooking methods :microwave" and "boiling" as methods that ensure the integrity of the w-3 PUFA. CONCLUSION: Hake samples analyzed present an optimal lipid profile. Its content of w-3 PUFA and their properties, make hake fish is distinguished as hearthealthy diets reference.

Introducción: En los últimos 2013s se ha demostrado que los AGPI omega-3 presentan múltiples efectos protectores cardiovasculares. Actualmente, el pescado constituye la principal y la más importante fuente de ácidos grasos Omega-3. Objetivo: Analizar la composición en ácidos grasos en dos especies de merluza, determinar su contenido en ácidos grasos omega-3 y estudiar su aportación en la prevención de enfermedades cardiovasculares. Material y métodos: Se han analizado muestras de dos especies de merluza (Merluccius capensis y Merluccius paradoxus) en su estado natural y congeladas, cocinadas al microondas y muestras hervidas. Se ha estudiado el contenido en humedad, contenido lipídico y el análisis, composición e identificación de ácidos grasos. Resultados: Se observó que el contenido de AGPI w-3 fue mayor que el de AGPI w-6. Los ácidos grasos omega-3 DHA y EPA fueron los más representativos de la familia omega-3, destacando el contenido de DHA en todas lasmuestras analizadas. Asimismo, se ha demostrado la seguridad de los métodos de cocción «microondas¼ y «hervido¼ como métodos que aseguran la integridad de los AGPI w-3. Conclusión: Las muestras de merluza analizadas presentan un óptimo perfil lipídico. Su contenido en AGPI w-3 y sus propiedades, hacen que la merluza se distinga como pescado de referencia en dietas cardiosaludables.

Amlodipine in pediatric patient with uncontrolled multifactorial hypertension. Formulation of amlodipine oral suspension.

OBJECTIVE: To describe the case of treatment with amlodipine in a poorly controlled hypertension in a pediatric patient diagnosed with tricodistrofia. CASE SUMMARY: Girl 5 years old, diagnosed of tricodistrofia included within the Tay-Sachs syndrome. As a consequence of a cardiac arrest suffered in the context of a respiratory distress syndrome associated with infection by influenza A, she developed hypertension initially treated with nifedipine and captopril. After several months of treatment and a poor control of the hypertension, a change of treatment was decided, substituting nifedipine by amlodipine (2.5 mg/24 hours orally) and captopril by enalapril (2.5 mg/24 hours orally). Pharmacy service is request to get a amlodipine syrup that allows a dose adjustment to the needs of the patient. After the change of treatment the patient begins to maintain diastolic blood pressure levels within the normal range, suspending the administration of enalapril, maintaining good control of blood pressure with amlodipine 2 mg/24 hours. DISCUSSION: Most of antihypertensive drugs used in adults do not have clinical trials to evaluate its effects in the pediatric population. Furthermore, the lack of familiarity with the pharmacokinetic characteristics of the child, raises problems to adjust the dose to the changing reality of a child. In this situation, clinical experience supports the use of some of these drugs in children with optimal results. With the addition to the pediatric field of calcium antagonists and ACE-inhibitors or ARB-II, they allow as to have greater potential therapeutic alternatives.

[Home parenteral nutrition in Crohn's Disease patient: a case report]. / Nutrición parenteral domiciliaria en paciente con enfermedad de Crohn: a propósito de un caso.

Patient diagnosed with Crohn's Disease with inflammatory pattern that evolves stenosing-piercing, causing abdominal perforation and fecal peritonitis. She was underwent to three surgeries, leading to numerous complications and a torpid clinical course. Given the state of malnutrition on admission it was prescribed Total Parenteral Nutrition (TPN), extending the administration for more than 10 months. In this period the TPN is suspended for 5 days, but the persistence of an enterocutaneous fistula causes the restoration of the TPN. After clinical stabilization, the patient is discharged to recover her nutritional status necessary to perform a bowel reconstruction surgery, continuing with TPN at home. After 7 and a half months, the patient with an optimal nutritional status, undergoes surgery, evolving favorably and suspending the TPN at 9 days.

[Efficacy and toxicity of erlotinib in non-small cell lung cancer treatment]. / Efectividad y toxicidad de erlotinib en la farmacoterapia del cáncer de pulmón no microcítico.

