• Tuberculosis and Respiratory Diseases
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• v.54 no.4
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• pp.415-428
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• 2003

Background : This study assessed the efficacy and toxicity of etoposide and carboplatin(EC) combination regimen as a first line therapy for small cell lung cancer(SCLC), and determined the efficacy and toxicity of topotecan for relapsed SCLC. Methods : One hundred and ten patients with previously untreated SCLC received etoposide($100mg/m^2$ i.v., day 1 to 3) and carboplatin($300mg/m^2$ i.v., day 1) combination chemotherapy every 3 weeks. For patients with relapsed SCLC after EC therapy, topotecan($1.5mg/m^2$) was administered for 5 consecutive days every 3 weeks. Response rate, survival and toxicity profiles were assessed. Response was recorded as CR(complete remission), PR(partial remission), SD(stable disease) and PD(progressive disease). Results : One hundred and one patients were assessed for response to EC. Overall response rate to EC was 57.4%(CR 15.8%, PR 41.6%) with a time to progression of 10.3 months(median). The toxicity was tolerable and there was no treatment-related death. Twenty one relapsed SCLC patients were treated with topotecan. Of those who relapsed within 3 months of EC(refractory relapse, RR), 15.4%(2/13) showed PR, while of those who relapsed after 3 months(sensitive relapse, SR), 25%(2/8) exhibited PR. Grade 4 neutropenia was noted in 9.5% and 14.3% showed thrombocytopenia(G4). Conclusion : The EC regimen showed a moderate response rate for SCLC with minimal toxicity. The use of topotecan for relapsed SCLC warrants further investigation.

• Tuberculosis and Respiratory Diseases
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• v.58 no.1
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• pp.31-42
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• 2005

Background : Peroxiredoxins (Prxs) are a relatively newly recognized, novel family of peroxidases that reduce $H_2O_2$ and alkylhydroperoxide into water and alcohol, respectively. There are 6 known isoforms of Prxs present in human cells. Normally, Prxs exist in a head-to-tail homodimeric state in a reduced form. However, in the presence of excess $H_2O_2$, it can be oxidized on its catalytically active cysteine site into inactive oxidized forms. This study surveyed the types of the Prx isoforms present in the pulmonary epithelial, macrophage, endothelial, and other cell lines and observed their response to oxidative stress. Methods : This study examined the effect of exogenous, excess $H_2O_2$ on the Prxs of established cell lines originating from the pulmonary epithelium, macrophages, and other cell lines, which are known to be exposed to high oxygen partial pressures or are believed to be subject to frequent oxidative stress, using non-reducing SDS polyacrylamide electrophoresis (PAGE) and 2 dimensional electrophoresis. Result : The addition of excess $H_2O_2$ to the culture media of the various cell-lines caused the immediate inactivation of Prxs, as evidenced by their inability to form dimers by a disulfide cross linkage. This was detected as a subsequent shift to its monomeric forms on the non-reducing SDS PAGE. These findings were further confirmed by 2 dimensional electrophoresis and immunoblot analysis by a shift toward a more acidic isoelectric point (pI). However, the subsequent reappearance of the dimeric Prxs with a comparable, corresponding decrease in the monomeric bands was noted on the non-reducing SDS PAGE as early as 30 minutes after the $H_2O_2$ treatment suggesting regeneration after oxidation. The regenerated dimers can again be converted to the inactivated form by a repeated $H_2O_2$ treatment, indicating that the protein is still catalytically active. The recovery of Prxs to the original dimeric state was not inhibited by a pre-treatment with cycloheximide, nor by a pretreatment with inhibitors of protein synthesis, which suggests that the reappearance of dimers occurs via a regeneration process rather than via the de novo synthesis of the active protein. Conclusion : The cells, in general, appeared to be equipped with an established system for regenerating inactivated Prxs, and this system may function as a molecular "on-off switch" in various oxidative signal transduction processes. The same mechanisms might applicable other proteins associated with signal transduction where the active catalytic site cysteines exist.

