A differential therapeutic consideration for use of corticosteroids according to established COVID-19 clinical phenotypes in critically ill patients.

OBJECTIVE: To determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. DESIGN: A secondary analysis derived from multicenter, observational study. SETTING: Critical Care Units. PATIENTS: Adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain. INTERVENTIONS: Corticosteroids vs. no corticosteroids. MAIN VARIABLES OF INTEREST: Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). We performed a multivariate analysis after propensity optimal full matching (PS) for whole population and weighted Cox regression (HR) and Fine-Gray analysis (sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes. RESULTS: A total of 2017 patients were analyzed, 1171 (58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR: 1.0; 95% CI: 0.98-1.15). Corticosteroids were administered in 298/537 (55.5%) patients of "A" phenotype and their use was not associated with ICU mortality (HR=0.85 [0.55-1.33]). A total of 338/623 (54.2%) patients in "B" phenotype received corticosteroids. No effect of corticosteroids on ICU mortality was observed when HR was performed (0.72 [0.49-1.05]). Finally, 535/857 (62.4%) patients in "C" phenotype received corticosteroids. In this phenotype HR (0.75 [0.58-0.98]) and sHR (0.79 [0.63-0.98]) suggest a protective effect of corticosteroids on ICU mortality. CONCLUSION: Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate dose. Only patients with the highest inflammatory levels could benefit from steroid treatment.

A differential therapeutic consideration for use of corticosteroids according to established COVID-19 clinical phenotypes in critically ill patients.

Objective: To determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. Design: A secondary analysis derived from multicenter, observational study. Setting: Critical Care Units. Patients: Adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain. Interventions: Corticosteroids vs. no corticosteroids. Main variables of interest: Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). We performed a multivariate analysis after propensity optimal full matching (PS) for whole population and weighted Cox regression (HR) and Fine-Gray analysis (sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes. Results: A total of 2017 patients were analyzed, 1171 (58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR: 1.0; 95% CI: 0.98-1.15). Corticosteroids were administered in 298/537 (55.5%) patients of "A" phenotype and their use was not associated with ICU mortality (HR = 0.85 [0.55-1.33]). A total of 338/623 (54.2%) patients in "B" phenotype received corticosteroids. No effect of corticosteroids on ICU mortality was observed when HR was performed (0.72 [0.49-1.05]). Finally, 535/857 (62.4%) patients in "C" phenotype received corticosteroids. In this phenotype HR (0.75 [0.58-0.98]) and sHR (0.79 [0.63-0.98]) suggest a protective effect of corticosteroids on ICU mortality. Conclusion: Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate dose. Only patients with the highest inflammatory levels could benefit from steroid treatment.

Objetivo: Evaluar si el uso de corticoesteroides (CC) se asocia con la mortalidad en la unidad de cuidados intensivos (UCI) en la población global y dentro de los fenotipos clínicos predeterminados. Diseño: Análisis secundario de estudio multicéntrico observacional. Ámbito: UCI. Pacientes: Pacientes adultos con COVID-19 confirmado ingresados en 63 UCI de España. Intervención: Corticoides vs. no corticoides. Variables de interés principales: A partir del análisis no supervisado de grupos, 3 fenotipos clínicos fueron derivados y clasificados como: A grave, B crítico y C potencialmente mortal. Se efectuó un análisis multivariado después de un propensity optimal full matching (PS) y una regresión ponderada de Cox (HR) y análisis de Fine-Gray (sHR) para evaluar el impacto del tratamiento con CC sobre la mortalidad en la población general y en cada fenotipo clínico. Resultados: Un total de 2.017 pacientes fueron analizados, 1.171 (58%) con CC. Después del PS, el uso de CC no se relacionó significativamente con la mortalidad en UCI (OR: 1,0; IC 95%: 0,98-1,15). Los CC fueron administrados en 298/537 (55,5%) pacientes del fenotipo A y no se observó asociación significativa con la mortalidad (HR = 0,85; 0,55-1,33). Un total de 338/623 (54,2%) pacientes del fenotipo B recibieron CC sin efecto significativo sobre la mortalidad (HR = 0,72; 0,49-1,05). Por último, 535/857 (62,4%) pacientes del fenotipo C recibieron CC. En este fenotipo, se evidenció un efecto protector de los CC sobre la mortalidad HR (0,75; 0,58-0,98). Conclusión: Nuestros hallazgos alertan sobre el uso indiscriminado de CC a dosis moderadas en todos los pacientes críticos con COVID-19. Solamente pacientes con elevado estado de inflamación podrían beneficiarse con el tratamiento con CC.

