One Hundred Cases of HLA-matched Sibling Allogeneic bone Marrow Transplantation in Children: Single Center Study

PURPOSE: We reviewed 100 cases of HLA-matched sibling allogeneic bone marrow transplantation(allo-BMT) in children and wish to share these results. MEHTODS: One hundred children had undergone allo-BMT from HLA-identical siblings between Nov. 1983 and May 1998. There were 50 males and 50 females with a median age of 10 years and a median follow-up of 38 months. Out of 100 cases, 43 children were transplanted for severe aplastic anemia (SAA), 29 for acute myelogenous leukemia (AML), 18 for acute lymphocytic leukemia (ALL), 8 for chronic myelogenous leukemia (CML) and 2 for hemophagocytic lympho-histiocytosis (HLH). RESULTS: SAA : The 5-year event free survival (EFS) of SAA was 91%. The types of events that occurred were 3 thrombotic thrombocytopenic purpura (TTP), 2 venoocclusive disease (VOD) and 1 rejection. AML : In 25 of 29 cases, the 4-year EFS after allogeneic BMT in first remission was 71%. That of the TBI-based and Busulfan-based group was 44% and 77%, respectively. The most favorable results were observed in the Busulfan-based group in first remission with an EFS of 81% (n=18). The types of events that occurred were 4 TTP, 3 VOD, 2 rejections and 1 relapse. ALL : Five-year EFS of children with complete remission (CR; n=14, 7 CR1, 7 CR2) was 81%. CML : For the 6 children who received transplants while in the first chronic phase, the event free survival was 67%. HLH : Both of the two children with HLH survived 9 months and 24 months after BMT, respectively. Acute GVHD (> or =Grade ll) was observed in 13 children. Chronic GVHD developed in 10 children; 8 cases were localized and 2 were extensive type. CONCLUSION: Allo-BMT can cure children with refractory stem cell disorders. The most important factor that influences survival after transplantation is interval between diagnosis and transplantation for patients with severe aplastic anemia and remission state at transplantation for patients with leu-

One Hundred Cases of HLA-matched Sibling Allogeneic bone Marrow Transplantation in Children: Single Center Study

PURPOSE: We reviewed 100 cases of HLA-matched sibling allogeneic bone marrow transplantation(allo-BMT) in children and wish to share these results. MEHTODS: One hundred children had undergone allo-BMT from HLA-identical siblings between Nov. 1983 and May 1998. There were 50 males and 50 females with a median age of 10 years and a median follow-up of 38 months. Out of 100 cases, 43 children were transplanted for severe aplastic anemia (SAA), 29 for acute myelogenous leukemia (AML), 18 for acute lymphocytic leukemia (ALL), 8 for chronic myelogenous leukemia (CML) and 2 for hemophagocytic lympho-histiocytosis (HLH). RESULTS: SAA : The 5-year event free survival (EFS) of SAA was 91%. The types of events that occurred were 3 thrombotic thrombocytopenic purpura (TTP), 2 venoocclusive disease (VOD) and 1 rejection. AML : In 25 of 29 cases, the 4-year EFS after allogeneic BMT in first remission was 71%. That of the TBI-based and Busulfan-based group was 44% and 77%, respectively. The most favorable results were observed in the Busulfan-based group in first remission with an EFS of 81% (n=18). The types of events that occurred were 4 TTP, 3 VOD, 2 rejections and 1 relapse. ALL : Five-year EFS of children with complete remission (CR; n=14, 7 CR1, 7 CR2) was 81%. CML : For the 6 children who received transplants while in the first chronic phase, the event free survival was 67%. HLH : Both of the two children with HLH survived 9 months and 24 months after BMT, respectively. Acute GVHD (> or =Grade ll) was observed in 13 children. Chronic GVHD developed in 10 children; 8 cases were localized and 2 were extensive type. CONCLUSION: Allo-BMT can cure children with refractory stem cell disorders. The most important factor that influences survival after transplantation is interval between diagnosis and transplantation for patients with severe aplastic anemia and remission state at transplantation for patients with leu-

Clinical Trends in Acute Rheumatic Fever in Korean Children: Mailed Questionnaire Survey from 1988 to 1997(Compared with 1978-1987)

