ABSTRACT
PURPOSE: Kawasaki disease(KD) manifests a systemic vasculitis of unknown etiology in young children. Vascular endothelial growth factor(VEGF), vascular cell adhesion molecule-1(VCAM-1) and interleukin-1 beta(IL-1beta) may play important roles in the pathogenesis of KD. Intravenous immunoglobulin(IVIG) and methylprednisolone(MP) are therapeutically effective for KD, however, the precise mechanisms of the two drugs are still unknown. We investigated the therapeutic efficacy of IVIG and/or MP for KD in vitro. METHODS: Human umbilical vein endothelial cells(HUVEC) obtained from umbilical cords of healthy newborns were cultured. After HUVEC were treated with IL-1beta, the effect of IVIG and/or MP on the in vitro activation of HUVEC were assessed by cell proliferation and reverse transcription-polymerase chain reaction-detected expression of mRNA coding for VEGF, VCAM-1, and IL-1beta. RESULTS: IVIG and MP down-regulated the expression of VEGF mRNA induced by IL-1beta(P<0.05, respectively) significantly. The combination of both showed a synergistic effect on the expressions with a dose dependent manner of MP compared to the IVIG or MP alone respectively(P<0.05). IVIG and MP down-regulated the expression of VCAM-1 mRNA induced by IL-1beta(P<0.05, respectively). The combination of both showed a synergistic effect on the expressions with a dose dependent manner of MP(P<0.05). IVIG and MP down-regulated the expression of IL-1beta mRNA induced by IL-1beta(P<0.001, P<0.05, respectively). The combination of both showed a synergistic effect on the expressions with a dose dependent manner of MP(P<0.001). CONCLUSION: These results suggested that IVIG and MP are therapeutically effective for KD in vitro as well as in vivo.
Subject(s)
Child , Humans , Infant, Newborn , Cell Adhesion , Cell Proliferation , Clinical Coding , Human Umbilical Vein Endothelial Cells , Immunoglobulins, Intravenous , Interleukin-1 , Interleukin-1beta , Methylprednisolone , Mucocutaneous Lymph Node Syndrome , RNA, Messenger , Systemic Vasculitis , Umbilical Cord , Umbilical Veins , Vascular Cell Adhesion Molecule-1 , Vascular Endothelial Growth Factor AABSTRACT
PURPOSE: In most cases, myelodysplastic syndrome(MDS) transforms into a more aggressive state or acute myelogenous leukemia; it's prognosis is very poor. It is believed that hematopoietic stem cell transplantation(HSCT) is the only curative treatment of MDS, but available data in children are very sparse. In this report, the short term outcome of HSCT in childhood MDS was analyzed. METHODS: Ten children with MDS(CMMoL 5, RAEB 3, RAEBt 2) underwent HSCT(HLA- matched sibling transplantation 4, HLA-matched unrelated transplantation 4, cord blood transplantation 1, HLA-mismatched familial transplantation 1) between November 1995 and January 2001 at St. Mary's Hospital. Median follow-up duration was 11 months. RESULTS: Engraftment was successful in all cases and 8 patients are alive without disease. Three cases of VOD were observed and improved without complication. Four cases of grade II and 1 case of grade III acute GVHD were observed and well controlled with treatment. Three patients relapsed after transplantation. One patient is alive without disease after cytoreduction with allogenic stem cell rescue and 2 patients died of relapse. CONCLUSION: HSCT is a curative strategy of MDS and the survival rate is relatively higher than that of adults. But there is an obvious need for more studies because of the small number of patients and the short duration of the follow-up.
Subject(s)
Adult , Child , Humans , Anemia, Refractory, with Excess of Blasts , Fetal Blood , Follow-Up Studies , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells , Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Prognosis , Recurrence , Siblings , Stem Cells , Survival RateABSTRACT
Pulmonary embolism is not a frequent cause of morbidity and mortality in patients with or without malignancies. Pulmonary embolism should be ruled out when sudden tachypnea and pulmonary hypertension develop in leukemic children, and chest radiograph shows no or minimal abnormalities. A 14-year-old girl with acute lymphoblastic leukemia was admitted due to neutropenic fever and dyspnea. Chest computed tomography and ventilation/perfusion scan showed pulmonary embolism, and embolectomy revealed aspergillosis. Invasive aspergillosis is the major opportunistic fungal pathogen in neutropenic patient and an important cause of death. The critical elements of successful management of invasive aspergillosis complicating neutropenia and pulmonary embolism are early diagnosis, initiation of aggressive doses of amphotericin B, reversal of immune suppression and feasible surgical resection of the lesions. To the best of our knowledge, this is the first report of pulmonary embolism caused by Aspergillus in an immunocompromised setting in Korea and we present a case report with a brief review.