Resultados y evolución funcional de pacientes críticos con ictus isquémico sometidos a trombectomía mecánica / Results and functional outcomes of acute ischemic stroke patients who underwent mechanical thrombectomy admitted to intensive care unit

OBJETIVO: Estudiar los resultados y las complicaciones del tratamiento endovascular (TEV) en pacientes con ictus isquémico agudo ingresados en una unidad de cuidados intensivos (UCI). Analizar los factores que podrían influir en la mortalidad y en el grado de discapacidad al alta y un año después del ictus. DISEÑO: Estudio prospectivo observacional. Ámbito: UCI polivalente. Hospital de tercer nivel. PACIENTES: Sesenta pacientes adultos. Muestra consecutiva. INTERVENCIONES: Ninguna. Variables de interés: Datos epidemiológicos, tiempo desde la clínica inicial hasta el TEV, resultado angiográfico, tiempo de estancia en UCI, días de ventilación mecánica, complicaciones neurológicas, National Institutes of Health Stroke Scale (NIHSS) al ingreso y al alta de UCI, escala de Rankin modificada (mRS) al año de evolución. RESULTADOS: Edad media 68,90±8,84años. Mediana de tiempo hasta el TEV: 180min. Mediana NIHSS al ingreso: 17,5; al alta: 3. Flujo distal en el 90% de los casos. Mediana estancia en UCI: 3días. Ventilación mecánica: 81,7%. Independencia funcional (mRS≤2) 50% al año del ictus. Fallecimientos: 22 (36,6%); 8 (13,3%) en la UCI y el resto durante el primer año. CONCLUSIONES: Las variables asociadas a un peor estado funcional fueron la transformación hemorrágica sintomática, la ausencia de recanalización y las complicaciones durante el procedimiento. La transformación hemorrágica y la hidrocefalia se asociaron a mayor mortalidad. Se consiguió flujo distal en la mayoría de los casos, con una baja tasa de complicaciones. La mitad de los pacientes alcanza independencia funcional al año del ictus

PURPOSE: To study the results and complications of endovascular treatment (EVT) in acute ischemic stroke patients admitted to Intensive Care Unit (ICU). To analyse the possible factors related to mortality and level of disability at ICU discharge and one year after stroke. DESIGN: Observational prospective study. SETTING: Mixed ICU. Third level hospital. PATIENTS: Sixty adult patients. Consecutive sample. INTERVENTIONS: None. Variables of interest: Epidemiological data, time from symptom onset to EVT, angiographic result, length of stay, days on mechanical ventilation, neurological complications, National Institutes of Health Stroke Scale (NIHSS) at ICU admission and discharge, modified Rankin scale score (mRS) at one year. RESULTS: Mean age 68,90±8,84years. Median time from symptom onset to EVT: 180minutes. Median NIHSS at admission: 17,5; at discharge: 3. Distal flow was achieved in 90% of cases. Median ICU stay: 3 days. Mechanical ventilation: 81,7.%. Functional independence (mRS≤2) 50% at one year. Deaths: 22 (36,6%) of which 8 (13,3%) died during UCI stay and the rest during the first year. CONCLUSIONS: The factors relating to a worse functional outcome were symptomatic hemorrhage transformation, lack of recanalization and complications during EVT. The factors relating to mortality were symptomatic hemorrhage and hydrocephalus. Distal flow was achieve in most cases with a low complication rate. Half of the patients presented functional independence one year after the stroke

Results and functional outcomes of acute ischemic stroke patients who underwent mechanical thrombectomy admitted to intensive care unit. / Resultados y evolución funcional de pacientes críticos con ictus isquémico sometidos a trombectomía mecánica.

