Citrulina plasmática como marcador de pérdida de masa enterocitaria en la enfermedad celíaca en la infancia / Plasma citrulline as a marker of loss of enterocitary mass in coeliac disease in childhood

Introducción: La citrulina plasmática no está incorporada a las proteínas endógenas ni exógenas y constituye un teórico marcador de la atrofia vellositaria. El objetivo del estudio es relacionar los niveles plasmáticos de citrulina y arginina con la severidad de la afectación de la mucosa intestinal en pacientes celiacos. Material y métodos: Estudio transversal de cohortes en niños entre 16 meses y 14 años: 46 con enfermedad celíaca al diagnóstico; 9 celíacos siguiendo dieta sin gluten y 42 controles. Se determina concentración plasmática de aminoácidos, en mmol/L, y variables clínicas y analíticas asociadas. Resultados: No diferencias estadísticamente significativas en IMC, edad o función renal, con ligero incremento de esteatorrea en celíacos. Citrulina, arginina y glutamina plasmáticas significativamente más bajas en los casos (17,7 μmol/l, 38,7 μmol/l, 479,6 μmol/l respectivamente)que en controles (28,9 μmol/l, 56,2 μmol/l, 563,7μmol/l). Citrulina plasmática significativamente más baja en grados avanzados de atrofia (13,8 μmol/l vs 19,7μmol/l, p < 0,05), no así con el resto de aminoácidos. Discusión: La medida postabsortiva de citrulina plasmática constituye buen marcador de reducción de masa enterocitaria en celíacos con atrofia vellositaria; secundariamente disminución también de arginina. Grados bajos de alteración histológica de la biopsia intestinal son suficientes como para diferenciar su citrulina de los controles y además se puede afirmar que grados altos de lesión histológica tienen menor citrulina plasmática que grados bajos (AU)

Introduction: Plasma citrulline is not incorporated in endogenous or exogenous proteins so it is a theoretical marker of villous atrophy. Our aim was to correlate plasma citrulline levels with severity of villous atrophy inceliac patients. Methods: Observational case-control study longitudinal in children 16 month-old to 14 year-old: 48 with untreated celiac disease, 9 celiac children under gluten free diet and 35 non-celiac healthy children. Plasma amino acids concentration is determined, expressed inμmol/L, and so are other clinical and analytical data. Results: No statistically significative difference found in the referring to BMI, age or renal function. Small increase in fecal fat in celiac children. Citrulline, arginine and glutamine are significantly lower in cases (17.7μmol/l, 38.7 μmol/l, 479.6 μmol/l respectively) than in controls(28.9 μmol/l, 56.2 μmol/l, 563.7 μmol/l). Citrulline levels are significantly lower in the severe degrees of atrophy than in mild ones (13.8 μmol/l vs. 19.7 μmol/l, p <0.05), not happening so with rest of amino acids. Summary: Postabsortive mean of plasma citrulline is a good marker of reduction in enterocyte mass in celiac patients with villous atrophy; secondary reduction in plasma arginine too. Just a small histological alteration in intestinal biopsy is enough to differentiate citrulline incases and controls and besides it can be seen that high levels of atrophy present with lower plasma citrulline (AU)

Predicción de lesión histológica intestinal en pacientes pediátricos con enfermedad celíaca / Prediction of intestinal histological lesions in paediatric patients with coeliac disease

Introducción: Los marcadores séricos son de gran utilidad como indicadores de enfermedad celíaca (EC), si bien la biopsia intestinal sigue siendo el patrón oro para establecer el diagnóstico. La positividad de los anticuerpos antitransglutaminasa tisular humana de clase IgA (AATGt-IgA) y los anticuerpos antiendomisio IgA (AAE-IgA) se correlaciona con histología intestinal patológica. La atrofia vellositaria (Marsh 3) representa una característica fundamental para el diagnóstico de EC. El tipo correspondiente a Marsh 2 (hiperplasia críptica) es debatido como lesión propia de la EC. Objetivo: Comprobar el nivel de AATGt-IgA que corresponda a un valor predictivo positivo (VPP) de lesión histológica de 100% para el diagnóstico de EC. Material y métodos: Serie de 120 pacientes menores de 14 años sin déficit de IgA sometidos a biopsia intestinal con serología positiva tanto a AATGt-IgA como AAE-IgA. Para los AATGt- IgA según recomendación del fabricante se consideran valores positivos cifras ≥ 16 U/ml. Se establece el VPP de AATGt-IgA a diferentes puntos de corte. Resultados: La distribución de los hallazgos histológicos en relación con el punto de corte de AATGt-IgA pone de manifiesto el mayor número de lesiones patológicas a medida que aumenta los valores de AATGt-IgA. Con valores del punto de corte por encima de 7,5-10,6 se corresponde con Marsh 2 2,1% y Marsh 3 93,4%; por encima de 10,6 veces el punto de corte, todas las biopsias se catalogan como Marsh 3 (100%). El VPP considerando solo las lesiones Marsh 3 alcanza bajo valor (55%) con serología positiva a AATGt-IgA con valores comprendidos entre 16 y 67 U/ml (1 a 4,2 x punto de corte), y elevado valor (92%) para las concentraciones entre 68 y 118 U/ml (4,3 a 7,4 x punto de corte), y para los casos con 69-170 U/ml (7,5 a 10,6 x punto de corte) (93%). Por encima de 170 U/ml (> 10,6 x punto de corte) el VPP es 100%. Conclusiones: El uso de valores superiores al punto de corte recomendado lógicamente debe mejorar aún más la especificidad del test y su VPP. En el 31,6% de los pacientes con positividad para AATGt-IgA y AAE-IgA (38/120) hubiera sido posible diagnosticar la enfermedad sin biopsia intestinal al contar con VPP de 100%. Como existen diversos kits comerciales con distintos puntos de corte, no es posible la estandarización de los resultados, por lo que hay que ser muy cautos para establecer recomendaciones basadas en los valores de AATGt-IgA (AU)

