S100 Calcium-Binding Protein A9, a Potential Novel Diagnostic Biomarker for Idiopathic Pulmonary Fibrosis

Background@#Neutrophilic inflammation is a characteristic feature of idiopathic pulmonary fibrosis (IPF). S100 calcium-binding protein A9 (S100A9) is a neutrophil-derived protein involved in the development of neutrophil-related chronic inflammatory disorders. However, the role of S100A9 in IPF remains unclear. @*Methods@#We used enzyme-linked immunosorbent assays to measure S100A9 levels in bronchoalveolar lavage fluid (BALF) and serum obtained from healthy controls (HCs) and patients with IPF, non-specific interstitial pneumonia, hypersensitivity pneumonitis, and sarcoidosis. @*Results@#Compared with HCs, BALF S100A9 levels were significantly higher in IPF patients (P 0.533 ng/ mL had lower survival rates, compared with patients who had levels ≤ 0.553 ng/mL (n = 49; hazard ratio [HR], 3.62; P = 0.021). Combination analysis revealed that IPF patients with S100A9 levels in BALF> 0.553 ng/mL or neutrophil percentages > 49.1% (n = 43) had significantly lower survival rates than patients with S100A9 levels in BALF ≤ 0.553 ng/mL and neutrophil percentages ≤ 49.1% (n = 41) (HR, 3.91; P = 0.014). Additionally, patients with serum S100A9 levels > 0.077 ng/mL (n = 29) had significantly lower survival rates than patients with levels ≤ 0.077 ng/mL (n = 53, HR, 2.52; P = 0.013). S100A9 was expressed on neutrophils and macrophages in BALF from IPF patients as well as α-smooth muscle actin positive cells in the lung tissues. @*Conclusion@#S100A9 is involved in the development and progression of IPF. Moreover, S100A9 levels in BALF and serum may be surrogate markers for IPF diagnosis and survival prediction, particularly when analyzed in combination with neutrophil percentages.

Prevalence of Respiratory Viral Infections in Korean Adult Asthmatics With Acute Exacerbations: Comparison With Those With Stable State

PURPOSE: Viral infections are involved in ~50% of exacerbations among Caucasian adult asthmatics. However, there have been few reports on the causative virus of exacerbations in Korean adult asthmatics. Thus, we compared frequencies and types of viruses between lower respiratory tract illnesses (LRTIs) with exacerbations (exacerbated LRTIs) and those without exacerbations (stable LRTIs) to evaluate contribution of respiratory viruses to exacerbations. METHODS: Viral RNA was extracted from sputum using the Viral Gene-spin™ Kit. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect adenovirus (ADV), metapneumovirus (MPV), parainfluenza virus (PIV) 1/2/3, influenza virus (IFV) A, IFV B, respiratory syncytial virus (RSV) A/B, and rhinovirus (RV) A. RESULTS: Among the 259 patients, 210 underwent a single sputum examination, and the remaining 49 underwent 2 to 4 sputum examinations. Virus was detected in 68 of the 259 exacerbated episodes and in 11 of the 64 stable episodes. Among the exacerbated episodes, RV was the most frequently detected virus, followed by influenza A, parainfluenza, RSV A/B, and ADV. Among the 11 stable episodes, RV was most frequently detected. Detection rates of these viruses did not differ between the 2 groups (P>0.05). Thirty-five patients underwent the virus examination at 2 episodes of exacerbation, while 14 patients underwent at each time of exacerbated and stable episodes. Virus detection rate at the second examination was significantly higher in cases with 2 exacerbation episodes than in those with initial exacerbation and sequential stable episodes (P=0.003). A seasonal pattern was noted in the detection rates of RV (September to December), IFV (January to April), PIV (May to September), and RSV A/B (September to April). CONCLUSIONS: Respiratory viruses were identified in approximately 20% of LRTI irrespective of the presence of asthma exacerbation. RV and IFV A/B were most frequently detected. A group of patients experienced frequent viral infections followed by asthma exacerbations.

