Expression of insulin receptor (IR) A and B isoforms, IGF-IR, and IR/IGF-IR hybrid receptors in vascular smooth muscle cells and their role in cell migration in atherosclerosis.

BACKGROUND: Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) is a major contributor to the development of atherosclerotic process. In a previous work, we demonstrated that the insulin receptor isoform A (IRA) and its association with the insulin-like growth factor-I receptor (IGF-IR) confer a proliferative advantage to VSMCs. However, the role of IR and IGF-IR in VSMC migration remains poorly understood. METHODS: Wound healing assays were performed in VSMCs bearing IR (IRLoxP+/+ VSMCs), or not (IR-/- VSMCs), expressing IRA (IRA VSMCs) or expressing IRB (IRB VSMCs). To study the role of IR isoforms and IGF-IR in experimental atherosclerosis, we used ApoE-/- mice at 8, 12, 18 and 24 weeks of age. Finally, we analyzed the mRNA expression of total IR, IRB isoform, IGF-IR and IGFs by qRT-PCR in the medial layer of human aortas. RESULTS: IGF-I strongly induced migration of the four cell lines through IGF-IR. In contrast, insulin and IGF-II only caused a significant increase of IRA VSMC migration which might be favored by the formation of IRA/IGF-IR receptors. Additionally, a specific IGF-IR inhibitor, picropodophyllin, completely abolished insulin- and IGF-II-induced migration in IRB, but not in IRA VSMCs. A significant increase of IRA and IGF-IR, and VSMC migration were observed in fibrous plaques from 24-week-old ApoE-/- mice. Finally, we observed a marked increase of IGF-IR, IGF-I and IGF-II in media from fatty streaks as compared with both healthy aortas and fibrolipidic lesions, favoring the ability of medial VSMCs to migrate into the intima. CONCLUSIONS: Our data suggest that overexpression of IGF-IR or IRA isoform, as homodimers or as part of IRA/IGF-IR hybrid receptors, confers a stronger migratory capability to VSMCs as might occur in early stages of atherosclerotic process.

[Randomised clinical trial to compare two tracheotomy care methods in an Intensive Care Unit]. / Ensayo clínico aleatorizado para la comparación de dos métodos de cura de traqueotomía en una Unidad de Cuidados Intensivos.

INTRODUCTION: Tracheotomy is a common technique in Intensive Care Units (ICU). It is known that nursing care during and after that procedure is directly related to its success, by reducing the possible complications to a minimum, such as the stoma infection, and contributing to a favourable outcome in critical patients. OBJECTIVES: To compare the use of polyhexanide (PLX) versus saline+povidone iodine (PY) as antiseptics and infection incidence in tracheostomies performed in Intensive Care Units. MATERIAL AND METHOD: A 2-year, experimental, randomised, open-label trial carried out in a multidiscipline ICU with 32 beds. The study was approved by the Research Ethics Committee of Principality of Asturias. RESULTS: The overall infection rate observed for every hundred patients was 1.34 (95% CI; 0.81-2.01), with 1.46 when using PLX and 1.21 for PY (P=.685). CONCLUSIONS: In spite of the experimental treatment (PLX) was shown to be effective in other types of wounds in our study. No significant differences were found between this technique and the standard one. Since there is no national registry of tracheotomy- associated infections, it is not possible to know whether the rate observed is within the usual parameters.

Role of deep brain stimulation therapy in the magnetic resonance-guided high-frequency focused ultrasound era: current situation and future prospects.

Introduction: Deep brain stimulation (DBS) is a well-established treatment of movement disorders; but recently there has been an increasing trend toward the ablative procedure magnetic resonance-guided focused ultrasound (MRgFU). DBS is an efficient neuromodulatory technique but associated with surgical complications. MRIgFUS is an incision-free method that allows thermal lesioning, with fewer surgical complications but irreversible effects.Areas covered: We look at current and prospective aspects of both techniques. In DBS, appropriate patient selection, improvement in surgical expertise, target accuracy (preoperative and intraoperative imaging), neurophysiological recordings, and novel segmented leads need to be considered. However, increased number of older patients with higher comorbidities and risk of DBS complications (mainly intracranial hemorrhage, but also infections, hardware complications) make them not eligible for surgery. With MRgFUS, hemorrhage risks are virtually nonexistent, infection or hardware malfunction are eliminated, while irreversible side effects can appear.Expert commentary: Comparison of the efficacy and risks associated with these techniques, in combination with a growing aged population in developed countries with higher comorbidities and a preference for less invasive treatments, necessitates a review of the indications for movement disorders and the most appropriate treatment modalities.

