[Optimising azathioprine treatment: determination of thiopurine methyltransferase activity and thiopurine metabolites]. / Optimización del tratamiento con azatioprina: determinación de la actividad de tiopurina metiltransferasa y las concentraciones de metabolitos tiopurínicos.

INTRODUCTION: Individualised doses of azathioprine (AZA) may be prescribed by monitoring the levels of the enzyme thiopurine methyltransferase (TPMT). The measurements of thiopurine metabolites of AZA, 6-thioguanine (6-TGN) and 6-methylmercaptopurine (6-MMP), have also been reported as new markers of AZA activity. OBJECTIVES: To describe TPMT phenotype in our population and to establish a relationship between thiopurine metabolites,and therapeutic activity and adverse effects. MATERIAL AND METHODS: Data on TPMT were retrospectively collected from 107 patients, and 6-TGN and 6-MMP levels in 18 patients currently on treatment with AZA (Crohn's disease 5, ulcerative colitis 5, autoimmune hepatitis 5). RESULTS: Mean value of TPMT was 20.19U/ml. None of the patients had a TPMT activity<5U/ml. Of the 18 patients on treatment, 13 showed sub-therapeutic levels of 6-TGN (<235pmol/8x10(8) red blood cells). Clinical remission was maintained in 45% of patients. Mean levels of 6-TGN in patients with clinical remission were 259pmol/8x10(8) red blood cells versus 209pmol/8x10(8) red blood cells in non-responders (p=0.37). There was an inverse relationship (r=-0.28) between TPMT and 6-TGN levels. Toxic effects occurred in 6 of 18 patients, with leukopenia in 5 and hyperamylasemia in 1. CONCLUSIONS: Determination of TPMT and monitoring of thiopurine metabolites allows AZA treatment to be optimised, although further studies are necessary to establish therapeutic effectiveness and toxicity ranges.

Optimización del tratamiento con azatioprina: determinación de la actividad de tiopurina metiltransferasa y las concentraciones de metabolitos tiopurínicos / Optimising azathioprine treatment: determination of thiopurine methyltransferase activity and thiopurine metabolites

Introducción: la determinación de la enzima tiopurina metiltransferasa (TPMT) nos permite pautar la dosis inicial individualizada de azatioprina (AZA). Las determinaciones de los metabolitos tiopurínicos de la AZA, la 6-tioguanina (6-TGN) y la 6-metilmercaptopurina (6-MMP) se han descrito como nuevos marcadores de la actividad del fármaco. Objetivos: describir el fenotipo de TPMT en nuestra población y relacionar los valores de los metabolitos tiopurínicos con la actividad terapéutica y los efectos adversos. Material y métodos: se recogieron retrospectivamente los valores de TPMT de 107 pacientes y de 6-TGN y 6-MMP de 18 pacientes en tratamiento con AZA (8 con enfermedad de Crohn, 5 con colitis ulcerosa y 5 con hepatitis autoinmune). Resultados: la media de determinación de TPMT fue 20,19U/ml. Ninguno presentó actividad de TPMT menor que 5U/ml. De los 18 pacientes, 13 mostraron concentraciones subterapéuticas de 6-TGN (<235pmol/8×108 hematíes). El 45% de los pacientes mantuvieron remisión clínica. La media de concentración de 6-TGN en los pacientes en remisión fue 259pmol/8×108 hematíes frente a 209pmol/8×108 hematíes en los no respondedores (p=0,37). Hay una relación inversa (r=−0,28) entre los valores de TPMT y los de 6-TGN. En 6/18 pacientes encontramos toxicidad: 5 con leucocitopenia y uno con hiperamilasemia. Conclusiones: la determinación de TPMT y la monitorización de los metabolitos tiopurínicos nos permite optimizar tratamiento con AZA, aunque son necesarios nuevos estudios que permitan el correcto conocimiento de los intervalos de efectividad terapéutica y toxicidad (AU)