Two Cases of Pre-descemet Corneal Dystrophy Associated with X-linked Ichthyosis: A Case Report by Genetic Analysis

PURPOSE: To report the first case of steroid sulfatase (STS) gene deletion, confirmed by multiplex ligation-dependent probe amplification (MLPA) analysis in identical twins with pre-Descemet corneal dystrophy associated with X-linked ichthyosis. CASE SUMMARY: 19-year old identical twin brothers with itching senses and hereditary thick scaly skin of the extremity and trunk visited our dermatologic clinic. Upon visiting, an ophthalmologic consultation with anterior segment examination showed diffuse punctate corneal opacities in the pre-Descemet layer. On MLPA analysis of the identical twin brothers, a definitive diagnosis of X-linked ichthyosis was made by identifying STS gene deletion. CONCLUSIONS: Identification of the deletion and mutation of the involved gene using gene analysis can provide insight to diagnosis and clinical characteristics of X-linked ichthyosis.

Recurrent macrophage activation syndrome since toddler age in an adolescent boy with HLA B27 positive juvenile ankylosing spondylitis / 소아과

Recurrent macrophage activation syndrome (MAS) is very rare. We present the case of an adolescent boy with human leukocyte antigen (HLA) B27-positive ankylosing spondylitis (AS), who experienced episodes of recurrent MAS since he was a toddler. A 16-year-old boy was admitted because of remittent fever with pancytopenia and splenomegaly after surgical intervention for an intractable perianal abscess. He had been diagnosed with hemophagocytic lymphohistiocytosis (HLH) 4 different times, which was well controlled with intravenous immunoglobulin and steroids since the age of 3. We were unable to identify the cause for the HLH. He remained symptom-free until the development of back pain and right ankle joint pain with swelling at 15 years of age. He was diagnosed with HLA B27-positive AS with bilateral active sacroiliitis. He showed symptom aggravation despite taking naproxen and methotrexate, and the symptoms improved with etanercept. On admission, his laboratory data showed leukopenia with high ferritin and triglyceride levels. Bone marrow biopsy examination showed histiocytic hyperplasia with hemophagocytosis. There was no evidence of infection. He received naproxen alone, and his symptoms and laboratory data improved without any other immunomodulatory medications. Genetic study revealed no primary HLH or inflammasome abnormalities. In this case, underlying autoimmune disease should have been considered as the cause of recurrent MAS in the young patient once primary HLH was excluded.

A Patient with Achalasia Misdiagnosed as Asthma Until Age 17 / 대한내과학회지

Achalasia is a primary esophageal motility disorder characterized by functional obstruction of the distal esophagus and subsequent dilation of the proximal esophagus. The most common symptoms in children and adolescents are vomiting, progressive dysphagia, weight loss, recurrent pneumonia, nocturnal cough, and chest pain. A girl who had been diagnosed with asthma poorly responsive to inhaled steroids until age 17, presented at the hospital with cough, sputum, and fever. Finally, she was diagnosed with achalasia and underwent esophageal balloon dilatation, which relieved her GI and pulmonary symptoms. We report this case with a literature review.

A case of familial X-linked thrombocytopenia with a novel WAS gene mutation / 소아과

Wiskott-Aldrich syndrome (WAS) is an inherited X-linked disorder. The WAS gene is located on the X chromosome and undergoes mutations, which affect various domains of the WAS protein, resulting in recurrent infection, eczema, and thrombocytopenia. However, the clinical features and severity of the disease vary according to the type of mutations in the WAS gene. Here, we describe the case of a 4-year-old boy with a history of marked thrombocytopenia since birth, who presented with recurrent herpes simplex infection and late onset of eczema. Examination of his family history revealed that older brother, who died from intracranial hemorrhage, had chronic idiopathic thrombocytopenia. Therefore, we proceeded with genetic analysis and found a new deletion mutation in the WAS gene: c.858delC (p.ser287Leufs*21) as a hemizygous form.

