Investigation of mutation distribution in DNA gyrase and topoisomerase IV genes in ciprofloxacin-non-susceptible Enterobacteriaceae isolated from blood cultures in a tertiary care university hospital in South Korea, 2005-2010.

This study investigated the distribution of mutations in DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE) genes and compared the distribution of these mutations with the distribution of plasmid-mediated quinolone resistance (PMQR) genes and extended-spectrum ß-lactamase (ESBL) production in 101 ciprofloxacin-non-susceptible Enterobacteriaceae from blood culture isolates (80 Escherichia coli and 21 Klebsiella pneumoniae) isolated in Kyung Hee University Hospital, a tertiary care university hospital in Seoul, South Korea. Among the 101 isolates, 80 (79.2%) contained PMQR genes and 28 (27.7%) produced ESBL. Mutations in the gyrA and parC genes were observed more frequently than in the gyrB and parE genes as well as more frequently in E. coli than in K. pneumoniae isolates, even in the same ciprofloxacin minimum inhibitory concentration (MIC) range of the two species. In E. coli isolates, the distribution of the codon 529 mutation (Ile→Leu) in parE was increased with an increase in the ciprofloxacin MIC. An increase in high-level resistance to quinolones may occur with double mutations compared with a single mutation in gyrA as well as with additional mutations in parC. However, this finding could not be applied to ciprofloxacin-resistant K. pneumoniae. A higher level of quinolone resistance may be correlated with an additional mutation in parE, especially Ile529→Leu.

Mean platelet volume/platelet count ratio in hepatocellular carcinoma.

Mean platelet volume (MPV) has been actively investigated in liver disease such as steatosis, cirrhosis and hepatitis. Recently, MPV/platelet count (PC) ratio has been proposed as a predictor of long-term mortality after myocardial infarction. As PC is known to be decreased in various liver diseases such as cirrhosis, hepatosplenomegaly and malignancy, we planned to evaluate MPV/PC ratio in patients with hepatocellular carcinoma (HCC) in this study. Mean of MPV levels showed significant difference, which were 8.69 fl (range 6.7-12.2 fl) in patients group and 8.02 fl in control group (range 6.7-11.0 fl). In receiver operating characteristic (ROC) curve analysis, the MPV/PC ratio (fl/(10(9)/l)) presented 74.5% of sensitivity and 96.5% of specificity at the criterion > 0.0491 (area under the curve (AUC) = 0.884), while MPV alone showed 57.4% of sensitivity and 81.4% of specificity at the criterion > 8.4 fl. Further studies should evaluate underlying pathogenic mechanisms of MPV/PC ratio difference and various possibilities of this ratio as an indicator of presence of a tumor in HCC.

Detection of RUNX1-MECOM fusion gene and t(3;21) in a very elderly patient having acute myeloid leukemia with myelodysplasia-related changes.

An 87-yr-old woman was diagnosed with AML with myelodysplasia-related changes (AML-MRC). The initial complete blood count showed Hb level of 5.9 g/dL, platelet counts of 27 × 10(9)/L, and white blood cell counts of 85.33 × 10(9)/L with 55% blasts. Peripheral blood samples were used in all the tests, as bone marrow examination could not be performed because of the patient's extremely advanced age and poor general health condition. Flow cytometric analysis, chromosome analysis, FISH, and reverse transcriptase-PCR (RT-PCR) results indicated AML-MRC resulting from t(3;21) with the RUNX1-MECOM fusion gene. To our knowledge, this is the second most elderly de novo AML patient associated with t(3;21) to be reported.

Simultaneous detection of Gaucher's disease and renal involvement of non-Hodgkin's lymphoma: the first Asian case report and a review of literature.

