• The Journal of Korean Society for Radiation Therapy
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• v.27 no.2
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• pp.157-166
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• 2015

Purpose : Cyber-Knife tumor tracking system, based on the correlation relationship between the position of a tumor which moves in response to the real time respiratory cycle signal and respiration was obtained by the LED marker attached to the outside of the patient, the location of the tumor to predict in advance, the movement of the tumor in synchronization with the therapeutic device to track real-time tumor, is a system for treating. The purpose of this study, in the cyber knife tumor tracking radiation therapy, trying to evaluate the accuracy of tumor tracking radiation therapy system due to the change in the form of unpredictable sudden breathing due to cough and sleep. Materials and Methods : Breathing Log files that were used in the study, based on the Respiratory gating radiotherapy and Cyber-knife tracking radiosurgery breathing Log files of patients who received herein, measured using the Log files in the form of a Sinusoidal pattern and Sudden change pattern. it has been reconstituted as possible. Enter the reconstructed respiratory Log file cyber knife dynamic chest Phantom, so that it is possible to implement a motion due to respiration, add manufacturing the driving apparatus of the existing dynamic chest Phantom, Phantom the form of respiration we have developed a program that can be applied to. Movement of the phantom inside the target (Ball cube target) was driven by the displacement of three sizes of according to the size of the respiratory vertical (Superior-Inferior) direction to the 5 mm, 10 mm, 20 mm. Insert crosses two EBT3 films in phantom inside the target in response to changes in the target movement, the End-to-End (E2E) test provided in Cyber-Knife manufacturer depending on the form of the breathing five times each. It was determined by carrying. Accuracy of tumor tracking system is indicated by the target error by analyzing the inserted film, additional E2E test is analyzed by measuring the correlation error while being advanced. Results : If the target error is a sine curve breathing form, the size of the target of the movement is in response to the 5 mm, 10 mm, 20 mm, respectively, of the average $1.14{\pm}0.13mm$, $1.05{\pm}0.20mm$, with $2.37{\pm}0.17mm$, suddenly for it is variations in breathing, respective average $1.87{\pm}0.19mm$, $2.15{\pm}0.21mm$, and analyzed with $2.44{\pm}0.26mm$. If the correlation error can be defined by the length of the displacement vector in the target track is a sinusoidal breathing mode, the size of the target of the movement in response to 5 mm, 10 mm, 20 mm, respective average $0.84{\pm}0.01mm$, $0.70{\pm}0.13mm$, with $1.63{\pm}0.10mm$, if it is a variant of sudden breathing respective average $0.97{\pm}0.06mm$, $1.44{\pm}0.11mm$, and analyzed with $1.98{\pm}0.10mm$. The larger the correlation error values in both the both the respiratory form, the target error value is large. If the motion size of the target of the sine curve breathing form is greater than or equal to 20 mm, was measured at 1.5 mm or more is a recommendation value of both cyber knife manufacturer of both error value. Conclusion : There is a tendency that the correlation error value between about target error value magnitude of the target motion is large is increased, the error value becomes large in variation of rapid respiration than breathing the form of a sine curve. The more the shape of the breathing large movements regular shape of sine curves target accuracy of the tumor tracking system can be judged to be reduced. Using the algorithm of Cyber-Knife tumor tracking system, when there is a change in the sudden unpredictable respiratory due patient coughing during treatment enforcement is to stop the treatment, it is assumed to carry out the internal target validation process again, it is necessary to readjust the form of respiration. Patients under treatment is determined to be able to improve the treatment of accuracy to induce the observed form of regular breathing and put like to see the goggles monitor capable of the respiratory form of the person.

• Radiation Oncology Journal
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• v.27 no.3
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• pp.126-132
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• 2009

