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1.
Exp Cell Res ; 430(1): 113722, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37442265

RESUMO

Osimertinib is a third-generation epidermal growth factor receptor (EGFR)1 tyrosine kinase inhibitor (TKI) approved for the treatment of EGFR-positive patients exhibiting a T790 M resistance mutation after treatment with an earlier generation of EGFR TKIs. However, resistance to osimertinib inevitably develops despite its efficacy, and the resistance mechanisms are complex and not fully understood. We established cell lines with acquired resistance to osimertinib from gefitinib- or erlotinib-resistant NSCLC cells using a dose-escalation method, and found that they had upregulated levels of phosphorylated ERK1/2. Targeted next-generation sequencing of 143 genes was performed, and interestingly, amplification of KRAS was observed in osimertinib-resistant cells. Transfection of siRNA against the KRAS gene notably reduced the activation of ERK1/2 and AKT and significantly enhanced the induction of apoptosis by osimertinib treatment in osimertinib-resistant cells. LY3009120, a RAF inhibitor, showed a significant synergistic effect with osimertinib on apoptotic cell death in osimertinib-resistant cells. Combined treatment with osimertinib and LY3009120 also demonstrated remarkable synergistic anti-tumor activity in mouse xenografts of these cells. This could be a potential new treatment option for KRAS amplification-induced osimertinib failure.


Assuntos
Neoplasias Pulmonares , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Animais , Camundongos , Proteínas Proto-Oncogênicas p21(ras)/genética , Resistencia a Medicamentos Antineoplásicos/genética , Linhagem Celular Tumoral , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Compostos de Anilina/farmacologia , Receptores ErbB/genética , Inibidores de Proteínas Quinases/farmacologia , Mutação
2.
Artigo em Inglês | MEDLINE | ID: mdl-35580017

RESUMO

A Gram-stain-positive coccus was isolated from the blood of a paediatric patient suffering from gastroenteritis. The taxonomic position of this catalase-positive, non-motile, non-spore-forming facultative anaerobe designated as strain MKL-02T was investigated using a polyphasic approach. Colonies grown on tryptic soy agar with 10 % sheep blood were circular, creamy yellow, and convex. Phylogenetic analysis based on 16S rRNA gene and whole-genome sequences revealed that this strain was most closely related to Arsenicicoccus bolidensis CCUG 47306T within the cluster of the genus Arsenicicoccus. Average nucleotide identity and digital DNA-DNA hybridization values between strain MKL-02T and A. bolidensis DSM 15745T, A. dermatophillus DSM 25571T and A. piscis DSM 22760T were 89.5 and 37.0 %, 79.6 and 22.4 %, and 75.9 and 21.0 %, respectively. The genomic size of strain MKL-02T was 3 423 857 bp with a 72.7 mol% G+C content. Growth was observed at 10-45 °C (optimum, 37-40 °C) and pH 6.0-10.0 (optimum, pH 7.0), in the presence of 0-10 % (w/v) NaCl (optimum, 0.5 %). Cells of strain MKL-02T were non-motile cocci and 0.50-0.60 µm long, as determined by transmission electron microscopy. The strain was catalase-positive and oxidase-negative. The major fatty acid type (>10 % of total) was C15 : 0. The polar lipid profile consisted of two unidentified phospholipids, three unidentified lipids and an unidentified aminophospholipid. The strain contained MK-8 (H4) as the predominant menaquinone. Based on phylogenetic and phenotypic considerations, it is proposed that strain MKL-02T be classified as a new species, named Arsenicicoccus cauae sp. nov. The type strain is MKL-02T (=NCCP 16967T=JCM 34624T).


