• Molecules and Cells
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• v.45 no.12
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• pp.896-910
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• 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and potentially fatal virus. So far, most comprehensive analyses encompassing clinical and transcriptional manifestation have concentrated on the lungs. Here, we confirmed evident signs of viral infection in the lungs and spleen of SARS-CoV-2-infected K18-hACE2 mice, which replicate the phenotype and infection symptoms in hospitalized humans. Seven days post viral detection in organs, infected mice showed decreased vital signs, leading to death. Bronchopneumonia due to infiltration of leukocytes in the lungs and reduction in the spleen lymphocyte region were observed. Transcriptome profiling implicated the meticulous regulation of distress and recovery from cytokine-mediated immunity by distinct immune cell types in a time-dependent manner. In lungs, the chemokine-driven response to viral invasion was highly elevated at 2 days post infection (dpi). In late infection, diseased lungs, post the innate immune process, showed recovery signs. The spleen established an even more immediate line of defense than the lungs, and the cytokine expression profile dropped at 7 dpi. At 5 dpi, spleen samples diverged into two distinct groups with different transcriptome profile and pathophysiology. Inhibition of consecutive host cell viral entry and massive immunoglobulin production and proteolysis inhibition seemed that one group endeavored to survive, while the other group struggled with developmental regeneration against consistent viral intrusion through the replication cycle. Our results may contribute to improved understanding of the longitudinal response to viral infection and development of potential therapeutics for hospitalized patients affected by SARS-CoV-2.

• Pediatric Infection and Vaccine
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• v.31 no.1
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• pp.75-82
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• 2024

Purpose: As the coronavirus disease 2019 (COVID-19) pandemic ended, the number of patients with respiratory syncytial virus (RSV) pneumonia increased during the spring/summer of 2022. This study aimed to analyze the clinical features and antibiotic usage of children hospitalized for RSV pneumonia in a recently established general hospital in Sejong city. Methods: In this retrospective review, we included inpatients of the Pediatric Department of Chungnam National University Sejong Hospital diagnosed with RSV pneumonia between March 2022 and April 2023. Patients were divided into 2 groups: with and without antibiotic treatment. Demographic data, initial presentations, and clinical courses were reviewed. Results: A total of 116 patients with RSV pneumonia were hospitalized during this period, of which 102 were analyzed, excluding 14 with underlying diseases or who did not fall within the definition of pneumonia. The median age was 17 months. Diagnoses of bacterial infections (acute otitis media and sinusitis) were documented in 9.8% of cases. Intravenous (IV) antibiotics were administered in 46% of cases. The group receiving IV antibiotics showed higher inflammatory levels (C-reactive protein; CRP), more infiltration on initial chest X-rays, and longer fever duration. There was no difference in the length of hospitalization between the groups with and without IV antibiotics. Conclusions: This study showed a tendency for the attending physician to prescribe IV antibiotics to patients with longer fever duration, pulmonary infiltrations on the initial chest X-ray, and higher CRP levels. However, given the high rate of IV antibiotic usage compared to previous studies, care should be taken in antibiotic use.

• Childhood Kidney Diseases
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• v.4 no.2
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• pp.136-143
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• 2000

Purpose : The hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia thrombocytopenia, and acute renal failure. It is ole of tile most common cause of acute renal failure in children but few reports are available in Korea. Thus we investigated the 23 patients diagnosed as HUS during last 14 years. Method : We retrospectively investigated the etiologic factor, clinical manifestations laboratory findings, treatment modalities, and final outcomes of the patients. Then patients were divided into two groups according to outcome, md comparison was performed. Group A(8) comprised patients who progressed to end-stage renal disease or expired. Group B(15) comprised patients who completely recovered after dialysis treatment. Result The number of patients aged less than 4 years were 17; between 5 and 10 were 4 and more than 10 were 2. The gende ratio was M:F=2 : 1. The etiologic factors were as follows: acute gastroenteritis in 14 patients including 4 bloody diarrhea, upper respiratory tract infection in 7 patients, and 1 patient with herbal mediation. The overall mortality rate was 22$\%$: 2 patients died of US complications, 2 patients died of sepsis, and 1 patient died of pulmonary hemorrhage. Group A (Hb 4.8${\pm}$1.2 g/dL) showed lower value in hemoglobin than group B (Hb 6.3${\pm}$1.7 g/dL) during hospital stay (P< 0.05), And the time interval between tile disease onset and dialysis treatment was significantly longer in group A ($11.9{\pm}9.1\;days\;vs\;2.8{\pm}2.1\;days$) (P< 0.05). Conclusion : Overall mortality rate was 22$\%$. Low hemoglobin value and the prolonged time interval between the disease onset and dialysis treatment were related with poor prognosis. So early diagnosis and appropriate intensive care including dialysis treatment is essential to achieve better outcome in children.

• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1265-1276
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• 1998

Background : Nitric oxide(NO) is an endogenously produced free radical that plays an important role in regulating vascular tone, inhibition of platelet aggregation and white blood cell adhesion to endothelial cells, and host defense against infection. The highly reactive nature of NO with oxygen radicals suggests that it may either promote or reduce oxidant-induced cell injury in several biological pathways. Oxidant injury and interactions between pulmonary vascular endothelium and leukocytes are important in the pathogenesis of acute lung injury, including acute respiratory distress syndrome(ARDS). In ARDS, therapeutic administration of NO is a clinical condition providing exogenous NO in oxidant-induced endothelial injury. The role of exogenous NO from NO donor or the suppression of endogenous NO production was evaluated in oxidant-induced endothelial injury. Method : The oxidant injury in cultured rat lung microvascular endothelial cells(RLMVC) was induced by hydrogen peroxide generated from glucose oxidase(GO). Cell injury was evaluated by $^{51}$chromium($^{51}Cr$) release technique. NO donor, such as S-nitroso-N-acetylpenicillamine(SNAP) or sodium nitroprusside(SNP), was added to the endothelial cells as a source of exogenous NO. Endogenous production of NO was suppressed with N-monomethyl-L-arginine(L-NMMA) which is an NO synthase inhibitor. L-NMMA was also used in increased endogenous NO production induced by combined stimulation with interferon-$\gamma$(INF-$\gamma$), tumor necrosis factor-$\alpha$(TNF-$\alpha$), and lipopolysaccharide(LPS). NO generation from NO donor or from the endothelial cells was evaluated by measuring nitrite concentration. Result : $^{51}Cr$ release was $8.7{\pm}0.5%$ in GO 5 mU/ml, $14.4{\pm}2.9%$ in GO 10 mU/ml, $32.3{\pm}2.9%$ in GO 15 mU/ml, $55.5{\pm}0.3%$ in GO 20 mU/ml and $67.8{\pm}0.9%$ in GO 30 mU/ml ; it was significantly increased in GO 15 mU/ml or higher concentrations when compared with $9.6{\pm}0.7%$ in control(p < 0.05; n=6). L-NMMA(0.5 mM) did not affect the $^{51}Cr$ release by GO. Nitrite concentration was increased to $3.9{\pm}0.3\;{\mu}M$ in culture media of RLMVC treated with INF-$\gamma$ (500 U/ml), TNF-$\alpha$(150 U/ml) and LPS($1\;{\mu}g/ml$) for 24 hours ; it was significantly suppressed by the addition of L-NMMA. The presence of L-NMMA did not affect $^{51}Cr$ release induced by GO in RLMVC pretreated with INF-$\gamma$, TNF-$\alpha$ and LPS. The increase of $^{51}Cr$ release with GO(20 mU/ml) was prevented completely by adding 100 ${\mu}M$ SNAP. But the add of SNP, potassium ferrocyanate or potassium ferricyanate did not protect the oxidant injury. Nitrite accumulation was $23{\pm}1.0\;{\mu}M$ from 100 ${\mu}M$ SNAP at 4 hours in phenol red free Hanks' balanced salt solution. But nitrite was not detectable from SNP upto 1 mM The presence of SNAP did not affect the time dependent generation of hydrogen peroxide by GO in phenol red free Hanks' balanced salt solution. Conclusion : Hydrogen peroxide generated by GO causes oxidant injury in RLMVC. Exogenous NO from NO donor prevents oxidant injury, and the protective effect may be related to the ability to release NO. These results suggest that the exogenous NO may be protective on oxidant injury to the endothelium.

