Screening for chemicals with thyroid hormone-disrupting effects using zebrafish embryo.

Thyroid disruption is an increasingly recognized issue in the use and development of chemicals and new drugs, especially to help toxicologist to complement the reproductive and developmental toxicology information of chemicals. Still, adequate assessment methods are scarce and often suffer a trade-off between physiological relevance and labor- and cost-intensive assays. Here, we present a tiered approach for a medium-throughput screening of chemicals to identify their thyroid disrupting potential in zebrafish embryos as a New Approach Methodology (NAM). After identifying the maximum tolerated concentrations, we exposed zebrafish larvae to sub-adverse effect levels of the reference compounds benzophenone-2, bisphenol A, phenylthiourea, potassium perchlorate, propylthiouracil, and phloroglucinol to exclude any systemic toxicity. Applying the transgenic zebrafish line that carries a gene for the red fluorescence protein (Tg(tg:mCherry)) under the thyroglobulin promoter, we could identify the thyroid disrupting effects of the chemicals by a time and cost-effective image analysis measuring the fluorescence levels in the thyroid glands. Our observations could be confirmed by altered expression patterns of genes involved in the hypothalamus-pituitary-thyroid (HPT) axis. Finally, to anchor the observed thyroid disruption, we determined some changes in the Thyroid hormone levels of triiodothyronine (T3) and Thyroxine (T4) using a newly developed liquid chromatography mass spectrometric (LCMS) method. The presented approach carries the potential to extend the toolbox for legislative authorities and chemical producers for the assessment of thyroid-specific endocrine disruption and to overcome current challenges in the evaluation of endocrine disruptors.

[Pharmacokinetic risk factors of beta-blockers overdose in the elderly: Case report and pharmacology approach]. / Facteurs de risque pharmacocinétiques de surdosage en bêta-bloquants chez les patients âgés : cas clinique et rationnel pharmacologique.

Beta-blockers are widely prescribed in elderly patients and may induce severe adverse drug reactions. We report a case of bisoprolol-induced bradycardia in an elderly patient with impaired renal function and use of cytochrome P450 inhibitors. A literature review has been performed in order to analyze pharmacokinetic risk factors of beta-blockers overdosing in geriatrics. Various mechanisms can result in decreased elimination of beta-blockers. These mechanisms vary according to the beta-blocker agent and may be combined in some individuals, especially elderly patients. This can lead to unexpected overexposure. Knowledge about drug interactions and pharmacokinetic elimination pathways is important for preventing overexposure and adverse drug reactions when using beta-blockers.

Inter-reflux and bolus clearance times in non-pathologic pediatric patients: data support computational models.

Previous contributions suggested that gastroesophageal reflux can be modeled in terms of a Poisson process. This study aims to provide empirical data to validate this statement in pediatric patients so that computational models can be broadly used as an alternative for research. A retrospective review of 63 pediatric patients who underwent 24-hour impedance-pH monitoring to discard gastroesophageal reflux disease was conducted in this study. Patients were grouped by age as preterm (21), infants (21), and children (21). All the tracings were analyzed by a trained physician who identified the reflux entry and the bolus clearance time of each episode. The time between reflux episodes was tested against three probability distributions (gamma, exponential and inverse Gaussian) whereas the bolus clearance time was tested against a normal probability distribution. Parameters were estimated using the maximum likelihood method. The Kolmogorov-Smirnov test and the Kullback-Leibler divergence were computed to evaluate the goodness of fit. One-way analysis of variance was applied to compare results along the three groups. Exponential fitting for inter-reflux time was successful in 90.48% of children older than 1 year. The overall reflux rate was 57.58 reflux episodes per day whereas the mean bolus clearance time ranged between 10.87 in preterm subjects and 12.05 in children, showing a good Gaussian fitting. The time between reflux episodes can be modeled in terms of a Poisson process in non tube-fed patients, whereas the bolus clearance time follows a normal distribution in all cases.

Monte Carlo method for the evaluation of symptom association.

