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Author's summary Hypertrophic cardiomyopathy (HCM) in infancy is rare and many fulminant cases are fatal. Infantile HCM shows a rapid progressive clinical course and different characteristics compared with late-onset HCM presenting during the prepubertal age. There are also spontaneously resolving phenotypes of HCM that are diagnosed in neonates being treated for bronchopulmonary dysplasia with corticosteroids or in those with other problems related to maternal endocrine diseases. The pathophysiology of infantile HCM has not been well described. Therefore, this review updates the pathophysiology of infantile HCM and includes molecular studies on maturation of cardiomyocytes from a clinician's point of view., Hypertrophic cardiomyopathy (HCM) is characterized by ventricular wall hypertrophy with diastolic dysfunction. Pediatric HCM is distinguished from the adult in many aspects. Most children with HCM do not present clinically until the adolescent period, even when they are born with genetic mutations. Some infants with early-onset HCM present with massive progressive myocardial hypertrophy in the first few months of life, which is often fatal. The mortality of pediatric HCM peaks during the infantile and adolescent periods. These periods roughly correlate with children's growth spurt. Non-sarcomeric causes of HCM are more frequent in pediatric HCM, while sarcomeric causes are more common in adults. From the perspective of cardiac development, the fetal heart has immature cardiomyocytes, which are characterized by proliferation and exit their cell cycles with a decreased regenerative property after birth. In the perinatal period, there is a dynamic change in maturation of cardiomyocytes from immature to mature cells. Infants who are treated with steroids or born to mothers with diabetes or hyperthyroidism often show phenotypes of HCM, which gradually resolve. With remarkable advancement of molecular biology, understanding on maturation of cardiomyocytes has increased. Neonates undergo abrupt environmental changes during the transitional circulation, which is affected by oxygen, metabolic and hormonal fluctuations. Derangement in physiological transition to the normal postnatal environment may influence maturation of proliferative immature cardiomyocytes during early infancy. This article reviews updates of infantile HCM and recent molecular studies related to maturation of cardiomyocytes from the clinical point of view of identifying distinct characteristics of infantile HCM.

The impact of the coronavirus disease 2019 (COVID-19) pandemic on Kawasaki disease (KD) has not yet been established. We investigated changes in the observed number and severity of KD cases and accompanying coronary artery complications during the COVID-19 pandemic in Korea.This retrospective observational study included patients aged18 years with acute-phase KD diagnosed between March 2018 and February 2021. Data were extracted from the Clinical Data Warehouse that houses data from five affiliated university hospitals in Korea. We analyzed changes in the number of patient admissions and clinical characteristics, including cardiac complications, before and after the onset of the COVID-19 pandemic.A total of 475 admissions were included in the analysis. After March 2020, we observed a significant decrease of 33% in the number of hospitalizations for KD compared with the average number of hospitalizations during the previous 2 years. The number of admissions per month significantly decreased by 7.9 persons/month (95% confidence interval, -13.8 to -2.0;Since the onset of the COVID-19 pandemic, the total number of hospital admissions for KD has decreased in Korea. Although the proportion of admissions of infants aged1 year increased, no changes were observed in clinical courses and complications.

Background and objectives Hypertension is becoming one of the most common health conditions in children and adolescents due to increasing childhood obesity. We aimed to provide the auscultatory blood pressure (BP) normative reference values for Korean non-overweight children and adolescents. Methods BP measurements in children and adolescents aged 10 to 18 years were performed in the Korean National Health and Nutrition Examination Survey (KNHANES) from 1998 to 2016. BP was measured using a mercury sphygmomanometer. Sex-, age- and height-specific systolic BP (SBP) and diastolic BP (DBP) percentiles were calculated in the non-overweight children (n=10,442). We used the General Additive Model for Location Scale and Shape method to calculate BP percentiles. Results The 50th, 90th, 95th, and 99th percentiles of SBP and DBP tables and graphs of non-overweight children and adolescents aged 10 to 18 years were presented by age and height percentiles. We found that the SBP and DBP at the 95th percentile were well correlated with height. The BP tables presented by height contained BP values from 124 cm to 190 cm for boys and from 120 cm to 178 cm for girls. Boys had higher SBP and DBP. Conclusions We provided the sex-, age- and height-specific auscultatory BP values using the KNHANES big data. These may be useful in diagnosis and treatment of hypertension in Korean children and adolescents.

