[Japanese guideline for treatment and management of childhood asthma and its originality].

Japanese guideline for treatment and management of childhood asthma was published in April, 2000. This is the Japan original guideline. The general and practical asthma treatment in Japan is described. We compared with this guideline and GINA. There is not a difference in the diagnosis and concept of bronchial asthma. This guideline for several Japan original therapies are described. The originality of this guideline is the early use of theophylline. There is not the entry of the use of oral steroid. There are many Japan original therapies such as the isoproterenol continuous inhalation therapy. Also, as for this guideline the education, vaccination and exercise of the patient are written in detail. We hope that this guideline is translated to English and be published.

Psychosocial factors and adherence to treatment advice in childhood atopic dermatitis.

Poor adherence to maintenance treatment for atopic dermatitis and anxiety about using topical steroids are common features seen among children with atopic dermatitis and their mothers. No systematic study exploring factors associated with adherence to treatment advice on atopic dermatitis has been carried out to date. This study seeks to generate hypotheses regarding the relationship between a range of psychosocial factors and adherence to treatment advice on atopic dermatitis. An anonymous self-completed questionnaire containing adherence items, psychosocial items, some demographic items, and attitudes to steroid use was given to 258 mothers of atopic dermatitis follow-up patients who attended the National Children's Hospital, Tokyo. Responses from 205 families (80%) with complete data were then analyzed to explore the correlation between each factor and to build a structure equation model. The strongest predictor of adherence to skin-care treatment was a good doctor-patient (mother) relationship, followed by the severity of the disease as perceived by the mother. Surprisingly, the mother's anxiety about using topical steroids had no significant influence on reported use of topical steroids nor on adherence to skin-care treatment. This may have been overcome by the well-established doctor-patient (mother) relationship. Maternal personality, husband's cooperation, and social support were indirectly correlated with adherence via the doctor-patient relationship. Maternal self-efficacy of treatment was strengthened by good doctor-patient (mother) relationship.

Inhibitory action of gemfibrozil on cholesterol absorption in rat intestine.

This study was designed to determine whether gemfibrozil inhibits intestinal lipid absorption. Male Sprague-Dawley rats received an oral dose of 30 mg gemfibrozil/kg body weight for 14 days. Mesenteric lymph cannulation was performed, and a lipid infusion containing 40 micromol/h (35.4 mg/h) of radiolabeled triolein and 2.74 micromol/h (1.06 mg/h) of radiolabeled cholesterol with the addition of 1 mg/h of gemfibrozil was infused intraduodenally at a rate of 3 ml/h for 8 h. The lymph was collected, and the radioactivity levels of the lumen and gut mucosa were measured after the infusion. Lymph cholesterol transport was depressed in gemfibrozil-treated rats, in terms of mass measurements as well as radioactivity in a lesser degree. More radioactive cholesterol remained in the proximal portion of the intestinal lumen and mucosa in the treated rats than in the control rats. More radioactive triglycerides also remained in the proximal intestinal lumen of treated rats, although no difference in lymphatic triglyceride transport was observed between the groups. A significant portion of the radioactive cholesterol remained in the lumen in the gemfibrozil-treated rats. Gemfibrozil increased biliary cholesterol excretion. Thus, this study shows that gemfibrozil inhibits cholesterol absorption in rat intestine.

Growth and endocrine function during school age in very low-birth weight infants.

BACKGROUND: Short stature and low bodyweight are commonly encountered problems in the clinical follow up of premature infants. However, details about the underlying pathophysiology are unknown in these cases. METHODS: Evaluations of growth and endocrine function were performed in 23 very low-birth weight (VLBW) infants between 11.3 and 14.3 years of age. RESULTS: The mean (+/-SD) scores for height and weight were -0.50+/-0.97 and -0.50+/-1.10 SD, respectively. Mean serum insulin-like growth factor (IGF)-I and urine growth hormone (GH) levels were 402+/-138 ng/mL and 18.0+/-17.5 pg/mg creatinine, respectively. Serum IGF-I and urine GH levels were within the normal range for all patients. The bone age values were consistent with the patient's true age. Physical signs of puberty were detected in 15 of 23 patients (65%). Using bone ages to predict final adult height yielded a score of -0.52+/-1.08 SD. CONCLUSIONS: Despite the almost normal results of serum IGF-I, urine GH levels and bone age, the physical growth of these VLBW infants was less than that of normal birth weight children, as was their predicted adult growth.

Adrenocortical function in patients with severe atopic dermatitis.