Gastroesophageal monitoring is limited to 96 hours by the current technology. This work presents a computational model to investigate symptom association in gastroesophageal reflux disease with larger data samples proving important deficiencies of the current methodology that must be taking into account in clinical evaluation. A computational model based on Monte Carlo analysis was implemented to simulate patients with known statistical characteristics Thus, sets of 2000 10-day-long recordings were simulated and analyzed using the symptom index (SI), the symptom sensitivity index (SSI), and the symptom association probability (SAP). Afterwards, linear regression was applied to define the dependency of these indexes with the number of reflux, the number of symptoms, the duration of the monitoring, and the probability of association. All the indexes were biased estimators of symptom association and therefore they do not consider the effect of chance: when symptom and reflux were completely uncorrelated, the values of the indexes under study were greater than zero. On the other hand, longer recording reduced variability in the estimation of the SI and the SSI while increasing the value of the SAP. Furthermore, if the number of symptoms remains below one-tenth of the number of reflux episodes, it is not possible to achieve a positive value of the SSI. A limitation of this computational model is that it does not consider feeding and sleeping periods, differences between reflux episodes or causation. However, the conclusions are not affected by these limitations. These facts represent important limitations in symptom association analysis, and therefore, invasive treatments must not be considered based on the value of these indexes only until a new methodology provides a more reliable assessment.

The binomial symptom index: toward an optimal method for the evaluation of symptom association in gastroesophageal reflux.

BACKGROUND: The evaluation of symptom association in gastroesophageal reflux is an open problem. The scientific literature reports important deficiencies and clinicians are claiming a new methodology. This article provides an optimal method for the evaluation of symptom association, the binomial symptom index (BSI). METHODS: A mathematical description of the BSI was presented for the study of association and causality. A total of n = 850,000 patients were simulated using a Monte Carlo model to perform a two-way sensitivity analysis. The average and the standard deviation of the BSI were evaluated in groups of 5000 patients with the same values of the reflux rate, symptom rate, association ratio, window of association, and monitoring time in order to contrast their influence on the estimator. KEY RESULTS: The BSI decreased with the number of reflux episodes when there was association, and remained constant and below 40% when there was not. The standard deviation was no higher than 40% and decreased with the reflux or symptom rates, and more sharply with the monitoring time, reaching approximately 0% for 50 days. A window length matching the characteristic reflux-symptom lag maximized the overall BSI and minimized its dispersion. Twenty-four hour and 96-h monitorings allowed detecting association ratios of 50% and 25%, respectively. CONCLUSIONS & INFERENCES: The BSI is a simple and reliable index for the evaluation of symptom association that considers all the parameters under analysis. Defining an appropriate cut-off value, the BSI can provide a measure of probability and strength of association simultaneously.

[Temporal relationship between gastroesophageal reflux and cardiorespiratory events]. / Relación temporal entre el episodio cardiorrespiratorio y reflujo gastroesofágico.

UNLABELLED: The acid and non acidic gastroesophageal reflux can trigger apnoea, desaturation and bradicardia events, as well as chronic pulmonary pathology due to microaspirations, whereas the acute or chronic airway closing increase the intrathoracic pressure, triggering the reflux. Our aims were to measurement in preterms newborn the correlations between cardiorespiratory events and gastroesophageal reflux, find out the direction of this relation, identify the patients with association GER->CRE and decide the suitability of antireflux surgery. METHOD: The study was made in the Motility Unit and in the Intensive Neonatal Care Unit, to preterms newborns without associated pathology except apnoea and/or bradicardia and/or desaturation. MATERIAL: 3 hours manometry study in the Motility Unit. 24 hours impedance, pH and cardiorespiratory parameters monitoring (respiratory and cardiac frequent, O2 saturation and CO2) in Intensive Neonatal Care Unit. We characterised the gastroesophageal barrier, all the reflux events and the association between GER and CRE. RESULTS: We made 28 records to 28 patients with CRE. The average of the total number of reflux was 61 (22,25-103,00), 29,2% acid reflux and 70,8% weakly acidic. 12 patients had some GER associated with CRE but in only 2 cases was statistically significant (Sympton index: SI; Sympton Sensitivity Index: SSI) (SI > or = 50%; SSI > or = 10%). The surgical management was successfully in these two babies and nowadays they are asymptomatic. CONCLUSION: There is not any general association between GER and CRE, nevertheless, in a little percentage of patients, this relationship is fulfilled and it is possible to measurement with impedance, pH and cardiorespiratory parameters. In these cases, the surgical management is the right treatment.

