Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 9 de 9
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
N Engl J Med ; 377(1): 52-61, 2017 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-28657829

RESUMO

BACKGROUND: Studies of monogenic gastrointestinal diseases have revealed molecular pathways critical to gut homeostasis and enabled the development of targeted therapies. METHODS: We studied 11 patients with abdominal pain and diarrhea caused by early-onset protein-losing enteropathy with primary intestinal lymphangiectasia, edema due to hypoproteinemia, malabsorption, and less frequently, bowel inflammation, recurrent infections, and angiopathic thromboembolic disease; the disorder followed an autosomal recessive pattern of inheritance. Whole-exome sequencing was performed to identify gene variants. We evaluated the function of CD55 in patients' cells, which we confirmed by means of exogenous induction of expression of CD55. RESULTS: We identified homozygous loss-of-function mutations in the gene encoding CD55 (decay-accelerating factor), which lead to loss of protein expression. Patients' T lymphocytes showed increased complement activation causing surface deposition of complement and the generation of soluble C5a. Costimulatory function and cytokine modulation by CD55 were defective. Genetic reconstitution of CD55 or treatment with a complement-inhibitory therapeutic antibody reversed abnormal complement activation. CONCLUSIONS: CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy (the CHAPLE syndrome) is caused by abnormal complement activation due to biallelic loss-of-function mutations in CD55. (Funded by the National Institute of Allergy and Infectious Diseases and others.).


Assuntos
Antígenos CD55/genética , Ativação do Complemento/genética , Proteínas do Sistema Complemento/metabolismo , Mutação , Enteropatias Perdedoras de Proteínas/genética , Trombose/genética , Antígenos CD55/sangue , Criança , Pré-Escolar , Ativação do Complemento/efeitos dos fármacos , Inativadores do Complemento/farmacologia , Feminino , Homozigoto , Humanos , Imunoglobulina A/sangue , Lactente , Intestino Delgado/patologia , Masculino , Linhagem , Enteropatias Perdedoras de Proteínas/complicações , Estatísticas não Paramétricas , Síndrome , Linfócitos T/metabolismo
2.
J Pediatr Gastroenterol Nutr ; 60(3): 332-8, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25373860

RESUMO

OBJECTIVES: In the present study, we studied a cohort of patients with very early onset inflammatory bowel disease (IBD) to determine the frequency of mutations in the interleukin 10 (IL10) receptor genes as a cause of early-onset IBD. METHODS: Sanger sequencing was performed to determine the presence of IL10 and/or IL10 receptor mutations in 17 patients with a diagnosis of very early onset IBD (disease onset <2 years of age in 15 patients, between 3 and 4 years in the other 2). Mutation screening was performed including all of the coding regions of the IL10, IL10RA, and IL10RB genes. We then compared the follow-up findings of the patients with IL10 receptor mutations in terms of demographic, clinical, laboratory, and treatment response properties with those of patients diagnosed as having very early onset IBD with no mutation. RESULTS: We identified 3 patients bearing mutations in the IL10 or IL10 receptor genes, including 1 mutation in IL10RB that has been described recently (c.G477A, p.Trp159*) and 2 novel mutations affecting the IL10RA gene (c.T192G, p.Tyr64 and c.T133G, p.Trp45Gly). Collectively, these mutations thus provided genetic etiology for 17.6% of the cohort under investigation. The presence of a family history of IBD and the clinical course of Crohn disease differed between patients with mutations in the IL-10 pathway and those without such mutations. Although perianal fistulas were found in all of the patients with IL10 receptor mutations, they were found in only 14.3% of those without such mutations. The lower values of weight-for-age and height-for-age z scores, necessity for more intensive therapy, achievement of longer periods until remission, and frequent relapses in the patients bearing mutations in the IL10 receptor genes all underlined the severity of the disease and its relatively poor response to treatment. CONCLUSIONS: In spite of the small number of patients with mutations affecting the IL-10 signaling pathway in our study, in all of the patients with IL10 receptor mutations, the disease onset occurs at an early age, the prognosis is poor, and the response to treatment is insufficient.