Subject(s)
Adolescent , Child , Female , Humans , Amphotericin B , Aspergillosis , Aspergillus , Cause of Death , Dyspnea , Early Diagnosis , Embolectomy , Fever , Hypertension, Pulmonary , Korea , Mortality , Neutropenia , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Pulmonary Embolism , Radiography, Thoracic , Tachypnea , ThoraxABSTRACT
Malignant melanoma is a very rare disease in children. There is an increased risk for the development of malignant melanoma in patient with giant congenital melanocytic nevus. The manifestations of distant metastases in malignant melanoma commonly indicate a poor prognosis. First line treatment of malignant melanoma is excision, but when associated with giant congenital melanocytic nevus, excision is very difficult due to the site and the size of the lesions. However, malignant melanoma is not sensitive to chemotherapy, but a child is more sensitive than an adult. We report a case of unresectable childhood malignant melanoma associated with a giant congenital melanocytic nevus in a 3 year-old female treated with chemotherapy.
Subject(s)
Adult , Child , Child, Preschool , Female , Humans , Drug Therapy , Melanoma , Neoplasm Metastasis , Nevus, Pigmented , Prognosis , Rare DiseasesABSTRACT
BACKGROUND: The green fluorescent protein (GFP) from jelly fish, Aequorea victoria, has become a versatile reporter for monitoring gene expression in a variety of cells and organisms. Using GFP as a marker protein we studied whether there are any differencies in the expression patterns among organs in mouse after intravenous injection of adenovirus vectors with GFP gene. METHODS: Recombinant E1, E3-defective type 5 adenovirus vectors (2x10(8)/mouse) with CMV promoter and GFP gene were injected into mice via tail vein. On 3, 6, 9, 14, 21, 28 days after gene transfer, 5 mice per experiments were sacrificed by cervical dislocation and obtained liver, lung, heart, kidney, spleen, small intestine and bone. Half of them were examined by optical microscope after H-E stain. Another half were examined by fluorescent microscope after frozen section. Western blottings were done for each samples with anti-GFP monoclonal antibody and obtained GFP bands were quantitatively compared using Gel-Doc (Bio-Rad, USA) image analyzer. RESULTS: In all organs that we obtained, expression of GFPs are noticed 3 days after gene transfer and reached a maximum around 9th to 14th days, after then the intensities are slightly decreased but maintained until 28th days as determined by Western blotting. On fluorescent microscopic examination, GFPs are well and most frequently expressed on lung among all the examined organs. There are little expression of GFPs on liver parenchymal area around the sinusoids and central veins, although patchy expression of GFPs are observed along the liver capsules. GFPs are highly expressed around the splenic trabecula area but splenic pulp area, it is very sparsely expressed. GFPs are more frequently and highly expressed around the renal tubular area than gromerular area in kidneys. In small intestine, GFPs are expressed on mid portion of microvilli. GFPs are not expressed on myocardium except scanty expression on endocardium. Bone marrow showed GFPs but precise localization is difficult because bony spicules mashed bone marrow during the preparation of frozen section. No specific pathologic lesions possibly related with adenovirus administration are observed on microscopic examination of H-E stained specimens. CONCLUSIONS: GFPs can be detected in cells without the fixing and staining and a good marker to studying the kinetics and persistence of adenovirus mediated gene therapy. And there are different GFP expression patterns according to the organs after intravenous injection of adenovirus vectors with GFP gene in mouse.