PURPOSE: The purpose of this study was to assess the frequency of acute rheumatic fever(ARF) among children in Korea and to describe trends in its clinical characteristics compared to data from a previous study(1978-1987). METHODS: A mailed questionnaire survey sent to the pediatric departments of 13 general hospitals in Korea requested the total number of patients with ARF and its clinical manifestations from Jan. 1988 to Dec. 1997. These data were compared with the data from a previous study (1978-1987) to evaluate the clinical trends in occurrence and clinical manifestations of ARF during the last 20 years in Korea. RESULTS: The average number of patients with ARF for the 10-year period(1988-1997) was 0.74 per 1,000 annual pediatric inward patients. There was a significant decrease in incidence during the study period. There were 115 male and 85 female patients with ARF, and 97.5% of total patients were 6 to 15 years old. 126 out of 200 patients(63.0%) had a history of preceding upper respiratory infection(URI). The percentage of major manifestations were as follows; carditis(66.5%),polyarthritis(54.0%), erythema marginatum(12.0%), chorea(7.5%) and subcutaneous nodule (6.0%). Clinical findings of carditiswere cardiac murmur(91.0%), cardiomegaly in chest PA(34.6%), congestive heart failure(15.8%). The electrocardiographic findings were PR interval prolongation (37.6%), right ventricular hypertrophy (RVH) and left ventricular hypertrophy(LVH)(15.8%), QT interval prolongation(13.5%). Doppler echocardiographic valvular lesions were mitral insufficiency(96.2 %), aortic insufficiency(39.8%). Minor and other clinical manifestations were fever(69.0%), arthralgia (56.5%), sore throat(28.5%). CONCLUSION: There was a steady decrease in the number of patients with ARF during the study period from 1988 to 1997. A sudden decrease in number of patients with ARF between the two study periods is likely due to patients with valvular heart disease, possibility of double registration, and wide spread use of echocardiography for accurate diagnosis.

Epidemiologic Study of Kawasaki Disease in Korea, 1994-1996: Comparison of Previous Study in 1991-1993

PURPOSE: To determine the epidemiology and rate of cardiac sequelae of Kawasaki disease in Korea. METHODS: On behalf of the Korean Pediatric Cardiology Society, we sent a questionnaire to 107 training hospitals two times; first period(Jan. 94-Sep. 95) and second period(Oct. 95-Dec. 96), and summarized the data of the survey from 58 hospitals which responded. RESULTS: The total number of patients was 2,680 cases, with male to female ratio and mean age 1.6 and 28.9+/-20.0 months, respectively. The total number of cases of 19 hospitals which participated in the first and second periods was 1,045, including 354 in 1994, 315 in 1995, and 376 in 1996, which showed no difference in annual incidence and higher incidence in Jan., May, June and July. The proportions of sibling cases was 0.26%(7/2,680) and rate of recurrent cases was 1.7% (46/2,680), and the proportion of patients with Kawasaki disease among total hospitalized pediatric patients was 1.13% in average, showing no significant difference according to regions. Echocardiogram was done in 93.5% of patients(2,507/2,680), and coronary abnormalities occurred in 20.1% of cases (505/2,507) including 16.8% of dilatations and 5.4% of aneurysms. CONCLUSION: Compared with a previous study in 1991-1993, this data showed somewhat increased mean age, increased recurrence rate and decreased incidence of coronary arterial abnormalities statistically. Studies like this needs to be continued in the future to determine the epidemiologic trends of Kawasaki disease in Korea.

Two Cases of Glaucoma Developed during Induction Chemotherapy Including Steroid in Childhood Acute Lymphoblastic Leukemia / 대한소아혈액종양학회지

The purpose of the study is to minimize the incidence of glaucoma and ocular hypertension caused by using corticosteroids during induction chemotherapy for acute lymphoblastic leukemia in children. We have periodically observed the intraocular pressure and the variation of C / D ratio of two 7 years old boys with chemotherapy in our pediatric department. We observed the increase in intraocular pressure using applanation tonometer, and we managed by beta- blockers, carbonic anhydrase inhibitor and etc. Increased intraocular pressure has been normalized after chemotherapy. The frequency of occurrence of the ocular hypertension and glaucoma can be controlled with the quantity of corticosteroids used.

