• Title/Summary/Keyword: bone disease

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Effects of Fructus and Semen from Rosa rugosa on Osteoimmune cells (해당화의 과육 및 종자 추출물이 골형성 관련 세포에 미치는 영향)

  • Kang, Se-Chan;Lim, Jung-Dae;Lee, Jae-Cheol;Park, Hye-Jin;Kang, Nam-Sung;Sohn, Eun-Hwa
    • Korean Journal of Plant Resources
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    • v.23 no.2
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    • pp.157-164
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    • 2010
  • Rosa rugosa has been used as a folk medicine with various pharmacological properties for a long time in Asia. We investigated effects of fructus extracts of Rosa rugosa (RRF) and semen extracts of this herb (RRS) on bone forming cells (osteoblastic and pre-osteoclastic cells) to evaluate the pharmacological possibilities in a variety of bone-related disease. RRF showed significant effect on proliferation of osteoblastic cells in dose-dependent manners at 72 hrs and $100\;{\mu}g/m{\ell}$ of RRS was effective at 48 and 72 hrs. RRF and RRS did not decreased production of TNF-$\alpha$ but NO by pre-osteoclastic cells under inflammation circumstance indeced by LPS. We also investigated the effects of RRF and RRS on the mitogen-induced lymphocyte proliferation in the old and young mice in ex vivo systems. RRF and RRS significantly enhanced proliferative effects of untreated and ConA-treated splenocytes from the old and young mice. But, RRS at $500\;{\mu}g/m{\ell}$ increased LPS-induced TNF-$\alpha$ production in pre-osteoclastic cells and reduced LPS-stimulated lymphoblastogenesis in the old and young at $1000\;{\mu}g/m{\ell}$. These results indicate that RRF has beneficial effects on osteoarthritis and give further possibilities for the immunomodulating effects not only in old that has more frequent bone related diseases but also in young.

The Analysis of Post Operative Treatment of Malignant Melanoma Using High Dose Interferon-${\alpha}2b$ Immunotherapy: Preliminary Report (악성흑색종 환자군에서 수술적 치료 후 시행한 고용량 인터페론-${\alpha}2b$ 면역요법에 의한 보조적 치료 결과 분석: 예비보고)

  • Chung, So Hak;Jo, Hyun Ik
    • The Journal of the Korean bone and joint tumor society
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    • v.18 no.2
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    • pp.78-82
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    • 2012
  • Purpose: Interferon-${\alpha}2b$ using immunotherapy of malignant melanoma is known to increase the microscopic enemies that remain after surgical resection of the tumor to prevent recurrence, disease-free survival and overall survival. Authors in patients with malignant melanoma after surgical resection and high-dose interferon-${\alpha}$ immunotherapy treated group of disease-free survival and overall survival compared with the results of the treatment of immune therapy to a preliminary report. Materials and Methods: From February 2010 to October 2012 at our institution between being diagnosed with malignant melanoma after surgical immunotherapy treated patients were analyzed. Patients was evaluated using the stage AJCC stage IIA 3 cases, IIB 1 cases, IV 1 were as follows. Follow-up period of at least 7 months, and a maximum of 32 months. As maintenance therapy after the first induction therapy group underwent immunotherapy interferon-${\alpha}$ of body-surface area per 200,000 IU five times in a week for 4 weeks sedentary and body surface area a total of 48 weeks per week to 100,000 IU three times subcutaneously. These patients for local recurrence and metastases, and distant metastasis were investigated disease-free survival was investigated. Results: Interferon-evaluation through follow-up chest computed tomography (CT) and positron emission computed tomography (PET CT) in patients who underwent the ${\alpha}$ immunotherapy results above both local recurrence and metastases without evidence of distant metastases. Conclusion: The high-dose ${\alpha}2b$ immunotherapy performed in patients to prevent the local recurrence of the tumor and metastasis to the current or future ultimate survival and disease-free survival improvement achieved is additional study and follow-up will be needed.