• Tuberculosis and Respiratory Diseases
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• v.47 no.1
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• pp.77-89
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• 1999

Background: High-dose chemotherapy is increasingly employed in many refractory malignant diseases. This therapy has been reported to increase response rate and survival benefits but it is also associated with higher treatment-related morbidity and mortality. We evaluated clinical characteristics and course of the pulmonary toxicity following high-dose chemotherapy with peripheral blood stem cell transplantation. Methods: Ninety-seven patients who had received high-dose chemotherapy with peripheral blood stem cell transplantation were evaluated. Five patients who developed lung lesions which were not related to infection nor primary malignant disease underwent transbronchial lung biopsy. The patients' clinical characteristics, treatments, and prognosis were reviewed retrospectively. Results: Five patients(5.1%) developed idiopathic pneumonia syndrome. The high dose chemotherapy regimens employed were cyclophosphamide, BCNU, and cisplatin in 3 cases, one case of BCNU, etoposide, Ara-C, and cyclophosphamide combination, and a regimen consisting of BCNU, etoposide, Ara-C, and melphalan. The total dose of BCNU used was 300-400 mg/$m^2$ and that of cyclophosphsmide was 6,000 mg/$m^2$. All of 5 patients received radiation therapy before this treatment. After an average duration of 14 weeks (4-26 weeks) of high-dose chemotherapy, patients developed cough, dyspnea and fever. The chest X-rays showed bilateral diffuse infiltration in 3 cases and the focal infiltration in the other 2 cases. All the patients received corticosteroid therapy as a treatment for the lung lesions. Two of them progressed to acute respiratory distress syndrome and died. Three patients recovered without residual lung lesion but one of them died of dilated cardiomyopathy. Conclusion: High-dose chemotherapy with peripheral blood stem cell transplantation especially which containing BCNU regimen may develop idiopathic pneumonia syndrome related to pulmonary toxicity and corticosteroid therapy may be bel1eficial in some cases.

• Tuberculosis and Respiratory Diseases
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• v.47 no.1
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• pp.57-65
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• 1999

Backround : Pneumoconiosis is the parenchymal lung disease that results from the inhalation and deposition of dust, usually mineral dust of occupational or environmental origin. Most of the pneumoconiosis can be categorized to coal workers' pneumoconiosis (CWP) in Korea. No effective treatement is currently available, and the therapy for symptomatic CWP is limited to treatment of complication. Therefore authors analyzed and reviewed clinical features and radiological findings of 95 patients with pneumoconiosis for assessing the prognostic factors in disease progression. Method: We reviewed medical records of 95 cases with pneumoconiosis including history, chest X-ray, pulmonary function test, electrocardiography, AFB stain and culture of sputum, and routine blood examination between June 1995 and June 1997 in Seonam University Namkwang Hospital. Results: All of cases are male(mean age, 57.4 years), 91 cases out of them are miners. The mean duration of exposure to dust is 18.8 years. Major clinical symptoms are dyspnea (100%), sputum (71.6%), chest pain (55.8%), cough (23.2%), and hemoptysis (6.3%). 82 % of cases are over Morgan-Seaton Grade 2 in the degree of dyspnea. Small opacity on chest x-ray is 82.1 % and large opacity is 17.9%. Small opacity has tit type (37.2%), q/q type (25.6%) and r/r type (11.5%). B type is 42.2% in large opacity. For the pulmonary function test, restrictive type is 40.3%, mixed type 19.5% and obstructive type 8.3%. The more increasing chest Xray density, the more decreasing $FEV_1$ (p<0.01). 38% of patients show tuberculosis in chest X-ray, 15.8% positive smear of acid fast bacilli in sputum. The prevalence of pulmonary tuberculosis is high in patients with poor clinical condition. The cases with the active pulmonary tuberculosis have severe dyspnea. Expired cases show 100% and 75% of positive pulmonary tuberculosis in chest X-ray and sputum examination, respectively. 75% of expired cases show the chronic cor pulmonale, who died of acute respiratory failure. Conclusion: These findings indicate that tuberculoois infection has a decisive influence on the progress and prognoois of pneumoconioois.