Assuntos
Infecções por Actinomycetales , Actinomycetales , Gastroenterite , Actinomycetales/isolamento & purificação , Infecções por Actinomycetales/sangue , Infecções por Actinomycetales/microbiologia , Animais , Técnicas de Tipagem Bacteriana , Composição de Bases , Catalase/genética , Criança , DNA Bacteriano/genética , Ácidos Graxos/química , Gastroenterite/sangue , Gastroenterite/microbiologia , Humanos , Hibridização de Ácido Nucleico , Fosfolipídeos/química , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Ovinos
3.
Ann Clin Microbiol Antimicrob ; 21(1): 55, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36474214

RESUMO

BACKGROUND: The prevalence of Tropheryma whipplei varies depending on age, region, and underlying disease. We estimated the prevalence of T. whipplei in the stools of Korean patients with diarrhea using real-time PCR (RT-PCR) and compared three RT-PCR targets, rpoB, hsp65, and Dig15. METHODS: A total of 1404 nucleic acid samples extracted from the stools of Korean patients with diarrhea were tested using an initial RT-PCR targeting T. whipplei-specific regions of 16S-23S rRNA intergenic spacer. Subsequently, the samples positive for the initial RT-PCR were tested using the follow-up RT-PCRs targeting rpoB, hsp65, and Dig15 and analyzed by sequencing to confirm the presence of T. whipplei. We estimated the prevalence of T. whipplei and compared them according to gender and age. We also compared the performance of three targets in the follow-up RT-PCRs. RESULTS: T. whipplei was detected in 1.4% of all samples (20 of 1404), and there were no differences according to gender and age. In pediatric samples (≤ 19 years), T. whipplei was detected higher in children aged 6-19 than in those aged 1-5 (2.7% vs. 0.7%, P = 0.01). Sensitivities of the rpoB, hsp65, and Dig15 RT-PCR were 50.0%, 85.0%, and 95.0%, respectively; specificities were 100.0%, 100.0%, and 84.6%, respectively. CONCLUSIONS: This is the first study that estimated the prevalence of T. whipplei in the stools of Korean patients with diarrhea. This study demonstrated the presence of T. whipplei in stools of Koreans, even though the bacterium was detected low. The RT-PCRs targeting hsp65 and Dig15 showed reliable performance, and a multiplex PCR including these targets is expected to be useful for T. whipplei detection.


Assuntos
Tropheryma , Humanos , Criança , Reação em Cadeia da Polimerase em Tempo Real
4.
J Korean Med Sci ; 37(43): e310, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36345256

RESUMO

Antigen rapid diagnostic tests (RDTs) became the most important tool for the diagnosis of the coronavirus disease 2019 (COVID-19), however there have been very few evaluations of the accuracy of the RDTs in actual use. In this study, we investigated the performance accuracy of the RDT, the STANDARD Q COVID-19 Ag (STANDARD Q), in the Republic of Korea. We collected a total of 5,792 results that underwent both RDT and reverse transcription polymerase chain reaction simultaneously, and overall sensitivity and specificity of the STANDARD Q were 57.6% and 99.9%, respectively. With binomial logistic regression analysis, we estimated that about half of the COVID-19 patients with a cycle threshold value of 25 for E and RdRP were RDT-negative. These results suggest that the clinical sensitivity of RDTs against severe acute respiratory syndrome coronavirus 2 is considerably low in a real-world setting, and we recommend that limitations of RDTs should be considered when setting up COVID-19 test strategies.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , Testes Diagnósticos de Rotina , Sensibilidade e Especificidade , República da Coreia , Antígenos Virais
5.
BMC Med Inform Decis Mak ; 22(1): 286, 2022 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-36344984

RESUMO

BACKGROUND: The tendency of amyloid-ß to form oligomers in the blood as measured with Multimer Detection System-Oligomeric Amyloid-ß (MDS-OAß) is a valuable biomarker for Alzheimer's disease and has been verified with heparin-based plasma. The objective of this study was to evaluate the performance of ethylenediaminetetraacetic acid (EDTA)-based MDS-OAß and to develop machine learning algorithms to predict amyloid positron emission tomography (PET) positivity. METHODS: The performance of EDTA-based MDS-OAß in predicting PET positivity was evaluated in 312 individuals with various machine learning models. The models with various combinations of features (i.e., MDS-OAß level, age, apolipoprotein E4 alleles, and Mini-Mental Status Examination [MMSE] score) were tested 50 times on each dataset. RESULTS: The random forest model best-predicted amyloid PET positivity based on MDS-OAß combined with other features with an accuracy of 77.14 ± 4.21% and an F1 of 85.44 ± 3.10%. The order of significance of predictive features was MDS-OAß, MMSE, Age, and APOE. The Support Vector Machine using the MDS-OAß value only showed an accuracy of 71.09 ± 3.27% and F-1 value of 80.18 ± 2.70%. CONCLUSIONS: The Random Forest model using EDTA-based MDS-OAß combined with the MMSE and apolipoprotein E status can be used to prescreen for amyloid PET positivity.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Ácido Edético , Peptídeos beta-Amiloides , Doença de Alzheimer/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Biomarcadores , Aprendizado de Máquina , Algoritmos , Disfunção Cognitiva/diagnóstico
6.
Artigo em Inglês | MEDLINE | ID: mdl-33847555