Introduction: Serological markers are of great interest in coeliac disease (CD), although intestinal biopsy is still the gold standard for establishing the diagnosis. Tissue transglutaminase IgA antibodies (AATGt-IgA) and antiendomysial antibodies IgA (AAE-IgA) are closely correlated to intestinal damage observed in biopsies. Villous atrophy (Marsh 3) plays a major role in CD diagnosis. Marsh 2 stage (crypt hyperplasia) as a CD marker is still under debate. Objective: To ascertain an AATGt-IgA level that corresponds to a positive predictive value (PPV) of 100% for a histological CD diagnosis. Material and methods: A series of 120 patients younger than 14 years, non- IgA deficient, whounderwent an intestinal biopsy and were positive for both serological markers (AATGt-IgA andAAE-IgA). For AATGt-IgA, according to the manufacturer’s recommendations, a value greaterthan 16 IU/mL is considered as a positive value. The PPV of AATGt was determined for different cut-off points. Results: The histological findings distribution is directly correlated to the AATGt-IgA cut-off point. When the cut-off point is set above 7.5-10.6 times the commercial reference value, there is a 2.1% of Marsh 2 lessions and 93.4% of Marsh 3; above 10.6 times the reference value, all biopsies where Marsh 3 (100%). The PPV that considers Marsh 3 is (93.4%). The PPV, for considering Marsh 3 is low (55%) when AATGt-IgA serology is positive with levels between 16and 67 IU/ml (1-4.2 times the cut-off point) and a higher value (92%) for concentrations between68 and 118 IU/ml (4.3-7.4 times) and for cases with 69-170 IU/ml (7.5-10.6 times); above 170IU/ml (>10.6 times) PPV is 100% (AU)

[Prediction of intestinal histological lesions in paediatric patients with coeliac disease]. / Predicción de lesión histológica intestinal en pacientes pediátricos con enfermedad celíaca.

INTRODUCTION: Serological markers are of great interest in coeliac disease (CD), although intestinal biopsy is still the gold standard for establishing the diagnosis. Tissue transglutaminase IgA antibodies (AATGt-IgA) and antiendomysial antibodies IgA (AAE-IgA) are closely correlated to intestinal damage observed in biopsies. Villous atrophy (Marsh 3) plays a major role in CD diagnosis. Marsh 2 stage (crypt hyperplasia) as a CD marker is still under debate. OBJECTIVE: To ascertain an AATGt-IgA level that corresponds to a positive predictive value (PPV) of 100% for a histological CD diagnosis. MATERIAL AND METHODS: A series of 120 patients younger than 14 years, non- IgA deficient, who underwent an intestinal biopsy and were positive for both serological markers (AATGt-IgA and AAE-IgA). For AATGt-IgA, according to the manufacturer's recommendations, a value greater than 16 IU/mL is considered as a positive value. The PPV of AATGt was determined for different cut-off points. RESULTS: The histological findings distribution is directly correlated to the AATGt-IgA cut-off point. When the cut-off point is set above 7.5-10.6 times the commercial reference value, there is a 2.1% of Marsh 2 lessions and 93.4% of Marsh 3; above 10.6 times the reference value, all biopsies where Marsh 3 (100%). The PPV that considers Marsh 3 is (93.4%). The PPV, for considering Marsh 3 is low (55%) when AATGt-IgA serology is positive with levels between 16 and 67 IU/ml (1-4.2 times the cut-off point) and a higher value (92%) for concentrations between 68 and 118 IU/ml (4.3-7.4 times) and for cases with 69-170 IU/ml (7.5-10.6 times); above 170 IU/ml (>10.6 times) PPV is 100%. CONCLUSION: The use of values higher than the recommended cut-off point must logically improve specificity and PPV. In 31.6% patients positive for AATGt-IgA and AAE-IgA (38/120) it would have been possible to diagnose the disease without intestinal biopsy as of the PPV was 100%. It is not possible to standardise results as there are different commercial kits with variable cut-off points, so we must be cautious when setting recommendations based on AATGt-IgA.

[Plasma citrulline as a marker of loss of enterocitary mass in coeliac disease in childhood]. / Citrulina plasmática como marcador de pérdida de masa enterocitaria en la enfermedad celíaca en la infancia.