• Journal of Yeungnam Medical Science
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• v.22 no.1
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• pp.52-61
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• 2005

Background: Guillain-Barre syndrome is defined as a recognizable clinical entity that is characterized by rapidly evolving symmetric limb weakness, the loss of tendon reflexes, absent or mild sensory signs, and variable autonomic dysfunctions. This study evaluated the clinical and electrophysiological findings retrospectively. Materials and Methods: Forty-five patients with Guillain-Barre syndrome, who were admitted to the Yeungnam University Hospital for six years from Jan. 1994 to Dec. 1999 were investigated. The correlation between the clinical manifestation and the electrophysiological study was evaluated. Results: The male to female ratio was 1.8:1 and there was a peak seasonal incidence in the winter. A preceding illness was noted in 66.7 % of cases, and an upper respiratory tract infection was the most common one. The most common clinical manifestations were a loss of tendon reflex and ascending muscle weakness and paralysis. The cerebrospinal fluid examinations revealed, albuminocytologic dissociation in 33 cases (73.3 %). Intravenous immunoglobulin therapy was performed in 29 cases (64.4 %). The sequential electrophysiological abnormalities were most marked at 2 to 4 weeks after onset. At that time the most significant change was a decrease in the compound muscle action potential amplitude. These 45 patients with Guillain-Barre syndrome were subclassified using the clinical and electrophysiological data. Conclusion: The result in this study, concured with other research on the clinical and electrophysiological data of Guillain-Barre syndrome. However, an extensive and dynamic investigation is necessary to determine the reason for the peak seasonal incidence in winter.

• IMMUNE NETWORK
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• v.24 no.2
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• pp.7.1-7.19
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• 2024

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019. In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×10⁵ plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×10² PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×10² PFU-virus-infected lungs from 2 dpi, but not in 1×10⁵ PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×10⁵ PFU; however, 1×1² PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

• Pediatric Infection and Vaccine
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• v.31 no.1
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• pp.12-24
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• 2024

The number of pediatric coronavirus disease 2019 (COVID-19) cases worldwide are increasing compared to the early phase of the pandemic, along with highly transmissible severe acute respiratory syndrome coronavirus variant and the increase in adult COVID-19 vaccination. We conducted a rapid systematic review and meta-analysis of published randomized clinical trials (RCTs) of the COVID-19 vaccines and the observational retrospective studies on adverse events after COVID-19 vaccination in adolescents. Seventeen studies were finally included in this systematic review. Meta-analysis showed that although vaccination in adolescents was significantly effective to prevent COVID-19 infection in retrospective studies (risk ratio [RR], 0.29; 95% confidence interval [CI], 0.22-0.37; I² =100%), however the effect of preventing COVID-19 infection was lower than in RCTs (RR, 0.05; 95% CI, 0.01-0.27). In five retrospective studies, the pooled estimated proportion of participants with myocarditis and/or pericarditis was 2.33 per 100,000 of the population (95% CI, 0.97-5.61 per 100,000). Sub-group analysis with sex and vaccine doses showed that male (5.35 per 100,000) and the second dose (9.71 per 100,000) had significantly higher incidence of myocarditis and/or pericarditis than female (1.09 per 100,000) and the first dose (1.61 per 100,000), respectively. Our study showed that mRNA COVID-19 vaccines in adolescent recipients were favorable and effective against COVID-19 in RCT as well as observational studies. The safety findings of BNT162b2 vaccine in adolescents were explored and we found the difference of safety according to sex and vaccine doses. The occurrence of adverse events after mRNA COVID-19 vaccination should be monitored.

• Pediatric Infection and Vaccine
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• v.21 no.1
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• pp.1-8
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• 2014

Purpose: The aim for this study was to investigate clinical manifestation of seasonal influenza A and B during the 2012 winter season in Wonju, South Korea. Their clinical and laboratorial characteristics and effect of oseltamivir were compared and analyzed. Methods: Children under the age of 18 years who visited the Wonju Severance Christian Hospital with fever or acute respiratory symptoms and who were diagnosed with influenza A or B by rapid antigen test from nasopharyngeal swab were selected for the study. The medical records of patients were retrospectively reviewed. Results: Influenza A was detected in 374 patients (83.7%), and influenza B in 72 (16.6%). The incidence of influenza A was highest in February (n=186), while that of influenza B was highest in March (n=36). The most common symptoms were fever (n=434, 97.1%) and cough (n=362, 81.0%). No significant differences were observed between influenza A and B in symptoms and laboratory data. Patients who had used oseltamivir within 2 days showed statistically lower admission rate, shorter admission duration, and lower incidence of pneumonia. Conclusion: This study found no statistical difference between influenza A and B, in symptoms, progression, and laboratory test, but those who were treated with oseltamivir given within 2 days of the onset of fever experienced more positive outcomes.