Relación temporal entre el episodio cardiorrespiratorio y reflujo gastroesofágico / Temporal relaionship between gastroesophageal reflux and cardiorespiratory events

El reflujo gastroesofágico ácido y no-ácido puede desencadenar episodios de apnea, de desaturación y de bradicardia, así como patología pulmonar crónica debido a las microaspiraciones, mientras que el cierre agudo o crónico de las vías aéreas aumenta la presión intratorácica, favoreciendo el reflujo. Objetivos. Nuestros objetivos fueron comprobar en recién nacidos pretérminos (RNPT) con sintomatología cardiorrespiratoria, si ésta tiene relación con el episodio de reflujo y el sentido de la misma e identificarlos casos en los que ésta asociación se produzca, tratándolos médico-quirúrgicamente. Metodología. El estudio se realiza en la Unidad de motilidad Intestinal y Unidad de cuidados intensivos (UCI) neonatal, a RNPT sin patología asociada excepto apnea y/o bradicardia y/o desaturación. Material. Manometría + Impedanciometría (IM) durante 3 horas en la Unidad de Motilidad. IM+ pH+ monitorización cardiorrespiratoria(FR, FC, SO2 y ETCO2) durante 24h en la unidad de cuidados intensivos neonatal. Se determinaron las características manométricas de la barrera antirreflujo, identificación de todos los episodios de reflujo y relación episodio de reflujo-síntoma cardiorrespiratorio. Resultados. Realizamos 28 estudios en neonatos pretérminos con bradicardia, apneas y desaturaciones. La media del número total de reflujos fue de 61 (22,25-103,00), de los que el 29,2 % representan los reflujos ácidos y el 70,8 % restante son débilmente ácidos. En 12 de los 28estudios realizados se encontraron episodios cardiorrespiratorios asociados a reflujo gastroesofágico, aunque tan sólo en 2 se encontró una relación estadísticamente significativa entre ellos (Symptom index: SI; Symptom Sensitivity Index: SSI) (SI >= 50%; SSI >= 10%). En ambos casos los pacientes se han intervenido quirúrgicamente con éxito, sin volverá presentar los síntomas cardiorrespiratorios. Conclusiones. No existe asociación generalizada entre reflujo gastroesofágico y episodios cardiorrespiratorios, sin embargo, en una escaso porcentaje de pacientes, ésta relación se cumple y se puede tratar de manera justificada mediante el estudio con impedancia, pH y constantes respiratorias. En estos casos, la intervención quirúrgica precoz es el tratamiento de elección (AU)

The acid and non acidic gastroesophageal reflux can trigger apnoea, desaturation and bradicardia events, as well as chronic pulmonary pathology due to microaspirations, whereas the acute or chronic airway closing increase the intrathoracic pressure, triggering the reflux. Our aims were to measurement in preterms new born the correlations between cardiorespiratory events and gastroesophageal reflux, find out the direction of this relation, identify the patients with association GER->CRE and decide the suitability of antireflux surgery. Method. The study was made in the Motility Unit and in the Intensive Neonatal Care Unit, to preterms newborns without associated pathology except apnoea and/or bradicardia and/or desaturation. Material. 3 hours manometry study in the Motility Unit. 24 hours impedance, pH and cardiorespiratory parameters monitoring (respiratory and cardiac frequent, O2 saturation and CO2) in Intensive Neonatal Care Unit. We characterised the gastroesophageal barrier, all the reflux events and the association between GER and CRE. Results. We made 28 records to 28 patients with CRE. The average of the total number of reflux was 61(22,25-103,00), 29,2% acid reflux and 70,8% weakly acidic. 12 patients had some GER associated with CRE but in only 2 cases was statistically significant (Symptonindex: SI; Sympton Sensitivity Index: SSI) (SI >= 50%; SSI >= 10%).The surgical management was successfully in these two babies and nowadays they are asymptomatic. Conclusion. There is not any general association between GER and CRE, nevertheless, in a little percentage of patients, this relationship is fulfilled and it is possible to measurement with impedance, pH and cardiorespiratory parameters. In these cases, the surgical management is the right treatment (AU)

Estudio de las interconsultas solicitadas por el Servicio de Cirugía General al Servicio de Medicina Interna / Analyces of the consult from the department of general surgery to the department of Internal Medicine