RESUMO

A novel Gram-stain-negative, facultative aerobic and rod-shaped bacterium, designated as MKL-01T and isolated from the blood of immunocompromised patient, was genotypically and phenotypically characterized. The colonies were found to be creamy yellow and convex. Phylogenetic analysis based on 16S rRNA gene and whole-genome sequences revealed that strain MKL-01T was most closely related to Cupriavidus gilardii LMG 5886T, present within a large cluster in the genus Cupriavidus. The genome sequence of strain MKL-01T showed the highest average nucleotide identity value of 92.1 % and digital DNA-DNA hybridization value of 44.8 % with the closely related species C. gilardii LMG 5886T. The genome size of the isolate was 5 750 268 bp, with a G+C content of 67.87 mol%. The strain could grow at 10-45 °C (optimum, 37-40 °C), in the presence of 0-10 % (w/v) NaCl (optimum, 0.5%) and at pH 6.0-10.0 (optimum, pH 7.0). Strain MKL-01T was positive for catalase and negative for oxidase. The major fatty acids were C16 : 0, summed feature 3 (C16 : 1 ω7c/C16 : 1 ω6c and/or C16 : 1 ω6c/C16 : 1 ω7c) and summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c). The polar lipid profile consisted of phosphatidylglycerol, phosphatidylethanolamine, two unidentified phospholipids and one unidentified polar lipid. Moreover, strain MKL-01T contained ubiquinone Q-8 as the sole respiratory quinone. Based on its molecular, phenotypic and chemotaxonomic properties, strain MKL-01T represents a novel species of the genus Cupriavidus; the name Cupriavidus cauae sp. nov. is proposed for this strain. The type strain is MKL-01T.


Assuntos
Sangue/microbiologia , Cupriavidus/classificação , Hospedeiro Imunocomprometido , Filogenia , Adulto , Técnicas de Tipagem Bacteriana , Composição de Bases , Cupriavidus/isolamento & purificação , DNA Bacteriano/genética , Ácidos Graxos/química , Feminino , Humanos , Hibridização de Ácido Nucleico , Fosfolipídeos/química , Pigmentação , RNA Ribossômico 16S/genética , República da Coreia , Análise de Sequência de DNA , Ubiquinona/química
7.
BMC Infect Dis ; 21(1): 851, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34418960

RESUMO

BACKGROUND: Inconclusive results in SARS-CoV-2 molecular assays cause confusion among clinicians and delay appropriate infection prevention and control. In this study, we aimed to characterize the respiratory specimens associated with inconclusive SARS-CoV-2 molecular assay results. METHODS: We re-evaluated inconclusive specimens by 3 additional RT-PCR assays and attempted to detect subgenomic RNA (sgRNA) in these specimens. RESULTS: Among follow-up tests from confirmed SARS-CoV-2 cases, 36.3% of the inconclusive results were classified as presumptive positive results (45/124). However, none of the specimens from 36 screening cases was classified as a presumptive positive result. Among 160 inconclusive specimens, sgRNAs were detected in 78 samples (48.8%): 58 were confirmed cases (58/124, 46.8%) and 20 were screening cases (20/36, 55.6%). CONCLUSIONS: The results of our study suggest the recommendation of considering inconclusive results as positive results for confirmed SARS-CoV-2 cases. In screening cases, viral remnants could be partially amplified in PCR assays, and these inconclusive results could be related to previous infections. In addition, sgRNAs were detected in about half of the inconclusive specimens; however, the clinical significance of sgRNA is not yet clear.