Effects of Interleukin-9 Blockade on Chronic Airway Inflammation in Murine Asthma Models

PURPOSE: Asthma is a chronic inflammatory disease of the airways associated with structural changes and airway remodeling. Interleukin (IL)-9 has pleiotropic effects on both inflammatory cells and airway structural cells, which are involved in asthma pathogenesis. We evaluated the effects of IL-9 blockade on chronic airway inflammation. METHODS: Acute airway inflammation was induced in Balb/c mice using aerosolized ovalbumin (OVA), whereas chronic asthma was induced by OVA exposure for 5 weeks with anti-IL-9 or isotype-matched antibody (Ab) treatment during the OVA challenge. Inflammatory cells in bronchoalveolar lavage fluid (BALF) were counted and lung tissues were stained to detect cellular infiltration, mucus deposition, and collagen accumulation. The levels of interferon (IFN)-gamma, IL-4, IL-5, IL-9, IL-17, and immunoglobulin E (IgE) in BALF were measured using enzyme linked immunosorbent assays, and profiles of inflammatory cells and subsets of T helper (Th) cells were analyzed using flow cytometry. RESULTS: IL-9, IL-17, and IFN-gamma levels were significantly increased in the chronic group compared to the acute asthma group. However, the number of IL-9-positive cells was not affected, with a decrease in Th17 cells in OVA-challenged caspase-1 knockout mice. Numbers of eosinophils, neutrophils, B cells, mast cells, and Th17 cells decreased after administration of anti-IL-9 Ab. Total IgE, IL-5, IL-9, and IL-17 levels were also lower in the anti-IL-9 group. CONCLUSIONS: Our results suggest that anti-IL-9 Ab treatment inhibits pulmonary infiltration of inflammatory cells and cytokine production, especially IL-17. These results provide a basis for the use of an anti-IL-9 Ab to combat IL-17-mediated airway inflammation.

Perspectives on Clinical Informatics: Integrating Large-Scale Clinical, Genomic, and Health Information for Clinical Care

The advances in electronic medical records (EMRs) and bioinformatics (BI) represent two significant trends in healthcare. The widespread adoption of EMR systems and the completion of the Human Genome Project developed the technologies for data acquisition, analysis, and visualization in two different domains. The massive amount of data from both clinical and biology domains is expected to provide personalized, preventive, and predictive healthcare services in the near future. The integrated use of EMR and BI data needs to consider four key informatics areas: data modeling, analytics, standardization, and privacy. Bioclinical data warehouses integrating heterogeneous patient-related clinical or omics data should be considered. The representative standardization effort by the Clinical Bioinformatics Ontology (CBO) aims to provide uniquely identified concepts to include molecular pathology terminologies. Since individual genome data are easily used to predict current and future health status, different safeguards to ensure confidentiality should be considered. In this paper, we focused on the informatics aspects of integrating the EMR community and BI community by identifying opportunities, challenges, and approaches to provide the best possible care service for our patients and the population.

Flow Cytometry-Assisted Basophil Activation Test as a Safe Diagnostic Tool for Aspirin/NSAID Hypersenstivity

PURPOSE: Aspirin and non-steroidal anti-inflammatory drugs (ASA/NSAIDs) are common causes of drug hypersensitivity. An oral provocation test is the only definitive diagnostic test. This study assessed the reliability of a flow cytometry-assisted basophil activation test (FAST) as a safe diagnostic method for ASA/NSAID-induced hypersensitivity, as its high sensitivity and specificity have been demonstrated for many other drugs. METHODS: Eighteen patients and 11 controls were enrolled. Using a Flow-CAST kit(R) (Buhlmann Laboratories AG, Schonenbuch, Switzerland), 29 analyses with aspirin, ibuprofen, and diclofenac were performed by flow cytometry to detect double-positive staining of anti-IgE and anti-CD63. The stimulation index was defined as the activated basophil percentage after drug stimulation/basally active basophil percentage. A stimulation index> or =2 and an absolute activated basophil percentage> or =5 were considered positive. RESULTS: Patients with hypersensitivity to ASA/NSAIDs were predominantly female, and the prevalence of atopy was higher in patients than in controls. A sensitivity of 61%, specificity of 91%, positive predictive value of 92%, and negative predictive value of 59% were achieved. CONCLUSIONS: FAST is a useful additional method for diagnosis of hypersensitivity reactions to ASA/NSAIDs. Further development is required to increase the sensitivity of the test.

