• Radiation Oncology Journal
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• v.22 no.1
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• pp.40-54
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• 2004

Purpose : Captopril (angiotension converting enzyme inhibitor) is known to have a radioproptective effect in the lungs, intestines and skin, but its effect in the heart is unclear. To investigate the radioprotectlve efiect and mechanism of captopril on the heart, the histopathological changes and immunohistochemical stains were compared with radiation alone, and radiation combined with captopril, in the rats. Materials and Methods : The histopathological changes and immunohistochemical stains ($TNF{\alpha}$, $TGF{\beta}1$, PDGF and FGF2) were examined in the radiation alone and the combined captopril and radiation groups, 2 and 8 weeks after irradiation. Each group consisted of 8 to 10 rats (Sprague-Dawley). Irradiation (12.5 Gy) was given to the left hemithorax in a single fraction. Captopril (50 mg/Kg/d) mixed with water, was given orally and continuously from the first week prior to, up to the 8th week of the experiment. Results : In the radiation alone group, the ventricle at 2 weeks after irradiation showed prominent edema (p=0.082) and fibrin deposit (p=0.018) compared to the control group. At 8 weeks, the edema was decreased and fibrosis increased compared to those at 2 weeks. The histopathological changes of the combined group were similar to those of the control group, due to the reduced radiation toxicity at 2 and 8 weeks. The endocardial fibrin deposit (p=0.047) in the atrium, and the interstitial fibrin deposit (p=0.019) and edema (p=0.042) of the ventricle were reduced significantly in the combined group compared to those in the radiation alone group at 2 weeks. The expressions of $TNF-{\alpha}$, $TGF-{\beta}1$, PDGF and FGF-2 in the radiation alone group were more increased than in the control group, especially in the pericardium and endocardium of the atrium at 2 weeks. At 8 weeks, the pericardial $TNF-{\alpha}$ and $TGF-{\beta}1$ in the radiation alone group continuously increased. The expressions of $TNF-{\alpha}$, $TGF-{\beta}1$ and PDGF were decreased in the combined group at 2 weeks. At 8 weeks, the expressions of $TNF-{\alpha}$ in the atrial and ventricular pericardia were markedly reduced (p=0.049, p=0.009). Conclusion : This study revealed that the early heart damage induced by radiation can be reduced by the addition of captopril in a rat model. The expressions of $TNF-{\alpha}$, $TGF-{\beta}1$ and PDGF were further decreased in the combined compared to the radiation alone group at both 2 and 8 weeks. From these results, it may be concluded that these cytokines probably play roles in the radioprotective mechanism of captopril from the radiation-induced heart toxicity, similarly to in other organs.

• Radiation Oncology Journal
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• v.22 no.1
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• pp.17-24
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• 2004