[Liver abscess: retrospective review of 68 cases]. / Abscesos hepáticos: análisis retrospectivo de 68 casos.

OBJECTIVE: To assess clinical and laboratory features of patients with liver abscesses (LA), and determine prognostic features. METHODS: We performed a retrospective analysis of medical records of patients receiving a diagnosis of LA in the Hospital Severo Ochoa, between 1989-2005. RESULTS: We were able to find 68 patients: 39 males and 29 females; the incidence amounts 26 cases/100,000 hospital admissions; mean age 63 years. A biliary source accounted for 37%, 16% were of portal origin, 7% were ascribed to hematogenous dissemination, 4% direct inoculation during a procedure and no cause could be found in 35%. Liver ultrasonography allowed diagnosis in 43% of cases, and CT scan un 57%. Sixty-two percent of LA were larger than 3 cm in diameter; 28% of cases had multiple abscesses. Cultures of abscess fluid were positive in 71%, and blood cultures in 52%. Globally, we were able to isolate the causal microorganism in 73.5% of cases. Hundred percent of patients received antimicrobials, 56% had percutaneous drainage performed and 25% were surgically managed. There were complications in 13%, 9% suffered recurrences and we found a 19% mortality rate. CONCLUSIONS: LA has an ill-defined clinical picture. A history of neurological disease or abdominal tumor, and multiple LA are associated with an increased complication rate. Following factors correlated with increased mortality: Age-adjusted Charlson's morbidity index > or =5; Quick index < 60% and development of complications. Drainage indication has to be individualized.

Prebiotic synthesis of aminooxazoline-5'-phosphates in water by oxidative phosphorylation.

RNA is essential to all life on Earth and is the leading candidate for the first biopolymer of life. Aminooxazolines have recently emerged as key prebiotic ribonucleotide precursors, and here we develop a novel strategy for aminooxazoline-5'-phosphate synthesis in water from prebiotic feedstocks. Oxidation of acrolein delivers glycidaldehyde (90%), which directs a regioselective phosphorylation in water and specifically affords 5'-phosphorylated nucleotide precursors in upto 36% yield. We also demonstrated a generational link between proteinogenic amino acids (Met, Glu, Gln) and nucleotide synthesis.

Association of ficolin-3 with abdominal aortic aneurysm presence and progression.

Essentials Abdominal aortic aneurysm (AAA) is asymptomatic and its evolution unpredictable. To find novel potential biomarkers of AAA, microvesicles are an excellent source of biomarkers. Ficolin-3 is increased in microvesicles obtained from activated platelets and AAA tissue. Increased ficolin-3 plasma levels are associated with AAA presence and progression. SUMMARY: Background Abdominal aortic aneurysm (AAA) patients are usually asymptomatic and AAA evolution is unpredictable. Ficolin-3, mainly synthesized by the liver, is a molecule of the lectin complement-activation pathway involved in AAA pathophysiology. Objectives To define extra-hepatic sources of ficolin-3 in AAA and investigate the role of ficolin-3 as a biomarker of the presence and progression of AAA. Methods Microvesicles (exosomes and microparticles) were isolated from culture-conditioned medium of ADP-activated platelets, as well as from AAA tissue-conditioned medium (thrombus and wall). Ficolin-3 levels were analyzed by western-blot, real-time PCR, immunohistochemistry and ELISA. Results Increased ficolin-3 levels were observed in microvesicles isolated from activated platelets. Similarly, microvesicles released from AAA tissue display increased ficolin-3 levels as compared with those from healthy tissue. Moreover, ficolin-3 mRNA levels in the AAA wall were greatly increased compared with healthy aortic walls. Immunohistochemistry of AAA tissue demonstrated increased ficolin-3, whereas little staining was present in healthy walls. Finally, increased ficolin-3 levels were observed in AAA patients' plasma (n = 478) compared with control plasma (n = 176), which persisted after adjustment for risk factors (adjusted odds ratio [OR], 5.29; 95% confidence interval [CI], 3.27, 8.57)]. Moreover, a positive association of ficolin-3 with aortic diameter (Rho, 0.25) and need for surgical repair was observed, also after adjustment for potential confounding factors (adjusted hazard ratio, 1.55; 95% CI, 1.11, 2.15). Conclusions In addition to its hepatic expression, ficolin-3 may be released into the extracellular medium via microvesicles, by both activated cells and pathological AAA tissue. Ficolin-3 plasma levels are associated with the presence and progression of AAA, suggesting its potential role as a biomarker of AAA.

