Fluticasone in mild to moderate atopic dermatitis relapse: A randomized controlled trial.

BACKGROUND: The long-term efficacy of corticosteroids to prevent atopic dermatitis (AD) relapses has partially been addressed in children. This study compared an intermittent dosing regimen of fluticasone propionate (FP) cream 0.05% with its vehicle base in reducing the risk of relapse in children with stabilized AD. METHODS: A randomized controlled, multicentric, double-blind trial was conducted. Children (2-10 years) with mild/moderate AD (exclusion criteria: >30% affected body surface area and/or head) were enrolled into an Open-label Stabilization Phase (OSP) of up to 2 weeks on twice daily FP. Those who achieved treatment success entered the Double-blind Maintenance Phase (DMP). They were randomly allocated to receive FP or vehicle twice-weekly on consecutive days for 16 weeks. The primary study endpoint was relapse rate; time to relapse and severity of disease were also studied. Kaplan-Meier estimates were calculated. RESULTS: Fifty-four patients (29 girls) entered the OSP (23 mild AD) and 49 (26 girls) continued into the DMP. Mean age was 5.5 (SD: 2.8) and 5.1 (SD: 2.3) yrs for FP and vehicle groups, respectively. Four patients withdrew from the DMP (two in every group). Patients treated with FP twice weekly had a 2.7 fold lower risk of experiencing a relapse than patients treated with vehicle (relative risk 2.72, SD: 1.28; p=0.034). FP was also superior to vehicle for delaying time to relapse. Both treatment therapies were well tolerated. CONCLUSION: This long-term study shows that twice weekly FP provides an effective maintenance treatment to control the risk of relapse in children with AD.

[Has the use of antipyretics been modified after the introduction of different concentrations of ibuprofen into the market?]. / ¿Se ha modificado el uso de antitérmicos tras la introducción de ibuprofeno a diferentes concentraciones?

INTRODUCTION: Due to the emergence of new pharmaceutical presentations of ibuprofen (40 mg/ml), an analysis was made on the use of antipyretics in pediatric outpatient in Spain. PATIENTS AND METHODS: A cross-sectional, observational, descriptive study was carried out on a sample of children under 14 years old with treated febrile syndrome, seen in the Emergency Room of the Hospital General Universitario de Valencia from November 2012 to January 2013. RESULTS: Of the 217 children included, 144 were treated with paracetamol or ibuprofen, 69 received both drugs, and one received paracetamol and metamizol. There were 58.7% of exposures to paracetamol and 40.9% to ibuprofen. The parents decided the use of antipyretics in 63.2% of cases. In 98 exposures the dose was different from that authorized in the labeling of the drug (off-label use). Ibuprofen was used off-label in 40.2% of cases, mostly by underdosing (35.9%). Paracetamol was used off-label in 29.8% of cases, predominantly overdose (26.8%), with the difference being statistically significant. No significant differences were observed in the off-label use in either monotherapy or combined use. There were also no differences when antipyretics prescribed by doctors or given directly by parents were evaluated separately. CONCLUSIONS: The majority of children with treated febrile syndrome seen in the Emergency Room were receiving antipyretic drugs after a parental decision. Paracetamol is the most commonly used drug and one in three children received it simultaneously with ibuprofen. The antipyretics were used off label in one-third of the cases. Off label use of ibuprofen is increasing, and is probably due to the existence of different pharmaceutical presentations.

Conceptos nuevos sobre el sistema renina angiotensina / New concepts on the renin-angiotensin system

En los últimos años se han descrito nuevos componentes del sistema renina angiotensina. Se han identificado 5 nuevos polipéptidos, sus vías de síntesis y las enzimas responsables de ella. Se han descrito también receptores para la angiotensina 1–7, la angiotensina IV y la renina. El conocimiento de los sistemas renina angiotensina locales se ha completado con el descubrimiento de los sistemas intracelulares. Se han descrito mutaciones y polimorfismos en los genes de los distintos componentes del sistema, que podrían relacionarse con el desarrollo de hipertensión y de enfermedad cardiovascular. Además, se ha introducido en terapéutica el aliskiren, primer representante del nuevo grupo de los inhibidores directos de la renina. También se han publicado los primeros resultados positivos obtenidos con una vacuna antihipertensiva que genera anticuerpos frente a la angiotensina II. Todos estos hallazgos han permitido postular nuevas hipótesis sobre la relación entre los componentes del sistema y la enfermedad cardiovascular (AU)