Assuntos
COVID-19 , SARS-CoV-2 , Teste para COVID-19 , Humanos , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
8.
Hered Cancer Clin Pract ; 19(1): 28, 2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34082788

RESUMO

BACKGROUND: Endometrial cancer is often the sentinel cancer in women with Lynch syndrome, among which endometrioid endometrial cancer is the most common. We found a Korean case of uterine carcinosarcoma associated with Lynch syndrome. And we reviewed 27 Korean women with endometrial cancer associated with Lynch syndrome already released in case report so far. CASE PRESENTATION: The proband, a 45-year-old Korean woman received treatment for endometrioid adenocarcinoma. Her older sister and niece were treated for endometrioid adenocarcinoma and carcinosarcoma, respectively. Family history met the Amsterdam II criteria and immunohistochemical analysis revealed a loss of MLH1 and PMS2. They all harbored a previously unreported germline likely pathogenic variant in c.1367delC in MLH1. They underwent staging operations including total hysterectomy, bilateral salpingo-oophorectomy, pelvic/paraaortic lymph node dissection, and washing cytology. All three women were healthy without evidence of relapse for over 4 years. CONCLUSION: This report indicates a novel germline c.1367delC variant in MLH1, and presents a Korean case of uterine carcinosarcoma associated with Lynch syndrome. Furthermore, the c.1757_1758insC variant in MLH1 was suggested as a founder mutation in Lynch syndrome in Korean women.

9.
Clin Infect Dis ; 70(12): 2683-2694, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-31353397

RESUMO

BACKGROUND: Human metapneumovirus (hMPV) commonly causes upper and lower respiratory tract infections. Here, we performed long-term retrospective surveillance of hMPV infection among patients hospitalized in South Korea between 2007 and 2016 and investigated seasonal dynamics and clinical characteristics associated with each virus subtype/genotype. METHODS: Patient specimens were tested for hMPV and other respiratory viruses by commercial molecular assays. Medical records of hMPV-positive patients were reviewed, and hMPV subtype/genotype analysis was performed. We also collected meteorological data and analyzed relationships with hMPV activity. RESULTS: Of 23 694 specimens, 1275 (5.4%) were positive; among them, 94.0% were classified into 5 subtypes (A1, A2a, A2b, B1, and B2). Some clinical manifestations differed according to hMPV genotype; however, there was no correlation between hMPV subtype and clinical outcome. Viral activity peaked at 13-20 weeks (April and May) and was associated with climate-specific factors, including temperature, relative humidity, diurnal temperature variation, wind speed, and sunshine duration. CONCLUSIONS: This large-scale, 10-year study provides valuable information about the clinical characteristics associated with hMPV subtypes and climate factors contributing to virus transmission.


Assuntos
Metapneumovirus , Infecções por Paramyxoviridae , Infecções Respiratórias , Genótipo , Humanos , Lactente , Metapneumovirus/genética , Infecções por Paramyxoviridae/epidemiologia , República da Coreia/epidemiologia , Infecções Respiratórias/epidemiologia , Estudos Retrospectivos
10.
Clin Chem Lab Med ; 58(9): 1525-1533, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32238603

RESUMO

Background: The assessment of measurement uncertainty (MU) in clinical laboratories is essential to the reliable interpretation of results in clinical laboratories. However, despite the introduction of various methods for the expression of uncertainty in measurement, the MUs of coagulation tests have not been extensively studied. The aim of this study was to quantify the MU of various coagulation assays according to international guidelines and to report an expected confidence in the quality of coagulation assays. Methods: We selected activated partial thromboplastin time, international normalized ratio (INR), protein C/S, antithrombin, fibrinogen, and Factor V/VIII/X to quantify the MUs of two coagulation testing systems: ACL TOP 750 CTS (Instrumentation Laboratory, Bedford, MA, USA) and STA Compact (Diagnostica Stago, Asnières-sur-Seine, France). We used international standards and interlaboratory comparison results in accordance with international guidelines in a top-down approach to the assessment of MU. For INR, MU was estimated in a bottom-up approach using reference thromboplastin and certified plasmas. Results: Top-down approaches resulted in MUs between 3.3% and 21.3% for each measurand. In the bottom-up approach, MUs of INR values ranged from 10.9% to 26.4% and showed an upward trend as INR increased. Conclusions: In this study, we were successful in quantifying MU of coagulation assays using practical methods. Our results demonstrated that top-down and bottom-up approaches were adequate for coagulation assays. However, some assays showed significant biases against international standards; therefore, standardization would be necessary to ensure more reliable patient results.