Introduction: Individualised doses of azathioprine (AZA) may be prescribed by monitoring the levels of the enzyme thiopurine methyltransferase (TPMT). The measurements of thiopurine metabolites of AZA, 6-thioguanine (6-TGN) and 6-methylmercaptopurine (6-MMP), have also been reported as new markers of AZA activity. Objectives: To describe TPMT phenotype in our population and to establish a relationship between thiopurine metabolites,and therapeutic activity and adverse effects. Material and methods: Data on TPMT were retrospectively collected from 107 patients, and 6-TGN and 6-MMP levels in 18 patients currently on treatment with AZA (Crohn’s disease 5, ulcerative colitis 5, autoimmune hepatitis 5). Results: Mean value of TPMT was 20.19U/ml. None of the patients had a TPMT activity<5U/ml. Of the 18 patients on treatment, 13 showed sub-therapeutic levels of 6-TGN (<235pmol/8×108 red blood cells). Clinical remission was maintained in 45% of patients. Mean levels of 6-TGN in patients with clinical remission were 259pmol/8×108 red blood cells versus 209pmol/8×108 red blood cells in non-responders (p=0.37). There was an inverse relationship (r=−0.28) between TPMT and 6-TGN levels. Toxic effects occurred in 6 of 18 patients, with leukopenia in 5 and hyperamylasemia in 1. Conclusions: Determination of TPMT and monitoring of thiopurine metabolites allows AZA treatment to be optimised, although further studies are necessary to establish therapeutic effectiveness and toxicity ranges (AU)

[Infliximab therapy for inflammatory bowel disease: seven years on]. / Tratamiento de la enfermedad inflamatoria intestinal con infliximab: 7 años de experiencia.

INTRODUCTION: The aim of this study was to describe the clinical experience of our center of the use of infliximab in pediatric patients with inflammatory bowel disease. MATERIAL AND METHODS: We retrospectively reviewed all infliximab infusions administered in the Pediatric Gastroenterology Unit from October of 1999 to October of 2006. Fourteen patients (nine with Crohn's disease, three with ulcerative colitis, and two with indeterminate colitis) with a mean age of 9.6 years at diagnosis were treated with infliximab. Seventy-seven infusions were administered. RESULTS: Efficacy was analyzed according to inflammatory bowel disease. Crohn's disease: in severe cases (PCDAI > 30), clinical remission (PCDAI < 10) was obtained in 80 % of the patients at week 10, decreasing to 60 % at week 54. Corticosteroid therapy could be reduced in 89 % of the patients and was discontinued in 55.5 %. Ulcerative colitis: clinical remission (modified Truelove-Witts index < 10) was initially obtained in 100 % of the patients but only 33 % were still in clinical remission at the end of the study. In the two corticosteroid-dependent patients, corticosteroid therapy could be reduced and even discontinued in one (50 %). Indeterminate colitis: neither of the two patients achieved clinical remission. The most frequent adverse effects observed were acute infusional reactions (42.8 % of the patients and 10.3 % of infusions), one of which was severe, and infections (28.6 % of patients), one of which (ileal abscess) required surgery. CONCLUSIONS: The efficacy of infliximab seems to differ considerably in the distinct types of inflammatory bowel disease and is practically null in indeterminate colitis. Randomized controlled studies in children are required to assess the exact efficacy of infliximab in our patients.

Tratamiento de la enfermedad inflamatoria intestinal con infliximab: 7 años de experiencia / Infliximab therapy for inflammatory bowel disease: seven years on

Introducción El objetivo de este artículo es describir la experiencia clínica de nuestro centro con infliximab en pacientes con enfermedad inflamatoria intestinal. Material y métodos Revisión retrospectiva de todas las infusiones de infliximab administradas en la Unidad de Gastroenterología Pediátrica desde su primera infusión en octubre de 1999 hasta octubre de 2006. Un total de 14 pacientes (9 de ellos con enfermedad de Crohn, 3 con colitis ulcerosa y 2 con colitis indeterminada), con una media de 9,6 años al diagnóstico, fueron sometidos a tratamiento con infliximab. Se administró un total de 77 infusiones. Resultados La eficacia se desglosó por tipo de enfermedad inflamatoria intestinal. Crohn: en las formas graves (índice de actividad de la enfermedad de Crohn pediátrica [PCDAI] > 30) se obtuvo una remisión clínica (PCDAI < 10) a la semana 10 del 80 %, que descendió al 60 % en la semana 54. Se pudo reducir la dosis de corticoides en el 89 % de los pacientes y suspenderla en el 55,5 %. Colitis ulcerosa: se obtuvo una remisión clínica (índice de Truelove-Witts modificado < 10) inicial del 100 %, pero tan sólo se mantuvo en el 33 % de los pacientes. Los dos pacientes con corticodependencia pudieron reducir la dosis corticoidea e incluso uno de ellos llegó a suspenderla (50 %). Colitis indeterminada: ninguno de los dos pacientes logró entrar en remisión clínica. Los efectos adversos más frecuentes observados fueron las reacciones infusionales agudas (42,8 % de los pacientes y 10,3 % de las infusiones), una de ellas grave, y las infecciones (28,6 % de los pacientes), una de las cuales (absceso ileal) requirió cirugía. Conclusiones La efectividad de infliximab parece diferir mucho por tipo de enfermedad inflamatoria intestinal, y es prácticamente nula en formas indeterminadas. Se requieren estudios controlados y aleatorizados en población pediátrica para definir de manera exacta la tasa de eficacia de infliximab en nuestros pacientes