Purpose: To evaluate the treatment outcomes after postmastectomy radiotherapy (PMRT) and chemotherapy in patients with breast cancer. Materials and Methods: The PMRT were retrospectively analyzed in 83 patients with stage II-III female breast cancer treated between 1989 and 1995. The median age was 46 years (range, 23-77): Seventy-seven patients had modified radical mastectomies, 5 radical mastectomies and 1 simple mastectomy. Three patients ($4\%$) had pathologically negative axillae, and the remaining 80 ($96\%$) had positive axillae. Eleven, 23, 44 and 5 patients had pathological stages IIA, IIB, IIIA, and IIIB, retrospectively. Eighty ($96\%$) patients were treated with hockey-stick fields. The median dose of PMRT was 50.4 ey, in 1.8 Gy fractions. Adjuvant systemic chemotherapy was given to 74 patients ($89\%$). CMF-based or doxorubicin-containing regimens were given to 54 patients ($55\%$). The median follow-up time was 82 months (range, 8-171) after the mastectomy. Results: The 5 and 10-year overall survival rates for all patients were 65 and $49\%$, respectively. The univariate and multivariate analyses of the factors affecting the overall survival revealed the stage to be the most significant prognostic factor (p=0.002), followed by the combination of chemotherapy. Thirteen patients $16\%$ developed a LRF, at an interval of 4-84 months after radiotherapy, with a median of 20 months. The only significant prognostic factor affecting LRF was the combination of chemotherapy, in both the univariate and multivariate analyses. With respect to the sequence of chemoradiation, the sequence had no saatistical significance (p=0.90). According to the time interval from mastectomy to the onset of radiotherapy, the LRFR of the patients group treated by RT within or after 6 month postmastectomy 6 months were 14 vs. $27\%$ respectively (p=0.24). One third of the pa41en1s (26/83) developed distant metastasis, in 2-92 months, after radiotherapy, with a median of 21 months. The most commonly involved site was bone in 13 cases. The pathological staging was the only significant prognostic factor in both the univariate and multivariate analyses that affected distant failure. Radiological finding of radiation pneumonitis on a simple chest x-ray was shown in $20\%$ (17/83), with a time interval ranging from 2 to 7 months post-radiotherapy, with a median of 3 months. The stable lung fibrosis settled in 11 patients ($65\%$). Conclusion: It was concluded through this analysis that the combination of PMRT with in chemotherapy resulted in better overall survival and local control than PMRT alone in patients needing PMRT.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.823-834
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• 1998

Background: Chronic inhalation of silica induces the lung fiborsis. The alveolar macrophages ingest the inhaled silica; they liberate the pro-inflammatory cytokines such as IL-1$\beta$, IL-6, TNF-$\alpha$ and fibrogenic cytokines, TGF-$\beta$ and PDGF. Cytokines liberated from macrophage have pivotal role in pulmonary fibrosis. There is a complex cytokine network toward fibrosis. However, the exact roles and the interaction among the proinflammatory cytokines and TGF-$\beta$, a fibrogenic cytokine, have not been defined, yet. In this study, we investigated silica induced IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$ production and the effect of IL-1$\beta$, IL-6, TNF-$\alpha$ on the production of TGF-$\beta$ from lung macrophages of Balb/C mice. Method: We extracted the lung of Balb/C mice and purified monocytes by Percoll gradient method. Macrphages were stimulated by silica ($SiO_2$) in the various concentration for 2, 4, 8, 12, and 24 hours. The supernatants were used for the measurement of protein levels by bioassay, and cells for the levels of mRNA by in situ hybridization. Results: The production of IL-6 was not observed till 4 hours, and reached the peak levels at 8 hours after stimulation of silica. The production of TNF-$\alpha$ increased from 2 hours and reached the peak levels at 4 hours after stimulation of silica. The spontaneous TGF-$\beta$ production reached the peak levels at 24 hours. TNF-$\alpha$ upregulated the silica induced TGF-$\beta$ production. Silica induced TGF-$\beta$ production was blocked by pretreated anti-TNF-$\alpha$ antibody. In situ hybridization revealed the increased positive signals at 4 hours in IL-6, at 4 hours TNF-$\alpha$ and 12 hours in TGF-$\beta$. Conclusion: The results above suggest that silica induced the sequential production of IL-6, 1NF-$\alpha$ and TGF-$\beta$ from macrophages and TNF-$\alpha$ upregultaes the production of TGF-$\beta$ from silica-induced macrophages.

• Tuberculosis and Respiratory Diseases
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• v.47 no.6
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• pp.775-785
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• 1999