The Effect of Allergen-Specific Immunotherapy on IL-10 and IL-13 mRNA Expression in Peripheral Blood Mononuclear Cells from Patients with Atopic Asthma / 소아알레르기및호흡기학회지

PURPOSE: Allergen-specific immunotherapy (IT) has been shown to be effective in the treatment for allergic diseases. But the immunologic mechanism of IT effect has not been fully elucidated. We studied house dust mite (HDM)-specific cytokine mRNA expression in peripheral blood mononuclear cells (PBMC) from patient with HDM- sensitive asthma and determined whether alterations in cytokine mRNA expression correlated with the clinical outcome of IT. METHODS: PBMC were obtained from 64 children with mite-sensitive asthma : 25 had never received HDM-IT (NIT), 39 had been receiving HDM-IT for more than 12 months. The 39 patients were divided into two groups according to the clinical response based on the asthma scores (symptom and medication scores) before and after IT. Good responders were those patients who showed an improvement greater than 50%, whereas poor responders were those who showed an improvement less than 50%. After a 18 hr culture with HDM, cytokine mRNA expression was analysed by RT-PCR and densitometry. RESULTS: 1) IL-10 mRNA expression in NIT was significantly lower than that in the normal controls and was significantly increased by IT. IL-10 mRNA expression in the good responders was significantly higher than that in the poor responders and NIT. 2) Little or no IL-13 mRNA were detected in the good responders and the normal controls. IL-13 mRNA expression in the good responders was significantly lower than that in the poor responders and NIT. 3) IFN-gamma mRNA expression in NIT was significantly lower than that in the normal controls and was significantly increased with IT. IFN-gamma mRNA expression in the good responders was significantly higher than that in the poor responders and NIT. 4) Little IL-4 mRNA were detected in the good responders and the normal controls. IL-4 mRNA expression in the good responders was significantly lower than that in the poor responders and NIT. CONCLUSION: These results show that IT not only induces a shift in cytokine expression from TH2 (IL-4 and IL-13) to TH1 cytokines (IFN-gamma), but also leads to induction of the antiinflammatory cytokine IL-10. These changes in cytokine expression may be responsible for clinical effects by immunotherapy.

Congenital Asymptomatic Cytomegalovirus Infection: A Comparison of Specific IgM Antibody Test and pp65 Antigenemia Assay

PURPOSE: It is increasingly important to diagnosis asymptomatic infections which make up a majority (90%) of congenital cytomegalovirus (CMV) infections and that they may have sequeles such as sensorineural hearing loss and mental retardation. Recently antigenemia assay has been developed by using monoclonal antibodies against early structural protein pp65 of CMV. This CMV antigenemia assay seems to be more quicker to diagnosis than conventional viral culture or other tests. In this study, we evaluated the CMV antigenemia assay in neonatal congenital asymptomatic CMV infections comparing it to the CMV specific IgM test that uses enzyme immunoassay. METHODS: From October 1995 to May 1996, 231 normal term newborns delivered with asymptomatic in St. Holy Hospital of Catholic University were included. The CMV antigenemia assay was performed with CMV-vueTM Kit by immunocytochemical staining and the CMV specific IgM test was performed with Enzygnost Anti-CMV/IgM by using an enzyme immunoassay. RESULTS: Three cases (male 2, female 1) were CMV pp65 antigenemia assay positive, but none of them were CMV specific IgM antibody test positive. The CMV pp65 antigenemia assay was more sensitive than CMV specific IgM antibody test for detection of congenital asymptomatic CMV infections by 1.3% and 0%, respectively. CONCLUSION: According to previous results, we suggest that the rate of congenital CMV infections using only CMV specific IgM tests have been underestimated. We recommend the CMV antigenemia assay as the preferred method for more rapid and accurate diagnosis of CMV infections. And congenital asymptomatic CMV infections should be diagnosed and followed up because of possible future sequeles.

