Real-world use of mycophenolate mofetil in inflammatory bowel disease: Results from the ENEIDA registry.

BACKGROUND: Studies to evaluate the use of mycophenolate mofetil (MMF) in inflammatory bowel disease (IBD) are limited after the appearance of biological treatments. AIMS: Our primary objective was to evaluate the effectiveness and safety of MMF in IBD. METHODS: IBD patients who had received MMF were retrieved from the ENEIDA registry. Clinical activity as per the Harvey-Bradshaw Index (HBI), partial Mayo score (pMS), physician global assessment (PGA) and C-reactive protein (CRP) were reviewed at baseline, at 3 and 6 months, and at final follow-up. Adverse events and causes of treatment discontinuation were documented. RESULTS: A total of 83 patients were included (66 Crohn's disease, 17 ulcerative colitis), 90% of whom had previously received other immunosuppressants. In 61% of patients systemic steroids were used at initiation of MMF, and in 27.3% biological agents were co-administered with MMF. Overall clinical effectiveness was observed in 64.7% of the population. At the end of treatment, 45.6% and 19.1% of subjects showed remission and clinical response, respectively. MMF treatment was maintained for a median of 28.9 months (IQR: 20.4-37.5). CONCLUSION: Our study suggests, in the largest cohort to date, that MMF may be an effective alternative to thiopurines and methotrexate in IBD.

Ectopic expression of the histone methyltransferase Ezh2 in haematopoietic stem cells causes myeloproliferative disease.

Recent evidence shows increased and decreased expression of Ezh2 in cancer, suggesting a dual role as an oncogene or tumour suppressor. To investigate the mechanism by which Ezh2-mediated H3K27 methylation leads to cancer, we generated conditional Ezh2 knock-in (Ezh2-KI) mice. Here we show that induced Ezh2 haematopoietic expression increases the number and proliferation of repopulating haematopoietic stem cells. Ezh2-KI mice develop myeloproliferative disorder, featuring excessive myeloid expansion in bone marrow and spleen, leukocytosis and splenomegaly. Competitive and serial transplantations demonstrate progressive myeloid commitment of Ezh2-KI haematopoietic stem cells. Transplanted self-renewing haematopoietic stem cells from Ezh2-KI mice induce myeloproliferative disorder, suggesting that the Ezh2 gain-of-function arises in the haematopoietic stem cell pool, and not at later stages of myelopoiesis. At the molecular level, Ezh2 regulates haematopoietic stem cell-specific genes such as Evi-1 and Ntrk3, aberrantly found in haematologic malignancies. These results demonstrate a stem cell-specific Ezh2 oncogenic role in myeloid disorders, and suggest possible therapeutic applications in Ezh2-related haematological malignancies.

Early maternal deprivation in rats: a proposed animal model for the study of developmental neuroimmunoendocrine interactions.

Adult animals that had been subjected to a single prolonged episode of maternal deprivation (MD) [24 h, postnatal day (PND) 9-10] show long-term behavioral alterations that resemble specific symptoms of schizophrenia. Moreover, at adolescence MD rats showed depressive-like behavior and altered motor responses. According to the neurodevelopmental hypothesis, certain behavioral abnormalities observed in MD animals may be related to altered neurodevelopmental processes triggered by MD-induced elevated glucocorticoids in relevant specific brain regions. We review here these neuroendocrine effects and show new data indicating that the MD procedure induces diverse detrimental effects on the immune system that are already revealed in the short term (PND 13) and persist into adulthood. These long-lasting effects might be related to altered hypothalamus-pituitary-adrenal axis activity and to social as well as nutrition-related factors. In fact, MD induces long-lasting decreases in body weight. In view of our findings we propose the present MD procedure as a potentially useful model to analyze developmental interactions between early psychophysiological stress and immunodeficient states.

[Forced spirometry in healthy preschool children]. / Espirometría forzada en preescolares sanos bajo las recomendaciones de la ATS/ERS: estudio CANDELA.

INTRODUCTION: Reference values for spirometry in healthy preschool children have not yet been obtained in accordance with American Thoracic Society (ATS) and the European Respiratory Society (ERS) guidelines. The objective was to establish reference values for spirometry in healthy preschoolers under the ATS/ERS 2007 statement. MATERIAL AND METHOD: Children of at least 2 and under 7 years of age were tested in 9 pediatric pulmonary function laboratories. The technicians were trained to apply a standardized protocol to perform spirometry. RESULTS: Valid spirometry results were obtained in 455 (81.54%) out of 558 children: 242 boys (53.2%) and 213 girls (46.8%). Ages were as follows: 31 at least 2 and under 3 years old; 96, at least 3 and under 4; 108, at least 4 and under 5; 122, at least 5 and under 6 years, and 98, at least 6 and under 7 years. Formulas were used to calculate the reference values for all the spirometry variables in preschoolers. CONCLUSIONS: Spirometry is feasible in the majority of preschool children under the new guidelines. The availability of the reference values presented is an important step, both for the care of preschoolers and for further research on pulmonary function.