Assuntos
Predisposição Genética para Doença , Doenças Inflamatórias Intestinais/genética , Subunidade alfa de Receptor de Interleucina-10/genética , Subunidade beta de Receptor de Interleucina-10/genética , Mutação , Fístula Retal/etiologia , Substituição de Aminoácidos , Pré-Escolar , Estudos de Coortes , Terapia Combinada , Doença de Crohn/diagnóstico , Doença de Crohn/genética , Doença de Crohn/fisiopatologia , Doença de Crohn/terapia , Éxons , Feminino , Seguimentos , Estudos de Associação Genética , Humanos , Lactente , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/fisiopatologia , Doenças Inflamatórias Intestinais/terapia , Interleucina-10/genética , Interleucina-10/metabolismo , Subunidade alfa de Receptor de Interleucina-10/metabolismo , Subunidade beta de Receptor de Interleucina-10/metabolismo , Masculino , Polimorfismo de Nucleotídeo Único , Prognóstico , Índice de Gravidade de Doença
3.
J Pediatr Gastroenterol Nutr ; 58(6): 750-5, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24552673

RESUMO

BACKGROUND: Shear-wave elastography (SWE) is a novel noninvasive method that involves application of local mechanical compression on soft tissue using focused ultrasonography and acquiring strain images that show tissue response. In this study, our goal was to assess the performance of SWE in the staging of liver fibrosis in children with chronic liver disease. METHODS: The study involved measuring SWE values in the right lobe of the liver in a patient group of 76 children with chronic liver disease and a control group of 50 healthy subjects. In the patient group, the shear elastic modulus values were correlated with biopsy results according to the Brunt scoring system (F0: portal fibrosis, F1: perisinusoidal or portal/periportal fibrosis, F2: both perisinusoidal and portal/periportal fibrosis, F3: bridging fibrosis, and F4: cirrhosis). Performance of SWE in estimating liver fibrosis in children was determined based on a receiver-operating characteristics (ROC) analysis. RESULTS: Mean SWE values of the control group and F0 group were not statistically significantly different (P = 0.106). The mean SWE values of the F1, F2, F3, and F4 groups were higher than that of the control group (all P < 0.001). Based on kiloPascal measurement values, the area under the ROC curve was 95.2% (95% confidence interval [CI] 92.1-99.5), with a sensitivity for diagnosing liver fibrosis of 91.5%, a specificity of 94.0%, a positive predictive value of 93.1%, and a negative predictive value of 92.6%. Based on meter-per-second measurement values, the area under the ROC curve was 96.3% (95% CI 92.7-99.8), with a sensitivity for diagnosing liver fibrosis of 93.2%, a specificity of 94.0%, a positive predictive value of 93.2%, and a negative predictive value of 94.0%. Mean SWE values for patients with nonalcoholic steatohepatitis were higher than those in the remainder of the study group. CONCLUSIONS: Although liver fibrosis can be detected using SWE, differentiation of fibrosis stages could not be achieved. The presence of steatosis significantly increased the mean SWE values on elastography and so care should be taken when assessing children with nonalcoholic steatohepatitis.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Cirrose Hepática/patologia , Fígado/patologia , Índice de Gravidade de Doença , Adolescente , Biópsia , Estudos de Casos e Controles , Criança , Pré-Escolar , Doença Crônica , Feminino , Fibrose , Humanos , Lactente , Hepatopatias/patologia , Masculino , Hepatopatia Gordurosa não Alcoólica/patologia , Curva ROC
4.
J Pediatr Gastroenterol Nutr ; 56(5): 498-502, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23164758