Graves disease (GD) can lead to complications such as cardiac arrhythmia and heart failure. Although dilated cardiomyopathy (DCMP) has been occasionally reported in adults with GD, it is rare in children. We present the case of a 32-month-old boy with DCMP due to GD. He presented with irritability, vomiting, and diarrhea. He also had a history of weight loss over the past few months. On physical examination, he had tachycardia without fever, a mild diffuse goiter, and hepatomegaly. The chest radiograph showed cardiomegaly with pulmonary edema, while the echocardiography revealed a dilated left ventricle with an ejection fraction (EF) of 28%. The thyroid function test (TFT) showed elevated serum T3 and decreased thyroid stimulating hormone (TSH) levels. The TSH receptor autoantibody titer was elevated. He was diagnosed with DCMP with GD; treatment with methylprednisolone, diuretics, inotropics, and methimazole was initiated. The EF improved after the TFT normalized. At follow-up several months later, although the TFT results again showed evidence of hyperthyroidism, his EF had not deteriorated. His cardiac function continues to remain normal 1.5 months after treatment was started, although he still has elevated T3 and high TSH receptor antibody titer levels due to poor compliance with drug therapy. To summarize, we report a young child with GD-induced DCMP who recovered completely with medical therapy and, even though the hyperthyroidism recurred several months later, there was no relapse of the DCMP.

Purpose: There are no specific tests for diagnosing Kawasaki disease (KD). Additional diagnostic criteria are needed to prevent the delayed diagnosis of incomplete Kawasaki disease (IKD). This study compared the frequency of coronary artery lesions (CALs) in IKD patients with and without anterior uveitis (AU) and elucidated whether the finding of AU supported the diagnosis of IKD. Methods: This study enrolled patients diagnosed with IKD at The Catholic University of Korea, Uijeongbu St. Mary’s Hospital from January 2010 to December 2014. The patients were divided into 2 groups: group 1 included patients with IKD having AU; and group 2 included patients with IKD without AU. We analyzed the demographic and clinical data (age, gender, duration of fever, and the number of diagnostic criteria), laboratory results, and echocardiographic findings. Results: Of 111 patients with IKD, 41 had uveitis (36.98%, group 1) and 70 did not (63.02%, group 2). Patients in group 1 had received a diagnosis and treatment earlier, and had fewer CALs (3 of 41, 1.7%) than those in group 2 (20 of 70, 28.5%) (P=0.008). All 3 patients with CALs in group 1 had coronary dilatation, while patients with CALs in group 2 had CALs ranging from coronary dilatation to giant aneurysm. Conclusion: The diagnosis of IKD is challenging but can be supported by the presence of features such as AU. Group 1 had a lower risk of coronary artery disease than group 2. Therefore, the presence of AU is helpful in the early diagnosis and treatment of IKD and can be used as an additional diagnostic tool.

Kawasaki disease (KD) may be an acute systemic immune-mediated disease which occurs after infection of unknown KD pathogen(s). The aim of this study is to evaluate the changes in platelet count and immunoglobulin (Ig) levels (IgG, IgM, IgA, and IgE) during hospitalization. Forty-three patients with complete KD who received intravenous Ig at 2 g/kg were enrolled in South Korea. The platelet count and Ig levels of the patients were examined twice at presentation and around discharge (mean 6.2 ± 2.4 days apart) and the relationships between platelet level and Ig levels were evaluated. The mean patient age was 31 ± 18 months; 28 patients were male and 15 were female. The values of all parameters measured, with the exception of IgE, were significantly increased at the second examination compared with their values at presentation. These values gradually increased over time after fever onset, over periods ranging from 2 to 16 days. The extent by which platelet levels increased over these 2 time points was correlated with the extents by which IgG (P

Dilated cardiomyopathy (DCMP) remains a life threatening disease in young patients and is often difficult to differentiate from myocarditis. Early recognition and treatment of DCMP are crucial for good prognoses in this patient population. The clinical course of patients with DCMP that result in cardiogenic shock varies according to the etiology as well as patient age. The volumetric expansion of the enlarged heart can compress adjacent structures causing a number of related symptoms, especially in infants with soft cartilaginous bronchi. Therapeutic strategies for treating these issues vary according to the type of complication encountered. We report a case of severe DCMP with sudden onset of massive cardiomegaly with heart failure complicated by bronchial obstruction in an infant.