Synchronous development of KIT positive acute myeloid leukemia in a patient with gastrointestinal stromal tumor

We report a case of synchronous occurrence of KIT-positive acute myeloid leukemia (AML) and gastrointestinal stromal tumor (GIST). A 63-year-old woman was hospitalized for dizziness, and abdominal computed tomography revealed an exophytic gastric mass and hepatic metastasis. The patient was diagnosed with GIST and was administered imatinib (400 mg/day) for the metastatic unresectable tumor. After 2 weeks of imatinib treatment, the patient developed pancytopenia, which persisted even after the drug was discontinued, thereby necessitating bone marrow biopsy. Biopsy examination indicated AML, and karyotyping revealed a complex karyotype. We did not observe point mutations at residues D816 and N822 of KIT. Therefore, the patient received standard induction chemotherapy, but on the 18th day after completion of chemotherapy, she died of septic shock and multi-organ failure. Since KIT plays an important role in both GIST and AML, we consider that both these malignancies may have been associated with each other.

Factors for poor prognosis of near-fatal asthma after recovery from a life-threatening asthma attack

BACKGROUND/AIMS: The aim of this study was to investigate poor prognostic factors associated with a near-fatal asthma attack following patient recovery. METHODS: We enrolled 68 patients who suffered near-fatal asthma attacks and were admitted to the intensive care units of five university hospitals. The patients were divided into two groups. The first group was comprised of patients who discontinued oral corticosteroids within 6 months after being discharged from the hospital and who maintained a forced expiratory volume in 1 s (FEV1) > or =60% of the maximum or estimated values of the corresponding patients. The second group included patients who continued on oral corticosteroids for > or =6 months or who maintained a FEV1 <60%. RESULTS: In patients with near-fatal asthma, factors for a poor prognosis included older age [48.47+/-3.53 vs. 64.69+/-2.59 years, p<0.05], chronic severe asthma, high values for inflammation-related laboratory markers (ESR, 8.75+/-2.05 vs. 23.88+/-4.40 mm/h, p=0.004; CRP, 1.72+/-0.46 vs. 6.68+/-9.36 mg/dL, p<0.05), asthma exacerbated by pneumonia (28.1 vs. 52.8%, p<0.05), and relatively low nutritional status (albumin, 4.00+/-0.14 vs. 3.51+/-0.10 g/dL, p<0.05). CONCLUSIONS: These prognostic factors may induce irreversible obstruction of the airways with subsequent acute exacerbation of asthma or the need for continual oral corticosteroids after being discharged from the hospital. Patients with these factors should be treated appropriately, under close surveillance.

Facial dysmorphisms associated with holoprosencephaly / 대한산부인과학회지

OBJECTIVE: The purpose of this study is to determine and classify holoprosencephlay with the associated facial abnormalities. METHODS: This was a retrospective study in which were reviewed the sonographic findings in correlation with the clinical and pathologic data of fetuses or neonates identified with holoprosencephaly at the Department of Obstetrics and Gynecology of the Catholic University in the period 1995-2007. RESULTS: Twelve cases with a Holoprosencephaly were found. Mean gestational age at diagnosis and delivery was 28 weeks of pregnancy (range from 14 to 41 weeks). Modes of delivery were 8 cases of preterm spontaneous delivery, 2 cases of missed abortion, 1 case of normal fullterm spontaneous delivery, and 1 case of full term cesarean delivery. Associated facial anomalies were present in 9/12 cases (75%) which involved with cyclopia, proboscis, cleft lip and palate, ethomocephaly and otocephaly. Among those anomalies, abnormal karyotypes were 3/6 cases (50%). CONCLUSIONS: When a midline brain anomaly is detected by antenatal sonography, accurate sonographic analysis of midline facial defect may allow more definitive diagnosis of holoprosencephaly, and the outcome of affected fetuses often have other major structural abnormalities and nearly always fatal.

Prenatal diagnosis of thrombocytopenia-absent radius syndrome using three-dimensional ultrasound / 대한산부인과학회지

We describe a case of thrombocytopenia-absent radius syndrome suspected by ultrasonography, later confirmed by fetal blood analysis. From this case we confirmed the usefulness of three-dimensional ultrasonography in diagnosing abnormalities in the fetal skeletal system and genetic counseling.