RESUMO

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) and familial Mediterranean fever (FMF) share common clinical and biological features. The prevalence of other inflammatory diseases, including IBD, is increased in FMF. We investigated the presence of IBD accompanying FMF in patients who were being followed up with a diagnosis of FMF and the relation of IBD with the MEFV gene mutation. METHODS: A total of 78 children with FMF were enrolled in the study. The patients were included in the study independent of the presence of complaints. Colonoscopy for IBD was performed if any of the following was present: blood mixed with mucus in the stool; chronic diarrhea (loose and frequent stools lasting >4 weeks); abdominal pain incompatible with FMF (localized in a certain part of the abdomen, not occurring during attacks, >3 days); and positive IgA and IgG anti-Saccharomyces cerevisiae antibodies and perinuclear antineutrophil cytoplasmic antibodies. MEFV gene mutations were analyzed in patients diagnosed as having IBD and FMF. RESULTS: Of the 78 patients with a diagnosis of FMF, colonoscopy was performed and biopsy samples were taken in 20 patients (25.6%) who had abdominal pain incompatible with FMF, chronic diarrhea, bloody stools, and/or positive perinuclear anti-neutrophil cytoplasmic antibody or anti-Saccharomyces cerevisiae antibody. Histopathological examination resulted in a diagnosis of IBD in 12 of the 78 patients (15.4%). MEFV gene mutations were present in all 12 patients diagnosed as having IBD. We observed M694 V mutations in 5 of 12 patients (41.7%), M680I mutations in 3 (25%), K695R mutations in 3 (25%), and E148Q mutations in 1 (8.3%). CONCLUSIONS: We found that the number of patients with FMF was higher than the number with IBD in the general population. When IBD accompanied FMF, the most common mutation was M694 V; however, the high rate (25%) of K695R mutation in our patients with FMF and IBD was not observed in previous studies.


Assuntos
Proteínas do Citoesqueleto/genética , Febre Familiar do Mediterrâneo/genética , Doenças Inflamatórias Intestinais/genética , Mutação , Biópsia , Criança , Pré-Escolar , Colonoscopia , Febre Familiar do Mediterrâneo/complicações , Feminino , Genótipo , Humanos , Doenças Inflamatórias Intestinais/complicações , Masculino , Pirina , Turquia
6.
Nutrition ; 48: 40-47, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29469018

RESUMO

OBJECTIVES: Many screening methods, such as the Screening Tool Risk on Nutritional Status and Growth (STRONGkids) and the Pediatric Yorkhill Malnutrition Score (PYMS), have been developed to detect malnutrition in pediatric patients. We aimed to explore the prevalence of malnutrition risk in hospitalized children via symptoms and identification of contributing factors, and to examine the efficacy of malnutrition screening tools for hospitalized children. METHODS: STRONGkids and PYMS were applied to 1513 inpatients at 37 hospitals in 26 cities from different regions of Turkey. Physical measurements were collected at hospital admission and at discharge. z-Scores of height-for-age, weight-for-age, weight-for-height, and body mass index-for-age were calculated. RESULTS: Overall, 1513 patients were included in the study. A body mass index standard deviation score of less than -2 was present in 9.5% of the study population at hospital admission, whereas 11.2% of the participants had a weight-for-length/height score of less than -2 at hospital admission. According to STRONGkids results, the proportion of the patients with an underlying chronic disease was higher for the patients at high risk of malnutrition than for the patients at medium or low risk (91% compared with 47% or 45%, respectively). PYMS results indicated that patients at high risk of malnutrition have more chronic diseases (75%) than the patients at medium or low risk of malnutrition (55% and 44%, respectively). CONCLUSIONS: Use of anthropometric measurements in addition to screening tools to identify hospital malnutrition (such as PYMS, STRONGkids) will prevent some nutritional risk patients from being overlooked.


Assuntos
Criança Hospitalizada/estatística & dados numéricos , Desnutrição/diagnóstico , Programas de Rastreamento/métodos , Avaliação Nutricional , Índice de Gravidade de Doença , Adolescente , Antropometria , Índice de Massa Corporal , Peso Corporal , Criança , Pré-Escolar , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Masculino , Desnutrição/epidemiologia , Desnutrição/etiologia , Estado Nutricional , Prevalência , Estudos Prospectivos , Fatores de Risco , Turquia/epidemiologia
7.
Children (Basel) ; 4(10)2017 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-29048383