INTRODUCTION: Plasma citrulline is not incorporated in endogenous or exogenous proteins so it is a theoretical marker of villous atrophy. Our aim was to correlate plasma citrulline levels with severity of villous atrophy in celiac patients. METHODS: Observational case-control study longitudinal in children 16 month-old to 14 year-old: 48 with untreated celiac disease, 9 celiac children under gluten free diet and 35 non-celiac healthy children. Plasma amino acids concentration is determined, expressed in µmol/L, and so are other clinical and analytical data. RESULTS: No statistically significative difference found in the referring to BMI, age or renal function. Small increase in fecal fat in celiac children. Citrulline, arginine and glutamine are significantly lower in cases (17.7 µmol/l, 38.7 µmol/l, 479.6 µmol/l respectively) than in controls (28.9 µmol/l, 56.2 µmol/l, 563.7 µmol/l). Citrulline levels are significantly lower in the severe degrees of atrophy than in mild ones (13.8 µmol/l vs. 19.7 µmol/l, p < 0.05), not happening so with rest of amminoacids. SUMMARY: Postabsortive mean of plasma citrulline is a good marker of reduction in enterocyte mass in celiac patients with villous atrophy; secondary reduction in plasma arginine too. Just a small histological alteration in intestinal biopsy is enough to differentiate citrulline in cases and controls and besides it can be seen that high levels of atrophy present with lower plasma citrulline.

Disminución de la densidad mineral ósea y otros factores de riesgo en niños prepuberales con fractura del antebrazo distal / Low bone mineral density and other risk factors in prepubertal children with fracture of the distal forearm

Objetivo: Investigar la relación entre densidad mineral ósea (DMO), edad, sexo, medidas antropométricas, ingesta dietética de calcio y actividad física diaria en niños prepúberes con fractura de antebrazo distal (FAD). Material y métodos: Ciento sesenta niños (80 varones y 80 mujeres) de 3 a 10 años de edad con FAD y grupo control de 160 niños (pareados por edad y sexo). Se documentaron edad, sexo, peso, talla, pliegue tricipital (PT), índice de masa corporal (IMC), ingesta diaria de calcio y nivel de actividad física (ejercicio físico extraescolar: bajo si <1h/día, alto si >1h/día). La DMO se evaluó por densitómetro periférico DXA. Resultados: El trauma por precipitación leve-moderado (85,6%) fue el causante de la mayoría de las fracturas (fractura del radio en la mayoría de ellas [87,5%]). El IMC fue mayor en los pacientes (19,14kg/m2±3,50 versus 17,46kg/m2±2,67; p<0,0001). El grosor del PT fue similar en ambos grupos (20,28mm±8,24 versus 19,61mm±6,60; p>0,05). La actividad física estaba disminuida en el grupo de fracturados (actividad física extraescolar >1h: el 21,25 versus el 46,87%; p< 0,001). La ingesta diaria de calcio no estuvo asociada con mayor incidencia de FAD (918,75mg/día±338,04 versus 886,13mg/día±382,77; p>0,05). La DMO fue menor en los fracturados (0,2591g/cm2±0,0413 versus 0,2801g/cm2±0,0300; p<0,0001). Discusión: Una significativa reducción de la DMO, el sobrepeso y la escasa actividad física son factores de riesgo potencial para la FAD; la escasa ingesta dietética de calcio no se encuentra asociada. Las intervenciones en el estilo de vida pueden contribuir a reducir el riesgo de FAD en la infancia (AU)

Aim: To investigate the relationship between bone mineral density (BMD), age, sex, anthropometric measurements, dietary calcium intake and daily physical activity, in prepubertal children with distal forearm fracture (DFF). Methods: 160 children (80 males, 80 females) 3–10 years of age with DFF; control group of 160 children (age-sex matched) were studied. Age, sex, weight, height, tricipital skin fold thickness (TS), body mass index, daily calcium intake, and level of physical activity (extra-school physical exercise: low <1hour/day, high >1hour/day) registered. BMD assessed by peripheral DXA densitometer. Results: Most fractures were caused by mild-moderate precipitating trauma by accidental fall (85.6%), with radius fracture in most cases (87.5%). BMI was higher in patients (19.14kg/m2±3.50 vs. 17.46kg/m2±2.67; p<0.0001). TS thickness was similar in both groups (20.28mm±8.24 vs. 19.61mm±6.60; p>0.05). Physical activity was lower in study group (extra-school physical activity >1h: 21.25% vs. 46.87%; p<0.001). Daily calcium intake was not associated with DFF incidence (918.75mg/day±338.04 vs. 886.13mg/day±382.77; p>0.05). BMD was lower in fractured children (0.2591g/cm2±0.0413 vs. 0.2801g/cm2±0.0300; p<0.0001). Summary: Our results suggest that significantly reduced bone mineral density, overweight and low physical activity are potential risk factors for fracture of the distal forearm, whilst low dietary intakes of calcium do not seem to be associated. The current epidemic of infantile overweight might explain the increased incidence of fractures of the distal forearm (AU)

[Low bone mineral density and other risk factors in prepubertal children with fracture of the distal forearm]. / Disminución de la densidad mineral ósea y otros factores de riesgo en niños prepuberales con fractura del antebrazo distal.

