Hippocampal diffusion abnormality after febrile status epilepticus is related to subsequent epilepsy.

OBJECTIVE: To assess hippocampal signal changes on diffusion-weighted imaging (DWI) during the acute period after febrile status epilepticus (FSE) and to examine the relationship between DWI and subsequent epilepsy. METHODS: A prospective, multicenter study of children with a first episode of FSE was performed. The patients underwent magnetic resonance imaging (MRI) within 3 days of FSE, and signal intensity was evaluated on DWI. Electroencephalography studies within 3 days of FSE were also assessed. Nine to 13 years after FSE, information on subsequent epilepsy was obtained. RESULTS: Twenty-two children with FSE were evaluated. DWI showed unilateral hippocampal hyperintensity in six patients (27%). Three of six patients with hippocampal hyperintensity had ipsilateral thalamic hyperintensity. On EEG within 3 days of FSE, five of six patients with hippocampal hyperintensity had ipsilateral focal slowing, spikes, or attenuation. Nine to 13 years later, the outcomes could be determined in five patients with hippocampal hyperintensity and in 10 without. All 5 patients with hippocampal hyperintensity had hippocampal atrophy and developed focal epilepsy, whereas only 1 of 10 patients without hippocampal hyperintensity developed epilepsy (P = 0.002). Ictal semiology was concordant with temporal lobe seizures in all patients. Ipsilateral temporal epileptiform abnormalities were seen on EEG in four of five at last follow-up. SIGNIFICANCE: Acute DWI hippocampal hyperintensity was seen in 27% of patients with FSE. Acute DWI hyperintensity suggests cytotoxic edema caused by prolonged seizure activity. Hippocampal DWI hyperintensity is related to mesial temporal lobe epilepsy and can be a target of neuroprotective treatments to prevent the onset of epilepsy.

Evaluation of the results of oral food challenges conducted in specialized and general hospitals.

BACKGROUND: Oral food challenge (OFC) tests are conducted in both specialized institutions and general hospitals. We aimed to compare the severity of the conditions of the patients between these 2 types of institutions in order to consider the role of such institutions in society. OBJECTIVE: We evaluated the results of OFC tests for hen's egg, cow's milk, and wheat that were conducted in a specialized institution (Aichi Children's Health and Medical Center [ACHMC], n = 835) and in 4 general hospitals (n = 327) in Aichi prefecture, Japan. METHODS: The symptoms provoked were scored using the total score (TS) of the Anaphylaxis Scoring Aichi scoring system in combination with the total ingested protein dose (Pro) before the appearance of allergic symptoms. RESULTS: The total ingested dose of the challenge-positive patients in ACHMC was significantly less than that in the general hospitals (p < 0.01). The median TS of the provoked symptoms in ACHMC and the general hospitals did not differ to a statistically significant extent in the hen's egg or cow's milk challenges; however, the median TS in ACHMC was significantly lower than that in the general hospitals for the wheat challenge (p = 0.02). The median TS/Pro values in ACHMC were almost identical to the upper 25% of the TS/Pro values in the general hospitals, suggesting that the specialized institution usually managed more severe patients. CONCLUSION: The specialized institution performed OFC tests at a lower threshold dose, but provoked similar TSs to the general hospitals. This evaluation may help in optimizing the distribution of patients to general hospitals and specialized institutions.

Identification of novel FATP4 mutations in a Japanese patient with ichthyosis prematurity syndrome.

Ichthyosis prematurity syndrome (IPS) is a rare autosomal recessive disorder characterized by prematurity, a thick caseous scale at birth and lifelong atopic diathesis. Here, we describe the first Japanese case of IPS and report novel compound heterozygous mutations (p.C403Y and p.R510H) in fatty acid transport protein 4 (FATP4). She is the first reported patient of Asian origin, entirely distinct from the Scandinavian population, in whom the heterozygote carrier frequency is very high.