Purpose: We wanted to evaluate the prognostic factors for the pathologic N2 non-small cell lung cancer (NSCLC) patients who were treated by postoperative radiotherapy. Materials and Methods: We retrospectively reviewed 112 pN2 NSCLC patients who underwent surgery and postoperative radiotherapy (PORT) From January 1999 to February 2008. Seventy-five (67%) patients received segmentectomy or lobectomy and 37 (33%) patients received pneumonectomy. The resection margin was negative in 94 patients, and it was positive or close in 18 patients. Chemotherapy was administered to 103 (92%) patients. Nine (8%) patients received PORT alone. The median radiation dose was 54 Gy (range, 45 to 66), and the fraction size was 1.8~2 Gy. Results: The 2-year overall survival (OS) rate was 60.2% and the disease free survival (DFS) rate was 44.7% for all the patients. Univariate analysis showed that the patients with multiple-station N2 disease had significantly reduced OS and DFS (p=0.047, p=0.007) and the patients with an advanced T stage ($\geq$T3) had significantly reduced OS and DFS (p<0.001, p=0.025). A large tumor size ($\geq$5 cm) and positive lymphovascular invasion reduced the OS (p=0.035, 0.034). Using multivariate analysis, we found that multiple-station N2 disease and an advanced T stage ($\geq$T3) significantly reduced the OS and DFS. Seventy one patients (63.4%) had recurrence of disease. The patterns of failure were loco-regional in 23 (20.5%) patients, distant failure in 62 (55.4%) and combined loco-regional and distant failure in 14 (12.5%) patients. Conclusion: Multiple involvement of mediastinal nodal stations for the pN2 NSCLC patients with PORT was a poor prognostic factor in this study. A prospective study is necessary to evaluate the N2 subclassification and to optimize the adjuvant treatment.

• The Korean Journal of Pain
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• v.1 no.1
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• pp.34-46
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• 1988

Intractable pain from advanced carcinoma of the upper abdomen is difficult to manage. One method used to control pain associated with these malignancies is to block off the splanchnic nerve. In 1919 Kappis described a technique by which the splanchnic nerve of the upper abdomen could be anesthetized, using a percutaneous injection. This method has been used for the relief of upper abdominal pain due to hematoma and cancer of the pancreas, stomach, gall bladder, bile duct, and colon. During the Period from November 1968 to January 1986, this method was used in 208 cases of malignancy at Severance Hospital and clinically evaluated. Patients were retroactively grouped according to the stage of development of technique used. Twelve patients who received the treatment in the period from November 1968 to March 1977 were designate4i as group 1, 26 patients from April 1977 to April 1979 as group 2, and 170 from May 1979 to January 1986 as group 3. The results are as follows: 1) The number of patients receiving splanchnic nerve block has been increasing since 1977. 2) A total of 208 patients, including 133 males and 75 females, ranging in age from 18 to 84 and averaging 51. 3) The causes of pain were stomach cancer 90, pancreatic cancer 69, and miscellaneous cancer 49 cases respectively. 4) There were 57.7% who had surgery. and 3.7% of whom had chemotherapy before the splanchnic nerve block was done. 5) These blocks were carried out with the patient in the prone position as described by Dr. Moore. For group 2 and 3, C-arm image intensifier was used. In group 1, a 22 gauze loom long needle was inserted at the lower border of the 12th rib on each aide about 7\;cm from the midline. The average distance from the midline was $6.60{\pm}0.61\;cm$ on the left side and $6.60{\pm}0.83\;cm$ on the right side in group 2, and $5.46{\pm}0.76\;cm$ on the left side and $5.49{\pm}0.69\;cm$ on the right side in group 3. The average depth to which the needle was inserted was $8.60{\pm}0.52\;cm$ on the left side and $8.74{\pm}0.60\;cm$ on the right side in group 2, and $8.96{\pm}0.63\;cm$ on the left side and $9.18{\pm}0.57\;cm$ on the right side in group 3. 6) The points of the inserted needles were positioned in the upper quarter anteriorly, 51.8% on the left side and 54.4% n the right side of the L1 vertebra by lateral roentgenogram in group 3. The inserted needle points were located in the upper and anterolateral part, of the L1 vertebra 68.5% on the left side and 60.6won the right side, on the anteroposterior rentgenogram in group 3. The needle tip was not advanced beyond the anterior margin of the vertebral body. 7) In some case of group 3, contrast media was injected before the block was done. It shows, the spread upward along the anterior mal gin of the vertebral body. 8) The concentration and the average amount of drug used in each group was as follows: In group 1, $39.17{\pm}6.69\;ml$ of 0.5% -l% lidocaine or 0.25% bupivacaine were injected for the test block and one to three days after the test block $40.00{\pm}4.26\;ml$ of 50% alcohol was injected for the semipermanent block. In group 2, $13.75{\pm}4.88\;ml$ of 1% lidocaine were used as the test block and followed by $46.17{\pm}4.37\;ml$ of 50% alcohol was injected as the semipermanent block. In group 3, $15.63{\pm}1.19\;ml$ of 1% lidocaine for test block followed by $15.62{\pm}1.20\;ml$ of pure alcohol and $16.05{\pm}2.58\;ml$ of 50% alcohol for semipermanent block were injected. 9) The result of the test block was satisfactory in all cases. However the semipermanent block was 83.3 percent of the patients in group 1 who received relief from pain for at least 2 weeks after the block, 73.1% in group 2, and 91.8% in group 3. In these unsuccessful cases, 2 cases in group 1 were controlled by narcotics but 7 cases in group 2 and 14 cases in group 3 received the same splanchnic nerve block 1 or 2 times again within 2 weeks. But, in some cases it was 3 to i months before the 2nd block and in 1 cases even 7 years. 10) The most common complications of splanchnic nerve block were hypotensino(25.5%) occasional flushing of the face, nausea, vomiting, and chest discomfort. 11) For the patients in group 3, the supplemental block most commonly used was a continuous epidural block; it was used as a diagnostic block and to afford relief from pain before the splanchnic nerve block was done. 12) The interval between the receiving of the alcohol block and discharge was from 5 to 8 days in 61 cases(31.1%) and from 1 to 2 days in 48 cases(24.5%). From the above results, it can be concluded that the splanchnic nerve block done in the prone position with pure and 50% alcohol immediately after an effective test block with 1% lidocaine under C-arm fluoroscopic control is satisfactory and reliable. How to minimize the repeat block is still a problem to be solved.

