Background : Primary multidrug-resistant tuberculosis is defined as Mycobacterium tuberculosis isolates that are resistant to at least isoniazid and rifampin in never-been-treated tuberculosis patients, and this malady is caused by the transmission of a resistant strain from one patient, who is infected with a resistant Mycobacterium tuberculosis strain, to another patient. The prevalence of primary multidrug-resistant tuberculosis could be a good indicator of the performance of tuberculosis control programs in recent years. We conducted a case-control study to identify the risk factors for primary multidrug-resistant tuberculosis. Methods : From January 1, 2001 to, June 30, 2003, by conducting prospective laboratory-based surveillance, we identified 29 hospitalized patients with P-MDRTB and these patients constituted a case group in this study. The controls were represented by all the patients with culture-confirmed drug susceptible tuberculosis who were admitted to National Masan Hospital during the same study period. The odds ratios for the patients with primary multidrug-resistant tuberculosis, as compared with those of the patients with drug susceptible tuberculosis, were calculated for each categorical variable with 95% confidence intervals. Results : Multivariate logistic regression showed that the presence of diabetes mellitus (odds ratio 2.68; 95% confidence interval, 1.05-6.86) was independently associated with having primary multidrug-resistant tuberculosis. Conclusion : This study has shown that diabetes mellitus might be one of the risk factors for primary multidrug-resistant tuberculosis.
The primary culture of human nasal epithelial cell monolayer was performed on a Transwell. The effect of various factors on the tight junction formation was observed in order to develop an in vitro experimental system for nasal transport studies. Human nasal epithelial cells, collected from human normal inferior turbinates, were plated onto diverse inserts. After 4 days, media of the apical surface was removed for air-liquid interface (ALI) culture. Morphological characteristics was observed by transmission electron microscopy (TEM). A polyester membrane of $0.4\;{\mu}m$ pore size was determined as the most effective insert based on the change in the transepithelial electric resistance (TEER) value as well as the $^{14}C-mannitol$ transport study. The ALI method was effective in developing the tight junction as observed in the further increase in the TEER value and reduction in the permeability coefficient $(P_{app})$ of $^{14}C-mannitol$ transport. Results of the transport study of a model drug, budesonide, showed that the primary culture system developed in this study could be further developed and applied for in vitro nasal transport studies.
A function of the kidney is elimination of a variety of xenobiotics ingested and wasted endogenous compounds from the body. Organic anion and cation transport systems play important roles to protect the body from harmful substances. The renal proximal tubule is the primary site of carrier-mediated transport from blood into urine. During the last decade, molecular cloning has identified several families of multispecific organic anion and cation transporters, such as organic anion transporter (OAT), organic cation transporter (OCT), and organic anion-transporting polypeptide (oatp). Additional findings also suggested ATP-dependent organic ion transporters such as MDR1/P-glycoprotein and the multidrug resistance-associated protein (MRP) as efflux pump. The substrate specificity of these transporters is multispecific. These transporters also play an important role as drug transporters. Studies on their functional properties and localization provide information in renal handling of drugs. This review summarizes the latest knowledge on molecular properties and pharmacological significance of renal organic ion transporters.
Quinolone resistance in Streptococcus pneumoniae is related to mutations in the DNA gyrase and topoisomerase IV genes. DW-286a displayed potent activity against S. pneumoniae C9211 (MIC, 0.015 ${\mu}$g/ml) compared with gemifloxacin (MIC, 0.06 ${\mu}$g/ml). This study was performed to analyze the ability of DW-286a to cause resistance development in S. pneumoniae and to establish whether DNA gyrase or topoisomerase IV is primary target. DW-286a resistant mutants of S. pneumoniae C9211 were generated by stepwise selection at increasing drug concentration. (omitted)
Park, Hye-Sook;Ha, Eun-Hee;Wie, Cha-Hyung;Kang, Ji-Yong
Journal of Preventive Medicine and Public Health
/
v.29
no.1
s.52
/
pp.67-78
/
1996
The purpose of this study was examine the general characteristics of relapsed pulmonary tuberculous patients (i.e. age, sex, weight, occupation, previous forms of treatment, drug sensitivity, and the frequency of relapse) in order to improve future treatments of tuberculosis as well as to perpetuate health education. The data was obtained from the medical records of 186 relapsed pulmonary tuberculosis patients who were registered for treatment at various public health offices in Seoul during the year of 1994. The major findings obtained from the study were as follows; 1) The male to female ratio of relapsed pulmonary tuberculous patients was about 7:3, more specifically 23.7% of the men and 30.9% of the women were between 20 and 29 years of age. 2) Comparing initial less aggravated states to relapsed states, patients with minimal X-ray findings later proved moderately advanced X-ray findings. Furthermore, patients with negative sputum AFB findings later proved positive sputum AFB findings. 3) Of the 186 patients studied, 91.9% suffered, relapse and 8.1% suffered 2 or more relapses. Of the patients who suffered at least 1 relapse, 54.8% received short-term treatment, 26.9% received long-term treatment, and 18.3% received treatment of an unknown during their initial tuberculosis treatment periods. 4) fifty five point four percent of the patients had no reaction to the drug treatment(not available), 25.9% of the patients had sensitive reaction to the drug treatment, 18.7% of the patients had resistant reaction to the- drug treatment. Drug resistance was higher in patients that exhibited positive X-ray findings as well as in patients that exhibited positive sputum AFB findings. furthermore, patients receiving treatment of an unknown nature(35.5%) exhibited higher drug resistance than those receiving short-term treatment(13.6%) and long-term treatment(17.0%). 5) Of the 160 patients who suffered relapses, 8.8% suffered a relapse within 1 year after treatment and 91.2% suffered a relapse at least 1 year after treatment. Furthermore, our study showed that women, under 30, who received short-term treatment and encounterd complications during their primary treatment suffered relapses faster than any other groups studied. In addition, minimal X-ray findings and sputum AFB findings were not correlated to the time relapse occured. Therefore, the seater efforts are needed to prevent relapsed pulmonary tuberculosis.
