Clinical Epidemiology and Treatment of Febrile and Afebrile Convulsions With Mild Gastroenteritis: A Multicenter Study.

BACKGROUND: We investigated features and responses to treatment in patients with febrile and afebrile convulsions with mild gastroenteritis and characterized convulsions with rotavirus and norovirus gastroenteritis. METHODS: We conducted a prospective, observational study to evaluate patients with febrile and afebrile convulsions with mild gastroenteritis who were hospitalized between November 2011 and March 2014 at 13 facilities in the National Hospital Organization. We classified the patients into two groups: presence or absence of fever. We investigated the background, clinical and laboratory characteristics, viral antigen in stool, and efficacy of anticonvulsant drugs. RESULTS: Of 126 patients enrolled in this study, 50 were febrile (Fc group) and 76 were afebrile (aFc group). A family history of febrile seizures was significantly more frequent in the Fc group than in the aFc group (28.0% vs 9.2%, P = 0.005). Clinical characteristics were similar between the rotavirus and norovirus groups, but fever was significantly more frequent in the rotavirus group (46.2% vs 8.3%, P < 0.001). Serum sodium levels were significantly negatively related to the number of seizures in the aFc group (ß = -0.13; 95% confidence interval, -0.24, -0.03; P = 0.01). Carbamazepine was significantly more efficacious than diazepam suppositories in the aFc group (odds ratio = 49.3, 95% confidence interval, 2.35, 1037; P = 0.01). CONCLUSION: Febrile convulsions with mild gastroenteritis show characteristics of both febrile seizures and convulsions with mild gastroenteritis. Carbamazepine is optimal for convulsions with mild gastroenteritis. Clinical features of convulsions with rotavirus and norovirus gastroenteritis are similar, except for fever. Serum sodium levels may play a major role in the onset of convulsions with mild gastroenteritis.

Oral challenge tests for soybean allergies in Japan: A summary of 142 cases.

BACKGROUND: Soybeans are one of causative foods for infantile onset allergies in Japan. This study aimed to analyze the results of soybean challenge tests that were conducted over approximately 7 years at our institution. Using the test data, we sought to identify the responses and clinical profiles of patients with soybean allergies, and to investigate the relationship between the responses and soybean sensitization status. METHODS: Between July 2004 and May 2010, 142 cases (125 patients) underwent food challenge tests (100 g of silken tofu) for the diagnosis of soybean allergy or confirmation of their tolerance. The patients' characteristics, soybean sensitization status, and responses to the challenge tests were retrospectively evaluated. RESULTS: Among the subjects who underwent the soybean challenge test, the male/female ratio was 1.6 (87/55), and the mean age at the test was 2.8 ± 1.7 years. The positive rate for the challenge test was 38.7%. Induced symptoms were observed in the skin (81.8%), respiratory system (50.9%), and gastrointestinal system/mucosal membrane/anaphylaxis (12.7%). Intramuscular epinephrine was administered to all 7 patients who experienced an anaphylactic reaction. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic efficiency of soybean-specific IgE titers were low for predicting the responses to the challenge test. CONCLUSIONS: Soybean allergies were diagnosed in only 18% of the subjects with positive sensitization to soybeans. Therefore, soybean-specific IgE titers are not an effective predictor of a positive response to the challenge test.

Provocation tests for the diagnosis of food-dependent exercise-induced anaphylaxis.

BACKGROUND: Little has been reported regarding provocation tests for the diagnosis of food-dependent exercise-induced anaphylaxis (FDEIA), especially in children and adolescents. Hence, we here aimed to examine the usefulness and safety of such tests for FDEIA. METHODS: We retrospectively analyzed 41 patients with 184 provocation tests. The patients underwent ergometer stress tests after ingesting the suspected foods along with aspirin. When one or more allergic symptoms appeared, we judged the provocation test as positive. RESULTS: Based on 30 positive test results (16%), we diagnosed 20 patients (49%) as FDEIA. The major causative foods were as follows: wheat alone (five patients), combination of wheat and shrimp (three patients), combination of wheat and apple (two patients), and peach alone (two patients). The symptoms appeared within 45 min after initiating exercise in 29 tests (97%). The most frequent symptoms were cutaneous symptoms, which appeared in 25 tests (83%). Of the 30 positive tests, 6 (20%) required administration of adrenaline. After discharge, the patients with negative test results had no episodes of FDEIA due to the suspected foods that they had been tested for. CONCLUSION: Provocation tests enabled us to confirm the diagnosis of FDEIA when positive and to exclude the diagnosis when negative. However, as severe symptoms may appear, these tests should be performed in a hospital under constant supervision of a physician.

