Treatment of Kawasaki syndrome: a comparison of two dosage regimens of intravenously administered immune globulin. Effect of corticosteroids on intracranial pressure, computed tomographic findings, and clinical outcome in young children with tuberculous meningitis. Aspirin, hydroxychloroquine, and hepatic enzyme abnormalities with methotrexate in rheumatoid arthritis. Optimal dosage and differences in therapeutic efficacy of IGIV in Kawasaki disease. Successful dose-intensive treatment of desmoplastic small round cell tumor in three children. Intravenous gamma-globulin for Kawasaki disease. Corticosteroids in status asthmaticus. The safety of twice-daily treatment with fluticasone propionate and salmeterol in pediatric patients with persistent asthma. Pharmacokinetic study of mefloquine in Thai children aged 5-12 years suffering from uncomplicated falciparum malaria treated with MSP or MSP plus primaquine.
Because intravenously administered immune globulin (IVIG) is effective in reducing the incidence of coronary artery aneurysms in Kawasaki syndrome when given at a dose of 400 mg/kg daily for 4 days, we undertook a multicenter clinical trial comparing two dosage regimens of IVIG. Patients were randomly assigned to receive IVIG at either 400 mg/kg daily for 4 days (22 patients) or 1 gm/kg as a single dose (22 patients). All patients received aspirin therapy, and all were enrolled within 7 days of onset of fever. The presence of coronary artery aneurysms was evaluated by means of two-dimensional echocardiography before infusion; at days 4 to 6, 14 to 21, and 42 to 49 after infusion; and at 1 year. Coronary artery aneurysms were detected in 3 of the 44 patients, including one patient receiving 400 mg/kg and two patients receiving 1 gm/kg (p value not significant). No giant aneurysms were detected. No major side effects occurred with either dosage regimen. Patients receiving the 1 gm/kg dose had a faster resolution of fever and were discharged from the hospital approximately 1 day sooner than the 400 mg/kg group (p = 0.01). Although the relatively small sample size in this trial does not allow for a more definitive statement regarding the occurrence of coronary artery aneurysms, it appears that the 1 gm/kg dose is associated with a more rapid clinical improvement and a shorter hospital stay. To study the effect of highdose prednisone on intracranial pressure (ICP), cranial computed tomographic (CT) findings, and clinical outcome in young children with moderate to severe tuberculous meningitis (TBM).
                Prospective, controlled, randomized study.
                Continuous lumbar, cerebrospinal fluid pressure monitoring and contrasted CT scanning were performed in 141 consecutive children with TBM at admission. All children were then randomly allocated to a nonsteroid group (71 children) or a steroid group (70 children) who received prednisone (first 16 children, 2 mg/kg per day; next 54 children, 4 mg/kg per day) for the first month of treatment. ICP monitoring and CT scanning were repeated regularly, and clinical outcome was assessed after 6 months of antituberculosis treatment.
                No statistically significant difference in ICP or the degree of hydrocephalus (as demonstrated by CT scan) was found between the steroid and nonsteroid groups after the first month of treatment. Basal ganglia infarcts developed in 16% of children in the steroid group and 24% in the nonsteroid group during the first month of treatment. Neither this incidence nor the eventual size of infarcts present at admission differed significantly between the two treatment groups. Single or multiple tuberculomas were seen on the first CT scans of 7 children (5%), whereas tuberculomas developed in 11 children (8%) at treatment. Both the response of the tuberculomas to treatment and the incidence of new tuberculomas were significantly improved by steroid therapy. Basal enhancement was also significantly less in the steroid group after 1 month of treatment. Steroids lowered mortality in stage III TBM significantly. Similarly, more surviving children in the steroid group had IQs of greater than 75 than did the those in the nonsteroid group. No significant difference was found in the incidence of motor deficit, blindness, or deafness.