Introduction The aim of this study was to describe the clinical experience of our center of the use of infliximab in pediatric patients with inflammatory bowel disease. Material and methods We retrospectively reviewed all infliximab infusions administered in the Pediatric Gastroenterology Unit from October of 1999 to October of 2006. Fourteen patients (nine with Crohn's disease, three with ulcerative colitis, and two with indeterminate colitis) with a mean age of 9.6 years at diagnosis were treated with infliximab. Seventy-seven infusions were administered. Results Efficacy was analyzed according to inflammatory bowel disease. Crohn's disease: in severe cases (PCDAI > 30), clinical remission (PCDAI < 10) was obtained in 80 % of the patients at week 10, decreasing to 60 % at week 54. Corticosteroid therapy could be reduced in 89 % of the patients and was discontinued in 55.5 %. Ulcerative colitis: clinical remission (modified Truelove-Witts index < 10) was initially obtained in 100 % of the patients but only 33 % were still in clinical remission at the end of the study. In the two corticosteroid-dependent patients, corticosteroid therapy could be reduced and even discontinued in one (50 %). Indeterminate colitis: neither of the two patients achieved clinical remission. The most frequent adverse effects observed were acute infusional reactions (42.8 % of the patients and 10.3 % of infusions), one of which was severe, and infections (28.6 % of patients), one of which (ileal abscess) required surgery. Conclusions The efficacy of infliximab seems to differ considerably in the distinct types of inflammatory bowel disease and is practically null in indeterminate colitis. Randomized controlled studies in children are required to assess the exact efficacy of infliximab in our patients

Probióticos. Concepto y mecanismos de acción / No disponible

Los probióticos pueden definirse como microorganismos vivos que, ingeridos en cantidad adecuada, ejercen efectos beneficiosos en la salud, más allá de los inherentes a la nutrición básica. Las bacterias más comunes relacionadas con la actividad probiótica son: Lactobacillus acidophilus, L. casei, L. reuteri, L. plantarum, L. casei GG; Bifidobacterium brevis, B. longum, B. infantis, B. animalis; Streptococcus salivaris subespecie thermophilus, y algunas variedades de levaduras como Saccharomyces boulardii. Los mecanismos de acción implicados incluyen inducción a pH inferior a 4, inhibición del crecimiento de bacterias patógenas, producción de ácido láctico, disminución de la permeabilidad intestinal, aumento en la actividad de la lactasa, efecto competitivo en otras bacterias patógenas, reducción en el tiempo de eliminación de rotavirus, incremento en la producción de los linfocitos T helper, y aumento de la inmunoglobulina A secretora. Es importante señalar que no todos los Lactobacillus y Bibidobacterium son iguales presentando especialidad según cepa y dosis, por lo que las propiedades pueden ser diferentes. Aunque se precisa investigación adicional sobre determinados aspectos en la aplicación de los probióticos, puede aconsejarse su empleo en la nutrición del lactante y del niño (AU)

No disponible

[D-lactic acidosis in an 11-year-old patient with short bowel syndrome]. / Acidosis D-láctica en un paciente de 11 años con síndrome de intestino corto.