Subject(s)
Animals , Mice , Adenoviridae , Blotting, Western , Bone Marrow , Capsules , Joint Dislocations , Endocardium , Fluorescence , Frozen Sections , Gene Expression , Genetic Markers , Genetic Therapy , Heart , Injections, Intravenous , Intestine, Small , Kidney , Kinetics , Liver , Lung , Microvilli , Myocardium , Spleen , Veins , VictoriaABSTRACT
PURPOSE: In this study we tested the hypothesis that vasodilatation and antithrombogenic effect in damaged vessels using low-dose Lipo PGE1 might result in increased sinusoidal blood flow and in decreased obstruction and minimize the incidence or severity of hepatic veno-occlusive disease (VOD). METHPDS: Children underwent hematopoietic stem cell transplantation for hematologic malignancies were enrolled in this study. Lipo PGE1 was begun one day prior to the start of conditioning to day 30 after stem cell transplantation in continuous intravenous infusion at a dose of 1 mug/kg/day (0.042 mug/ kg/hr). We evaluate the incidence and severity of hepatic VOD and the toxicity of Lipo PGE1. RESULTS: From November 1999 to Jun 2000, 20 patients (M:F=15:5, median age 5 years) underwent hematopoietic stem cell (5 matched sibling bone marrow, 4 autologous bone marrow, 8 unrelated bone marrow, 3 unrelated cord blood) transplantation for hematologic malignancies (9 ALL, 8 AML, 3 CML) were enrolled in this study. There was no occurrence of VOD within 30 day of transplant. Only one out of 20 patients was diagnosed as delayed VOD, easily controlled moderate form, on post-transplant day 58. There was no toxicity attributed to Lipo PGE1. CONCLUSION: This study suggests that prophylactic low-dose Lipo PGE1 treatment may decrease the incidence of VOD in patients treated for hematologic malignancies by hematopoietic stem cell transplantation.
Subject(s)
Child , Humans , Alprostadil , Bone Marrow , Hematologic Neoplasms , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells , Hepatic Veno-Occlusive Disease , Incidence , Infusions, Intravenous , Siblings , Stem Cell Transplantation , VasodilationABSTRACT
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-
Subject(s)
Child , Female , Humans , Male , Anemia, Aplastic , Bone Marrow Transplantation , Bone Marrow , Diagnosis , Disease-Free Survival , Follow-Up Studies , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Leukemia, Myeloid, Acute , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Purpura, Thrombotic Thrombocytopenic , Recurrence , Siblings , Stem CellsABSTRACT
Intracranial aspergillosis is a rare pathologic condition, difficult to treat and often fatal, which generally affects immuosuppressed patients. A case of brain abscess secondary to pulmonary localization in a child with acute lymphoblastic leukemia with a favorable outcome is described. A 4-year-old boy diagnosed with acute lymphoblastic leukemia was induced with vincristine, cyclophosphamide, daunorubicin, L-asparaginase and dexamethasone. On the second week of induction chemotherapy, he suffered febrile neutropenia (absolute neutrophil count below 100). Blood and sputum culture disclosed the presence of Aspergillus fumigatus, and chest X-ray examination showed thin-walled cavitation of infiltrates compatible with aspergilloma. The patient was treated with amphotericin B (1 mg/kg/day) and with G-CSF for neutropenia. Fever subsided a few days later and complete hematologic remission was attained on the sixth hospital week, during which antifungal treatment with amphotericin B was continued. Repeated blood and sputum cultures were sterile. On the fifty-sixth hospital day, the patient suffered from afebrile tonic seizure with right side weakness. CT scan of the brain showed multiple well-circumscribed, rim-enhancing round lesions in right frontal lobe and bilateral parieto-occipital area causing gross edema and displacement of the central structures. Itraconazole was added from eightieth hospital day and supportive care was provided for brain edema. After 2 weeks, there was marked clinical improvement, and the pulmonary aspergilloma had completely regressed on follow-up chest X-ray at the sixty-fifth hospital day. Follow-up brain CT scan at the sixty-eighth hospital day showed marked decrease in size, thickness of abscess wall, and brain edema. Patient also attained neurologic improvement. Amphotericin B therapy was continued for 9 weeks (cumulative dose 908 mg, 58 mg/kg) without discer-nable side effects and the patient was discharged on the ninety-sixth hospital day with improved condition. 6 months after detection of brain abscess, magnetic resonance image of the brain showed resolution of all brain lesions. To the best of our knowledge, this is the first reported case survived CNS aspergillosis in an immunocompromised setting in Korea which was successfully treated with medical therapy only. We present a case report with a brief review.
