Association between CYP2C19 extensive metabolizer phenotype and childhood anti-reflux surgery following failed proton pump inhibitor medication treatment.

When pediatric gastroesophageal reflux disease (GERD) that is refractory to proton pump inhibitor (PPI) medication treatment is identified in clinical practice and anti-reflux surgery (ARS) is being considered, genetic factors related to PPI metabolism by the CYP2C19 enzyme are currently not part of the clinical decision-making process. Our objective was to test the hypothesis that the distribution of the extensive metabolizer (EM) phenotypes among children undergoing ARS after failing PPI therapy would differ compared to controls (children with no history of ARS). We conducted a case-control study between children across the Nemours Health System from 2000 to 2014 who received ARS after failing PPI therapy and a control group comprised of healthy children. Our results demonstrated 2.9% of ARSs vs 20.8% of controls were poor metabolizers (PMs), 55.9% of ARSs vs 49.0% of controls were normal metabolizers (NMs), and 41.2% of ARSs vs 30.2% of controls were EMs; p = 0.035. Next, we performed a multiple-regression model to account for race as a potential confounding variable and the EM group was significantly associated with ARS compared to controls (OR 9.78, CI 1.25-76.55, p < 0.03). CONCLUSION: Among children with medically refractory GERD despite PPI therapy, carriage of CYP2C19*17 allele corresponding to the EM phenotype was associated with ARS. Prospective comparative personalized medicine effectiveness studies are needed to determine if CYP2C19 genotype-guided dosing improves response to PPI therapy without a corresponding increase in adverse effects in children. What is known: • Anti-reflux surgery (ARS) is one of the most common surgical procedures performed in children for the indication of refractory gastroesophageal reflux disease (GERD). What is new: • Individualizing PPI medication dosing based on CYP2C19 diplotype may avoid GERD treatment failures and reduce the need for anti-reflux surgery (ARS).

Ca2+ responses in enteric glia are mediated by connexin-43 hemichannels and modulate colonic transit in mice.

BACKGROUND & AIMS: In the enteric nervous system, neurotransmitters initiate changes in calcium (Ca(2+) responses) in glia, but it is not clear how this process affects intestinal function. We investigated whether Ca(2+)-mediated responses in enteric glia are required to maintain gastrointestinal function. METHODS: We used in situ Ca(2+) imaging to monitor glial Ca(2+) responses, which were manipulated with pharmacologic agents or via glia-specific disruption of the gene encoding connexin-43 (Cx43) (hGFAP::CreER(T2+/-)/Cx43(f/f) mice). Gastrointestinal function was assessed based on pellet output, total gut transit, colonic bead expulsion, and muscle tension recordings. Proteins were localized and quantified by immunohistochemistry, immunoblot, and reverse transcription polymerase chain reaction analyses. RESULTS: Ca(2+) responses in enteric glia of mice were mediated by Cx43 hemichannels. Cx43 immunoreactivity was confined to enteric glia within the myenteric plexus of the mouse colon; the Cx43 inhibitors carbenoxolone and 43Gap26 inhibited the ability of enteric glia to propagate Ca(2+) responses. In vivo attenuation of Ca(2+) responses in the enteric glial network slowed gut transit overall and delayed colonic transit--these changes are also observed during normal aging. Altered motility with increasing age was associated with reduced glial Ca(2+)-mediated responses and changes in glial expression of Cx43 messenger RNA and protein. CONCLUSIONS: Ca(2+)-mediated responses in enteric glia regulate gastrointestinal function in mice. Altered intercellular signaling between enteric glia and neurons might contribute to motility disorders.

Prevalencia de anticuerpos contra el virus de la hepatitis C en personal médico del Instituto Nacional de Pediatría / Prevalence of anti hepatitis C virus antibodies among medical staff at the Instituto Nacional de Pediatría

Se analiza la prevalencia de anticuerpos contra el virus de la hepatitis C en 289 médicos y paramédicos del Instituto Nacional de Pediatría, con edades entre los 18 y 55 años. El estudio se hizo en los meses de junio y julio de 1993, la prevalencia fue de 2.1 por ciento; no hubo diferencia significativa en cuanto al sexo

Absorción intestinal deficiente de lactosa (AIDL) en niños con diarrea aguda sin deshidratación / Lactose deficient intestinal apsortion in children with acute diarrhea without dehydration

Se estudiaron 55 niños con diarrea aguda sin deshidratación para determinar si presentaban o no absorción intestinal deficiente de lactosa (AIDL) por medio de la prueba de iones hidrógeno en aire espirado. La AIDL se encontró en 24/55 niños. Al contrastar la prueba de iones hidrógeno en aire espirado contra pH y azúcares reductores en heces para el diagnóstico de AIDL, no hubo diferencias estadísticamente significativas. Rotavirus fue el agente patógeno más frecuentemente involucrado (12/55 casos); sin embargo, sólo en dos se demostró AIDL. Se formaron dos grupos de acuerdo al resultado de la prueba. Grupo I, sin AIDL y Grupo II con AIDL. Al primero se le administró leche entera, leche modificada o ambas en proteínas con lactosa y el grupo II se dividió en tres subgrupos alimentados con fórmulas con lactosa, sin lactosa y soya sin lactosa. No hubo diferencias estadísticamente significativas en la frecuencia de niños por la prueba de iones hidrógeno, en tanto que en 5/24 niños ocurrió entre la 2a y 4a semana y en 2/24 en la semana 9 y 10. por lo tanto, el empleo de fórmulas sin lactosa, o sin soya ni lactosa en niños con diarrea aguda sin deshidratación no parece justificarse

Prevalencia de anticuerpos contra el virus de la hepatitis C en niños hemofílicos: resultados preliminares / Prevalence of hepatitis C virus antibodies in hemophylic children: preliminary results

Se investigó 111 niños hemofílicos que asistieron a los Servicios de Hematología y Gastroenterología del Inastituto de Pediatría. En todos se hicieron pruebas para anti HCV por el método de ELISA; HBs Ag; AVB anti core; TGO y TGP. Paralelamente se investigaron 180 niños sin antecedentes previo de transfusión y sin síntomas ni signos clínicos de hepatopatía, y se les tomó una muestra para anti HCV mediante la misma técnica. De 111 hemofílicos, 35 tuvieron anti HVC positivo; de los 180 controles sólo tres fueron positivos, Hubo una diferencia muy significativa entre ambos grupos: Ji cuadrada (gl=1) = 53.93 (p< 0.001). No hubo diferencias significativas en la elevación de las transaminasas en los pacientes hemofílicos en relación a la presencia del anti HCV. Se encontró asociación estadísticamente significativa entre la presencia de HBs Ag y la presencia de anti HVC en los niños hemofílicos (p< 0.01). Igualmente se encontró una asociación estadísticamente significativa entre el HVB anti core y la presencia de anti HVC en el mismo grupo (p< 0.001)