BACKGROUND: Adrenocortical suppression is a potential complication of the use of topical corticosteroids in patients with atopic dermatitis (AD). OBJECTIVES: To determine whether or not the adrenocortical suppression observed in patients with severe AD is a sole result of the application of topical steroids. METHODS: A total of 45 patients with severe AD that required hospitalization for treatment were enrolled. These patients were divided into two groups according to the treatment received before hospitalization: group 1 had not used topical corticosteroids for at least three months (n = 17), while group 2 had used topical corticosteroids daily (n = 28). Otherwise, these two groups were matched to clinical characteristics. A rapid ACTH test was performed upon hospital admission. Topical corticosteroids were then applied to both groups. The second ACTH test was performed just before discharge, an average of 23 days after the first test. RESULTS: The basal serum cortisol levels as well as the response to ACTH stimulation in the first examination were significantly lower in the AD patients than in the controls (P < .001), although there were no significant differences in the results between groups 1 and 2. The followup study of adrenocortical function at hospital discharge showed that morning basal serum cortisol levels were significantly increased in group 1 (P < .01), despite their topical corticosteroid treatment, while no significant increase or decrease was seen in group 2. CONCLUSION: Our findings suggest that the adrenocortical suppression seen in patients with AD may be caused by the percutaneous absorption of topical corticosteroids as well as by other factors related to the disease.

Beta-adrenergic agonists and bronchial hyperreactivity: role of beta2-adrenergic and tachykinin neurokinin-2 receptors.

BACKGROUND: beta(2)-Adrenergic agonists are the most widely used bronchodilators for the treatment of asthma. On the other hand, there is concern that excessive use of beta(2)-agonists may contribute to the exacerbation of asthma. However, the mechanism of such adverse effects of beta(2)-agonists is not completely clear. OBJECTIVE: The aim of this study was to assess the direct influence of beta(2)-agonists on airways by analyzing the effect of a beta(2)-agonist, fenoterol, on airway sensitivity in an animal model and on tachykinin neurokinin-2 receptor expression in bovine tracheal smooth muscle. METHODS: We performed an acetylcholine challenge test on ovalbumin sensitized guinea pigs that were exposed to daily inhalation of ovalbumin and fenoterol. We also investigated the effects of fenoterol on neurokinin-2 receptor messenger RNA and density with Northern blot analysis and receptor binding assay. RESULT: The increase of airway responsiveness and the decrease of beta(2)-adrenergic receptors were found in guinea pigs that were treated with fenoterol. There were time- and dose-dependent increases of neurokinin-2 receptor mRNA and of density in tracheal smooth muscle that was treated with fenoterol. CONCLUSION: This increased airway responsiveness, increased neurokinin-2 receptor expression, and decreased beta(2)-adrenergic receptor density may be relevant to asthma exacerbation.

[Analysis of the theophylline pharmacokinetics of sustained-release theophylline (Theodur) dry syrup in children].

Sustained-release theophylline (Theodur) drysyrup was administered to 23 children aged 3-8 years and its pharmacokinetics were analyzed. Blood was drawn 9 times during 24 hours for serum theophylline concentrations after reaching to the steady state. Results were as follows: (1) All of 9 serum theophylline concentrations were between 5-15 micrograms/ml among 20 children. (2) Serum theophylline concentrations were higher than 15 micrograms/ml in three children. Two of them showed decreased clearance and body weight of the other was significantly heavier than the average weight for her height. (3) VdTD and theophylline clearance each showed 0.77-0.88 L/kg and 0.070-0.091 L/kg/hr. (4) Tmax was 2.9-3.5 hours and T1/2 was 7.1-8.8 hours. (5) There were no significant differences in pharmacokinetics paramaters between each age group. Therefore, sustained-release theophylline (Theodur) drysyrup 16 mg/kg/day seems to be reasonable dose for 3-8 years but monitoring of serum theophylline concentrations is advisable if possible.

[Assessment of adrenal function on steroid using renal diseases in children using the modified original ACTH tolerance test: comparing nephrotic syndrome with non-nephrotic syndrome].

Steroid therapy occupies a very important position in various types of kidney diseases in children. The period of steroid therapy in kidney disease tends to extend over a long time and the amount of medication tends to be high. Inhibition of the adrenal function because of steroid therapy is one of the major side effects requiring considerable care. In the present investigation, we examined the inhibition of adrenal function in various pediatric renal diseases using synthetic ACTH. In this study, we checked the serum 11-OHCS and cortisol levels and found that in nephrotic syndrome, the inhibition already existed at sideration. In other diseases we found inhibition of adrenal function using steroid and improvement of the function on reduction of the steroid dose. Patients who used steroid every other day showed better improvement. Therefore, we suggest that in nephrotic syndrome, the inhibition of adrenal function may participate in sideration in the syndrome. It was also found that reduction of the steroid given every other day inhibited the adrenal function to a lesser extent. We found that our challenge test using ACTH is safe and very useful for determining adrenal function.

The effects of anti-asthma drugs on mediator release from cultured human mast cells.