Fundamento y objetivo: Conocer mejor las características de las interconsultas solicitadas por el servicio de Cirugía General a un servicio de Medicina Interna, valorar los resultados y la experiencia desde la visión del internista. Pacientes y método: Estudio prospectivo de las 129 interconsultas de pacientes ingresados en el servicio de Cirugía General solicitadas durante el año 2005 al servicio de Medicina Interna. Resultados: Equivalen al 4% de todos los ingresos del servicio de Cirugía General (el 6,5% de los pacientes ingresados desde urgencias y el 2% de los ingresados de forma programada). La media de edad de los pacientes fue de 74 años. Los pacientes fueron visitados una media de 3,3 días. Las causas más frecuentes que motivaron la solicitud fueron la disnea (29%), la fiebre (21%), la tos (11%) y las arritmias (8%). Los diagnósticos más frecuentemente realizados fueron la insuficiencia cardiaca (17%), la enfermedad pulmonar obstructiva crónica (15%), la sobre infección respiratoria y/o acumulación de secreciones bronquiales (13%), la neumonía (9%) y la fibrilación auricular (7%). El 31% de los diagnósticos ha correspondido a agudización de enfermedad crónica previamente conocida. Los fallecimientos han sido 19 (15%), porcentaje mayor al global en el servicio de Cirugía General (2%). La media de edad de los fallecidos fue de 82 años. La mortalidad fue mayor cuando el ingreso se realizó desde urgencias (17 de 91) que cuando se realizó de forma programada (2 de 38). La causa más frecuente ha sido el fallo de sutura con peritonitis y sepsis en 5 pacientes. Conclusiones: La labor del internista no sólo se ha dirigido al tratamiento de las enfermedades crónicas, sino que también ha ayudado en el diagnóstico y tratamiento de procesos agudos relacionados o no con el motivo inicial de ingreso. A destacar la nula especificidad de la tos como síntoma guía en el diagnóstico de pacientes previamente intervenidos. Las causas del fallecimiento se han relacionado casi exclusivamente con el proceso que requirió el ingreso en Cirugía General o las complicaciones de éste (17 de 19)

Rational and aim: to better understand the nature of the consults solicited by the Department of General Surgery to the Department of Internal Medicine and to examine the results and the experience from the point of view of an Internal Medicine specialist. Patients and methods: Prospective analysis of the 129 consults from patients admitted in General Surgery to the Department of Internal Medicine during 2005. Results: The number of consults was 4% of all patients admitted in General Surgery (6,5% of de admitted patients were from the emergency service and 2% from the planning programme). The median age was 74 years. The patients were visited a mean of 3.3 days. The most frequent reasons for consultation were dyspnea (29%), fever (21%), cough (11%) and dysrhythmias (8%). The most frequent diagnosis were cardiac failure (17%), chronic obstructive pulmonary disease (15%), respiratory infection and/or accumulation of bronchial secretions (13%), pneumonia (9%) and a trial fibrillation (7%). In 31% of cases the diagnosis was decompensation of previously diagnosed chronic disease. Nineteen patients died (15%), higher than the global average admitted in General Surgery (2%). The average age of these patients was 82 years. The mortality was higher when the admission was from the emergency service (17 of 91) than when it was from the planning programme. The most frequent cause of death was suture failure and peritonitis with secondary septicemia in 5 patients. Conclusions: The task of the Internal Medicine specialist was not only the treatment of chronic diseases, but also to assist in the diagnosis and treatment of acute diseases related or unrelated to the cause of the admission. To point up the invalid specificity of cough as a guide symptomin the diagnosis of previously operated patients. The causes of death were almost exclusively related to the disease that resulted in the admission to the Department of Surgery or with its complications (17 of 19)

[Analyses [corrected] of the consults from the Department of General Surgery to the Department of Internal Medicine]. / Estudio de las interconsultas solicitadas por el Servicio de Cirugía General al Servicio de Medicina Interna.

UNLABELLED: RATIONAL AND AIM: to better understand the nature of the consults solicited by the Department of General Surgery to the Department of Internal Medicine and to examine the results and the experience from the point of view of an Internal Medicine specialist. PATIENTS AND METHODS: Prospective analysis of the 129 consults from patients admitted in General Surgery to the Department of Internal Medi-cine during 2005. RESULTS: The number of consults was 4% of all patients admitted in General Surgery (6,5% of de admitted patients were from the emergency service and 2% from the planning programme). The median age was 74 years. The patients were visited a mean of 3.3 days. The most frequent reasons for consultation were dyspnea (29%), fever (21%), cough (11%) and dysrhythmias (8%). The most frequent diagnosis were cardiac failure (17%), chronic obstructive pulmonary disease (15%), respiratory infection and/or accumulation of bronchial secretions (13%), pneumonia (9%) and atrial fibrillation (7%). In 31% of cases the diagnosis was decompensation of previously diagnosed chronic disease. Nineteen patients died (15%), higher than the global average admitted in General Surgery (2%). The average age of these patients was 82 years. The mortality was higher when the admission was from the emergency service (17 of 91) than when it was from the planning programme. The most frequent cause of death was suture failure and peritonitis with secondary septicemia in 5 patients. CONCLUSIONS: The task of the Internal Medicine specialist was not only the treatment of chronic diseases, but also to assist in the diagnosis and treatment of acute diseases related or unrelated to the cause of the admission. To point up the invalid specificity of cough as a guide symptom in the diagnosis of previously operated patients. The causes of death were almost exclusively related to the disease that resulted in the admission to the Department of Surgery or with its complications (17 of 19).