• Tuberculosis and Respiratory Diseases
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• v.59 no.4
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• pp.389-396
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• 2005

Background : Central venous catheters(CVCs) area major source of nosocomial infection. Chlorhexidine-silver sulfadiazine coated catheters (CHSS) were developed to reduce the rate of CVC infection. However, the clinical effectiveness of CHSS in comparison wth non-coated catheter (NCC) remains to be evaluated. Methods : From January 2004 to December 2004 in medical intensive care unit (ICU) of Asan Medical Center, CVCs were inserted in 446 cases. We retrospectively analyzed characteristics of patients and catheterization,the catheter-related infection rate and colonization, microbiologic findings, and insertion sites (subclavian, jugular, femoral) according to the type of inserted CVCs (NCC: 187 cases, CHSS: 259 cases). Catheter related infection is defined as catheter related bacteremia and catheter related non-bacteremic sepsis. Results : 1) The mean age of the patients in each group was $62{\pm}16$ years, $63{\pm}15$ years (p=0.42), and sex ratio 94:50, 141:69 (p=0.9) in NCC and CHSS. Duration of ICU admission ($29{\pm}37$, $26{\pm}44$ p=0.42), duration of mechanical ventilation ($17{\pm}22$, $15{\pm}19$ p=0.17), and APACHE III score at the time of CVC insertion ($81{\pm}34$, $82{\pm}37$ p=0.61) were not different between both groups. 2) Mean duration of catheterization was 118 in NCC and 119 in CHSS (p=0.98). Number of catheter-days was 2176 days in NCC and 3035 days in CHSS. Catheter-related infection occurred in 9 (4.8%) cases receiving NCC and 4 cases (1.5%) receiving CHSS. Catheterrelated infection incidence per 1000 catheter-days was 4.1 and 1.3, respectively (p=0.04). CHSS was associated with a significant reduction of infection in jugular catheters regarding to insertion sites (p=0.01). 3) Microorganisms causing infection were Staphylococcus aureus (n=3), Candida (n=3), coagulase-negative Staphylococci (n=2), and Klebsiella (n=1) in NCC, and Candida species (n=2), coagulase-negative Staphylococci (n=2), Proteus (n=1) in CHSS. Conclusion : CHSS has significantly reduced the episodes of infection compared to NCC in jugular catheterization in medical ICU.

• Tuberculosis and Respiratory Diseases
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• v.59 no.5
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• pp.522-529
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• 2005

Background : Several national societies have published guidelines for empirical antimicrobial therapy in patients with severe community-acquired pneumonia (SCAP). This study investigated the etiologies of SCAP in the Asan Medical Center and assessed the relationship between the initial empirical antimicrobial regimen and 30 day mortality rate. Method : retrospective analysis was performed on patients with SCAP admitted to the ICU between March 2002 and February 2004 in the Asan Medical Center. The basic demographic data, bacteriologic study results and initial antimicrobial regimen were examined for all patients. The clinical outcomes including the ICU length of stay, the ICU mortality rate, and 30 days mortality rates were assessed by the initial antimicrobial regimen. Results : One hundred sixteen consecutive patients were admitted to the ICU (mean age 66.5 years, 81.9 % male, 30 days mortality 28.4 %). The microbiologic diagnosis was established in 58 patients (50 %). The most common pathogens were S. pneumoniae (n=12), P. aeruginosae (n=9), K. pneumonia (n=9) and S. aureus (n=8). The initial empirical antimicrobial regimens were classified as: ${\beta}$-lactam plus macrolide; ${\beta}$-lactam plus fluoroquinolone; anti-Pseudomonal ${\beta}$-lactam plus fluoroquinolone; Aminoglycoside combination regimen; ${\beta}$-lactam plus clindamycin; and ${\beta}$-lactam alone. There were no statistical significant differences in the 30-day mortality rate according to the initial antimicrobial regimen (p = 0.682). Multivariate analysis revealed that acute renal failure, acute respiratory distress syndrome and K. pneumonae were independent risk factors related to the 30 day mortality rate. Conclusion : S. pneumoniae, P. aeruginosae, K. pneumonia and S. aureus were the most common causative pathogens in patients with SCAP and K. pneumoniae was an independent risk factor for 30 day mortality. The initial antimicrobial regimen was not associated with the 30-day mortality.

• Tuberculosis and Respiratory Diseases
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• v.59 no.5
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• pp.510-516
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• 2005