Comparison of Serum Osteopontin Levels in Patients with Stable and Chronic Obstructive Pulmonary Disease and Exacerbation (안정된 만성 폐쇄성 폐질환환자와 급성 악화상태의 혈중 Osteopontin 농도 비교)

  • Ma, Jeong-Eun;Lee, Seung-Hun;Kim, Yu-Eun;Lim, Su-Jin;Lee, Seung-Jun;Jeong, Yi-Yeong;Kim, Ho-Cheol;Lee, Jong-Deog;Hwang, Young-Sil;Cho, Yu-Ji
    • Tuberculosis and Respiratory Diseases
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    • v.71 no.3
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    • pp.195-201
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    • 2011
  • Background: Osteopontin (Opn) is recognized as an important adhesive bone matrix protein and a key cytokine involved in immune cell recruitment and tissue repair and remolding. However, serum levels of osteopontin have not been evaluated in patients with chronic obstructive pulmonary disease (COPD). Thus, the aim of this study was to evaluate and compare the serum levels of osteopontin in patients experiencing COPD exacerbations and in patients with stable COPD. Methods: Serum samples were obtained from 22 healthy control subjects, 18 stable COPD patients, and 15 COPD with exacerbation patients. Serum concentrations of osteopontin were measured by the ELISA method. Results: Serum levels of osteopontin were higher in patients with acute exacerbation than with stable COPD and in healthy control subjects ($62.4{\pm}51.9ng/mL$, $36.9{\pm}11.1ng/mL$, $30{\pm}11ng/mL$, test for trend p=0.003). In the patients with COPD exacerbation, the osteopontin levels when the patient was discharged from the hospital tended to decrease compared to those at admission ($45{\pm}52.1ng/mL$, $62.4{\pm}51.9ng/mL$, p=0.160). Osteopontin levels significantly increased according to patient factors, including never-smoker, ex-smoker and current smoker ($23{\pm}5.7ng/mL$, $35.5{\pm}17.6ng/mL$, $58.6{\pm}47.8ng/mL$, test for trend p=0.006). Also, osteopontin levels showed a significantly negative correlation with forced expiratory volume in one second ($FEV_1$%) predicted in healthy controls and stable COPD patients (r=-0.389; p=0.013). C-reactive protein (CRP) was positively correlated with osteopontin levels in patients with COPD exacerbation (r=0.775; p=0.002). Conclusion: The serum levels of osteopontin increased in patients with COPD exacerbation and tended to decrease after clinical improvement. These results suggest the possible role of osteopontin as a biomarker of acute exacerbation of COPD.

Result of Radiation Therapy for the Lung Cancer (폐암의 방사선치료 결과)