Assuntos
Testes de Coagulação Sanguínea/métodos , Testes de Coagulação Sanguínea/normas , Laboratórios/normas , Incerteza , Coagulação Sanguínea , Humanos
11.
J Clin Microbiol ; 57(12)2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31533984

RESUMO

The laboratory diagnosis of latent tuberculosis infection (LTBI) is mainly performed with interferon gamma release assays (IGRAs). We compared the performance of a new enzyme-linked immunosorbent assay (ELISA)-based IGRA, the Standard E TB-Feron ELISA (TBF; SD Biosensor, Gyeonggi-do, Republic of Korea), with that of a widely used assay, the QuantiFERON-TB Gold In-Tube assay (QFT-GIT; Qiagen, Hilden, Germany), in a population of 425 health care workers (HCWs). All HCWs were screened by both assays per the manufacturers' protocols and in a cross-manner, where tube sets from one assay were used with the alternative ELISA. The results were compared both qualitatively and quantitatively. TBF and QFT-GIT identified 11.3% (48/425) and 12.9% (55/425) of the positive samples, respectively. TBF demonstrated 81.6% positive and 97.4% negative percent agreement with QFT-GIT, with a Cohen's kappa value of 0.78 (strong agreement). Discordant results were detected in 20 subjects (4.3%): 13 samples (65.0%) were TBF negative and QFT-GIT positive, 6 samples (30.0%) were TBF positive and QFT-GIT negative, and 1 sample provided TBF and QFT-GIT indeterminate/negative results. We observed a statistically significant degree of correlation between the interferon gamma reactivity between the two assays (Spearman's rho [rs ] value = 0.551, P < 0.01) and between standard assays and cross-manner tests (rs value range, 0.449 to 0.816; P < 0.01 for all combinations). Cross-manner tests also revealed that the ELISA kit of TBF provided higher values for the tube containing the tuberculosis (TB) antigen and the negative-control tube than the ELISA of QFT-GIT under the same conditions (P < 0.01), although these differences disappeared when the value for the negative-control tube was subtracted from that for the TB antigen tube. TBF showed a comparable and acceptable clinical performance in detecting LTBI compared to QFT-GIT. TBF represents a useful alternative tool as an ELISA-based IGRA, especially for large-scale screening for LTBI in HCWs.


Assuntos
Testes Diagnósticos de Rotina/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Pessoal de Saúde , Testes de Liberação de Interferon-gama/métodos , Tuberculose Latente/diagnóstico , Exposição Ocupacional , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia , Adulto Jovem
12.
J Med Virol ; 91(6): 1056-1062, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30668895

RESUMO

ABSTRACTBACKGROUND: Although immunoassays play a major role in the detection of hepatitis viruses, there is a need for a point-of-care (POC) test. We evaluated the EuDx-HE (A,B,C) kit (EUDIPIA, Cheongju, Korea), which detects anti-hepatitis A virus (HAV) immunoglobulin M (IgM), hepatitis B virus surface antigen (HBsAg), and anti-hepatitis C virus (HCV) immunoglobulin G (IgG) simultaneously using an immunochromatographic method within 15 minutes. METHODS: A total of 1581 serum samples including 57, 477, and 451 samples positive for anti-HAV IgM, HBsAg, and anti-HBV IgG, respectively, were analyzed. We investigated the diagnostic accuracy of the EuDx-HE (A,B,C) kit by comparison with SD BIOLINE POC kits (Abbott, Chicago, IL) using Architect immunoassays as a reference method. RESULTS: For anti-HAV IgM and HBsAg detection, the EuDx-HE (A,B,C) kit showed a higher sensitivity and a slightly lower specificity than the SD BIOLINE kit. For anti-HCV IgG detection, the EuDx-HE (A,B,C) kit had a higher sensitivity and a higher specificity than the SD BIOLINE kit. The agreement for positivity between the POC tests was >89.47%, with κ values of 0.844, 0.941, and 0.943 for HAV, HBV, and HCV, respectively. CONCLUSION: The EuDx-HE (A,B,C) kit showed an acceptable clinical performance for detecting anti-HAV IgM, HBsAg, and anti-HCV.