Background : Though surgery plays an important role in the management of patients with Mycobacterium tuberculosis infection, there is little information regarding the timing of resection. We tried to find out the ideal timing of operation. Method: A retrospective review was performed in 69 patients underwent pulmonary resection for pulmonary tuberculosis between January 1993 and December 1997. They were categorized into various groups according to the length of preoperative specific drug therapy. The rates of treatment failure, realpse and complication in each group were compared statistically by $x^2$-test. Results: Eighty one point two percent were men and 18.8 % women with a median age of 33 years(range, 16 to 63 years). The mean number of resistant drugs was 3.l(range, 0 to 9). Patients were treated preoperatively with multidrug regimens, which mean number of preoperative specific drugs was 4.6, in an effort to reduce the mycobacterial burden with the mean length of preoperative drug therapy, 5.0 months. Postoperative treatment was conducted for a mean period of 13.0 months with a mean number of postoperative specific drugs, 4.4. Postoperative treatment failures were confirmed in 8 among 69 patients(11.6%). 2 of these 8 patients were showed up in the preoperative 3 to 4 months medication group and each of the rest was occurred in the preoperative 2 to 3, 5 to 6, 6 to 7, 12 to 13, 17 to 18 months, less than one month medication group, respectively. 59 of 69 patients were available for evaluation of the relapse rate with the mean duration of the postoperative follow-up, 19.8 months. In 4 patients bacterial relapse was confirmed(6.8%). Each of these 4 was in the preoperative 1 to 2, 2 to 3, 3 to 4, 5 to 6 months medication group. Categorized into various groups according to the length of preoperative specific therapy, there were no statistical significances of the treatment failure rate, relapse rate and complication rate in the groups. There were seven treatment failures of 28 who were AFB culture positive until the time of operation(25%, p<0.01). Categorized the preoperative AFB culture positive group into various groups according to the length of preoperative drug therapy, there were no statistical significances, either. Conclusion: We believe that operation plays an important ancillary role in the treatment of pulmonary tuberculosis. Our results indicate that the timing of resection according to the length of preoperative drug therapy may not cause trouble.

• Journal of Hospice and Palliative Care
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• v.6 no.1
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• pp.22-33
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• 2003

Purpose : The purpose of this study was to evaluate the present status of patients' satisfaction and the reasons for any satisfaction or dissatisfaction in cancer pain management Methods : A cross-sectional survey was used to obtain the feedback about pain management. The results of the survey were collected from 59 in- or out-patient who had cancer treatment at two of the teaching hospitals in Seoul from July, 2002 to November, 2002. The data was obtained by a structured questionnaire based on the American Cancer Society Patient Outcome Questionnaire(APS-POQ) and other previous research. The clinical information for all patients were compiled by reviewing their medical records. Resuts : 1) The subjects' mean score of the worst pain was 6.77, the average pain score was 3.80, and the pain score after management was 2.93 for the past 24 hours. The mean score of total pain interference was $25.03{\pm}12.82$. Many of the subjects had false beliefs about pain such as 'the experience of pain is a sign that the illness has gotten worse', 'pain medicine should be 'saved' in case the pain gets worse' and 'people get addicted to pain medicine easily'. 2) 66.1% of the subjects were properly medicated with analgesics. 33.9% of the subjects reported use of various methods in controlling pain other than the prescribed medication. Only 33.9% of the subjects had a chance to be educated about pain management by doctors or nurses. 3) The mean score of patients' satisfaction with pain management was $4.19{\pm}1.14$. 72.9% of the subjects answered 'satisfied' with pain management. The reasons for dissatisfaction were 'the pain was not relieved even after the pain management', 'I was not quickly and promptly treated when I complained of pain', 'doctors and nurses didn't pay much attention to my complaints of pain.', and 'there was no appropriate information given on the methods of administration, effect duration and side effects of pain medicine.' The reasons for satisfaction were: 'the pain was relieved after the pain management.', 'doctors and nurses quickly and promptly controlled my pain.', 'doctors and nurses paid enough attention to my complaints of pain.' and 'trust in my physician'. 4) In pain severity or pain interference, no significant difference was found between the satisfied group and dissatisfied group. On the belief 'good patients avoid talking about pain', a significant difference was found between the satisfied group and dissatisfied group. Conclusions : The patients' satisfaction with cancer pain management has increased over the years but still about 30% of patients reported to be 'not satisfied' for various reasons. The results of this study suggest that patients' education should be done to improve satisfaction in the pain management program.