[Clinical and subclinical neuropathy in patients with human immunodeficiency virus receiving antiretroviral therapy]. / Neuropatía clínica y subclínica de pacientes con virus de inmunodeficiencia humana en tratamiento antirretroviral.

INTRODUCTION: There is a clear association between human immunodeficiency virus (HIV) and peripheral neuropathy. Peripheral polyneuropathy (PPN) is the most frequent neurological complication due to both the infection itself and the neurotoxicity deriving from highly active antiretroviral therapies (HAART). AIMS: The aim of this study was to determine the incidence of symptomatic PPN associated to HAART and to find out the true prevalence rate of subclinical neuropathy following over several years' treatment. PATIENTS AND METHODS: In order to evaluate the incidence of symptomatic PPN we conducted a study of patients undergoing treatment with HAART with a combination of didanosine (ddI), lamivudine (3TC) and efavirenz, and its presence was confirmed both clinically and electromyographically. Moreover, to study the prevalence rate of asymptomatic or subclinical PPN we chose patients without PPN who had been receiving this treatment for more than two years, with a viral load that had remained undetectable for over a year and with no further risk factors for PPN, and submitted them to a voluntary electromyographic study for PPN. RESULTS: Of the 108 patients studied, only two cases of symptomatic PPN were found. CONCLUSIONS: The incidence rate of clinical neuropathy following the administration of HAART is low (1.85%); PPN is a rare cause of withdrawal. Nevertheless, the prevalence rate found for subclinical PPN in patients undergoing prolonged therapy is high (66%). We therefore find ourselves with a problem that is little known, rarely suspected and more common than is believed.

Acetylenic and allenic derivatives of 2-(5-methoxy-1-methylindolyl)alkylamines as selective inhibitors of MAO-A and MAO-B.

A new series of thirty derivatives of 2-(5-methoxy-1-methylindolyl)alkylamines has been synthesized and the compounds assayed as inhibitors of MAO-A and MAO-B from bovine brain mitochondria. IC50 values for both isoenzymes were determined using tyramine as a common substrate. Structure-activity and selectivity relationships are discussed.

[Situation in Spain of the diagnostic resources and of the treatment with continuous positive pressure respiration in sleep obstructive apnea-hypopnea syndrome]. / Situación en España de los recursos diagnósticos y de los tratamientos con presión positiva continua sobre la vía aérea, en el síndrome de apneas-hipopneas obstructivas del sueño.

Sleep apnea-hypopnea syndrome (SAHS) is a major health problem whose estimated prevalence is 2 to 4% of the population. The Respiratory Insufficiency and Sleep Disorders Task Force estimated in 1995 that over one million people suffer SAHS with clinical repercussions in Spain while the number of patients receiving treatment was 8,000; diagnostic resources were not widely available. The aim of this study was to analyze the current situation in Spain. A survey carried out nation-wide in the period from 1995 to 1997 revealed that approximately 28,000 individuals were receiving nighttime support ventilation, signifying a prevalence of 72 per 100,000 inhabitants for this type of treatment. This situation has come about in a context of insufficient availability of diagnostic tools, with nocturnal oxygen levels having been established for some 37% of patients. We conclude that a broad plan to diagnose and treat patients with SAHS is required. The plan should include: a) greater availability of diagnostic tools; b) protocols for coordination; c) programs for continuous training and updating of knowledge of this disease, and d) revision of systems for financing support ventilation.