                Corticosteroids significantly improved the survival rate and intellectual outcome of children with TBM. Enhanced resolution of the basal exudate and tuberculomas by steroids was shown by serial CT scanning. Corticosteroids did not affect ICP or the incidence of basal ganglia infarction significantly. Levels of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) in patients with rheumatoid arthritis from 5 centers involved in the Arthritis, Rheumatism, and Aging Medical Information System were correlated with the use of specific antirheumatic medications. Elevated levels of SGOT and SGPT were most frequent in patients taking salicylates and methotrexate (MTX) and least frequent in patients taking hydroxychloroquine. The combination of MTX and salicylates greatly increased the frequency of abnormal liver enzyme values. In contrast, the addition of hydroxychloroquine to a regimen of either MTX or aspirin essentially eliminated the SGOT and SGPT abnormalities. Results from all 5 centers were consistent and remained so after adjustment for age, sex, and disease duration. Knowledge of these important drug interactions may permit continuation of MTX therapy in patients in whom the drug might otherwise be discontinued. In an initial study, three groups of patients with Kawasaki disease received either aspirin alone or alkylated immunoglobulin G intravenous preparation (IGIV) 200 mg/kg daily x 3 days + aspirin, or 400 mg/kg alkylated IGIV daily x 3 days + aspirin. In a second study, three groups of patients were treated with either 100, 200 or 400 mg/kg of native IGIV in combination with aspirin daily for 5 days. While the regimen of 200 mg/kg native IGIV daily x 5 days was found to be effective, the incidence of coronary artery lesions (CAL) was even less on a regimen of 400 mg/kg daily x 5 days. It is therefore suggested that a better therapeutic effect can be achieved with a 400 mg/kg dose of native IGIV. Based on the results from these two studies, it is assumed that native IGIV is more effective in inhibiting CAL formation and persistence than the chemically modified preparation in which the biological activity of the Fc region in the immunoglobulin G molecule is altered. Desmoplastic small round cell tumor (DSRCT) is a rare soft tissue tumor of primitive origin occurring primarily in children and young adults. Based on published reports in the literature, the response to conventional chemotherapy is poor. We report three pediatric patients successfully treated with dose-intensive, multimodal therapy. Between August 1994 and March 1998, we evaluated three consecutive patients with DSRCT at Children's Hospital and Regional Medical Center, Seattle, Washington. We established the diagnosis based on clinical presentation, radiologic staging, and pathologic review with immunohistochemical staining. All patients received a combined modality protocol including dose-intensive chemotherapy (two of them with peripheral blood stem cell [PBSC] support), second look surgery, and consolidative local irradiation. The patients remain in continuous remission at 66, 42, and 26 months after diagnosis, respectively. Two of our patients were younger than any previously reported patient, extending the age group for which DSRCT should be considered on diagnosis of small round cell tumors. The uniform survival achieved in our series indicates potential benefit for the combination of dose-intensive multiagent chemotherapy, local irradiation, and aggressive surgical approach in this disease. We studied the effect of gamma-globulin (IVGG) and aspirin (ASA) on the development of the coronary artery lesions (CAL) of Kawasaki disease (KD) in three different protocols. Within 29 days of the onset of KD the echocardiographic evidence of CAL had developed in 39-42% of the patients in the ASA group, but only in 13.7-20.8% of the patients treated with IVGG (200 or 400 mg/kg X 5). In long-term follow-up observation of CAL of these patients the evidence of CAL in both the ASA and the IVGG group regressed gradually; however, the residual rate of CAL was significantly low in the IVGG group at all times up to 24 months after onset. These facts suggest that when using IVGG for KD, we should select a dose of intact gamma-globulin, 1,000 mg/kg or more in total, to prevent the occurrence of CAL. We have demonstrated not only a significant reduction in the occurrence of CAL in patients treated with IVGG but a reduction in the residual rate of CAL for two years as compared with those treated by ASA. Nineteen children who were not steroid dependent and were hospitalized in status asthmaticus were studied to evaluate the effect of corticosteroids. They were randomized into two groups. Each group received salbutamol inhalations and intravenous aminophylline therapy. One group received 7 mg/kg hydrocortisone intravenously every six hours; the other group served as a control. Each group showed significant improvement in clinical score and peak expiratory flow rate after 36 hours; there was no statistical difference in the degree of improvement. Six of ten steroid-treated children and six of nine controls achieved a PEFR of 50% predicted by 36 hours. The response to inhaled salbutamol was similar in each group. The results show that in the first 36 hours of therapy, corticosteroids have no additive effect on the bronchodilator response of aminophylline and salbutamol and do not hasten the recovery of nonsteroid-dependent children in status asthmaticus. Although the results show that an inhaled sympathomimetic drug is beneficial in status asthmaticus, corticosteroid therapy does not increase the responsiveness of the airways to these agents. For children older than 5 years with asthma who remain symptomatic despite inhaled corticosteroid (ICS) therapy, the preferred treatment is to add an inhaled long-acting beta2-agonist vs increasing the ICS dose.