Backgroud : Lung cancer is the leading cause of cancer deaths in Korea and the number of lung cancer deaths is increasing. The higher response rates, decreased toxicity and improved performance status of the first-line treatments have resulted in an increased number of patients becoming candidates for second-line therapy. Several new antineoplastic agents, including gemcitabine, docetaxel and paclitaxel, have recently demonstrated second-line activity. This phase II study evaluated the efficacy and toxicity of gemcitabine and vinorelbine as combination chemotherapy for Korean patients with NSCLC as a second-line treatment. Methods : Sixty response-evaluable patients were enrolled from December 2000 to July 2003. We conducted a phase II study of a combination gemcitabine and vinorelbine chemotherapy for patients with histologically confirmed NSCLC that was stage IIIB and IV disease at the time of diagnosis, and the disease had progressed onward or the patients had relapsed after first-line platinum-based chemotherapy. They were treated with intravenous gemcitabine $1000mg/m^2$ and intravenous vinorelbine $25mg/m^2$ on days 1 and 8. This chemotherapy regimen was repeated every 3 weeks. Results : A total of 215 cycles of treatment were given and the mean number of cycles was 3.6 cycles. All the patients were evaluable for the toxicity profile. The response rate was 10% according to the WHO criteria. The median progression free survival was 3.8 months and the median survival time was 10.1 months. The 1-year survival rate was 32.9%. Grade III and IV neutropenia were seen in 20 (33.3%) and 7 (11.7%) patients, respectively. Conclusion : The combination of gemcitabine and vinorelbine is active and well tolerated as a second-line therapy for patients with advanced nonsmall cell lung carcinoma.

• Radiation Oncology Journal
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• v.22 no.2
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• pp.106-114
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• 2004

Purpose : This study was done to evaluate xerostomia fellowing intensity modulated radiotherapy for patients with head and neck cancer, and to analyze the correlation between the dosimetric parameters and xerostomia parameters. Materials and Methods : From February till October 2003, 13 patients with 3 months of follow-up were evaluated for xerostomia after being treated for head and neck cancer with IMRT. Their median age was 57 years(range: 43$\~$77). Xerostomia were assessed with a 4-question xerostomia questionnaire score (XQS) and a test for salivary flow rates (unstimulated and stimulated). The patients were also given a validated LENT SOMA scale (LSC) questionnaire. The evaluations were completed before radiation therapy (pre-RT) and at 1 and, 3 months after radiation therapy (RT). We evaluated xerostomia at pre-RT, 1 and, 3 months after RT. The association between the xerostomia parameters (XQS and LSC) and salivary flow rates (unstimulated and stimulated: USFR and SSFR) was assessed at 1 and 3 months after RT. Resrlts : All 13 patients showed no significant changes in XQS, LSC and Salivary Flow rates. As a result, we couldn't find out about xerostomia development. Based on the total mean parotid dose, 3,500 cGy, we divided these patients into two groups. The 8 patients (<3,500 cGy) showed no significant changes in XQS, LSC and Salivary Flow rates However, in 5 Patients ($\geq$3,500 cOGy), there was a significant increase in USFR and, SSFR at 3 months after RT, and for the XQS and, LSC at 1 and 3 months after RT. The correlation between XQS and, LSC, and USFR and, SSFR in ail patients (13) was significant at 3 months after RT. The correlation had a tendency to the decrease for USFR and, SSFR in proportion to the increase of XQS and, LSC. Conclusion : Based on the results of this study, IMRT seem to be an effective treatment to significantly decrease the xerostomia. XQS and, LSC seem to be a effective tool for predicting the xerostomia. A total parotid gland mean dose of <3,500 cGy should be a planning goal if substantial sparing of the gland function is desired. Furthermore, patients should be enrolled in a study to define a more accurate threshold dose for the parotid gland.

• Radiation Oncology Journal
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• v.26 no.4
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• pp.204-212
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• 2008

Purpose: This study was performed to evaluate the disease-free survival and risk factors of recurrence in early breast cancer patients who have undergone breast conserving surgery and radiation therapy. Materials and Methods: From March 1997 to December 2002, 77 breast cancer patients who underwent breast conserving surgery and radiation therapy were reviewed retrospectively. The median follow-up time was 58.4 months (range $43.8{\sim}129.4$ months) and the mean subject age was 41 years. The frequency distribution of the different T stages, based on the tumor characteristics was 38 (49.3%) for T1, 28 (36.3%) for T2, 3 for T3, 7 for T is and 1 for an unidentified sized tumor. In addition, 52 patients (67.5%) did not have axillary lymph metastasis, whereas 14 patients (18.1%) had $1{\sim}3$ lymph node metastases and 3 (0.03%) had more than 4 lymph node metastases. The resection margin was negative in 59 patients, close (${\leq}2\;mm$) in 15, and positive in 4. All patients received radiation therapy at the intact breast using tangential fields with a subsequent electron beam boost to the tumor bed at a total dose ranging from 59.4 Gy to 66.4 Gy. Patients with more than four positive axillary lymph nodes received radiation therapy ($41.4{\sim}60.4\;Gy$) at the axillary and supraclavicular area. Chemotherapy was administered in 59 patients and tamoxifen or fareston was administered in 29 patients. Results: The 5 year overall survival and disease-free survival rates were 98.08% and 93.49%, respectively. Of the 77 patients, a total of 4 relapses (5.2%), including 1 isolated supraclavicular relapse, 1 supraclavicular relapse with synchronous multiple distant relapses, and 2 distant relapses were observed. No cases of local breast relapses were observed. Lymph node metastasis or number of metastatic lymph nodes was not found to be statistically related with a relapse (p=0.3289) nor disease-free survival (p=0.1430). Patients with positive margins had a significantly shorter disease-free survival period (p<0.0001) and higher relapse rates (p=0.0507). However, patients with close margins were at equal risk of relapse and disease-free survival as with negative margins (p=1.000). Patients younger than 40 years of age had higher relapse rates (9.3% vs. 0%) and lower disease-free survival periods, but the difference was not statistically significant (p=0.1255). The relapse rates for patients with tumors was 14% for tumor stage T2, compared to 0% for tumor stage T1 tumors (p=0.0284). A univariate analysis found that disease-free survival and relapse rates, T stage, positive resection margin and mutation of p53 were significant factors for clinical outcome. Conclusion: The results of this study have shown that breast conservation surgery and radiation therapy in early breast cancer patients has proven to be a safe treatment modality with a low relapse rate and high disease-free survival rate. The patients with a positive margin, T2 stage, and mutation of p53 are associated with statistically higher relapse rates and lower disease-free survival.

