Hye Lim Jung

Clinical Significance of Serum Procalcitonin in Patients with Community-acquired Lobar Pneumonia

BACKGROUNDnCommunity-acquired pneumonia (CAP) is a common respiratory disorder in children, which necessitates hospitalization. Bacterial pneumonia, especially lobar pneumonia and parapneumonic effusions, is associated with considerably severe clinical course and extensive alveolar infiltrates. Serum procalcitonin (PCT) level has been used to distinguish bacterial from viral infections, but its usefulness is disputed. The diagnostic accuracy and usefulness of PCT, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell (WBC) count were determined by comparing their values in the patients with CAP with those in healthy controls.nnnMETHODSnThe serum PCT levels, as well as CRP level, ESR, and WBC counts, were measured in 76 hospitalized patients with CAP (lobar pneumonia, 16; bronchopneumonia, 60) and 18 healthy controls. Serum PCT level was measured using VIDAS BRAHMS PCT (Biomerieux, France), and ROC curve analysis was performed to evaluate its diagnostic accuracy.nnnRESULTSnSerum PCT levels were higher in the patients with CAP than in healthy controls, especially in the patients with lobar pneumonia than in those with bronchopneumonia. Serum CRP level was also significantly elevated in the patients with CAP, especially in those with lobar pneumonia. The diagnostic accuracy of serum PCT level for the diagnosis of lobar pneumonia was better than those of serum CRP level and ESR. The serum PCT level was significantly correlated with the CRP level, ESR, and WBC count.nnnCONCLUSIONSnSerum PCT level was a better marker than CRP level or ESR for the diagnosis of lobar pneumonia in children with CAP.

Loss of heterozygosity analysis of chromosome 17p13.1-13.3 and its correlation with clinical outcome in medulloblastomas.

Cytogenetic and molecular genetic studies have shown that deletions on the short arm of chromosome 17 distal to p53 locus are the most common genetic events in medulloblastoma. We examined the occurrences and frequencies of allelic deletions on chromosome 17p13.1–13.3 by loss of heterozygosity (LOH) analysis to investigate the possible involvement of 17p13.1–13.3 in medulloblastoma development. We also performed survival analysis to determine whether LOH analysis of 17p13.1–13.3 can be used to predict prognosis in medulloblastoma.Loss of heterozygosity was analyzed by polymerase chain reaction on chromosome 17p13.1–13.3 using three microsatellite markers, TP53 on 17p13.1, D17S796 on 17p13.1–13.2, and D17S1574 on 17p13.3, in 17 medulloblastoma DNAs extracted either from archival tissue or fresh frozen tissue specimens.Allelic deletions were detected in five of 17 informative cases (29%) on TP53, eight of 17 informative cases (47%) on D17S796, and four of 17 informative cases (24%) on D17S1574. Overall, nine of 17 cases (53%) showed LOH on chromosome 17p13.1–13.3. The 5-year progression free survival (PFS) and 5-year overall survival rates were identical (59%). The 5-year PFS for nine medulloblastoma patients with LOH on 17p13.1–13.3 was 56%, and the 5-year PFS for eight medulloblastoma patients without LOH on 17p13.1–13.3 was 63%. In our survival analysis, we did not find a significant association between survival and LOH on 17p13.1–13.3.Our results support the notion that deletions of chromosome 17p13.1–13.3 may be involved in the pathogenesis of medulloblastoma. From survival analysis, we conclude that LOH on chromosome 17p13.1–13.3 may not be a significant predictor of prognosis in medulloblastoma.

Clinical features and treatment outcomes of Langerhans cell histiocytosis: a nationwide survey from Korea histiocytosis working party.

A nationwide survey was conducted to clarify the clinical features and outcomes of Korean children with Langerhans cell histiocytosis (LCH). Korea Histiocytosis Working Party analyzed the data of 603 patients who were diagnosed with LCH between 1986 and 2010 from 28 institutions in Korea. Median age at diagnosis was 65 months (range, 0 to 276 mo). Bone was the most frequently affected organ (79.6%) followed by skin (19.2%). Initially, 419 patients (69.5%) had single-system involvement (SS), 85 (14.1%) with multisystem (MS) disease without risk organ involvement (MS-RO−), and 99 (16.4%) multisystem disease with risk organ involvement (MS-RO+). The 5-year overall survival (OS) rates in the SS, MS-RO−, and MS-RO+ groups were 99.8%, 98.4%, and 77.0%, respectively (P<0.001), and the 5-year reactivation rates were 17.9%, 33.5%, and 34.3%, respectively (P<0.001). The OS rate was lower in patients with RO involvement (P=0.025) and lack of response to initial treatment (P=0.001). MS involvement (P=0.036) was an independent risk factor for reactivation. Permanent consequences were documented in 99 patients (16.4%). Reactivation of disease, MS involvement, and age at diagnosis ⩽2 years were associated with higher incidence of permanent consequences. This study emphasized that further efforts are required to improve survival of MS-RO+ patients and reduce reactivation in younger patients with MS involvement.

Serum vascular endothelial growth factor in pediatric patients with community-acquired pneumonia and pleural effusion.

