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Short-Term Efficacy of Steroid and Immunosuppressive Drugs in Patients with Idiopathic Pulmonary Fibrosis and Pre-treatment Factors Associated with Favorable Response (특발성폐섬유화증에서 스테로이드와 면역억제제의 단기 치료효과 및 치료반응 예측인자)

  • Kang, Kyeong-Woo;Park, Sang-Joon;Koh, Young-Min;Lee, Sang-Pyo;Suh, Gee-Young;Chung, Man-Pyo;Han, Jung-Ho;Kim, Ho-Joong;Kwon, O-Jung;Lee, Kyung-Soo;Rhee, Chong-H.
    • Tuberculosis and Respiratory Diseases
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    • v.46 no.5
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    • pp.685-696
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    • 1999
  • Background : Idiopathic pulmonary fibrosis (IPF) is a diffuse inflammatory and fibrosing process that occurs within the interstitium and alveolus of the lung with invariably poor prognosis. The major problem in management of IPF results from the variable rate of disease progression and the difficulties in predicting the response to therapy. The purpose of this retrospective study was to evaluate the short-term efficacy of steroid and immunosuppressive therapy for IPF and to identify the pre-treatment determinants of favorable response. Method : Twenty patients of IPF were included. Diagnosis of IPF was proven by thoracoscopic lung biopsy and they were presumed to have active progressive disease. The baseline evaluation in these patients included clinical history, pulmonary function test, bronchoalveolar lavage (BAL), and chest high resolution computed tomography (HRCT). Fourteen patients received oral prednisolone treatment with initial dose of 1mg/kg/day for 8 to 12 weeks and then tapering to low-dose prednisolone (0.25mg/kg/day). Six patients who previously had experienced significant side effects to steroid received 2mg/kg/day of oral cyclophosphamide with or without low-dose prednisolone. Follow-up evaluation was performed after 6 months of therapy. If patients met more than one of followings, they were considered to be responders : (1) improvement of more than one grade in dyspnea index, (2) improvement in FVC or TLC more than 10% or improvement in DLco more than 20% (3) decreased extent of disease in chest HRCT findings. Result : One patient died of extrapulmonary cause after 3 month of therapy, and another patient gave up any further medical therapy due to side effect of steroid. Eventually medical records of 18 patients were analyzed. Nine of 18 patients were classified into responders and the other nine patients into nonresponders. The histopathologic diagnosis of the responders were all nonspecific interstitial pneumonia (NSIP) and that of nonresponders were all usual interstitial pneumonia (UIP) (p<0.001). The other significant differences between the two groups were female predominance (p<0.01), smoking history (p<0.001), severe grade of dyspnea (p<0.05), lymphocytosis in BAL fluid ($23.8{\pm}16.3%$ vs $7.8{\pm}3.6%$, p<0.05), and less honeycombing in chest HRCT findings (0% vs $9.2{\pm}2.3%$, p<0.001). Conclusion : Our results suggest that patients with histopathologic diagnosis of NSIP or lymphocytosis in BAL fluid are more likely to respond to steroid or immunosuppressive therapy. Clinical results in large numbers of IPF patients will be required to identify the independent variables.

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Effects of Pranlukast on Ovalbumin Induced Early-Phase Bronchoconstriction in Guinea Pigs (기니픽에서 Ovalbumin으로 유발된 즉시형 기관지 수축반응에 대한 Pranlukast의 효과)

