Assessing Asthma Control by Impulse Oscillometry and Fractional Expiratory Nitric Oxide in Children With Normal Spirometry.

BACKGROUND: Because spirometric parameters fail to address current status of asthma in some patients, additional tests are required for better evaluation of asthma. OBJECTIVE: We aimed to test the ability of impulse oscillometry (IOS) and fractional expiratory nitric oxide (FeNO) in identifying inadequately controlled asthma (ICA) that was not uncovered by spirometry. METHODS: Recruited asthmatic children between ages of 8 and 16 years underwent spirometry, IOS, and FeNO measurements on the same day. Only subjects who had spirometric indices within normal range were included. Asthma Control Questionnaire-6 scores of 0.75 or lower and greater than 0.75 indicated well-controlled asthma (WCA) and ICA. Percent predicted values of IOS parameters and IOS reference values for upper and lower limits of normal (>95th and <5th percentiles, respectively) were calculated on the basis of previously published equations. RESULTS: There were no significant differences in all spirometric indices between the WCA (n = 59) and the ICA (n = 101) groups. The % predicted values of IOS parameters except resistance at 20 Hz (R20) were significantly different between the 2 groups. Receiver operating characteristic analysis showed that the highest and lowest areas under the curve were 0.81 and 0.67 for the difference between the resistances at 5 Hz and 20 Hz (R5-R20) and R20 in discrimination of ICA versus WCA. The areas under the curve for IOS parameters were improved by combination with FeNO. The better discriminative ability of IOS was also supported by the higher values of the concordance index for the resistance at 5 Hz (R5), R5-R20, the reactance at 5 Hz (X5), and the resonant frequency of reactance than those for spirometric parameters. Compared with those with normal values, subjects with abnormal IOS parameters or high FeNO had significantly higher odds of having ICA. CONCLUSIONS: The IOS parameters and FeNO were shown to be useful in identifying children with ICA when spirometry was normal.

The study of association between human papillomavirus and Chlamydia trachomatis infection in cervical intraepithelial neoplasia / 대한산부인과학회지

OBJECTIVE: The aim of this study is to comparing the prevalence and correlationships between human papillomavirus (HPV) and Chlamydia trachomatis (CT) infection in cervical samples among women with abnormal cervical cytology. METHODS: This study was included three hundred seventy four patients with a abnormal liquid-based cytology in Dankook University hospital. All of them underwent HPV DNA test and CT analysis with polymerase chain reaction. All patients also went through colposcopic directed cervical biopsies or Loop Electrosurgical Excision Procedure, conization. The histo-pathologic results were classified as normal, cervical intraepithelial neoplasia (CIN) 1, CIN 2, CIN 3 and carcinoma in situ (CIS). RESULTS: Abnormal liquid-based cytology patients were pathologically proven to have CIN. Among 374 patients, the number of within normal limits (chronic cervicitis) and koilocytosis was 186 cases (49.7%), CIN 1, 64 cases (17.1%), CIN 2, 16 cases (4.3%) CIN 3, 55 cases (14.7%), and CIS, 53 cases (14.2%). HPV DNA positive patients were 235 cases and HPV DNA negative patients were 139 cases. The impact of CT infection seems not to interfere with the development or even the progression of CIN. Thirty one patients had positive infection of CT (8.3%) and 343 patients were negative infection of CT (91.7%). Both HPV and CT positive infected patients were 25 cases (6.7%) in abnormal cytologic women. The correlation between HPV and CT DNA positive among women with abnormal cytology was statistically significant. (P=0.022) CONCLUSION: This study suggests that CT infection is associated with HPV infection, but the clinical significance of the association between CT and HPV infection remains to be elucidated.

A case of fetal intracranial hemorrhage diagnosed by antenatal ultrasonographic examination / 대한주산의학회잡지

Fetal intracranial hemorrhage is quite rare. Antenatal fetal intracranial hemorrhage may occur spontaneously, or in association with various maternal or fetal conditions. Currently, antenatal fetal intracranial hemorrhage may be diagnosed by imaging techniques including ultrasonography and less frequently, magnetic resonance imaging (MRI). We report a case of spontaneous fetal intracranial hemorrhage that was diagnosed antenatally in the third trimester with a brief review of literatures.