• Tuberculosis and Respiratory Diseases
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• v.42 no.6
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• pp.855-861
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• 1995

Background: Parathyroid hormone-related protein(PTHrp) was first identified as the cause of hypercalcemia in malignancy. Hypercalcemia can be found in malignancy, especially in the epidermoid carcinoma of the lung, even without extensive metastases to the bones. The application of sensitive assays for PTHrp may help in the early diagnosis of lung cancer, in the monitoring of treatment and in the detection of recurrence. Method: Serum PTHrp was measured by radioimmunoassay detecting the N-terminal 1~34 peptide of human PTHrp(PTHrp 1-34) in 63 histologically confirmed lung cancer patients and 22 healthy controls. Result: Serum PTHrp(mean$\pm$S.E.) was $312{\pm}68.9pg/ml$ in 63 lung cancer patients and $158{\pm}38.2pg/ml$ in 22 controls(p>0.05). PTHrp was $356{\pm}103.9pg/ml$ in 34 epidermoid carcinoma patients, $281{\pm}148.7pg/ml$ in 15 adenocarcinoma patients and $316{\pm}140.8pg/ml$ in 9 small cell carcinoma patients. In epidermoid carcinoma patients, PTHrp was $570{\pm}472.3pg/ml$ in stage II(n=3; p<0.05 vs controls), $166{\pm}22.4pg/ml$ in stage IIIa(n=9), $282{\pm}113.3pg/ml$ in stage IIIb(n=12) and $668{\pm}367.9pg/ml$ in stage IV(n=9; p<0.05 vs controls). PTHrp was significantly increased in 8 epidermoid carcinoma patients with bone metastases($1526{\pm}811.2\;pg/ml$; p<0.0005 vs controls). Hypercalcemia was observed in an epidermoid carcinoma patient whose PTHrp value was 244 pg/ml. Conclusion: The serum PTHrp was increased in advanced epidermoid carcinoma patients even without hypercalcemia. The measurement of PTHrp may be not helpful in the early diagnosis of lung cancer. But the lung cancer should be suspected in the marked elevation of PTHrp. It may be of value in detecting patients of advanced diseases with bone metastases or patients who might develop the malignancy associated hypercalcemia.