[Predictive mortality factors and the development of major complications in non-traumatic subarachnoid hemorrhage]. / Factores predictores de mortalidad y de desarrollo de complicaciones mayores en la hemorragia subaracnoidea no traumática.

Our aim was to analyze death prognostic factors in the first six months or the development of major neurological complications (delayed brain ischaemia and rebleeding) or general complications (cardiorespiratory, hydroelectrolytic or infectious) in non-traumatic subarachnoid haemorrhage. We carried out an observational study of a historical cohort of 111 patients admitted consecutively to our Centre between 1986 and 1992 and who were diagnosed as having subarachnoid haemorrhage based upon clinical data and confirmed in all cases by brain computerized tomography (CT) scan and/or lumbar puncture. Clinical variables upon admission were collected prospectively and radiological data were obtained retrospectively. We performed a logistic regression analysis which showed as significant predictive variables for death in the first six months a score on the Hunt-Hess scale greater than 2, a score on the Glassow scale of less than 9, female, aged over 50 and rebleeding. As predictive factors for delayed brain ischaemia we identified the female sex and the existence of earlier general complications. In the development of rebleeding a significant predictive factor was high blood pressure antecedents although this may have been controlled upon admission. For the appearance of general complications, significant predictive factors were more than 2 on the Hunt-Hess scale and hypertension antecedents. The use of these predictive parameters may help evaluate a prognosis in subarachnoid haemorrhage patients and also help make decisions in the management of this pathology.

[What sort of stroke requires patient admittance to the hospital? Factors for deciding on hospitalization]. / Cómo es el ictus del paciente que ingresamos? Factores de decisión en la hospitalización.

OBJECTIVE: To study main factors determining medical decision in admitting patients with acute cerebrovascular disease (ACVD). PATIENTS AND METHODS: This is an observational and transversal study. We analyze a hospitalary cohort made by all consecutive patients with ACVD coming to Emergency Room to Hospital Universitario de la Princesa during 1 year. Neurologist on call made on his/her own decision to admit the patient to hospital. Clinical and epidemiological characteristics of those patients admitted with those who went home are compared. RESULTS: 517 patients were studied, 147 had transient ischemic attacks (TIA) and 370 had a stroke, 12.3% TIA and 68.4% stroke patients were hospitalized. Age, Canadian Stroke Scale (CSS) on admission, subtype of stroke, atrial fibrillation and abnormal EKG, old lesions in CT, previous TIA and/or CVD, diminished conscious level, orientation and language, sphincter control and evolution time greater than 48 hours were statistically significative in deciding admission. Logistic regression analysis (84.2% total predictive value) showed independent predictive value in age, CSS, previous CVD and some subtypes of stroke (ischemic non lacunar and hemorrhage). CONCLUSIONS: We hospitalize younger patients, with a worse clinical condition and overall hemorrhagic stroke. The percentage of admissions among TIA patients is low. On the other hand, date, time and physicians-team features do not affect the percentage of admissions.

[Stereotactic target identification for neurosurgery of Parkinson disease]. / Identificación de las dianas estereotáxicas en la cirugía de la enfermedad de Parkinson.

INTRODUCTION: The use of applied neurophysiological methods to improve the stereotactic localization of devices in the deep human brain is a high and systematic technology in Parkinson's neurosurgery today. The available standard equipment for clinical neurophysiology practice may constitute the basic set for high tech functional neurosurgery. Free run and event related multiunit recording, naturalistic and electrical evoked potentials, and deep brain microstimulation responses are the basic methodological set to neurophysiological target localization. DEVELOPMENT AND CONCLUSIONS: This article is concerned with the topic: set out a high technology using low cost equipment. So our 41 cases experienced in pallidal and thalamic nucleolisis and thalamus and subthalamus DBS results suggest that the proposed equipment and methods are the required to assure accuracy and safety for target location.