In recent years, new components of the renin-angiotensin system have been described. Five new polypeptides with their synthesis routes and the enzymes involved in their synthesis have been identified. Receptors for angiotensin 1–7, angiotensin IV and rennin have also been described. The knowledge of local renin-angiotensin systems has been extended with the discovery of the intracellular systems. Mutations and polymorphisms in the genes of the different components of the renin-angiotensin system have been described. These could be involved in the development of hypertension and cardiovascular disease. In addition, aliskiren, the first component of the new group of renin directinhibitors, has been introduced in the therapeutics. The first positive results of a clinical trial with an antihypertensive vaccine that generates antibodies against angiotensin II have been published. All these findings have made it possible to generate new hypotheses on the relationship between the components of the system and cardiovascular diseases (AU)

[Drugs used in paediatric outpatients: do we have enough information available?]. / Medicamentos utilizados en pediatría extrahospitalaria: disponemos de información suficiente?

OBJECTIVE: To analyse the drugs taken in paediatric outpatients and the information available on these drugs. PATIENTS AND METHODS: A cross-sectional, observational, descriptive study was carried out. The study involved a sample of children under 14 years seen in the Emergency Room of the HGUV from June 2005 to August 2006. The medicines they received were quantified and classified, and the information on these drugs available in the Vademecum International Medicom and in the Summary of Product Characteristics, were analysed. RESULTS: Of the 462 children (mean age 5.2 (95 % CI 4.9-5.6)) included, 336 received 667 medicines (152 different medicines) that contained 864 drugs (161 different drugs). In 34.3 % of the cases it was for self-medication. Children under 4 years received more drugs than the older group (80.2 % in the younger group and 67.4 % in the older). Patients received from 1 to 7 medicines (mean 2.0). Children receiving 2 or 3 medicines were younger than those who received one. Five therapeutic groups of the Anatomical-Therapeutical-Chemical Classification (ATC) include the 93.1 % of the drugs administered (R: 26.5 %; M: 23.8 %; N: 22.8 %; J: 10.6 % and A: 10.0 %). In the information sources consulted there was no information available on paediatric use for 40 of the 152 medicines used. CONCLUSIONS: Almost 75 % of patients seen in the Emergency Room were already receiving drugs before they arrived at the hospital, in many cases as a result of self-medication. The information available on the paediatric use of drugs is deficient. Clinical research is required to study the effects of pharmacological treatment on children and to improve the information on their use.

Medicamentos utilizados en pediatría extrahospitalaria: ¿disponemos de información suficiente? / Drugs used in paediatric outpatients: Do we have enough information available?

Objetivo: Analizar los medicamentos que reciben los pacientes pediátricos en el ámbito extrahospitalario y la información disponible sobre los mismos. Pacientes y métodos: Estudio transversal, observacional y descriptivo realizado en una muestra de pacientes menores de 14 años atendidos en urgencias del Servicio de Pediatría del Consorcio Hospital General Universitario de Valencia entre junio 2005 y agosto 2006. Se cuantifican y clasifican los medicamentos utilizados antes de acudir a urgencias y se analiza la información sobre su uso que contiene el Vademécum Internacional Medicom y la ficha técnica. Resultados: Se recogió información sobre 462 niños con media de edad de 5,2 años (intervalo de confianza del 95 % [IC 95 %]: 4,9-5,6). De ellos, 336 reciben 667 medicamentos (152 distintos) que contienen 864 principios activos (161 diferentes). En el 34,3 % de los casos el uso es por automedicación. Los menores de 4 años reciben medicamentos en mayor proporción que los mayores (80,2 y 67,4 %, respectivamente). Los pacientes reciben entre 1 y 7 medicamentos (media 2,0). Los que toman 2 o 3 medicamentos son menores que los que toman uno. Cinco grupos terapéuticos de la Clasificación anatómico-terapéutico-química (ATC) incluyen el 93,1 % de los medicamentos (R [aparato respiratorio]: 26,5 %; M [aparato locomotor]: 23,8 %; N [sistema nervioso central]: 22,8 %; J [antiinfecciosos por vía general]: 10,6 % y A [aparato digestivo y metabolismo]: 10,0 %). Para 40 de los 152 medicamentos no hay información pediátrica en las fuentes consultadas. Conclusiones: Casi tres cuartas partes de los niños atendidos en urgencias toman medicamentos antes de acudir a este servicio, en muchos casos por automedicación. La información sobre uso pediátrico de medicamentos es incompleta y presenta incongruencias. Es necesario fomentar la investigación clínica sobre los efectos del tratamiento farmacológico en los niños para mejorar la información sobre su uso (AU)