                To compare the safety of twice-daily treatment with inhaled fluticasone propionate plus the inhaled long-acting beta2-agonist salmeterol with that of fluticasone propionate used alone in children aged 4 to 11 years with persistent asthma.
                A randomized, multicenter, double-blind, active-controlled, parallel-group study in 203 children with persistent asthma who were symptomatic during ICS therapy. Patients received fluticasone propionate-salmeterol (100/50 microg) or fluticasone propionate (100 microg) alone twice daily for 12 weeks.
                The safety profile of fluticasone propionate-salmeterol was similar to that of fluticasone propionate alone. The overall incidence of adverse events was 59% for fluticasone propionate-salmeterol and 57% for fluticasone propionate. Both treatments were well tolerated. Two patients receiving fluticasone propionate-salmeterol and 5 receiving fluticasone propionate withdrew from the study because of worsening asthma. Changes in heart rate, blood pressure, and laboratory variables were infrequent and were similar between treatments. No patients had clinically significant abnormal electrocardiographic findings during treatment. Geometric mean 24-hour urinary cortisol excretion at baseline and after 12 weeks of treatment was comparable within and between groups; no patient in either group had abnormally low 24-hour urinary cortisol excretion after 12 weeks of treatment. The incidence of withdrawals due to asthma exacerbations was 2% in the fluticasone propionate-salmeterol group and 5% in the fluticasone propionate group.
                In pediatric patients with persistent asthma, fluticasone propionate-salmeterol twice daily was well tolerated, with a safety profile similar to that of fluticasone propionate used alone. A triple combination of mefloquine, sulfadoxine and pyrimethamine (MSP) was used with primaquine for the radical treatment of falciparum malaria in Thailand. Primaquine was reported to inhibit hepatic microsomal enzymes and drug metabolism in animal and man. 23 children hospitalized in the Hospital for Tropical Diseases, Faculty of Tropical Medicine, Bangkok, Thailand, were randomly allocated into two groups, group I received MSP equivalent to 20 mg base of mefloquine/kg body weight and group II received MSP plus primaquine (0.75 mg/kg). No statistical difference was noted for clinical response except the gametocyte clearance time was shorter in children given MSP plus primaquine (7 +/- 2.7 days) than the children given MSP alone (21.9 +/- 4.4 days) (P < 0.01). No serious side effects were recorded in this study. The plasma samples were obtained for kinetic calculations by HPLC in 18 children (11 in group I, 7 in group II). Mean Cmax was 7.4 +/- 5.2 h in group I and 6.6 +/- 7.0 h in group II. Mean t1/2, Cl/f and Vd/f were 9.8 +/- 1.6 days, 0.43 +/- 0.16 ml/min/kg and 8.84 +/- 4.21 l/kg in group I, 9.3 +/- 1.4 days, 0.41 +/- 0.12 ml/min/kg and 8.91 +/- 3.00 l/kg group II, respectively. The comparison of kinetic parameters in groups I and II revealed no significant difference (P > 0.05) suggesting no drug interaction. These kinetic values in children given MSP suspension were considerably different to those in adult patients with shorter tmax, t1/2 and MRT. The coadministration of MSP and primaquine in children would benefit by reducing the transmission of malaria in endemic areas.
Until good quality RCTs are carried out, there is insufficient evidence to indicate whether children with Kawasaki disease should continue to receive salicylate as part of their treatment regimen.