This study investigated the serum vascular endothelial growth factor (VEGF) levels in children with community-acquired pneumonia. Serum VEGF levels were measured in patients with pneumonia (n=29) and in control subjects (n=27) by a sandwich enzyme-linked immunosorbent assay. The pneumonia group was classified into bronchopneumonia with pleural effusion (n=1), bronchopneumonia without pleural effusion (n=15), lobar pneumonia with pleural effusion (n=4), and lobar pneumonia without pleural effusion (n=9) groups based on the findings of chest radiographs. We also measured serum IL-6 levels and the other acute inflammatory parameters. Serum levels of VEGF in children with pneumonia were significantly higher than those in control subjects (p<0.01). Children with lobar pneumonia with or without effusion showed significantly higher levels of serum VEGF than children with bronchopneumonia. For lobar pneumonia, children with pleural effusion showed higher levels of VEGF than those without pleural effusion. Children with a positive urinary S. pneumonia antigen test also showed higher levels of VEGF than those with a negative result. Serum IL-6 levels did not show significant differences between children with pneumonia and control subjects. Serum levels of VEGF showed a positive correlation with the erythrocyte sedimentation rate in the children with pneumonia. In conclusion, VEGF may be one of the key mediators that lead to lobar pneumonia and parapneumonic effusion.

Comparison Study of the Eosin-5′-Maleimide Binding Test, Flow Cytometric Osmotic Fragility Test, and Cryohemolysis Test in the Diagnosis of Hereditary Spherocytosis

OBJECTIVESnCurrent guidelines recommend the eosin-5-maleimide (EMA) binding test and cryohemolysis test for screening for hereditary spherocytosis (HS), and the flow cytometric osmotic fragility (FC OF) test was recently developed to replace the classic OF test. We evaluatedthe performance of the EMA binding test, FC OF test, cryohemolysis test, and the hemoglobin (Hb)/mean corpuscular hemoglobin concentration (MCHC) ratio in the diagnosis of HS and assessed whether these tests reflect the clinical severity of HS.nnnMETHODSnA total of 153 patients with anemia (33 with HS, 40 with autoimmune hemolytic anemia, 40 with anemia of chronic disease, and 40 with iron deficiency anemia [IDA]) and 140 healthy controls were enrolled, and the performance of the three tests was evaluated.nnnRESULTSnBoth the EMA binding test (area under the curve [AUC], 0.996) and the FC OF test (AUC, 0.992) performed satisfactorily, but the cryohemolysis test (AUC, 0.723) performed significantly worse because of false positivity in patients with IDA. The Hb/MCHC ratio (P < .001) was able to reflect the clinical severity of HS.nnnCONCLUSIONSnOur results demonstrate that both the EMA binding and FC OF tests are useful as screening tests for the diagnosis of HS, but the cryohemolysis test has limited use due to its false positivity in IDA, with the Hb/MCHC ratio the most useful parameter for assessing the clinical severity of HS.

Epidemiology and clinical long-term outcome of childhood aplastic anemia in Korea for 15 years: retrospective study of the Korean Society of Pediatric Hematology Oncology (KSPHO).

Purpose Aplastic anemia (AA) is a rare hematologic disease characterized by pancytopenia and hypocellular marrow. The Korean Society of Pediatric Hematology Oncology investigated retrospectively the incidence, survival, and transfusion independency according to treatment strategies in AA. Methods All the questionnaires were sent to members for medical records. We collected and analyzed 702 available data. Results The male and female ratio was 1.2, and the median age at diagnosis was 9.3 years. The annual incidence of Korean children with AA was 5.16 per million per year. Constitutional anemia was diagnosed in 44 children. In acquired AA, causes were identified in 39 children. Severe AA (SAA) at initial diagnosis was more common than nonsevere AA. The overall survival was 47.8% with supportive care, 68.1% with immunosuppressive therapy (IST), and 81.8% with hematopoietic stem cell transplantation. In IST, response rate was 65.7%, and relapse rate after response was 54.4% within a median of 23.0 months. The factors with overall survival were severity of disease in supportive care, severity and response in IST, donor type, graft failure, and posttransplant events in hematopoietic stem cell transplantation. Conclusions Long-term outcome in AA was dependent on treatment strategies. These Korean results may help research and prospective international clinical trials for childhood AA.

Hereditary hemolytic anemia in Korea from 2007 to 2011: A study by the Korean Hereditary Hemolytic Anemia Working Party of the Korean Society of Hematology