  • Kim Joo-Young;Choi Myung-Sun;Suh Won-Hyck
    • Radiation Oncology Journal
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    • v.7 no.2
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    • pp.213-225
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    • 1989
  • An analysis has been made of two hundred seven patients who were treated at the department of Radiation Oncology of Korea University Hospital for lung cancer from January 1981 through December 1986. There were 137 patients of nonsmall cell carcinoma (137/207, 66%), 26 patients of small cell carcinoma (26/207, 12.5%) and 44 patients of unproven histology. By aims of treatment, there were 104 patients (104/207, 50%) treated for cure, 89 patients (89/207, 42.9%) for palliation and 14 patients treated postoperatively. In 22 out of 207 patients, chemotherapy was done with radiotherapy, 12 of which were patients with small cell carcinoma. Stage II patients were 49 (49/207, 23.6%), stage III patients were 157 (157/207, 75.8%) and one patient had an occult cancer The tumor was initial Iy measured by CAT scan and chest X-rays in the 165 (165/207, 79.7%) patients, among which 117 patients had tumor diameter more than 5cm and 48 patients less than 5cm. Radiation therapy was given with Cobalt 60 teletherapy unit and the treatment volume encompassed primary tumor and the mediastinum. For curative aim, daily tumor dose of 180 cGy was given up to the range of 5,400~6,120cGy/30~34F/6~7 week period and for palliative aim, daily tumor dose of 300 cGy was given up to the range of 3,600~4,500 cGy/12~15F/2~3 week period. Postoperatively, mediastinum was treated for total dose of 5,040 cGy/28F/5.5 week period. 123 patients (123/207, 59%) were followed up after completion of radiotherapy for 14 months to 7 years. Local tumor response to the irradiation was measured by chest X-ray taken at one month follow up and was evaluated for response rate, if they were regressed more than 50% or less than 50% of the initial tumor size. The treatment results were as follows; 1. The median survival time was 8.5 months and survival rates for 1 year, 2 year and 5 year was 25%, 3.5% and 1% of nonsmall cell lung ca of 74 evaluable patients. 2. More than 50% of local tumor response rate was obtained in about half of overall cases; 90.5% for small cell ca, 50% for squamous cell ca, 25% for adenoca and 57% for large cell ca. 3. Response rate more than 50% was seen in the 50% of the patient group with tumor diameter more than 5cm and in the 55% of those with tumor diameter less than 5cm. 4. By total raidation dose given, patient group which was given 5,400~6,120 cGy equivalent dose or higher showed tumor response rate more than 50% in 53% of the patients, whereas the group with dose less than 5,400cGy equivalent, in 25% of the patients. 5. Survival rate for 6 month, 1 year and 2 year was compared between the group of local tumor response rate more than 50% vs. group with response rate less than 50%; 74% vs. 43%, 33% vs, 23%, 10% vs. 1%, respectively. 6. Local failure was seen in 21%(44/207) of the patients, which occured mostly within 15 months after completion of radiation therapy. Distant metastases were seen in 49.7%(103/207) of the patients, of which 43 cases were found before initiation of radiotherapy. The most common metastatic sites were bone and brain. In this sutdy, 1 year,2 year and S year survival rates were somewhat poor compared to the other studies. It mainly seems to be due to the poor general status of the patients and the far-advanced stage of the disease. In nonsmall cell cancer patients who had limited local disease and had small primary tumor size, we observed better local response. In addition, dose higher than 6,000 cGy group showed better tumor control than lower dose group. Survival rate was better for the local control group. For imporvement of local control of the lung cancer and hence, the survival of the patients with lung cancer, proper radical radiotherapy with high dose for localized disease is needed. New modality of treatment such as high LET beam in radiation therapy or drugs for the advanced disease as well as early diagnosis is also needed.

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Results of Total Body Irradiation in Allogeneic Bone Marrow Transplantation for Acute Non-Lymphocytic Leukemia (급성 골수성 백혈병에서 동종골수이식을 위한 전신 방사선 조사의 치료 결과)

  • Chung Su Mi;Choi Ihl Bohng;Kim In Ah;Kim Sung Hwan;Kang Ki Mun;Shinn Kyung Sub;Kim Choon Choo;Kim Dong Jip
    • Radiation Oncology Journal
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    • v.10 no.2
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    • pp.247-253
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    • 1992
  • Between August 1987 and July 1991, 22 patients with acute nonlymphocytic leukemia have received allogeneic bone marrow transplantation (BMT) with non-T-lymphocyte-depleted marrow obtained from matched sibling donors. Of these patients, 12 patients were in first complete remission (CR) and 10 patients in second CR or greater or in relapse. All patients were treated with a preparative regimen consisting of cyclophosphamide (CTX, 60 mg/kg) or combined drugs, and 850 cGy single-dose or $150\~200$ cGy fractionated total body irradiation (TBI) administered twice daily for a total dose of $1200\~1320$ cGy. Survivors have been followed from 8 to 64.5 months (median, 24 months). The overall 2 year survival rate, relapse rate and incidence of radiation pneumonitis and graft versus host disease (GVHD) have been evaluated by age, phase of disease, initial WBC count, modality of TBI or conditioning chemotherapy. Overall 2 year survival was $58{\%}$. The median survival was 31 months and mean survival was 23.2 months. Overall survival have significant impact in patients of age >19 years old (p=0.008), patients in first CR (p=0.09). Two year survival rate is significantly correlated with age ( >19 vs $\leqq$19, $79.4\%$ vs $14.3\%$, p=0.0008), regimen of chemotherapy (CTX vs combined drug, $76.9\%\;vs\;33.3\%$, p=0.04), phase of disease (1st CR vs \geqq2nd$ CR or relapse, $83.3\%\;vs\;30\%$, p=0.01) and method of TBI (fractionated vs single dose, $70.7\%\;vs\;37.5\%$, p=0.05). The influence of French-American-British (FAB) subtypes on relapse rate is not significant, but initial WBC count > 20000/$mm^3$ is associated with increased relapse rate. There is difference in the rate of radiation pneumonitis ($14.3\%\;vs\;25\%$), GVHD ($14.3\%\;vs\;50\%$) and relapse ($21.4\%\;vs\;50\%$) according to fractionated versus single-dose TBI. As mentioned above, fractionated TBI is compatible for the preparative regimen combined with chemotherapy En allogeneic BMT of first CR patients under 41 years of age with suitable donor. Those results from a retrospective, non-randomized study clearly need additional clinical data, ideally from a randomized study.