Assuntos
Anticorpos Antivirais/sangue , Antígenos Virais/sangue , Hepatite A/diagnóstico , Hepatite B/diagnóstico , Hepatite C/diagnóstico , Imunoensaio/normas , Sistemas Automatizados de Assistência Junto ao Leito/normas , Antígenos Virais/imunologia , Hepacivirus/isolamento & purificação , Vírus da Hepatite A/isolamento & purificação , Vírus da Hepatite B/isolamento & purificação , Humanos , Imunoensaio/métodos , Testes Imediatos/normas , Sensibilidade e Especificidade
13.
J Cardiothorac Vasc Anesth ; 33(5): 1224-1229, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30655204

RESUMO

OBJECTIVE: To quantify the degree of lethal and sublethal damage to red blood cells (RBCs) by cell saver (CS) processing among different conditions of shed blood in cardiac surgery. DESIGN: Prospective randomized, double-blinded, controlled study. SETTING: Single university hospital. PARTICIPANTS: Twenty rabbits were divided randomly into non-heparinized and heparinized groups. Thereafter, each group was subdivided into non-gauze and gauze groups based on whether the blood was collected with gauze and squeezed out. INTERVENTIONS: Blood from each group was aspirated directly from the heart and underwent CS processing. Mechanical fragility index (MFI) and percent hemolysis were measured pre- and post-CS processing. MEASUREMENTS AND MAIN RESULTS: In RBCs after CS processing, the MFI and percent hemolysis were increased significantly in both the non-heparinized and heparinized groups compared to pre-CS processing. The MFI was significantly higher in the heparinized group than in the non-heparinized group (p = 0.002). However, no differences in percent hemolysis were detected between groups (p = 0.696). The MFI and percent hemolysis of the non-gauze and gauze groups did not differ. CONCLUSION: This study reports the increase in sublethal and lethal injuries to RBCs from heparinized and non-heparinized blood after CS processing. CS-processed heparinized blood contained more sublethally injured RBCs compared to CS-processed non-heparinized blood. RBCs collected by squeezing blood-saturated gauze did not exhibit additional trauma. Further investigation is required to determine the clinical implications of transfusing rescued but injured RBCs using a CS.


Assuntos
Coleta de Amostras Sanguíneas/métodos , Coleta de Amostras Sanguíneas/normas , Eritrócitos/fisiologia , Animais , Método Duplo-Cego , Transfusão de Eritrócitos/métodos , Transfusão de Eritrócitos/normas , Estudos Prospectivos , Coelhos , Distribuição Aleatória
14.
Int J Colorectal Dis ; 33(4): 441-447, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29488087

RESUMO

PURPOSE: Essential treatment of acute appendicitis is surgical resection with the use of appropriate antibiotics. In order to effectively treat acute appendicitis, it is important to identify the microorganism of acute appendicitis and evaluate the effective antibiotics. METHODS: A total of 694 patients who underwent appendectomy for acute appendicitis and had positive microbial result between 2006 and 2015 were recruited. For microbial assessment, luminal contents of the appendix were swabbed after appendectomy. In patients with periappendiceal abscess, the specimens were obtained from abscess fluid. The patient characteristics, operative data, use of antibiotics, the results of microbiology, and postoperative morbidities including surgical site infection (SSI) were retrospectively reviewed. RESULTS: The mean age was 38.2 (± 19.8) years, and 422 patients (60.8%) were male. Most of the operations were performed by conventional laparoscopy (83.1%), followed by single-port laparoscopy (11.8%). The most common microorganism was Escherichia coli (64.6%), which was susceptible to amoxicillin/clavulanate, ciprofloxacin, most cephalosporins, piperacillin/tazobactam, and imipenem. The second most common microorganism was Pseudomonas aeruginosa (16.4%), which was resistant to amoxicillin/clavulanate and cefotaxime. The rate of postoperative morbidity was 8.6%, and the most common type was superficial SSI (6.2%), followed by ileus (1.2%), gastroenteritis (0.7%), and organ/space SSI (0.3%). P. aeruginosa (odds ratio = 2.128, 95% confidence interval 1.077-4.206, P = 0.030) was the only significant microorganism associated with SSI according to multivariate analysis adjusting for other clinical factors. CONCLUSIONS: In perforated appendicitis, the use of empirical antibiotics seems to be safe. In some cases of Pseudomonas infection, adequate antibiotics should be considered.


