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To elucidate the mechanisms of intractable pediatric bronchial asthma and the indication of low-dose erythromycin (EM) therapy, the serum chemokine levels of and the angiogenic factor were evaluated in 55 pediatric patients with bronchial asthma; 7.4 +/- 3.5 yr old, who had been treated with inhaled steroid, leukotriene receptor antagonist, theophylline and others for more than a year. Both the levels of interleukin (IL) 8 (p = 0.036) and vascular endothelial growth factor (VEGF) (p = 0.005) were higher in patients with severe type than those of patients with the milder type, while other chemokine levels such as serum eotaxin and MCP1 did not show the correlation with the severity of bronchial asthma. Induction of therapy with low-dose EM induced improvement of the clinical symptoms in patients with severe type and decrease of their serum chemokine levels: IL8; from 736 +/- 88 to 75 +/- 85 pg/ml (p < 0.0005), and VEGF; from 352.0 +/- 160.5 to 132.2 +/- 59.9 pg/ml (p = 0.021) within the next 6 months. Moreover, low-dose EM resulted in a decreased daily peak-trough fluctuation rate of the serum theophylline concentration; (C(max )- C(min))/C(min), from 1.3 +/- 0.5 to 0.5 +/- 0.3, which led to the maintenance of effective serum levels. These results indicated that IL8 and VEGF affect the severity of standard therapies resistance intractable bronchial asthma. Through the suppression of these chemokines and maintenance of effective theophylline levels, low-dose EM therapy improves the symptoms of bronchial asthma.

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BACKGROUND: To elucidate the basic mechanism of theophylline-associated seizures (TAS), the clinical symptoms, electroencephalogram (EEG) and neuroradiological imaging of eight pediatric patients were all retrospectively evaluated. METHODS: Patients whose seizures represented their first episode were selected, while patients with cerebrospinal fluid abnormalities including pleocytosis and protein elevation, present illness of head trauma, epilepsy, febrile convulsion or any psychomotor retardation were excluded although they were given theophylline. RESULTS: Eight patients, 3.5 +/- 1.7 years of age, thus fulfilled the definition of TAS in the past 5 years. Based on their seizure patterns, EEG findings, brain single-photon emission computed tomography and head magnetic resonance imaging, a total of seven of eight patients had either localized or unilateral dominant lesions. They all had fever, > or =38 degrees C, and six of eight patients had a family history of febrile convulsions and/or idiopathic epilepsy. Thereafter none of them had convulsions after the cessation of theophylline administration. Through the TAS event, a 6-year-old female patient was found to have a right deep lateral cerebral venous angioma. CONCLUSION: In infants with idiopathic low seizure threshold and fever, theophylline administration might possibly trigger a seizure. Moreover, based on these patients' clinical findings, some kind of cerebral vascular involvements is speculated to be related with TAS.

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BACKGROUND: For the treatment of bronchial asthma, two types of fluticasone inhaler devices are available, namely, metered-dose inhaler with spacer (MDI-S) and the dry powder inhaler (DPI). The former is recommended for young children with a low peak inspiratory flow (PIF) and the latter for adolescents and adults. But the difference in the therapeutic efficacy between them has been studied only rarely in adolescent patients. METHODS: In the present study, 21 post-elementary school-age patients with moderate persistent bronchial asthma (age 8-15 years, 10.3 +/- 2.1 years), who all had a sufficient PIF of 114 +/- 29 L/min, were examined in order to compare the two types of fluticasone inhalers. Eleven of 21 patients inhaled 200 microg/day Flutide using the MDI-S twice daily for 1 month in the first month, and the same dose using the DPI for the next month. The other 10 patients inhaled the opposite regimens. At the end of the each treatment, spirometry was examined. RESULTS: Measurements done before therapy and then at the end of MDI-S and DPI therapy, respectively, were as follows: forced expiratory volume in 1 s (FEV(1.0)), 72.4 +/- 18.2%, 91.5 +/- 18.2% and 84.1 +/- 16.3% (MDI-S vs DPI, P > 0.040); maximal mid-expiratory flow (MMEF), 62.0 +/- 23.6%, 88.7 +/- 26.5%, 79.3 +/- 33.4% (P > 0.044) and the peak expiratory flow (PEF) was 73.9 +/- 25.0%, 95.6 +/- 32.8%, and 90.5 +/- 29.5%, respectively (n.s.). MDI-S was thus found to be more effective in terms of %FEV(1.0) and in %MMEF. CONCLUSIONS: High therapeutic efficacy was obtained with the use of the MDI-S in fluticasone inhalation for post-elementary school-age patients with sufficient inspiration ability.

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The spread of human immunodeficiency virus (HIV) infection has exploded over the past two decades and such infections in young people are no longer uncommon. However, the major infection route of pediatric patients remains vertical transmission, and sexual, especially homosexual transmission, is highly unusual. We herein describe the case of a 17-year-old boy who developed hemophagocytic lymphohistiocytosis (HLH). Although HLH was remitted soon with dexamethasone therapy, an HIV infection caused by homosexual transmission was detected.

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BACKGROUND: The central nervous system (CNS) inflammation of Kawasaki disease (KD) has not been sufficiently evaluated in spite of the complications of irritability and CSF pleocytosis. PATIENTS AND METHODS: Cerebrospinal fluid (CSF) and serum inflammatory cytokine values were simultaneously examined in 10 patients (2.6 +/- 2.1 year of age) during the acute phase. They were all irritable and demonstrated mild consciousness disturbance. RESULTS: The CSF IL6 was elevated (>3.0 pg/mL) in 6 patients, and 4 of them showed higher CSF than serum values. The CSF sTNFR1 was elevated (>0.5 microg/mL) in 6 patients, and 1 showed higher CSF than serum values. These CSF cytokine (IL6; 81.4 +/- 192.8 pg/mL, sTNFR1; 1.1 +/- 0.8 microg/mL) and CSF/serum ratio (IL6; 2.8 +/- 5.2, sTNFR1 0.4 +/- 0.4) in patients with KD were the same as those of patients with acute encephalitis/acute encephalopathy. CONCLUSIONS: The differences in the inflammatory cytokine value between CSF and serum suggest that the degree of systemic vasculitis is different between CSF and the circulating blood, and some patients with KD showed a higher degree of CSF inflammation.

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The negative co-stimulatory receptor, programmed cell death 1 (PD-1), is induced on activated T cells and delivers inhibitory signals upon engagement with its ligands PD-L1 and PD-L2, which are expressed on various somatic cells and certain cancers. Accumulating evidence suggests that interfering with the PD-1-PD-L1 interaction may result in the restoration of defective T cell functions in cancer and chronic viral infection. Herein, we established procedures to produce large amounts of renatured recombinant extracellular domain proteins of mouse PD-1 (mPD-1) and PD-L1. While monomeric mPD-1 and mouse PD-L1 (mPD-L1) only marginally interacted with the cells expressing their counterpart proteins, their tetramerization markedly enhanced the affinity with the K(d) of mPD-L1 tetramer being nearly 100-fold lower than that of the corresponding monomer. The affinity of mPD-L1 tetramer was even higher than a high-affinity anti-PD-1 mAb, and it efficiently inhibited the binding of mPD-L1/Fc-chimeric protein to mPD-1(+) cells. Functionally, mPD-L1 tetramer significantly enhanced the proliferative responses as well as the cytotoxic activity of T cells against specific target cells in vitro. The results suggest that oligomeric PD-L1 extracellular domains may provide a potential means to restore T cell functions in cancer and viral infection in humans.

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