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Clinical Characteristics of precocious puberty girls and Comparison Analysis of GnRH Test results with Diagnosis type (성조숙증 여아들의 임상적 특징 및 진단별 성선자극호르몬 분비호르몬 GnRH (Gonado Tropin Releasing Hormone) 검사결과의 비교분석평가)

  • Kim, Jung-In;Kwon, Won-Hyun;Moon, Ki-Choon;Lee, In-Won
    • The Korean Journal of Nuclear Medicine Technology
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    • v.20 no.2
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    • pp.54-61
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    • 2016
  • Purpose Precocious Puberty is defined as the development of secondary sexual characteristics in girls younger than 8 years, and boys 9 years. Cause premature closure of the epiphysis is a disease that eventually decreases the final adult height. In this study, we retrospectively analyzed to evaluate the diagnostic difference the GnRH (Gonado-tropin-releasing Hormone) stimulation test results with medical records of precocious puberty in girls. Materials and Methods From February 2015 to December 2015 it was enrolled in the girls 118 people who visited the Seoul National University Bundang Hospital, Pediatrics, Endocrinology Internal Medicine. True precocious puberty group (n=57), early puberty group (n=39), were divided into Premature thelarche (n=22) group. A Tanner stage, chronological age, bone age, height, body weight for each group was determined by examining the mean${\pm}$standard deviation. GnRH test result was compared LH (Basal, 30 min, 45 min, 60 min), FSH (Basal, 30 min, 60 min) for each group, Each group LH, FSH Peak value distribution, the mean${\pm}$standard deviation was calculated for the peak LH/LH basal ratio, peak LH/Peak FSH ratio. The significance probability (P-value) between the value of each third group was determined. Results The average height of the true precocious puberty group $131{\pm}14.85$, the mean weight was $28.80{\pm}4.93$, the average chronological age $7.1{\pm}0.81$, the mean bone age was $9.9{\pm}0.9$, The average height of early puberty group was $134{\pm}5.10$, the average weight $28.50{\pm}4.43$, the average chronological age $8.05{\pm}0.03$, the mean bone age was $10.0{\pm}0.62$, The average height of Premature thelarche $129{\pm}6,01$, the average weight was $28.65{\pm}5.98$, the average chronological age $7.02{\pm}0.58$, the mean bone age was $8.04{\pm}1.29$. There was no significant difference when compared to the height and weight. There was a significant difference between the groups in the chronologic age and bone age difference (P <0.0002) True precocious puberty group showed peak LH levels at 30'(82.5%), 45'(12.3%), 60'(5.3%), in Peak FSH 30'(8.8%), 60'(91.2%). Early Puberty group showed high values in Peak LH at 30'(79.5%), 45'(17.9%), 60'(2.6%), in peak FSH levels at 30'(7.7%), 60'(92.32%). In Premature thelarche Group it showed the Peak LH levels at 30'(30%), 45'(59%), 60'(9.09%), Peak FSH levels at 30'(0%) 60'(100%). When compared with the The Peak LH/basal LH ratio, True precocious puberty group was $19.09{\pm}17.15$, early puberty group was $15.23{\pm}10.88$, Premature thelarche group showed significant differences between the three groups as $4.93{\pm}4.36$.(P <0.0001) LH Peak/FSH Peak ratio, true precocious puberty group was $1.222{\pm}0.77$, early puberty group was $1.34{\pm}1.23$, Premature thelarche group showed significant differences between the three groups as $0.3{\pm}0.09$(P <0.0001) Conclusion In order to diagnose the true precocious puberty have a diagnostic value when the LH peak after GnRH stimulation is increased by more than two to three times compared to baseline or a predetermined level or more than 5~10 IU/L increases. GnRH Test is a test for a long time and the patient discomfort due to repeated blood sampling, but the hypothalamus-pituitary gland- gonad axis activity evaluate and is the most basic accurate test in the differential diagnosis of precocious puberty disorders.