Background: There are many retreatment failure patients admitted in National Kongju Tuberculosis Hospital. But there is not satisfactory treatment method for them at present. We think that more attentions and active measures for them are needed. Method: We reviewed sex and age, duration of illness, previously used antituberculosis drugs, drug resistance, extent of disease, reasons for early stopping or irregular medication and schooling of 50 retreatment failure patients admitted in National Kongju Tuberculosis Hospital from April 1992 to February 1993. Results: 1) The male to female ratio was 3:2 and 62% of the patients were between 21 and 40 years of age. 2) Twenty eight cases (56%) had the duration of illness over 10 years. 3) All cases had used most of the antituberculosis drugs. 4) Drug sensitivity test showed resistance to RMP in 46 cases (96%), INH in 40 cases (83%) and other drugs in 3-32 cases (6-67%). 5) Forty eight cases (96%) had far advanced disease on chest P-A film. 6) Twenty eight cases (56%) in primary chemotherapy and twenty one cases (42%) in retreatment had the histories of premature stopping or irregular ingestion of the drug. The reasons for premature stopping or irregular ingestion of the drug were as follows; in primary chemotherapy, 29 cases (75%) were due to 'having no symptoms', while in retreatment, 6 cases (29%) were due to 'having no symtoms', 6 cases (29%) were 'too, busy' and 3 cases (14%) were for 'financial problem'. 7) Twenty seven cases (54%) had at least graduated from high school. Conclusion: Greater efforts are needed to prevent tratment failure. More supports and admission treatment for retreatment failure patients are needed to prevent infection and to treat properly.
Objectives: Although outbreak of MDR Tb has been a recent problem in western countries, it has been a longstanding problem in Korea. The poor outcome of MDR Tb is mainly due to poor compliance, high rate of side reaction of secondary drugs, and limitation in number of available drugs. Thus, to improve the outcome of MDR Tb, it is crucial to make individualized adequate prescription based on the knowledge of the patterns of resistance to each drugs in the community as well as the natural history. The purpose of present study is to evaluate the clinical features of Korean MDR Tb patients including patterns of drug resistance and success rate of treatment which was prescribed according to the sensitivity tests. Methods: Retroscpective analysis of 71 Korean patients with MDR Tb was made. All strains isolated from patients showed resistence to at least two first line drugs. Patients profile, previous treatment history, patterns of drug resistance, outcome of treatment was analysed. Initial treatment regimen was selected according to the previous treatment history and was modified according to the sensitivity reports. The regimen was composed to include at least 4 sensitive drugs when possible. Results: The patients showed resistance to 4.1 drugs on average. 90% of them were resistant to INH and RFP. Among 71 patients, 35 patients(49%) had cavitary lesions in CXR. Treatment outcome was analysed in 55 patients. 35 patients(67%) were improved after treatment and 18 patients(33%) showed treatment failure. 5 patients showed primary resistance. Treatment outcome could be evaluated in 4 of them and all showed improvement after treatment. 14 patients(20%) had to change their regimens due to drug side effects. The most frequent side effect was elevation of liver enzymes(6 patients). Others included dizziness, hyperuricemia, tinnitus, skin rash, GI troubles. More than 50% of side effects developed within 3 months. In repeated drug sensitivity test, the concordance rate of resistance to INH was 100% and RFP 98%. EMB, PZA showed 80% concordance rate. But in the other drugs, the concordances were less than 50%. Operation was done in 5 patient - 1 patients as a adjunctive means of chemotherapy -. In that case, negative conversion of sputum AFB was done. Conclusion: 2/3 patients of multidrug-resistant tuberculosis were improved by appropriate prescription and regular medication suggesting that more aggressive management and monitoring is indicated in multidrug-resistant tuberculosis.
