• Tuberculosis and Respiratory Diseases
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• v.47 no.5
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• pp.586-597
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• 1999

Background: Many diagnostic tests have developed to diagnose tuberculosis and other mycobacterial diseases but the diagnosis of tuberculosis relies largely on radiological findings and acid-fast staining of sputum and/or culture. Recently, new serologic diagnostic methods, which are safe and easy to use have been introduced into Korea. In this study, the usefulness of serologic diagnosis for tuberculosis and the disease pattern induced variation of the test were evaluated. Methods: Serological assay was performed upon 108 patients with two test kits, the ICT tuberculosis and the BioSign$^{TM}$TB, which are based upon a rapid immunochromatographic assay technique, capable of being interpreted within 15 minutes. The case groups consisted of 61 patients with active pulmonary tuberculosis(36 patients), extrapulmonary tuberculosis(3 patients), or both(22 patients). Control groups consisted of 47 patients with inactive old pulmonary tuberculosis(17 patients), nontuberculous pulmonary disease(16 patients) and nonpulmonary cardiac disease(14 patients). Results : The diagnostic sensitivity, specificity, positive predictive value(PPV) and negative predictive value(NPV) of the ICT tuberculosis were 64.3%, 91.5%, 90.0% and 68.3% respectively. The diagnostic sensitivity, specificity, PPV and NPV of the BioSign$^{TM}$TB were 76.5%, 95.3%, 94.1 % and 78.8% respectively. Differences in sensitivity were not significant between patients with previous history of tuberculosis or patients without prior history of tuberculosis. The ICT tuberculosis test showed higher sensitivity in pulmonary tuberculosis patients(76.5%) than extrapulmonary tuberculosis patients(33.3%). There was no difference in sensitivity between patients with or without cavitary lesion by chest X-ray. Conclusion: Considering high specificity and PPV, serologic diagnosis using a rapid immunochromatographic assay device is another helpful diagnostic method in the diagnosis of tuberculosis, when combined with previous diagnostic methods such as chest X-ray, microbiologic study but it has limitation in terms of confirming the diagnosis for tuberculosis as the only diagnostic method because of relatively low sensitivity and NPV.

• Tuberculosis and Respiratory Diseases
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• v.47 no.5
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• pp.618-628
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• 1999

Background: Cell growth is a balance between cell proliferation and cell death. Insulin-like growth factor-I(IGF-I), which binds IGF-I receptor(IGF-IR), mediates cellular proliferation as a potent mitogen. IGF binding protein-3(IGFBP-3) as a circulating major IGFBP can inhibit or enhance the effects of IGF-I on cellular growth by binding IGFs. Methods: We investigated the expressions of mRNA of IGF-I and IGF-IR by northern blot and phosphorylation of IGF-IR with the treatment of IGF-I by western blot in 3T3 fibroblast cells. The cellular proliferations of 3T3 cells with the treatments of IGF-I were evaluated using $^3H$-thymidine incorporation and MTT assay. Also to observe the effect of IGFBP-3 on cellular proliferation, 3T3 cells were treated with anti-IGFBP-3 and ${\alpha}IR_3$(monoclonal antibody to IGF-IR) alone or in combination. Results: Our results demonstrated that 3T3 cells showed mRNA expressions of IGF-I and IGF-IR and the IGF-I increased phosphorylation of IGF-IR. The treatments of 3T3 cells with IGF-I increased cellular proliferation in 5 % and 1 % seruma-containing media, not in serum-free media. The addition of anti-IGFBP-3 to neutralize IGFBP-3 showed 2-fold increase of cellular proliferation, and also co-incubation of anti-IGFBP-3 and ${\alpha}IR_3$ together showed similar increase of cellular proliferation in 3T3 cells. Interestingly, when the cells were pretreated with ${\alpha}IR_3$ for 4 hr, prior to the simultaneous addition of ${\alpha}IR_3$ and anti-IGFBP-3, anti-IGFBP-3-mediated cellular proliferation was decreased to control level. All of these results suggest that free IGF-I released from IGF-I/IGFBP-3 complex would be involved in the cellular proliferation. Conclusion: IGF-I is a mitogen through the activation of IGF-IR in 3T3 cells, and IGFBP-3 could be a potent inhibitor for IGF-I action by binding IGF-I.