Objective: To analyse the drugs taken in paediatric outpatients and the information available on these drugs. Patients and methods: A cross-sectional, observational, descriptive study was carried out. The study involved a sample of children under 14 years seen in the Emergency Room of the HGUV from June 2005 to August 2006. The medicines they received were quantified and classified, and the information on these drugs available in the Vademecum International Medicom and in the Summary of Product Characteristics, were analysed. Results: Of the 462 children (mean age 5.2 (95 % CI 4.9-5.6)) included, 336 received 667 medicines (152 different medicines) that contained 864 drugs (161 different drugs). In 34.3 % of the cases it was for self-medication. Children under 4 years received more drugs than the older group (80.2 % in the younger group and 67.4 % in the older). Patients received from 1 to 7 medicines (mean 2.0). Children receiving 2 or 3 medicines were younger than those who received one. Five therapeutic groups of the Anatomical-Therapeutical-Chemical Classification (ATC) include the 93.1 % of the drugs administered (R: 26.5 %; M: 23.8 %; N: 22.8 %; J: 10.6 % and A: 10.0 %). In the information sources consulted there was no information available on paediatric use for 40 of the 152 medicines used. Conclusions: Almost 75 % of patients seen in the Emergency Room were already receiving drugs before they arrived at the hospital, in many cases as a result of self-medication. The information available on the paediatric use of drugs is deficient. Clinical research is required to study the effects of pharmacological treatment on children and to improve the information on their use (AU)

[Are the Spanish hypertensive children therapeutic orphans?]. / Son los niños hipertensos españoles huérfanos terapéuticos?

INTRODUCTION: According to current guidelines, hypertension in children should be treated with the same drugs as those used in adults, with adjustment of the dose to their body size. The term therapeutic orphans refers to the lack of information on how to use drugs in children. The aim of this study was to investigate whether the information in the International Vademecum (I-V) is sufficient for the correct use of antihypertensive drugs in children. MATERIAL AND METHOD: We reviewed the data on pediatric dosages of antihypertensive drugs in the I-V (44th and 45th editions). When there were several drugs for the same molecule, the last one marked with the Spanish Ministry of Health and Consumption's logo was selected. When information on a particular drug was not available, the entries for other drugs with the same active principle were reviewed. The information was compared with that provided by the Fourth Report of the National High Blood Pressure Education Program Working Group (NHBPEP). RESULTS: A total of 111 entries for 41 antihypertensive drugs were reviewed. Information on use in children is available for only 3 diuretics and 2 angiotensin converting enzyme inhibitors. The remaining entries either contain no information or indicate that the effectiveness and safety in children has not been evaluated. Some drugs are contraindicated in children. The Fourth Report of the NHBPEP includes pediatric dosages for 28 antihypertensive drugs. The Food and Drug Administration has authorized 10 antihypertensive drugs for use in children. CONCLUSIONS: The information in the V-I can be used to determine the correct dosage of only 5 antihypertensive drugs in children, making this age group authentic therapeutic orphans.

¿Son los niños hipertensos españoles huérfanos terapéuticos? / Are the Spanish hypertensive children therapeutic orphans?

Introducción: Según las guías, la hipertensión en los niños debe tratarse con los mismos fármacos usados en adultos ajustando las dosis al tamaño corporal. El término huérfano terapéutico se refiere a la falta de información sobre el uso de medicamentos en niños. El objetivo es investigar si el Vademécum Internacional (V-I) contiene información para el uso correcto de antihipertensivos en niños. Material y método: Revisión en el V-I de la posología pediátrica de antihipertensivos. Si existen varias especialidades para un fármaco se selecciona el del logotipo del Ministerio de Sanidad y Consumo más reciente. Si en una monografía no hay información, se revisan las de otras especialidades del mismo principio activo. La información se compara con la del 4.º informe del National High Blood Pressure Education Program Working Group (NHBPEP). Resultados: Se revisan 111 monografías de 41 fármacos con indicación de antihipertensivo. Sólo para 3 diuréticos y 2 inhibidores de la enzima conversora de angiotensina (IECA) hay información pediátrica. Las otras advierten de que no se ha establecido la eficacia y seguridad o no hacen referencia a niños. En algunos casos se contraindican. El 4.º informe del NHBPEP incluye dosificación pediátrica de 28 antihipertensivos. La Food and Drug Administration (FDA) tiene autorizados 10 antihipertensivos para uso en niños. Conclusiones: Con la información del V-I sólo es posible dosificar correctamente 5 antihipertensivos en niños, lo que los convierte en auténticos huérfanos terapéuticos