PURPOSE: To study the results and complications of endovascular treatment (EVT) in acute ischemic stroke patients admitted to Intensive Care Unit (ICU). To analyse the possible factors related to mortality and level of disability at ICU discharge and one year after stroke. DESIGN: Observational prospective study. SETTING: Mixed ICU. Third level hospital. PATIENTS: Sixty adult patients. Consecutive sample. INTERVENTIONS: None. VARIABLES OF INTEREST: Epidemiological data, time from symptom onset to EVT, angiographic result, length of stay, days on mechanical ventilation, neurological complications, National Institutes of Health Stroke Scale (NIHSS) at ICU admission and discharge, modified Rankin scale score (mRS) at one year. RESULTS: Mean age 68,90±8,84years. Median time from symptom onset to EVT: 180minutes. Median NIHSS at admission: 17,5; at discharge: 3. Distal flow was achieved in 90% of cases. Median ICU stay: 3 days. Mechanical ventilation: 81,7.%. Functional independence (mRS≤2) 50% at one year. Deaths: 22 (36,6%) of which 8 (13,3%) died during UCI stay and the rest during the first year. CONCLUSIONS: The factors relating to a worse functional outcome were symptomatic hemorrhage transformation, lack of recanalization and complications during EVT. The factors relating to mortality were symptomatic hemorrhage and hydrocephalus. Distal flow was achieve in most cases with a low complication rate. Half of the patients presented functional independence one year after the stroke.

Antimicrobial activity of suspensions and nanoemulsions of citral in combination with heat or pulsed electric fields.

The application of essential oils in form of nanoemulsions has been proposed as a method to improve their solubility in aqueous solutions, and hence their antimicrobial activity. The objective of this study was to evaluate the antimicrobial activity of citral, applied directly or in combined treatments with heat or pulsed electric fields (PEF), as a function of the inoculation procedure assayed: (i) a simple, vigorous shaking method by vortex agitation (suspension of citral; s-citral) or (ii) the previous preparation of nanoemulsions by the emulsion phase inversion (EPI) method (nanoemulsion of citral; n-citral). n-Citral was more effective in either inhibiting or inactivating Escherichia coli O157:H7 Sakai than s-citral. However, when combined with heat, a greater synergistic effect was observed with s-citral rather than with n-citral, either in lab media (pH 7·0 and 4·0) or apple juice. For instance, while almost 5 log10 cell cycles were inactivated in apple juice after 15 min at 53°C in the presence of 0·1 µl ml-1 of s-citral, the use of n-citral required 30 min. The use of nanoemulsions did not modify the slight synergism observed when citral and mild PEF were combined (150 µs, 30 kV cm-1 ). SIGNIFICANCE AND IMPACT OF THE STUDY: The exploration of different delivery systems of antimicrobial compounds such as citral in aqueous food products aids in the establishment of successful combined treatments for food preservation. While at room temperature, citral in form of a nanoemulsion shows a higher antimicrobial activity; its combination with heat would imply a partial loss of the outstanding synergistic lethal effect achieved when added in suspension form. Therefore, the most suitable procedure to magnify the synergism between heat and citral when processing juices would merely require an intense homogenization step prior to the combined treatment.

Increased Systemic Cytokine/Chemokine Expression in Asthmatic and Non-asthmatic Patients with Bacterial, Viral or Mixed Lung Infection.

This study was aimed to determine the profiles of serum cytokines (IL-1ß, TNF-α, IL-4, IL-5) and chemokines (MCP-1: monocyte chemoattract protein-1 and RANTES: regulated on activation normal T cell expressed and secreted) in individuals with an asthmatic versus a non-asthmatic background with bacterial, viral or mixed acute respiratory infection. Asthmatic (n = 14) and non-asthmatic (n = 29) patients with acute viral, bacterial or mixed (bacterial and viruses) respiratory infection were studied. Patients were also analysed as individuals with pneumonia or bronchitis. Healthy individuals with similar age and sex (n = 10) were used as controls. Cytokine/chemokine content in serum was determined by ELISA. Increased cytokine/chemokine concentration in asthmatic and non-asthmatic patients was observed. However, higher concentrations of chemokines (MCP-1 and RANTES) in asthmatic patients infected by viruses, bacteria or bacteria and viruses (mixed) than in non-asthmatic patients were observed. In general, viral and mixed infections were better cytokine/chemokine inducers than bacterial infection. Cytokine/chemokine expression was similarly increased in both asthmatic and non-asthmatic patients with pneumonia or bronchitis, except that RANTES remained at normal levels in bronchitis. Circulating cytokine profiles induced by acute viral, bacterial or mixed lung infection were not related to asthmatic background, except for chemokines that were increased in asthmatic status.

[Multidisciplinary meeting on application techniques for restitution of synovial fluid in patients with knee arthritis: update]. / Reunión multidisciplinaria sobre técnicas de aplicación para la restitución de fluido sinovial en pacientes con artritis de rodilla: puesta al día.