The short bowel syndrome is the result of a congenital or acquired loss of a large part of the small intestine. The most frequent causes of surgical resection of the intestine in infants are arterial or venous thrombosis, intestinal volvulus, necrotizing enterocolitis, and Crohn's disease. Symptoms include nutrient and electrolyte malabsorption, steatorrhea and diarrhea, which can result in failure to thrive. The consequences of extensive small bowel resections consist of nutritional deficiencies, gastric acid hypersecretion, nephrolithiasis, cholelithiasis and lactic acidosis. Of these, D-lactic acidosis is an infrequent but important complication because of the symptoms that it can produce. D-lactic acid in the human organism is generated by intestinal bacteria, D-lactate ingestion, or endogenous production in the methyl glycoxylase pathway. Neurological symptoms such as somnolence, ataxia or altered behavior in a patient with short bowel syndrome should make us think of D-lactic acidosis caused by bacterial overgrowth. We present the case of an 11-year-old boy with short bowel syndrome secondary to multiple resections during the postnatal period who was admitted to hospital for episodes of confusion and altered behavior. The diagnosis was lactic acidosis. Outcome was favorable due to prompt instauration of treatment.

Acidosis D-láctica en un paciente de 11 años con síndrome de intestino corto / D-lactic acidosis in an 11-year-old patient with short bowel syndrome

El síndrome de intestino corto es el resultado de la pérdida congénita (atresia intestinal) o adquirida, de gran parte de intestino delgado. Las causas más frecuentes de resección intestinal en la infancia son patologías como la trombosis arterial o venosa, los vólvulos intestinales, la enterocolitis necrosante o la enfermedad de Crohn. Su clínica consiste en malabsorción de nutrientes y electrólitos, junto con esteatorrea y diarrea que dificultan el desarrollo ponderoestatural. Las consecuencias de las resecciones extensas del intestino delgado son deficiencias nutricionales, hipersecreción de ácido gástrico, nefrolitiasis, colelitiasis y acidosis láctica. Dentro de éstas, la acidosis láctica representa una complicación poco frecuente pero importante por la sintomatología que puede presentar. El ácido D-láctico en el organismo es generado por bacterias del tracto intestinal, por ingesta de D-lactato o por producción endógena en la vía de la metil glucosilasa. La sintomatología neurológica (somnolencia, ataxia, alteraciones de la conducta) en un paciente afectado de intestino corto debe hacer pensar en un posible cuadro de acidosis D-láctica secundaria a sobrecrecimiento bacteriano intestinal. Se presenta el caso de un paciente de 11 años de edad con síndrome de intestino corto por múltiples resecciones durante el período posnatal que ingresa por episodios de disminución del estado de conciencia y alteración de la conducta, llegando al diagnóstico de acidosis láctica. La evolución fue favorable debido a la rápida instauración del tratamiento

The short bowel syndrome is the result of a congenital or acquired loss of a large part of the small intestine. The most frequent causes of surgical resection of the intestine in infants are arterial or venous thrombosis, intestinal volvulus, necrotizing enterocolitis, and Crohn's disease. Symptoms include nutrient and electrolyte malabsorption, steatorrhea and diarrhea, which can result in failure to thrive. The consequences of extensive small bowel resections consist of nutritional deficiencies, gastric acid hypersecretion, nephrolithiasis, cholelithiasis and lactic acidosis. Of these, D-lactic acidosis is an infrequent but important complication because of the symptoms that it can produce. D-lactic acid in the human organism is generated by intestinal bacteria, D-lactate ingestion, or endogenous production in the methyl glycoxylase pathway. Neurological symptoms such as somnolence, ataxia or altered behavior in a patient with short bowel syndrome should make us think of D-lactic acidosis caused by bacterial overgrowth. We present the case of an 11-year-old boy with short bowel syndrome secondary to multiple resections during the postnatal period who was admitted to hospital for episodes of confusion and altered behavior. The diagnosis was lactic acidosis. Outcome was favorable due to prompt instauration of treatment

Empleo de leche de cabra en pacientes con alergia a las proteínas de la leche de vaca / Use of goat's milk in patients with cow's milk allergy