Assuntos
Antibacterianos/uso terapêutico , Apendicite/tratamento farmacológico , Apendicite/microbiologia , Doença Aguda , Adulto , Antibacterianos/farmacologia , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Infecção da Ferida Cirúrgica/tratamento farmacológico
16.
BMC Neurol ; 16: 71, 2016 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-27206484

RESUMO

BACKGROUND: Three main genes are described as causative genes for early-onset Alzheimer dementia (EOAD): APP, PSEN1 and PSEN2. We describe a woman with EOAD had a novel PSEN1 mutation. CASE REPORT: A 54-year-old right-handed woman presented 12-year history of progressive memory decline. She was clinically diagnosed as familial Alzheimer's disease due to a PSEN1 mutation. One of two daughters also has the same mutation, G209A in the TM-IV of PS1 protein. Her mother had unspecified dementia that began at the age of 40s. PolyPhen2 and SIFT prediction suggested that G209A might be a damaging variant with high scores. 3D modeling revealed that G209A exchange could result significant changes in the PS1 protein. CONCLUSION: We report a case of EOAD having probable novel PSEN1 (G209A) mutation verified with structural prediction.


Assuntos
Doença de Alzheimer/genética , Modelos Genéticos , Presenilina-1/química , Presenilina-1/genética , Idade de Início , Doença de Alzheimer/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Mutação
17.
Int J Cancer ; 136(11): 2717-29, 2015 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-25382705

RESUMO

To overcome T790M-mediated acquired resistance of lung cancer cells to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), second generation TKIs such as BIBW2992 (afatinib) and third generation TKIs including WZ4002 have been developed. However, clinical data on their efficacy in treating T790M mutant tumors are lacking. Histone deacetylase (HDAC) inhibitors have been reported to arrest cell growth and to lead to differentiation and apoptosis of various cancer cells, both in vitro and in vivo. In the present study, we assessed whether the combination of suberoylanilide hydroxamic acid (SAHA, vorinostat), a potent HDAC inhibitor, and BIBW2992 or WZ4002 could overcome EGFR TKI resistance associated with T790M mutation in lung cancer cells. While treatment with BIBW2992 or WZ4002 alone slightly reduced the viability of PC-9G and H1975 cells, which possess T790M mutation, combining them with SAHA resulted in significantly decreased cell viability through the activation of the apoptotic pathway. This combination also enhanced autophagy occurrence and inhibition of autophagy significantly reduced the apoptosis induced by the combination treatment, showing that autophagy is required for the enhanced apoptosis. Caspase-independent autophagic cell death was also induced by the combination treatment with SAHA and either BIBW2992 or WZ4002. Finally, the combined treatment with SAHA and either BIBW2992 or WZ4002 showed an enhanced anti-tumor effect on xenografts of H1975 cells in vivo. In conclusion, the combination of new generation EGFR TKIs and SAHA may be a new strategy to overcome the acquired resistance to EGFR TKIs in T790M mutant lung cancer.