  • Lee, Sin-Hyung;Shim, Jae-Jeong;Kim, Kyung-Kyu;Jeong, Hye-Cheol;Kwon, Young-Hwan;Kim, Je-Hyeong;Lee, Sung-Yong;Lee, So-Ra;Lee, Sang-Youb;Cho, Jae-Youn;In, Kwang-Ho;Yoo, Se-Hwa;Kang, Kyung-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.46 no.5
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    • pp.697-708
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    • 1999
  • Background : Leukotriene (LT) $C_4$, $D_4$, and $E_4$, the main components of slow-reacting substance of anaphylaxis (SRS-A), have been suggested to play an important role in bronchial asthma such as antigen-induced bronchoconstriction, airway hyperreactivity, and pulmonary eosinophil accumulation. The purpose of this study was to evaluate the effects of treatment with the cysteinyl-LTs (cys-LTs) antagonist, pranlukast on allergen-induced guinea pig asthma model. Methods : Guinea pigs of treatment and placebo groups were sensitized by subcutaneous injection of ovalbumin(OVA) and challenged by inhalation of aerosolized OVA (1% weight/volume OVA). Normal control group did not sensitize with OVA. Oral ingestion of pranlukast and normal saline to the treatment and placebo groups was performed. In the treatment and placebo groups, airway resistance was measured before and after oral ingestion. Serum $LTC_4$ and eosinophilic infiltration of the bronchiolar and peribronchiolar tissues were measured after ingestion in the treatment and placebo groups. Results : Allergen-induced airway constriction developed in 20 (8 in treatment group, 12 in placebo group) among 35 guinea pigs. Airway resistance was significantly decreased at 3 and 6 minutes after OVA challenge in the pranlukast treatment group. In the placebo group, there was no difference of airway resistance between before and after saline ingestion. Serum $LTC_4$ levels showed 348.4 pg/ml in the treatment group, 373.9 pg/ml in the placebo group, and 364.4 pg/ml in the control group. There were no statistically significant difference between treatment and placebo group (p=0.232), and treatment and control group (p=0.501). Eosinophilic infiltrations in the peribronchiolar region per one-microscopic field ($\times$400 high power fields) demonstrated 7.06 in the treatment group, 19.2 in the placebo group, and 4.50 in the control group. There was significant decrement of eosinophilic infiltration in the treatment group which was compared with placebo group (p=0.001). Conclusion : These results demonstrate that pranlukast, a cys-LTs receptor antagonist, can attenuate allergen induced early-phase bronchoconstriction and eosinophilic infiltration in the bronchiolar tissues.

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The Role of Poly(ADP-ribose) Polymerase-1 in Ventilator-Induced Lung Injury (기계환기로 인한 급성 폐손상에서 poly(ADP-ribose) polymerase-1의 역할)

  • Kim, Je-Hyeong;Yoon, Dae Wui;Hur, Gyu Young;Jung, Ki Hwan;Lee, Sung Yong;Lee, Sang Yeub;Shin, Chol;Shim, Jae Jeong;In, Kwang Ho;Yoo, Se Hwa;Kang, Kyung Ho
    • Tuberculosis and Respiratory Diseases
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    • v.60 no.4
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    • pp.451-463
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    • 2006
  • Background : Reactive oxygen species (ROS) take center stage as executers in ventilator-induced lung injury (VILI). The protein with DNA-damage scanning activity, poly (ADP-ribose) polymerase-1 (PARP1), signals DNA rupture and participates in base-excision repair. Paradoxically,overactivation of PARP1 in response to massive genotoxic injury such as ROS can induce cell death through ${\beta}$ -nicotinamide adenine dinucleotide ($NAD^+$) depletion, resulting in inflammation. The purpose of this study is to investigate the role of PARP1 and the effect of its inhibitor in VILI. Methods : Forty-eight male C57BL/6 mice were divided into sham, lung protective ventilation(LPV), VILI, and PARP1 inhibitor (PJ34)+VILI (PJ34+VILI) groups. Mechanical ventilator setting for the LPV group was $PIP\;15cmH_2O$ + $PEEP\;3cmH_2O$ + RR 90/min + 2 hours. The VILI and PJ34+VILI groups were ventilated on a setting of $PIP\;40cmH_2O$ + $PEEP\;0cmH_2O$ + RR 90/min + 2 hours. As a PARP1 inhibitor for the PJ34+VILI group, 20 mg/Kg of PJ34 was treated intraperitoneally 2 hours before mechanical ventilation. Wet-to-dry weight ratio and acute lung injury (ALI) score were measured to determine the degree of VILI. PARP1 activity was evaluated by using an immunohistochemical method utilizing biotinylated NAD. Myeloperoxidase (MPO) activity and the concentration of inflammatory cytokines such as tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, and IL-6 were measured in bronchoalveolar lavage fluid (BALF). Results : In the PJ34+VILI group, PJ34 pretreatment significantly reduced the degree of lung injury, compared with the VILI group (p<0.05). The number of cells expressing PARP1 activity was significantly increased in the VILI group, but significantly decreased in the PJ34+VILI group (p=0.001). In BALF, MPO activity, $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6 were also significantly lower in the PJ34+VILI group (all, p<0.05). Conclusion : PARP1 overactivation plays a major role in the mechanism of VILI. PARP1 inhibitor prevents VILI, and decreases MPO activity and inflammatory cytokines.