[Changes in HIV-related attitudes and knowledge of teenagers following the Aulasida intervention in 1996-1997]. / Cambios en las actitudes y conocimientos de los adolescentes sobre la infección por VIH tras la intervención escolar Aulasida, 1996-1997.

BACKGROUND: Schools being the ideal setting for carrying out Health Education activities, the aim of this study was that of pinpointing and quantifying the changes in attitudes and knowledge on the part of teenagers enrolled in school in Algemesí (Valencia) following an educational intervention regarding HIV infection. METHOD: Eleven schools at which a total of 2,599 teenagers (ages 12-19) were enrolled in eleven different years of study (Secondary Education, Secondary Ed. and School Leaving Certificate, College Preparation Course and Vocational Training) were invited to take part. The Aulasida intervention carried out during the 1996-1997 school year consisted of an informative lecture-panel discussion and student involvement activities in small groups using educational materials. The gauging instrument was a questionnaire. This questionnaire was designed in a before-and-after cross-sectional study. An analysis was made divided into age and educational level strata. The averages were compared with the Student "t" test and the percentages of change with ji square. RESULTS: A total of nine schools accepted taking part. 1575 students answered the "before" test (47.4% males and 52.1% females), the average age being 15.2 (1.96) years old. The average number of correct answers to the "before" test was 13.5 (2.8). The "after" test showed an overall increase of up to 14.7 (3.0) correct answers (p < 0.01). By educational levels, this increase was highly appreciable in the younger age group. The most common sources of information on HIV were: television (80.8%); Aulasida (76.8%), teachers (60.9%), pamphlets (58.4%) and films (53.7%9. CONCLUSIONS: Educational interventions are useful tools for increasing knowledge and improving attitudes regarding HIV infection. Secondary schools are the best environment for this purpose, it being necessary to carry out interventions among younger groups, as a greater impact is thus achieved.

Incidencia de enfermedad pulmonar obstructiva crónica en pacientes con el virus de la inmunodeficiencia humana. Análisis post-hoc del estudio viva / Incidence of chronic obstructive pulmonary disease in patients with human immunodeficiency virus. Post-hoc analysis of the viva study

Introducción: desde la aparición de la terapia antiretroviral la supervivencia de los pacientes infectados por el virus de la inmunodeficiencia humana (VIH) ha aumentado considerablemente tomando importancia la aparición de otras patologías crónicas en estos pacientes como puede ser la enfermedad pulmonar obstructiva crónica (EPOC). Nuestro objetivo fue conocer la incidencia de EPOC en una cohorte de pacientes VIH derivados en un programa de detección de hipertensión pulmonar (HTP). Material y Métodos: análisis post-hoc, de un prospectivo, pseudo-experimental de pacientes con infección del VIH a los que se les preguntaba por disnea y en caso afirmativo eran derivados a consultas de neumología para despistaje de HTP. Resultado: desde 2014 hasta 2016, reclutamos un total de 32 pacientes, con un predominio de varones (75%). La disnea según la mMRC (Medical Reserach Council) fue grado 1, 2 y 3 en el 37,5%, 43,8% y 18,8%, respectivamente. La prevalencia de tabaquismo fue del 87,1% (intervalo de confianza [IC] 95%: 71- 96,4%), y 18 pacientes fueron catalogados de EPOC (62%; IC95%: 42,2 - 79,3%). Conclusión: la incidencia de EPOC en nuestra serie fue muy superior a la de la población general. Es necesario plantear estrategias de búsqueda activa de EPOC en estos pacientes para un diagnóstico y tratamiento precoz

Introduction: Since the advent of antiretroviral therapy, the survival of patients infected with the human immunodeficiency virus (HIV) has considerably increased, with the occurrence of other chronic diseases such as chronic obstructive pulmonary disease (COPD) gaining importance in these patients. Our objective was to find out the incidence of COPD in a cohort of HIV patients that were referred to a program to detect pulmonary hypertension (PH). Materials and Methods: Post hoc analysis of a prospective, quasi-experimental study on HIV-infected patients who were asked whether they had dyspnea. If this was the case, they were referred to a pulmonologist for PH screening. Results: From 2014 to 2016, we recruited a total of 32 patients, with a predominance of male recruits (75%). According to the mMRC (Modified Medical Research Council) Dyspnea Scale, 37.5%, 43.8% and 18.8% were classified as Grade 1, 2 and 3, respectively. The prevalence of smoking was 87.1% (95% confidence interval [CI]: 71 - 96.4%), and 18 patients were classified with COPD (62%; 95% CI: 42.2 - 79.3%). Conclusion: The incidence of COPD in our sample was much higher than that of the general population. It is necessary to plan active search strategies for COPD in these patients for early diagnosis and treatment

