TGF-ß Concentration in Breast Milk is Associated With the Development of Eczema in Infants.

Background: Transforming growth factor (TGF)-ß in breast milk is crucial for mucosal immune system in the neonatal period. We hypothesized that the level of exposure to TGF-ß from breast milk in the first month of life is related to the development of eczema later in life. Thus, the present study investigated whether changes in TGF-ß levels between colostrum and mature milk are associated with such occurrence in a birth cohort study. Methods: Colostrum and 1-month breast milk samples were collected from mothers who participated in our birth cohort study. TGF-ß1 and TGF-ß2 levels in breast milk were measured using a commercial ELISA kit. The development of eczema in the first 6 months after birth was assessed based on parent's response to a questionnaire. Levels of TGF-ß1 and TGF-ß2 were compared in breast milk from mothers of infants with and without eczema. Results: In children with eczema, TGF-ß1 levels were higher in colostrum, but lower in 1-month milk. A lower TGF-ß1 ratio (1-month milk/colostrum) was related to the development of eczema during the first 6 months of life. There was no difference in TGF-ß2 ratio (1-month milk/colostrum) between eczema group and control group. Conclusions: Concentration of TGF-ß1 but not TGF-ß2 in breast milk during the first month after birth may be associated with eczema later in life. Factors that increase TGF-ß1 levels in breast milk may play a role in preventing allergic disease.

Effectiveness of Medium-Chain Triglyceride Oil Therapy in Two Japanese Citrin-Deficient Siblings: Evaluation Using Oral Glucose Tolerance Tests.

Citrin deficiency, an inherited defect of the liver-type mitochondrial aspartate/glutamate carrier isoform (citrin), may cause impairment of glycolysis because of an increase in the cytosolic NADH/NAD+ ratio. We report a Japanese boy whose main complaint was recurrent hypoglycemic episodes. He was suspected as having citrin deficiency because of his peculiar preference for protein- and fat-rich food. His young sister also had a similar food preference. Both siblings were diagnosed with citrin deficiency by genetic analysis. The brother and sister underwent an oral glucose tolerance test (OGTT) at 10 and 7 yr of age, respectively. Blood glucose, ammonia, lactic acid, pyruvic acid, and insulin levels were monitored before starting the test, and then every 30 min. During this test, they maintained blood glucose levels until 180 min. At 210 min, they experienced vomiting, feeling ill, and decreased blood glucose levels (2.9 and 2.8 mmol/l in the brother and sister, respectively). The sister and brother recovered uneventfully by intravenous glucose injection. In a second OGTT, 4 months after medium-chain triglyceride (MCT) oil supplementation, they had no major symptoms and normal glucose levels were maintained, even after 240 min. Additionally, after MCT oil therapy, their food preference slightly changed as they started eating more carbohydrates. Our OGTT data suggest excess carbohydrate intake has adverse consequences in patients with citrin deficiency, including hypoglycemia after a few hours. MCT oil therapy may be effective in preventing such hypoglycemia and improving metabolic derangement, even during the so-called apparently healthy period.

ACTH therapy for West syndrome with severe hemophilia A.

Hemophilia A is an X-linked recessive disorder caused by factor VIII deficiency, which is an important factor in the coagulation system. Here, we describe a 1-year-old boy with hemophilia A who developed West syndrome (WS). Recombinant factor VIII was administered during adrenocorticotropic hormone (ACTH) therapy to prevent intracranial hemorrhage. Infusion of factor VIII at fixed intervals is useful for the safe administration of ACTH therapy for patients with WS with severe hemophilia A. A coagulation screening test should be performed before ACTH therapy.

Successive MRI Findings of Reversible Cerebral White Matter Lesions in a Patient with Cystathionine ß-Synthase Deficiency.

Cystathionine ß-synthase (CBS) deficiency, well known as classical homocystinuria, is a rare autosomal recessive inborn error of homocysteine and sulfur metabolism. CBS converts homocysteine to cystathionine. The clinical features of untreated CBS deficiency include myopia, ectopia lentis, mental retardation, skeletal anomalies resembling Marfan syndrome, and thromboembolic events. Cerebral white matter lesions (CWMLs), identified in magnetic resonance imaging (MRI), are related to various clinical conditions including ischemia, inflammation, demyelination, infection, a tumor, and metabolic disorders such as phenylketonuria. The presence of CWMLs is, however, believed to be a very rare condition in CBS-deficient patients. Herein, we report reversible CWMLs associated with hypermethioninemia caused by poor protein restriction and betaine therapy in a 21-year-old male with pyridoxine-nonresponsive CBS deficiency. T2-weighted images (T2WI) and fluid-attenuated inversion-recovery (FLAIR) images showed diffuse high signal intensity in subcortical areas extending to the deep white matter. Diffusion-weighted images (DWI) showed high signal intensity, while apparent diffusion coefficient (ADC) map demonstrated decreased ADC value in the lesions. The course of improvement after correct methionine restriction was successively followed by brain MRI. The CWMLs had regressed at 1 month after restriction, and disappeared after 5 months. ADC values were very low before proper methionine restriction, but normalized after 2 months. Use of betaine in the presence of elevated plasma methionine may increase the risk of reversible CWMLs in some CBS-deficient patients.

