RESUMO
WHAT IS KNOWN AND OBJECTIVE: Dried blood spot (DBS) sampling is a minimally invasive method of blood sampling that enables monitoring of drug concentrations to be more convenient. This study aimed at developing a DBS sampling method for an accurate and precise prediction of radotinib plasma concentrations (Cp ) in patients with chronic myeloid leukaemia (CML). METHODS: Dried blood spot and venous blood samples were simultaneously collected from fifty CML patients who had been receiving radotinib for at least a week. Radotinib concentrations were measured using a high-performance liquid chromatographic method with tandem mass spectrometric detection. Unmeasured Cp was predicted directly based on a Deming regression between DBS concentrations (CDBS ) and Cp . Unmeasured Cp was also predicted from CDBS corrected by each patient's haematocrit (Hct). Both prediction methods were evaluated for their accuracy and precision using Deming regression and Bland-Altman analysis. RESULTS AND DISCUSSION: The Deming regression equation between CDBS and Cp was obtained as follows: Cp = 1.34âCDBS + 4.26 (r2 = .97). Cp was directly predictable using Cp,pred1 = 1.34âCDBS + 4.26. With Hct correction, Cp was alternatively predictable using Cp,pred2 = CDBS / (1-Hct + Hct2 ). The slopes of Deming regression line between predicted and measured Cp were 0.99 and 1.02 for the direct and Hct-corrected method, respectively. The mean biases (accuracy) were -0.44% and 1.6% with the 95% limits of agreement (precision) of -22.4% to 21.5% and -20.5% to 23.7%, respectively. More than 93% of predicted and measured Cp pairs had their differences within 20% of the mean of each pair in both methods. WHAT IS NEW AND CONCLUSIONS: Radotinib CDBS are highly correlated with radotinib Cp. Radotinib Cp can be accurately and precisely predicted from CDBS using direct or Hct-corrected prediction methods. Both appear to be appropriate for the therapeutic monitoring of radotinib in patients with CML.
Assuntos
Benzamidas/administração & dosagem , Teste em Amostras de Sangue Seco/métodos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Pirazinas/administração & dosagem , Adulto , Idoso , Benzamidas/farmacocinética , Cromatografia Líquida de Alta Pressão/métodos , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/farmacocinética , Pirazinas/farmacocinética , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos , Adulto JovemRESUMO
BACKGROUND: The aim of this study was to determine the prevalence rate of latent TB infection (LTBI) and active TB among homeless in Seoul metropolitan city, South Korea, and to compare the TB burden among homeless people with that of a control group. METHODS: The homeless participants were recruited from five sites between October 30, 2009 and April 12, 2010. LTBI was diagnosed through the QuantiFERON(R) TB Gold In-Tube(QFT-GIT) assay and a tuberculin skin test(TST) and, and active PTB was diagnosed based on chest radiography. RESULTS: Among 313 participants, the prevalence of LTBI was 75.9% (95% CI, 71.1-80.8%) and 79.8% (95% CI, 74.9-84.7%) based on a QFT-GIT assay and the TST, respectively, and that of active PTB was 5.8% (95% CI, 3.2-8.3%). The prevalence of LTBI among homeless participants was about five times higher than controls. Also, the age-specific prevalence rate ratio of active PTB was as high as 24.86. CONCLUSIONS: The prevalence rate of LTBI as well as active PTB among homeless people was much higher than that of the general population in South Korea. Thus, adequate strategies to reduce the TB burden among homeless people are needed.
Assuntos
Pessoas Mal Alojadas/estatística & dados numéricos , Tuberculose Latente/epidemiologia , Tuberculose Pulmonar/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Efeitos Psicossociais da Doença , Estudos Transversais , Feminino , Humanos , Tuberculose Latente/diagnóstico , Masculino , Pessoa de Meia-Idade , Prevalência , República da Coreia/epidemiologia , Tuberculose Pulmonar/diagnóstico , População UrbanaRESUMO
In this study, volatile urinary components were collected using three different types of samples from patients suffering from urinary incontinence (UI): (1) urine (A); (2) urine + non-used pad (B); and (3) urine + used pad (C). In addition, urine + non-used pad (D) samples from non-patients were also collected as a reference. The collection of urinary volatiles was conducted with the aid of a glass impinger-based mini-chamber method. Each of the four sample types (A through D) was placed in a glass impinger and incubated for 4 hours at 37 °C. Ultra pure air was then passed through the chamber, and volatile urine gas components were collected into Tedlar bags at the other end. These bag samples were then analyzed for a wide range of VOCs and major offensive odorants (e.g., reduced sulfur compounds (RSCs), carbonyls, trimethylamine (TMA), ammonia, etc.). Among the various odorants, sulfur compounds (methanethiol and hydrogen sulfide) and aldehydes (acetaldehyde, butylaldehyde, and isovaleraldehyde) were detected above odor threshold and predicted to contribute most effectively to odor intensity of urine incontinence.