BACKGROUND The goal of this study is to evaluate the changes in the epidemiologic and clinical features of Kawasaki disease (KD) in a period of 20 years. METHODS We compared the epidemiologic features of 3 KD patient groups: those admitted from 1987 to 1990 (122 cases), from 1997 to 2000 (137 cases) and from 2007 to 2010 (102 cases). For clinical features, we reviewed the medical records of patients admitted from 1996 to 2000 (141 cases) and from 2006 to 2010 (121 cases). RESULTS There were a total of 772 KD patients during the study period (mean age: 27.2 months; male-to-female ratio: 1.6:1). There were some variations in the mean ages (23.8, 27.8 and 30 months), in the male-to-female ratios (1.9:1, 1.3:1 and 1.8:1) and in the age distributions, including the patients of ages 5 years, but the differences were not statistically significant across the groups. The seasonal distributions were relatively consistent with some variations. In clinical features, the preadmission and total fever durations were shorter (P < 0.001, respectively), and the proportions of incomplete KD tended to increase, and the rates of coronary artery aneurysm tended to decrease in recently admitted patients. CONCLUSIONS There were no significant changes in the demographic and seasonal features of KD, although the evaluation of the clinical features showed shorter fever duration suggestive of improved identification and treatment of KD over time.

Respiratory difficulty resulting from congenital chylothorax is usually relieved by postnatal thoracentesis, closed chest drainage, and oxygen therapy. However, early occurrence of congenital chylothorax or accumulation of a large amount of chylous fluid sometimes leads to pulmonary hypoplasia or persistent pulmonary hypertension of the newborn, which requires further customized mechanical ventilatory support. In these cases, conventional mechanical ventilation is primarily used during initial treatment and is later replaced by high-frequency ventilation, but the advantages of inhaled nitric oxide treatment have rarely been described. This case suggests the benefits of inhaled nitric oxide in patients with congenital chylothorax, even when mechanical ventilation cannot improve respiratory distress because of severe pulmonary hypertension of the newborn leading to right cardiac dysfunction and possibly cholestasis.

The present study explores the problem of the placelessness and alienation through spaces of redevelopment in South Korean animation film since the 2000`s. Actual space in South Korean society has been destroyed and changed unceasingly, and, in that space, humans have experienced existential conflict. While the swift development of digital technology has transcended physical restrictions to form one great network, humans are still limited as materially based beings. The recent steps in South Korean animation film are noteworthy because sociocultural changes since the 1990`s and the relationship between the individual and the system are perceived in ways different from those of the past. and , the works analyzed in the present study, reveal the special sense of place in South Korean society, where the destructive reorganization of space leads to the instability of life. By intentionally bypassing a sense of place and the authority automatically bestowed on representational images, these works prompt the viewer to reexamine the relationship between reality and images. Space in these two works are presented representationally but immediately destroyed, and humans or the characters in the works accept this unfeelingly. The loss of place, which is committed by the massive system, and listless humans` weakness and alienation in response are depicted as signs of sociocultural abnormality. By showing the destructive loss of place and individuals who respond with self-anesthesia and self-estrangement, these works open viewers` eyes to South Korean society, where not only social alienation but also self-alienation is occurring. By perceiving South Korean animation film as a sociocultural phenomenon and analyzing it through the concepts of the placelessness and alienation, the present study seeks to expand further discussions on animation film.

A missense mutation in mouse Nek8 , which encodes a ciliary kinase, produces the juvenile cystic kidneys ( jck ) model of polycystic kidney disease, but the functions of Nek8 are incompletely understood. Here, we generated a Nek8- null allele and found that homozygous mutant mice die at birth and exhibit randomization of left-right asymmetry, cardiac anomalies, and glomerular kidney cysts. The requirement for Nek8 in left-right patterning is conserved, as knockdown of the zebrafish ortholog caused randomized heart looping. Ciliogenesis was intact in Nek8- deficient embryos and cells, but we observed misexpression of left-sided marker genes early in development, suggesting that nodal ciliary signaling was perturbed. We also generated jck/Nek8 compound heterozygotes; these mutants developed less severe cystic disease than jck homozygotes and provided genetic evidence that the jck allele may encode a gain-of-function protein. Notably, NEK8 and polycystin-2 (PC2) proteins interact, and we found that Nek8 −/− and Pkd2 −/− embryonic phenotypes are strikingly similar. Nek8 -deficient embryos and cells did express PC2 normally, which localized properly to the cilia. However, similar to cells lacking PC2, NEK8-depleted inner medullary collecting duct cells exhibited a defective response to fluid shear, suggesting that NEK8 may play a role in mediating PC2-dependent signaling.