• Radiation Oncology Journal
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• v.13 no.2
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• pp.157-162
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• 1995

Lung cancer study group at Asan Medical Center has conducted the second prospective study to determine the efficacy and feasibility of MVP chemotherapy with concurrent hyperfractionated radiotherapy for Patients with stage III unresectable non-small cell lung cancer(NSCLC). All eligible Patients with stage III unresectable NSCLC were treated with hyperfractionated radiotherapy(120 cGy/fx BID. 6480 cGy/54fx) and concurrent 2 cycles of MVP(Mitomycin C $6mg/m^2,$ d2 & d29.Vinblastine $6mg/m^2,$ d2 & d29, Cisplatin $60mg/m^2,$ dl & d28) chemotherapy. Between Aug. 1993 and Nov. 1994, 62 patients entered this study; $6(10\%)$ had advanced stage IIIa and $56(90\%)$ had IIIb disease including 11 with pleural effusion and 10 with supraclavicular metastases. Among 62 patients, $48(77\%)$ completed planned therapy. Fourteen patients refused further treatment during chemoradiotherapy. Of 46 patients evaluable for response, $34(74\%)$ showed major response including $10(22\%)$ with complete and $24(52\%)$ with partial responses. Of 48 patients evaluable for toxicity, $13(27\%)$ showed grade IV hematologic toxicity but treatment delay did not exceed 5 days Two patients died of sepsis during chemoradiotherapy. Severe weight loss(more than $10\%)$ occurred in 9 patients$(19\%)$ during treatment. Nine patients$(19\%)$ developed radiation pneumonitis Six of these patients had grade 1 (mild) Pneumonitis with radiographic changes within the treatment fields Three other patients had grade 11 Pneumonitis, but none of these patients had continuous symptoms after steroid treatment. Concurrent chemoradiotherapy for patients with advanced NSCLC was well tolerated with acceptable toxicity and achieved higher response rates than the first study, but rather low compliance $rate(77\%)$ in this study is worrisome. We need to improve nutritional support during treatment and to use G-CSF to improve leukopenia and if necessary. supportive care will be given as in patients, Longer follow-up and larger sample size is needed to observe survival advantage.

• Journal of Radiation Protection and Research
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• v.15 no.2
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• pp.27-39
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• 1990