El reflujo gastroesofágico pandrial en pretérminos sanos / Pandrial gastroesophageal reflux in healthy preterm infants

La neutralización del ácido gástrico durante las comidas y en el período pospandrial inmediato, ha determinado que hasta hace poco tiempo estos períodos fueran excluidos en los estudios de la enfermedad por reflujo gastroesofágico (ERGE) que se realizaban mediante pH-metría. El objetivo de este estudio fue en un primer momento caracterizar los episodios de reflujo ocurridos durante las comidas mediante pH e impedancia, para posteriormente compararlos con lo que ocurre en los períodos de ayunas. Material y método. Medimos pH e impedancia esofágica en 21 niños pretérmino sin patología asociada, excepto la prematuridad, durante 8 períodos de comida-ayunas (1 hora de comida y 2 horas de descanso), reemplazando la sonda de alimentación por un catéter de alimentación + impedancia, previa firma paterna de consentimiento informado. Resultados. La media de reflujos durante las comidas por hora fue de 3,36 h ± 1,23 h, mientras que en los períodos de ayunas fue de 2,65 h ± 1,02 h (p = 0,068). El número de reflujos ácidos por hora durante el ayuno fue más alto [1,05 (0,34-1,23) h] que en las comidas [0,20 (0- 1,12) h] (p = 0,044). El número de reflujos débilmente ácidos por hora era significativamente más alto en los períodos de comida [2,71 (2,03- 3,30) h] que en los períodos de ayunas [1,35 (1,13-1,97) h] (p = 0,05). La exposición ácida durante las comidas fue del 2,35% mientras que (..) (AU)

The neutralization of gastric content during feeding and in the immediate postpandrial period, has determined that until recently time these periods were excluded in the studies of the gastroesophageal reflux disease (GERD) that were made with pH-metría. The aim of this study was to characterize the events of reflux during feeding with pH and impedance,and later to compare them with which it happens in fasting periods. Material and method.We recording pH and Impedance in 21 preterms neonates without associated pathology, except the prematurity, during (..) (AU)

[Pandrial gastroesophageal reflux in healthy preterm infants]. / El reflujo gastroesofágico pandrial en pretérminos sanos.

UNLABELLED: The neutralization of gastric content during feeding and in the immediate postpandrial period, has determined that until recently time these periods were excluded in the studies of the gastroesophageal reflux disease (GERD) that were made with pH-metría. The aim of this study was to characterize the events of reflux during feeding with pH and impedance,and later to compare them with which it happens in fasting periods. MATERIAL AND METHOD: We recording pH and Impedance in 21 preterms neonates without associated pathology, except the prematurity, during 8 periods of feeding-fasting (1 hour of feeding and 2 hours of rest), replacing the nasogastric tube by a catheter of feeding + impedance, previous informed consent. RESULTS: The average of reflux during the meals per hour was of 3.36 h +/- 1.23 h, whereas in fasting periods was 1.02 h was of 2.65 h +/- (p = 0.068). The number of acid reflux per hour during the fasting was higher [1, 05 (0.34-1.23) h] than in feeding periods [0, 20 (0-1.12) h] (p = 0,044). The number of weakly acid reflux per hour was significantly higher in feeding periods [2, 71 (2.03-3.30) h] than in fasting periods [1, 35 (1.13-1.97) h] (p = 0, 05). The acid exposure during the meals was of 2, 35% whereas in fasting periods was of 7, 23%. CONCLUSION: The incorporation of the Impedance within the battery of tests for the diagnosis of the gastroesophageal reflux in the pediatric population, at the moment allows us to know the pattern behavior of esophagus during the meals: feeding periods were associated with a greater number of reflux per hour, most of which weakly acidic; the acid exposure was significantly greater during fasting periods.