Increased antibacterial activity of DW286, a novel fluoronaphthyridone antibiotic, against Staphylococcus aureus strains with defined mutations in DNA gyrase and topoisomerase IV.

To investigate the activity of DW286, a new fluoronaphthyridone, the quinolone resistance determining regions (QRDRs) of gyrA, gyrB, grlA and grlB genes in 64 Staphylococcus aureus clinical isolates were analyzed and the MICs of DW286 and comparator quinolones determined. Double and triple mutants in gyrA and grlA were resistant to ciprofloxacin, sparfloxacin, trovafloxacin and gemifloxacin but susceptible to DW286 (MIC 0.25-0.5 mg/l). The fourth alteration, Ser85Pro of GyrA was required to make a strain resistant to DW286 (MIC 4-32 mg/l). For a strain with the mutations at GyrA Ser84Leu and GrlA Ser80Phe, the MBC of DW286 was two-fold higher than its corresponding MIC, in contrast to ciprofloxacin which was not bactericidal.

Heterogeneity of macrolide-lincosamide-streptogramin B resistance phenotypes in enterococci.

We determined the macrolide resistance phenotypes of 241 clinical isolates of erythromycin-resistant enterococci (MICs, > or = 1 microg/ml), including 147 Enterococcus faecalis strains and 94 Enterococcus faecium strains, collected from a hospital in Seoul, Korea, between 1999 and 2000. By the erythromycin (40 micro g)-josamycin (100 microg) double-disk test, 93 strains were assigned to the constitutive macrolide, lincosamide, and streptogramin B (MLS(B)) resistance (cMLS(B)) phenotype, and the remaining 148 strains were assigned to the inducible MLS(B) resistance (iMLS(B)) phenotype. Of the strains with the iMLS(B) phenotype, 36 exhibited a reversibly inducible MLS(B) (riMLS(B)) phenotype, i.e., blunting of the erythromycin zone of inhibition, which indicates that the 16-membered-ring macrolide josamycin is a more effective inducer than the 14-membered-ring macrolide erythromycin. Sequence analysis of the regulatory regions of the erm(B) genes from all of the strains exhibiting the riMLS(B) phenotype revealed not only erm(Bv) [where v represents variant; previously erm(AMR)] (n = 13), as reported previously, but also three kinds of erm(B) variants, which were designated erm(Bv1) (n = 17), erm(Bv2) (n = 3), and erm(Bv3) (n = 3), respectively. In lacZ reporter gene assays of these variants, the 16-membered-ring macrolide tylosin had stronger inducibility than erythromycin at > or = 0.1 microg/ml. These findings highlight the versatility of erm(B) in induction specificity.

Prevalence and mechanisms of low- and high-level mupirocin resistance in staphylococci isolated from a Korean hospital.

Mupirocin has been used against Gram-positive pathogenic bacteria, and is a specific inhibitor of bacterial isoleucyl-tRNA synthetase. In this work, we have determined the prevalence of mupirocin resistance among staphylococci isolated from a Korean hospital, and have investigated the characteristics of the resistance. In Staphylococcus aureus, the prevalence of high-level mupirocin resistance was 5% (16 of 319), whereas low-level mupirocin resistance was not detected. In coagulase-negative staphylococci (CoNS) the rates of high- and low-level mupirocin resistance were 16.7% (34 of 204) and 10.3% (21 of 204), respectively. The high-level resistant strains contained the ileS-2 gene, which encodes a novel staphylococcal isoleucyl-tRNA synthetase. In contrast, all of the low-level mupirocin-resistant CoNS contained the mutation V588F, which is located near the conserved motif KMSKS, within the chromosomal staphylococcal isoleucyl-tRNA synthetase gene (ileS). In conclusion, this work describes the recent, but rapid, emergence of two different types of mupirocin-resistant staphylococci in Korea, and the sequence and mutant characterization of the isoleucyl-tRNA synthetase of CoNS.

In vitro development of resistance to a novel fluoroquinolone, DW286, in methicillin-resistant Staphylococcus aureus clinical isolates.