A Clinical Study on Transpulmonary Leukostasis and Prophylactic Effects of Steroid in Cardiac Surgery (심장수술시 백혈구의 폐내정체와 스테로이드의 예방적 효과에 관한 연구)

  • 최석철
    • Biomedical Science Letters
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    • v.2 no.2
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    • pp.133-151
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    • 1996
  • After cardiac surgery, it has been recognized that various complications were associated with injured humoral and cellular immunity by cardiopulmonary bypass(CPB). Especially, in postoperative pulmonary dysfunction, transpulmonary leukostasis followed complement activation and inflammatory responses are major pathogen. Some studies have showed that pretreated-corticosteroids before CPB protected postoperative pulmonary dysfunction. Corticosteroids may inhibit complement and leukocyte activation. On based previous studies, present investigator determined changes of leukocyte counts and transpulmonary leukostasis during cardiac surgery and postoperative periods. For the evaluation of postoperative pulmonary function and edema, $PaO_2$ and chest X-ray were compared between pre-CPB and post-CPB. Fever and other parameters were also observed postoperatively. The aim of this study was to define for the prophylactic effects of corticosteroid(Solu-Medrol: 30mg/kg) on all the researched parameters. This study was prospectively designed with randomized-blind fashion for 50 patients undergoing cardiac surgery. According to the purpose of study, all patients were divided into placebo and steroid group. : Placebo group was 25 patients received normal saline(not corticosteroid), and steroid group was 25patients received corticosteroid(Solu-Medrol: 30mg/kg) before initiation of CPB. The results of study were summarized as follows. 1. Total peripheral leukocyte counts decreased significantly at 5 minutes of CPB in all patients(P<0.01), and began to increase progressively at later periods of CPB with neutrophilia. The significant rise remained at postoperative 7th day(P<0.05). 2. During partial CPB, transpulmonary leukostasis occurred in placebo group(P<0.001), whereas it was prevented in steroid group. 3. In both groups, peripheral lymphocyte counts were stable during CPB, but began to reduce at time of intensive care unit(ICU) and the lymphocytopenia remained until postoperative 3rd day. The lymphocyte counts recovered on postoperative 7th day. 4. In both groups, peripheral counts of monocyte were relatively stable in the early peroid of CPB, and increased gradually in the later periods of CPB. This significant monocytosis remained throughout postoperlative periods(P<0.05). 5. The mean value of postoperative $paO)_2$ was lower than that of pre-CPB in placebo group(P=0.01) but didn't significant in steroid group(P=0.90). In the incidence of pulmonary edema signs and fever, placebo group was higher than steroid group(P=0.001, p=0.01, respectively). However mechanical respiratory supporting and care periods at intensive care unit were not significant difference between two groups(P>.0.05).With the above results, the investigator concluded that leukocyte activation and pulmonary sequestration were caused by cardiac surgery with CPB and demonstrated that high dose corticosteroid will provide prophylactic effect for pulmonary leukostasis and higher neutrophilia. These effects may ameliorate postoperative pulmonary dysfunction and contribute to postoperative less morbidity. However, further study should be performed because postoperative lymphocytopenia continued for 3 days in both groups, which may suspected damage or suppression of cell-mediated immunity with used corticosteroid.