[Acid and non-acid gastro-esophageal reflux in newborns. Preliminar results using intraluminal impedance]. / Reflujo gastroesofágico ácido y no ácido en el recién nacido. Datos preliminares de estudio con impedancia intraesofágica.

Preterm infants present often Gastroesophageal refluxes (GER). Esophageal pH monitoring to reflux detection is of limited use in this infants because their gastric pH is normally higher than 4 for 90% of the time. Other methods such as the Intraluminal Impedance Technique (MII) technique and the use of micromanometric catheters try to palliate the difficulties for measuring GER by pH monitoring. The aim of this study, in a first step, was to obtain the normal Intraluminal Impedance values on control children and, in a second step, to study the relationship between GER and cardiorespiratory episodes using simultaneous recording of the end-tidal fraction of expired CO2, 02 saturation by pulse-oximetry, respiratory frequency, esophageal impedance and manometry, gastro-esophageal pHmetry, and electrocardiography in selected patients. Data from simultaneous pH and Intraluminal Impedance during 24 hours in 7 control preterms showed 89 acid refluxes, 192 non-acid refluxes, 79.36% of all refluxes reached the proximal esophagus. Therefore the impedance is an innocuous method which opens new horizons in the study of such a common illness as the GER in the preterm infants.

Reflujo gastroesofágico ácido y no ácido en el recién nacido. Datos preliminares de estudio con impedancia intraesofágica / Acid and non-acid gastro-esophageal reflux in newborns. Preliminar results using intraluminal impedance

El reflujo gastroesofágico (RGE) es un hecho muy común en niños pretérmino. La prueba gold standard hasta ahora para medir el reflujo, la pHmetría, se ve limitada en estos niños debido a que supH gástrico es superior a 4 un 90% del tiempo. Nuevos métodos como la impedanciometría, y los catéteres de micromanometría,intentan paliar el déficit existente hasta ahora en este campo. Los objetivos de nuestro estudio son en una primera fase obtener valores normales de impedanciometría en niños controles y estudiar,en una segunda fase, la relación entre RGE y enfermedad respiratoria en recién nacidos pretérmino, con un registro multivariable de impedancia y pH para identificar los episodios de reflujo y las variaciones del electrocardiograma (ECG), la saturación de O2 (SO2), la frecuencia respiratoria (FR) y el CO2 espirado (ETCO2), para objetivar si los episodios de reflujo tienen alguna relación con la enfermedad respiratoria. Hemos estudiado hasta ahora a 7 niños pretérmino, con controles mediante monitorización durante 24 horas de pHmetría + impedancia. Nº de reflujos ácidos: 89. Nº de reflujos pH>4: 192. Reflujos que llegan a esófago distal: 79,36%.La impedancia, por tanto, se trata de un método inocuo que abre nuevos horizontes en el estudio de una enfermedad tan común como el RGE (AU)

Preterm infants present often Gastroesophageal refluxes (GER). Esophageal pH monitoring to reflux detection is of limited use in this infants because their gastric pH is normally higher than 4 for 90% of the time. Other methods such as the Intraluminal Impedance Technique (MII) technique and the use of micromanometric catheters try to palliate the difficulties for measuring GER by pH monitoring. The aim of this study, in a first step, was to obtain the normal Intraluminal Impedance values on control children and, in a second step, to study the relationship between GER and cardiorespiratory episodes using simultaneous recording of the end-tidal fraction of expired CO2, O2 saturation by pulse-oximetry, respiratory frequency, esophageal impedance and manometry, gastro-esophageal pHmetry, and electrocardiography in selected patients. Data from simultaneous pH and Intraluminal Impedance during 24 hours in 7 control preterms showed 89 acid refluxes, 192 non-acid refluxes, 79.36% of all refluxes reached the proximal esophagus. Therefore the impedance is an innocuous method which opens new horizons in the study of such a common illness as the GER in the preterm infantsPreterm infants present often Gastroesophageal refluxes(GER). Esophageal pH monitoring to reflux detection is of limited use in this infants because their gastric pH is normally higher than 4 for 90% of the time. Other methods such as the Intraluminal Impedance Technique (MII) technique and the use of micromanometric catheterstry to palliate the difficulties for measuring GER by pH monitoring. The aim of this study, in a first step, was to obtain the normal Intraluminal Impedance values on control children and, in a second step, to study the relationship between GER and cardiorespiratory episodes using simultaneous recording of the end-tidal fraction of expired CO2,O2 saturation by pulse-oximetry, respiratory frequency, esophageal impedance and manometry, gastro-esophageal pHmetry, and electrocardiographyin selected patients. Data from simultaneous pH and Intraluminal Impedance during 24 hours in 7 control preterms showed 89 acid refluxes, 192 non-acid refluxes, 79.36% of all refluxes reached the proximal esophagus.Therefore the impedance is an innocuous method which opens new horizons in the study of such a common illness as the GER in the preterm infants (AU)