Park, Seung-Kyu;Choi, In-Hwan;Kim, Cheon-Tae;Song, Sun-Dae
Tuberculosis and Respiratory Diseases
/
v.44
no.6
/
pp.1234-1244
/
1997
Background : Nowadays drug resistant tuberculosis is making problems in the treatment of pulmonary tuberculosis and its number is increasing. Several reasons for this are considered including irregular medication, poor drug compliance and wrong regimens. But there are treatment failure cases in spite of regular medication with short-term standard regimens. We reviewed clinical data of 50 patients to find out possible causes of this. Method : Subject of this study was 50 patients who failed in the primary treatment of pulmonary tuberculosis in spite of regular medication with short-term standard regimens. All of them were under treatment with secondary regimens in National Masan Tuberculosis Hospital on Oct 1996. The patient's records were analyzed retrospectively and direct interviews with patients were done. Results : There were relatively more patients in the age of 20th. Male overwhelmed in number. There were smoking in 22 patients and drinking in 24 patients during medication. 17(34%) patients had family history of tuberculosis. Public health center was the most common site for the initial diagnosis among medical institutes. 42 patients had subjective symptoms for pulmonary tuberculosis. 38 patients got sufficient explanation from medical institute about tuberculosis and medication courses. 24 patients had bilateral lesions on chest X-ray film and 43 patients had cavitary lesions. 29 patients had past history for pulmonary tuberculosis with regular medication. The results of drug sensitivity test showed resistance in 41 patients of whom we could get the results. Conclusion : Main cause of treatment failure of pulmonary tuberculosis in spite of regular medication with short-term standard regimens was drug resistance. Several factors were considered to be related to high prevalence of drug resistance, including age of 20th, male, family history for tuberculosis, bilateral lesions or remaining cavitary lesion on chest X-ray film.
Human epidermal growth factor receptor 2 (HER2) inhibitors, such as trastuzumab and lapatinib are used to treat HER2-positive breast and gastric cancers. However, as with other targeted therapies, intrinsic or acquired resistance to HER2 inhibitors presents unresolved therapeutic problems for HER2-positive gastric cancer. The present study describes investigations with AUY922, a heat shock protein 90 (HSP90) inhibitor, in primary lapatinib-resistant (ESO26 and OE33) and lapatinib-sensitive gastric cancer cells (OE19, N87, and SNU-216) harboring HER2 amplification/over-expression. In order to investigate whether AUY922 could overcome intrinsic and acquired resistance to HER2 inhibitors in HER2-positive gastric cancer, we generated lapatinib-resistant gastric cancer cell lines (OE19/LR and N87/LR) by continuous exposure to lapatinib in vitro. We found that activation of HER2 and protein kinase B (AKT) were key factors in inducing intrinsic and acquired lapatinib-resistant gastric cancer cell lines, and that AUY922 effectively suppressed activation of both HER2 and AKT in acquired lapatinib-resistant gastric cancer cell lines. In conclusion, AUY922 showed a synergistic anti-cancer effect with lapatinib and sensitized gastric cancer cells with intrinsic resistance to lapatinib. Dual inhibition of the HSP90 and HER2 signaling pathways could represent a potent therapeutic strategy to treat HER2-positive gastric cancer with intrinsic and acquired resistance to lapatinib.
As the field of interventional pain management (IPM) grows, the risk of surgical site infections (SSIs) is increasing. SSI is defined as an infection of the incision or organ/space that occurs within one month after operation or three months after implantation. It is also common to find patients with suspected infection in an outpatient clinic. The most frequent IPM procedures are performed in the spine. Even though primary pyogenic spondylodiscitis via hematogenous spread is the most common type among spinal infections, secondary spinal infections from direct inoculation should be monitored after IPM procedures. Various preventive guidelines for SSI have been published. Cefazolin, followed by vancomycin, is the most commonly used surgical antibiotic prophylaxis in IPM. Diagnosis of SSI is confirmed by purulent discharge, isolation of causative organisms, pain/tenderness, swelling, redness, or heat, or diagnosis by a surgeon or attending physician. Inflammatory markers include traditional (C-reactive protein, erythrocyte sedimentation rate, and white blood cell count) and novel (procalcitonin, serum amyloid A, and presepsin) markers. Empirical antibiotic therapy is defined as the initial administration of antibiotics within at least 24 hours prior to the results of blood culture and antibiotic susceptibility testing. Definitive antibiotic therapy is initiated based on the above culture and testing. Combination antibiotic therapy for multidrug-resistant Gram-negative bacteria infections appears to be superior to monotherapy in mortality with the risk of increasing antibiotic resistance rates. The never-ending war between bacterial resistance and new antibiotics is continuing. This article reviews prevention, diagnosis, and treatment of infection in pain medicine.
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