Introduction: According to current guidelines, hypertension in children should be treated with the same drugs as those used in adults, with adjustment of the dose to their body size. The term therapeutic orphans refers to the lack of information on how to use drugs in children. The aim of this study was to investigate whether the information in the International Vademecum (I-V) is sufficient for the correct use of antihypertensive drugs in children. Material and method: We reviewed the data on pediatric dosages of antihypertensive drugs in the I-V (44th and 45th editions). When there were several drugs for the same molecule, the last one marked with the Spanish Ministry of Health and Consumption's logo was selected. When information on a particular drug was not available, the entries for other drugs with the same active principle were reviewed. The information was compared with that provided by the Fourth Report of the National High Blood Pressure Education Program Working Group (NHBPEP). Results: A total of 111 entries for 41 antihypertensive drugs were reviewed. Information on use in children is available for only 3 diuretics and 2 angiotensin converting enzyme inhibitors. The remaining entries either contain no information or indicate that the effectiveness and safety in children has not been evaluated. Some drugs are contraindicated in children. The Fourth Report of the NHBPEP includes pediatric dosages for 28 antihypertensive drugs. The Food and Drug Administration has authorized 10 antihypertensive drugs for use in children. Conclusions: The information in the V-I can be used to determine the correct dosage of only 5 antihypertensive drugs in children, making this age group authentic therapeutic orphans

Clinical trials in children.

Randomized controlled clinical trials are felt by the medical community to provide the best evidence. Participation in trials involves the possibility of obtaining benefits but also of suffering some risks. Those risks are often considered unacceptable for children but if clinical trials are not conducted in children, clinicians are forced to extrapolate study data from adults. In 1968 H. Shirkey termed children "therapeutic orphans" because of the lack of adequately tested and labeled drugs available in appropriate formulations. Research involving children entails specific difficulties as the need to study children of different ages, the small number of children affected by certain diseases or ethical issues. This paper considers aspects of pediatric clinical pharmacology and children's responses to drugs. It also reviews some of the current situations in pediatric clinical trials, covering aspects such as: the benefits and risks of trial participation; the specificity of pediatric trial design; the ethical issues such as consent; the use of placebo or the participation of healthy children; and the current legal situation in Europe and in the USA.

Efecto del fosinopril sobre los niveles plasmáticos de fibrinógeno en hipertensos esenciales / Effect of fosinopril on plasma fibrinogen levels in essential hypertensive patients

Objetivo. Valorar si fosinopril es capaz de reducir las cifras de fibrinógeno en pacientes con hipertensión arterial esencial (HTA) y valorar la influencia de otros factores de riesgo cardiovascular.Métodos. Hipertensos esenciales (PAD: 90-114; PAS: 140-180 mmHg) de cualquier sexo y edad superior a 30 años sin contraindicaciones para el uso de fosinopril.Tres visitas con registro de presión arterial (PA) y fibrinógeno por nefelometría (basal, 3 meses, 6 meses). Tratamiento con fosinopril 20 mg/día. Resultados. Setenta y cinco pacientes (54,7 por ciento mujeres); edad media: 59,8 ñ 10,4 años; peso: 73,9 ñ 10,9 kg; IMC: 28,0 ñ 3,8 kg/m2. Fosinopril disminuye significativamente la PA y el fibrinógeno plasmático en las visitas 2 y 3. El 54,7 por ciento y el 88 por ciento de los pacientes normalizan la presión arterial sistólica (PAS) y la presión arterial diastólica (PAD), respectivamente, en la visita 3.No existe correlación entre los efectos sobre PAS, PAD y fibrinógeno. No existen diferencias en el efecto sobre fibrinógeno para sexo, IMC o hábito tabáquico.Conclusiones. Fosinopril reduce la presión arterial y el fibrinógeno plasmático en pacientes hipertensos sin que exista correlación entre ambos efectos. El efecto puede estar ligado a la inhibición de la enzima conversora de la angiotensina (IECA), sin que pueda descartarse la participación de otros efectos metabólicos de este IECA. (AU)

¿Interacciones o asociaciones potencialmente peligrosas? / Interactions or potentially dangerous associations?