Assuntos
Absorventes Higiênicos , Odorantes/análise , Olfatometria/instrumentação , Manejo de Espécimes/instrumentação , Urinálise/instrumentação , Incontinência Urinária/urina , Compostos Orgânicos Voláteis/urina , Idoso , Desenho de Equipamento , Análise de Falha de Equipamento , Feminino , Análise de Injeção de Fluxo/instrumentação , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Incontinência Urinária/reabilitaçãoRESUMO
The diagnostic accuracy of the data reported in the Korean tuberculosis surveillance system (KTBS) has not been adequately investigated. We reviewed the clinical data of pulmonary tuberculosis (PTB) cases notified from private medical facilities through KTBS between January and June, 2004. PTB cases were classified into definite (culture-proven), probable (based on smear, polymerase chain reaction, histology, bronchoscopic finding, computed tomography, or both chest radiograph and symptoms) or possible (based only on chest radiograph) tuberculosis. Of the 1126 PTB cases, sputum AFB smear and culture were requested in 79% and 51% of the cases, respectively. Positive results of sputum smear and culture were obtained in 43% and 29% of all the patients, respectively. A total of 73.2% of the notified PTB cases could be classified as definite or probable and 81.7% as definite, probable, or possible. However, where infection was not confirmed bacteriologically or histologically, only 60.1% of the patients were definite, probable, or possible cases. More than 70% of PTB notified from private sectors in Korea can be regarded as real TB. The results may also suggest the possibility of over-estimation of TB burden in the use of the notification-based TB data.
Assuntos
Tuberculose Pulmonar/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Setor Privado , República da Coreia/epidemiologia , Índice de Gravidade de Doença , Escarro/microbiologia , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/patologia , Adulto JovemRESUMO
BACKGROUND: The purpose of our study was to investigate the effects of extracorporeal shock wave therapy (ESWT) and hand massage therapy (HMT) on serum lipids and body composition in Korean women. MATERIALS AND METHODS: We randomly classified 60 participants into overweight and obese groups. Subjects received ESWT and HMT twice a week for six weeks (a total of 12 sessions). RESULTS: Body weight and body mass index decreased significantly in obese women from both groups. Waist circumference significantly declined in obese women and overweight women in both treatment groups (p < 0.001). Body fat significantly decreased in the ESWT group of obese women (p < 0.01), while a significant reduction in abdominal obesity was noted only in the HMT group of overweight women (p < 0.01) and the ESWT group of obese women (p < 0.01). There was a significant decrease in triglycerides in the ESWT group of obese women (p < 0.01). CONCLUSIONS: These results suggest that ESWT and HMT could be helpful for the management of people with excess abdominal fat and obesity. Moreover, ESWT is more effective than HMT for improving abdominal obesity and triglyceride levels in obese women as compared to overweight women.
RESUMO
Sorafenib is an oral multikinase inhibitor with clinical activity against hepatocellular carcinoma (HCC) and renal cell carcinoma. Administration of sorafenib carries a variety of adverse cutaneous reactions. Common adverse effects induced by sorafenib include hand-foot skin reactions, facial erythema, splinter subungual hemorrhage, and alopecia. Although erythema multiforme (EM) related to sorafenib has been reported, delayed-type cutaneous hypersensitivity reactions are rare in patients treated with sorafenib and there has been no case of Stevens-Johnson syndrome (SJS) reported so far. We recently experienced 3 cases of delayed-type cutaneous hypersensitivity related to administration of sorafenib. The first case was a 47-year female had targetoid erythematous rashes on her arms 12 days after starting sorafenib for HCC. The rashes spread from the arms to the trunk rapidly except for the hands and feet, and erosive lesions developed in the oral mucosa and lips. She was diagnosed as SJS. The second case was an 81-year-old male had maculopapular eruptions with multiple targetoid lesions on the trunk, arms, and legs 10 days after starting sorafenib for his HCC. There was no evidence of mucosal involvement. He was diagnosed with EM. The last one was a 20-year-old female developed generalized maculopapular eruptions in the whole body 10 days after starting sorafenib for the treatment of HCC. All 3 patients completely recovered after discontinuation of sorafenib.