Background The number of patients diagnosed with hereditary hemolytic anemia (HHA) has increased since the advent of novel diagnostic techniques that accurately identify this disorder. Here, we report data from a survey on the prevalence and characteristics of patients diagnosed with HHA in Korea from 2007 to 2011. Methods Information on patients diagnosed with HHA in Korea and their clinical and laboratory results were collected using a survey questionnaire. Globin gene and red blood cell (RBC) enzyme analyses were performed. In addition, we analyzed data collected by pediatricians. Results In total, 195 cases of HHA were identified. Etiologies identified for HHA were RBC membranopathies, hemoglobinopathies, and RBC enzymopathies, which accounted for 127 (64%), 39 (19.9%), and 26 (13.3%) cases, respectively. Of the 39 patients with hemoglobinopathies, 26 were confirmed by globin gene analysis, including 20 patients with β-thalassemia minor, 5 patients with α-thalassemia minor, and 1 patient with unstable hemoglobin disease. Conclusion The number of patients diagnosed with hemoglobinopathies and RBC enzymopathies has increased considerably since the previous survey on HHA in Korea, dated from 1997 to 2006. This is likely the result of improved diagnostic techniques. Nevertheless, there is still a need for more sensitive diagnostic tests utilizing flow cytometry and for better standardization of test results to improve the accuracy of diagnosis of RBC membranopathies in Korea. Additionally, more accurate assays for the identification of RBC enzymopathies are warranted.

Successful and safe treatment of hemangioma with oral propranolol in a single institution.

Purpose Dramatic improvement of hemangioma to propranolol has been recently reported; however, details on dose and duration of treatment, potential risks, and monitoring have not been determined. The objective of this study is to describe and analyze the use of propranolol as a first-line treatment or as a single therapy in management of complicated hemangioma. Methods A retrospective chart review of eight patients diagnosed with hemangioma and treated with propranolol in Kangbuk Samsung Hospital from February 2010 to April 2011 was performed. Results Eight patients with hemangioma with functional impairment, cosmetic disfigurement, or rapid growth were treated with propranolol. Five patients had solitary facial hemangioma. The mean age of symptoms at onset was 5 weeks. The median age for starting propranolol treatment was 5.5 months. Propranolol at 2 mg/kg/day was finally administered in divided doses with a gradual increase. Significant regression was observed in seven patients, and shrinkage in size, softening in consistency, and decrease in redness were evident within 4 weeks. Among them, six patients were still taking propranolol, and one patient had stopped after 12 months. Other one patient did not show significant improvement with satisfactory result after 3 months of propranolol use. Treatment with propranolol was well tolerated and had few side effects. No rebound growth was observed in any of the patients. Conclusion We observed that use of propranolol was very effective in treatment of hemangioma without obvious adverse effects or relapse.

The Effect of Interleukin-4 and Amphiregulin on the Proliferation of Human Airway Smooth Muscle Cells and Cytokine Release

Airway smooth muscle (ASM) hyperplasia and angiogenesis are important features associated with airway remodeling. We investigated the effect of IL-4 and amphiregulin, an epidermal growth factor family member, on the proliferation of human ASM cells and on the release of vascular endothelial growth factor (VEGF) and monocyte chemotactic protein (MCP)-1 from human ASM cells. Human ASM cells were growth-arrested for 48 hr and incubated with platelet-derived growth factor (PDGF)-BB, interleukin (IL)-4, amphiregulin, and VEGF to evaluate cell proliferation. The cells were treated with PDGF, IL-4 and amphiregulin to evaluate the release of VEGF, MCP-1. IL-4 suppressed unstimulated and PDGF-stimulated ASM cell proliferation. Amphiregulin stimulated ASM cell proliferation in a dose-dependent manner. VEGF did not have any influence on ASM cell proliferation. IL-4 stimulated VEGF secretion by the ASM cells in a dose-dependent manner and showed added stimulatory effects when co-incubated with PDGF. Amphiregulin did not promote VEGF secretion. IL-4 and amphiregulin showed no stimulatory effects on MCP-1 secretion. The results of this study showed that IL-4 had bifunctional effects on airway remodeling, one was the suppression of the proliferation of the ASM cells and the other was the promotion of VEGF release by the ASM cells, and amphiregulin can promote human ASM cell proliferation.

Effects of Diet-Induced Mild Obesity on Airway Hyperreactivity and Lung Inflammation in Mice

Purpose Obesity has been suggested to be linked to asthma. However, it is not yet known whether obesity directly leads to airway hyperreactivity (AHR) or obesity-induced airway inflammation associated with asthma. We investigated obesity-related changes in adipokines, AHR, and lung inflammation in a murine model of asthma and obesity. Materials and Methods We developed mouse models of chronic asthma via ovalbumin (OVA)-challenge and of obesity by feeding a high-fat diet, and then performed the methacholine bronchial provocation test, and real-time PCR for leptin, leptin receptor, adiponectin, adiponectin receptor (adipor1 and 2), vascular endothelial growth factor (VEGF), transforming growth factor (TGF) β, and tumor necrosis factor (TNF) α in lung tissue. We also measured cell counts in bronchoalveolar lavage fluid. Results Both obese and lean mice chronically exposed to OVA developed eosinophilic lung inflammation and AHR to methacholine. However, obese mice without OVA challenge did not develop AHR or eosinophilic inflammation in lung tissue. In obese mice, lung mRNA expressions of leptin, leptin receptor, VEGF, TGF, and TNF were enhanced, and adipor1 and 2 expressions were decreased compared to mice in the control group. On the other hand, there were no differences between obese mice with or without OVA challenge. Conclusion Diet-induced mild obesity may not augment AHR or eosinophilic lung inflammation in asthma.