Budesonide inhalation suspension versus methylprednisolone for treatment of moderate bronchial asthma attacks.

BACKGROUND: Owing to their side effects, administration of steroids for bronchial asthma attacks should be minimized. We investigated whether budesonide inhalation suspension (BIS) could replace intravenous steroid administration for the treatment of moderate bronchial asthma attacks. SUBJECTS AND METHODS: The subjects were children aged 5 years and younger hospitalized for moderate bronchial asthma attacks. Patients were randomly assigned to one of two groups: 20 patients received methylprednisolone (mPSL) and 20 were treated with BIS. The mPSL group began treatment with inhalation of procaterol hydrochloride (0.3 mL) and disodium cromoglycate (2 mL) three times a day and systemic administration of mPSL (1 mg/kg) three times a day. The BIS group began treatment with inhalation of procaterol hydrochloride (0.3 mL) and BIS (0.5 mg) three times a day. The frequency of inhalations and steroid administration was adjusted according to the severity of symptoms. The cortisol level at discharge was measured. RESULTS: There were no significant differences between the two groups in terms of the severity of attacks and duration of management, or in terms of therapeutic efficacy, duration of wheezing, or period of hospitalization. The frequency of inhalations on days 3 to 6 of hospitalization was lower in the BIS group than in the mPSL group, and the cortisol level at discharge was significantly higher in the BIS group (13.9 ± 6.1 µg/dL) than in the mPSL group (8.0 ± 2.1 µg/dL) (p = 0.008). CONCLUSION: In patients with recurrent wheezing or bronchial asthma of <5 years, the efficacy of BIS is equivalent or better than mPSL for moderate bronchial asthma attacks, and in contrast to steroid treatment, BIS treatment do not suppress adrenocortical function.

Comparison of multipotency and molecular profile of MSCs between CKD and healthy rats.

We previously showed that mesenchymal stem cells (MSCs) can differentiate into a functional miniature kidney, suggesting that MSCs may be a cell source for kidney regeneration. However, MSCs from long-term dialysis patients, which have been exposed to uremic toxin, can exhibit reduced viability. Therefore, the aim of this study was to examine the gene expression profiles and differentiation capabilities of bone marrow- and adipose-derived MSCs from chronic kidney disease (CKD) model rats. CKD was induced in rats by adenine feeding, and then MSCs were isolated from bone marrow (BMSCs) and adipose tissue (ASCs). After confirming MSC surface marker expression, comprehensive gene expression profiles were obtained by RT-PCR array. MSCs were differentiated into adipocytes, osteoblasts, and chondrocytes, and histological and/or functional assays were performed. Tgfb3 expression was up-regulated, while Bmp6, Gdf15, Mmp2, and Vegfa were down-regulated in CKD-ASCs compared with Control-ASCs. There were no significant differences in the gene expression of stemness markers, and the morphology of cells that underwent adipogenesis, osteogenesis, and chondrogenesis, or GPDH activity between CKD and control groups. Comparing BMSCs with ASCs, gene expression of Bglap, Bmp4, Igf1, Itgax, Pparg, Ptprc, and Tnf were up-regulated, while Col1a1, Mmp2, Sox9, and Vegfa were down-regulated in both CKD and control groups. Uremic toxin in CKD rats had a small effect on the gene expression and differentiation of MSCs. However, long-term exposure to uremic toxin and the differences in gene expression of MSCs derived from bone marrow or adipose tissue may affect renal regeneration.

Utility of the peripheral blood basophil histamine release test in the diagnosis of hen's egg, cow's milk, and wheat allergy in children.