Reduction in pediatric invasive pneumococcal disease in the Basque Country and Navarre, Spain, after introduction of the heptavalent pneumococcal conjugate vaccine.

This study evaluated the incidence of invasive pneumococcal disease, identified the causal serotypes, and tracked the evolution of the antibiotic susceptibility of Streptococcus pneumoniae isolates in the regions of the Basque Country and Navarre, Spain, before and after the introduction of the heptavalent pneumococcal conjugate vaccine. The study included all children aged between birth and 5 years diagnosed with bacteremia, meningitis, or bacteremic pneumonia caused by pneumococci. By the second year after introduction of the heptavalent pneumococcal conjugate vaccine, compared with the period 1998-2001, the incidence of invasive disease decreased by 64.3% in children less than 12 months of age, by 39.7% in children less than 24 months of age, and by 37.5% in children less than 60 months of age. The prevalence of clinical isolates of S. pneumoniae that lacked susceptibility to penicillin decreased by 58.2% among children less than 60 months of age. With an estimated coverage by four-dose heptavalent pneumococcal conjugate vaccine of 28-45% in 2003, the number of invasive pneumococcal infections in the Basque Country and in Navarre fell significantly after just 2 years of immunization, underscoring the importance of improving vaccination coverage under a universal childhood immunization program.

[Hospital admissions for varicella complications in children aged less than 15 years old]. / Hospitalizaciones por complicaciones de la varicela en niños menores de 15 años.

BACKGROUND: The complications of varicella are one of the arguments in favor of universal vaccination programs in children. OBJECTIVE: To describe the complications of varicella requiring hospital admission in a well-defined population (Gipuzkoa, Spain) and to compare the incidence of hospitalization with that reported in other series. MATERIAL AND METHODS: Observational, retrospective, multicenter study of admissions for varicella. The medical histories codified as varicella (minimum data set, CIE-0, codes 952.0-052.9) from 1 January 1993 to 31 December 2002 were reviewed. Calculation of hospitalization rates was based on emergency department visits and population data. The pediatric population of Gipuzkoa seeking medical attention at one of the four Basque Country Health Service hospitals in the area: Hondarribia, Mendaro, San Sebastian and Zumarraga. The mean coverage in Gipuzkoa is 54,999 children aged less than 15 years/year. All the children aged 0-15 years old admitted for more than 24 h with a discharge diagnosis of varicella complications. The variables studied are: age, gender, personal history, varicella immunization, immune status, fever, chest X-ray, complementary investigations, length of hospital stay, treatment, discharge diagnosis, clinical course, complications and sequelae at discharge. RESULTS: Seventy-one children were hospitalized. None had been vaccinated against the varicella-zoster virus. Eighty percent were aged less than 5 years and three were immunocompromised. Fifty-six percent had bacterial superinfection and invasive forms were found in seven patients. The mean length of admission was 6.5 days +/- 5.1. No deaths or sequelae were reported. CONCLUSIONS: The annual incidence rate of admissions longer than 24 hours due to varicella complications was 12.9 cases per 100,000 children aged less than 15 years, representing 0.31% of all annual admissions in this age group.

Hospitalizaciones por complicaciones de la varicela en niños menores de 15 años / Hospital admissions for varicella complications in children aged less than 15 years old

Antecedentes Las complicaciones por varicela se consideran una de las indicaciones que apoyan la cobertura vacunal universal. Objetivo Describir las complicaciones por varicela que han precisado hospitalización en una población definida (Guipuzkoa, España) y comparar la incidencia de hospitalizaciones con otras series. Material y métodos Estudio multicéntrico, retrospectivo, observacional, por revisión de historias clínicas, codificadas como varicela (CMBD, CIE-9, códigos 052.0-052.9) desde 1 de enero de 1993 a 31 de diciembre de 2002, y cálculo de las tasas de hospitalización en base a las urgencias asistidas y a los datos poblacionales. Población infantil de Guipuzkoa (España) asistida en el ámbito geográfico de los servicios de pediatría de los hospitales de agudos de Osakidetza-Servicio Vasco de Salud de Hondarribia, Mendaro, San Sebastián y Zumárraga, con una cobertura poblacional media de 54.999 niños menores de 15 años por año. Todos los niños y niñas de 0 a 15 años de edad, hospitalizados más de 24 h con el diagnóstico de varicela complicada. Se estudiaron las siguientes variables: edad, sexo, antecedentes personales, vacuna antivaricela, estado inmunológico, fiebre, radiografía de tórax, exámenes complementarios, duración del ingreso, tratamiento, diagnósticos de alta, evolución, complicaciones y secuelas al alta. Resultados Ingresaron 71 niños no vacunados frente al virus varicela-zoster, 80 por ciento menores de 5 años de edad, 68 inmunocompetentes y 3 no inmunocompetentes. Han predominado las sobreinfecciones bacterianas (56 por ciento) y destacan 7 casos con enfermedad invasiva. La estancia media ha sido de 6,50 5,15 día, sin mortalidad y sin secuelas. Conclusiones La incidencia anual de ingresos hospitalarios por varicela complicada superiores a 24 h ha sido 12,90 casos por cada 100.000 menores de 15 años, lo cual representa el 0,31 por ciento de los ingresos anuales hospitalarios en ese grupo (AU)

Dosimetric and radiation protection considerations based on some cases of patient skin injuries in interventional cardiology.