OBJECTIVE: To evaluate the efficacy and toxicity of erlotinib in patients with non-small cell lung cancer. METHOD: Patients were selected from an outpatients' dispensing database. The time period selected was from January 2008 to January 2010. Data was collected from patient's medical history - electronic and paper based. We used Response Evaluation Criteria in Solid Tumours (RECIST) to measure response and measured time to progression and overall survival. Toxicity was evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE). RESULTS: We found partial response in 5/46 patients and stable disease in 14/46 patients. Time to disease progression was 4.01 months (median 2.33 months) and overall survival was 5.63 months (median 4.67). The most common toxicities were rash, anorexia, asthenia, infection and gastrointestinal side effects. Patients who developed skin toxicity had a (statistically significant) greater time to progression and overall survival rate than the group that did not develop this toxicity (mean time to progression: 2.76 vs. 7.87 months; mean overall survival: 10.74 months vs. 3.98). CONCLUSIONS: Survival analysis findings suggest lower efficacy in our patient population in comparison with data seen in other publications, and adverse events followed the expected pattern. Although our greatest limitation was sample size, which must be kept in mind, this therapy could be an alternative for patients with non-small cell lung cancer.

Poliquistosis hidatidica pulmonar / Poliquistosis hidatidita lung

Se trata de un caso clínico, diagnosticado como quiste hidatídico en forma casual, que ingresa al servicio de medicina interna con el diagnóstico de neumonía. El estudio radiológico informa tres masas circunscritas, uno en el pulmon derecho y dos en el izquierdo, se sospecha de poliquistosis hidatídica pulmonar versus CA metastásico pulmonar, el examen ecográfico indica contenido liquido y la TAC lo confirma

Characterization of the HCV core virus-like particles produced in the methylotrophic yeast Pichia pastoris.

Little is known about the mechanism of hepatitis C virion assembly. So the capacity of the entire Hepatitis C virus core protein (HCcAg) produced in Pichia pastoris to form particles either in its native soluble state or after detergent treatment of HCcAg associated to cell debris were studied. Size exclusion chromatography suggested that HCcAg assembled into high molecular weight structures. HCcAg was also specifically recognized by a serum from a chronic HCV carrier patient. This antigen migrated with buoyant density values similar to those obtained for native nucleocapsid particles from infected patients when analyzed using sucrose density gradient centrifugation. The analysis by electron microscopy of purified HCcAg showed aggregates resembling virus-like particles (VLPs) with an average diameter of 30 nm. These results indicated that the HCcAg obtained from P. pastoris assembled into VLPs resembling HCV nucleocapsid particles in a mature stage. Such HCcAg aggregates characterized here could be a valuable tool to elucidate the mechanisms of HCV nucleocapsid assembly.

[Comparative study of piperacillin/tazobactam versus imipenem/cilastatin in febrile neutropenia (1994-1996)]. / Estudio comparativo de piperacilina/tazobactam frente a imipenem/cilastatina en la neutropenia febril (1994-1996).

BACKGROUND: We aimed at comparing the effectiveness and safety of piperacillin/tazobactam(PIP-TAZ) versus imipenem/cilastin (IMI) administered as empiric monotherapy in patients with febrile neutropenia. PATIENTS AND METHOD: Patients with hematological diseases who were randomly assigned either PIP-TAZor IMI were enrolled in the study. A sequential strategy of antibiotic therapy addition was applied as long as fever persisted or microorganisms were isolated at 72 h. Moreover, if bacteriologically unconfirmed fever persisted after 5-7 days, an antifungal therapy was started. The treatment was considered successful if fever and clinical signs resolved and/or pathogens were cleared without adding further antibiotics at 72 h. Differences between percentages were analyzed using the *2test. RESULTS: 137 patients were evaluated. The successful response rate of PIP-TAZ after 72 h was similar to IMI (32.2 and 35.2%). The defervescence time was shorter (3.6 and 4.2 days) and the bacterial response more favourable with PIP-TAZ than with IMI, but statistically significant differences were not reached. The overall response in both groups was 91%.18.2% of episodes were bacteriologically confirmed. The most frequent isolated microorganism was Staphylococcus coagulase-negative(48.8%). There was one only case of septic shock, within the IMI group, and the overall mortality of the group was 8.7%. The occurrence of vomiting in the IMI group was significantly higher than in the PIP-TAZ group (39.9 and 5.6%; p < 0.0001). CONCLUSIONS: PIP-TAZ is as effective as IMI and it constitutes a good choice as an initial empiric monotherapy of febrile neutropenia.