In the degradation of articular cartilage, functional limitation and pain cardinal signs of osteoarthritis underlies, as a central factor, the quantitative and qualitative alteration of hyaluronic acid, the main component of synovial fluid and cartilage, in a pathophysiological process influenced by a wide variety of risk factors whose impact complicates the disease and radically reduces the quality of life of the patient. Conventional pharmacological management for osteoarthritis is often insufficient. Fortunately, in our days, there are viscosupplements capable of improving, replacing and promoting the endogenous production of degraded hyaluronic acid in osteoarthritis. The use of these compounds requires the adherence to a set of specific techniques, designed for the correct intra-articular infiltration of the viscosupplement without the need to inflict an additional traumatic load on the patient; these techniques with special reference to the patient affected by knee osteoarthritis (gonarthritis) are described in this article, which also highlights the criteria for choosing the ideal viscosupplement, the one most similar to hyaluronic acid native in healthy young people, and one whose therapeutic use reports greater clinical benefits in the short and long term.

En la degradación del cartílago articular, la limitación funcional y el dolor se asocian a la alteración cuantitativa y cualitativa del ácido hialurónico en un proceso fisiopatológico sobre el que influye una amplia variedad de factores cuyo impacto agrava la enfermedad y disminuye la calidad de vida del paciente. El manejo farmacológico convencional para la osteoartritis es a menudo insuficiente. Por fortuna, en el mundo actual se cuenta con viscosuplementos capaces de mejorar, restituir y promover la producción endógena del ácido hialurónico degradado en los cuadros de osteoartritis. El uso de estos compuestos exige el apego a un conjunto de técnicas específicas, diseñadas para la correcta infiltración intraarticular del viscosuplemento sin necesidad de infligir una carga traumática adicional al paciente; estas técnicas con referencia especial al paciente afectado por la osteoartritis de rodilla (gonartritis) se describen en el presente artículo, en el que además se destacan los criterios para la elección del viscosuplemento idóneo, el más semejante al ácido hialurónico nativo de personas jóvenes y sanas y aquel cuyo uso terapéutico reporta mayores beneficios clínicos a corto y a largo plazo.

New insights in mechanisms of bacterial inactivation by carvacrol.

AIMS: To study the mechanism of bacterial inactivation by carvacrol and the influence of genetic and environmental factors in its antimicrobial activity. METHODS AND RESULTS: In general, bacterial inactivation by carvacrol was higher in the Gram-positive Listeria monocytogenes than in the Gram-negative Escherichia coli and at acidic pH. At pH 4.0, 25 µl l(-1) of carvacrol for 5 h inactivated 1 and more than 5 log(10) cycles of E. coli and L. monocytogenes populations, respectively. Genetic and environmental factors also influenced cell resistance to carvacrol: rpoS and sigB deletion decreased carvacrol resistance in E. coli and L. monocytogenes, respectively; a heat shock induced a phenomenon of cross-protection to carvacrol treatments. Repair of sublethal injuries in cell envelopes suggested that carvacrol targets lipid fractions and proteins of these structures. This result was corroborated by attenuated total reflectance infrared microspectroscopy analysis. CONCLUSIONS: This study shows critical genetic and environmental factors, such as rpoS or sigB and heat shocks, and reveals new microbial structures involved in the mechanism of bacterial inactivation by carvacrol. SIGNIFICANCE AND IMPACT OF THE STUDY: A better understanding of the mechanisms of microbial inactivation is of great relevance to design more appropriate carvacrol treatments with high antimicrobial effects.

sigB absence decreased Listeria monocytogenes EGD-e heat resistance but not its Pulsed Electric Fields resistance.

This study shows the behaviour of Listeria monocytogenes under heat and Pulsed Electric Fields (PEF) treatments, as well as the influence of sigB in bacterial resistance and recovery. Absence of the sigB gene resulted in a decreased heat tolerance, showing that sigma(B) influences L. monocytogenes heat survival. Heat treatments at 60 degrees C (40s) caused sublethal membrane injuries in 99.99% of survivors. The repair of heat damage required energy production and lipid, protein, and RNA synthesis, and it lasted 6h. Furthermore, deletion of sigB did not affect the heat injuries repair. PEF resistance at pH 4.0 and 7.0 was not influenced by sigB. Sublethal damage after PEF treatments was only detected when PEF-treated cells had previously been heat-shocked (45 degrees C/1h). The membrane repair only required energy production, and it was independent of sigB. Although both heat and PEF treatments have an effect on cellular membrane, the repair of the sublethal damages suggests different membrane targets, and thus we propose a different mechanism of inactivation by these food preservation technologies.