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The Cognitive Performance, Emotional and Behavioral Problems of the Children with ADHD Showing the Difference between Visual and Auditory Attention (시각 주의력과 청각 주의력의 차이를 보이는 주의력 결핍.과잉활동장애 아동의 인지기능과 정서 및 행동 문제)

  • Son, Jung Woo
    • Korean Journal of Biological Psychiatry
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    • v.13 no.2
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    • pp.70-81
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    • 2006
  • Objective : The purpose of this study was to investigate the differences of the cognitive performance, emotional and behavioral problems among the attention-deficit/hyperactivity disorder(ADHD) groups that show the difference between visual and auditory attention. Method : Using 'ADHD Diagnostic System(ADS)', visual attention and auditory attention of 98 children diagnosed as ADHD were measured. According to the omission and commission error of ADS, they were divided into three groups ; 1) the group whose each visual omission and commission error scores were higher than each auditory omission and commission error scores(VV group), 2) the group whose each auditory omission and commission error scores were higher than each visual omission and commission error scores(AA group), 3) the group that was the rest of VV and AA group(M group). And the results of both the subscales of Korean Educational Development Institute-Wechsler Intelligence Scale for Children(KEDI-WISC) and the subscales of Korean Child Behavior Checklist(K-CBCL) among three groups were compared. Finally, the correlation between the visual omission, visual commission, auditory omission, auditory commission error and the results of KEDI-WISC, K-CBCL were investigated. Results : The results were as follows ; 1) In 98 ADHD children, the number of VV group(N=56) was higher than that of AA (N=10) and M group (N=32). 2) All mean scores of the subscales of KEDI-WISC of VV group were higher than those of M and AA group. The score of verbal IQ(p=.039) of VV group was significantly higher than that of AA group and the scores of block design(p=.015), Kaufman's factor 2(p=.045), performance IQ(p=.004) were significantly higher than those of M group. The score of full IQ(p=.004) were significantly higher than that of M and AA group. 3) The mean scores of all K-CBCL subscales of VV group were higher than those of M and AA group, except the score of Somatic complaint subscale. The score of Social subscale(p=.041) of VV group was significantly higher than that of AA group. The score of Withdrawn subscale(p=.021) of AA group was significantly higher than that of VV group. 4) There were no significant correlation between the scores of visual omission/commission error and those of each subscale of KEDI-WISC. But, there were many significant correlations between the scores of auditory omission/commission error and those of each subscale of KEDI-WISC. 5) There were significant correlation between the score of the visual omission error and that of Thought problem subscale(r=.205, p=.043) of K-CBCL. There were significant correlation between the scores of the auditory omission error and those of Social subscale(r=-.319, p=.001), Social problems subscale(r=.206, p=.042), Thought problem subscale(r=.235, p=.021). Finally, there were significant correlation between the scores of auditory commission error and those of Social subscale(r=-.241, p=.017), Thought problem subscale(r=.235, p=.020). Conclusion : The ADHD children whose auditory attention ability were higher than visual attention ability had relatively better cognitive performance and less emotional/behavioral problems than the others. The more comprehensive experiment will be needed about the cognitive performance, emotion and behavior problems of the ADHD children showing the difference between visual and auditory attention.

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Validity of Clinically Used Tray Transmission Factor (임상적으로 쓰이는 차폐선반투과율의 타당성에 관한 연구)

