• Title/Summary/Keyword: Randomized response

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Clinical Efficacy of Belotecan (CKD-602), Newly Developed Camptothecin Analog, in the 2nd Line Treatment of Relapsed Small Cell Lung Cancer (재발된 소세포폐암환자에서 이차 약제로 사용되는 Belotecan (CKD-602)의 임상적 효용성)

  • Ban, Hee-Jung;Oh, In-Jae;Kim, Kyu-Sik;Ju, Jin-Yung;Kwon, Yong-Soo;Kim, Yu-Il;Lim, Sung-Chul;Kim, Young-Chul
    • Tuberculosis and Respiratory Diseases
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    • v.66 no.2
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    • pp.93-97
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    • 2009
  • Background: Belotecan (Camtobell, CKD-602, Chongkundang Pharm., Korea), a camptothecin derivative, has anticancer effects by inhibiting topoisomerase I such as topotecan. This study observed the response, survival and toxicity of belotecan monotherapy after the failure of etoposide and platinum (EP). Methods: Forty nine small cell lung cancer (SCLC) patients (M/F=41/8; age, 64.5${\pm}$7.6 (mean${\pm}$SD) years), who failed in their first line chemotherapy were enrolled in this study. Twenty one SCLC patients showed relapsed lung cancer more than 90 days after their priorEP chemotherapy (sensitive relapse group, SR) and 28 patients relapsed within 90 days (refractory relapse group, RR). Results: The response rate was 25%. Eleven patients showed partial responses and 5 patients could not be checked. The response rate of the SR and RR patients was similar. The relative dose intensity was lower in the responders (78${\pm}$15%) than non-responders (83${\pm}$13%, p=0.03). The median survival time (MST) was 10.3 months (290 days). The MST of the non-responders and responders was 186 days (95% CI; 67-305) and 401 days (95% CI; 234-568, p=0.07), respectively. The median progression free survival (MPFS) was similar in the SR (79 days) and RR (67 days) patients. Grade 3-4 neutropenia, anemia, and thrombocytopenia were observed in 59.6%, 12.8% and 23.4% of patients, respectively. Conclusion: The efficacy and survival were demonstrated in the second-line setting. However, a randomized comparative trial with topotecan will be needed.

Comparison of Single vs Combined Modality Treatment in Locally Advanced Non-Small Cell Lung Cancer (국소 진행된 비소세포 폐암에서 복합요법과 단일요법의 비교)

  • Kim, Ae-Kyoung;Jeong, Seong-Su;Shin, Kyoung-Sang;Park, Sang-Gee;Jo, Hai-Jeong;Lee, Jong-Jin;Seo, Jee-Won;Kim, Ju-Ock;Kim, Sun-Young
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.4
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    • pp.502-512
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    • 1995
  • Background: One quarter to one third of patients with NSCLC present with primary tumors that although confined to the thorax are too extensive for surgical resection. Until resently standard treatment for these patients had been thoracic radiation, which produces tumor regression in most patients but few cures and dismal 5-year survival rate. The fact that death for most patients with stage III tumors is caused by distant metastases has promped a reevaluation of combined modality treatment approaches that include systemic chemotherapy. Therefore, we report the results observed in a study to evaluate the effect of multimodality treatment in locally advanced non-small cell lung cancer from 1/91 to 8/93 in CNUH. Method: We grouped the patients according to the treatment modalities and evaluated response rate, median survival and the effect of prognostic variables. Among 67 patients evaluated, twenty seven patients classified with group A, received cisplatin and etoposide containing combination chemotherapy alone, eighteen patients, classified with group B, received chemotherapy and radiotherapy, fifteen patients, group C, received neoadjuvant or adjuvant chemotherapy and surgery with/without radiation therapy, seven patients, group D, received only supportive care. Result: The major response rate for group A and B was 37% and 61% respectively. There was no statistically significant difference in response rate between A and B groups(p=0.97). The analysis of prognostic factors showed that differences of age, sex, pathology, blood type, smoking year, stage and ECOG performance did not related to improvement in survival. Median survival time was 8.6 months for group A, 13.4 months for group B, 19.2 months for group C, and 5.4 months for group D, respectively and there was statistically significant difference(p=0.003), suggesting that multimodality therapy was associated with signigicant improvement in survival. Subset survival analysis showed a significant therapeutic effect for earlier stage and good performance state(p=0.007, 0.009, respectively). A possible survival advantages were observed for major response groups. Conclusion: It was suggested that multimodality therapy for the management of patients who had stage III disease, has yielded good median survival and long survival for seleted patients. But, it is necessory to validate above result with further investigation in large scale and in prospective randomized trials.