Reccurent Unilateral Lung Collapse in an Asthmatic Child

Abnomalities in the production and transport of airway secretions play an important role in the pathophysiology of asthma. Segmental atelectasis as a complication of asthma, is relatively common in children. On the other hand, massive atelectasis such as the collapse of one lung is a very rare occurence. We report a seven-year-old male asthmatic patient with right lung collapse caused by mucoid impaction. Fourteen months before admission, the patient experiened bronchopneumonia with left unilateral lung collapse due to mucus plugging and recovered by bronchoscopic removal. The clinical findings, chest X-ray and chest CT suggested the collapse of the right lung was caused by mucus plugging. Fiberoptic bronchoscopy revealed the obstruction of the right main bronchus due to thick mucoid impaction. The histologic finding of mucoid material removed by brochoscopy showed only eosinophil clusters. In addition to fibroptic broncoscopic removal of mucoid secretions, hydration, chest physiotherapy, brochodilators and steroids, the patient received tracheostomy because of difficulty in sputum expectoration, poor improvement of clinical symptoms and chest X-ray findings, with rapid improvements. This case showed that early aspiration of bronchial mucoid secretions by bronchoscopy and tracheostomy was very critical, without waiting for a further deterioration of respiratory function.

Antineutrophil Cytoplasmic Antibody in Kawasaki Disease

PURPOSE: Antineutrophil cytoplasmic antibody (ANCA) has been identified in various disorders including Wegener's granulomatosis, microscopic polyarteritis and Kawasaki disease. Measuring this antibody has a diagnostic role. It facilitates monitoring disease activity and may also help understand the pathogenesis of the diseases in which it is found. We investigated the correlation between the hematologic findings and ANCA in acute Kawasaki disease and the diagnostic potential of ANCA to predict coronary artery involvement. METHODS: Thirty-eight patients who met the diagnostic criteria for Kawasaki disease were enrolled in this study. We sampled and investigated the hematologic findings and the assay of ANCA before intravenous immunoglobulin treatment and weekly echocardiographs weekly. RESULTS: There was no sexual difference between ANCA positive and negative group. The age in ANCA positive group was significantly lower than in ANCA negative group. Duration of fever before treatment in ANCA positive group were not significantly different from those in ANCA negative group. In ANCA positive group, the mean WBC count and the mean ESRs were higher than in ANCA negative group. There was no relation between ANCA and coronary artery involvement. CONCLUSION: The assays of ANCA in acute Kawasaki disease does not help to predict disease activity and coronary artery involvement.

Immunologic Alterations of Peripheral Mononuclear Cells by Intravenous Immunoglobulin in the Acute Stage of Kawasaki disease

PURPOSE: High dose intravenous immunoglobulin (IVIG) therapy is effective in reducing the incidence of coronary artery aneurysm in Kawasaki disease (KD) patients, however, the precise mechanisms by which IVIG reverses the immune activation is unknown. METHODS: The sera and peripheral mononuclear cells (PBMCs) were obtained from 10 KD patients in the acute stage (24 hrs before) and 24 hrs after one dose of IVIG (2g/kg) treatment. We measured serum interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) and compared them to the messenger RNA expression of the PBMCs by reverse transcription polymerase chain reaction. We also investigated the cytokines' or immunoglobulins' production of PBMCs which were stimulated with phytohemagglutinin-P (PHA-P) or pokeweed mitogen (PWM, without in vitro IVIG treatment) by enzyme-linked immunosorbent assay. RESULTS: The serum levels of IL-6 and TNF-alpha decreased significantly after IVIG treatment. However, the gene expression of IL-6 and TNF-alpha showed no significant difference after IVIG treatment. IL-6 and TNF-alpha productions of PBMCs stimulated with PHA-P decreased significantly after IVIG treatment, however, IL-4 and IFN-gamma production showed no significant differences. IL-6 production of PBMCs stimulated with PWM also decreased significantly after IVIG treatment, but TNF-alpha did not change significantly. The synthesis of IgG, IgM, IgA and IgG1 after IVIG treatment showed a significant decrease, and that of IgG2 showed a slight decrease, but was not statistically significant. CONCLUSION: The results demonstrate that the administration of IVIG in the acute stage of KD resulted in the alterations of activated immunologic abnormalities, especially in monocytes and B cells.