  • 윤형근
    • Progress in Medical Physics
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    • v.14 no.4
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    • pp.218-224
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    • 2003
  • Purpose:By evaluating the dependence of the tray transmission factor (tray factor) on collimator setting and tray thickness, we determined the validity of the clinically used single tray factor for standard radiation field size (10${\times}$10 $\textrm{cm}^2$). Methods and Materials:For each X ray energies (6 and 10 MV), outputs were measured by using 5 steps of tray thickness (0, 6, 8, 10, 12 mm) and 7 steps of radiation field size (5${\times}$5, 10${\times}$10, 15${\times}$15, 20${\times}$20, 25${\times}$25, 30${\times}$30, 35${\times}$35 $\textrm{cm}^2$) at 10 cm phantom depth. Outputs were measured in both 'with tray' and 'without tray' conditions by using radiation with the same monitor units, and the tray factors were determined by the ratios of the two outputs. To evaluate the validity of a single tray factor obtained for standard radiation field, we analyzed the pattern of the field sizes in cases treated at our hospital in 2002. Results : In the 6 MV X-ray, the increases in the tray factor between the standard field (l0${\times}$10 $\textrm{cm}^2$) and the largest field (35${\times}$35 $\textrm{cm}^2$) were 0.517%, 0.835%, 1.058%, 1.066% in 6, 8, 10, and 12 mm thickness tray, respectively. In the 10 MV X-ray, the increases in the fray factor between the standard field (10${\times}$10 $\textrm{cm}^2$) and the largest field (35${\times}$35 $\textrm{cm}^2$) were 0.517%, 0.836%, 1.058%, 1.066% in 6, 8, 10, 12 mm thickness tray, respectively. In a major portion of clinical cases, when the field size was smaller than 20${\times}$20 $\textrm{cm}^2$, the tray factor was in good agreement with the standard tray factor. However, in cases where the field sizes were 30${\times}$30 $\textrm{cm}^2$ and 35${\times}$35 $\textrm{cm}^2$, the error could exceed 1.0%. Conclusion:The tray factor increased with increasing field size or decreasing tray thickness. The difference of tray factor between the small field and the large field increased with increasing tray thickness. Furthermore, the standard tray factor was valid in most clinical cases except for when the field size was greater than 30${\times}$30 $\textrm{cm}^2$, wherein the error could exceed 1.0%.

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Estimation of Internal Motion for Quantitative Improvement of Lung Tumor in Small Animal (소동물 폐종양의 정량적 개선을 위한 내부 움직임 평가)

  • Yu, Jung-Woo;Woo, Sang-Keun;Lee, Yong-Jin;Kim, Kyeong-Min;Kim, Jin-Su;Lee, Kyo-Chul;Park, Sang-Jun;Yu, Ran-Ji;Kang, Joo-Hyun;Ji, Young-Hoon;Chung, Yong-Hyun;Kim, Byung-Il;Lim, Sang-Moo
    • Progress in Medical Physics
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    • v.22 no.3
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    • pp.140-147
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    • 2011
  • The purpose of this study was to estimate internal motion using molecular sieve for quantitative improvement of lung tumor and to localize lung tumor in the small animal PET image by evaluated data. Internal motion has been demonstrated in small animal lung region by molecular sieve contained radioactive substance. Molecular sieve for internal lung motion target was contained approximately 37 kBq Cu-64. The small animal PET images were obtained from Siemens Inveon scanner using external trigger system (BioVet). SD-Rat PET images were obtained at 60 min post injection of FDG 37 MBq/0.2 mL via tail vein for 20 min. Each line of response in the list-mode data was converted to sinogram gated frames (2~16 bin) by trigger signal obtained from BioVet. The sinogram data was reconstructed using OSEM 2D with 4 iterations. PET images were evaluated with count, SNR, FWHM from ROI drawn in the target region for quantitative tumor analysis. The size of molecular sieve motion target was $1.59{\times}2.50mm$. The reference motion target FWHM of vertical and horizontal was 2.91 mm and 1.43 mm, respectively. The vertical FWHM of static, 4 bin and 8 bin was 3.90 mm, 3.74 mm, and 3.16 mm, respectively. The horizontal FWHM of static, 4 bin and 8 bin was 2.21 mm, 2.06 mm, and 1.60 mm, respectively. Count of static, 4 bin, 8 bin, 12 bin and 16 bin was 4.10, 4.83, 5.59, 5.38, and 5.31, respectively. The SNR of static, 4 bin, 8 bin, 12 bin and 16 bin was 4.18, 4.05, 4.22, 3.89, and 3.58, respectively. The FWHM were improved in accordance with gate number increase. The count and SNR were not proportionately improve with gate number, but shown the highest value in specific bin number. We measured the optimal gate number what minimize the SNR loss and gain improved count when imaging lung tumor in small animal. The internal motion estimation provide localized tumor image and will be a useful method for organ motion prediction modeling without external motion monitoring system.