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Randomized Trial of Early Versus Late Alternating Radiotherapy/ Chemotherapy in Limited-Disease Patients with Small Cell Lung Cancer (국한성병기 소세포폐암 환자에서 조기 혹은 지연 교대 방사선-항암제치료의 전향적 비교연구)

  • Lee Chang Geol;Kim Joo Hang;Kim Sung Kyu;Kim Sei Kyu;Kim Gwi Eon;Suh Chang Ok
    • Radiation Oncology Journal
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    • v.20 no.2
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    • pp.116-122
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    • 2002
  • Purpose : A randomized prospective study was conducted to compare the efficacy of early or late alternating schedules of radiotherapy, and carboplatin and ifosfamide chemotherapy in patients with limited-disease small cell lung cancer. Materials and Methods: From August 1993 to August 1996, a total of 44 patients with newly diagnosed, limited-disease small cell lung cancer, PS $H0\~2$, wt $loss<10\%$ were enrolled in a randomized trial which compared early alternating radiotherapy (RT)/chemotherapy (CT) and late alternating RT/CT. The CT regimen included ifosfamide $1.5\;g/m^2$ IV, d1-5 and carboplatin AUC 5/d IV, d2 peformed at 4 week intervals for a total of 6 cycles. RT (54 Gy/30 fr) was started after the first cycle of CT (early arm, N=22) or after the third cycle of CT (late arm, N=22) with a split course of treatment. Results : The pretreatment characteristics between the two arms were well balanced. The response rates in the early $(86\%)$ and late $(85\%)$ arm were similar. The median survival durations and 2-year survival rates were 15 months and $22.7\%$ in the early arm, and 17 months and $14.9\%$ in the late arm (p=0.47 by the log-rank test). The two-year progression free survival rates were $19.1\%$ in the early arm and $19.6\%$ in the late arm (p=0.52 by the log-rank test). Acute grade 3 or 4 hematologic and nonhematologic toxicities were similar between the two arms. Eighteen patients $(82\%)$ completed 6 cycles of CT in the early arm and 17 $(77\%)$ in the late arm. Four patients received less than 45 Gy of RT in the early arm and two in the late arm. There was no significant difference in the failure patterns. The local failure rate was $43\%$ in the early arm and $45\%$ in the late arm. The first site of failure was the brain in $24\%$ of the early arm patients compared to $35\%$ in the late arm (p=0.51). Conclusion : There were no statistical differences in the overall survival rate and the pattern of failure between the early and late alternating RT/CT in patients with limited-disease small cell lung cancer.

Combined Modality Therapy with Selective Bladder Preservation for Muscle Invading Bladder Cancer (침윤성 방광암 환자에서 방광 보존 치료)