No disponible

[Effect of arterial pressure and age on renal function, The "Care for the Kidney" study]. / Influencia de la presión arterial y la edad en la función renal. Estudio "Cuidar el riñón".

BACKGROUND: The kidney is one of the principal target organs of hypertension. The mechanism by which hypertension damages the kidney and the relative contribution of high blood pressure to the progression of renal failure remains incompletely defined. The clinical quantification of renal function is usually thought to require determination of plasma clearance of endogenous creatinine (ClCr), an impractical test for epidemiological evaluation. For this reason several formulae have been proposed to estimate the ClCr from the serum creatinine concentration, such as sex, age, and body weight. The most often used formula is the one proposed by Crockroft and Gault in 1976. OBJECTIVE: To determine the prevalence of loss of renal function and the influence of hypertension and age on this loss in hypertensive and normotensive patients. PATIENTS AND METHOD: An observational, cross-sectional comparative study was carried out. 3,420 patients (1,171 normotensive and 2,249 hypertensive) were studied. Average age was 70 years (19.4% of patients < 65 years; 23.3% > 75 years). 98.1 of hypertensive patients were treated with drugs, 26.7% of them with more than one drug. 27.9% of treated patients achieved blood pressure control (< 140-90 mm Hg). The level of renal function was estimated by means of ClCr using the Crockroft and Gault formula. RESULTS: 3.9% of normotensive and 12.2% of hypertensive patients had serum creatinine values > 1.3 mg/dl, but 28.6% of normotensive and 40.4% of hypertensive had ClCr < 60 ml/min. The patients over 75 years had ClCr mean values < 60 ml/min. There was correlation between ClCr and age, but there was no correlation between ClCr and blood pressure values. CONCLUSIONS: The estimated ClCr decrease with age and there existed correlation between both variables. The ClCr is lower in hypertensive than in normotensive patients. Hypertension and age influence loss of renal function, but age is a determining factor. The estimated ClCr was a more sensible method of evaluating the loss of renal function than the serum creatinine values. The use of Crockroft and Gault formula can be useful for making diagnostic and therapeutic decisions in primary care.

Fármacos antihipertensivos en Atención Primaria / Antihypertensive drugs in Primary Health Care

No disponible

Influencia de la presión arterial y la edad en la función renal. Estudio «Cuidar el riñón» / Influence of age and blood pressure on renal function: the study «cuidar el riñón»

Fundamento: Estudios epidemiológicos han puesto de manifiesto la elevada prevalencia de insuficiencia renal crónica (IRC) en hipertensos, sobre todo ancianos, siendo continua la relación entre cifras tensionales y función renal. Objetivo: Evaluar la prevalencia de deterioro renal, mediante el aclaramiento de creatinina según la fórmula de Cockroft y Gault, en pacientes hipertensos comparando con normotensos de la misma edad. Pacientes y métodos: Estudio observacional, transversal y comparativo en pacientes hipertensos y normotensos, atendidos por médicos de Atención Primaria. 3.420 pacientes (1.171 normotensos y 2.249 hipertensos), Edad media 70 años ( 75: 23,3%). El 53,8% eran mujeres. El 27,9% de los hipertensos estaban controlados (< 140-90 mmHg) y el 98,1% tratados con fármacos, el 26,7% con más de un fármaco antihipertensivo. La función renal se ha valorado mediante la fórmula de Crockroft y Gault usando una calculadora preprogramada. Resultados: Un 3,9% de los normotensos y un 12,2% de los hipertensos tenía valores de creatinina superiores a 1,3 mg/dl, pero un 28,6% y un 40,4% presentaban aclaramiento de creatinina inferior a 60 ml/min. Los pacientes de más de 75 años presentan valores medios de aclaramiento inferiores a 60 ml/min. Existe correlación entre edad y aclaramiento de creatinina, pero no entre éste y cifras tensionales. Conclusiones: El aclaramiento de creatinina y la función renal disminuye con la edad y es menor en hipertensos que en normotensos. La hipertensión arterial y la edad producen deterioro de la función renal, pero la edad parece tener mayor influencia que el grado de control tensional. El aclaramiento de creatinina calculado mediante la fórmula de Crockroft y Gault parece un método más sensible para valorar la función renal que la creatinina plasmática. El empleo de la fórmula de Crockoft y Gault puede ser útil para la toma de decisiones diagnósticas y terapéuticas en Atención Primaria