Appreciable radiation exposures certainly were occurred in the reactor burn-up, the nuelear fall-out and the surroundings of nuclear installations with radioactive effluents. Therefore, radioactive nuclides is not only potentially hazardous to workers of nuclear power plants and related industrials, but also the wokers who handle radioactive nuclides in biochemical research and nuclear medicine diagnostics. And in the case of occurring the nuclear accidents, the early medical treatment of radiation injury should be necessary but little is established medical procedures to decontaminate the victims of internal contamination of radioactive nuclides in korea. Accordingly, to achieve the basic data for protective roles and medical treatment of radiation injury, the present studies were carrid out to evaluate the decontamination of uranium by the chemical drugs. The results observed were summarized as follows: 1. The combined treatmet group of sodium bicarbonate and saline with uranyl nitrate injection simultaneously and the dithiothreitol group that was administered 30 minutes after uranyl nitrate injection were increased significantly in the change of body weight than uranyl nitrate-only group (P<0.005). 2. All the experimental groups were increased the fluid intake and urine volume on the uranyl nitrate-induced acute renal failure. but the combined treatment group of sodium bicarbonate and saline with uranyl nitrate injection simultaneously and the dithiothreitol group that was administered 30 minutes after uranyl nitrate injection have the higher increment of fluid intake and urine volume (P<0.05). 3. When sodium bicarbonate and saline was treated with uranyl nitrate injection simultaneously. and dithiothreitol was administered 30 minutes after uranyl nitrate injection. there was significantly reduced in BUN concentration (P<0.01). 4. When dithiothreitol was administered 30 minutes after uranyl nitrate injection. there was reduced more significantly on the increment of serum creatinine concentration than that observed in uranyl nitrate-only group(P<0.01). but when the combined treatment of sodium bicarbonate and saline with uranyl nitrate simultaneously, there was still. albeit much less marked. decrease in serum creatinine concentration. 5. The sodium bicarbonate and saline was treated with uranyl nitrate simultaneously and dithiothreitol was administered at 30 minutes after uranyl nitrate were excreted markedly higher urine creatinine concentration than the uranyl nitrate-only group. 6. Uranyl nitrate has been used in experimental animals to produce hydropic degeneration and swelling of proximal tubules, disappearance of microvilli and brush border or necrosis in the kidney and centrilobular necrosis, congestion, and telangiectasia of the liver. When the sodium bicarbonate and saline was treated with uranyl nitrate simultaneously, and dithiothreitol was administered. 30 minutes after uranyl nitrate, there was more marked the protective effect than uranyl nitrate-only group. Finally, if the sodium bicarbonate and saline may administered as quickly as possible each time that some risk for internal contamination, with uranium, and dithiothreitol is administered 30 minutes after uranium contamination, there ameliorates the course of uranyl nitrate-induced acute renal failure.and this effect is assocciated with prevention of uranium (heavy metal)-induced alterations in BUN, serum creatinine, urine creatinine, fluid intake, urine volume and body weight.

• Tuberculosis and Respiratory Diseases
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• v.51 no.6
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• pp.559-569
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• 2001

Background : Pleural effusion is one of the most common clinical manifestations associated with a variety of pulmonary diseases such as malignancy, tuberculosis, and pneumonia. However, there are no useful laboratory tests to determine the specific cause of pleural effusion. Therefore, an attempt was made to analyze the various types of pleural effusion and search for useful laboratory tests for pleural effusion in order to differentiate between the diseases, especially between a malignant pleural effusion and a non-malignant pleural effusion. Methods : 93 patients with a pleural effusion, who visited the Severance hospital from January 1998 to August 1999, were enrolled in this study. Ultrasound-guided thoracentesis was done and a confirmational diagnosis was made by a gram stain, bacterial culture, Ziehl-Neelsen stain, a mycobacterial culture, a pleural biopsy and cytology. Results : The male to female ratio was 56 : 37 and the average age was $47.1{\pm}21.8$ years. There were 16 cases with a malignant effusion, 12 cases with a para-malignant effusion, 36 cases with tuberculosis, 22 cases with a para-pneumonic effusion, and 7 cases with transudate. The LDH2 fraction was significantly higher in the para-malignant effusion group compared to the para-pneumonic effusion group [$30.6{\pm}6.4%$ and $20.2{\pm}7.5%$, respectively (p<0.05)] and both the LDH1 and LDH2 fraction was significantly in the para-malignant effusion group compared to those with tuberculosis [$16.4{\pm}7.2%$ vs. $7.6{\pm}4.7%$, and $30.6{\pm}6.4%$ vs.$17.6{\pm}6.3%$, respectively (p<0.05)]. The pleural effusion/serum LDH4 fraction ratio was significantly lower in the malignant effusion group compared to those with tuberculosis [$1.5{\pm}0.8$ vs. $2.1{\pm}0.6$, respectively (p<0.05)]. The LDH4 fraction and the pleural effusion/serum LDH4 fraction ratio was significantly lower in the para-malignant effusion group compared to those with tuberculosis [$17.0{\pm}5.8%$ vs. $23.5{\pm}4.6%$ and $1.3{\pm}0.4$ vs. $2.1{\pm}0.6$, respectively (p<0.05)]. Conclusion : These results suggest that the LDH isoenzyme was the only useful biochemical test for a differential diagnosis of the various diseases. In particular, the most useful test was the pleural effusion/serum LDH4 fraction ratio to distinguish between a para-malignant effusion and a tuberculous effusion.