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Radiotherapy in Medically Inoperable Early Stage Non-small Cell Lung Cancer (내과적 문제로 수술이 불가능한 조기 비소세포성 폐암에서의 방사선치료)

  • Kim, Bo-Kyoung;Park, Charn-Il
    • Radiation Oncology Journal
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    • v.18 no.4
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    • pp.257-264
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    • 2000
  • Purpose: For early stage non-small-cell lung cancer, surgical resection is the treatment of choice. But when the patients are not able to tolerate it because of medical problem and when refuse surgery, radiation therapy is considered an acceptable alternative. We report on the treatment results and the effect of achieving local control of primary tumors on survival end points, and analyze factors that may influence survival and local control. Materials and Method : We reviewed the medical records of 32 patients with medically inoperable non-small cell lung cancer treated at our institution from June, 1987 through June, 1997. All patients had a pathologic diagnosis of non-small cell lung cancer and were not candidate for surgical resection because of either patients refusal (4), old age (2), lung problem (21), chest wail invasion (3) and heart problems (3). In 8 patients, there were more than 2 problems. The median age of the patients was 68 years (ranging from 60 to 86 years). Histologic cell type included souamous (24), adenocarcinoma (6) and unclassiried squamous cell (2). The clinical stages of the patients were 71 in 5, 72 in 25, 73 in 2 patients. Initial tumor size was 3.0 cm in 11, between 3.0 cm and 5.0 cm in 13 and more than 5.0 cm in 8 patients. Ail patients had taken chest x-rays, chest CT, abdomen USG and bone scan. Radiotherapy was delivered using 6 MV or 10 MV linear accelerators. The doses of primary tumor were the ranging from 54.0 Gy to 68.8 Gy (median; 61.2 Gy). The duration of treatment was from 37 days through 64 days (median; 0.5 days) and there was no treatment interruption except 1 patient due to poor general status. In 12 patients, concomitant boost technique was used. There were no neoadjuvant or adjuvant treatments such as surgery or chemotherapy. The period of follow-up was ranging from 2 months through 93 months (median; 23 months). Survival was measured from the date radiation therapy was initiated. Results : The overall survival rate was 44.6$\%$ at 2 years and 24.5$\%$ at 5 years, with the median survival time of 23 months. of the 25 deaths, 7 patients died of intercurrent illness, and cause-specific survival rate was 61.0$\%$ at 2 years and 33.5$\%$ at 5 years. The disease-free survival rate was 38.9$\%$ at 2 years and 28.3$\%$ at 5 years. The local-relapse-free survival rate was 35.1$\%$, 28.1$\%$, respectively. On univariate analysis, tumor size was significant variable of overall survival (p=0.0015, 95$\%$ C.1.; 1.4814-5.2815), disease-free survival (P=0.0022, 95$\%$ C.1., 1.4707-5.7780) and local-relapse-free survival (p=0.0015, 95$\%$ C.1., 1.2910- 4.1197). 7 stage was significant variable of overall survival (p=0.0395, 95$\%$ C.1.; 1.1084-55.9112) and had borderline significance on disease-free survival (p=0.0649, 95$\%$ C.1.; 0.8888-50.7123) and local-relapse-free survival (p=0.0582, 95$\%$ C,1.; 0.9342-52.7755). On multivariate analysis, tumor size had borderline significance on overall survival (p=0.6919, 955 C.1., 0.9610-5.1277) and local-relapse-free survival ( p=0.0585, 95$\%$ C.1.; 0.9720-4.9657). Tumor size was also significant variable of disease-free survival (p=0.0317, 95% C.1.; 1.1028-8.4968). Conclusion : Radical radiotherapy is an effective treatment for small (71 or f3 cm) tumors and can be offered as alternative to surgery in elderly or infirmed patients. But when the size of tumor is larger than 5 cm, there were few long-term survivors treated with radiotherapy alone. The use of hypefractionated radiotherapy, endobronchial boost, radisensitizer and conformal or IMRT should be consider to improve the local control rate and disease-specific survival rate.