Assembly of truncated HCV core antigen into virus-like particles in Escherichia coli.

Core protein is one of the most conserved and immunogenic of the hepatitis C virus proteins. Several pieces of experimental evidence suggest its ability for formation of virus like particles alone or in association with other viral proteins in mammalian or yeast cells with great similarity to those detected in patient sera and liver extract. In this work we report an Escherichia coli-derived truncated hepatitis C core protein that is able to aggregate. SDS-PAGE and size exclusion chromatography patterns bring to mind the aggregation of monomers of recombinant protein Co.120. The Co.120 protein migrated with buoyant density of 1.28 g/cm(3) when analyzed using CsCl density gradient centrifugation. Spherical structures with an average diameter of 30 nm were observed using electron microscopy. We report here that VLPs are generated when the first 120 aa of HCV core protein are expressed in E. coli.

Expression and immunological evaluation of the Escherichia coli-derived hepatitis C virus envelope E1 protein.

Immunological response against envelope protein E1 is very important in natural hepatitis C virus (HCV) infection, although it is insufficient to clear the viraemia. The HCV genomic region encoding the first 149 amino acids of the envelope E1 protein (E1(340), amino acids 192-340) was expressed in Escherichia coli (to a level of 30% of the whole cellular proteins) and purified to 85%. We measured the immune response in rabbits and mice as well as the reactivity against 37 human sera raised against the whole recombinant protein and E1-encoding peptides. From this, 51.1% of human sera were found to react with E1(340). High-level antibodies against E1(340) were obtained in rabbits and mice when immunized. These antibodies had a similar peptide-recognition pattern to that described previously for human sera. The most reactive region was located at the N-terminus of the E1 protein. Cellular immunity in mice was evaluated by delayed-type hypersensitivity assay. It revealed the induction of a CD4+ T-cell-mediated response by this protein. This E1(340) protein and the animal-derived anti-E1 sera are immunological tools that could aid in the monitoring and development of anti-HCV therapies.

[Clinical, epidemiological and microbiological aspects of Mobiluncus sp. in bacterial vaginosis]. / Aspectos clínicos, epidemiológicos y microbiológicos de Mobiluncus sp. en la vaginosis bacteriana.

BACKGROUND: In this paper, our goal was to determine the optimal isolation conditions, biochemical characterization, and preservation of species of the genus Mobiluncus, associated with bacterial vaginosis in patients attending the family planning clinic. Also, we tried to relate its presence with demographic variables and criteria used in the clinical diagnosis of bacterial diagnosis. METHODS: The specimen from the posterior fornix were collected and transported to the laboratory in a Stuart medium, one at room temperature and the other at 4 degrees C. These samples were inoculated in anaerobic culture media. RESULTS: Of a total of 92 patients studied, 61 (66.3%) were normal, 28 (30.4%) bacterial vaginosis, and 3 (3.3%) had intermediate vaginosis. There was statistically significant relationship only with intrauterine device use (p = 0.00499). The presence of curved rod, using Gram's method, was significantly related with pH (p = 0.00000) positive amines test (p = 0.00000), and the presence of clue cells (p = 0.00000). Mobiluncus was observed in 23 samples (82%), and the majority (15) using RLK agar (cold enrichment technique). With conventional techniques, we identified 12 strains as Mobiluncus curtisii and 3 strains as Mobiluncus mulieris. The strains of Mobiluncus sp. grew better from litmus milk conserved at -30 degrees C. CONCLUSION: Isolating Mobiluncus sp. is fairly easy, if the right media and the techniques are used.

IL-4 and IL-10 are both required for the induction of oral tolerance.

