• Tuberculosis and Respiratory Diseases
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• v.52 no.4
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• pp.355-366
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• 2002

Background : The heat shock protein (HSP) 70 families are known to protect cells against the irreversible tissue injury induced by stress and to induce the recovery of cell function during stress. Heat pretreatment was reported to decrease the acute lung injury (ALI) of rats induced by lipopolysaccharide (LPS). However, the role of heat shock with LPS co-treatmenton ALI is unclear. The purpose of this study was to investigate the effect of heat treatment, which was given immediately after the beginning of ALI induced by LPS intratracheally administered in rats. Methods : Either saline (saline group) or LPS was intratracheally instilled without heat treatment (LPS group). In addition, heat was conducted 18 hours prior to the instillation of LPS (pre-treatment group) and conducted immediately after instillation of LPS (co-treatment group). Six hours after the LPS or saline treatment, blood, bronchoalveolar lavage (BAL) fluid and lung tissue samples were obtained. The myeloperoxidase (MPO) activity and the heat shock protein expression in the lung tissue, the differential counts of the polymorphonuclear leukocytes (PMN) in the BAL fluids, and the LDH, protein, $IL-1{\beta}$, $TNF-{\alpha}$ and IL-10 levels in BAL fluid and serum were measured. Results : 1) The MPO activity, the differential PMN counts in the BAL fluid, BAL fluid and serum cytokines were higher in the LPS, the heat pre-treatment and co-treatment group than those of the saline group (p value <0.05). 2) The MPO activity and the protein level in the BAL fluid from the heat co-treatment group were similar to those of the LPS group. 3) The serum $TNF-{\alpha}$ level of the heat co-treatment group was significantly higher than that of the LPS group (p=0.01). Conclusion : Heat shock response administered immediately after a LPS instillation did not attenuate the ALI in this model.

• Tuberculosis and Respiratory Diseases
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• v.52 no.4
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• pp.376-384
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• 2002

Background : The mortality from acute respiratory distress syndrome(ARDS) in the late stage, which is characterized by progressive pulmonary fibroproliferation, is ${\geq}80%$. Although previous prospective trials failed to show a survival benefit of steroid therapy in early ARDS, recently, a few of reports have described the survival benefit of the long-term use of steroid in patients with late ARDS. In this study, we analyzed the effect of steroid therapy on patients with late ARDS retrospectively in a single. Medral intensive care unit (MICU). Methods : Over a 3-year period, the medical records of 48 ARDS patients who had been on mechanical ventilation more than 8 days were reviewed. 14 patients were treated by the long-term use of methylprednisolone and another 34 patients served as a control. Both groups were comparable regarding clinical and physiologic data lung injury score(LIS), multiple organ failure score, APACHE III and SAPS II score. Because steroid was instituted after 8 days of advanced mechanical ventilatory support in average, we arbitrarily defined the $8^{th}$ day of ARDS as first day of the study. Results : Initially, the groups had similar PF($PaO_2/FiO_2$) ratio, LIS, APACHE III and SAPS II score. By 7th day after the start of steroid therapy, there were significant improvements in PF ratio, LIS, APACHE III and SAPS II score. The mortality in the steroid treated group was significantly lower(42.9% vs 73.5%, p<0.05). Conclusion : Although the data of this study was retrospective and was not randomized, in order to improve the patient's outcomes, steroid therapy should be considered in late ARDS patients. However, prospective trials are needed to define the indication and the effect of steroid therapy in late ARDS.

• Tuberculosis and Respiratory Diseases
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• v.52 no.4
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• pp.367-375
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• 2002

Background : Murine typhus is a flea-borne, worldwide Rickettsial disease caused by Rickettsia typhi. Its symptoms are typically mild but sometimes can be fatal. The major clinical features include fever, rash, and headache. Recently, we experienced 6 cases of ARDS associated with a Rickettsia typhi infection. This study was aimed to analyze the attributing factors for fatal murine typhus and to review the characteristics of the patients who showed acute respiratory distress syndrome as the initial presentation. Methods : The medical records of 15 patients diagnosed as murine typhus were reviewed. The diagnosis was made by single titers of 1:512 or higher, or a 4-fold rise with compatible clinical features. Acute Respiratory Distress Syndrome (ARDS) was defined according to the American-European Consensus Conference. The Characteristics between the ARDS group and the non-ARDS group of murine typhus were compared. Results : Six patients developed ARDS as their initial presentation. Two of them were women and three of them had lived urban area. None of Them a showed skin rash. One of them expired during treatment. The time lapse until the commencement of the specific treatment, the lower serum albumin level, the higher serum total bilirubin level, the higher APACHE III score and the higher MOD score were significantly associated with the ARDS group compared to the non-ARDS group. Conclusion : Murine typhus should be considered as one of the etiologies for the ARDS of unknown cause, particularly in an endemic regions. ARDS caused by Murine typhus generally has a good prognosis.