Gaucher's disease (GD) is a rare autosomal recessive (AR) disorder characterized by a deficiency of glucocerebrosidase (glucosylceramidase, acid ß-glucosidase). This enzyme deficiency results in an accumulation of sphingolipids in the cells of GD patients, which may contribute to the dysregulation of the immune system, B-cell dysfunction and expression of specific cytokines such as interleukin (IL) -1, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF). Accumulated substrate may directly affect the patient's immunity and pose a higher risk for cancer, especially hematologic malignancies. However, recent large-scale studies suggest that the relative risks of GD and hematologic malignancies are not statistically significant and, therefore, their association with each other remains controversial. In this report, we present the first Asian GD case where the patient was simultaneously diagnosed with a non-Hodgkin's lymphoma. A renal biopsy confirmed that the patient had diffuse large B-cell lymphoma (DLBCL). A bone marrow study during lymphoma staging revealed Gaucher cells with abundant fibrillary, blue-gray cytoplasm and a wrinkled, tissue paper-like appearance. Subsequently, an acid ß-glucosidase (GbA) gene mutation study demonstrating two heterozygote mutations, G202R (c.721G>A; p.G241R), a known pathogenic mutation, and a novel mutation R277C (c.946C>T; p.R316C) prompted the diagnosis of GD. Previous case reports have demonstrated concurrent GD and lymphoma in type 1 GD patients, with 40% of patients diagnosed with GD when a lymphoma is detected during disease evaluation. In Korea, GD cases with the G202R gene mutation have been reported in neuropathic patients with a very low frequency. To our knowledge, this case represents the first observation of the G202R mutation in a type 1 GD patient associated with lymphoma. Furthermore, this report is the first patient with DLBCL with kidney involvement along with GD.

Combined Bacillus licheniformis and Bacillus subtilis infection in a patient with oesophageal perforation.

Species of the genus Bacillus are a common laboratory contaminant, therefore, isolation of these organisms from blood cultures does not always indicate infection. In fact, except for Bacillus anthracis and Bacillus cereus, most species of the genus Bacillus are not considered human pathogens, especially in immunocompetent individuals. Here, we report an unusual presentation of bacteraemia and mediastinitis due to co-infection with Bacillus subtilis and Bacillus licheniformis, which were identified by 16S RNA gene sequencing, in a patient with an oesophageal perforation.

The clinical significance of serum cystatin C in critically ill newborns with normal serum creatinine.

BACKGROUND: The aim of this study is to evaluate the clinical significance of cystatin C(CysC) in the newborns who show normal serum creatinine (Cr) and who are in an intensive care unit. METHODS: From July 2009 to May 2010, a total of 106 patients (53 male and 53 female newborns) in a neonatal intensive care unit at Kyung Hee Medical Center were enrolled in this study. When clinicians ordered CysC, it was tested using HiSens Cystatin-C LTIA(HBi, An-yang, Korea) on a Toshiba chemical analyzer (Toshiba, Nasushiobara, Japan). RESULTS: The range of serum Cr and CysCwas from 0.1 to 0.8 mg/dL and from 1.0 to 2.3 mg/L, respectively. CysCpresented the wider amplitude of the changes in acute renal failure. CONCLUSION: In this study, CysCwithout an increased Cr showed only a mild increase. However, CysCreflected more delicate changes in newborns than the serum Cr. This characteristic of CysCcould make it very appropriate for a pediatric population, especially for critically ill newborns.

Prevalence of the plasmid-mediated quinolone resistance genes, aac(6')-Ib-cr, qepA, and oqxAB in clinical isolates of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae in Korea.

In this study, we sought to determine the prevalence of the plasmid-mediated quinolone resistance (PMQR) genes aac(6')-Ib-cr, qepA, and oqxAB in extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae clinical isolates in South Korea. In total, 104 isolates (63 E. coli and 41 K. pneumoniae) were collected. We found that 23 of the 63 (36.5%) E. coli and nine of the 41 (22.0%) K. pneumoniae isolates were positive for aac(6')-Ib-cr. No isolate was positive for qepA, while transferable oqxAB was detected only in 10 (24.4%) K. pneumoniae isolates. Among the 32 aac(6')-Ib-cr-positive isolates, 30 (93.8%) were positive for both aac(6')-Ib-cr and bla(CTX-M) (CTX-M-15, -14, and -57). Our results suggest that PMQR determinants are highly prevalent in ESBL-producing E. coli and K. pneumoniae isolates in Korea.

Characteristics of outpatients with pandemic H1N1/09 influenza in a tertiary care university hospital in Korea.