AIM: To investigate the relationship between bone mineral density (BMD), age, sex, anthropometric measurements, dietary calcium intake and daily physical activity, in prepubertal children with distal forearm fracture (DFF). METHODS: 160 children (80 males, 80 females) 3-10 years of age with DFF; control group of 160 children (age-sex matched) were studied. Age, sex, weight, height, tricipital skin fold thickness (TS), body mass index, daily calcium intake, and level of physical activity (extra-school physical exercise: low <1hour/day, high >1hour/day) registered. BMD assessed by peripheral DXA densitometer. RESULTS: Most fractures were caused by mild-moderate precipitating trauma by accidental fall (85.6%), with radius fracture in most cases (87.5%). BMI was higher in patients (19.14 kg/m(2)+/-3.50 vs. 17.46 kg/m(2)+/-2.67; p<0.0001). TS thickness was similar in both groups (20.28 mm+/-8.24 vs. 19.61 mm+/-6.60; p>0.05). Physical activity was lower in study group (extra-school physical activity >1h: 21.25% vs. 46.87%; p<0.001). Daily calcium intake was not associated with DFF incidence (918.75 mg/day+/-338.04 vs. 886.13 mg/day+/-382.77; p>0.05). BMD was lower in fractured children (0.2591 g/cm(2)+/-0.0413 vs. 0.2801 g/cm(2)+/-0.0300; p<0.0001) SUMMARY: Our results suggest that significantly reduced bone mineral density, overweight and low physical activity are potential risk factors for fracture of the distal forearm, whilst low dietary intakes of calcium do not seem to be associated. The current epidemic of infantile overweight might explain the increased incidence of fractures of the distal forearm.

Lavados colónicos anterógrados para el estreñimiento refractario en niños sin encefalopatía / Antegrade colonic enemas for intractable constipation in non-mentally retarded children

Revisión retrospectiva de las cecostomías realizadas para lavados anterógrados colónicos. Doce apendicocecostomías desde enero de 2002 a febrero de 2008, 9 apendicostomías en pacientes con mielomeningocele y 3 cecostomías en niños con estreñimiento crónico no orgánico sin encefalopatía ni retraso mental. De los 9 primeros pacientes, de entre 3 y 13 años, 8 tuvieron muy buena evolución y uno requirió retirada por mal empleo familiar. A un niño de 7 años, por lo demás sano, con estreñimiento crónico desde los 10 meses, pese a laxantes múltiples (varias tandas de desimpactación y dilatación anal bajo anestesia), con estudio morfofuncional normal, se le realizó, hace 5 años, cecostomía; persistió cierta tendencia a impactación pero con buena calidad de vida. Otro niño, previamente sano, de 12 años de edad, presentaba incontinencia fecal diaria asociada a estreñimiento desde los 3 años, con manometría anorrectal normal y biopsia con leve displasia neuronal; se le realizó cecostomía hace 3 años, con mejoría evidente y menor trastorno emocional secundario. El último caso de cecostomía tenía 8 años, con cuadro similar al anterior y se realizó procedimiento endoscópico con botón de Chait, con lo que mejoró francamente el cuadro. La progresión del estreñimiento rebelde a edad adulta tiene un impacto negativo en la adaptación social y el estado emocional del paciente, y puede alterar la vida familiar. Los lavados anterógrados colónicos proporcionan independencia y mejoran la calidad de vida. Se necesitan realizar en más pacientes para poder establecer verdaderos datos de efectividad (AU)

A descriptive review of 12 patients who underwent appendicocecostomy or caecostomy for antegrade colonic lavage from January 2002 to February 2008. There were 9 appendicocecostomies performed patients from 3 to 13 years suffering from myelomeningocele, of which 8 of them had a very good outcome, with one case with drawn due to poor use by the family. Three caecostomies were performed in non-mentally retarded constipated children. One was an otherwise healthy 7 year-old boy with hards tools since he was 10 months old, in spite of multiple laxative treatments, with normal morphology and function. He had a percutaneous caecostomy five years ago, with some improvement and a good quality of life, but still some occasional partial impactions. Another healthy 12 year-old boy with daily constipation associated faecal incontinence since he was 3 years old (normal manometry and rectal biopsy with signs of mild neuronal dysplasia)had a percutaneous caecostomy performed three years ago, with improvement in the faecal incontinence and better psychological out come. The last caecostomy patient was an 8 year-old boy, with a similar clinical history and good progress in last three years after placing a Chait’s button using an endoscopic procedure. Stubborn constipation continuing in to adult life has a negative impact on the social and emotional adaptation of the paediatric patient, affecting family interactions. Antegrade colonic lavage allows independence and improves the quality of life in patients affected by recurrent faecal impactions. This technique needs to be performed on more patients to find out its true effectiveness (AU)

[Antegrade colonic enemas for intractable constipation in non-mentally retarded children]. / Lavados colónicos anterógrados para el estreñimiento refractario en niños sin encefalopatía.