• Tuberculosis and Respiratory Diseases
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• v.57 no.3
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• pp.226-233
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• 2004

Background : Interferon-gamma (IFN-${\gamma}$) is a critical cytokine in the defense against a Mycobacterium tuberculosis infection. Even though IFN-${\gamma}$ has occasionally been used in the treatment of refractory multidrug-resistant tuberculosis (MDR-TB) with some promising results, there is still some controversy regarding the therapeutic efficacy of IFN-${\gamma}$. This study was performed to examine the effect of subcutaneous IFN-${\gamma}$ in the treatment of MDR-TB patients. Methods : Six patients with refractory MDR-TB were enrolled in this study. Two million IU of IFN-${\gamma}$ was administered subcutaneously three times a week with the concomitant administration of antituberculous drugs for at least for 28 weeks. During the IFN-${\gamma}$ therapy, the sputum smear and culture, radiological and clinical evaluations were performed every 4 weeks throughout the study period. Results : The mean age of the 6 patients was 37 years (ranges, 15-61 years). The drug susceptibility test to standard antituberculous drugs revealed resistance to an average of 6.8 (${\pm}1.2$) agents including isoniazid and rifampicin. An average of 10.8 (${\pm}1.3$) antituberculous drugs were prescribed before IFN-${\gamma}$ therapy. The culture became negative in 2 patients (33%) after initiating IFN-${\gamma}$ therapy; one at 8 weeks, and the other at 24 weeks. Finally, after stopping the IFN-${\gamma}$ therapy after 28 weeks, the culture became positive again in the two patients who were culture-negative. The other 4 patients who failed in the culture conversion are still on antituberculous treatment except for one who died of tuberculosis. Conclusion : Even though 28 weeks of subcutaneous IFN-${\gamma}$ therapy in combination with antituberculous drugs was successful in inducing the culture-negative conversion in some patients with refractory MDR-TB, the culture became positive again after stopping the IFN-${\gamma}$ therapy. This suggests that subcutaneous IFN-${\gamma}$ therapy may have suppressive effect on tuberculosis only during the IFN-${\gamma}$ therapy period in some patients. Further studies will be needed to determine the optimum dose, the administration route, the duration of therapy, and the predicting factors of the response to adjuvant IFN-${\gamma}$ therapy.

• Tuberculosis and Respiratory Diseases
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• v.54 no.3
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• pp.283-294
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• 2003

Introduction : Rapidly growing nontuberculous mycobacteria (RGM) can produce numerous types of manifestations including a pulmonary infection. Managing a pulmonary infection due to RGM is unusually difficult to treat because the organism is invariably resistant to traditional antituberculous drugs and has a varying susceptibility to other antibiotics. The experiences of treatments for a RGM pulmonary infection with various antibiotics are also limited. This study evaluated the clinical manifestations, treatment, and the therapeutic outcomes of a RGM pulmonary infection. Subjects and method : Fifty-four cases with RGM from respiratory specimens were identified between November of 1996 and September of 2002 in the Asan medical center. The medical records and radiographic findings in 20 patients who fulfilled the diagnostic criteria of nontuberculous mycobacteria (NTM) pulmonary disease by ATS guidelines. The clinical, laboratory, and radiological parameters between subgroups. Results : Of the 20 patients, 15 were female. The mean age was 57.7 yrs (${\pm}7.5$), and all of the patients had a history of pulmonary tuberculosis. Most (90%) had an underlying lung disease. The majority of the isolates (80%) were M. abscessus. Chest radiography showed bilateral involvement in 80% of the patients. Bronchiectasis and multiple nodules were the main findings. Cavitation was present in 35% of the patients. Even though 70 % of the patients received antituberculous drugs prior to the correct diagnosis, all of the patients eventually received antibiotics. A mean of 3.5 antibiotics were given for an average of 439 days(${\pm}168$). After completing treatment, nine patients showed improvement after a mean 591(${\pm}311$) days of treatment, whereas the antibiotic treatment was unsuccessful in 2 patients. Conclusion : Many patients with a RGM pulmonary infection show an atypical pattern of radiological findings (bronchiectasis and multiple centrilobular nodules). It is very important to differentiate between M. tuberculosis and NTM and to identify the causative organisms among the NTM because a misdiagnosis can lead to an inappropriate and prolonged treatment. Combined antibiotic treatment yielded promising results, and is recommended for treating patients with a RGM pulmonary infection.

