Paul Harris D

Identificación de mutaciones en el gen CFTR en pacientes chilenos con fibrosis quística

Background: Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the CFTR gene, that codes for a chloride channel located in the apical surface of epithelial cells. The main role of this protein is the regulation of chloride transport, and secondarily, of sodium and water to the extracellular space. More than 900 gene mutations have been described, and their relative frequency in different populations depends on their ethnic origin. Aim: To report the findings of Chilean patients with cystic fibrosis, in whom the presence of 20 common mutations was analyzed. Patients and methods: Fifty seven patients with established diagnosis or suspicion of CF were studied. The simultaneous identification of 20 mutations and the normal DF508 allele was done using polymerase chain reactions with a commercial assay. Results: Eight mutations were found. Fifty patients fulfilled diagnostic criteria proposed by the Consensus Panel of the CF Foundation and 66% of alleles were identified in this group. ∆F508 mutation was found in 45%. We did not identify mutations in any of the remaining 7 patients. Conclusions: Our results suggest that the majority of undetected mutations are associated with atypical phenotypes or that some patients in this series could have other diseases. We recommend to include mutation analysis in the evaluation of Chilean patients with CF. It is useful to establish prognosis and genetic counselling (Rev Med Chile 2001; 129: 841-7).

Correlación genotipo-fenotipo de un grupo de pacientes con fibrosis quística

Background: Cystic fibrosis (CF) is the most common lethal autosomic disease in Caucasians, with a global incidence of 1:3000 newborns. More than 900 mutations have been described, involving the Cystic Fibrosis Transmembrane Regulator (CFTR). The ∆F508 mutation is present in 60% of alleles studied worldwide. Aim: To report 25 patients with cystic fibrosis in whom a genetic study was done. Material and methods: Twenty five patients (14 men, aged between 18 months and 25 years) with a diagnosis of cystic fibrosis based on clinical features plus two abnormal sweat tests are reported. The genetic study considered the 20 most common mutations in cystic fibrosis and was done in genomic DNA of peripheral lymphocytes, by polymerase chain reaction. Results: A mutation was found in 75% of analyzed alleles. DF508 was present in 50% of cases (DF508/DF508 in 8 and DF508/other in 11). When DF508 was present, pancreatic insufficiency was always a feature and nutritional status was worse. Respiratory involvement was variable, both for homozygous and heterozygous cases. Other severe mutations such as W1282X and G542X were related to clinical manifestations similar to those found in DF508 mutation. Diagnosis was made before six months of age in 12 patients. The clinical presentation was meconium ileus and there was a family history of the disease in most cases. The majority of cases of early diagnosis presented severe mutations, but milder respiratory symptoms and lesser nutritional compromise at the time of assessment. Conclusions: Most patients studied had a severe cystic fibrosis mutation, which was associated with more severe respiratory, pancreatic and nutritional involvement. The early diagnosis of the disease, which would allow to improve the prognosis and the quality of life, must be emphasized (Rev Med Chile 2002; 130: 475-81)

Vacunas en desarrollo: Helicobacter pylori

La infeccion con Helicobacter pylori es la causa de patologias gastrointestinales como ulcera peptica y cancer gastrico. Una vacuna contra H. pylori es relevante debido a la alta prevalencia de la infeccion y a la morbi-mortalidad asociada a esta en nuestro pais. El uso masivo de terapias antimicrobianas actuales no es una estrategia factible, especialmente en paises en desarrollo, en parte debido al alto costo, los multiples efectos adversos, el riesgo de reinfeccion y la emergencia de resistencia a los antimicrobianos. Numerosos modelos animales han sido utilizados durante anos para determinar el curso de la infeccion por H. pylori y explorar la factibilidad de una vacuna, ya sea para erradicar o prevenir la infeccion. Dichos modelos, con la posible excepcion de los monos, no son suficientes para responder preguntas fundamentales debido a resultados contradictorios. Un modelo humano de infeccion por H. pylori debe ser desarrollado con el principal proposito de seleccionar vacunas optimas. El objetivo final es el desarrollo de estudios de campos de vacunas candidatas, pero el estado actual del conocimiento no proporciona una metodica adecuada para seleccionar tales vacunas candidatas promisorias. Dichos estudios pueden ser disenados para proporcionar informacion relevante sobre la inmunidad y patogenesis de la infeccion por H. pylori

La producción científica en Chile y Latinoamérica

?Es benefi cioso, para un pais cualquiera, destinar recursos al apoyo de su investigacion cientifi ca??Debiera Chile aumentar su inversion en ciencia y tecnologia?Con estas 2 simples preguntas se inicia el documento “Ciencia y Tecnologia en Chile. Para que?” (http://www.conicyt.cl/documen-tos/CyTConicytparaque.pdf) publicado el ano 2010 por la Comision Nacional de Investiga-cion Cientifi ca y Tecnologica, CONICYT. Como antecedente se cita la declaracion de la Agencia Estatal Norteamericana hace mas de 50 anos, que indicaba: “la investigacion ba-sica le entrega a la sociedad conocimientos in-valuables y, considerando un periodo de tiem-po, tambien retornos considerables a cambio de inversiones relativamente pequenas. De he-cho, los retornos son tan cuantiosos que resulta practicamente innecesario justifi car o evaluar la inversion realizada.”Hoy, 50 anos mas tarde, nadie podria dis-cutir que Investigacion y Desarrollo (I+D) (