A descriptive review of 12 patients who underwent appendicocecostomy or caecostomy for antegrade colonic lavage from January 2002 to February 2008. There were 9 appendicocecostomies performed patients from 3 to 13 years suffering from myelomeningocele, of which 8 of them had a very good outcome, with one case withdrawn due to poor use by the family. Three caecostomies were performed in non-mentally retarded constipated children. One was an otherwise healthy 7 year-old boy with hard stools since he was 10 months old, in spite of multiple laxative treatments, with normal morphology and function. He had a percutaneous caecostomy five years ago, with some improvement and a good quality of life, but still some occasional partial impactions. Another healthy 12 year-old boy with daily constipation associated faecal incontinence since he was 3 years old (normal manometry and rectal biopsy with signs of mild neuronal dysplasia) had a percutaneous caecostomy performed three years ago, with improvement in the faecal incontinence and better psychological outcome. The last caecostomy patient was an 8-year-old boy, with a similar clinical history and good progress in last three years after placing a Chait's button using an endoscopic procedure. Stubborn constipation continuing into adult life has a negative impact on the social and emotional adaptation of the paediatric patient, affecting family interactions. Antegrade colonic lavage allows independence and improves the quality of life in patients affected by recurrent faecal impactions. This technique needs to be performed on more patients to find out its true effectiveness.

Eficacia y seguridad de tacrolimus oral para el tratamiento de la enfermedad inflamatoria intestinal pediátrica / Safety and efficacy of oral tacrolimus in the treatment of paediatric inflammatory bowel disease

Introducción: En determinadas situaciones clínicas, como es el caso de la colitis ulcerosa (CU) o de la enfermedad de Crohn (EC) graves, que no responden a tratamiento esteroideo intravenoso, es preciso disponer de alternativas terapéuticas a la cirugía. Objetivo: Evaluar la eficacia y seguridad de tacrolimus oral en el tratamiento del brote grave de EC o CU para inducir la remisión y, asimismo, valorar su eficacia para evitar o diferir la intervención quirúrgica. Material y método: Estudio retrospectivo que incluyó a todos los pacientes menores de 18 años afectados de EC o CU con brote grave tratados con tacrolimus oral en el período comprendido entre enero de 1998 y diciembre de 2007 en nuestro centro. Resultados: Se incluyó un total de 8 pacientes (4 varones): 6 con CU y 2 con EC. La edad mediana al inicio del tratamiento fue de 11,8 años (rango de 2,75 a 16,58), el tiempo de evolución fue de 4 meses (rango de 1 a 96) y la respuesta inicial se obtuvo en el 50% de los pacientes. Las concentraciones plasmáticas de tacrolimus se mantuvieron entre 5 y 11ng/ml. Un total de 6 de los 8 pacientes (75%) precisó intervención quirúrgica. En un paciente con CU y en otro con EC se evitó la cirugía. En 2 de los 6 pacientes afectados de CU se pudo posponer la intervención quirúrgica más allá de 6 meses. Conclusiones: Tacrolimus es útil en pacientes con brotes graves de CU y colitis de Crohn, modifica el curso de la enfermedad, evita o retrasa la intervención quirúrgica y permite preparar al paciente y a su familia ante la probable intervención quirúrgica. Puede emplearse como tratamiento puente en aquellos pacientes hasta que el nuevo tratamiento de mantenimiento sea efectivo (AU)

Background: In certain clinical situations, such as acute and severe episodes of ulcerative colitis (UC) or Crohn's Disease (CD), that do not respond to conventional intravenous steroid treatment, we need potent, fast-acting drugs to induce clinical remission and avoid surgery. Objectives: To evaluate the efficacy and safety of oral tacrolimus treatment of acute and severe UC or CD to induce their remission, and also to assess its efficacy in delaying or avoiding surgery. Material and methods: We present a retrospective study that included all patients under 18 years of age with acute and severe bouts of CD (colonic or ileocolonic location) or UC who were treated with oral tacrolimus at our institution from January 1998 to December 2007. Results: We included a total of 8 patients (4 males and 4 females), 6 presented with UC and 2 had CD. The mean age of our patients at the start of the treatment was 11.8 years (range 2.75–16.58 y) and the mean time from diagnosis to the start of tacrolimus therapy was 4 months (range 1–96m). An initial response was obtained in 50% of patients. Plasma trough levels of tacrolimus remained between 5–11ng/ml. Six of the eight patients (75%) required surgery. In one patient with UC and in another with CD, surgery was avoided. In 2 of the 6 patients with UC, surgery was postponed beyond 6 months. Conclusions: Tacrolimus is useful in inducing clinical remission in patients with acute and severe bouts of UC or CD, and so can avoid or delay the surgery; it may also be used as a bridging agent until the new maintenance therapy with other immunosuppressants is effective (AU)

[Safety and efficacy of oral tacrolimus in the treatment of paediatric inflammatory bowel disease]. / Eficacia y seguridad de tacrolimus oral para el tratamiento de la enfermedad inflamatoria intestinal pediátrica.