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The Results and Prognostic Factors of Postoperative Radiation Therapy in the Early Stages of Endometrial Cancer (초기 자궁내막암의 수술 후 방사선치료의 결과와 예후인자)

  • Lee, Kyung-Ja
    • Radiation Oncology Journal
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    • v.26 no.3
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    • pp.149-159
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    • 2008
  • Purpose: To evaluate the results and prognostic factors for postoperative adjuvant radiation therapy in patients at stages I and II of endometrial cancer. Materials and Methods: Between January 1991 and December 2006, 35 patients with FIGO stages I and II disease, who received adjuvant radiation therapy following surgery for endometrial cancer at Ewha Womans University Hospital, were enrolled in this study. A total of 17 patients received postoperative pelvic external beam radiation therapy; whereas, 12 patients received vaginal brachytherapy alone, and 6 patients received both pelvic radiation therapy and vaginal brachytherapy. Results: The median follow-up period for all patients was 54 months. The 5-yr overall survival and disease-free survival rates for all patients were 91.4% and 81.7%, respectively. The 5-yr overall survival rates for low-risk, intermediate-risk, and high-risk groups were 100%, 100% and 55.6%, respectively. In addition, the 5-yr disease-free survival rates were 100%, 70.0%, and 45.7%, respectively. Although no locoregional relapses were identified, distant metastases were observed in 5 patients (14%). The most common site of distant metastases was the lung, followed by bone, liver, adrenal gland, and peritoneum. A univariate analysis revealed a significant correlation between distant metastases and risk-group (p=0.018), pathology type (p=0.001), and grade (p=0.019). A multivariate analysis also revealed that distant metastases were correlated with pathology type (p=0.009). Papillary, serous and clear cell carcinoma cases demonstrated a poor patient survival rate compared to cases of endometrioid adenocarcinoma or adenosquamous carcinoma. The most common complication of pelvic external beam radiation therapy was enteritis (30%), followed by proctitis, leucopenia, and lymphedema. All these complications were of RTOG grades 1 and 2; no grades 3 and 4 were observed. Conclusion: For the low-risk and intermediate-risk groups (stages 1 and 2) endometrial cancer, pelvic control, and overall survival rate was free of severe toxicity when pelvic radiation therapy or vaginal brachytherapy was performed. In the high-risk group, pelvic control rate was excellent, but the survival rate was poor due to distant metastases, in spite of the pelvic radiation therapy. The combined modality of chemotherapy and radiation therapy is recommended for high-risk groups. For the intermediate-risk group, a prospective randomized study is required to compare the efficacy between whole pelvic radiation therapy and vaginal brachytherapy.

Therapeutic Compliance for Calcium Supplements and Its Related Factors in Rural Osteoporotic Women (일부 농촌지역 여성 골다공증 환자의 칼슘보조제 치료순응도와 결정요인)