REFER TO THE PAGE 123-127 Recent advancement of technology of medical imaging systems has enabled in-depth real time spatiotemporal diagnosis of human heart disease. It is regardless to mention that prognosis of cardiac disease is based critically on prompt 3 dimensional (3D) diagnosis of a structural anomaly, functional analysis and followed by a proper treatment. Although we are in current era of 3D skills in the spotlight, yet real time 3D echocardiography (RT3DE) is not so appealing to very busy pediatric and adult cardiologists. Mental reconstruction of harvested 2 dimensional (2D) echocardiographic images is a still much faster and simpler way to understand complex cardiac structural anomaly than doing a few more steps for subsequent data analysis with a software program of RT3DE. On the other hand, considering superiority of function of volume assessment, RT3DE can be very useful in clinical application as it can provide numeric data more precisely than morphologic visual assessment of each cardiac chambers that enables assessment longitudinally during the clinical course. In congenital heart disease (CHD), volume or pressure overloaded condition frequently results in distortion of septal planes followed by a geometric change in either ventricles that hampers precise ventricular volume assessment using conventional 2D echocardiography.1),2) There are many reports on the reproducibility of RT3DE in clinical application to adults population without a complex heart disease.3) It is known that current RT3DE has relatively a high intraobserver and interobserver variability.4) In pediatric cases with a complex CHD, additional time consuming effort is required for the assessment of detailed anatomical defect during navigation of intriguing small cardiac structures to acquire optimal planes for secondary 3D reconstruction. Novel imaging tools including RT3DE always require its validation steps. Many studies on the left ventricular volume and ejection fraction compared to cardiac magnetic resonance imaging (MRI) data, currently a gold standard method of cardiac volume assessment have been published during the last ten years.5),6) It is known that the results acquired by RT3DE of left ventricular volume assessment has strong correlation with cardiac MRI although ventricular volume by RT3DE has tendency of underestimation.6),7),8) Studying with cardiac MRI in pediatric patients in critical condition with CHD has several limitations as to its long scanning time and practical issues on patient's sedation and infeasibility in patients with pacemaker. If we mention about volumetric assessment of right ventricle considering its 3 dimensionally distorted morphology compared to left ventricle, there should be no doubt on the superiority of RT3DE to 2D echocardiography and related issues are published.9),10) As RT3DE is a noninvasive method, if it can overcome current several issues of its limitation, it might be the most useful tool to examine children with CHD. Many experts in the field of echocardiography believe that its clinical application by skillful clinicians will provide infinite derivative outcomes in longitudinal monitoring of functional abnormality especially in cases with surgically corrected complex CHD.11),12) However in reality, likewise cardiac MRI, RT3DE is still a secondary option to conventional 2D echocardiography with its limitations and infeasibility to pediatric populations with CHD. Therefore, further studies on this issue are strongly encouraged for further analysis. An inspiring outcome shown here titled 'Assessment of left ventricular volume and function using real-time 3D echocardiography versus angiocardiography in children with Tetralogy of Fallot' is that RT3DE can be practically and convincingly used in volumetric assessment in CHD patients with real time and non-invasive scanning.13) Authors tried to validate RT3DE comparing with angiographic data. Considering hard working in assessment of complicated geometric deformation of left ventricle in tetralogy of Fallot and technical difficulty in handling pediatric patients, this study is deserved the spotlight. They showed that there was a strong correlation between the mean value of the left ventricular end diastolic volume and its index measured by RT3DE and angiography with good intra- and inter-observer reliability. With training time and experience, unquestionably a simple 'crop box' will give us an infinitely useful information with simplified off-line analysis of harvested images with a cutting-edge software program. With an optimistic view towards the RT3DE in CHD, current doubt on values of RT3DE hopefully should be faded with an accelerated speed with the help of advancement of technology in the near future.

This study examines online social media diffusion across different countries that will help to provide a picture of current global online social network services (SNSs). Analyzing country-level data drawn from 78 nations, we find that non-technological factors such as culture and language as well as technological factors including Internet penetration rate and smartphone adoption rate have significant effects on online social media diffusion. These findings, derived from a broad range of different countries, not only provide theoretical insights into understanding critical factors that enable successful global expansion of online social media services but also help practitioners plan their marketing strategies more effectively in a global context.