A Case of Cronkhite-Canada Syndrome Showing Resolution with Helicobactor pylori Eradication and Omeprazole / 대한소화기학회지

We describe a 58-year-old woman who was incidentally found to have gastric and colonic polyposis, hypoalbuminemia, cutaneous hyperpigmentation and onychodystrophy (Cronkhite-Canada syndrome). Histology of polyps from the stomach showed features of juvenile or retention type (hamartomatous) polyps with Helicobacter pylori (H. pylori) infection. The large pedunculated colonic polyps showed hamartomatous polyps with adenomatous component and polypectomy was performed. After the treatment with H. pylori eradication and omeprazole, the gastric polyposis, hypoalbuminemia and anemia regressed, and endoscopic polypectomy of gastric polyps were performed. After the continuous use of omeprazole for 14 months, the patient showed complete resolution of clinical features of Cronkhite-Canada syndome. The experience of this case suggests that eradication of H. pylori and proton pump inhibitor treatment might be considered in patients with gastric polyposis combined with Cronkhite-Canada syndome.

The risk factors and prognosis of methicillin-resistant staphylococcus aureus bacteremia: focus on nosocomial acquisition / 대한내과학회지

BACKGROUND: Staphylococcus aureus is the most common pathogen causing nosocomial infection; it contributes significantly to patient morbidity and mortality. The incidence of S. aureus bacteremia in hospitals as well as communities has significantly increased during the past decade. The purpose of this study was to determine the risk factors and prognosis of methicillin-resistant S. aureus bacteremia. METHODS: We reviewed the medical records of 164 cases of S. aureus bacteremia during 1999-2003 at the Ewha Womans University MokDong hospital. We retrospectively analyzed the cases, which satisfied the definition of clinically significant bacteremia and whose medical records were available. RESULTS: The number of methicillin-sensitive Staphylococcus aureus infections (MSSA) was 87 cases and methicillin-resistant Staphylococcus aureus (MRSA) 77 cases. There were 65 cases (84.4%) of nosocomial infection, 9 cases (11.7%) of health-care associated and 3 cases (3.9%) of community-acquired MRSA bacteremia. The risk factors associated with nosocomial MRSA were previous use of antibiotics (OR 15.6, p<0.001) and advanced age (OR 4.9, p=0.017). The risk factor for increased mortality in patients with nosocomial S. aureus bacteremia was septic shock (Hazard ratio 13.2, p<0.001). CONCLUSIONS: MRSA bacteremia was more frequent in patients with previous antibiotic therapy and advanced age. In addition, the risk factor for mortality in patients with S. aureus bacteremia was septic shock. Additional prospective randomized trials to assess the efficacy and initiation of empirical antibiotics in a well matched cohort study are necessary.

The Effect of Activity of Daily Living Exercise for Self-care Ability and Family Burden in Stroke Patients / 재활간호학회지

PURPOSE: The purpose of this study was to determine the effect of ADL exercise in stroke patients and to define to strategy to promote their self-care ability, decrease to their family burden. METHOD: The experimental design was designed nonequivalent control group non-synchronized design. The study method had been done by investigating the experimental group and control group through the questionaire on 33 patients. ADL exercise was conducted by the researcher and was carried out experimental group once per day for 20 minutes for daily 28 days. RESULTS: For the ADL exercise, self-care ability score was increased and family burden score was decreased significantly. CONCLUSION: The exercise increased the self-care ability and effect of family burden of stroke patients. Based upon these results, it is recommended that the nurses who take care of stroke patient carry out them the ADL exercise continuously.