In vitro development of resistance to a novel fluoroquinolone, DW286, as well as to ciprofloxacin, gemifloxacin, sparfloxacin and trovafloxacin, was investigated in eight methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates. The strains were subcultured in subinhibitory concentrations of each agent during a 50 day period. Subculturing in most agents led to the selection of 37 mutants with increased MICs. The DW286 MICs were increased from 0.004-0.031 to 0.125-0.5 mg/L in five strains after 13-47 passages, and were not increased in three strains. The ciprofloxacin, gemifloxacin, sparfloxacin and trovafloxacin-selected mutants showed relatively weak cross-resistance to DW286. DNA sequencing analyses of all of the selected mutants revealed a few point mutations responsible for the high level of resistance, but actually these variations did not confer high resistance to fluoroquinolones. In the presence of reserpine, an inhibitor of the Gram-positive efflux pump, of 36 mutants 22 had two- to 16-fold lower ciprofloxacin MICs, and 20 had two- to 16-fold lower gemifloxacin MICs. However, sparfloxacin, trovafloxacin and DW286 were not good substrates for efflux pumps.

In vitro and in vivo antibacterial activities of DW286, a new fluoronaphthyridone antibiotic.

The in vitro and in vivo activities of DW286, a novel fluoronaphthyridone with potent antibacterial activity, were compared with those of ciprofloxacin, gemifloxacin, sparfloxacin, and trovafloxacin. Against gram-positive bacteria, such as Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, and Enterococcus faecalis, the in vitro activity of DW286 was stronger than that of any other reference antibiotic. Against gram-negative bacteria, the activity of DW286 was similar to those of trovafloxacin and gemifloxacin but was weaker than that of ciprofloxacin. In a mouse systemic infection caused by three S. aureus strains, including methicillin-resistant S. aureus and quinolone-resistant S. aureus (QRSA), DW286 demonstrated the most potent activity, as found in vitro. Specially, DW286 is >or=8-fold more active against QRSA than the other fluoroquinolones. And the 50% protective doses for DW286 were correspondent with the in vitro activities.

Role of proline, cysteine and a disulphide bridge in the structure and activity of the anti-microbial peptide gaegurin 5.

Gaegurin 5 (GGN5) is a cationic 24-residue anti-microbial peptide isolated from the skin of a Korean frog, Rana rugosa. It contains a central proline residue and an intra-residue disulphide bridge in its C-terminus, which are common to the anti-microbial peptides found in Ranidae. We determined the solution structure of GGN5 bound to SDS micelles for the first time and investigated the role of proline, cysteine and a disulphide bridge on the structure and activity of GGN5. GGN5 adopts an amphipathic alpha-helical structure spanning residues 3-20 kinked around Pro-14, which allows the hydrophobic residues to reside in the concave helical region, and a disulphide-bridged loop-like conformation in its C-terminus. By replacement of proline with alanine (PAGGN5), a straight and rigid helix was formed in the central region and was more stable than the kinked helix. Reduction of a disulphide bridge in the C-terminus (GGN5SH) maintained the loosely ordered loop-like conformation, while the replacement of two cysteines with serines (CSGGN5) caused the C-terminal conformation to be completely disordered. The magnitude of anti-microbial activity of the peptides was closely related to their helical stability in the order PAGGN5>GGN5>GGN5SH>CSGGN5, suggesting that the helical stability of the peptides is important for anti-microbial activity. On the other hand, the significant increase of haemolytic activity of PAGGN5 implies that a helical kink of GGN5 could be involved in the selectivity of target cells. The location of GGN5 and PAGGN5, analysed using paramagnetic probes, was mainly at the surface of SDS micelles, although the location of the N-terminal region was slightly different between them.

A Case of Ectopic ACTH Syndrome Caused by Thymic Carcinoid Tumor and Localized by PET / 대한내분비학회지

Ectopic ACTH syndrome is frequently caused by lung cancer and uncommonly by other tumors such as thymic carcinoid. For its treatment, early diagnosis and complete resection is irresponsible, but some cases are remained unlocalized in spite of all diagnostic modalities. Here we report a case of ectopic ACTH syndrome which was localized by PET but could not be localized by conventional technique. A tumor at thymic area was ACTH secreting thymic carcinoid which was operated but couldnt resect completly. Glucocorticoid hypersecretion was persisted with chemotherapy, radiotherapy, and ketoconazole treatment. Patient died of sepsis after 12 months of diagnosis.