Myocardial infarction (MI) is one of the leading causes of morbidity and mortality world-wide. Whether endogenous repair and regenerative ability could be augmented by drug administration is an important issue for generation of novel therapeutic approach. Recently it was reported that in mice pretreated with thymosin beta 4 (TB4) and subsequently subjected to experimental MI, a subset of epicardial cells differentiated into cardiomyocytes. In clinical settings, epicardial priming with TB4 prior to MI is impractical. Here we tested if TB4 treatment after MI could reprogram epicardium into cardiomyocytes and augment the epicardium's injury response. Using epicardium genetic lineage trace line Wt1CreERT2/+ and double reporter line Rosa26mTmG/+, we found post-MI TB4 treatment significantly increased the thickness of epicardium and coronary capillary density. However, epicardium-derived cells did not adopt cardiomyocyte fate, nor did they migrate into myocardium to become coronary endothelial cells. Our result thus indicates that TB4 treatment after MI does not alter epicardial cell fate to include the cardiomyocyte lineage, providing both cautions and insights for the full exploration of the potential benefits of TB4 in the clinical settings. This article is part of a Special Issue entitled ‘Possible Editorial’.

In this study, the recrystallization of valsartan by ASES (Aerosol Solvent Extraction System), a supercritical micronization process, using compressed CO 2 was carried out to improve the bioavailability of valsartan through preparation of micro sized particles without excessive agglomeration. Fine valsartan particles from an ethyl acetate (EA) solution were precipitated using compressed CO 2 as an antisolvent at low temperature. The EA was considered a proper organic solvent to prevent agglomeration of the prepared valsartan associating to the solubility parameters of the solvents. Ultra fine valsartan particles with a mean diameter of 0.1 μm were obtained without excessive agglomeration at the subcritical CO 2 of 70 bar and 5 °C. When the supercritical CO 2 was at 100 bar and 40 °C, valsartan was precipitated to fine particles that tended to agglomerated due to the melting point depression produced by CO 2 . During the agglomeration process, particles were sintered by the Ostwald ripening mechanism, which resulted in an increase in particle size. Agglomeration of the particles was shown to be prevented at low temperature, where re-melting of the precipitated valsartan particles is minimized. Hence, processed valsartan with compressed CO 2 at a low temperature improved its dissolution rate due to the small size of the particles attributing to low level of particle agglomeration.

The epicardium makes essential cellular and paracrine contributions to the growth of the fetal myocardium and the formation of the coronary vasculature. However, whether the epicardium has similar roles postnatally in the normal and injured heart remains enigmatic. Here, we have investigated this question using genetic fate-mapping approaches in mice. In uninjured postnatal heart, epicardial cells were quiescent. Myocardial infarction increased epicardial cell proliferation and stimulated formation of epicardium-derived cells (EPDCs), which remained in a thickened layer on the surface of the heart. EPDCs did not adopt cardiomyocyte or coronary EC fates, but rather differentiated into mesenchymal cells expressing fibroblast and smooth muscle cell markers. In vitro and in vivo assays demonstrated that EPDCs secreted paracrine factors that strongly promoted angiogenesis. In a myocardial infarction model, EPDC-conditioned medium reduced infarct size and improved heart function. Our findings indicate that epicardium modulates the cardiac injury response by conditioning the subepicardial environment, potentially offering a new therapeutic strategy for cardiac protection.

Background: Idiopathic cardiomyopathies (CMPs) are an important heterogeneous group of diseases. With the advance of therapeutic strategies, epidemiologic data on CMP have become very important, but only a few have been reported in Asian children. We conducted a retrospective epidemiologic study of primary CMP in Korean children. Methods and Results: Using a multicenter survey, we studied primary CMP among Korean children from January 1998 to December 2006 based on classification (2006) of CMP by the American Heart Association. A total of 277 primary CMP patients were reported from 17 cardiovascular centers. The average annual occurrence of new cases of primary CMP was 0.28 per 100,000 Korean children younger than 15 years of age (95% confidence interval (CI) 0.24-0.31). Dilated CMP (DCMP) was 66.43%, hypertrophic CMP (HCMP) 23.47%, restrictive CMP (RCMP) 6.50% and others 3.61%. The point prevalence of primary CMP at the end of the study was estimated as 2.11/100,000 (95%CI 1.83-2.43), DCMP 1.39/100,000, HCMP 0.51/100,000, RCMP 0.16/100,000 and others 0.04/100,000. Survival rates over 9 years were 69.8% in DCMP, 90.3% in HCMP, and 47.2% in RCMP. Conclusions: Recent point prevalence of childhood primary CMP in Korea was estimated as 2.11/100,000. Further epidemiologic study with a nationwide survey is necessary. (Circ J 2011; 75: 2228-2234)