  • Youn Seon Min;Yang Kwang Mo;Lee Hyung Sik;Hur Won Joo;Oh Sin Geun;Lee Jong Cheol;Yoon Jin Han;Kwon Heon Young;Jung Kyung Woo;Jung Se Il
    • Radiation Oncology Journal
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    • v.19 no.3
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    • pp.237-244
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    • 2001
  • Purpose : To assess the tolerance, complete response rate, bladder preservation rate and survival rate in patients with muscle-invading bladder cancer treated with selective bladder preservation protocol. Method and Materials : From October 1990 to June 1998, twenty six patients with muscle-invading bladder cancer (clinical stage T2-4, N0-3, M0) were enrolled for the treatment protocol of bladder preservation. They were treated with maximal TURBT (transurethral resection of bladder tumor) and 2 cycles of MCV chemotherapy (methotrexate, crisplatin, and vinblastine) followed by $39.6\~45\;Gy$ pelvic irradiation with concomitant cisplatin. After complete urologic evaluation (biopsy or cytology), the patients who achieved complete response were planed for bladder preservation treatment and treated with consolidation cisplatin and radiotherapy (19.8 Gy). The patients who had incomplete response were planed to immediate radical cystectomy. If they refused radical cystectomy, they were treated either with TURBT followed by MCV or cisplatin chemotherapy and radiotherapy. The median follow-up duration is 49.5 months. Results : The Patients with stage T2-3a and T3b-4a underwent complete removal of tumor or gross tumor removal by TURBT, respectively. Twenty one out of 26 patients $(81\%)$ successfully completed the protocol of the planned chemo-radiotherapy. Seven patients had documented complete response. Six of them were treated with additional consolidation cisplatin and radiotherapy. One patient was treated with 2 cycles of MCV chemotherapy due to refusal of chemo-radiotherapy. Five of 7 complete responders had functioning tumor-free bladder. Fourteen patients of incomplete responders were further treated with one of the followings : radical cystectomy (1 patient), or TURBT and 2 cycles of MCV chemotherapy (3 patients), or cisplatin and radiotherapy (10 patients). Thirteen patients of them were not treated with planned radical cystectomy due to patients' refusal (9 patients) or underlying medical problems (4 patients). Among twenty one patients, 12 patients $(58\%)$ were alive with their preserved bladder, 8 patients died with the disease, 1 patient died of intercurrent disease. The 5 years actuarial survival rates according to CR and PR after MCV chemotherapy and cisplatin chemoradiotherapy were $80\%\;and\;14\%$, respectively (u=0.001). Conclusion : In selected patients with muscle-invading bladder cancer, the bladder preservation could be achieved by MCV chemotherapy and cisplatin chemo-radiotherapy. All patients tolerated well this bladder preservation protoco. The availability of complete TURBT and the responsibility of neoadjuvant chemotherapy and chemoradiotherapy were important predictors for bladder preservation and survival. The patients who had not achieved complete response after neoadjuvant chemotherapy and chemoradiotherapy should be immediate radical cystectomy. A randomized prospective trial might be essential to determine more accurate indications between cystectomy or bladder preservation.

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Survival Difference of Combination Chemotherapy versus Supportive Care in the Patients with Stage Ⅳ Non-Small Cell Lung Cancer (4기 비소세포폐암 환자에서 복합화학요법군과 보존적치료군의 생존율 비교연구)

  • Kim, Byeong Hun;Lee, Kyung Hee;Doh, Gab Suk;Lee, Eun Jung;Kim, Seong Mok;Chung, Jin Hong;Lee, Kwan Ho;Hyun, Myung Soo
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.4
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    • pp.536-546
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    • 1996
  • Background : The survival benefit of combination chemotherapy comparing supportive care to patients with advanced non-small cell lung cancel, especially stage IV non-small cell lung cancer patients with metastatic disease, is controversial. The main goal of this study was to evaluate the difference in survival between patients treated with chemotherapy and those who were not and to identify prognostic factors in the patients with stage IV non-small cell lung cancer. Methods : From January 1989 to December 1994, total 67 patients including 20 patients treated with combination chemotherapy and 47 patients treated with only supportive care in stage IV non-small cell lung cancer patients with metastatic disease were enrolled in this study. Combination chemotherapy consisted of etoposide $120mg/m^2$ iv for 3 days and cis-platin iv day 1 every 4 weeks. The treatment groups were retrospectively analyzed by age, sex, histologic cell type, weight loss, serum LDH level, ECOG performance status and major organ metastasis. Results : The significant prognostic factors influencing survival on this study were ECOG performance status and histologic subtype. Overall response rate by combination chemotherapy was 30%(complete response 0%, partial response 30%). Median survival of overall patients was 13.6 weeks and median survival of Chemotherapy group, 20 weeks, was significantly longer than that of supportive care group, 11.7 week(p<0.01). Median survival of responded in patients receiving chemotherapy, 45.5 weeks, was significantly longer than that of non-responder, 17.3 weeks(p<0.05). 1 year-survival rate of chemotherapy group and supportive care group was 15N and 8%, respectively. Nausea or vomiting, alopecia and anemia were seen in nearly most cases after this combination chemotherapy. Toxicities above grade 3 included neutropenia, anemia, thrombocytopenia, infection, fever, nausea, vomiting and alopecia. But this combination chemotherapy was relatively well tolerated except one treatment-related death from sepsis associated with severe granulocytopenia. Conclusion : These results suggest that systemic chemotherapy might be helpful to the stage IV non-small cell lung cancer patients with good performance status and large scale randomized prospective trials should be performed.