Effect of citral on the thermal inactivation of Escherichia coli O157:H7 in citrate phosphate buffer and apple juice.

Inactivation and sublethal injury of Escherichia coli O157:H7 cells induced by heat in citrate phosphate buffer and apple juice (both at pH 3.8) were studied, and the effect of a combined preservation treatment using citral and heat treatments was determined. Heat resistance of E. coli O157:H7 was similar in both treatment media; after 27 min at 54°C, 3 log units of the initial cell population was inactivated in both treatment media. However, under less harsh conditions a protective effect of apple juice was found. Whereas inactivation followed linear kinetics in the citrate phosphate buffer, when cells were treated in apple juice the survival curves were concave downward. Heat treatment caused a great degree of sublethal injury; 4 min at 54°C inactivated less than 0.5 log CFU/ml but sublethally injured more than 3 log CFU/ml. The addition of 18 and 200 ppm of citral to the treatment medium acted synergistically with heat at 54°C to inactivate 3 × 10(4) and 3 × 10(7) CFU/ml, respectively. Addition of citral thus reduced the time needed to inactivate 1 log unit of the initial E. coli O157:H7 population from 8.9 to 1.7 min. These results indicate that a combined process of heat and citral can inactivate E. coli O157:H7 cells and reduce their potential negative effects.

Elevated levels of interleukin-2 receptor and intercellular adhesion molecule 1 in sera from a venezuelan cohort of patients with dengue.

This study evaluated the levels of soluble interleukin-2 receptor (sIL-2R) and soluble intercellular adhesion molecule-1 (sICAM-1) in patients with dengue. Sera from 17 patients with dengue fever (DF), 15 with dengue hemorrhagic fever (DHF) and 12 healthy individuals were obtained. Increased levels of sIL-2R and sICAM-1 were found in patients with DF and DHF when compared to normal; those were not correlated with leukocytes, hepatic serum enzyme levels or haemostatic parameters. Levels of sIL-2R were related to the different grades of DHF. These results suggest that increased levels of sIL-2R and sICAM-1 are a common feature of dengue.

Daño neurológico en intoxicación por monóxido de carbono / Neurologic damage in carbon monoxide

No disponible

Toxicidad y actividad inmunológica in vitro e in vitro del extracto metanólico de la especie vegetal Cordia sebestena / Toxicity and immunologic activity in vivo and in vitro of the metanolic extract of the vegetal species Cordia sebestena

El ha investigado la utilidad terapéutica de las plantas basado principalmente en el uso folklórico por su aplicación en un amplio rango de enfermedades. En el presente trabajo, se evaluó la toxicidad y la actividad inmunológica in vivo e in vitro del extracto metanílico de la Cordia sebetena. Cultivos de celuals mononucleares de sangre periférica humana, donde se investigó el efecto de la viabilidad (coloración supravital azul tripán), linfoproliferación (Timidina Tritiada) y concentraciones del Factor Estimulador de Colonias Granulocítico-Macrofágico (FEC-GM) en los sobrenadantes, empleando la técnica de ELISA de captura, así como la actividad quimiotáctica de celulas polimorfonucleares humanas a través de la técnica en gel de agarosa. Se estudio la toxicidad in vivo en hígado, vaso y riñón en ratones bajo tratamiento oral e intraperitoneal a través de estudios histológicos, niveles sanguíneos de leucocitos totales y plaquetas/mm3 y el efecto en la ingesta diaria y el peso corporal de dichos ratones. Los resultados indican que el extracto metanolico de Cordia sebestena es inocuo a las celulas ensayadas, estimula la producción del FEC-GM, y por ende a la formación de nuevas células linfoides comportándose como un quimioatractante celular, hallazgos que podrían, en parte, explicar los efectos farmacológicos atribuidos a esta especie vegetal

Blood pressure responsiveness to sympathetic agonists in anaesthetised diabetic rats.

