The pharmacokinetics of theophylline were studied in 11 asthmatic children (7.6 ± 0.6 years old). Each received multiple oral doses of aminophylline in tablet form, in amounts ranging from 2.35 to 4.65 mg/kg. Plasma theophylline concentrations were determined using substrate-labeled fluorescent immunoassay. The data were analyzed by applying a one-compartment open-system kinetic model using the NONLIN program. The apparent volume of distribution and plasma theophylline clearance were 0.446 ± 0.041 L/kg and 48.96 ± 2.87ml/hr/kg, respectively. Using kinetic parameters derived from the multiple administration, the mean oral absorption rate constant was calculated to be 1.529 ± 0.232 hr^-1 and the mean elimination rate constant was calculated to be 0.116 ± 0.009 hr^-1 with an elimination half-life of 6.27 ± 0.42 hr. During multiple drug therapy, the mean theophylline concentration was observed to be greater than 8μg/ml, and there was a statistically significant correlation (r=0.674, p<0.05) between the value of dosage (mg/kg/day) and the steady state plasma concentrations of theophylline. The dose schedule for children in this study required to maintain plasma concentration in the range 8-20μg/ml was shown to be from 4.1 to 7.2mg/kg/dose every 8 hours in ten of the eleven patients. These pharmacokinetic data may assist in the clinical use of theophylline for asthmatic children.

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Of 375 children with nasal allergy diagnosed in our clinic from 1973 to 1979, 179(47.7%)were available for long term follow-up. The peak of onset of symptoms in nasal allergic children was at between 5 and 6 years of age, and the peak of remmision in the same group occurred between the ages of 12 and 15 years. The peak of remmision occurred during the same period for children with and without asthma. Out of 48 untreated patients, 30(58.3%) were completely or almost completely free from nasal symptoms. However, the rate of remmision was significantly higher in nasal allergic children with hyposensitization immunotherapy than in the untreated children or among adults with nasal allergy, with and without immunotherapy. Out of 20 untreated children, 10(50.0%) had developed new nasal allergy to new allergens. This was significantly higher than that in the treated children. Our follow-up study showed that nasal allergy had been resolved in 58.3% of the untreated children. It revealed, moreover, that hyposensitization immunotherapy in childhood had been effective treatment of nasal allergy and that it might be able to prevent the development of new nasal allergy.

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Thirty-four school children institutionalized with asthma in Saitama Convalescent Hospital performed the treadmill test before and after 6 months of swimming training to assess the effect of the physical training. The patients were divided into two groups: 21 children (group A) experienced better progress and the other 13 (group B) poorer after the training period. There was no significant difference in pulse rate before and after treadmill test in the two groups pre- or post-training. The improvement of the pattern of Wright peak expiratory flow rate (WPFR) was found in 16 children in group A and 4 in group B, and the differences was statistically significant. Although no differences were found in the pulmonary function test results of the two groups before training, FVC, FEV_1.0, PEFR, MMF, V_25/PEFR and V_25/Height were significantly lower in group B after training. The study demonstrates a beneficial effect of training on exercise-induced bronchospasm and indicates that the pattern of WPFR after treadmill test may predict the future course of the disease in institutionalized asthmatic children.

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When human peripheral blood mononuclear cells were stimulated with pokeweed mitogen (PWM) in the presence of glycyrrhizin, polyclonal antibody production was significantly enhanced compared with the case in which mononuclear cells were stimulated with PWM alone. These increases in antibody formation were attributed at least partially to the activation of monocytes, because the culture supernatant form glycyrrhizin-treated monocytes caused an enhancement of PWM-induced antibody response. By gel filtration using a Sephadex G-75 column, the active material contained in the culture supernatant of glycyrrhizin-treated monocytes was presumed to be interleukin-1, because the molecular size was similar to that of interleukin-1 and the fractionated substance caused an increase in DNA synthesis of PHA-stimulated thymocytes. Although these results suggest that glycyrrhizin may have an enhancing effect on antibody response and that this may be due at least partially to monocytes activation, further careful studies are undoubtedly necessary to confirm whether this substance exerts a similar effect on antibody response in vivo.