Purpose Medium-dose (1 g/kg) intravenous immunoglobulin (IVIG) is effective in the majority of patients with Kawasaki disease (KD) but some patients who do not respond to medium-dose IVIG are at high risk for the development of coronary artery lesions (CALs). The purpose of this study was to identify the clinical predictors associated with unresponsiveness to medium-dose IVIG and the development of CALs. Methods A retrospective study was performed in 91 children with KD who were treated with medium-dose IVIG at our institution from January 2004 to December 2013. We classified the patients into responders (group 1; n=68) and nonresponders (group 2; n=23). We compared demographic, laboratory, and echocardiographic data between the 2 groups. Results Multivariate logistic regression analysis identified 6 variables as predictors for resistance to medium-dose IVIG. We generated a predictive scoring system assigning 1 point each for percentage of neutrophils ≥65%, C-reactive protein≥100 mg/L, aspartate aminotransferase≥100 IU/L, and alanine aminotransferase≥100 IU/L, as well as 2 points for less than 5 days of illness, and serum sodium level≤136 mmol/L. Using a cutoff point of ≥4 with this scoring system, we could predict nonresponsiveness to medium-dose IVIG with 74% sensitivity and 71% specificity. Conclusion If a patient has a low-risk score in this system, medium-dose IVIG can be recommended as the initial treatment. Through this process, we can minimize the adverse effects of high-dose IVIG and incidence of CALs.

The lung is enveloped by a layer of specialized epithelium, the pulmonary mesothelium. In other organs, mesothelial cells undergo epithelial–mesenchymal transition and contribute to organ stromal cells. The contribution of pulmonary mesothelial cells (PMCs) to the developing lung has been evaluated with differing conclusions. PMCs have also been indirectly implicated in lung fibrosis in the progressive, fatal lung disease idiopathic pulmonary fibrosis. We used fetal or postnatal genetic pulse labeling of PMCs to assess their fate in murine development, normal lung homeostasis, and models of pulmonary fibrosis. We found that most fetal PMC-derived mesenchymal cells (PMCDCs) expressed markers of pericytes and fibroblasts, only a small minority expressed smooth muscle markers, and none expressed endothelial cell markers. Postnatal PMCs did not contribute to lung mesenchyme during normal lung homeostasis or in models of lung fibrosis. However, fetal PMCDCs were abundant and actively proliferating within fibrotic regions in lung fibrosis models, suggesting that they actively participate in the fibrotic process. These data clarify the role of fetal and postnatal PMCDCs in lung development and disease.

Background: Some patients with intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) do not respond to intravenous methylprednisolone (IVMP). Infliximab (IFX; anti-TNF-α antibody) is an alternative medication for intractable KD. Its effectiveness in preventing coronary aneurysms from progressing is being reported. We herein report a case of intractable KD that slowly progressed to giant aneurysm despite a second IFX infusion. Methods: A 2-year-old boy visited our hospital with a 2-day history of fever. On day 3 after fever onset, a swollen cervical lymph node, redness of the BCG (bacilli Calmette Guérin) inoculation site, and indurated erythema of the palms with soles were observed. On day 5, conjunctival injection, strawberry tongue, red lips and truncal rash were present. The patient was diagnosed with KD and treated with IVIG and acetylsalicylic acid (ASA). Results: The fever persisted for 24 h after IVIG treatment. A second dose of IVIG was infused. However, the fever continued. Then IVMP was infused. On day 9, the fever resolved. On day 10, two-dimensional echocardiography (2DE) showed mild dilations (Φ 3.0 mm) of both coronary arteries (CAs). On day 18, the fever recurred. Follow-up 2DE showed dilated CAs (left main coronary artery [LM], Φ 4.0 mm; right coronary artery [RCA], Φ 4.0 mm). Therefore, IFX was intravenously infused. On day 19, the fever had resolved and the patient went home. On day 22, the fever recurred. Thus, a second infusion of IFX was done. On day 24, the fever resolved. Follow-up 2DE showed that the diameters of the CAs were 4.0 mm (LM), 7.0 mm (left anterior descending coronary artery [LAD]), 3.0 mm (RCA). On day 28, a mild fever was still present. On day 47, follow-up 2DE indicated that the diameters of the CAs were 3.0 mm (LM), 8.0 mm (LAD), 2.5 mm (RCA). On day 159, follow-up 2DE showed slightly increased regression of CAs. The patient has been undergoing regular 2DE and taking ASA since he left the hospital. Conclusions: This was a very rare case of KD that was resistant to standard treatment comprising high-dose steroids and TNF-α blockade. We have reported this case to inform clinicians who may encounter such patients with KD in the future. A high index of suspicion and keen observations are strongly recommended for cases of intractable KD.