[Hypogammaglobulinemia as risk factor for Cryptococcus neoformans infection: report of 2 cases]. / Hipogamaglobulinemia como fator de risco para infecção por Cryptococcus neoformans: a propósito de dois casos.

Two HIV-seronegative patients with cryptococcal disease refractory to conventional antifungal therapy were submitted to an evaluation of the immune system. Hypogammaglobulinemia was found in both and associated with abnormal function of cell-mediated immunity. Hypogammaglobulinemia is considered as a possible predisposing factor for cryptococcal infection. The importance of the antibodies on the control of Cryptococcus neoformans infection is discussed.

[In old age ... AIDS. Is it worth to initiate antiretroviral treatment? Review of 37 patients more than 60 years of age]. / A la vejez ... el SIDA. Merece la pena iniciar tratamiento antirretroviral? Revision de 37 pacientes con más de 60 años.

INTRODUCTION: HIV infection is common in young persons and its clinical picture, outcome and response to antiretroviral therapy is well known, but it is not the case in the elderly. OBJECTIVES: To evaluate the clinical characteristics and response to antiretroviral therapy of HIV elderly patients. DESIGN: Retrospective study of 37 patients elder than 60 years. The control group comprised of 64 HIV positive patients with less than 60 years. None of them were drug abusers. RESULTS: The mean age of patients was 65 years (range 60-79), 86% were males. The most frequent causes for HIV testing were: wasting (22%), P. carinii pneumonia (19%), tuberculosis (13%) and Kaposi sarcoma (10%), but in the control group voluntary testing was the most common reason (64%). The mean CD4 count at diagnosis was lower in the elderly group (233 cells/microL vs 323 cells/microL). During follow up, the most frequent complications for those with less than 200 CD4 cells were: oral candidiasis (44%), P. carinii pneumonia (27%), Kaposi sarcoma (22%) and esophageal candidiasis (22%), while in the young group P. carinii pneumonia (22%), Kaposi sarcoma (9%) and esophageal candidiasis (9%) were less frequent. 67% of the elderly received antiretroviral therapy. Zidovudine had to be discontinued due to anaemia in half of them. Survival at 6 and 12 months was significantly longer in treated patients compared to those who did not received antiretrovirals (100% vs 14% at 6 months, P < 0.001; and 54% vs 0% at 12 months, p = 0.03); and at 2 years it was almost similar to that of the young group (36% vs 52%, p = 0.38). CONCLUSIONS: HIV infection in the elderly is generally diagnosed in an advance stage, but antiretroviral therapy prolongs survival. Zidovudine should be reserve as a second line drug because its frequent haematological toxicity.

Anti-NK antibodies injected into recipient mice enhance engraftment and chimerism after allogeneic transplantation of fetal liver stem cells.

Natural killer (NK) cells have been shown to play a role in the phenomenon of resistance to transplantation of allogeneic stem cells. To explore and prevent such resistance, we treated severe combined immunodeficiency mice (SCID) with anti-NK antibodies and analysed the improved engraftment of stem cells induced by this treatment. Two groups of nine SCID mice (H-2d) were compared: group A received two injections of anti-asialo GM1 rabbit antibodies (anti-NK) on days 1 and 4; group B received two injections of normal rabbit serum. All mice were injected intravenously with 7 x 10(6) fetal liver cells from B6 mice (H-2b) on day 2. One month after fetal liver cell transplantation, all mice from group A demonstrated engraftment and chimerism; at this time, donor cells accounted for more than 50% of peripheral blood mononuclear cells (PBMC). In contrast, in group B, only one mouse had 26% of donor cells among PBMC and all other mice had less than 10%. At two months, results were virtually identical in group A (over 72% of donor cells among PBMC from all mice) and slightly improved in group B (0-38% of donor cells). After the third month and continuously until the 12th month, the stability of chimerism was established in group A (over 55% of donor cells in 7 of the 9 mice) but had virtually disappeared in group B (0-2% of donor cells in all mice). Tissue analysis demonstrated the improved reconstitution of the thymus and the spleen in mice from group A. The proliferative responses of spleen cells to phytomitogens were significantly higher in all mice from group A than in any mouse from group B. Skin allografts from a third party (H-2k) were rejected within 10 days by group A mice but not by group B mice, one year after fetal liver cell transplantation. On the whole, anti-NK antibodies were able to improve engraftment, chimerism and stability of allogeneic stem cell transplants.