Treatment of Intravenous Immune-Globulin Resistant Kawasaki Disease with Corticosteroids

PURPOSE: To evaluate the efficacy of steroid therapy on prevention of development and progression of coronary artery aneurysm in intravenous immune globulin (IVIG)-resistant Kawasaki disease, we treated three children with high dose of intravenous methylprednisolone followed by low dose oral prednisolone. METHODS: We selected three children with Kawasaki disease who did not repond or who initially responded but soon developed recrudescent fever after retreatment of IVIG (total 4gm/kg). These three patients were treated with high dose methylprednisolone (10mg/kg) intravenously and followed by low dose prednisolone (1mg/kg) orally for 7 days. Echocardiographic evalutions were performed within 8 days of admission (before steroid therapy), at discharge and 1 month after discharge. RESULTS: All three patients showed rapid normalization of clinical symptoms and did not developed significant coronry artery abnormalities. No adverse reaction was observed. CONCLUSIONS: Steroid therapy (mini pulse methylprednisolone and prednisolone therapy) is valuable for patients with Kawasaki disease resistant to intravenous immune globulin therapy.

A Case of Pena-Shokeir Phenotype in Trisomy 18 Syndrome

Pena-Shokeir syndrome is a rare, often lethal disease, characterized by intrauterine growth retardation, craniofacial anomalies, limb ankylosis, polyhydramnios and pulmonary hypoplasia. This autosomal recessive disease should be differentiated from trisomy 18, which the second most common multiple congenital malformation syndrome. It is therefore clear that the two syndromes have certain features in common, the most consistent being craniofacial and limb abnormalities and intrathoracic pathology. Therefore, final diagnosis should be based on chromosome study. The case that we experienced had typical Pena-Shokeir phenotype, but chromosomal study show 47, XY, +18.

A Case of von Gierke Disease

von Gierke disease (type Ia glycogen storage disease) is an inherited disease associated with accumulation of glycogen in the liver, kidney, intestine and erythrocytes due to the defect of glucose-6-phosphatase activity. Hepatomegaly, doll face, anemia, bleeding tendency and increased susceptability to infection are common features observed during infancy. Hypoglycemia especially fasting hypoglycemia is typical metabolic derangement in this disease, followed by metabolic acidosis, lactic acidemia, hyperlipidemia, hyperuricemia, and platelets dysfunction. We experienced a case of von Gierke disease in 6 month-old boy with doll face, hepatomegaly, fasting hypoglycemia, acidosis, anemia, hyperlipidemia, hyperuricemia, and acetonuria. Diagnosis was confirmed by light- and electron microscopic examination of liver biopsy specimen, which revealed hepatocytes filled with dense pools of glycogen and many lipid droplets. Cornstarch dietary therapy for him had favorable responses showing improvement of hypoglycemia, other metabolic derangements, and regression of hepatomegaly.

A Case of von Gierke Disease

von Gierke disease (type Ia glycogen storage disease) is an inherited disease associated with accumulation of glycogen in the liver, kidney, intestine and erythrocytes due to the defect of glucose-6-phosphatase activity. Hepatomegaly, doll face, anemia, bleeding tendency and increased susceptability to infection are common features observed during infancy. Hypoglycemia especially fasting hypoglycemia is typical metabolic derangement in this disease, followed by metabolic acidosis, lactic acidemia, hyperlipidemia, hyperuricemia, and platelets dysfunction. We experienced a case of von Gierke disease in 6 month-old boy with doll face, hepatomegaly, fasting hypoglycemia, acidosis, anemia, hyperlipidemia, hyperuricemia, and acetonuria. Diagnosis was confirmed by light- and electron microscopic examination of liver biopsy specimen, which revealed hepatocytes filled with dense pools of glycogen and many lipid droplets. Cornstarch dietary therapy for him had favorable responses showing improvement of hypoglycemia, other metabolic derangements, and regression of hepatomegaly.

Pertussis Antibodies in the Sera of Children after Acellular Pertussis Vaccination

PURPOSE: The pertussis vaccines are divided into whole-cell vaccine and acellular vaccine. Purified component acellular pertussis vaccine, originally developed in Japan, has been used for primary immunization series in Korea since 1984. We performed this study to evaluate the prevalence of pertussis antibodies following vaccination with acellular pertussis vaccine. METHODS: We randomized 80 children who were immunized according to vaccine schedules including less than 2 month-old infants at Department of Pediatrics, Catholic University Medical College from February 1995 to October 1995. We measured agglutination titers of children by bacterial agglutination test. RESULTS: 1) The age distribution ranged from 5 days to 7 years old, the mean age was 14.5+/- 12.8 months and male to female ratio was 1:1. 2) Only 23 cases (28.8%) of the 80 cases were positive results. 3) Among 7 infants who were less than 2 months-old and were not immunized, 5 infants (71.4%) were seropositive. 4) There was no significant difference in positive rates among age groups which include 2 to 6 months age group, 7 to 18 months age group, and older than 18 months age group. CONCLUSIONS: The prevalence of pertussis positive rates is only 28.8% and there was no difference among age groups.