Total IgE at 6 months predicts remittance or persistence of atopic dermatitis at 14 months.

Some patients with infantile atopic dermatitis (AD) achieve remission around 1 year old, but in others it persists. The difference between them is unclear. We performed a birth cohort study to find the markers predicting the outcome of infantile AD. We followed up a cohort (n = 314) from birth to 14 months of age, and cord blood was taken from the participants. Some of them (n = 144) had a physical examination and a blood test at 6 and 14 months of age. The subjects who had AD at 6 months (n = 34) were divided into two groups, named the transient group (those who had no AD at 14 months of age; n = 16) and the persistent group (those who still had AD at 14 months of age; n = 18). Then, laboratory data were compared between these two groups. Percentage of CD8 in cord blood lymphocytes and total IgE at 6 months of age in the persistent group was significantly higher than those of the transient group. The area under the curves of a receiver operating characteristic analysis were 0.792 (p = 0.007) and 0.722 (p = 0.027). In the persistent group, total IgE, percentages of T-helper (Th) 2 and phytohemagglutinin-induced IL-4 production from peripheral blood mononuclear cells at 14 months of age were also significantly higher than those of the transient group. Thus Th2 polarization in the persistent group was confirmed. In clinical use, total IgE at 6 months of age is the most useful predictive marker to know the outcome of infantile AD. The clinical trial registration ID is UMIN000002926.

[QOL questionnaire for pediatric patients with bronchial asthma and their parents or caregivers. Preparation and evaluation of the short form version 2008 (Gifu)].

BACKGROUND: The QOL questionnaire version 2001 for pediatric patients with bronchial asthma and their parents or caregivers includes 15 questions for patients under the age of 4 years and 20 questions for patients over the age of 4 years. We have already reported that the QOL questionnaire version 2001 reflects reliability (including reproducibility), factorial validity, and changes in paroxysmal attacks of asthma. In this study, we revised the questionnaire for use in routine medical practice. METHODS AND RESULTS: In this study, based on the data of a previous report, the number of questions was reduced further and it was revised to the questionnaire the short form by integrated data. The revised version 2008 (Gifu) consisted of emotional burden, asthma attack, instability of symptoms and proper acceptance of asthma as a common factor, moreover 4 or more years old added load of exercise factor which consisted of two questions in each factor. This QOL short form questionnaire version 2008 (Gifu) is a disease specific questionnaire in comparison with health control, bronchial asthma and non-asthmatic patients, such as atopic dermatitis and allergic rhinitis. CONCLUSION: Although Cronbach's alpha fell with reduction of the number of questions, we conclude that it was acceptable in the clinical practice.

IL-10 plays an important role as an immune-modulator in the pathogenesis of atopic diseases.

Interleukin (IL)-10 has anti-inflammatory activities in various immune reactions and plays an important role in the regulation of immune diseases. In the present study, we examined the role of IL-10 in atopic diseases. Peripheral blood mononuclear cells (PBMCs) from healthy control subjects, patients with atopic dermatitis and patients with bronchial asthma were cultured with lipopolysaccharide (LPS). The production of IL-10, IL-12 or IFN-γ by PBMCs stimulated with LPS was measured. Next, we investigated whether the haplotype in the IL-10 gene promoter region had an effect on the production of IL-10 by PBMCs. PBMCs from patients were cultured with phytohemagglutinin, to which recombinant human IL-10 had been added. IL-12, IFN-γ and IL-4 production by PBMCs was measured. ß-lactoglobulin (BLG)-specific T cell clones were cultured with BLG peptide (P-17), antigen-presenting cells and recombinant human IL-10. The antigen-induced proliferation of the T cell clones and cytokine production were assayed. Results demonstrated that IL-10 production by LPS-stimulated PBMCs was lower in atopic patients than in healthy control subjects. Three different haplotypes in the IL-10 gene promoter region were detected. These haplotypes did not correlate with IL-10 production by PBMCs. IL-10 inhibited Th1 cytokine production by PBMCs, and also inhibited the antigen-induced proliferation of T cell clones and Th2 cytokine production. In conclusion, IL-10 inhibits both the production of Th1 and Th2 cytokines and the antigen-induced proliferation of T cell clones. Thus, IL-10 modulates other cytokines and plays an important role as an immune-modulator in the pathogenesis of atopic diseases.