BACKGROUND: The diagnosis of food allergy (FA) is made by oral food challenge tests (OFCs) that occasionally produce serious symptoms in patients; therefore, whether to perform OFCs should be carefully considered. The utility of the histamine release test (HRT) in the diagnosis of childhood FA has not been fully examined. METHODS: Sixty-four subjects with suspected hen's egg allergy, cow's milk allergy (CMA), and wheat allergy (WA) were enrolled. The diagnosis of FA was made based on the outcomes of OFCs or a convincing history of symptoms after food ingestion within 6 months before or after sample collection. HRT was performed using an HRT Shionogi kit. The threshold of histamine release (HRT threshold), which was defined as the minimum concentration of food antigen to induce a 10% net histamine release, was analyzed in association with FA diagnosis. RESULTS: Receiver operating characteristic analysis showed that the HRT threshold was useful in the diagnosis of heated egg allergy (HEA), raw egg allergy (REA), CMA, and WA. We were able to determine the cutoff value for the HRT threshold in relation to outcomes of OFCs. The cutoff value was 6 ng/ml of egg white antigen in HEA and REA (p < 0.01), 40 ng/ml of milk antigen in CMA (p < 0.01), and 500 ng/ml of wheat antigen in WA (p < 0.05). The efficiency was 70.3% for HEA, 78.0% for REA, 77.6% for CMA, and 70.7% for WA. CONCLUSIONS: We conclude that the HRT threshold measurement for egg white, milk, and wheat antigen is related to outcomes of OFCs and is useful in determining when OFCs should be performed.

[Usefulness of skin prick test using bifurcated needle for the diagnosis of food allergy among infantile atopic dermatitis--second report. In the case of cow's milk allergy].

OBJECTIVE: We investigated the usefulness of skin prick test (SPT) using bifurcated needle (BN) for the diagnosis of cow's milk allergy (CMA) in early infancy. SUBJECTS AND METHODS: Among atopic dermatitis infants with suspicion of food allergy who visited Sagamihara National hospital from January 2001 to April in 2005, 168 cases had received both SPT and IgE ImmunoCAP of CM (CM-IgE) at first visit. We analyzed results of SPT and CM-IgE, focused on infants with negative CM-IgE to examine the usefulness of SPT, and checked positive conversion of CM-IgE with aging. RESULTS: Among 124 infants (73.8%) with negative CM-IgE, 34 infants (27.4%) showed positive SPT results. Forty two infants (33.6%) among the 124 cases were diagnosed as CMA by combination of elimination and provocation test, and 21 infants (50.0%) had positive SPT. In the follow up study of 39 negative CM-IgE cases with CMA, 21 CM-IgE (53.8%) turned positive later infantile period (mean CM-IgE: 4.2+/-4.8 Ua/ml at 9.3+/-5.3 months old). CONCLUSIONS: SPT using BN seemed to be more useful than CM-IgE for the diagnosis of CMA in early infancy with AD. But, the sensitivity is lower than in the egg case.

Basophil activation marker CD203c is useful in the diagnosis of hen's egg and cow's milk allergies in children.

BACKGROUND: The diagnosis of food allergy (FA) is usually based on oral food challenge tests (OFC). However, OFCs occasionally induce severe adverse reactions. CD203c expression on basophils is emerging as a potential diagnostic index. We evaluated whether CD203c expression on basophils would be a useful marker of OFC-associated symptoms in hen's egg and cow's milk allergies in children. METHODS: Seventy-one patients who had been diagnosed with FA based on OFCs or a convincing history of FA symptoms in the Department of Pediatrics, Sagamihara National Hospital, were recruited. CD203c expression was assessed after stimulation with antigens (egg white, ovomucoid, milk or casein) using allergenicity kits. The CD203c stimulation index (SI = the allergen-induced CD203c expression level divided by the baseline expression level) and the threshold of CD203c expression (the minimum concentration of antigen to induce CD203c SI >or=2) were analyzed in association with tolerance acquisition. RESULTS: For the CD203c SI, the areas under the receiver-operating characteristic curve were 0.72 for egg white, 0.82 for ovomucoid, 0.84 for milk and 0.67 for casein. The positive predictive value for the threshold of CD203c expression was 94.7% for egg white, 100% for ovomucoid, 85.7% for milk and 75.0% for casein. CONCLUSIONS: Assessment of food antigen-induced CD203c expression on basophils is useful to determine if children will outgrow FA as well as in decision making regarding whether or not to perform OFCs.

[Single blind food challenge using dried food powder --2nd Report. milk].