The Effect of Auranofin on Thrombomodulin Expression in Acute Promyelocytic Leukemia Cell

BACKGROUND: Acute promyelocytic leukemia (APL) is distinguished from other forms of leukemia by its association with bleeding diatheses. All-trans retinoic acid (ATRA) and arsenic trioxide (As2O3), which have been effectively used in the treatment of the APL, promptly improve coagulation/bleeding syndromes by regulating the expressions of tissue factor (TF) and thrombomodulin (TM). We have previously shown a novel activity of auranofin (AF), in that it induced apoptosis and differentiation of NB4 cells. To study whether AF also possesses similar anticoagulant effects to those of ATRA and As2O3, its effects on the expressions of TM and TF were investigated. METHODS: NB4 cells derived from APL were incubated with 1 micrometer of AF. After incubation for 12, 24 and 48 hours, the AF-regulated expressions of TM and TF were analyzed by RT-PCR, Northern blot and Western blot. The assay for the TM antigen on the cell surface was performed using a flow cytometry. RESULTS: The expression of the TM gene was increased for upto 12 hours after the AF treatment, but no change was observed in the expression of the TF gene. Western blot analysis also demonstrated that AF increased the level of TM proteinin a time-dependent manner. FACS data showed the TM antigen on the cell surface to gradually increase for upto 48 hours in AF-treated cells. CONCLUSION: The results of this study indicate that AF can have an antithrombotic function via the up-regulation of the expression of TM, which suggests it may partially contribute to the improvement of coagulopathies in APL.

A Case of Henoch-Schonlein Purpura with Duodenal Involvement / 대한소화기내시경학회지

Henoch-Schonlein purpura is a form of systemic small-vessel vasculitis characterized by vascular purpura, predominantly occured on the lower limbs and articules with gastrointestinal and renal symptoms. The symptoms occur consecutively and purpura is the most common initial manifestation but if another symptoms prevails, the diagnosis often can be delayed. Any portion of the gastrointestinal tract distal to the esophagus may be involved, but most frequently affected sites are jejunum and ileum. Mucosal lesions found predominantly in the second portion of the duodenum seem to be characteristic of Henoch-Schonlein purpura and may assist the diagnosis in patients with atypical nonspecific symptoms. We report a case of Henoch-Schonlein purpura with the characteristic endoscopic finding in the second portion of duodenum, which helps to make the correct diagnosis and proper management of the patient.

Clinical Significance of Serum CA 125 in Patients with Chronic Liver Diseases / 대한소화기학회지

BACKGROUND/AIMS: The clinical significance of serum CA 125 levels in patients with chronic liver disease has not been widely appreciated in relation to the severity of the disease. We examined serum CA 125 levels in patients with chronic liver disease according to the severity of liver disease and the presence of ascites. METHODS: Fasting serum CA 125 levels were measured by a commercial RIA kit in 92 patients with chronic liver disease: 22 with chronic hepatitis and 70 with liver cirrhosis (Child class A, 19; B, 28; C, 23). Forty-one patients (45%) had ascites. RESULTS: The patients with Child class C liver cirrhosis had significantly higher mean serum CA 125 level than those with class A (p<0.05). In Child class B patients, the mean serum CA 125 level was significantly higher in patients with ascites than in those without (p<0.05). A multiple regression analysis showed that the presence of ascites, serum albumin, and prothrombin time were independent factors related to the increase of serum CA 125 levels. CONCLUSIONS: The presence of ascites is more closely related to the increase of CA125 levels in patients with liver cirrhosis than the severity of liver disease.

Two Cases of Erythroleukemic Blast Crisis in Chronic Myelogenous Leukemia / 대한임상병리학회지

The erythroleukemic blast crisis in chronic myelogenous leukemia (CML) is rarely reported. We present two cases of erythroleukemic blast crisis of CML. In both cases, they had been treated with interferon and hydroxyurea prior to a blast crisis of CML. On blastic transformation, one patient underwent an acute clinical transformation marked with fever and hematochezia but the other showed no clinical deterioration. The blasts appeared in the peripheral blood. The bone marrow aspirates revealed megaloblastic erythroid hyperplasia (about 72%, 54% of all nucleated cells), increasing the number of myeloblasts (about 46%, 59% of all non-erythroid cells), and erythroblasts with a positive PAS stain. The cytogenetic studies revealed Philadelphia chromosomes with additional chromosomal abnormalities, t(3;21)(q26;q22) and the FISH studies revealed bcr-abl fusion signals in bone marrow cells. One case expired 8 months later despite of hydroxyuria therapy. The other case received allogeneic bone marrow transplantation (alloBMT) without complete remission but expired 34 weeks after alloBMT due to GVHD.