FPI: Consolidando alternativas de tratamiento / No disponible

La fibrosis pulmonar idiopática es una patología sobre la cual se está incidiendo tanto en el diagnóstico, a través de estudios acerca de las alteraciones genéticas que modifican el curso de la enfermedad, como en estudios que nos aportan diferentes alternativas en cuanto al tratamiento. Actualmente disponemos de dos fármacos que han demostrado mejorar tanto el pronóstico de la enfermedad como la calidad de vida de los pacientes que se someten a dichos tratamientos, ellos son Pirfenidona y Nintedanib

Idiopathic pulmonary fibrosis is a pathology that is affecting both the diagnosis, through studies about genetic alterations that modify the course of the disease and studies that provide us with different treatment alternatives. We currently have two drugs that have been shown to improve both the prognosis of the disease and the quality of life of patients who undergo such treatments, such as Pirfenidone and Nintedanib

Ensayo clínico aleatorizado para la comparación de dos métodos de cura de traqueotomía en una Unidad de Cuidados Intensivos / Randomised clinical trial to compare two tracheotomy care methods in an Intensive Care Unit

Introducción: La traqueotomía es una técnica habitual en las Unidades de Cuidados Intensivos (UCI). Es sabido que los cuidados enfermeros durante y posteriores al procedimiento están directamente relacionados con el éxito del mismo, minimizando el riesgo de aparición de complicaciones como la infección del estoma y favoreciendo la adecuada evolución del paciente crítico. Objetivos: Comparar la incidencia de infección en las traqueotomías realizadas en UCI según el antiséptico empleado: cura con polihexanida (PLX) y cura con suero fisiológico + povidona yodada (PY). Material y método: Ensayo experimental, aleatorizado y abierto, realizado en una UCI polivalente de 32 camas durante 2 años. El estudio fue aprobado por el Comité Ético de Investigación del Principado de Asturias. Resultados: La tasa observada de infecciones por 100 pacientes-día de traqueotomía fue de 1,34 (IC del 95%, 0,81-2,01): 1,46 en PLX y 1,21 PY (p valor 0,685). Conclusiones: A pesar de que el tratamiento experimental (PLX) ha mostrado su eficacia en otro tipo de heridas, en nuestro estudio no se encontraron diferencias significativas entre esta técnica y la estándar. Dado que no existe un registro nacional de incidencia de infección asociada a traqueotomías, no se puede saber si la observada está dentro de los parámetros habituales

Introduction: Tracheotomy is a common technique in Intensive Care Units (ICU). It is known that nursing care during and after that procedure is directly related to its success, by reducing the possible complications to a minimum, such as the stoma infection, and contributing to a favourable outcome in critical patients. Objectives: To compare the use of polyhexanide (PLX) versus saline + povidone iodine (PY) as antiseptics and infection incidence in tracheostomies performed in Intensive Care Units. Material and method: A 2-year, experimental, randomised, open-label trial carried out in a multidiscipline ICU with 32 beds. The study was approved by the Research Ethics Committee of Principality of Asturias. Results: The overall infection rate observed for every hundred patients was 1.34 (95% CI; 0.81-2.01), with 1.46 when using PLX and 1.21 for PY (P=.685). Conclusions: In spite of the experimental treatment (PLX) was shown to be effective in other types of wounds in our study. No significant differences were found between this technique and the standard one. Since there is no national registry of tracheotomy- associated infections, it is not possible to know whether the rate observed is within the usual parameters

Neumorraquis y neumomediastino espontaneo, rara complicación asmática / Pneumorrhachis and spontaneous pneumomediastinum, asthmatic rare complication

No disponible