BACKGROUND: In certain clinical situations, such as acute and severe episodes of ulcerative colitis (UC) or Crohn's Disease (CD), that do not respond to conventional intravenous steroid treatment, we need potent, fast-acting drugs to induce clinical remission and avoid surgery. OBJECTIVES: To evaluate the efficacy and safety of oral tacrolimus treatment of acute and severe UC or CD to induce their remission, and also to assess its efficacy in delaying or avoiding surgery. MATERIAL AND METHODS: We present a retrospective study that included all patients under 18 years of age with acute and severe bouts of CD (colonic or ileocolonic location) or UC who were treated with oral tacrolimus at our institution from January 1998 to December 2007. RESULTS: We included a total of 8 patients (4 males and 4 females), 6 presented with UC and 2 had CD. The mean age of our patients at the start of the treatment was 11.8 years (range 2.75-16.58 y) and the mean time from diagnosis to the start of tacrolimus therapy was 4 months (range 1-96 m). An initial response was obtained in 50% of patients. Plasma trough levels of tacrolimus remained between 5-11 ng/ml. Six of the eight patients (75%) required surgery. In one patient with UC and in another with CD, surgery was avoided. In 2 of the 6 patients with UC, surgery was postponed beyond 6 months. CONCLUSIONS: Tacrolimus is useful in inducing clinical remission in patients with acute and severe bouts of UC or CD, and so can avoid or delay the surgery; it may also be used as a bridging agent until the new maintenance therapy with other immunosuppressants is effective.

Eficacia del tratamiento nutricional primario en la enfermedad de Crohn pediátrica / Efficacy of exclusive enteral feeding as primary therapy for paediatric Crohn´s disease

Introducción: El tratamiento nutricional primario (TNP), que consiste en la administración de dieta exclusiva con fórmula enteral (polimérica, semielemental o elemental) durante un período no inferior a 6-8 semanas, ha demostrado ser efectivo para inducir la remisión clínica en niños afectados de enfermedad de Crohn. La remisión clínica no siempre conlleva la remisión histológica o la curación de la mucosa. La calprotectina fecal es un excelente marcador de la actividad inflamatoria intestinal y sus concentraciones se correlacionan estrechamente con el grado de inflamación de la mucosa intestinal. Pacientes y métodos: Se ha realizado un estudio prospectivo observacional en el que se incluyeron todos los pacientes menores de14 años diagnosticados de enfermedad de Crohn entreenero de 2002 y octubre de 2007 que recibieron alimentación exclusiva con fórmula polimérica (Modulen IBD, Nestlé, Vevey, Suiza) durante su primer brote de enfermedad. Se establecieron controles clínicos (peso, talla, índice de masa corporal, índice de actividad de la enfermedad de Crohn pediátrica [PCDAI]) y determinaciones de calprotectina fecal al inicio, y a las 4 y 8 semanas de tratamiento. La remisión clínica se definió cuando el PCDAI era igual o inferior a 10. Se consideraron normales valores de calprotectina fecal inferiores a 50 mg/g de heces. Resultados: Se incluyeron 14 pacientes (9 varones), con una edad media en el momento del diagnóstico de 10,74 +/- 2,56 años. A las 4 semanas, el 71 % de los pacientes alcanzaron la remisión clínica, que se acompañó de un descenso no significativo de las cifras de calprotectina fecal. A las 8 semanas, el 85 % de los pacientes logró la remisión clínica y los valores de calprotectina fecal habían descendido de forma significativa, aunque sin alcanzar concentraciones normales. Conclusión: El TNP administrado durante un período de 8 semanas puede inducir la remisión clínica y mejorar el grado de inflamación de la mucosa intestinal (AU)

Introduction: The primary nutritional therapy (PNT), which consists in the administration of exclusive enteral formula feeds(polymeric, semi-elemental or elemental formula) for a period of no less than 6-8 weeks, has proven to be effective in inducing clinical remission in children with Crohn’s disease. The clinical remission does not always include histological remission or cure of the mucosa. Faecal calprotectin is closely correlated with endoscopic and histological findings but is slightly associated with clinical activity scores. Patients and methods: An observational prospective study including all patients under 14 years of age diagnosed with Crohn’s disease between January 2002 and October 2007, and who were fed exclusively with polymeric formula (Modulen IBD, Nestle, Vevey, Switzerland) during the onset of the disease. Clinical controls were carried out (weight, height, body mass index [BMI) and the Paediatric Crohn’s Disease Activity Index [PCDAI)) and faecal calprotectin was measured at the beginning and at weeks 4 and 8 of treatment. The clinical remission was defined as having a PCDAI less than or equal to 10. Faecal calprotectin values below 50 mg/g faeces were considered as normal. Results: There were 14 patients (9 males), mean age at diagnosis of 10.74 +/- 2.56 years. At week 4, 71 % of patients (10/14)had achieved clinical remission and a decrease in faecal calprotectin levels that was not significant. After 8 weeks, 85 % of our patients were in clinical remission and faecal calprotectin values had declined significantly without treaching normal levels. Conclusion: Primary nutritional therapy administered over a period of 8 weeks is capable of inducing clinical remission and improving the degree of inflammation of the intestinal mucosa (AU)

Colestasis intrahepática familiar progresiva tip 3. Defecto de MDR3 / Progressive familial intrahepatic cholestasis type 3. An MDR3 defect

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[Efficacy of exclusive enteral feeding as primary therapy for paediatric Crohn's disease]. / Eficacia del tratamiento nutricional primario en la enfermedad de Crohn pediátrica.