  • Chun, Byung-Yeol;Kam, Sin;Lee, Young-Ja;Lee, Sang-Won;Lee, Kyung-Eun;Lee, Young-Seok;Kim, Bong-Kee
    • Journal of agricultural medicine and community health
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    • v.26 no.2
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    • pp.111-132
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    • 2001
  • This study was conducted to examine the therapeutic compliance and its related factors in rural women with osteoporosis. A questionnaire survey was performed from April to May in 2000 for 140 osteoporotic patients who were diagnosed from April to June in 1999 through community health program. The study employed the health belief model for predicting and explaining sick role behavior. The analysis techniques employed included contingency table analysis and path analysis using LISREL. The major results of this study were as follows: Of the subjects, 12.1% were continuously complaint, 53.6% were intermittently compliant, and 34.3% were non- compliant to calcium supplement therapy. As the result of path analysis, the therapeutic compliance was significantly higher(${\mid}T{\mid}$ >2.0) as patients had higher perceived severity of disease, lower perceived barriers of treatment, and when patients thought their disease status as severe. As the patients had higher educational level, more experience of mass media contact or health education about osteoporosis, and when family had more concern for patient treatment, they had higher perceived susceptibility of complication(bone fracture)${\mid}T{\mid}$ >2.0). The patients had higher perceived severity(${\mid}T{\mid}$ >2.0) as they had more educational level, more advice for treatment from their doctors, and when family had more concern for their treatment. As the patients had more advice for treatment from their doctors and when family had more concern for their treatment, they had higher perceived benefit of treatment and lower perceived barriers to treatment(${\mid}T{\mid}$ >2.0). In order to improve the therapeutic compliance in rural osteoporotic women, it would be necessary that the patient should recognize their disease severity properly. And the perceived barriers should be removed through supportive environments for osteoporosis treatment such as doctor 's more advice and family 's more concern for treatment. In addition, effective and continuous management system for osteoporotic patients should be established.

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Effects of Cyclosporin A, FK506, and 3-Deazaadenosine on Acute Graft-versus-host Disease and Survival in Allogeneic Murine Hematopoietic Stem Cell Transplantation (마우스 동종 조혈모세포 이식모델에서 Cyclosporin A, FK506, 3-Deazaadenosine 등의 약제가 급성 이식편대 숙주병과 생존에 미치는 영향)

  • Jin, Jong Youl;Jeong, Dae Chul;Eom, Hyeon Seok;Chung, Nak Gyun;Park, Soo Jeong;Choi, Byung Ock;Min, Woo Sung;Kim, Hack Ki;Kim, Chun Choo;Han, Chi Wha
    • IMMUNE NETWORK
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    • v.3 no.2
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    • pp.150-155
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    • 2003
  • Background: We investigated the effect of donor marrow T cell depletion, administration of FK506, cyclosporin A (CSA), and 3-deazaadenosine (DZA) on graft versus host disease (GVHD) after allogeneic murine hematopoietic stem cell transplantation (HSCT). Methods: We used 4 to 6 week old Balb/c ($H-2^d$, recipient), and C3H/He ($H-2^k$, donor) mice. Total body irradiated recipients received $1{\times}10^7$ bone marrow cells (BM) and $0.5{\times}10^7$ splenocytes of donor under FK506 (36 mg/kg/day), CSA (5 mg/kg/day, 20 mg/kg/day), and DZA (45 mg/kg/day), which were injected intraperitoneally from day 1 to day 14 daily and then three times a week for another 2 weeks. To prevent the GVHD, irradiated Balb/c mice were transplanted with $1{\times}10^7$ rotor-off (R/O) cells of donor BM. The severity of GVHD was assessed daily by clinical scoring method. Results: All experimental groups were well grafted after HSCT. Mice in experimental group showed higher GVHD score and more rapid progression of GVHD than the mice with R/O cells (R/O group) (p<0.01). There were relatively low GVHD scores and slow progressions in FK506 and low dose CSAgroups than high dose CSA group (p<0.01). The survival was better in FK506 group than low dose CSA group. All mice treated with CSA died within 12 days after HSCT. The GVHD score in DZA group was low and slow in comparison with control group (p<0.05), but severity and progression were similar with low dose CSA group (p=0.11). All mice without immunosuppressive treatment died within 8 days, but all survived in R/O group (p<0.01). Survival in low dose CSA group was longer than in control group (p<0.05), but in high dose CSA group, survival was similar to control group. The survival benefit in DZA group was similar with low dose CSA group. FK506 group has the best survival benefit than other groups (p<0.01), comparable with R/O group (p=0.18), although probability of survival was 60%. Conclusion: We developed lethal GVHD model after allogeneic murine HSCT. In this model, immunosuppressive agents showed survival benefits in prevention of GVHD. DZA showed similar survival benefits to low dose CSA. We propose that DZA can be used as a new immunosuppressive agent to prevent GVHD after allogeneic HSCT.