Demonstration of novel gain-of-function mutations of αIIbß3: association with macrothrombocytopenia and glanzmann thrombasthenia-like phenotype.

Integrin αIIbß3 is indispensable for normal hemostasis, but its role for thrombopoiesis is still controversial. Recently, αIIb and ß3 mutations have been identified in patients with congenital macrothrombocytopenia. We analyzed three unrelated Japanese families with congenital macrothrombocytopenia. Expression and activation state of αIIbß3 in platelets was examined by flow cytometry and immunoblotting. Sequence of whole coding region and exon-intron boundaries of ITGA2B and ITGB3 genes was performed. The effects of mutations on αIIbß3 activation state and phosphorylation of FAK were analyzed in transfected cells. We newly identified three mutations: two mutations in highly conserved Gly-Phe-Phe-Lys-Arg sequence in juxtamembrane region of αIIb, p.Gly991Cys and p.Phe993del, and one donor site mutation of intron 13 of ITGB3 leading to 40 amino acids deletion, p.(Asp621_Glu660del), in the membrane proximal ß-tail domain of ß3. One patient, who showed Glanzmann thrombasthenia-like marked reduction in surface αIIbß3 expression (3-11% of normal control), was a compound heterozygote with ITGA2B p.Gly991Cys and a novel nonsense mutation, ITGA2B p.Arg422*. All three mutations, ITGA2B p.Gly991Cys, ITGA2B p.Phe993del, and ITGB3 p.(Asp621_Glu660del), led to highly activated conformation of αIIbß3 and spontaneous tyrosine phosphorylation of FAK in transfected cells. These results suggest that gain-of-function mutations around membrane region of αIIbß3 lead to abnormal platelet number and morphology with impaired surface αIIbß3 expression.

[Open food challenge with milk, egg white and wheat].

BACKGROUND: A method for open food challenge test to determine food allergy has not been established in an evidence-based manner. METHODS: We conducted an analysis of 438 open food challenges of raw milk (n=133, mean age 2.7+/-1.9 years), boiled egg white (n=216, 2.8+/-2.1 years) or udon noodles (n=89, 2.7+/-1.7 years) for the patients aged 1 year or more. Doses were increased (trace amounts, 1 g, 2 g, 5 g, 10 g, 20-30 g) every 20 minutes. RESULTS: In total, 151 (38.5%) of food challenges were positive. The positive rates of milk, egg and wheat challenges were 35.8%, 42.4% and 33.3%, respectively. Of these, 76.2%, 32.5%, 27.8% and 0.7% had, respectively, skin, respiratory, gastrointestinal and cardiovascular symptoms. Although the prevalence of positive challenge increased with level of specific IgE, it did not correlate with the threshold amount of positive food challenge or the severity of symptoms. Among the challenge positive patients, 10.6% required injection of antihistamines, corticosteroids or adrenalines for the treatment of the symptoms. CONCLUSIONS: This challenge protocol seemed to be appropriate and safe.

Vitamin A reduces lung granulomatous inflammation with eosinophilic and neutrophilic infiltration in Sephadex-treated rats.

Vitamin A is known to suppress the activity of the transcription factors, nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1), as do glucocorticoids. The possibility that vitamin A exerts various anti-inflammatory effects therefore seems likely. Sephadex beads were administered intravenously to anesthesized rats pretreated with a subcutaneous injection of vitamin A (3000, 10,000, or 30,000 IU/kg) or vehicle once daily for 3 days. After 16 h, the leukocyte differential, tumor necrosis factor (TNF)-alpha and eotaxin, and the DNA-binding activity of NF-kappaB were measured in bronchoalveolar lavage fluid (BALF). Additionally, lung histology was assessed using preparations stained with May-Giemsa stain. Sephadex beads caused histological granulomatous changes and eosinophilic and neutrophilic infiltration into the lung, and markedly increased cell counts of eosinophils and neutrophils, concentrations of TNF-alpha and eotaxin, and NF-kappaB binding to DNA in BALF. Vitamin A significantly inhibited all responses. Vitamin A may inhibit Sephadex-induced lung granulomatous formation, and eosinophilic and neutrophilic infiltration due to its suppression of TNF-alpha and eotaxin production, and NF-kappaB activation.