INTRODUCTION: The primary nutritional therapy (PNT), which consists in the administration of exclusive enteral formula feeds (polymeric, semi-elemental or elemental formula) for a period of no less than 6-8 weeks, has proven to be effective in inducing clinical remission in children with Crohn's disease. The clinical remission does not always include histological remission or cure of the mucosa. Faecal calprotectin is closely correlated with endoscopic and histological findings but is slightly associated with clinical activity scores. PATIENTS AND METHODS: An observational prospective study including all patients under 14 years of age diagnosed with Crohn's disease between January 2002 and October 2007, and who were fed exclusively with polymeric formula (Modulen IBD, Nestle, Vevey, Switzerland) during the onset of the disease. Clinical controls were carried out (weight, height, body mass index [BMI) and the Paediatric Crohn's Disease Activity Index [PCDAI)) and faecal calprotectin was measured at the beginning and at weeks 4 and 8 of treatment. The clinical remission was defined as having a PCDAI less than or equal to 10. Faecal calprotectin values below 50 microg/g faeces were considered as normal. RESULTS: There were 14 patients (9 males), mean age at diagnosis of 10.74 +/- 2.56 years. At week 4, 71 % of patients (10/14) had achieved clinical remission and a decrease in faecal calprotectin levels that was not significant. After 8 weeks, 85 % of our patients were in clinical remission and faecal calprotectin values had declined significantly without reaching normal levels. CONCLUSION: Primary nutritional therapy administered over a period of 8 weeks is capable of inducing clinical remission and improving the degree of inflammation of the intestinal mucosa.

[Allergic colitis in exclusively breast-fed infants]. / Colitis alérgica en lactantes exclusivamente amamantados al pecho.

INTRODUCTION: Eosinophilic colitis is induced by antigens present in cow's milk proteins in formula or human milk. In the last few years, an increasing number of cases have been diagnosed in exclusively breast-fed infants. PATIENTS AND METHODS: We performed a retrospective study of 13 infants diagnosed with allergic colitis in our unit between January 1997 and January 2004. All the infants had been exclusively breast-fed. RESULTS: In all patients, initial symptoms were digestive (12 with mucus and bloody stools). Onset of symptoms occurred at 0-3 months in 77 %. Laboratory data of the allergic compound were negative. The main locations were the descending and sigmoid colon (75 %). Biopsy demonstrated acute inflammation, with neutrophil infiltration and an increase in eosinophils. In all patients, initial treatment consisted of exclusion of cow's milk proteins from the mother's diet. Ten of the 13 patients showed no improvement, requiring exclusive administration of protein-free hydrolyzate. In 3 infants, breastfeeding was maintained (breastfeeding without cow's milk proteins plus hydrolyzate). CONCLUSIONS: Diagnosis of eosinophilic colitis is based on exclusion of other causes of specific colitis and typical endoscopic and ultrastructural findings. Moreover, a satisfactory response to dietary treatment must be demonstrated. This diagnosis should be considered in breast-fed infants with rectal bleeding without involvement of general health status.

Colitis alérgica en lactantes exclusivamente amamantados al pecho / Allergic colitis in exclusively breast-fed infants

Introducción: La proctocolitis eosinofílica está inducida por antígenos presentes en las proteínas de leche de vaca contenidas en las fórmulas o en la leche humana y, en los últimos años, se describen cada vez más casos en lactantes pequeños alimentados exclusivamente con la leche materna. Pacientes y métodos: Se presenta un estudio retrospectivo de los 13 casos de colitis alérgica diagnosticados en nuestra unidad entre enero de 1997 y enero de 2004, todos ellos lactantes que estaban recibiendo exclusivamente leche materna. Resultados: La sintomatología de inicio fue siempre la digestiva (12 debutaron con heces con moco y hebras de sangre) y en el 77 % de los casos apareció entre los 0 y los 3 meses de edad. Los datos analíticos del componente alérgico fueron negativos. Las lesiones se localizaron, principalmente (75 %), en las zonas descendente y sigma del colon. La anatomía patológica demostró datos inflamatorios agudos, con infiltración por polimorfonucleares y aumento de eosinófilos. En todos los pacientes se inició tratamiento excluyendo la leche de vaca y sus derivados en la dieta de la madre. En 10/13 no se evidenció mejoría, por lo que requirieron administración exclusiva de hidrolizado extenso de proteínas. En 3 niños se mantuvo lactancia mixta (sin proteínas vacunas 1 hidrolizado). Conclusiones: El diagnóstico exige exclusión de otras causas de colitis específica y hallazgos endoscópicos y anatomopatológicos característicos; además, se debe demostrar respuesta adecuada al tratamiento dietético. Se debe pensar en esta patología al afrontar el diagnóstico de lactantes amamantados que presenten sangrado rectal sin afectación del crecimiento o del estado general