RESUMO
BACKGROUND: The tuberculin skin test (TST) is the standard tool to diagnose latent tuberculosis infection (LTBI) in mass screening. The aim of this study is to find an optimal cut-off point of the TST+ rate within tuberculosis (TB) contacts to predict the active TB development among adolescents in school TB outbreaks. METHODS: The Korean National Health Insurance Review and Assessment database was used to identify active TB development in relation to the initial TST (cut-off, 10 mm). The 7,475 contacts in 89 schools were divided into two groups: Incident TB group (43 schools) and no incident TB group (46 schools). LTBI treatment was initiated in 607 of the 1,761 TST+ contacts. The association with active TB progression was examined at different cut-off points of the TST+ rate. RESULTS: The mean duration of follow-up was 3.9±0.9 years. Thirty-three contacts developed active TB during the 4,504 person-years among the TST+ contacts without LTBI treatment (n=1,154). The average TST+ rate for the incident TB group (n=43) and no incident TB group (n=46) were 31.0% and 15.5%, respectively. The TST+ rate per group was related with TB progression (odds ratio [OR], 1.025; 95% confidence interval [CI], 1.001-1.050; p=0.037). Based on the TST+ rate per group, active TB was best predicted at TST+ ≥ 16% (OR, 3.11; 95% CI, 1.29-7.51; area under curve, 0.64). CONCLUSION: Sixteen percent of the TST+ rate per group within the same grade students can be suggested as an optimal cut-off to predict active TB development in middle and high schools TB outbreaks.
RESUMO
A high-performance liquid chromatographic (HPLC) method was developed for the determination of nitrendipine in human plasma using solid-phase extraction (SPE) and ultraviolet detection. A 30-microl aliquot of methanol (containing 2 microg/ml of the internal standard, nimodipine) was added to a 1-ml aliquot of biological sample. After vortex-mixing, the mixture was loaded on C(18) SPE cartridge which was conditioned with methanol and distilled water. After washing with distilled water, the SPE cartridge was eluted with 1-ml aliquot of diethyl ether. The organic phase was collected and evaporated under nitrogen gas. The residue was then reconstituted with a 100 microl aliquot of mobile phase, and a 50 microl aliquot was injected onto the C(18) reverse-phased column. The mobile phase, 10 mM phosphate buffer (pH 4.5):acetonitrile (50:50, v/v), was run at a flow rate of 1.2 ml/min. The column effluent was monitored using ultraviolet detector at 238 nm. The retention times for nitrendipine and the internal standard were approximately 10.1 and 12.6 min, respectively. The detection limit of nitrendipine in human plasma was 2.0 ng/ml. The coefficients of variation (CV) of the assay were below 16.5% for human plasma, and no interferences from endogenous substances were found. This specific, accurate and precise assay was useful in the study for the pharmacokinetic characteristics of nitrendipine.
Assuntos
Nitrendipino/sangue , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Nitrendipino/química , Nitrendipino/farmacocinética , Espectrofotometria Ultravioleta/métodosRESUMO
BACKGROUND: Epidemiologic data regarding tuberculin skin test (TST) responses are an important basis for TB control strategies. This study analyzed TST responses in Korea, which experienced a rapid change in BCG vaccination status. METHODS: TST responses in young adults were examined over 5 years. Participants with active TB lesions were excluded. RESULTS: A total of 5,552 participants were enrolled with median age of 21 years. When an induration diameter ≥10 mm was used as the criterion for a positive test, TST positivity fell (from 28.0% in 2005 to 15.3% in 2009); however, they remained steady when the criterion was ≥15-20 mm. A positive TST was associated with a personal or family of TB, the presence of a Bacille Calmette-Guérin (BCG) scar, and age (odds ratio [95% confidence interval]â=â4.03 [2.61-6.22], 2.91 [1.80-4.71], 1.50 [1.31-1.72], and 1.15 [1.09-1.20], respectively). Among these factors, the decrease of participants with BCG scars was the most prominent change, which appeared to be associated with the change of TST positivity rate. CONCLUSION: Overall, the rate of TST positivity in Korea decreased. However, this trend seems associated with the change of BCG vaccination strategy rather than successful control of LTBI. This study showed that change in BCG vaccination strategy can have great impact on TB epidemiologic survey based on TST.