Recently, several cases of skin injuries have been detected in patients undergoing cardiac radiofrequency catheter ablation. These procedures were performed on a biplane X-ray system used in a large Spanish hospital for interventional cardiology procedures. Interventional procedures performed and radiation lesions produced on patients are described. The radiation lesions were mainly erythematous lesions and chronic radiodermatitis. Results of the dosimetric evaluations and an analysis of the operational aspects of radiological protection are discussed. Poor image quality could have influenced the length of the procedures. Dose rate at the image intensifier entrance was within usual reported values in literature. However, the focus-to-skin distance for the horizontal X-ray beam was too short, resulting in a high skin dose rate. Additionally, X-ray beams are of fixed orientation, and accumulated skin dose in the patient's right side has been estimated as 11-15 Gy per procedure. In conclusion, practical radiation protection considerations to avoid further incidents of this sort are proposed, concerning the use of X-ray systems specially designed for interventional radiology, the improvement of cardiologists' training in radiation protection and routine patient dose measurements for complex interventional procedures.

Metabolic effects of the delay in obliteration of the umbilical cord in the newborn rat.

The effect of delay in obliteration of the umbilical cord on the time-courses of liver glycogen, blood glucose and lactate concentrations and blood PO2, PCO2 and pH during the first 6 h of extrauterine life were studied. Obliteration of the umbilical cord 2 h after delivery resulted in an increase in liver glycogenolysis without significantly affecting the other parameters studied. A 6-hour delay in obliteration of the umbilical cord increased lactiacidemia and decreased blood PO2 and pH without significantly affecting the other parameters studied. A supply of pure oxygen to the newborns decreased lactiacidemia and increased PO2, although the differences between obliterated and nonobliterated newborns remained. These results suggest that hypoxia due to the persistence of placental circulation results in an increase in lactiacidemia as a consequence of a decrease in lactate utilization.

[Primary vesicoureteral reflux. II. Renal growth in kidneys with pyelonephritis]. / Reflujo vesicoureteral primario. II: Crecimiento renal en riñones con pielonefritis.

We have studied kidney growth and function in 38 patients with either unilateral (23) or bilateral (15) vesicoureteral reflux (VUR) and reflux nephropathy (RN). Average follow-up was 38 (range 12-84) months. Surgery was performed in 93.3% of units. Renal length measurement alone was not satisfactory for detection of focal scarring, whereas cortico-renal index was much more discriminant. Growth of kidneys with bilateral RN was impaired, but there were no correlations with either VUR grade not with urinary infection relapses after VUR cure. Growth was also impaired in unilaterally scarred kidneys and renal length measurement revealed itself as very unsatisfactory in them. Contralateral unscarred kidneys underwent hypertrophy in some cases and growth patterns suggested that hypertrophy will become more evident as follow-up goes on. Neither glomerular filtration rate nor fractionated Na excretion were useful to detect renal lesions, whereas concentration capacity revealed renal damage in bilateral cases. There was hypertension in only one child, but peripheral blood renin was elevated in 15.62% of patients.

[Primary vesicoureteral reflux. I: Renal growth in kidneys without pyelonephritis]. / Reflujo vesicoureteral primario. I: Crecimiento renal en riñones sin pielonefritis.

We have studied renal growth in 133 children with 195 refluxing ureters (VUR). Average follow-up was 38 (range 12-84) months. Low grade VUR (I-III) were more frequent and left-sided ones predominated among unilateral cases. There was a clear correlation between VUR grade and the presence of reflux nephropathy (RN). Seventy percent of low-grade VUR cured under long-term urine disinfection, whereas surgery was successful in 97.5% of high-grade, often scarred, units. Recurrent urinary infections after cure of VUR were equally frequent in both groups. The growth of the 140 unscarred refluxing kidneys was evaluated by means of renal length, corticorenal index and growth speed measurements. All values remained within ranges considered statistically undistinguishable from those of normal kidneys. Our findings confirm that, in our conditions of treatment, VUR without RN does not impair renal growth for the period of time studied.

[Acquired methemoglobinaemia (author's transl)]. / Metahemoglobinemia adquirida.

Authors report five cases of toxic methemoglobinaemia. Four of them were observed in newborns and the remaining one in a toddler. Acute gastroenteritis, carrot soup and spinachs were recognized as etiologic factors. Up-dated information about this clinical entity, its gasometric diagnosis, hemoglobin spectrophotometry and treatment with methylene blue is briefly recalled.