Litiasis biliar en niños: un estudio clínico-morfológico

Background: The use of ultrasonography increased the frequency of diagnosis of cholelithiasis in childhood. Aim: To determine the clinical and laboratory features and follow up of children with biliary stones. Patients and methods: Twenty six children (13 male, aged 1 month to 14 years) were prospectively enrolled. Results: Nine children had a past medical history of factors potentially predisposing to stones. A clinical presentation with vomiting (50%), abdominal pain (46%) and jaundice (23%) was the most common indication for surgery. The diagnosis was based on abdominal ultrasound in all children. Cholecystectomy was performed in 15 children (laparoscopy in 13 and open surgery in 2). Children who underwent surgery were older than those who did not undergo surgery (p <0.001), but they did not have differences in liver function tests. Eight children had pigmented stones and seven had cholesterol stones. Conclusions: In our patients, neither family history nor laboratory tests were useful in the diagnosis as well as in the clinical decision of surgery, which was based on symptoms. The presence of cholesterol stones in a high proportion of these children may be a unique situation in Chile, considering the high prevalence of this disease in the adult population (Rev Med Chile 2003; 131: 37-45)

Regulación de la respuesta inmune frente a la infección por Helicobacter pylori

Frente a una infeccion por Helicobacter pylori (H. pylori), el huesped desarrolla una respuesta inmune que es inefectiva en eliminar la bacteria. El sistema inmune innato, juega un rol central procesando y presentando antigenos de H. pylori. La presencia de citoquinas reguladoras (IL-10 o IL-12) podrian modular una respuesta linfocitica (Th) tipo 1 estableciendo una gastritis cronica, o una respuesta Th2 con produccion de anticuerpos y la erradicacion de la bacteria. IFN-g (respuesta Th1) podria mediar la induccion y la expresion de proteinas que pertenecen al complejo de histocompatibilidad tipo II (HLA-II) en celulas epiteliales, aumentando la adherencia de H. pylori al epitelio gastrico e induciendo apoptosis. IL-4 (respuesta Th2) podria aumentar la expresion del HLA-II, la produccion de IgG e IgE, el crecimiento de celulas T. Finalmente estudios recientes se han focalizado en la induccion de apoptosis celular como un mecanismo de proliferacion celular balanceada y como metodo de defensa del huesped frente a la infeccion por H. pylori

Evaluación prospectiva de la seguridad y tolerancia de los procedimientos colonoscópicos en pacientes pediátricos

Prospective study of 123 children referred for colonoscopy. Demographic data,type of colon preparation, sedation, type of endoscope and endoscopic results were obtained.The following day, a phone interview was carried out inquiring about duration, quality andadverse effects of the sedation and procedure.

Dolor abdominal, dispepsia y gastritis en pediatría: Rol del Helicobacter pylori

Helicobacter pylori (H. pylori) is the most common bacterial pathogen of the gastrointestinal tract in humans and also the most common cause of chronic gastritis and is aetiologically associated with duodenal and gastric ulcer, gastric adenocarcinoma and MALT lymphoma. The explosive accumulation of published reports makes it necessary to review the concepts of gastritis, recurrent abdominal pain and dyspepsia in children. Therefore the aim of this study was to update the concepts and to clarify their relationship with H. pylori and to discuss their validity in order to promote good clinical practice. Causative associations between H. pylori infection and other conditions are tenuous and speculative, these conditions include recurrent abdominal pain and non-ulcer dyspepsia. H. pylori is firmly established as a human pathogen because it fulfills each of Koch´s postulates as an infective agent causing chronic-active gastritis. Indeed H. pylori plays a critical and necessary role in the pathogenesis of chronic -active gastritis in adults. Whether H. pylori is a cause of peptic ulcer disease is less well established in children, nevertheless, the evidence for its causation is compelling. There is a strong epidemiological association between H. pylori and peptic ulceration in the absence of drug ingestion in adults. Although many people are infected, only a samll proportion will have clinical manifestations of disease. Approximately 10% of those infected will develop peptic ulcer disease during their lifetime. Infected persons have a 2-6 fold increased risk of developing cancer or MALT lymphoma compared to their uninfected counterparts.

Pancreatitis aguda grave y pseudoquiste pancreático por uso de drogas en niños: Presentación de tres casos clínicos y revisión de la literatura

Acute severe pancreatitis associated with drugs is an uncommon disorder in children but its incidence is increasing with more extensive use of certain drugs. We present three children with severe drug induced pancreatitis caused by valproic acid and L-asparaginase who developed pancreatic pseudocysts. The children required medical supportive therapy in the Intensive Case Unit and one needed surgical intervention for the pseudocyst. National and international reports were reviewed. The aetiology, clinical presentation, diagnostic methods and current management of acute severe pancreatitis and pseudocysts in children are discussed.

Un análisis retrospectivo de cavernomatosis de la vena porta en Chile: II. Hemorragia, tratamiento y pronóstico

Objetivo: El tratamiento de la hipertension portal de origen prehepatico en ninos es motivo de controversia. El objetivo de este estudio retrospectivo fue analizar la evolucion, tratamiento y morbimortalidad de 34 ninos con cavermomatosis de la vena porta. Pacientes y metodo: Se analizo la evolucion antropometrica y hematologica, las caracteristicas del sangramiento digestivo, el tratamiento medico, endoscopico y quirurgico, y la morbimortalidad. Resultados: El 74% de los ninos presento uno o mas episodios de sangramiento. El 56% de los ninos recibio propanolol como profilaxis y el 38% fue sometido a escleroterapia de varices esofagicas. Solo seis ninos requirieron de cirugia derivativa. La mortalidad fue del 5,6% y el seguimiento fue de 3,6 anos por nino. Conclusion: Aun cuando la hemorragia digestiva alta por ruptura de las varices esofagicas fue la complicacion mas frecuente de la cavernomatosis de la porta en esta serie, el exito del tratamiento medico y endoscopico en evitar un nuevo episodio de sangramiento sugieren que a futuro un numero menor de pacientes requerira de cirugia derivativa portosistemica