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Evaluation of Probiotics as an Alternative to Antibiotic on Growth Performance, Nutrient Digestibility, Occurrence of Diarrhea and Immune Response in Weaning Pigs (항생제 대체제로서 생균제가 이유자돈의 성장능력 및 영양소 이용률, 설사 빈도, 면역 반응에 미치는 영향)

  • Jang, Young-Dal;Oh, Hee-Kyung;Piao, Long-Guo;Choi, Hyun-Bong;Yun, Jin-Hyeon;Kim, Yoo-Yong
    • Journal of Animal Science and Technology
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    • v.51 no.1
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    • pp.25-32
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    • 2009
  • This study was conducted to determine the effects of probiotics supplementation on growth performance, nutrient digestibility, occurrence of diarrhea and immune response in weaning pigs. Treatments were 1) NC (basal diet), 2) PC (basal diet + 0.12% avilamycin) and 3) A (basal diet + 0.2% Aspergillus oryzae), 4) B (basal diet + 0.2% Lactobacillus casei), 5) C (basal diet + 0.2% Bacillus subtilis), 6) D (basal diet + 0.2% Lactobacillus crispatus). A total of 120 pigs ($7.16\pm0.01$ kg average body weight, weaned at $23\pm3$days of age) were assigned to 6 treatments, 5 replicates and 4 pigs per pen in a randomized complete block (RCB) design. During the whole experimental period, body weight (P<0.01), average daily gain (ADG; P<0.01), and average daily feed intake (ADFI; P<0.05) of treatment PC were higher than other treatments. However, the probiotics treatments tended to increase ADG and G:F ratio compared to treatment NC. The G:F ratio in treatment A (Aspergillus oryzae) was similar to treatment PC during the whole experimental period (P<0.05). The supplementation of probiotics in the diet of weaning pig did not change nutrient digestibility (dry matter, crude protein, crude fat and ash) and nitrogen retention of weaning pigs. In blood urea nitrogen (BUN) concentration, treatment B had lower value than other treatments at 2 and 4 weeks (P<0.05). Treatments PC and C tended to decrease diarrhea score than other treatments (P=0.18). At 3h after lipopolysaccharide (LPS) injection, treatments NC and PC had higher count of $CD^{4+}$ T-cells than probiotics treatments, and treatment C showed the lowest value (P<0.01). There were no differences on count of $CD^{8+}$ T-cells and $CD^{4+}:CD^{8+}$ ratio among all treatments (P>0.10). These results suggest that the dietary probiotics are likely able to improve the growth performance, occurrence of diarrhea and immune response although they do not have similar effects like antibiotics in weaning pigs.

Thermophysiological Responses of Wearing Safety Hat for Working at a Hot Environment (서열환경하에서 안전모 착용시의 인체생리학적 반응)

  • 박소진;김희은
    • Journal of the Korean Society of Clothing and Textiles
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    • v.26 no.1
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    • pp.74-82
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    • 2002
  • The present study is aimed to investigate the effect of the safety hat on the balance of body temperature by observation of the physiological response under hot working environment. The experiment was carried out in a climate chamber of 3$0^{\circ}C$, 50%RH for 70 minutes. To compare the two kinds of safety hat, 5 healthy male subjects worn safety hat without hole (called 'without hole') or safety hat with hole (called 'with hole') according to a randomized cross-over design. The main results of this study are as fellows: Rectal temperature and heart rate were significantly lower level in 'with hole'than in 'without hole'. The mean skin temperature was significantly higher in 'without hole'than in 'with hole'. Blood pressure were significantly low in 'with hole'. Sweat rate which was measured by weight loss before and after experiment was higher in 'without hole'. In subjective ratings, subjects replied more hot, more uncomfortable and more wet, they felt more fatigue in condition of 'without hole'. Work ability which was measured by a grip strength dynamometer was higher in 'with hole'. Safety hat which can be used for safety of the brain in work place is meaningful device of behavioral thermoregulatory response under the hot working environment. The safety hat which is designed for proper ventilation and hygiene can maintain the homeostasis of body temperature by releasing body temperature efficiently.