First Report of Fusarium solani f. sp. cucurbitae Race 1 in Spain.

A crown, root, and fruit rot of squash (Cucurbita maxima Duchesne) was first observed in 1995 and again in 1996 in several fields in the eastern provinces of Valencia and Castellón. When plants approach maturity they exhibited a severe cortical rot at the base of the stem and the upper portion of the taproot causing yellowing and wilting of the leaves. Within a few days of the first symptoms of crown rot, affected plants usually died. Soft, circular lesions developed where fruit were in contact with soil. Isolations on potato dextrose agar supplemented with 0.5 mg/ml of streptomycin sulfate (PDAS) from the crown of symptomatic plants and fruits yielded primarily a Fusarium sp. Isolates were transferred to potato sucrose agar (PSA) and Bilay's medium, modified by Joffe (SNA), and incubated at 25°C for 10 days with a 12-h photoperiod. The isolates were identified as Fusarium solani (Mart.) Sacc. based on colony morphology on PSA and fungal morphology on SNA. C. maxima (cv. Dulce de Horno) seedlings (eight replicates per isolate) grown on a sterilized mixture of equal portions (vol/vol) of soil, sand, and peat moss were inoculated at the first true leaf stage by introducing a 10-ml spore suspension (106 spores per ml) at the base of plants. Symptoms appeared in 14 to 21 days as linear, coalescing, cortical lesions in the hypocotyl of inoculated plants and ultimately caused seedling death. There were no differences observed in the five isolates tested, regardless of origin. Mature fruits were inoculated by injecting spore suspension (106 spores per ml) into the mesocarp. Within 14 to 21 days after inoculation, lesions developed similar to those observed in the field. Stem isolates were pathogenic on the fruit, and fruit isolates were pathogenic on stems. Reference isolates NRLL 22165 and NRRL 22449 for race 1, and NRRL 20545 and NRRL 22144 for race 2, provided by K. O'Donnell, were also tested as positive controls. Only race 1 isolates caused seedling death. In each study, the fungus was reisolated, confirming Koch's postulates. Based on these results and disease symptoms in the field, the fungus was classified as F. solani f. sp. cucurbitae W. C. Snyder & H. N. Hans race 1, which causes a root, stem, and fruit rot, whereas race 2 causes only a fruit rot (1). F. solani also was isolated from seeds removed from diseased fruits. This is the first report of the presence of F. solani f. sp. cucurbitae race 1 in Spain. Reference: (1) T. A. Tousson and W. C. Snyder. Phytopathology 51:17, 1961.

[The relationship between paracoccidioidomycosis and alcoholism]. / Associação entre paracoccidioidomicose e alcoolismo.

The relationship between alcoholism and paracoccidioidomycosis was evaluated by the case-control method. The alcohol consumption of 4 groups of patients was compared: 50 patients with chronic paracoccidioidomycosis, 20 patients with the acute or subacute form of this mycosis and their respective control groups of hospitalized patients, each case matched by sex and age. Between September 1986 and July 1988 the cases and their controls were interviewed by one and the same investigator using a questionnaire on drinking habits: quantity and type of beverage consumed, time of onset and frequency of use and whether they had manifested symptoms of inebriation or of alcohol dependence previously. As compared with control patients, the mean daily ingestion of alcohol in excess of 60 ml was more frequent in the chronic paracoccidioidomycosis group (50.0% x 30.0%). These patients also preferred to drink sugar cane brandy more frequently (89.4% x 68.3%). When the average daily consumption of ethyl alcohol exceeded 100 ml, most patients presented a recurrence of infection during or after antifungal therapy. In the acute-subacute paracoccidioidomycosis group, 64.3% of the patients reported inebriation on one or more occasions, versus 17.6% in the respective control group. The results suggest that alcoholism can be a predisposing factor to paracoccidioidomycosis and, probably, accounts for a worse prognosis for this infection.