Protection from the development of experimental autoimmune uveitis (EAU) can be induced by feeding mice interphotoreceptor retinoid binding protein before uveitogenic challenge with the same protein. Two different regimens are equally effective in inducing protective tolerance, although they seem to do so through different mechanisms: one involving regulatory cytokines (IL-4, IL-10, and TGF-beta), and the other with minimal involvement of cytokines. Here we studied the importance of IL-4 and IL-10 for the development of oral tolerance using mice genetically engineered to lack either one or both of these cytokines. In these animals we were able to protect against EAU only through the regimen inducing cytokine-independent tolerance. When these animals were fed a regimen that in the wild-type animal is thought to predominantly induce regulatory cells and is associated with cytokine secretion, they were not protected from EAU. Interestingly, both regimens were associated with reduced IL-2 production and proliferation in response to interphotoreceptor retinoid binding protein. These findings indicate that both IL-4 and IL-10 are required for induction of protective oral tolerance dependent on regulatory cytokines, and that one cytokine cannot substitute for the other in this process. These data also underscore the fact that oral tolerance, manifested as suppression of proliferation and IL-2 production, is not synonymous with protection from disease.

Cytokine-dependent modulation of oral tolerance in a murine model of autoimmune uveitis.

In summary, our data suggest that oral tolerance in the mouse EAU model may occur by anergy/deletion or by suppression, depending on the feeding regimen. Tolerance involving putative regulatory cells appears to require the ability to produce both IL-4 and IL-10, whereas induction of tolerance involving anergy may not require the presence of Il-4 and IL-10. We propose that regulatory cells induced by three feedings of IRBP can be selectively enhanced through the use of cytokines. From the point of view of clinical therapy, it would be worthwhile to explore postimmunization feeding regimens involving administration of IL-4 and IL-10.

Interleukin-2 treatment potentiates induction of oral tolerance in a murine model of autoimmunity.

The present study addresses the feasibility of potentiating oral tolerance by immunomanipulation, using the murine model of experimental autoimmune uveoretinitis (EAU) induced by immunization with the retinal antigen interphotoreceptor retinoid binding protein (IRBP). Three feedings of 0.2 mg IRBP every other day before immunization did not protect against EAU, whereas a similar regimen of five doses was protective. However, supplementing the nonprotective 3x regimen with as little as one injection of 1,000 U of human recombinant interleukin-2 (IL-2) resulted in disease suppression that was equal to that of the protective 5x regimen. The protective effect was maintained across a range of IL-2 doses and times of administration; none of the IL-2 regimens tested resulted in disease enhancement. Peyer's Patch cells of 3x-fed and IL-2-treated mice showed greatly increased production of TGF-beta, IL-4, and IL-10 compared with animals given the nonprotective 3x regimen and to animals given the protective 5x regimen. We propose that IL-2 treatment enhances protection from EAU at least in part by stimulating production of antiinflammatory cytokines by regulatory cells in Payer's Patches. Moreover, the observed lymphokine production patterns suggest that whereas protection induced by the 3x + IL-2 regimen is likely to involve antiinflammatory cytokines, protection induced by the 5x regimen might involve anergy or deletion of the uveitogenic T cells. These results could have practical implications for use of IL-2 as a safe and effective way of potentiating oral tolerance.

Hypocalcemia in critically ill children.

To determine the prevalence and clinical consequences of hypocalcemia in pediatric intensive care unit patients, we prospectively studied calcium homeostasis in 145 of these patients. The total serum calcium concentration was measured in all patients. The serum ionized calcium concentration was measured in blood samples collected from those 71 (49%) patients who had low total serum calcium values (less than 8.5 mg/dl (2.12 mmol/L). Of the 71 patients, 26 (36.6%) had ionized hypocalcemia. Therefore the prevalence of ionized hypocalcemia was at least 17.9% (26/145). Death occurred in 8 (31%) of 26 patients with ionized hypocalcemia versus 3 (2.5%) of 119 patients with normocalcemia (p less than 0.0001). However, the severity of illness score was higher (p less than 0.05) in the children with ionized hypocalcemia than in normocalcemic children (mean Therapeutic Intervention Scoring System score 33 +/- 17 vs 22 +/- 11, respectively). More of the children with ionized hypocalcemia had sepsis (p = 0.0299) and they required the administration of vasopressor agents more often (p = 0.0002) than their normocalcemic counterparts. Of the 26 patients with ionized hypocalcemia, 17 (65.4%) had biochemical evidence of either absolute or relative hypoparathyroidism, determined by means of an immunoradiometric assay that measures only biologically active parathyroid hormone. We conclude the following: (1) ionized hypocalcemia is common in severely ill children. (2) Patients with ionized hypocalcemia have a higher mortality rate than those with normocalcemia; however, because the former are more severely ill, no causality is apparent or suggested. (3) Functional hypoparathyroidism may occur in critically ill children.