• 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.66 no.6
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• pp.444-450
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• 2009

Background: Biomarkers for cancer have several potential clinical uses, including the following: early cancer detection, monitoring for recurrence prognostication, and risk stratification. However, no biomarker has been shown to have adequate sensitivity and specificity. Many investigators have tried to validate biomarkers for the early detection and recurrence of lung cancer. To evaluate plasma G-CSF as such a biomarker, protein levels were measured and were found to correlate with the clinicopathological features of primary lung tumors. Methods: Between December 2006 and May 2008, 100 patients with histologically-validated primary lung cancer were enrolled into this study. To serve as controls, 127 healthy volunteers were enrolled into this study. Plasma G-CSF levels were measured in lung cancer patients using the sandwich ELISA system (R & D inc.) prior to treatment. Results: The mean plasma G-CSF levels were 12.2$\pm$0.3 pg/mL and 46.0$\pm$3.8 pg/mL (mean$\pm$SE) in the normal and in the cancer groups, respectively. In addition, plasma G-CSF levels were higher in patients with early lung cancer than in healthy volunteers (p<.001). Plasma G-CSF levels were higher in patients who were under 65 years old or smokers. Within the cancer group, plasma G-CSF levels were higher in patients with non small cell lung cancer than in patients with small cell lung cancer (p<.05). Overall, plasma G-CSF levels were shown to increase dependent upon the type of lung cancer diagnsosed. In the order from highest to lowest, the levels of plasma G-CSF tended to decrease in the following order: large cell carcinoma, squamous cell carcinoma, adenocarcinoma, and bronchioloalveolar carcinoma. Plasma G-CSF levels tended to be higher in patients with advanced TNM stage than in localized TNM stage (I, II

• Journal of Yeungnam Medical Science
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• v.16 no.2
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• pp.169-180
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• 1999

Background: Uterine cervical cancer is the most common malignant tumor of the women in Korea. This study was undertaken to evaluate the usefulness of the cervicography as a screening test of cervical cancer. Materials and Methods: Cervicography was taken from 482 women at department of obstetrics and gynecology, at Yeungnam University Hospital from March 1, 1998 to October 31, 1999. Of the 482 women, 172 women were exc1uded from the study for various reasons, and 310 women completed the study. Three-hundred and ten women had cervical cytology (Papanicolaou smear), cervicography and colposcopy, and punch biopsy was undertaken if any of the test result was abnormal. Results: The most common age group was 35-39, and 40-44, 45-49 in order and most common reason for having a screening test was regular check for cervical cancer. The mean duration from the last Pap smear was 17.1 months, and 64 women(20.4%) never had any prior screening tests. Of the 310 women, 254 women were categorized as normal or having benign disease such as cervicitis, erosion or metaplasia. Biopsy was taken from 56 patients and the results were 26 chronic cervicitis, 4 mild dysplasia, 6 moderate dysplasia, 2 severe dysplasia, 14 carcinoma in situ and 4 invasive carcinoma. The results of cytology and cervicography were well correlated(p<0.05). The sensitivity and specificity of cytology were 86.7% and 76.9%, respectively and the sensitivity and specificity of cervicography were 56.7% and 96.2%, respectively. False negative rate of cervicography(43.3%) was much higher than those of cytology(13. 3%) (p<0.05), but false positive rate of cervicography(3.8%) was much lower than that of cytology(23.1%) (p<0.05). Conclusion: It seems inappropriate to use cervicography as a single screening test for cervival cancer, but it may be an effective complementary test for cytology to lower the false negative rate of cytology.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1811-1815
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• 2014

Background: In clinical trials with no upper age limit, the proportion of older patients is usually small, probably reflecting the more conservative approach adopted by clinicians when treating the elderly. An exploratory analysis of elderly patients in the RECORD-1 Trial showed that patients ${\geq}$ 65 y.o. had superior median PFS than overall RECORD-1 population (5.4 months and 4.9 months, respectively). We investigated the efficacy, relative benefit and safety of Everolimus (EVE) as sequential therapy after failure of VEGFr-TKI therapy for older patients with metastatic renal cell cancer (mRCC), in daily practice. Materials and Methods: 172 consecutive IRB approved patients with mRCC (median age 65, M:F 135/37, 78% clear cell) who received salvage EVE at 39 tertiary institutions between October 2009 and August 2011 were included in this analysis. Some 31% had progressed on sunitinib, 22% on sorafenib, 1% on axitinib, 41% on sequential therapy, and 5% had received other therapy. Patients with brain metastases were not included and 95% of the patients had a ECOG (Eastern Cooperative Oncology Group) performance status (PS) of 0 or 1. Previous radiotherapy was an exclusion criterion, but prior chemotherapy was permitted. Adequate organ function and hematologic parameters were mandatory. EVE administration was approved by the institutional review board at each participating institution and signed informed consent was obtained from all patients. Results: Median time of the whole cohort to last follow-up was 3.5 months (range 0.4-15.2 months). Forty four percent were continuing to take EVE at last followup. There were 86 (50%) patients ${\geq}$ 65 y.o. and 86 (50%) <65 y.o. The percentage of patients who showed PR/SD was higher in the older group than in the younger one (5.9%/61.2% vs 1.2%/46.5%, respectively). Median survival of older patients was also significantly longer (3.5 +/- 0.31 vs 3.1 +/- 0.34, hazard ratio=0.45, CI; 0.255-0.802). Analysis using Cox regression model adjusted for gender, PS, number of metastases, site of metastases, histology, smoking history and age detected an association between age and PFS (p=0.011). The frequency of adverse events in elderly patients treated with EVE was no greater than that in younger patients, although such toxicity may have had a greater impact on their quality of life. Conclusions: Older patients should not generally be excluded from accepted therapies (mTOR inhibitors after failure of VEGFr-TKI therapy) for mRCC.