• Radiation Oncology Journal
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• v.23 no.3
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• pp.186-193
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• 2005

Purpose: To improve the management of a medical linear accelerator, the records of operational failures of a Varian CL2l00C over a ten year period were retrospectively analyzed. Materials and Methods: The failures were classified according to the involved functional subunits, with each class rated Into one of three levels depending on the operational conditions. The relationships between the failure rate and working ratio and between the failure rate and outside temperature were investigated. In addition, the average life time of the main part and the operating efficiency over the last 4 years were analyzed. Results: Among the recorded failures (total 587 failures), the most frequent failure was observed in the parts related with the collimation system, including the monitor chamber, which accounted for $20\%$ of all failures. With regard to the operational conditions, 2nd level of failures, which temporally interrupted treatments, were the most frequent. Third level of failures, which interrupted treatment for more than several hours, were mostly caused by the accelerating subunit. The number of failures was increased with number of treatments and operating time. The average life-times of the Klystron and Thyratron became shorter as the working ratio increased, and were 42 and $83\%$ of the expected values, respectively. The operating efficiency was maintained at $95\%$ or higher, but this value slightly decreased. There was no significant correlation between the number of failures and the outside temperature. Conclusion: The maintenance of detailed equipment problems and failures records over a long period of time can provide good knowledge of equipment function as well as the capability of predicting future failure. Wore rigorous equipment maintenance Is required for old medical linear accelerators for the advanced avoidance of serious failure and to improve the qualify of patient treatment.

• Journal of Korean Society of Environmental Engineers
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• v.35 no.12
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• pp.889-896
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• 2013

Advanced Oxidation Processes (AOP) have been interested for removing micropollutants in water. Most of water treatment plants (WTPs) located along the lower part of Nakdong River have adopted the $O_3/BAC$ process and have interesting in peroxone process a kind of AOP. This study evaluated the removal characteristics of residual hydrogen peroxide ($H_2O_2$) combining with the biofiltration process in the next BAC process when the hydrogen peroxide is applied for the WTP operating $O_3/BAC$ process. In the experiment, changing the temperature and the concentration of $H_2O_2$ of influent, the biofiltration process showed rapidly dropped the biodegradability when the $H_2O_2$ concentration was increased and lowered water temperature while BAC process maintained relatively stable efficiency. The influent fixed at $20^{\circ}C$ and the concentration of $H_2O_2$ at 300 mg/L was continuously input for 78 hours. Most of the $H_2O_2$ in the influent did not remove at the biofiltration process controlled 5 to 15 minutes EBCT condition after 24~71 hours operating time while BAC process controlled 5 to 15 minutes EBCT showed 38~91% removal efficiency condition after 78 hours operating time. Besides, after 78 hours continuously input experiment, the biomass and activity of attached bacterial on the biofilter and BAC were $6.0{\times}10^4CFU/g$, $0.54mg{\cdot}C/m^3{\cdot}hr$ and $0.4{\times}10^8CFU/g$, $1.42mg{\cdot}C/m^3{\cdot}hr$ respectively. These biomass and activity values were decreased 99% and 72% in biofilter and 68% and 53% in BAC compared with initial condition. The biodegradation rate constant ($k_{bio}$) and half-life ($t_{1/2}$) in BAC were decreased from $1.173min^{-1}$ to $0.183min^{-1}$ and 0.591 min to 3.787 min respectively according to increasing the $H_2O_2$ concentration from 10 mg/L to 300 mg/L at $5^{\circ}C$ water temperature and the $k_{bio}$ and $t_{1/2}$ were $1.510min^{-1}$ to $0.498min^{-1}$ and 0.459 min to 1.392 min at $25^{\circ}C$ water temperature. By increasing the water temperature from $5^{\circ}C$ to $15^{\circ}C$ or $25^{\circ}C$, the $k_{bio}$ were increased 1.1~2.1 times and 1.3~4.4 times. If a water treatment plant operating $O_3/BAC$ process is considering the hydrogen peroxide for the peroxone process, post BAC could effectively decrease the residual $H_2O_2$, moreover, in case of spilling the $H_2O_2$ into the water process line, these spilled $H_2O_2$ concentration can be able to decrease by increasing the EBCT at the BAC process.

• Radiation Oncology Journal
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• v.21 no.2
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• pp.125-134
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• 2003