Production of granulomatous inflammation in lungs of rat pups and adults by Sephadex beads.

Granulomatous inflammation is a process that involves mononuclear leukocytes as well as other inflammatory cells. The heterogeneity of its appearance may be due to the variety of cytokines and chemokines that are involved. In this study, we compared granuloma formation and bronchoalveolar leukocyte differential in the lungs of rats (2- and 8-wk-old) that were treated intravenously with Sephadex beads. In addition, the kinetics of cytokine and chemokine production was determined in these groups. In adults, the beads caused lung granulomas associated with infiltration of eosinophils and neutrophils and increased eosinophil and neutrophil counts in the bronchoalveolar lavage fluid within 16 h. In pups, the granulomas were formed slowly and did not reach the size achieved in adults. Eosinophils and neutrophils were sparsely found in the periphery of the granulomas, even at 32 h. Pups were also unable to respond rapidly to Sephadex bead treatment with eosinophil and neutrophil infiltration in the bronchoalveolar lavage fluid. Tumor necrosis factor-alpha was significantly increased in both groups, but the cytokine was lower in pups than in adults. Interferon-gamma and eotaxin were increased only in adults, and IL-4 and regulated on activation, normal T cell expressed, and secreted was increased only in pups. In conclusion, the i.v. administration of Sephadex beads produced granulomatous inflammation in the lungs of adult rats, but pups were unable to respond as rapidly to the treatment. In addition, the difference in response between the two age groups was associated with the kinetics of cytokine and chemokine production.

[Immediate type food hypersensitivity associated with atopic dermatitis in children].

Food allergy is frequently associated with atopic dermatitis (AD) in children. Appropriate elimination diet is necessary in the case of immediate food hypersensitivity, regardless it causes worsening of the chronic eczema or not. Here we report the prevalence of immediate type food allergy diagnosed by oral food challenge or the episodes of apparent acute allergic reaction in the AD patients (n=182, average age 4.9+/-5.1), who visited our clinic within one year. The prevalence of food allergy in the AD patients was 85.7% in age 0 years, 75.6% in age 1,65.4% in age 2, and declined to 13.9% in age 7 years old or more. The offending foods were egg, milk, wheat, fish and so on. The symptoms of food allergy included skin, gastrointestinal or respiratory manifestations, and also anaphylaxis. In conclusion, immediate type food allergy is frequently associated with childhood AD, and appropriate elimination of the offending food is necessary to avoid the acute allergic reaction including anaphylaxis.

Dexamethasone reduces lung eosinophilia, and VCAM-1 and ICAM-1 expression induced by Sephadex beads in rats.

Airway eosinophilia is one of the key pathophysiologic features in asthma. The endothelial adhesion molecules, vascular cell adhesion molecule (VCAM-1) and intercellular adhesion molecule (ICAM-1), have previously been shown to play a crucial role in eosinophil recruitment into the inflamed airway. We have investigated the effects of dexamethasone on eosinophilia into the bronchoalveolar lavage fluid, and the upregulation of VCAM-1 and ICAM-1 expression, measured by immunoblotting, induced by i.v. injection of Sephadex beads into rats. The beads significantly increased the lung eosinophilia, and expression of VCAM-1 and ICAM-1 in the lung. Pretreatment with dexamethasone (0.1 to 2 mg/kg i.p.) strongly inhibited all the airway inflammatory events in a dose-dependent manner. In conclusion, glucocorticoids may be potent inhibitors of lung eosinophilia, at least in part, due to the prevention of the upregulation of VCAM-1 and ICAM-1 expression.