The Evaluations of Phoria and AC/A Ratio by Watching 3D TV at Near (3D TV 근거리 시청에 따른 사위도와 조절성폭주비 평가)

  • Son, Jeong-Sik;Kim, Dong-Su;Kim, Jung-Ho;Kim, Jae-Do;Hamacher, Alaric;Yu, Dong-Sik
    • Journal of Korean Ophthalmic Optics Society
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    • v.20 no.3
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    • pp.319-324
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    • 2015
  • Purpose: This study was designed to evaluate the changes of phoria and calculated AC/A ratio, and their recovery time points by watching 3D television (3D TV). Methods: 50 subjects (male 30, female 20) of 20s to 40s ages who can watch 3D, were measured phoria using a Howell phoria card at 3 m for distance and 40 cm for near. The phoria was evaluated before watching 3D TV and every 10 minutes from starting of watching 3D TV for 30 minutes, and every 5 minutes after finishing of watching 3D TV for 30 minutes again. Results: For the distance phoria during and after watching 3D TV, it was increased to more exophoria $-0.98{\pm}1.37{\Delta}$ (prism diopters) after 10 minutes from starting of 3D TV watching (p=0.063) and increased to more exophoria $-1.00{\pm}1.28{\Delta}$ after 30 minutes (p=0.024), and started to decrease after finishing of watching 3D TV and recovered to the level of before 3D TV watching ($-0.78{\pm}1.11{\Delta}$) after 20 minutes (p=0.32) with comparing to phoria of before watching 3D TV ($-0.80{\pm}1.12{\Delta}$). For the near phoria, it was also increased to more exophoria $-5.71{\pm}4.45{\Delta}$ after 10 minutes from starting of watching 3D TV (p=0.000) and $-6.58{\pm}4.36{\Delta}$ after 30 minutes (p=0.000), and started to decrease after finishing of watching 3D TV and recovered to the level of before watching 3D TV after 20 minutes ($-4.34{\pm}3.67{\Delta}$) (p=0.32) with comparing to the phoria of before watching 3D TV ($-4.36{\pm}3.66{\Delta}$). AC/A ratio was decreased from $4.92{\pm}1.17{\Delta}/D$ for before 3D TV watching to $4.11{\pm}1.50{\Delta}/D$ for after 30 minutes from starting of watching 3D TV (p=0.000), and increased after the end of watching 3D TV and recovered to the level of before 3D TV watching ($4.93{\pm}1.18{\Delta}/D$) after 25 minutes (p=0.598). Conclusions: During watching 3D TV at near, it showed a tendency of convergence insufficiency by decrease of calculated AC/A ratio as result that exophoria at near was higher increased than exophoria at distance. However, the increased exophoria at both near and distance was recovered to the level of base line after 25 minutes from the end of watching 3D TV. Through this study, it seems to need rational proposals of advice for watching 3D TV.

The comparison of predicted adult height change and height gain after gonadotropin-releasing hormone agonist and combined growth hormone treatment in girls with idiopathic central precocious puberty (진성 성조숙증으로 진단 받은 여아에서 gonadotropin-releasing hormone agonist 단독치료 및 growth hormone의 병합치료 시 예측 성인키의 변화 및 성장 획득의 비교)