Antecedentes: Diversos estudios epidemiológicos sitúan la incidencia de alergia a las proteínas de la leche de vaca (APLV) en el 3-5 por ciento de los lactantes en los países industrializados. Las fórmulas a base de aislado de proteína de soja o de hidrolizados extensos de proteínas-vacunas garantizan un adecuado desarrollo nutricional de los lactantes, aunque pueden ser inadecuados para pacientes de más edad. Objetivo: Estudiar la posibilidad del empleo de la leche de cabra en estos pacientes, investigando in vivo e in vitro la posible alergenicidad cruzada entre ambas proteínas. Métodos: Doce niños afectados de APLV se incluyeron en el estudio de tolerancia a las proteínas de la leche de cabra: RAST IgE específico, prueba por punción (prick test) y prueba de tolerancia. Resultados: El 25 por ciento de los casos presentaron una buena tolerancia oral inmediata y tardía, y tests inmunológicos de reacción adversa negativos. Conclusiones: No se puede aconsejar a los pacientes con APLV el aporte de leche de cabra sin asegurarse previamente de su posible tolerancia bajo control de especialista. Para el 25 por ciento que la toleran, la leche de cabra puede ser un excelente sustituto en los niños de más de 2 años de vida (AU)

[Use of goat's milk in patients with cow's milk allergy]. / Empleo de leche de cabra en pacientes con alergia a las proteínas de la leche de vaca.

BACKGROUND: Several epidemiological studies estimate that cow's milk allergy affects approximately 3-5 % of infants in industrialized countries. Infant formulae based on soy protein or hydrolysates free of cow's milk protein guarantee adequate nutritional development, although they may be inadequate for older patients. OBJECTIVE: To evaluate the possibility of using goat's milk in these patients by investigating possible cross-reactivity between both proteins in vivo and in vitro. METHODS: Twelve patients with cow's milk allergy were tested for tolerance to goat's milk protein through radioallergosorbent assay (RAST), specific IgE, skin prick and challenge tests. RESULTS: Only 25 % of the patients showed adequate immediate and late oral tolerance and had negative results of immunological tests for adverse reactions. CONCLUSIONS: The use of goat's milk cannot be recommended to patients with cow's milk allergy without investigation of possible tolerance by a specialist. For the 25 % of patients that tolerate goat's protein, goat's milk can be a excellent substitute in children older than 2 years old.

The influence of dietary palmitic acid triacylglyceride position on the fatty acid, calcium and magnesium contents of at term newborn faeces.

The distribution of long-chain saturated fatty acids in triglycerides is different in infant formulas to that in human milk. In human milk, palmitic acid is predominantly esterified in the sn-2 position (beta-position) of the triglycerides, whereas in infant formulas, it is esterified mainly in the sn-1,3 positions (alpha,alpha'-positions). The specific distribution of the fatty acids in the triglyceride plays a key role in lipid digestion and absorption. We studied fatty-acid, calcium and magnesium composition in the faeces of three groups of at term newborn infants fed different diets: Group A (n=12) was fed from birth to 2 months with human milk (66% palmitic acid in beta-position), Group B (n=12) was fed with formula alpha (19% palmitic acid esterified in beta-position) for 2 months, and Group C (n=12) was fed with formula alpha during the first month and with formula beta (44.5% palmitic acid in beta-position) during the second month. Samples were taken at the end of the first month (t0) and at the end of the second month (t1). Groups A and C presented significantly lower contents of palmitic acid in faeces at t1 than at t0, whereas in Group B, amounts remained similar. Faecal calcium in Groups A and C decreased in the second month (t1), although the fall was no statistically significant. In Group B, calcium amounts showed no change. We found that infant formula beta when compared with infant formula alpha reduced significantly the contents of total fatty acids and palmitic acid in faeces. We conclude that palmitic acid in beta-position is, therefore, beneficial for term infants.

Revisión del papel de la fibra en nutrición infantil / Review over the role of fiber in infants and children nutrition