The pandemic H1N1/09 emerged rapidly in Korea. Here, we describe the clinical characteristics of outpatients in Seoul, Korea who were infected in the 2009 H1N1 pandemic. We reviewed the cases of outpatients with pandemic H1N1/09 who visited a tertiary care teaching hospital between September 1 and December 31, 2009. Infection with pandemic H1N1/09 was confirmed by molecular tests. Of a total of 7,182 tests, 3,020 (42.0%) were positive. Compared with 473 cases of influenza- like illness (ILI), the 586 confirmed cases of pandemic H1N1/09 differed in age [odds ratio (OR) 0.975] and fulfilling at least one of the following factors: age < 5 or ≥ 65 years, history of contact with other pandemic H1N1/09-infected individuals (OR 0.611), fever ≥ 37.8°C (OR 3.567), cough (OR 2.290), and myalgia (OR 1.559). The sensitivity of the best criteria, "fever (≥ 37.8°C) plus cough" (41.03%) in this study was lower than that of the Korea Centers for Disease Control and Prevention (KCDC) criteria (47.95%), whereas the positive likelihood ratio (3.55) and positive predictive value (81.6) of this criteria was higher than those of the KCDC criteria (2.98 and 78.7, respectively). The clinical characteristics of pandemic H1N1/09 are, in many regards, indistinguishable from those of ILI. Moreover, the accuracy and predictability of criteria which include only symptoms or signs were not sufficient to diagnose pandemic H1N1/09 infection. Therefore, use of a combination of symptoms with confirmatory laboratory testing is necessary for accurate diagnosis of pandemic H1N1/09.

Adjuvant laboratory marker of Kawasaki disease; NT-pro-BNP or hs-CRP?

BACKGROUND: The diagnosis of Kawasaki disease (KD) is based on clinical data and non-pathognomonic symptoms. As no specific diagnostic test for KD exists, BNP or NT-pro-BNP might be of importance in identifying KD. We compared serum hs-CRP and NT-pro-BNP level in the acute phase of 59 KD patients and evaluated the diagnostic performance of these laboratory markers in KD to estimate the cut-off level for differentiating KD from other febrile illnesses as age-matched controls. MATERIALS AND METHODS: The study groups consisted of 59 KD patients in the disease group and 45 other patients with febrile illnesses as age-matched controls. NT-pro-BNP was measured using Elecsys proBNP (Roche Diagnostics, Mannheim, Germany), and hs-CRP was tested with CardioPhase hs-CRP (Siemens Healthcare Diagnostics, Marburg, Germany). RESULTS: NT-pro-BNP levels were significantly higher in the KD patients than in the controls (P < 0.001). In the ROC curve analysis, the sensitivity was 66.10%, and the specificity was 77.08% at 235.2 pg/mL. hs-CRP levels tended to be higher in KD patients compared to controls. DISCUSSION: This study indicates that NT-pro-BNP might be a more useful laboratory marker as an adjuvant diagnostic tool for KD than hs-CRP. Especially in a patient with incomplete clinical features of KD, the diagnosis and the start of treatment were delayed to confirm a fever persisting for at least 5 days. Therefore, we expect that NT-pro- BNP would be especially useful for KD patients with these atypical clinical presentations.

Primary Plasma Cell Leukemia Associated with t(6;14)(p21;q32) and IGH Rearrangement: A Case Study and Review of the Literature.

Because plasma cell leukemia (PCL) is a rare and distinct variant among plasma cell dyscrasias, recent clinical and cytogenetic studies have been performed in different ethnic groups to define the characteristics of these PCL patients. As far as we know, IGH rearrangements involving t(11;14) and (14;16) are significantly more frequent in PCL than in myeloma patients. However, PCL cases associated with t(6;14)(p21;q32) or IGH-CCND3 rearrangement are extremely rare in the literature; only one PCL case with t(6;14) has been documented. A 61-year-old female was admitted due to fatigue, weight loss, and exertional dyspnea. Plasmacytoid cells were counted up to 76% at a peripheral blood film, but bone marrow aspiration failed because of dry-tapping. Flow cytometric analysis showed positive for CD138 and cytoplasmic kappa light chain. Chromosome analysis revealed t(6;14)(p21;q32), which was confirmed by an IGH split-out probe in FISH analysis. Immunofixation electrophoresis also presented monoclonal bands identified as IgG and kappa light chain. Finally, she was diagnosed as primary PCL associated with t(6;14) and IGH rearrangement. Although considerable advances have been made in the understanding of the biology and molecular pathogenesis of PCL, further clinical, laboratory, and genetic studies of PCL associated with such a rare IGH rearrangement would be necessary in the future. To the best of our knowledge, this is the first report of PCL associated with t(6;14) as a sole chromosomal abnormality.