Purpose: To report the early results of preopeartive concurrent radio-chemotherapy (CRCT) for treating rectal cancer. Materials and Methods: From June 1999 to April 2002, 40 rectal cancer patients who either had lesions with a questionable resectability or were candidates for sphincter-sacrificing surgery received preoperative CRCT. Thirty-seven patients completed the planned CRCT course. 45 Gy by 1.8 Gy daily fraction over 5 weeks was delivered to the whole pelvis in the prone position. The chemotherapy regimens were oral UFT plus oral leucovorin (LV) in 12 patients, intravenous bolus 5-FU plus LV in 10 patients, and intravenous 5-FU alone in 15 patients (bolus infusion in 10, continuous infusion in 5). Surgery was planned in 4$\~$6 weeks of the completion of the preoperative CRCT course, and surgery was attempted in 35 patients. Results: The compliance to the current preoperative CRCT protocol was excellent, where 92.5$\%$ (37/40) completed the planned treatment. Among 35 patients, in whom surgery was attempted after excluding two patients with new metastatic lesions in the liver and the lung, sphincter-preservation was achieved in 22 patients (62.9$\%$), while resection was abandoned during laparotomy in two patients (5.7$\%$). Gross complete resection was peformed in 30 patients, gross incomplete resection was peformed in one patient, and no detailed information on the extent of surgery was available in two patients. Based on the surgical and pathological findings, the down-staging rate was 45.5$\%$ (15/33), and the complete resection rate with the negative resection margin 78.8$\%$ (26/33). During the CRCT course, grade 3 $\~$4 neutropenia developed in four patients (10.8$\%$). Local recurrence after surgical resection developed in 12.1$\%$ (4/33), and distant metastases after the preoperative CRCT start developed in 21.6$\%$ (8/37). The overall 3-years survival rate was 87$\%$. Conclusion: Preoperative CRCT in locally advanced rectal cancer is well tolerated and can lead to high resection rate, down-staging rate, sphincter preservation rate, however, longer term follow-up will be necessary to confirm these results.

• 한국유가공학회:학술대회논문집
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• 2007.09a
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• pp.49-58
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• 2007

Inflammatory process leads to the well-known mucosal damage and therefore a further disturbance of the epithelial barrier function, resulting abnormal intestinal wall function, even further accelerating the inflammatory process[1]. Despite of the records, etiology and pathogenesis of IBD remain rather unclear. There are many studies over the past couple of years have led to great advanced in understanding the inflammatory bowel disease(IBD) and their underlying pathophysiologic mechanisms. From the current understanding, it is likely that chronic inflammation in IBD is due to aggressive cellular immune responses including increased serum concentrations of different cytokines. Therefore, targeted molecules can be specifically eliminated in their expression directly on the transcriptional level. Interesting therapeutic trials are expected against adhesion molecules and pro-inflammatory cytokines such as TNF-${\alpha}$. The future development of immune therapies in IBD therefore holds great promises for better treatment modalities of IBD but will also open important new insights into a further understanding of inflammation pathophysiology. Treatment of cytokine inhibitors such as Immunex(Enbrel) and J&J/Centocor(Remicade) which are mouse-derived monoclonal antibodies have been shown in several studies to modulate the symptoms of patients, however, theses TNF inhibitors also have an adverse effect immune-related problems and also are costly and must be administered by injection. Because of the eventual development of unwanted side effects, these two products are used in only a select patient population. The present study was performed to elucidate the ability of TNF-${\alpha}$ antibodies produced in sheep colostrums to neutralize TNF-${\alpha}$ action in a cell-based bioassay and in a small animal model of intestinal inflammation. In vitro study, inhibitory effect of anti-TNF-${\alpha}$ antibody from the sheep was determined by cell bioassay. The antibody from the sheep at 1 in 10,000 dilution was able to completely inhibit TNF-${\alpha}$ activity in the cell bioassay. The antibodies from the same sheep, but different milkings, exhibited some variability in inhibition of TNF-${\alpha}$ activity, but were all greater than the control sample. In vivo study, the degree of inflammation was severe to experiment, despite of the initial pilot trial, main trial 1 was unable to figure out of any effect of antibody to reduce the impact of PAF and LPS. Main rat trial 2 resulted no significant symptoms like characteristic acute diarrhea and weight loss of colitis. This study suggested that colostrums from sheep immunized against TNF-${\alpha}$ significantly inhibited TNF-${\alpha}$ bioactivity in the cell based assay. And the higher than anticipated variability in the two animal models precluded assessment of the ability of antibody to prevent TNF-${\alpha}$ induced intestinal damage in the intact animal. Further study will require to find out an alternative animal model, which is more acceptable to test anti-TNF-${\alpha}$ IgA therapy for reducing the impact of inflammation on gut dysfunction. And subsequent pre-clinical and clinical testing also need generation of more antibody as current supplies are low.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.871-881
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• 1996