Background: The kidney is one of the principal target organs of hypertension. The mechanism by which hypertension damages the kidney and the relative contribution of high blood pressure to the progression of renal failure remains incompletely defined. The clinical quantification of renal function is usually thought to require determination of plasma clearance of endogenous creatinine (CICr), an impractical test for epidemiological evaluation. For this reason several formulae have been proposed to estimate the CICr from the serum creatinine concentration, such as sex, age, and body weight. The most often used formula is the one proposed by Crockroft and Gault in 1976. Objective: To determine the prevalence of loss of renal function and the influence of hypertension and age on this loss in hypertensive and normotensive patients. Patients and method: An observational, cross-sectional comparative study was carried out. 3,420 patients (1,171 normotensive and 2,249 hypertensive) were studied. Average age was 70 years (19.4% of patients 75 years). 98.1 of hypertensive patients were treated with drugs, 26.7% of them with more than one drug. 27.9% of trated patients achieved blood pressure control ( 1.3 mg/dl, but 28.6% of normotensive and 40.4% of hypertensive had CICr < 60 ml/min. The patients over 75 years had CICr mean values < 60 ml/min. There was correlation between CICr and age, but there was no correlation between CICr and blood pressure values. Conclusions: The estimated CICr decrease with age and there existed correlation between both variables. The CICr is lower in hypertensive than in normotensive patients. Hypertension and age influence loss of renal function, but age is a determining factor. The estimated CICr was a more sensible method of evaluating the loss of renal function than the serum creatinine values. The use of Crockroft and Gault formula can be useful for making diagnostic and therapeutic decisions in primary care

Estudio de la utilización de medicamentos en la artrosis / Study of medication utilization in osteoarthritis

Objetivo: Describir el perfil de uso de medicamentos en pacientes con artrosis periférica y evaluar la adecuación terapéutica de los tratamientos analgésicos y antiinflamatorios en España. Diseño: Estudio observacional, descriptivo, transversal y multicéntrico de ámbito estatal. Pacientes: Se estudió a 3.002 pacientes diagnosticados de artrosis periférica y tratados con analgésicos o antiinflamatorios en los últimos 3 meses. Ámbito: Consultas de atención primaria. Resultados: En el momento de realizar el estudio, el 58,2 per cent de los pacientes tomaba paracetamol, el 44,8 per cent, antiinflamatorios no esteroideos (AINE) clásicos, el 11,8 per cent, inhibidores de la ciclooxigenasa 2 (COX-2) y el 6,6 per cent, otros fármacos. El tratamiento con AINE se prescribía a pacientes más jóvenes y varones (p = 0,001), mientras que los pacientes tratados con paracetamol tenían más enfermedades gástricas de base y diabetes que los que tomaban AINE (p = 0,006 y 0,035, respectivamente); pese a ello, se registró un mayor porcentaje de acontecimientos adversos gastrointestinales en los pacientes tratados con AINE (8,5 per cent) respecto a los tratados con paracetamol (5,8 per cent) (p = 0,05). La automedicación en pacientes tratados con paracetamol es menor que en aquellos a los que se les ha prescrito AINE (54,3 frente a 63,6 per cent; p < 0,001). Un 51 per cent de los pacientes tomaba dosis de paracetamol inferiores a 3 g/día, mientras que el 48,6 per cent recibía 3-4 g/día. Conclusiones: El paracetamol es el fármaco más utilizado para el tratamiento de la artrosis periférica en España. Se usa más en personas ancianas y con enfermedades concomitantes, presenta menos acontecimientos adversos gastrointestinales y su prescripción disminuye la automedicación. Las dosis medias utilizadas son inferiores a las indicadas en las recomendaciones de ACR y EULAR (AU)

Influencia de la edad gestacional en la contractilidad de los vasos coriónicos humanos in vitro / The influence of gestational age on in vitro contractility of human chorionic vessels

