Mathematical Modeling of the Novel Influenza A (H1N1) Virus and Evaluation of the Epidemic Response Strategies in the Republic of Korea / 예방의학회지

OBJECTIVES: The pandemic of novel influenza A (H1N1) virus has required decision-makers to act in the face of the substantial uncertainties. In this study, we evaluated the potential impact of the pandemic response strategies in the Republic of Korea using a mathematical model. METHODS: We developed a deterministic model of a pandemic (H1N1) 2009 in a structured population using the demographic data from the Korean population and the epidemiological feature of the pandemic (H1N1) 2009. To estimate the parameter values for the deterministic model, we used the available data from the previous studies on pandemic influenza. The pandemic response strategies of the Republic of Korea for novel influenza A (H1N1) virus such as school closure, mass vaccination (70% of population in 30 days), and a policy for anti-viral drug (treatment or prophylaxis) were applied to the deterministic model. RESULTS: The effect of two-week school closure on the attack rate was low regardless of the timing of the intervention. The earlier vaccination showed the effect of greater delays in reaching the peak of outbreaks. When it was no vaccination, vaccination at initiation of outbreak, vaccination 90 days after the initiation of outbreak and vaccination at the epidemic peak point, the total number of clinical cases for 400 days were 20.8 million, 4.4 million, 4.7 million and 12.6 million, respectively. The pandemic response strategies of the Republic of Korea delayed the peak of outbreaks (about 40 days) and decreased the number of cumulative clinical cases (8 million). CONCLUSIONS: Rapid vaccination was the most important factor to control the spread of pandemic influenza, and the response strategies of the Republic of Korea were shown to delay the spread of pandemic influenza in this deterministic model.

Puberty and Gonadal Function after Bone Marrow Transplantation During Childhood / 대한소아내분비학회지

PURPOSE: Bone marrow transplantation (BMT) involving high dose chemotherapy and irradiation can seriously affect the gonad and reproductive axis. We studied puberty and gonadal function in the subjects who underwent BMT during childhood for the treatment of acute leukemia. METHODS: 25 females (age at examination:15.7+/-3.1 years; age at BMT:10.3+/-3.0 years) and 22 males (age at examination:16.4+/-2.0 years; age at BMT:11.1+/-2.2 years) who underwent BMT for acute leukemia were included. We evaluated their pubertal status and gonadal function before and after BMT, and investigated the clinical factors influencing disturbances of gonadal function in these patients. RESULTS: Of the 13 females who were prepubertal before BMT, two had no breast development by 13 years of age, and the others entered puberty spontaneously. Of the 8 females who were older than 16 years at the last evaluation, 5 had primary amenorrhea, and 3 developed secondary amenorrhea. Sixteen (64.0%) out of 25 pubertal females had abnormally elevated serum concentrations of luteinizing hormone (LH), and 23 (92.0%) had abnormally elevated serum concentrations of follicle-stimulating hormone (FSH). Abnormal elevation of LH was more frequent in the females who had entered puberty at BMT compared with those before puberty (91.7% vs 45.5%, OR=13.2, P<0.05). Of the 19 males who were prepubertal before BMT, 3 did not enter puberty spontaneously by 14 years of age, and the others entered puberty spontaneously. Four (18.2%) out of 22 pubertal males had abnormally elevated plasma concentrations of LH, and 9 (42.9%) had abnormally elevated plasma concentrations of FSH. Abnormal elevation of FSH was more frequent in males who underwent BMT after relapse than those without relapse (87.5% vs 20.0%, OR=28.0; P<0.05). CONCLUSION: More than 40% of the girls who underwent BMT cannot retain adequate ovarian function to complete puberty and menstruate regularly. The ovaries of the pubertal girls seem to be more vulnerable to BMT. The majority of the boys experience normal pubertal development after BMT, but about 40% of the boys had abnormally elevated levels of FSH, which is indicative of germ cell dysfunction.

Inhibition of Vascular Endothelial Growth Factor-induced Endothelial Cell Differentiation by Intravenous Immunoglobulin and Methylprednisolone / 소아과

PURPOSE: Kawasaki disease is the most common cause of systemic vasculitis in children less than 5 years of age. Recent immunohistochemistry findings suggest that many vascular growth factors play a role in the formation of the coronary artery lesions. Active remodeling of the coronary artery lesions in Kawasaki disease continues in the form of intimal proliferation and neoangiogenesis for several years after the onset of the disease. Intravenous immunoglobulin (IVIG) and corticosteroid have been used in the treatment of Kawasaki disease but the exact mechanism is not clear. We have investigated that IVIG and corticosteroid inhibited vascular endothelial growth factor (VEGF)- induced tube formation of endothelial cells in vitro on Matrigel assay. METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured and seeded on Matrigel coated 24 well plates in medium with or without the following agents: VEGF, VEGF plus IVIG, VEGF plus VEGF antibody, VEGF plus methylprednisolone, VEGF, IVIG plus methylprednisolone for 18 hours. The total length of tube structures in each photograph was quantified. RESULTS: IVIG significantly inhibited the proliferation of HUVECs. The inhibitory effect of IVIG was also reversible. In the meantime, VEGF induced the differentiation of HUVECs into capillary like structures on Matrigel, which was inhibited by VEGF antibody in a dose-dependent manner. Interestingly, IVIG and methylprednisolone inhibited VEGF-induced tube formation of HUVECs. IVIG was more effective in inhibition than methylprednisolone alone. CONCLUSION: We revealed that VEGF induced the differentiation of HUVECs and this effect was inhibited by IVIG and methylprednisolone.