Objective: In the early short-term therapy of pulmonary tuberculosis, PZA is used for the first two months on 6EHRZ therapy but PZA is not effective in the case of long-tenn use PZA for retreatment in the sensitive relapse or acquired drug resistance for PZA. But in the endemic area as Korea, if we can't use PZA in the retreatment of pulmonary tuberculosis, we can't expect the success for retreatment of pulmonary tuberculosis, therefore we need new drugs substituting for PZA. In these days, 4 - fluoroquinolone derivatives were investigated and only ofloxacin and ciprofloxacin of derivatives were known to be effective but the effectiveness was also not certain because the result was experimental or combined with other bacteriocidal drugs and datas on effectiveness of pulmonary tuberculosis were so little. Therefore these drugs should be use with other two or three strong-acting drugs in the last period of retreatment of pulmonary tuberculosis. The ofloxacin or ciprofloxacin is used in some area in Korea but randomly and needed more study. We did this study for proving the effectiveness of these drugs and establishment of retreatment regimen for pulmonary tuberculosis. Methods: Retrospective cohort study of 83 drug-resistant pulmonary tuberculosis patients at National Masan Tuberculosis Hospital from Jan. 1994 to dec. 1995 was made. All the patients taken medicine for 2nd ami-tuberculosis regimens for the first lime. We separated the patients by two groups.(Group I : OFX+ PTA + CS+PAS + Injection, Group II: PZA + PTA+ CS + PAS + Injection). We compared the difference between two groups and tested the confidence limit about results after treatment by $\chi$2-test and T-test. Results : 1. The age distribution was most frequent in fourth decade(29.2% in Group I, 37.1% in Group II) and the mean age was 43.9 year in Group I, and 39.0 year in Group II, but had no significant difference between two groups. The sex distribution was more frequent in the males(68.8% in Group I, 85.7% in Group II), but had no significant difference. 2. Family history was 29.2% in Group I, 28.6% in Group II, but had no significant difference. 3. In the respect of extent of disease, far-advanced stare was 60.4% in Group I, 74.3% in Group II, but had no significant difference. 4. The side effects for drugs showed in 58.3% in Group I and 65.7% in Group II, and the gastrointestinal trouble showed 25.0% in Group and arthralgia 34.3% in Group II predominantly respectively and had the significant difference(p<0.05). 5. The negative conversion rate on sputum AFB smear was 87.5% in Group I and 80.0% in Group II, but had no significant difference. But the negative conversion rate on sputum AFB culture was 83.3% in Group I and 57.1 % in Group II and had the significant difference(p<0.05). 6. The success rate of treatment was 87.5 % in Group I and 83.3 % in Group II but had no significant difference. Conclusion : In the retreatment of pulmonary tuberculosis, ofloxacin is useful drug for the patients who are not available to use PZA and can be use effectively substituting for PZA.

• Journal of the Korean Chemical Society
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• v.37 no.2
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• pp.237-243
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• 1993

The primary and secondary structure of the 5S rRNA isolated from Xanthomonas celebensis were determined by enzymatic and chemical degradation methods. It consists of 119 nucleotides and contains no modified nucleosides. As with the 5S rRNAs of X. maltophilia and X. citri, it contains an additional uridine residue on the 5'-terminus. Its secondary structure was almost identical to the models previously proposed by us for the 5S rRNA of two Xanthomonas species. Its secondary structure consists of five helices, five loops and two bulges. The tertiary interactions in the 5S rRNA molecule were analyzed by Fe(II)-EDTA treatment and hybridization method using deoxyhexamer. From the fact that some adenine residues in loop M, region $I_1-C$, loop $H_1$, and loop $H_2$ become susceptible to diethylpyrocarbonate when the 5S rRNA was hybridized with deoxyhexamer complementary to the sequence $U_{35}CCCAU_{40}$ and that some nucleotide residues in loop M, loop $H_1$ and region $D-I_2$ become resistant Fe(II)-EDTA cleavage in the presence of $Mg^{2+}$, it is presumed that loops $H_1$ and $H_2$ interact with loop M in some way. In the tertiary interaction, the regions $I_1-C$ and $D-I_2$ seem to act as hinges in folding the stems $B-I_1-C$ and $D-I_2-E.$ It was found that loop $H_1$ changes into a smaller loop of three bases by forming noncanonical A : C base-pairs ih acidic environment.