La fibra, es un componente importante de la alimentación humana y a pesar de ello es un concepto difícil de determinar, ya que se trata de un grupo de sustancias que sólo podemos unir por sus funciones en el intestino. El conocimiento de estas funciones ha ido mejorando en los últimos tiempos, aumentando progresivamente la importancia que le concedemos a la fibra para mantener la salud del ser humano y diferenciando los componentes de esta familia entre fibra soluble e insoluble. Uno de los problemas que plantea el estudio de la fibra de la dieta es unificar los criterios de análisis para evaluar el contenido de la misma en cada alimento. Esto se agrava debido a que el procesado de los alimentos altera en nivel de fibra e incluso enmascara su análisis.Sólo hace falta repasar los efectos de la fibra en diferentes puntos del tracto digestivo y en el metabolismo de glucosa y lípidos, para comprender su importancia en la alimentación normal y sus posibilidades terapéuticas. Pero es más difícil valorar si la ingesta real en nuestro medio, y sobre todo en niños, se adecua a las necesidades para cumplir con estas funciones. Por los datos existentes parece que el nivel de aporte es bajo y que los alimentos proveedores de la fibra están cambiando con la dieta actual. La idea, muy extendida, de que un bebé no toma fibra no es exactamente cierta y vale la pena estudiar su aporte el la lactancia materna y en la alimentación complementaria.Finalmente es necesario buscar una recomendación útil y correcta en nuestro medio para que sirva de guía en la alimentación infantil y en el intento de mejorar los hábitos (AU)

[The response of the hepatitis C and hepatitis G viruses to treatment with recombinant interferon alfa-2b]. / Respuesta del virus de la hepatitis C y del virus de la hepatitis G al tratamiento con interferon alfa-2b recombinante.

OBJECTIVE: The efficacy of recombinant alfa-2b interferon therapy in C-virus (HCV) and G-virus (HGV) in children with chronic hepatitis C was evaluated. PATIENTS AND METHODS: Fifteen patients, between 6 and 16 years of age and positive for HCV of which four were also infected with HGV, were treated with interferon (3 M three times a week for 6 months). The responders were treated for 12 months. HCV RNA, antibodies to HCV, HVC viral genome (expressed as 1000 copy equivalents of HCV genome = 1 keq), HGV RNA (RT/PCR, 5'NCR-NS5), and E2-HGV antibodies were determined before treatment and at 3 and 6 months in all patients and at 12-24 months in the responders. RESULTS: Four HCV patients (27%) with low viral load (mean 36 keg/ml) showed good results after interferon treatment and two of them (13%) with genotypes 1b and 3 according to Simmond's classification showed a maintained response. The four HGV children also showed the same good results and the RNA was negative without sero-conversion to anti-E2 after 12 months of interferon treatment. In the post-interferon treatment period, the HGV RNA appeared again in the serum in 3 of the 4 children. In the child with a maintained response, serum conversion to anti-E2 was not detected. CONCLUSIONS: 1) The current results, with only 13% of the patients reaching a sustained response, question the systematic treatment of all children affected with hepatitis C virus. Since the cost-benefit ratio is not yielding the expected results, such therapy may be reserved for patients with genotype other than 1b and a low level of viral genome. 2) HGV is sensitive to treatment with interferon, although the infection frequently appears again once the treatment is over.

[Relationship between primary lactose malabsorption and consumption of dairy products]. / Influencia de la hipolactasia primaria sobre el consumo de productos lácteos.

This study was designed to determine the influence of lactose malabsorption on the consumption of dairy products. We studied 157 children and 43 adults. The Breath-hydrogen test was used to define their level of lactose digestion. The prevalence of lactose maldigesters was 12%. We found a large relationship between the consumption of milk and milk products and age. Malabsorbers consumed more fermented dairy products (ripened cheese and yogurt) than did absorbers (p < 0.05). Subjects with normal lactose absorption consumed more milk, butter, cream cheese and global lactose than the maldigesters (p < 0.05). Lactose intolerance, familiar consumption and geographic origins had little influence on an individual's consumption habits.

[Neonatal cholestatic icterus simulating atresia of the bile ducts in a patient with alpha-1-antitrypsin deficiency]. / Ictericia colestásica neonatal simulando atresia de vías biliares en un paciente con déficit de alfa-1-antitripsina.

A 40 days old infant with cholestasis is described. The liver was enlarged at 3 cm below the costal margin. No bile ducts were seen at the liver scan (IDA Tc 99) neither bile was collected after cholecystokinine IV administration. Fibrosi, bile ducts proliferation, and cholestasis without intracellular PAS positive material were seen at liver biopsy. Serum alpha-1-antitrypsin level was 42 mg/100 ml. Follow-up was satisfactory after phenobarbital and cholestiramine treatment. Cholestasis decreased and two weeks later bile excretion was obtained after cholecystokinine administration. This stress the importance of alpha-1-antitrypsin determination in cholestasis in infancy.