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To clarify what values of peripheral blood mononuclear cell subpopulations in healthy neonates, infants, young children and school children are normal, surface T cell, B cell and macrophage/monocyte antigen was measured by fluorescence-activated cell sorter using monoclonal antibodies. The results were as follows: 1. Percent Leu 4 positive cells (pan T cells) in cord blood of neonates was significantly lower than that in infants and children, and reached as high as the adult mean values at the infant period. Percent Leu 2 positive cells (suppressor/cytotoxic T cells) gradually increased with age and reached as high as the adult mean values at the young children. Percent Leu 3 positive cells (helper/inducer T cells) in infants was significantly higher than adult mean values. Percent Leu 7 positive cells (natural killer/killer cells) gradually increased with age. 2. Percent Leu 10 positive cells (B cells/macrophages) did not differ remarkably among the groups. 3. Percent Leu M3 positive cells (macrophages/monocytes) was significantly high in cord blood of neonates. However, percent Leu M3 positive cells was low in infants and increased with age. 4. Percent HLA-DR positive cells was lower in cord blood of neonates and adults than in the other groups. These results suggest that the values of the peripheral blood mononuclear cell subpopulations are an indication of the maturity of the immune system in childhood and may be useful in understanding the pathogenesis of allergic and immunologic disorders.

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Prevalence of Hymenoptera hypersensitivity was studied through questionnaires distributed by public health-workers in 6 towns in Tochigi prefecture, which have a combined population of 88202. Epidemiological and immunological analyses were performed on some of the hypersensitive patients. The results were as follows: 1) Questionnaires delivered by 1000 public health-workers revealed 101 individuals who had been hypersensitive to Hymenoptera stings. In addition, a survey by direct telephone call to 200 families, who had not returned the questionnaire, revealed only one hypersensitive patient. A survey conducted in some of the nursey schools, primary schools and junior and senior high schools, revealed that there were 21 hypersensitive individuals. 2) Incidence of hypersensitivity in the general population was estimated to be 0.36%. 3) Incidence of hypersensitivity in school boys and girls was 0.8%. However, in the 40- to 69-year-old age bracket, including patients with severe generalized reaction, results showed and incidence of 0.07%. 4) Hypersensitivity symptoms were classified into four types; local reaction, silight generalized reaction, severe generalized reaction and severe local reaction. Each of these symptoms in the hypersensitive patients was observed at 57%, 32%, 5% and 5%, respectively. 5) Wasp species and yellow jacket species were found to be the cause of Hymenoptera hypersensitivity in 73.3% and 11.8% of the patients, respectively. 6) Incidence of hypersensitivity in forestry workers was 7.26%. 7) Scratch tests using venom antigens at a concentration of 1000 μg/ml were carried out on 29 hypersensitive patients. All except one patient showed a positive reaction to at least one of the antigens. Sera of 14 patients who showed positive reaction on scratch tests, showed a positive RAST to more than one antigen. However, none of the 8 control subjects who had not had a history of anaphylaxis after Hymenoptera stings, showed a positive reaction to both scratch tests and RAST using venom antigens. 8) A positive reaction was shown in only 20% to 30% of the patients on both scratch tests and RAST using whole body antigens, suggesting that whole body antigens are not useful in the diagnosis of Hymenoptera hypersensitive patients. 9) Twenty percent of the hypersensitive patients were found to be suffering from atopic diseases and their average serum IgE level was 268.8IU/ml, which was higher than in normal subjects. A high level of serum IgE seems to be a risk-factor in the development of hypersensitivity of Hymenoptera stings.

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For the purpose of elucidating on mechanisms of effectiveness of hyposensitization therapy in patients with sea-squirt asthma, in vitro histamine release tests were performed using three types of sea-squirt antigen; the crude antigen and two purified antigens of EiM and Gi-rep. The following results were obtained from this study: The percent histamine release caused by various ses-squirt antigens was singificantly lower in patients who had been receiving hyposensitization therapy than those with treatment. In addition, the percent histamine release in the treated group did not deffer in and out of oyster-shucking season. As compared to the pretreatment levels, the percent histamine release by each sea-squirt antigen significantry were found to have been lowerd 5-8 months after hyposensitization therapy. Whole blood histamine levels were significantly higher in patients who had been treated with prolonged hyposensitization therapy than those in normal subjects and in patients who had undergone no such a therapy. However, no differences were observed in values before and after treatment in patients who had been treated with shout-term hyposensitization therapy (2 years or less). These results suggest that the suppression of histamine release may explain in part the mechanisms of effectiveness of specific hyposensitization therapy in sea-squirt asthma.

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