Subject(s)
Child , Child, Preschool , Humans , Male , Abscess , Amphotericin B , Aspergillosis , Aspergillus fumigatus , Brain , Brain Abscess , Brain Edema , Cyclophosphamide , Daunorubicin , Dexamethasone , Edema , Febrile Neutropenia , Fever , Follow-Up Studies , Frontal Lobe , Granulocyte Colony-Stimulating Factor , Induction Chemotherapy , Itraconazole , Korea , Neutropenia , Neutrophils , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Seizures , Sputum , Thorax , Tomography, X-Ray Computed , VincristineABSTRACT
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-
Subject(s)
Child , Female , Humans , Male , Anemia, Aplastic , Bone Marrow Transplantation , Bone Marrow , Diagnosis , Disease-Free Survival , Follow-Up Studies , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Leukemia, Myeloid, Acute , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Purpura, Thrombotic Thrombocytopenic , Recurrence , Siblings , Stem CellsABSTRACT
BACKGROUND: Though immunotherapy(IT) has become an effective rnethod in extrinsic allergic patients who didn't respond to pharmacologic therapy or couldn't avoid allergen, the mechanism, termination index and prognostic index of IT have not been clarified yet. METHOD: We selected 81 asthmatic children on immunotherapy with house dust mite (Dermatophagoides pteronyssinus and Dermatophagoides farinae). We measured the hematologic findings, the levels of serum IgG and IgE, allergen(house dust, Dermatophagoides pteronyssinus and Dermatophagoides farinae)-specific IgE concentrations, lymphocyte subsets and methacholine challenge test yearly during IT, and checked the radiographs of chest and paranasal sinus. RESULTS: Peripheral white blood cell count, the percentage of eosinophil and total eosinophil count decreased significantly after 2 years of IT. Serum IgG level increased significantly after 3 years of IT. Serum total and specific IgE levels decreased significantly after 3 years of IT, but they were still higher than the normal values. CD4+, CD8+, and B lymphocytes did not change with the IT, but CD3+ lymphocytes increased significantly after 2 years of IT. PC20-methacholine increased significantly after 1 year of IT, but no correlation was found between the duration of IT and bronchial hyperreactivity. Twenty-eight patients(34.6%) had abnormal findings on chest radiographs: 15 patients(53.6%) as bronchitis, 10 patients(35.7%) as bronchopneumonia, 2 patients(7.1%) as hyperinflation and 1 patient(3.6%) as atelectasis. Sixty-three patients(77.8%) had abnormal findings on paranasal sinus radiographs. In the follow-up radiographs of 49 patients, 28 patients(57.1%) showed improvement of paranasal sinusitis after 1 year of IT. CONCLUSION: This study showed some changes of the immunologic findings such as eosinophil count, IgG, IgE, allergen-specific IgE and CD3+ lymphocytes, and improvement of bronchial hyperreactivity and paranasal sinusitis' in asthmatic children during IT. These findings were closely related to clinical improvement.
Subject(s)
Child , Humans , B-Lymphocytes , Bronchial Hyperreactivity , Bronchitis , Bronchopneumonia , Dermatophagoides pteronyssinus , Dust , Eosinophils , Follow-Up Studies , Immunoglobulin E , Immunoglobulin G , Immunotherapy , Leukocyte Count , Lymphocyte Subsets , Lymphocytes , Methacholine Chloride , Pulmonary Atelectasis , Pyroglyphidae , Radiography, Thoracic , Reference Values , Sinusitis , ThoraxABSTRACT
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.
Subject(s)
Humans , Antibodies, Antineutrophil Cytoplasmic , Coronary Vessels , Fever , Immunoglobulins , Mucocutaneous Lymph Node Syndrome , Granulomatosis with PolyangiitisABSTRACT
Thirty eight cases of moyamoa disease, 21 children, 17 adults were encountered during a 16-year period at Yonsei University Medical Center. Clinical manifestations, together with computed tomography (CT) and angiographic findings were analyzed with a review of the literature. The mean age was 6.3 +/- 3.5 years in children and 36.8 +/- 9.9 years in adults. The majority of attacks occurred in spring in both adults and children. The most common chief complaint on admission was hemiparesis followed by convulsion in children, while in adults, loss of consciousness was most common followed by headache. Of transient neurologic deficits, hemiplegia was most common in children, while cranial nerve involvement was common in adults. Hemiplegia, also was the most common permanent neurologic manifestation in children, while hemiparesis and intellectual deterioration were the most common in adults. Of the children, 90.6% showed infarction on CT, while 88.2% of adults had hemorrhage. Bilateral occlusion of the carotid arteries was the most common site of lesions in both adults and children on cerebral angiogaphy.
Subject(s)
Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Age Factors , Central Nervous System Diseases/physiopathology , Cranial Nerves/pathology , Korea/epidemiology , Middle Aged , Moyamoya Disease/epidemiology , Retrospective Studies , Seasons , Tomography, X-Ray ComputedABSTRACT
No abstract available.