The Prognostic Factors Affecting Survival in Muscle Invasive Bladder Cancer Treated with Radiotherapy (방사선치료를 받은 근 침윤성 방광암의 예후 인자)

  • Chung Woong-Ki;Oh Bong-Ryoul;Ahn Sung Ja;Nah Byung Sik;Kwon Dong-Deuk;Park Kwangsung;Ryu Soo-Bang;Park Yang-IL
    • Radiation Oncology Journal
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    • v.20 no.2
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    • pp.130-138
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    • 2002
  • Purpose : This study analyzed the prognostic factors affecting the survival rate and evaluated the role of radiation therapy in muscle-invading bladder cancer. Materials and Methods : Twenty eight patients with bladder cancer who completed planned definitive radiotherapy in the Departments of Therapeutic Radiology and Urology, Chonnam National University Hospital between Jan. 1986 to Dec. 1998 were retrospectively analyzed. The reviews were peformed based on the patients' medical records. There were 21 males and 7 females in this study. The median of age was 72 years old ranging from 49 to 84 years. All patients were confirmed as having transitional cell carcinoma with histological grade 1 in one patient, grade 2 in 15, grade 3 in 9, and uninformed in 3. Radiation therapy was peformed using a linear accelerator with 6 or 10 MV X-rays. Radiation was delivered daily with a 1.8 or 2.0 Gy fraction size by 4 ports (anterior-posterior, both lateral, alternatively) or 3 ports (Anterior and both lateral). The median radiation dose delivered to the isocenter of the target volume was 61.24 Gy ranging from 59 to 66.6 Gy. The survival rate was calculated by the Kaplan-Meier method. Multivariate analysis was peformed on the prognostic factors affecting the survival rate. Results : The survival rate was $76\%,\;46\%,\;33\%,\;33\%$ at 1, 2, 3, 5 years, respectively, with 19 months of median survival. The potential factors of age (less than 70 years vs above 70), sex, diabetes mellitus, hypertension, hydronephrosis, 1-stage (T3a vs T3b), TUR, chemotherapy, total duration of radiotherapy, radiation dose (less than 60 Gy vs above 60 Gy), and the treatment response were investigated with uniand multivariate analysis. Un univariate analysis, the T-stage (p=0.078) and radiation dose (p=0.051) were marginally significant, and the treatment response (p=0.011) was a statistically significant factor on the survival rate. Multivariate analysis showed there were no significant prognostic factors affecting the survival rate. Conclusion : The treatment response and radiation dose are suggested as th은 statistically significant factors affecting the survival rate of muscle invasive bladder cancer. A Further prospective randomized study is needed to confirm these prognostic factors.

Preliminary Results of Concurrent Radiation Therapy and Chemotherapy in Locally Advanced Cervical Carcinoma (국소적으로 진행된 자궁 경부암에서 방사선과 항암화학요법 병행치료의 예비적 결과)