Objectives: A high-dose (2g/kg) intravenous immunoglobulin (IVIG) has been generally incorporated into the acute treatment protocols for Kawasaki disease (KD), with ongoing debates on this issue. The aim of this study was to assess the effectiveness of medium-dose (1g/kg) IVIG as an initial treatment of KD in Korean children. Methods: A retrospective study was done in a total of 255 children with KD, in whom 91 patients (group 1, mean age; 2.8 ± 2.5 years) had 2g/kg of IVIG and 164 patients (group 2, mean age; 2.7 ± 1.7 years) had 1g/kg of IVIG as an initial treatment of KD, along with 30-50 mg/kg of aspirin. Echocardiography (Echo) was done during admission, around 2 weeks, 2 months, and 1 year after the onset of fever according to our protocol. Patients who completed one-year Echo study were included in this study. Patients’ demographic, laboratory, and Echo findings were recorded, and compared between groups. Coronary artery lesions (CAL) were defined as a coronary artery diameter > 2 SD of normal mean for age or coronary artery stenosis. The primary end point was the incidence of CAL at 1 year after treatment. The secondary end points were the incidence of CAL at 2 weeks and 2 months study, and clinical outcomes. Comparisons between groups were done using an unpaired t-test or Fisher’s exact test. Results: There was no significant difference in age, gender, and laboratory findings before treatment between the two groups. Group 1 had higher incidence of CAL at 2 weeks (32/91, 35.2 % vs. 33/164, 20.2 %, p = 0.011), but similar incidence of CAL at 2 months (18/91, 19.8% vs. 24/164, 14.6%, p > 0.05) and 1 year (6/91, 6.6% vs. 10/164, 6.1%, p > 0.05) compared with group 2. Group 1 had a higher proportion of patients needed additional dose of IVIG (23/91, 25.3% vs. 15/164, 9.1%, p = 0.001), but received significantly lower total dose of IVIG (1.3 ± 0.7 g/kg vs. 2.1 ± 0.5 g/kg, p < 0.001) compared with group 2. There was no difference in duration of fever after IVIG and duration of hospital stay between the two groups. Conclusion: This study demonstrated that medium-dose IVIG is as effective as high-dose IVIG for the treatment of KD in terms of CAL prevention, defervescence, and duration of hospital stay. Further prospective and randomized study is needed to verify this.

Background: Very young infants with Kawasaki disease (KD) often present with atypical features that render diagnosis difficult and the incidence of coronary complications high. Picking up clues at early phase of KD can be critical. Herein we present 3 cases of KD in very young infants who showed mitral regurgitation (MR) around the 7th day from the onset of fever. They received IVIG around 7th fever day. However, the advice for short-term follow up echocardiography (ECHO) was neglected as clinical course thereafter were so unusual. Giant coronary aneurysms developed in all the patients later. Case 1: A 31-day-old infant got admission care for sepsis. ECHO at the 7th day from the onset of fever showed trivial MR and the patient received IVIG. Follow up ECHO was recommended, but was not conducted as clinical course was ambiguous for KD thereafter. Being treated with steroids due to skin rash and eosinophilia that masked patient’s fever, the infant reappeared to hospital with cardiogenic shock 10 days later. ECHO revealed giant aneurysms in the right coronary artery (RCA) and CT angiography for pulsating axillary masses revealed axillary aneurysms. Case 2; A 67-day-old infant was admitted with fever and persistent thrombodytopenia. ECHO done at the 5th day from the onset of fever due to red lips showed non-specific findings. Follow up ECHO at the 7th fever day showed newly developed MR. IVIG and steroids was added on for persistent fever, but severe leukocytosis ensued and clinical course was also ambiguous for KD. Defervescence was achieved with infliximab. The infant showed coronary aneurysms. Case 3; A 80-day-old infant was admitted with fever and seizure, and treated for sepsis. On the 6th day from the onset of fever, MR was shown on ECHO and the patient received IVIG and steroids. However, fever and severe anemia, left shift of leukocytes, and severe thrombocytopenia persisted for two weeks. Giant coronary aneurysms, as large as the ascending aorta, developed in the RCA. Pulsatile masses identified in the axilla were found to be large aneurysms on CT angiography. Conclusion: A newly developed MR, even trivial, around the 7th day from the onset of fever may be a clue to the diagnosis of KD and short term follow up ECHO is recommended for ongoing febrile infants younger than 3 months.