• International Journal of Vascular Biomedical Engineering
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• v.4 no.2
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• pp.19-24
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• 2006

Background: Pulse wave velocity (PWV), which is inversely related to the distensibility of an arterial wall, offers a simple and potentially useful approach for an evaluation of cardiovascular diseases. In spite of the clinical importance and widespread use of PWV, there exist no standard either for pulse sensors or for system requirements for accurate pulse wave measurement. Objective of this study was to assess the reproducibility of PWV values using a newly developed PWV measurement system in healthy subjects prior to a large-scale clinical study. Methods: System used for the study was the PP-1000 (Hanbyul Meditech Co., Korea), which provides regional PWV values based on the measurements of electrocardiography (ECG), phonocardiography (PCG), and pulse waves from four different sites of arteries (carotid, femoral, radial, and dorsalis pedis) simultaneously. Seventeen healthy male subjects with a mean age of 33 years (ranges 22 to 52 years) without any cardiovascular disease were participated for the experiment. Two observers (observer A and B) performed two consecutive measurements from the same subject in a random order. For an evaluation of system reproducibility, two analyses (within-observer and between-observer) were performed, and expressed in terms of mean difference ${\pm}2SD$, as described by Bland and Altman plots. Results: Mean and SD of PWVs for aorta, arm, and leg were $7.07{\pm}1.48m/sec,\;8.43{\pm}1.14m/sec,\;and\;8.09{\pm}0.98m/sec$ measured from observer A and $6.76{\pm}1.00m/sec,\;7.97{\pm}0.80m/sec,\;and\;\7.97{\pm}0.72m/sec$ from observer B, respectively. Between-observer differences ($mean{\pm}2SD$) for aorta, arm, and leg were $0.14{\pm\}0.62m/sec,\;0.18{\pm\}0.84m/sec,\;and\;0.07{\pm}0.86m/sec$, and the correlation coefficients were high especially 0.93 for aortic PWV. Within-observer differences ($mean{\pm}2SD$) for aorta, arm, and leg were $0.01{\pm}0.26m/sec,\;0.02{\pm}0.26m/sec,\;and\;0.08{\pm}0.32m/sec$ from observer A and $0.01{\pm}0.24m/sec,\;0.04{\pm}0.28m/sec,\;and\;0.01{\pm}0.20m/sec$ from observer B, respectively. All the measurements showed significantly high correlation coefficients ranges from 0.94 to 0.99. Conclusion: PWV measurement system used for the study offers comfortable and simple operation and provides accurate analysis results with high reproducibility. Since the reproducibility of the measurement is critical for the diagnosis in clinical use, it is necessary to provide an accurate algorithm for the detection of additional features such as flow wave, reflection wave, and dicrotic notch from a pulse waveform. This study will be extended for the comparison of PWV values from patients with various vascular risks for clinical application. Data acquired from the study could be used for the determination of the appropriate sample size for further studies relating various types of arteriosclerosis-related vascular disease.

• Tuberculosis and Respiratory Diseases
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• v.49 no.4
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• pp.466-473
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• 2000

Background : Patients with locally advanced non-small cell lung cancer are often treated with radiation alone or in combination with chemotherapy. Both modalities have a potentially damaging effect on pulmonary function. In order to examine changes in the cardiopulmonary exercise function of patients with locally advanced non-small cell lung cancer before and after conventional radiotherapy, we conducted a prospective study involving patients with such cancer, that had received radiation therapy. Method : Resting pulmonary function test, thoracic radiographic finding and cardiopulmonary exercise test(CPET) were assessed prior to and 4 weeks following radiation therapy in 11 male patients with locally advanced non-small cell lung cancer. Patient with endobronchial mass were excluded. Results : The forces vital capacity (FVC), forced expiratory volume in 1 second ($FEV_1$ and maximal voluntary ventilation (MVV) did not decreased between before and 4 weeks after radiation but the diffusing capacity (DLCO) had decreased by 11% 4 weeks after radiation, which was not statistically significant. No changes in maximal oxygen consumption ($VO_2$max), carbon dioxide production ($VCO_2$), exercise time and work load were attributed to radiation therapy. Follow up cardiopulmonary exercise testing revealed unchanged cardiovascular function, ventilatory function and gas exchange. No difference in cardiopulmonary exercise test performance was observed between pre- and post-radiation. Conclusion : Cardiopulmonary exercise function did not decrease within the short-term after the radiation of patients with locally advanced non-small cell lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.52 no.5
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• pp.529-538
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• 2002