• Tuberculosis and Respiratory Diseases
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• v.58 no.5
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• pp.452-458
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• 2005

Background : In Korea, polymerase chain reaction (PCR) test for M. tuberculosis has been used for the diagnosis of acid-fast bacilli (AFB) smear-negative tuberculosis in order to increase diagnostic sensitivity. However, there have been no data dealing with the clinical utility of PCR in AFB smear-positive patients to differentiate between M. tuberculosis and nontuberculous mycobacteria. Method : We retrospectively analyzed the PCR test results which have been performed in patients who had AFB smear-positive sputum but had ambiguous clinical manifestations of active tuberculosis. PCR test was done using $AMPLICOR^{\hat{a}}$ M. tuberculosis kit. The sensitivity, specificity, and positive and negative predictive values of the PCR test were calculated based on culture and final clinical diagnosis result. Results : Fifty-six consecutive patients (62 PCR tests) were included in the study. Active tuberculosis was diagnosed in 23 patients (41.0%), while 9 patients had NTM infection (16.0%). The sensitivity, specificity, positive- and negative-predictive value of PCR test were 88.8%, 86.8%, 76.1% and 94.3%, respectively, according to the culture result. In comparison, they were 91.3%, 100%, 100%, 94.3%, respectively, according to the final clinical diagnosis. All 15 patients with NTM isolates, including 6 patients who had other lung diseases but expectorated NTM isolate, were negative for PCR test. Conclusion : Even though tuberculosis is still prevalent in Korea, PCR test is useful to differentiate between M. tuberculosis and NTM in patients with AFB-smear positive sputum but with ambiguous clinical manifestations of active tuberculosis.

• Radiation Oncology Journal
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• v.20 no.2
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• pp.147-154
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• 2002

Purpose : Gingko biloba extract (GBE), a natural product extracted from Gingko leaves, is known to increase the radiosensitivity of tumors. This radiosensitization probably arises from the increase in the peripheral blood flow by decreasing the blood viscosity and relaxing the vasospasm. The influence of a GBE on the metabolic status in fibrosarcoma II (FSall) of a C3H mouse was investigated using $^{31}P$ magnetic resonance spectroscopy (MRS). Materials and Methods : Eighteen C3H mice with fibrosarcoma II $(from\;100\;mm^3\;to\;130\;mm^3)$ were prepared for this experiment. The mice were divided into 2 groups; one (9 mice) without a priming dose, and the other (9 mice) with a priming dose of GBE. The GBE priming dose (100 mg/kg) was administered by an intraperitoneal (i.p.) injection 24 hours prior to the measurement. First $^{31}P$ MRS spectra were measured in the mice from each group as a baseline and test dose of GBE (100 mg/kg) was then administered to each group. One hour later, the $^{31}P$ MRS spectra were measured again to evaluate the change in the energy metabolic status. Results : In the group without the priming dose, the mean pH, PCr/Pi, PME/ATP, Pi/ATP, PCr/(Pi+PME) values 1 hour after the test dose were not changed significantly compared to the values at the baseline. However, in the group with the priming dose, the mean PCr/Pi, Pi/ATP, PCr/(Pi+PME) values 1 hour after the test dose changed from the baseline values of 0.49, 0.77, 0.17 to 0.74, 0.57, 0.28 respectively. According to the paired t-test, the differences were statistically significant. Conclusion : The above findings suggest that the metabolic status is significantly improved after administering GBE if the priming dose is given 24 hours earlier. This shows that the radiosensitizing effect of GBE is based on the increase of tumor blood flow and the improvement in the metabolic status.

• Tuberculosis and Respiratory Diseases
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• v.41 no.4
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• pp.372-378
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• 1994

Background: Pressure support ventilation(PSV) is a new form of mechanical ventilatory support that assists spontaneous inspiraory effort of an intubated patient with a clinician-selected amount of positive airway pressure. Low level pressure support during inspiration can overcome the resistive component of inspiratory work imposed by an endotracheal tube. However the clinical efficacy of PSV as a weaning method has not been established yet. Object: The aim of study was to evaluate the efficacy of PSV when it is added to intermittent mandatory ventilation(IMV) in facilitating weaning precess compaired to IMV mode alone. Method: When the subject patients became clinically stable with their arterial blood gas analysis in acceptable range, they underwent weaning process either by IMV alone or by IMV plus PSV. The level of pressure support was held constant throught the weaning period. For the patients who required mechanical ventilation for less than 72 hr, 2h weaning trial was performed with IMV rate starting from 6/min. For the patients who required mechanical ventilation more than 72 hr, 7 hr weaning trial was performed with IMV rate starting from 8/min. For the patients who failed three consecutive trials of weaning, retrial of weaning was attempted over 3 days with IMV rate starting from 8/min. Clinical characteristics, APACHE II score and nutritional status were compared. For all patients, heart rate, mean blood pressure and respiratory rate were mornitored for 48 hrs after weaning trial started. Results: The total number of weaning trial was 37 in 23 patients(18 by IMV, 19 by IMV+PSV). Total ventilation time, APACHE II score and nutritional status were not statistically different between the two groups. The weaning success rate were not statistically different(38.3% by IMV, 42.1% by IMV+PSV) and the changes of mean blood pressure, heart rate, respiratory rate during first 48 hours were not different between the two groups. Conclusion: Low level PSV when added to IMV for weaning trial does not seem to improve the success rate of weaning from mechanical ventilation. PSV at 10cm $H_2O$ did not induce significant physiologic changes during weaning process.