Chronic diabetes alters sympathetic modulation of the cardiovascular system. In the present work, we examined if the cardiovascular system also demonstrates an impaired responsiveness to sympathetic control. The effects of streptozotocin-induced diabetes on pressure responses to noradrenaline or isoproterenol infusion of diabetic rats in vivo are studied. Systolic and diastolic pressures were recorded through a cannula implanted in the right carotid artery. Increasing doses of noradrenaline or isoproterenol were infused through a catheter implanted in the left jugular vein. The dose-response curves for the effects of noradrenaline on blood pressure were altered in streptozotozin-induced diabetic rats. Noradrenaline induced a statistically significant higher increase of both systolic and diastolic pressure in control than in diabetic rats. The maximum depressor response of systolic pressure to isoproterenol was lower in diabetic than in control animals. Diabetes fully abolishes the effect of beta-adrenoceptor stimulation on diastolic blood pressure. The present results demonstrate that streptozotocin-induced diabetes reduces systolic and diastolic arterial pressure, and diminishes the arterial pressure reactivity to sympathetic stimulation.

Spironolactone and captopril attenuates isoproterenol-induced cardiac remodelling in rats.

The role of renin-angiotensin-aldosterone system in cardiac remodelling was studied in isoproterenol-induced cardiac hypertrophy in rats. The effects of captopril and spironolactone were compared. Isoproterenol treatment increased ventricular to body weight ratio (4.6 vs 3.7) and collagen area (22.6 vs 8.2%), and reduced systolic (89.93 vs 107.5 mm Hg) and diastolic (59.6 vs 70.8 mm Hg) pressure. In these animals, captopril decreased systolic (67.4 mm Hg) and diastolic pressure (31.9 mm Hg), whereas spironolactone regressed systolic pressure to control values (101.2 mm Hg). Captopril and spironolactone prevented cardiac hypertrophy (4.01 and 3.95). However, only spironolactone prevented myocardial fibrosis (11.3%).

[Evaluation of immunity against Venezuelan equine encephalitis virus and dengue in the human population of San Carlos, the Almirante Padilla Island Municipality, Zulia State, Venezuela. 1996]. / Evaluación de la inmunidad contra los virus de encefalitis equina venezolana y dengue en la población humana de San Carlos, Municipio Insular Almirante Padilla, Estado Zulia, Venezuela. Año 1996.

The Insular Municipality of Almirante Padilla, historically, has been affected by Venezuelan Equine Encephalitis (VEE) epidemics, that have occurred cyclically in the Paez, Mara and Almirante Padilla Municipalities of the State of Zulia. During the last epidemic outbreak (1995), the studies reported a great number of cases of VEE in humans, based on epidemiologic-clinical diagnosis; occupying this municipality, the first place in the attack rate by the virus. At the same time, Dengue has been defined as an endemic illness affecting different regions, whose etiologic agent has previously circulated in the studied zone. In order to evaluate the immunity acquired against these viruses, a serological study was conducted in San Carlos Island. Two hundred and ten blood samples were obtained at random, among individuals of an age range between < 1 and 69 years, with and without antecedents of viral illness symptomatology at the moment of the epidemic outbreak, occurred in 1995. The samples were classified according to sex and age, and analyzed through the test of ELISA for specific IgG antibodies against the VEE and Dengue viruses. From the total of the samples processed, 116 (55.2%) were positive for VEE, affecting uniformly all age-groups with a slight masculine predominance. Likewise, 88 cases (41.9%) were determined positive for Dengue virus, affecting mainly the group ranging from 10 to 19 years. These results let us suggest that the epidemic outbreak occurred in 1995 at the Almirante Padilla Insular Municipality, had a double nature with both viruses being involved in the etiology of febrile cases.

Monitorización de niveles plasmáticos de fenitoína / Phenytoin plasma levels monitoring

La fenitoína es un fármaco utilizado ampliamente en la práctica clínica para el tratamiento de la epilepsia mayor, de las crisis convulsivas parciales y convulsiones tónico-clónicas generalizadas y menos frecuentemente para otros trastonos como las arritmias cardiacas o las neuralgias del trigémino. Es uno de los fármacos que más frecuentemente se monitorizan por el laboratorio clínico debido a varios motivos: 1. posee un margen terapeútico estrecho con un índice terapeútico bajo; 2. la relación entre la dosis y el nivel plasmático puede resultar impredecible debido a la gran variación interindividual; 3. la cinética de metabolismo es saturable dentro del rango terapeútico, lo que significa que pequeñas variaciones de la dosis pueden producir grandes aumentos de niveles plasmáticos. Las indicaciones de su monitorización son las sospechas de falta de cumplimiento terapéutico o de intoxicación y la presentación de convulsiones. En este trabajo revisamos las propiedades farmacológicas de la fenitoína estudiando especialmente la farmacocinética, las reacciones adversas debidas a sobredosis y los métodos analíticos empleados en el laboratorio para su medida (AU)

[Viral agents in patients with infectious processes of the central nervous system]. / Agentes virales en pacientes con procesos infecciosos del Sistema Nervioso Central.