Assuntos
Mycobacterium tuberculosis/imunologia , Tuberculose Pulmonar/prevenção & controle , Vacinação/legislação & jurisprudência , Adolescente , Adulto , Vacina BCG , Humanos , Masculino , República da Coreia , Teste Tuberculínico , Adulto JovemRESUMO
BACKGROUNDS: Glimepiride is a commonly used sulfonylurea hypoglycemic agent. There is considerable interindividual variation in the response to sulfonylurea for patients with type 2 diabetes. The purpose of this study was to investigate whether genetic variations influence the efficacy of glimepiride in healthy Korean subjects. METHODS: A single 2-mg oral dose of glimepiride was administered to 46 healthy volunteers. Serial blood sampling for 12h after oral dosing was performed for determination of plasma glimepiride, glucose and insulin levels. We tested the association of seven single nucleotide polymorphisms (SNPs) in four candidate genes with the efficacy of glimepiride. RESULTS: Pharmacodynamic profiles for plasma glucose and insulin showed no statistically significant differences among genotype groups, and parameters were not different from one another. There were no association of the KCNJ11, NOS1AP, TCF7L2 and ABCC8 gene polymorphisms and the efficacy of glimepiride. CONCLUSIONS: Knowledge of these polymorphisms provides no clinical useful information for the pharmacogenetic therapeutic approach for Korean patients with type 2 diabetes.
Assuntos
Hipoglicemiantes/farmacocinética , Hipoglicemiantes/uso terapêutico , Polimorfismo de Nucleotídeo Único , Compostos de Sulfonilureia/farmacocinética , Compostos de Sulfonilureia/uso terapêutico , Adulto , Glicemia/análise , Humanos , Insulina/sangue , Coreia (Geográfico) , MasculinoAssuntos
Neoplasias Pulmonares/patologia , Linfoma de Zona Marginal Tipo Células B/patologia , Neoplasias Gástricas/patologia , Idoso , Mucosa Gástrica/patologia , Humanos , Inflamação/patologia , Neoplasias Pulmonares/etiologia , Linfoma de Zona Marginal Tipo Células B/etiologia , Masculino , Mucosa Respiratória/patologia , Neoplasias Gástricas/etiologia , Tuberculose Pulmonar/complicaçõesRESUMO
Even though some studies have reported the results of serial interferon-gamma release assays (IGRAs) during isoniazid prophylactic treatment, serial results have not been reported after rifampicin prophylaxis. A contact investigation was conducted after a tuberculosis (TB) outbreak in an accommodation facility. The tuberculin skin test (TST) and the QuantiFERON-TB Gold In-Tube (QFT-GIT) test were performed in 214 contacts with normal chest radiographs. Rifampicin prophylaxis was initiated in TST+/QFT-GIT+ subjects, and the QFT-GIT test was repeated upon completion of 4 months of rifampicin treatment. Among the 214 contacts, the TST and QFT-GIT test results were positive in 67.7% and 56.7%, respectively, and the agreement between the two tests was fair-to-good (78.3%, kappa=0.55, p<0.001). The QFT-GIT test was positive in 77% (97/126) of contacts with positive TST results. Rifampicin prophylaxis was completed in 81 subjects with good compliance. Among 74 subjects with valid serial QFT-GIT test results, IFN-gamma levels decreased in 97.3% (72/74) of the subjects and QFT-GIT test reversion (positive to negative) was achieved in 31 subjects (41.9%). Subjects without QFT-GIT test reversion had a significantly higher baseline TST induration sizes (18.3+/-4.8 vs. 14.9+/-3.4mm, p<0.01) and IFN-gamma levels (18.6+/-17.9 vs. 3.2+/-7.5IU/mL, p<0.01) than the subjects with QFT-GIT test reversion. Thus, IGRAs may be useful in evaluating the therapeutic response to rifampicin prophylaxis in TB contacts. However, considering that this was not a controlled study, a prospective controlled study is needed to determine whether rifampicin prophylaxis truly affects QFT-GIT reversion.