Background : Many clinicians are reluctant to prescribe systemic corticosteroids to manage an asthmatic attack because of many complications such as osteoporosis, cushing's syndrome, diabetes, hypertension and bleeding tendency. The use of nebulized budesonide may be of value in some infants, old men, and in particular adult asthmatic patients who complain of severe dyspnea. A clinical validation and steroid-sparing effect of nebulized budesonide in asthmatic adults and COPD were evaluated, and the short-term effects of budesonide use on the HPA axis were assessed. Materials and Methods : Study A was prospectively done with 41 patients diagnosed with pure asthma and 30 patients diagnosed with COPD (including asthmatic component) in Soonchunhyang Hospital, Chunan from June. 2000 to Sep. 2001. They were treated with nebulized budesonide including systemic steroids (Group 1), a budesonide tubuhaler including a systemic steroid (Group 2), or only the systemic steroid(Group 3). The peak flow rate, arterial blood gas in room air, pulmonary function test, symptom scoring, steroid amount and hospital stay were analyzed. Study B was conducted with 19 patients to evaluate the short-term effects on the HPA axis of treatment with nebulized budesonide 1mg twice daily and a budesonide turbuhaler 5 puffs twice daily. The adrenal function was assessed prior to budesonide inhalation and after 7 days of budesonide inhalation. Results : In the pure asthmatic patients, the mean value of the symptoms (dyspnea, wheezing, cough, night asthma) or the arterial BGAs, total amounts of steroid or hospital stay and the difference in the results of the pulmonary function tests or peak expiratory flow rate were similar in the three groups. In COPD with an asthmatic component, there were no significant differences among the three groups. Although nebulized budesonide suppressed HPA function,(p=0.006) the HPA responses from the nebulized budesonide and turbuhaler budesonide were similar (p=0.288) Conclusion : This result suggests that systemic steroid should only be made available for acute asthmatic patients irrespective of the inhaled budesonides. Nebulized budesonide at the therapeutic dose has similar effects on the HPA axis compared to that of turbuhaler budesonide.

• Tuberculosis and Respiratory Diseases
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• v.52 no.5
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• pp.497-505
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• 2002

Background : INF-${\gamma}$ plays an important role in the host response to a mycobacterial infection. A complete IFN-${\gamma}$ receptor 1 deficiency is a life threatening condition because it renders patients highly susceptible to a mycobacterial infection. Several mutations in the IFN-${\gamma}$ receptor and STAT1 gene have been identified in the rare mycobacterial infections. These mutations have partial function of the IFN-${\gamma}$ receptor and similar pathologic features to clinical tuberculosis. Materials and Methods : The function of the IFN-${\gamma}$ receptor was evaluated in the patients with clinical tuberculosis. In addition, the DNA coding sequence of the IFNgR1 and STAT1 gene was also analyzed in disseminated tuberculosis patients who might have a defective IFN-${\gamma}$ receptor. Results : The cell surface expression levels of HLA-DR and CD64 in the PMBC after being stimulation with IFN-${\gamma}$ (100IU/ml, 1000IU/ml) were increased in both controls and patients. However, the rate of increase in both groups was similar. The production of TNF-${\alpha}$ in the response to stimulation with LPS was higher in the both groups ($850.7{\pm}687.8$ vs. $836.7{\pm}564.3$ pg/ml). Pretreatment with IFN-${\gamma}$ prior to LPS stimulation resulted in further increase in TNF-${\alpha}$ production between both groups ($2203.5{\pm}242.5$ vs. $2227.5{\pm}560.4$ pg/ml). However, the rate of the increase in TNF-${\alpha}$ production in the both groups was similar. The known mutations in the IFNgR1 and STAT1 coding sequences were not found in the genomic DNA of patients with disseminated tuberculosis. Conclusion : The functional and genetic defects of the IFN-${\gamma}$ receptor were not identified in clinical tuberculosis. This suggests the defective IFN-${\gamma}$ receptor that predispoe patients to a BCG or NTM infection can not alone account for the cases of clinical tuberculosis.