A Case of Acute Viral Myositis

Diffuse myalgia is common in transient systemic viral infections but overt myositis, with weakness and signs of muscle inflammation, rarely accompanies viral infection in chidren. We describe a 8-year-old boy with severe myalgia and tenderness in both lower extremities, whose unusual skeletal muscle uptake on Technetium-methylene diphosphate bone scan helped to diagnosis of myositis. Clinical course, muscle-derived enzyme studies(AST, ALT, LD, CK), electromyogram findings, histopathologic findings obtained from left gastrocnemius muscle biopsy and serologic studies for enteroviral antibodies (enterovirus type 71 and Coxsackie B4 neutralization antibody titer 1:128 respectively) were all compatible with acute viral myositis.

Use of Fluorescent in Situ Hybridization to Evaluate the Number of Chromosomes in Buccal Smear Cells in Normal Newborn Infants

No abstract available.

A Clinical Study of Tsutsugamushi Disease in Children

No abstract available.

Treatment of aplastic anemia

We performed this study to evaluate the therapeutic responses of bone marrow transplantation and immunosuppressive therapy for aplastic anemia in 103 cases (68 severe and 35 moderate). Among them, 15 cases with severe aplastic anemia having HLA-identical sibling donor underwent bone marrow transplantation, and cases(53 severe and 35 moderate cases)without available HLA-identical sibling donor had received immunosuppressive therapy using antilymphocye globulin and cyclosporin-A. The results were as follows; 1) For cases given bone marrow transplantation, successful engraftment was accomplished in all cases, but 2 cases showed rejection and 1 case died of thrombotic thrombocytopenic purpura (TTP), resulting 80% disease-free survival rate. acute graft-versus-host disease above grade II was noted in 2 cases and chronic graft-versus host disease was seen in other 2 cases. The most common pathogenic organism in post-transplantation infection was Herpes zoster (6 cases), and one each cases of Herpes simplex, candidiasis, measles and hemorrhagic cystitis developed. 2) Among 88 cases of receiving immunsouppressive therapy, complete response was seen in 26 cases (29.5%) and partial respones in 37 cases (42.0%), resulting 71.6% of overall response rate and recurrence rate was 19.5% (12 cases). In 53 severe cases, complete response was seen in 9 cases (17.0%) and partial response in 25 cases (47.2%), resulting 64.2% of overall response rate. In 35 moderate cases, complete response was seen in 17 cases (48.6%) and partial response in 12 cases(34.3%), overall response rate was 82.9%. All initial responses were seen within 6 months post-treatment period, and the time interval to initial response was 8 to 162 days (median; 53 days). There was no sex difference concerning response rate, however, partial response was predominant in male and more complete response in female. The complications of immunosuppressive therapy were thrombocytopenia (93.2%), fever (67.7%), hypertension (50.0%), skin eruption (45.8%), gingivitis (17.0%). In conclusion, our date suggest that bone marrow transplantation is preferred initial treatment modality to immunosuppressive therapy in severe aplastic anemia patient with HLA-identical sibling donor, and immunosuppression is a satisfactory alternative therapy for children with severe aplastic anemia in the absence of HLA-identical sibling and for whom with moderate aplastic anemia.

Intermittent central nervous system irradiation and intrathecal chemotherapy for recurrent central nervous system leukemia in children

Between 1986 and 1990, four children with recurrent CNS leukemia who had previous CNS prophylaxis therapy were treated with intermittent central nervous system irradiation and intrathecal chemotherapy (IIIC). There was no isolated CNS recurrence. One patient died form bone marrow relapse. Three patients are alive without evidence of disease for 3E3/12 year to 3E6/12 year after the diagnosis of recurrence of CNS leukemia. This experience suggests that IIIC may be an effective treatment for preventing the recurrence of CNS leukemia without any serious side effects.