Ferulic acid (3-methoxy, 4-hydroxy cinnamic acid) is a flavoid component possessing antioxidant property. The compound is currently under development as a new drug candidate for the treatment of the dementia. The objective of this preformulation study was to determine the physicochemical properties of ferulic acid. The n-octanol to water partition coefficients of ferulic acid were 0.375 and 0.489 at the pHs of 3 and 10, respectively. Accelerated stability study for ferulic acid indicated that the t 90 value for the drug was estimated to be 459 days at 25 degrees C. Ferulic acid was also found to be unstable under the relative humidity of more than 76%, probably because of the hygroscopic nature of the drug. In order to study compatibility of ferulic acid with typical excipients, potential change in differential scanning calorimetry spectrum was studied in 1:1 binary mixtures of ferulic acid and typical pharmaceutical excipients (e.g., Aerosil, Avicel, CMC, Eudragit, lactose, PEG, PVP, starch and talc). Avicel, CMC, PVP and starch were found to be incompatible with ferulic acid, indicating the addition of these excipients may complicate the manufacturing of the formulation for the drug. Particle size distribution of ferulic acid powder was in the size range of 10-190 microm with the mean particle size of 61 microm. The flowability of ferulic acid was apparently inadequate, indicating the granulation may be necessary for the processing of the drug to solid dosage forms. Two polymorphic forms were obtained by recrystallization from various solvents used in formulation. New polymorphic form of ferulic acid, Form II, was obtained by recrystallization from 1,4-dioxane. The equilibrium solubility for Form I was approximately twice of that for Form II. The dissolution rate of Form II was higher than that of Form I in the early phase (

Purpose: This study aimed to evaluate the autonomic imbalance in syncope by comparing the baseline heart rate variability (HRV) between healthy children and those with vasovagal syncope. Methods: To characterize the autonomic profile in children experiencing vasovagal syncope, we evaluated the HRV of 23 patients aged 7–18 years and 20 healthy children. These children were divided into preadolescent (

Various haematological and immunological studies on patients infected with Plasmodium vivax were undertaken, at diagnosis (day 0), after treatment with chloroquine but during primaquine treatment (day 10) and after all treatment (day 59), in South Korea (where there has been a recent and abrupt increase in the incidence of such infection). The main aims were to gain an understanding of the haemato-immunological alterations of this malarial infection, both before and after treatment, and to identify at least one useful marker for the diagnosis and post-treatment monitoring of P. vivax malaria. Thirty-eight patients with P. vivax malaria were compared with 20, apparently healthy controls. At diagnosis, the patients had lymphopenia, marked eosinopenia (the eosinophil count being correlated with the platelet count) and thrombopenia. Cells of most of the lymphocyte subsets investigated [i.e. CD3 + , CD8 + , CD19 + , CD56 + , CD3 - /CD56 + and CD8 + /CD56 + but not CD4 + , CD3 + /CD56 + or CD25 + ] were significantly less common among the lymphocytes of patients at diagnosis than among those of the controls. After initiating treatment, the numbers of CD19 + lymphocytes gradually increased (to normal values by day 59), whereas those of CD3 + /56 lymphocytes remained abnormally low throughout the follow-up period. The proportions of lymphocytes identified as CD4 + appeared to be unaffected by treatment. Although serum concentrations of IgE (and, to a lesser extent, IgM) were elevated in the patients at diagnosis, they were subnormal on day 10 post-treatment and normal at the day-59 follow-up. Serum concentrations of IgG and IgA in the patients were always found to be similar to those in the controls. At diagnosis the serum concentrations of complements C3 and C4 were significantly elevated in the patients. C3 remained at the same high concentration during follow-up but the concentration of C4, like that of IgE, was found to be subnormal on day 10 and normal 7 weeks later. The level of parasitaemia (%) was only found to be significantly correlated with haemoglobin concentration. The observation of eosinopenia with elevated IgE and C4 could be a useful indicator of P. vivax malaria, and treatment response could be followed by serial monitoring of serum concentrations of IgE and C4.