BACKGROUND: A method for generating human mast cells in vitro was recently established. Little is known about the pharmacological profiles of allergic mediator release from cultured mast cells. OBJECTIVE: The main objective was to investigate the nature of cultured mast cells from a pharmacological point of view. We examined the effect of anti-asthma drugs on the release of histamine, sulfidoleukotrienes (LTs) and prostaglandin D2 (PGD2) from the cultured mast cells. METHODS: Using the method established by Saito et al. we cultured cord blood mononuclear cells in the presence of 80 ng/mL stem cell factor (SCF), 50 ng/mL interleukin-6 (IL-6) and 300 nmol/L prostaglandin E2 (PGE2), and obtained almost pure (> 99%) mast cells. We sensitized cultured mast cells with immunoglobulin E (IgE)-rich serum, and then treated them with some anti-asthma drugs before challenge with anti-human IgE. Released histamine, LTs and PGD2 were measured by high-performance liquid chromatography, commercial enzyme-linked immunosorbent assay (ELISA) and enzyme immunoassay (EIA) systems, respectively. RESULTS: The cultured mast cells released histamine, LTs and PGD2 following immunological stimulation through IgE. The mast cell stabilizing agents disodium cromoglycate (DSCG, 1 mmol/L) and azelastine (100 micromol/L) significantly inhibited the release of these three mediators. The beta-adrenoceptor agonists isoproterenol, salbutamol, and clenbuterol also inhibited all three mediators' release in a concentration-dependent manner. The non-selective and selective phosphodiesterase (PDE) inhibitors theophylline, rolipram, and cilostazol had no significant effect on mediator release at clinically useful concentrations. BAY x 1005 (a 5-lipoxygenase-activating protein inhibitor) inhibited the LTs release, whereas indomethacin (a cyclo-oxygenase I and II inhibitor) and NS-398 (a cyclo-oxygenase II inhibitor) inhibited PGD2 release. CONCLUSIONS: The present results indicate that cultured mast cells release histamine, LTs and PGD2 following IgE crosslinking. Anti-asthma drugs showed a characteristic suppression of the release of each mediator. The suppressive actions of these drugs are similar to their pharmacological actions on human lung mast cells. These results suggest that cultured mast cells are useful for the analysis of function and pharmacological profiles of lung mast cells.

[Safe administration of influenza vaccine in asthmatic children].

Thirty asthmatic children were examined allergic reaction against egg white, gelatin and vaccine solution before and after vaccination using skin prick test. We also measured the levels of specific IgE and IgG antibody against gelatin. The changes in clinical symptoms before and after vaccination were investigated in 25 asthmatic children by evaluating symptom and treatment score. The results were as follows; 1. In one subject who had delayed type of skin reaction to gelatin, the adverse reaction was also recognized at the skin site around 24 hrs after vaccination. In this subject, the levels of serum specific IgE and IgG to gelatin became positive after 5 months. 2. Specific IgE antibodies to gelatin were not detected in all subjects before and after vaccination. 3. The mean values of asthma symptom score before and after vaccination were 3.3 +/- 4.2 and 1.5 +/- 3.3 respectively. Those of treatment score before and after vaccination were 75.6 +/- 35.2 and 76.0 +/- 35.0 respectively. These results suggest that skin testing with gelatin and vaccine solution is useful as a screening method for predicting adverse reactions in asthmatic children and that influenza vaccination can be performed safely in skin test negative children.

Time course of changes in the intestinal permeability of food-sensitized rats after oral allergen challenge.

Rats were sensitized with ovalbumin (OVA) with a molecular weight of 45 kd, challenged with OVA orally, followed by orally administered beta-lactoglobulin (BLG) as an intestinal permeability marker. BLG is a macro-molecular protein with a molecular weight of 18 kd. Blood BLG concentrations were measured (by ELISA) serially over 4 hours following BLG administration, which in turn was given 1 hour after OVA challenges. The maximum BLG concentration was at 2 hours. BLG was then administered orally 1, 3, 6, 12 and 24 hours after oral OVA challenge, and the serum BLG concentration at 2 hours after BLG administration was compared among the five groups. BLG appeared in the circulation of the animals 1, 6 and 24 hours after allergen challenge, but not after 3 and 12 hours. The serum BLG concentration was not significantly different at 1, 6 and 24 hours. Histopathological examinations of the intestines showed mast cell infiltration of the intestinal mucosa at 1 hour, remarkable edema of villi at 3 hours, eosinophil infiltration at 6 hours, an increase of goblet cells at 12 hours and villous atrophy and lymphocyte infiltration at 24 hours. The appearance in the serum of three BLG peaks of comparable heights suggested that the intestinal absorption of BLG may be related to a late and delayed phase as well as the immediate IgE-dependent phase response.

MRI lesions masked by brain development: a case of infant-onset focal epilepsy.

A 3-month-old male presented with right-side-dominant focal seizures. Focal spikes were observed on the left side of an electroencephalogram obtained at the time of onset. The immature development in the left middle temporal lobe was observed by initial magnetic resonance imaging (MRI). The hypoperfusion in the left temporal lobe observed with single-photon computed tomography was consistent with MRI findings. These MRI findings were not observed in a second MRI at 11 months of age. This observation may explain one of the causes of infant-onset focal epilepsy.