Local statistics report a great number of cases of neurological diseases of unidentified cause. The purpose of this research was to determine the presence of viral agents in patients with affection of the central nervous system, in Zulia State, Venezuela. In different health centers throughout the state, we collected 129 randomized samples of cerebrospinal fluid (CSF) and serum from patients ranging from 1 day to 41 years of age, showing symptoms of CNS disease and whose bacteriological test resulted negative. The serum/CSF albumin ratio was determined to exclude contaminated CSF samples, thus 54 optimal samples were obtained for the research. We determined serum IgM and CSF IgG specific for Venezuelan equine encephalomyelitis (VEE), Herpes simplex (HSV), Epstein Barr (EBV), Dengue, Rubella and Measles virus, through ELISA and indirect immunofluorescence techniques. Of the 54 samples studied, 33 (61.11%) were positive. %). The etiological agents implicated were VEE 14 cases (42.42%); HSV 11 cases (33.33%); EBV 5 cases (15.15%) and Dengue 3 cases (9.09%). We did not detect Rubella o Measles. Regarding the age distribution, the most affected group was that of children under 12 (83.34%). We analyzed the clinical manifestations and the CSF characteristics and did not find differences suggestive of an specific etiological diagnosis, even though certain signs could be considered early indications of CNS alterations due to viral causes. Our study shows that a large percentage of CNS affections of unknown etiology are produced by viral agents, indicating that in our region, most of this cases are not registered.

Effects of amphetamine on calcium and potassium currents in rat heart.

We used the patch-clamp technique to study the effects of amphetamine on the membrane currents responsible for rat cardiac action-potential duration. Amphetamine has no effect on the slow inward Ca2+ current (I(Ca)-L), the inwardly rectifying K+ current (I(K1) and the outward K+ delayed rectifier (I(K)) and sustained (I(SS)) currents. Amphetamine blocks the transient outward K+ current (I(to)) both in the open and in the rested state. The transient outward K+ current is largely responsible for action-potential repolarization and for the regional differences in action-potential duration in rat ventricle. Therefore, the reduction of the transient outward K+ current (I(to)) caused by amphetamine may facilitate the appearance of ventricular tachycardia and fibrillation, a reported cause of death in amphetamine users.

Clinical and epidemiologic studies of cleft lip and palate in the Philippines.

Clinical and epidemiologic studies of defined geographic populations can serve as a means of establishing data important for genetic counseling and as a first step in identifying strategies best suited for identification of causes. Under the sponsorship of Operation Smile International, clinical, genetic, and epidemiologic studies were carried out at six sites within the Philippines between 1989 and 1996. Patients who were being evaluated for surgical repair of craniofacial anomalies (primarily clefts of the lip and palate) were briefly examined for the presence of associated anomalies, and a family history was obtained to look for the frequency of cleft lip and palate in siblings. Birth records of 47,969 newborns over an 8-year period at one hospital in Bacolod City in the province of Negros Occidental were reviewed. Medical records of infants born with clefts of the lip and/or palate and other major anomalies were reviewed and birth prevalence rates calculated. Findings include a birth prevalence of 1.94 per 1000 live births for cleft lip with/without palate in the Philippines. Recurrence rates in siblings for nonsyndromic clefts of the lip and palate were 23 per 1000 for cleft lip with or without cleft palate, and 14 per 1000 for cleft palate only. The percentage of clefts associated with multiple anomalies was 21% at birth and 6% for individuals examined during the screening process, providing evidence for a high postnatal death rate. These data provide groundwork for additional etiologic studies including segregation analysis and molecular genetic studies involving linkage or association, as well as for studies of environmental contributions to clefting such as vitamin deficiencies. Preliminary molecular analysis using an association approach is reported in a companion paper. The findings suggest a high incidence of cleft lip and palate in native-born Filipinos.