  • Yang KM;Ahn SD;Choi EK;Chang HS;Kim YT;Nam JH;Mok JE
    • Radiation Oncology Journal
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    • v.11 no.2
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    • pp.355-361
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    • 1993
  • Since May 1991, authors have conducted a pilot study to determine the feasibility and evaluate the effect of concurrent radiation therapy and chemotherapy with 5-FU and Cis-platinum for locally advanced cervical cancer (stage IIB-IVA). Radiation therapy consisted of external irradiation to whole pelvis (4140 cGy/23 fx) in 4.5 weeks followed by high dose rate intracavitary radiation therapy (HDR ICRT) to deliver a dose of 30 to 35 Gy to A point in 6 to 7 fractions. After the intracavitary radiation therapy, parametrial boost was delivered for B point dose of 60 Gy in Stage IIB and 65 Gy in stage IIIB. 5-FU (1000 $mg/m^2/24hr$ for 96 hour iv infusion) and Cis-platinum (20 $mg/m^2/day$ IV bolus for 3 days) were given during the second week of external RT and the second course chemotherapy administered at the first HDR ICRT with the same method as the first chemotherapy. Sixteen patients (10 stage IIB,4 stage IIIB,2 stage IVA) were registered to this protocol. Among these 16 patients, two refused treatment after 2 fractions of external irradiation, and one could not continue intracavitary irradiation because of treatment related genitourinary toxicity. So 14 patients were evaluated for toxicity and 13 patients were evaluated for response analysis. Five of 14 patients developed grade 3 gastrointestinal toxicity but 4 of them recovered at the completion of treatment. One stage IIIB patient with inguinal lymph node metastasis who received higher dose of radiation in spite of initial poor performance status did not recover from gastrointestinal toxicity at the completion of treatment. And she died of distant metastasis at one month after the completion of treatment. Two of 14 evaluable patients showed weight loss, more than $10\%$ of initial weight. One patient developed grade 3 leukopenia. In this study, the average total treatment period of completely treated patients was 75 days and three of them took more than 80 days (84, 84, 89 days). Toxicities were generally acceptable and there were no treatment related death. At the last follow-up, complete response was achieved in $62\%(8/13)$ and especially of nine patients with stage IIB, eight patients showed complete response. This study suggests that concurrent radiation therapy and chemotherapy (5-FU and Cis-platinum) is tolerable and effective. Further follow-up is needed to determine whether this protocol will have a favorable impact on survival and to evaluate the late effect on normal tissues. In future, prospective randomized trials are needed to compare the standard radiation therapy alone with concurrent chemotherapy and radiation therapy for locally advanced cervical carcinoma.

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Effects of Supplementary Immune Modulators(MOS, Lectin) and Organic Acid Mixture(Organic acid F, Organic acid G) on the Performance, Profile of Leukocytes and Erythrocytes, Small Intestinal Microflora and Immune Response in Laying Hens (면역기능 조절제(MOS, Lectin)와 유기산제(Organic acid F, Organic acid G)가 산란계의 생산성, 혈액성상과 소장내 미생물 균총 및 면역체계에 미치는 영향)

  • Woo, K.C.;Kim, C.H.;Paik, I.K.
    • Journal of Animal Science and Technology
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    • v.49 no.4
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    • pp.481-490
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    • 2007
  • An experiment was conducted to investigate the effects of dietary supplementation of MOS, lectin and organic acid mixture(Organic acid F, Organic acid G) on the egg production, egg quality, profile of leukocytes and erythrocytes, small intestinal microflora and immune response in laying hens. A total of 900 Hy-line BrownⓇ laying hens of 48 wks old were assigned to one of the following 6 dietary treatments:control(C), C+AvillamycinⓇ 6ppm, C+MOS 250ppm, C+lectin 12.5ppm, C+Organic acid F(formic acid 35.4%, formate 34.6%, potassium 30.0%) 0.3% and C+0rgarnic acid G(fumaric acid 23%, calcium formate 14%, potassium sorbate 5%, calcium propionate 7%) 0.06%. Each treatment was replicated five times with thirty birds per replicate, housed in 2 bird cages. Feeding trial lasted for 6 wks under 16 hours lighting regimen. All supplemental groups were higher than the control in 6 wks hen-day and hen-housed egg production showing the highest with MOS treatment(P<0.05). Soft & broken egg productions were lower in supplemental groups than in the control except lectin treatment(P<0.05). Eggyolk color of supplemental groups was higher than that of the control except Organic acid G treatment(P<0.05). The values of RBC, HB, MCHC were highest in lectin treatment and lowest in MOS treatment(P<0.05). The numbers of intestinal microflora were not significantly different among the treatments. Serum IgG levels of all supplemental groups were higher than those of the control(P<0.05). In conclusion, for supplementation of antibiotics, immune modulators and organic acid mixture improved production parameters in general. Among the supplements, MOS showed the best performance in egg production and eggyolk color.