Introduction: Eosinophilic colitis is induced by antigens present in cow's milk proteins in formula or human milk. In the last few years, an increasing number of cases have been diagnosed in exclusively breast-fed infants. Patients and methods: We performed a retrospective study of 13 infants diagnosed with allergic colitis in our unit between January 1997 and January 2004. All the infants had been exclusively breast-fed. Results: In all patients, initial symptoms were digestive (12 with mucus and bloody stools). Onset of symptoms occurred at 0-3 months in 77 %. Laboratory data of the allergic compound were negative. The main locations were the descending and sigmoid colon (75 %). Biopsy demonstrated acute inflammation, with neutrophil infiltration and an increase in eosinophils. In all patients, initial treatment consisted of exclusion of cow's milk proteins from the mother's diet. Ten of the 13 patients showed no improvement, requiring exclusive administration of protein-free hydrolyzate. In 3 infants, breastfeeding was maintained (breastfeeding without cow's milk proteins plus hydrolyzate). Conclusions: Diagnosis of eosinophilic colitis is based on exclusion of other causes of specific colitis and typical endoscopic and ultrastructural findings. Moreover, a satisfactory response to dietary treatment must be demonstrated. This diagnosis should be considered in breast-fed infants with rectal bleeding without involvement of general health status

Disfagia persistente en una niña de 9 años / Persistent dysphagia in a 9-year-old girl

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[Influence of energy expenditure on childhood obesity]. / Influencia del gasto energético en la obesidad infantil.

OBJECTIVES: To study differences in resting energy expenditure (REE) according to its determining factors (sex, weight, body fat mass, lean body mass) and in the oxidation of energy substrates in obese and non-obese children. PATIENTS AND METHODS: We studied 71 children (39 obese and 32 non-obese) aged from 4.1 to 13.6 years. The male/female ratio was 34/37. Energy expenditure (EE) was measured by using open circuit indirect calorimetry. The oxidation of energy substrates was calculated from oxygen consumption, carbon dioxide production, and urinary nitrogen excretion from urea. Body composition was determined by anthropometry. RESULTS: REE (kcal/day), adjusted for anthropometric parameters and body composition, was higher in boys than in girls. The absolute REE was significantly higher in obese than in non-obese children (1512.82 6 234.47 vs 1172.59 6 190.20) and was higher or the same when adjusted for its determinants. Compared with the non-obese group, the obese group presented a significantly higher percentage of fat oxidation (57.15 6 10.68 vs 51.08 6 13.61, p 5 0.04), a lower percentage of carbohydrate oxidation (30.10 6 9.85 vs 36.34 6 13.61, p 5 0.03) and a lower respiratory quotient (0.79 6 0.03 vs 0.82 6 0.04, p 5 0.02). No differences were found between male and female subjects in the percentages of carbohydrate, fat, and protein oxidation. CONCLUSIONS: We obtained the followings conclusions: a) When adjusted for anthropometric measurements and body composition, REE was significantly higher in boys than in girls; b) REE was higher in obese than in non-obese children, after adjustment for lean body mass; and c) Compared with the control group, obese children presented a higher percentage of fat oxidation, a lower percentage of carbohydrate oxidation, and a lower respiratory quotient.

Influencia del gasto energético en la obesidad infantil / Influence of energy expenditure on childhood obesity

Objetivos Estudiar las diferencias en el gasto energético en reposo (GER) en función de sus determinantes (sexo, peso, masa grasa, masa magra) y la oxidación de los sustratos energéticos entre niños obesos y no obesos. Pacientes y métodos Se ha estudiado una muestra de 71 niños, 39 obesos y 32 controles, con rango de edad entre 4,1 y 13,6 años, de los cuales 37 eran mujeres y 34 varones, a los que se realiza medida del gasto energético mediante calorimetría indirecta de circuito abierto. La oxidación de sustratos se calculó a partir del consumo de oxígeno, producción de anhídrido carbónico y excreción de nitrógeno ureico urinario. Se determinó la composición corporal por antropometría. Resultados El GER (kcal/día) ajustado en función de los parámetros antropométricos y de composición corporal es superior en niños que en niñas. El GER en valor absoluto es significativamente superior en los obesos (1.512,82 234,47 frente a 1.172,59 190,20), y al expresarlo en función de sus determinantes, sigue siendo mayor en los obesos o se iguala en ambos grupos. Los obesos presentan mayor porcentaje de oxidación de grasas (57,15 10,68 frente a 51,08 13,61; p 0,04), menor porcentaje de oxidación de hidratos de carbono (30,10 9,85 frente a 36,34 13,61; p 0,03) y menor cociente respiratorio (0,79 0,03 frente a 0,82 0,04; p 0,02). No existen diferencias en los porcentajes de oxidación de hidratos de carbono, grasas y proteínas según el sexo. Conclusiones Del estudio se han extraído las siguientes conclusiones: a) el GER ajustado en función de los parámetros antropométricos y de composición corporal es significativamente superior en el sexo masculino que en el femenino; b) el GER es superior en los obesos, y sigue siéndolo al estandarizarlo en función de la masa corporal magra, y c) los niños obesos presentan mayor porcentaje de oxidación de grasas, menor porcentaje de oxidación de hidratos de carbono y un cociente respiratorio menor que los niños no obesos. (AU)