• Tuberculosis and Respiratory Diseases
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• v.50 no.3
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• pp.334-342
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• 2001

Background : RpoB gene mutations have been found in about 96-98% of rifampicin (RMP)-resistant Mycobacterium tuberculosis. Recent reports confirm that the in laboratory settings a rpoB gene mutation can be used as a surrogate marker for multi-drug resistant tuberculosis. However, its usefulness in clinical applications has not been evaluated. This study was performed to confirm whether mutation analysis of the rpoB gene of M. tuberculosis is useful in clinical settings. Methods : The medical records of 33 patients in whom rpoB gene analysis was conducted using an INNOLiPA Rif. TB assay (LiPA) from June, 1998, to July, 2000, at the Asan Medical Center were retrospectively reviewed in 33 patients. The clinical characteristics in addition to the drug susceptibility and LiPA results were analyzed. The drug susceptibility test was considered as a gold standard method for M. tuberculosis susceptibility and these results were compared with those of the rpoB gene study and sequencing analysis. Sequencing analysis of the rpoB gene was done in cases where there was a discrepancy between the results of the drug susceptibility an d rpoB gene study. Results : The mean age and sex ratio was $42{\pm}18$, and 24:9 (M:F), respectively. There were 19 RMP susceptible (58%) and 14 RMP-resistant cases (42%) according to the rpoB gene study. The mean time from the request to reporting the results of the rpoB gene study was $5.2{\pm}2.6$ days. The mean gap from reporting the rpoB gene study to reporting the susceptibility was $56{\pm}35$ days. Twenty-eight cases (85%) showed identical results compared with the drug susceptibility results, whereas five cases (15%) showed contradictory results. When compared with the sequencing analysis, of the five cases that showed contradictory results, two had LiP A analysis errors and the remaining three were identical to the sequencing results. The rpoB gene study was of assistance in choosing the appropriate drugs in 28 cases (85%). Conclusions : An rpoB gene study using an LiP A assay was useful in rapidly diagnosing RMP-resistant tuberculosis, which enabled a proper choice of the appropriate drugs in clinical practices. However, an LiPA assay always should be performed in conjunction with microscopy, culture, and susceptibility tests.

• Tuberculosis and Respiratory Diseases
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• v.49 no.3
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• pp.343-352
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• 2000

Backgrounds : Respiratory care for patients in intensive care units (ICUs) has been performed mainly by nurses in Korea. However, the current status of respiratory care in the Korea ICUs is not well known. Respiratory care and the methods of delivery in ICUs were surveyed. Method : A confidential questionnaire was distributed to the head nurses working the ICUs at 117 hospitals in Korea. One hundred hospitals returned the questionnaires, for a response rate of 85%. The hospitals were divided into three groups : Main university hospitals (MUH), university associated hospitals (UAH), and general hospitals (GH) Result : Eighteen units of 66 units in MUH and 35 units of 58 units in GH were organized as a general ICUs. The percentage of ICUs with full-time doctors was 47.1%. The nurses usually delivered respiratory care spending from 1 to 4 h during their 8 h of working time. Although the respondents felt that respiratory care should be delivered by trained respiratory therapists, these therapists were not found at the hospitals. Most of the units performed percussion, tracheal suctioning, and positional changes. However, vibration and IPPB were less frequently performed in GH. Among oxygen supply apparatus, venturi mask and T-piece were not frequently used in GH. GH applied a noninvasive ventilator mode less frequently than MUH and UAH. The percentage of Swan-Ganz catheter monitoring was only 21.4% in GH. Conclusion : Respiratory care for patients in the Korean ICUs was provided by nurses on the whole. In addition, there were many differences in the level of respiratory care according to the type of hospital. To overcome the current problems revealed, an effective in-hospital training program for the development of full-time respiratory care therapists should be established urgently in Korea.