  • Seo, Ji-Young;Yoon, In-Suk;Shin, Choong-Ho;Yang, Sei-Won
    • Clinical and Experimental Pediatrics
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    • v.49 no.3
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    • pp.305-311
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    • 2006
  • Purpose : GnRH analogues(GnRHa) are used to treat central precocious puberty(CPP). However, in some patients, the GV decrease is so remarkable that it impairs predicted adult height(PAH); and there fore, the addition of growth hormone(GH) is suggested. We analysed the growth changes during two years and final adult height(FAH) in girls with idiopathic CPP treated with combined therapy, compared with those of girls treated with GnRHa alone. Methods : For the analysis, we classified the patients, who was treated for longer than two years, into three groups depending on the initial PAH and combination of GH; PAH_L, treated with GnRHa and PAH less than midparental height(MPH) - 5 cm. PAH_H, treated with GnRHa and PAH greater than MPH - 5 cm. GnRHa+GH, combined GH treatment, regardless of PAH before treatment. We analysed the GV and PAH change during the first two years and FAH. Results : In PAH_L, the PAH(SDS) at first year of therapy was significantly increased to $153.5{\pm}6.5cm(-1.4{\pm}1.3)$ from $149.7{\pm}6.4cm(-2.1{\pm}1.3)$ before treatment(P=0.004). In PAH_H, there was no significant increase in PAH during the two years of treatment. During the first year of combination of GH and GnRHa, GV and PAH increased significantly. We observed significant increases in FAH, comparing to the initial PAH in the PAH_L and GnRHa+GH groups. The height gains(FAH - initial PAH) were significantly higher in the PAH_L and GnRHa+GH groups than that in the PAH_H group. Conclusion : This study suggests the FAH and height gains are improved in patients, whose predicted adult height before treatment was shorter than those with higher predicted adult height, with the treatment of GnRHa alone or in combination with GH. GH could not improve the final adult height, but compensated the growth in patients whose growth velocity was decelerated by GnRHa alone.

Effects of NG-monomethyl-L-arginine and L-arginine on cerebral hemodynamics and energy metabolism during reoxygenation-reperfusion after cerebral hypoxia-ischemia in newborn piglets (급성 저산소성 허혈성 뇌손상이 유발된 신생자돈에서 재산소-재관류기 동안 NG-monomethyl-L-arginine과 L-arginine이 뇌의 혈역학 및 에너지 대사에 미치는 영향)

  • Ko, Sun Young;Kang, Saem;Chang, Yun Sil;Park, Eun Ae;Park, Won Soon
    • Clinical and Experimental Pediatrics
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    • v.49 no.3
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    • pp.317-325
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    • 2006
  • Purpose : This study was carried out to elucidate the effects of nitric oxide synthase(NOS) inhibitor, NG-monomethyl-L-arginine(L-NMMA) and nitric oxide precursor, L-arginine(L-Arg) on cerebral hemodynamics and energy metabolism during reoxygenation-reperfusion(RR) after hypoxia-ischemia(HI) in newborn piglets. Methods : Twenty-eight newborn piglets were divided into 4 groups; Sham normal control(NC), experimental control(EC), L-NMMA(HI & RR with L-NMMA), and L-Arg(HI & RR with L-Arg) groups. HI was induced by occlusion of bilateral common carotid arteries and simultaneously breathing with 8 percent oxygen for 30 mins, and followed RR by release of carotid occlusion and normoxic ventilation for one hour. All groups were monitored with cerebral hemodynamics and cytochrome $aa_3$ (Cyt $aa_3$) using near infrared spectroscopy(NIRS). $Na^+$, $K^+$-ATPase activity, lipid peroxidation products, and tissue high energy phosphate levels were determined biochemically in the cerebral cortex. Results : In experimental groups, mean arterial blood pressure, $PaO_2$, and pH decreased, and base excess and blood lactate level increased after HI compared to NC group(P<0.05). These variables subsequently returned to baseline after RR except pH. There were no differences among the experimental groups. In NIRS, oxidized hemoglobin($HbO_2$) decreased and hemoglobin(Hb) increased during HI(P<0.05) but returned to base line immediately after RR; 40 min after RR, the $HbO_2$ had decreased significantly compared to NC group(P<0.05). Changes of Cyt $aa_3$ decreased significantly compared to NC after HI and recovered at the end of the experiment. Significantly reduced cerebral cortical cell membrane $Na^+$, $K^+$-ATPase activity and increased lipid peroxidation products(P<0.05) were not improved with L-NMMA or L-Arg. Conclusion : These findings suggest that NO is not involved in the mechanism of HI and RR brain damage during the early acute phase of RR.