AIM: We analyzed data obtained from cow's milk challenge with single-blind manner in our department. SUBJECTS AND METHODS: We have performed 83 cow's milk challenges in the hospital from 1995 to 2005, and patient profiles and results of the challenges were analyzed. RESULTS: Positive rate of cow's milk challenges were 44.6% (37/83), and evoked symptoms by cow's milk challenges were most frequently seen in skin, followed by respiratory tract, and gastrointestinal system. Cases of anaphylaxis were seen in 8.1%. Seventy six percentages of symptoms started within one hour after the challenge, and 56.8% among positive cases were medicated. Adrenaline was injected in 9 cases out of 37 positive challenge cases. And all anaphylaxis patients recovered. We performed 19 open challenges with heated-cow's milk among 37 positive cases, and only one negative case existed. When we compared profiles of negative cow's milk challenges and positive ones, significant higher rate on positive skin prick tests (SPT) against cow's milk and complication of bronchial asthma were recognized in positive group. Sensitivity of SPT was 97.3% and specificity was 17.4%. Sensitivity of IgE CAP-RAST was 100% and specificity was 15.2%. CONCLUSIONS: Single-blinded challenge tests were safe. And they were useful in judgment of the acquisition of oral tolerance in cow's milk allergy. It was only one case that effect of the heating un-matched in food provocation test results. Although we experienced fairly high prevalence of respiratory symptoms during cow's milk challenge tests, appropriate medication especially adrenaline introduction made our test safe enough.

[Single blind food challenge using dried food powder--1st report. Raw whole egg and egg yolk].

AIM: We have analyzed data of raw whole egg and egg yolk challenges performed in single-blinded manner. SUBJECTS AND METHODS: We have performed 92 whole egg challenges and 109 egg yolk challenges in admission from 1995 to 2005. RESULTS: The positive rate of whole egg challenges was 76.1%, and the most frequent symptoms seen during challenges involved gastrointestinal (GI) system, followed by skin, and respiratory system. The rate of anaphylaxis was 4.3%. Among 70 raw-egg positive cases, 62 heated-egg challenges were performed in open manner, which resulted in 18 negative cases (29%) against it. When we compared IgE CAP RAST against egg white between challenge positive cases and negative ones, IgE CAP RAST against egg white was significantly higher in positive group. With regards to yolk egg challenges, positive rate was 23.9%, and evoked symptoms were most frequently seen in skin, followed by GI system, and respiratory system. No case of anaphylaxis was observed. CONCLUSIONS: Single-blinded challenge tests against whole egg and egg yolk were useful for the diagnosis of pediatric egg allergy. IgE CAP RAST against egg white was useful when we considered timing of egg challenge tests. Among raw egg allergies, around 30% of patients could eat heated-whole egg. In order to improve egg allergy patients' quality of life, it is important to first introduce egg yolk challenges followed by heated-whole egg challenges, and finally raw-egg challenges, if it is necessary, in blinded manner.

[Prolonged type of food allergy].

OBJECT: Prevalence of food allergy is the most frequent during infancy, and it is gradually decreasing with age. We can not distinguish patients developing tolerance from those with persistent food allergy, therefore we are unable to advice patients accelerating the development of tolerance. To clarify the factors developing tolerance or intolerance, we conducted the following study. METHOD: Patients who were diagnosed as food allergy to hen's egg, or cow's milk or wheat in infancy by the definitive history of positive food allergic reactions or food provocation tests were recruited to this study. Patients were divided into two groups; one (prolonged group, n=27) is those who needed to eliminate some of the main offending foods even at the age of 6 years old and the other (tolerized group, n=37) is those who had released all main offending foods by the age of 6 years old. RESULT: The factors which distinguished the prolonged group from the tolerized group were the positive clinical history of the atopic dermatitis and its prolonged clinical course, past history of anaphylactic shock, and maximum number of offending foods in the past clinical history. The specific IgE against main antigens such as egg white, cow's milk and wheat in the tolerized group was lower compared to that in the prolonged group, whereas no significant difference was found in non specific IgE value, peripheral eosinophil counts, and specific IgE against other antigens. CONCLUSION: We could find the clinical factors discriminating food allergy patients against three major food allergen among children developing tolerance by the age of 6 years old form those without tolerance.

[The prognosis of asthmatic children with status asthmatics in early childhood].

To clarify the prognosis of asthmatic children with status asthmatics in early childhood, we retrospectively investigated 113 patients (boys: 62, girls: 51) who had been treated as status asthmatics since 1995 through 2000 in National Sagamihara Hospital. In this study, the frequency of admission was decreased year by year, 62.8% (1st year), 29.2% (3rd year), and 5% (5th year). All patients were evaluated as severe or moderate patients during the 1st year from the episode of status asthmatics. Three years after the episode, 38% of patients were evaluated as severe or moderate patients. Five years later, only 20% of patients were evaluated as severe or moderate patients and 35% became free from treatment and asthma attack. Most of the patients were treated by DSCG inhalation and RTC therapy. Nine patients needed BDI therapy in addition to DSCG and RTC. With appropriate and careful treatment, the prognosis of the patients who had experienced status asthmatics in the early childhood was kept relatively well.