Assuntos
Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Receptores ErbB/genética , Ácidos Hidroxâmicos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Acrilamidas/farmacologia , Afatinib , Animais , Protocolos de Quimioterapia Combinada Antineoplásica , Apoptose , Autofagia , Caspases/metabolismo , Linhagem Celular Tumoral , Sinergismo Farmacológico , Receptores ErbB/antagonistas & inibidores , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/genética , Camundongos , Mutação , Transplante de Neoplasias , Pirimidinas/farmacologia , Quinazolinas/farmacologia , Vorinostat , Ensaios Antitumorais Modelo de Xenoenxerto
18.
J Clin Microbiol ; 53(4): 1172-7, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25631799

RESUMO

Because increasing numbers of nasopharyngeal swab specimens from adult patients with acute respiratory illness (ARI) are being tested by respiratory virus (RV) multiplex reverse transcriptase PCR (RVM-RT-PCR), multiple RV detection (MRVD) is being encountered more frequently. However, the clinical relevance of MRVD in adult patients has rarely been evaluated. The clinical characteristics of hospitalized adult patients with ARI and MRVD by RVM-RT-PCR tests were compared to those of patients with single RV detection (SRVD) during a single year at a tertiary care center. MRVD was observed in 26 of the 190 adult patients (13.7%). The patients with MRVD had a higher incidence of chronic lung disease than the patients with SRVD (34.6% versus 15.9%, crude odds ratio [OR]=2.81, 95% confidence interval [CI]=1.13 to 6.98, P=0.03). Although the former were more likely than the latter to receive mechanical ventilation (19.2% versus 6.7%, crude OR=3.31, 95% CI=1.05 to 10.47, P=0.049), the length of hospital stay (median, 7 versus 6.5 days; P=0.66), and the in-hospital mortality rate (7.7% versus 4.3%, crude OR=1.87, 95% CI=0.37 to 9.53, P=0.35) were not different between the two groups. In multivariate analysis, chronic lung disease was associated with MRVD (adjusted OR=3.08, 95% CI=1.12 to 8.46, P=0.03). In summary, it was not uncommon to encounter adult patients with ARI and MRVD by RVM-RT-PCR tests of nasopharyngeal swab specimens. MRVD was associated with chronic lung disease rather than the severity of the ARI.


Assuntos
Coinfecção/epidemiologia , Coinfecção/virologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Vírus/genética , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , República da Coreia/epidemiologia , Virologia/métodos , Vírus/classificação , Adulto Jovem
19.
J Clin Microbiol ; 53(6): 1976-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25832303

RESUMO

We report a case of Campylobacter volucris bacteremia in an immunocompromised patient with polycythemia vera and alcoholic liver cirrhosis. To our knowledge, this is the first case report in which this organism has been isolated from a human clinical specimen.


Assuntos
Bacteriemia , Infecções por Campylobacter , Campylobacter , Hospedeiro Imunocomprometido , Idoso , Antibacterianos/uso terapêutico , Campylobacter/efeitos dos fármacos , Campylobacter/genética , Campylobacter/isolamento & purificação , Farmacorresistência Bacteriana , Humanos , Masculino , Meropeném , Tienamicinas/uso terapêutico
20.
J Clin Lab Anal ; 29(4): 255-8, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24849416

RESUMO

BACKGROUND: Our goal was to enhance the productivity of phlebotomists and reduce outpatient wait times. Here, we aimed to develop a computer simulation program in which resources would be shifted from the laboratory to assist with phlebotomy. We evaluated the efficacy of computer simulation approaches for phlebotomy wait time and provide phlebotomy help time. METHODS: We evaluated the performance of the following three approaches: no helping system (NHS), the conventional assistance system (CAS), and the computer simulated helping system (CSHS). The CSHS predicted the phlebotomy waiting times based on computer simulation approaches, decided the assist times, and sounded an alarm. RESULTS: The wait time for the NHS was significantly longer than that of the CAS and the CSHS (P < 0.05). We divided the wait time into the three parts: <5 min, 5-10 min, and >10 min. Significant differences between the three systems were detected (P < 0.05). The phlebotomy computer simulation system significantly decreased the help time of the phlebotomists (CAS was 93.3 ± 19.7 min vs. CSHS was 79.5 ± 17.7 min, P = 0.03). CONCLUSION: We designed a computer-based predicted alarm system. This system could effectively decrease help time for phlebotomists and outpatients phlebotomy wait times.


Assuntos
Simulação por Computador , Sistemas Computacionais , Pacientes Ambulatoriais , Flebotomia , Humanos , Fatores de Tempo
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