Los vasos placentarios humanos carecen de inervación autónoma y, por lo tanto, la resistencia vascular debe ser controlada por factores humorales y mecanismos anteriores autocrinos o paracrinos. Estos factores pueden variar en las diferentes etapas de la gestación; asimismo, la respuesta de los vasos placentarios puede ser diferente según la edad gestacional. Se conocen diversas sustancias que, originadas en el feto, la madre o el cordón umbilical, pueden afectar al tono vascular fetoplacentario de forma directa o indirecta. Investigamos si la edad gestacional modifica la respuesta vascular in vitro de los vasos placentarios a un agente vasoconstrictor como el cloruro potásico (ClK) (AU)

Characteristics of histamine tachyphylaxis in rat uterine smooth muscle.

OBJECTIVE AND DESIGN: To study both the desensitisation induced by short-term exposure to histamine and the mechanism responsible in the isolated rat uterus. MATERIAL: Precontracted isolated uterus (37 mM KCl) from oestrogenised Wistar rats were used. TREATMENT: Repetitive responses to histamine (10(-6), 10(-5), 10(-4), 10(-3) M), dimaprit and clonidine (10(-4) M) were tested at 15, 30, 45 and 105 min., with their modifications by (5 mg/kg, 24 h before sacrifice) reserpine, 10(-7) M propranolol, 10(-8) M atropine, and 10(-6) M indomethacin. Dose-response curves for adrenaline were carried out as standard protocol. METHODS: In vitro techniques (de Jalon's solution, 31 degrees C, carbogen, isotonic registration, resting tension 1 g). Levels of cAMP were studied in response to histamine, adrenaline and isoproterenol by radioassay. RESULTS: Repeated histamine produced a rapid loss of inhibitory uterine response depending on the number of exposures and increase in concentration. The tachyphylaxis phenomenon is not modified by the different pretreatments used. Dimaprit, but not clonidine or adrenaline, produced tachyphylaxis. The second exposition to 10(-3) M histamine produced a 38.8% reduction in cAMP production. CONCLUSION: Histamine appears to induce homologous and probably cAMP-dependent desensitisation of H2-receptors.

Adverse drug reactions in children reported by means of the yellow card in Spain.

OBJECTIVE: To analyze the case reports concerning children (14 years or younger) in the Spanish Pharmacovigilance System over a 10-year period (1982-1991). FINDINGS: The study of 1419 reports of adverse drug reaction (9.8% of all those received) showed the most commonly involved organs and systems to be the skin, digestive tract, and nervous system (62.8%). The most commonly involved pharmacological groups were antibiotics, respiratory medications, and vaccines (69%). The absolute number of reports is higher in children between 1 and 4 years of age (37.9%). There were more reports among males than in females. Less than 5% of the reports notified directly life-threatening or fatal reactions. CONCLUSIONS: Adverse drug reaction are not common in pediatric patients, and most are mild. However, due to limitations of clinical trials in children, pharmacoepidemiological studies may be the only source of information on the benefit-risk profile of drugs received by these patients, and as such require special attention.

A prospective study of adverse drug reactions in hospitalized children.

AIMS: There are few publications of adverse drug reactions (ADRs) among paediatric patients, though ADR incidence is usually stated to be higher during the first year of life and in male patients. We have carried out a prospective study to assess the extent, pattern and profile risk for ADRs in hospitalized patients between 1 and 24 months of age. METHODS: An intensive events monitoring scheme was used. A total of 512 successive admissions to two medical paediatric wards (47 beds) were analysed. The hospital records were screened daily during two periods (summer, 105 days and winter, 99 days), and adverse clinical events observed were recorded. RESULTS: A total of 282 events were detected; of these, 112 were considered to be manifestations of ADRs. The cumulative incidence was 16.6%, no differences being observed between periods. Although there were no differences between patients under and over 12 months of age, risk was found to be significantly higher among girls compared with boys (RR=1.66, 95% CI 1.03-2.52). The gastro-intestinal system was most frequently affected. The therapeutic group most commonly implicated was anti-infective drugs and vaccines (41.5%). The ADRs were mild or moderate in over 90% of cases. A consistent relationship was noted between the number of drugs administered and the incidence of ADRs. CONCLUSIONS: Hospitalized patients exhibited an ADR risk profile that included female sex and the number of drugs administered. No particular age predisposition was observed. The most commonly prescribed drugs are those most often implicated in ADRs in paediatric patients.