RESUMO

Although intussusception and food allergy are common health problems in childhood, the relation between these two diseases remain obscure. The aim of this study is to investigate the relationship between food allergy and intussusception, and the factors associated with both. Patients diagnosed with intussusception by the Brighton Collaboration Intussusception Working Group criteria were prospectively investigated for food allergy per the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Guideline. They were analyzed per demographic features, clinical, physical and laboratory findings. There were eight (38.1%) patients diagnosed with food allergy, while 13 (61.9%) patients were non-allergic. The mean number of days of presenting symptoms was 1.13 days in the allergy group and 7.85 days in the non-allergy group. The mean number of intussusception attacks was 1.63 in the allergy group while 1 in the non-allergy group (p < 0.05, relative risk (RR) = 2.6). In the allergy group, one (13%) patient was followed up, six (75%) patients were reduced with pneumatic and one (13%) patient reduced manually. In the non-allergy group, four (31%) patients were followed up, six (46%) patients were reduced with pneumotic, one (7%) patient was reduced manually, and resection anastomosis was performed in two (15%) patients. Food allergy is an unrecognized associated factor for intussusception patients, which increases the risk for recurrence. Due to the small patient population, these results should be interpreted with caution.

8.
Allergy Asthma Immunol Res ; 6(1): 33-8, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24404391

RESUMO

PURPOSE: Calprotectin is a cytosolic protein with immunomodulatory, antimicrobial, and antiproliferative actions. The concentration of calprotectin increases in infection, inflammation, and malignancy. We determined if calprotectin can be used as a marker for the diagnosis and follow-up of bowel inflammation in cow's milk protein allergy (CMPA). METHODS: In total, 32 patients newly diagnosed with CMPA were included (24 IgE-mediated, 8 non-IgE-mediated). In all subjects, a complete blood count, total IgE, cow's milk-specific IgE, and fecal calprotectin (FC) were assessed before and after a cow's milk protein (CMP) elimination diet was started. The results were compared with those of 39 healthy children. RESULTS: The mean FC value before the CMP elimination diet was 516±311 µg/g in the 32 patients with CMPA and 296±94 µg/g in the control group (P=0.011). The mean FC value after the diet in these patients was 254±169 µg/g, which was significantly different from the mean value before the CMP elimination diet (P<0.001). When we compared FC levels before the CMP elimination diet in the IgE-mediated group with the control group, we found no significant statistical difference (P=0.142). The mean FC value before the CMP elimination diet was 886±278 µg/g in the non-IgE-mediated group and 296±94 µg/g in the control group; this difference was statistically significant (P<0.001). In the IgE-mediated and non-IgE-mediated groups, FC values after CMP elimination diet were 218±90 µg/g and 359±288 µg/g, respectively, and FC values before CMP elimination diet were 392±209 µg/g and 886±278 µg/g, respectively; these differences were statistically significant (P=0.001 and P=0.025, respectively). CONCLUSIONS: FC levels may be a useful marker for follow-up treatment and recurrence determination in CMPA.

9.
J Neurogastroenterol Motil ; 19(1): 90-3, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23350053

RESUMO

BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders and when compared to the vast knowledge pertaining to adults with IBS, very little is known about IBS in children and adolescents. We aimed to explore the prevalence of IBS, identify symptoms and contributing factors and also to examine the efficacy of trimebutine maleate in children and adolescents. METHODS: The study involved 345 children and adolescents (4-18 years) and parents were requested to fill in a questionnaire, Rome III criteria was used to diagnose IBS. To exclude organic disease, all patients underwent medical investigations. Half of the randomly selected IBS patients were treated with trimebutine maleate while the rest of IBS patients were not. The IBS patients were reevaluated at the end of 3 weeks. RESULTS: The prevalence of IBS according to Rome III criteria in children and adolescents was 22.6% and IBS with constipation was the predominant subtype. Back pain (OR, 6.68), headache (OR, 4.72) and chronic fatigue (OR, 3.74) were significantly higher in IBS group. The prevalence of IBS in both parents and depression in mothers was greater for the patient group than the healthy controls (P < 0.0001). The prevalence of functional dyspepsia in IBS group was 80.8% and was significantly higher than control group. Clinical recovery was seen in 94.9% of the trimebutine maleate group versus spontaneous recovery in 20.5% of the non-medicated group. The difference was significant (P < 0.0001). CONCLUSIONS: IBS is a common disorder in children and adolescents. IBS is closely associated with somatic and familial factors. Trimebutine maleate is effective for pediatric IBS patients.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA