Clinical Characteristics of Macrolide-Resistant Mycoplasma pneumoniae from Children in Jeju.

Mycoplasma pneumoniae is the major pathogen of community-acquired pneumonia in children. The prevalence of macrolide-resistant M. pneumoniae (MRMP) is important owing to the limited alternative therapies for children. We analyzed 111 M. pneumoniae obtained from 107 children admitted for lower respiratory tract infection at Jeju National University Hospital between 2010 and 2015. Macrolide resistance of M. pneumoniae was searched for using polymerase chain reaction (PCR) and sequencing. Of 107 clinical M. pneumoniae, 11 (10.3%) carried macrolide resistance mutations in the 23S rRNA gene. All macrolide resistance mutations were A2063G transitions. We found an acquired A2063G mutation of M. pneumoniae from a patient during macrolide treatment. Patients' characteristics and clinical severity did not differ between those with MRMP and macrolide-sensitive M. pneumoniae, with the exception of frequent pleural effusion in the MRMP group. The prevalence of MRMP (10.3%) in Jeju Island was relatively lower than those of surrounding countries in East Asia. Previous antimicrobial usage and timing of diagnostic test should be considered when determining of macrolide resistance of M. pneumoniae.

Sonographic Growth Charts for Kidney Length in Normal Korean Children: a Prospective Observational Study.

Kidney length is the most useful parameter for clinical measurement of kidney size, and is useful to distinguish acute kidney injury from chronic kidney disease. In this prospective observational study of 437 normal children aged between 0 and < 13 years, kidney length was measured using sonography. There were good correlations between kidney length and somatic values, including age, weight, height, and body surface area. The rapid growth of height during the first 2 years of life was intimately associated with a similar increase in kidney length, suggesting that height should be considered an important factor correlating with kidney length. Based on our findings, the following regression equation for the reference values of bilateral kidney length for Korean children was obtained: kidney length of the right kidney (cm) = 0.051 × height (cm) + 2.102; kidney length of the left kidney (cm) = 0.051 × height (cm) + 2.280. This equation may aid in the diagnosis of various kidney disorders.

Concomitant use of corticosteroid and antimicrobials for liver abscesses in patients with chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a rare inherited disorder caused by defective nicotinamide adenine dinucleotide phosphate oxidase enzyme and characterized by recurrent bacterial and fungal infections. Although liver abscess is a common manifestation of CGD, its management in CGD patients is not well-defined. In addition, the generalized guidelines for treating liver abscesses do not necessarily apply to CGD patients. Corticosteroids are commonly used to control granulomatous complications, such as inflammatory gastrointestinal and genitourinary lesions, in patients with CGD, Corticosteroids have also been used in combination with antimicrobials to treat refractory infections in patients with CGD. Because corticosteroids are capable of suppressing symptomatic inflammation, all potential infections must be adequately controlled prior to corticosteroid initiation. We report 3 typical CGD cases with liver abscesses refractory to conventional treatments that were successfully treated with the concomitant use of corticosteroid and antimicrobials. It remains unclear whether corticosteroid therapy is required for liver abscesses in CGD refractory to conventional treatments. However, based on our observations, use of corticosteroids in combination with optimal antimicrobials should be considered for refractory liver abscesses in CGD.

Long-term outcome of patients with p22 (phox) -deficient chronic granulomatous disease on Jeju Island, Korea.

PURPOSE: This study investigated the long-term clinical outcomes of patients with p22 (phox) -deficient chronic granulomatous disease (CGD) on Jeju Island and retrospectively evaluated the effects of interferon-gamma (IFN-γ) prophylaxis. METHODS: The medical records of 15 patients with CGD were retrospectively reviewed. The efficacy of IFN-γ prophylaxis was evaluated by comparing the frequency of severe infections before and after starting continuous prophylaxis with IFN-γ. RESULTS: At the time of the analysis, 14 patients were alive, with a median age of 14.3 years. The diagnosis of CGD was made at a median age of 2.4 years, and the median age at onset of severe infection was 0.3 years. Thirteen of the 15 patients had their first severe infection within the first year of life. The overall incidence of severe infection was 1.36 infections per patient-year; pneumonia, suppurative lymphadenitis, and skin and subcutaneous abscesses were the most common infections. Aspergillus species were the most frequently isolated microorganisms, present in 15.8% of isolates. IFN-γ did not significantly change the rate of severe infection. The survival rate for patients after 2 years of age was 93%; there was a prolonged survival plateau beyond the age of 2. CONCLUSION: Compared with cases of X-linked CGD reported in other studies, patients with CGD on Jeju Island did not show obviously different clinical manifestations, but they had a significantly higher survival rate. Further studies with a substantially longer period of observation, and with more patients under intensive surveillance are necessary to elucidate the prophylactic efficiency of IFN-γ.

Genetic analysis of CYBB gene in 26 korean families with X-linked chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a rare hereditary disorder that is characterized by a greatly increased susceptibility to life-threatening bacterial and fungal infections. CGD is caused by mutations in any one of the genes encoding subunits of phagocyte NADPH oxidase. X-linked CGD, more than half of all CGD cases, is caused by mutations in CYBB gene encoding gp91-phox subunit. We identified the mutations in the CYBB gene of 29 Korean patients with X-linked CGD from 26 unrelated families. Twenty-three mutations were identified: five splice site mutations (c.45 + 1G > C, c.141 + 5G > A, c.897 + 2T > C c.1461 + 1G > T, c.1586 + 2T > A), four frameshift mutations (c.27dupG, [c.737A > C; c.742delA], c.742dupA, c.1636 del C), seven non-sense mutations (c217C > T, c.469C > T, c.676C > T, c.868C > T, c.1222G > T, c.1272G > A, c.1281T > A), five missense mutations (c.164 C > A, c.422T > C, c.665 A > G, c.1012C > T, c.1461G > T) and two gross deletions. Eight out of 23 mutations identified in this study are novel mutations: two splice mutations(c.897 + 2T > C, c.1586 + 2T > A), two frame shift mutations ([c.737A > C; c.742delA], c.1636 del C), two nonsense mutations (c.1222G > T, c.1281T > A), one missense mutation (c.1461G > T), one gross deletion (c.1667_1629 del.). Our results confirmed that mutations of CYBB gene in the X-CGD are very heterogeneous and not show the peculiarity of the ethnic group.

Systemic classification for a new diagnostic approach to acute abdominal pain in children.

PURPOSE: With previous methods based on only age and location, there are many difficulties in identifying the etiology of acute abdominal pain in children. We sought to develop a new systematic classification of acute abdominal pain and to give some helps to physicians encountering difficulties in diagnoses. METHODS: From March 2005 to May 2010, clinical data were collected retrospectively from 442 children hospitalized due to acute abdominal pain with no apparent underlying disease. According to the final diagnoses, diseases that caused acute abdominal pain were classified into nine groups. RESULTS: The nine groups were group I "catastrophic surgical abdomen" (7 patients, 1.6%), group II "acute appendicitis and mesenteric lymphadenitis" (56 patients, 12.7%), group III "intestinal obstruction" (57 patients, 12.9%), group IV "viral and bacterial acute gastroenteritis" (90 patients, 20.4%), group V "peptic ulcer and gastroduodenitis" (66 patients, 14.9%), group VI "hepatobiliary and pancreatic disease" (14 patients, 3.2%), group VII "febrile viral illness and extraintestinal infection" (69 patients, 15.6%), group VIII "functional gastrointestinal disorder (acute manifestation)" (20 patients, 4.5%), and group IX "unclassified acute abdominal pain" (63 patients, 14.3%). Four patients were enrolled in two disease groups each. CONCLUSION: Patients were distributed unevenly across the nine groups of acute abdominal pain. In particular, the "unclassified abdominal pain" only group was not uncommon. Considering a systemic classification for acute abdominal pain may be helpful in the diagnostic approach in children.

Poly IC triggers a cathepsin D- and IPS-1-dependent pathway to enhance cytokine production and mediate dendritic cell necroptosis.

RIG-I-like receptors (RLRs) sense virus-derived RNA or polyinosinic-polycytidylic acid (poly IC) to exert antiviral immune responses. Here, we examine the mechanisms underlying the adjuvant effects of poly IC. Poly IC was taken up by dendritic cells (DCs), and it induced lysosomal destabilization, which, in turn, activated an RLR-dependent signaling pathway. Upon poly IC stimulation, cathepsin D was released into the cytoplasm from the lysosome to interact with IPS-1, an adaptor molecule for RLRs. This interaction facilitated cathepsin D cleavage of caspase 8 and the activation of the transcription factor NF-κB, resulting in enhanced cytokine production. Further recruitment of the kinase RIP-1 to this complex initiated the necroptosis of a small number of DCs. HMGB1 released by dying cells enhanced IFN-ß production in concert with poly IC. Collectively, these findings suggest that cathepsin D-triggered, IPS-1-dependent necroptosis is a mechanism that propagates the adjuvant efficacy of poly IC.

Prevalence of primary immunodeficiency in Korea.

This study represents the first epidemiological study based on the national registry of primary immunodeficiencies (PID) in Korea. Patient data were collected from 23 major hospitals. A total of 152 patients with PID (under 19 yr of age), who were observed from 2001 to 2005, have been entered in this registry. The period prevalence of PID in Korea in 2005 is 11.25 per million children. The following frequencies were found: antibody deficiencies, 53.3% (n = 81), phagocytic disorders, 28.9% (n = 44); combined immunodeficiencies, 13.2% (n = 20); and T cell deficiencies, 4.6% (n = 7). Congenital agammaglobulinemia (n = 21) and selective IgA deficiency (n = 21) were the most frequently reported antibody deficiency. Other reported deficiencies were common variable immunodeficiencies (n = 16), X-linked agammaglobulinemia (n = 15), IgG subclass deficiency (n = 4). Phagocytic disorder was mostly chronic granulomatous disease. A small number of patients with Wiskott-Aldrich syndrome, hyper-IgE syndrome, and severe combined immunodeficiency were also registered. Overall, the most common first manifestation was pneumonia. This study provides data that permit a more accurate estimation PID patients in Korea.

Genetic analysis of 10 unrelated Korean families with p22-phox-deficient chronic granulomatous disease: an unusually identical mutation of the CYBA gene on Jeju Island, Korea.

Chronic granulomatous disease (CGD) is a rare hereditary disorder characterized by recurrent life-threatening bacterial and fungal infections. The underlying defect in CGD is an inability of phagocytes to produce reactive oxygen species as a result of defects in NADPH oxidase. Considering that CGD generally affects about 3-4 in 1,000,000 individuals, it is surprising that the prevalence of CGD on Jeju Island is 20.7 in 1,000,000 individuals. We performed genetic analysis on 12 patients from 10 unrelated families and found that all patients had an identical homozygous single-base substitution of C to T in exon 1 (c.7C>T) of the CYBA gene, which was expected to result in a nonsense mutation (p.Q3X). Because Jeju Island has long been a geologically isolated region, the high prevalence of CGD on Jeju Island is presumably associated with an identical mutation inherited from a common ancestor or proband.

[Estimating the prevalence of atopic dermatitis in school students of jejudo, Korea].

OBJECTIVES: The frequency of visiting clinics in Jejudo for treating atopic dermatitis (AD) has been reported to be higher than that for other counties of Korea. The aim of this work was to estimate the prevalence of AD for the students of the primary, middle and high schools in Jejudo, Korea. METHODS: We planned to evaluate about 5,000 students, so classes were randomly selected by random systematic sampling methods. The parents of all the students in the selected classes were asked to respond to a structured questionnaire concerned with the prevalence of AD. RESULTS: The prevalence of AD based on ever being diagnosed by a doctor, on currently being diagnosed by a doctor, on ever being treated for AD by a doctor, on currently being treated for AD by a doctor was 25.57% (95% CI=25.3-25.8), 14.67% (95% CI=14.5-14.9), 21.90% (95% CI=21.6-22.2) and 14.41% (95% CI=14.2-14.6), respectively. CONCLUSIONS: On comparing the prevalence of AD, the students in Jejudo had a higher number of recurrence events in spite of their lower number of cases. Further studies are needed to evaluate these aspects of AD.

Polymorphism of matrix metalloproteinase-3 promoter gene as a risk factor for coronary artery lesions in Kawasaki disease.

Kawasaki disease (KD) is a major cause of acquired coronary artery diseases in childhood. The serum levels of matrix metalloproteinase (MMP)-3 and MMP-9 in KD have been reported to be significantly higher than other diseases. Several studies have demonstrated that MMP-3 5A/6A polymorphism and MMP-9 C-1562T polymorphism modify each transcriptional activity in allele specific manner. We hypothesized that these polymorphisms may play a role as a risk factor for development of coronary artery lesions (CAL) in KD. Eighty-three patients, diagnosed with KD in Cheju National University Hospital from January 2000 to February 2004, were divided into two groups according to the presence of CAL. Genotyping of MMP-3 and MMP-9 gene polymorphisms were determined by restriction fragment length polymorphism. With regard to MMP-3 gene polymorphism, the KD with CAL group had a higher frequency of 6A/6A genotype than control group (p=0.0127) and the KD without CAL group (p=0.0036). However, no significant differences in the allele and genotype distributions of the MMP-9 polymorphism were observed. These findings suggest that MMP-3 6A/6A genotype may be an independent risk factor for CAL formation in KD.

Immunohistochemical study of p47Phox and gp91Phox distributions in rat brain.

NADPH oxidase is multi-component enzyme, which comprises the cytosolic proteins p40Phox, p47Phox, and p67Phox and the two membrane proteins, gp91Phox and p22Phox, and which is well characterized in phagocytic cells. NADPH oxidase is a primary source of reactive oxygen species (ROS), and recent studies indicate that free radicals and ROS might be causative factors of several brain degenerative diseases and dysfunctions. However, though previous studies have shown the presence of NADPH oxidase subunits in cell culture and mouse brain, they have not provided detailed high power resolution data. Therefore, we investigated the distributions of the p47Phox and gp91Phox subunits in rat brain using immunohistochemical approach. Cortex, hippocampus, and Purkinje cells of cerebellum were prominently stained by p47Phox and gp91Phox antibodies. As compared with the distributions of p47Phox, gp91Phox in mouse, some differences in the rat brain were observed in the hippocampus, thalamus, amygdala, reticular nucleus, and basal ganglia. Additionally, at the cellular level, most p47Phox immunoreactivity was largely confined to cell bodies and proximal portions of the dendritic tree. Taken together, the widespread observed distributions of p47Phox and gp91Phox subunits indicate that they are probably needed to maintain normal brain function.