• Korean Journal of Agricultural Science
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• v.22 no.2
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• pp.170-179
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• 1995

This study was conducted to investigate the genetic constitution of blood proteins and enzymes in 238 Korean Native cattle reared at Korean Native Cattle Breeding Center, National Livestock Cooperative Federation. The genetic polymorphisms of post-transferrin-2(pTf-2), transferrin(Tf), post-albumin(pAlb), albumin(Alb), ceruloplamin(Cp), amylase-I(Am-I) and hemoglobin(Hb) were analyzed by using PAGE(polyacrylamide gel electrophoresis) and STAGE(starch gel electrophoresis). The genotypes and gene frequencies were estimated at these loci for each blood proteins and enzymes. The results obtained from this study were summarized as follows : 1. The pTf-2 locus were identified to be genetically controlled by codominant alleles designated pTf-2 F and S, and the distribution of genotypes were 46.22, 46.64 and 7.14% for pTf-2 FF, FS and SS types, and the gene frequencies of the pTf-2 F and S allele were 0,695 and 0.305, respectiveley. 2. The Tf locus were found to be controlled by Tf A, D1, D2 and E alleles, and the distributioin of genotypes were 0.84, 13.87, 13.03, 10.92, 22.27, 12.61, 2.94, 15.51, 6.72 and 1.68% for Tf AA, AD1, AD2, AE, D1D1, D1D2, D1E, D2E and EE types, and the gene frequencies of Tf A, D1, D2 and E were 0.197, 0.430, 0.191 and 0.081, respectively. 3. The pAlb locus were observed to be controlled by two alleles, pAlb F and S, and the distribution of genotypes were 42.86, 33.19 and 23.95% for pAlb FF, FS and SS types, and the gene frequencies were 0.595 and 0.405 for Tf F and S allele, respectively. Also the gene frequencies of Alb was 1.000 of Alb A allele. 4. The Cp locus were identified to be controlled by Cp F and S allele, and the distribution of genotypes were 23.11, 34.87 and 42.02% for Cp FF, FS and SS types, and the gene frequencies were 0.405 and 0.595 for Cp F and S allele, respectively. 5. The Am-I locus were observed to be genetically controlled by Am-I B and C allele, and the distribution of genotypes were 51.26, 16.81 and 31.92% for Am-I BB, BC and CC types, and the gene frequencies of Am-I B and C alleles were 0.597 and 0.403, respectively. 6. The Hb locus were found to be controlled by Hb A and B alleles, and the distribution of genotypes were 93.19, 16.39 and 0.42% for Hb AA, AB and BB types, and the gene frequencies of Hb A and B alleles were 0.914 and 0.086, respectively.

• Radiation Oncology Journal
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• v.13 no.2
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• pp.157-162
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• 1995

Lung cancer study group at Asan Medical Center has conducted the second prospective study to determine the efficacy and feasibility of MVP chemotherapy with concurrent hyperfractionated radiotherapy for Patients with stage III unresectable non-small cell lung cancer(NSCLC). All eligible Patients with stage III unresectable NSCLC were treated with hyperfractionated radiotherapy(120 cGy/fx BID. 6480 cGy/54fx) and concurrent 2 cycles of MVP(Mitomycin C $6mg/m^2,$ d2 & d29.Vinblastine $6mg/m^2,$ d2 & d29, Cisplatin $60mg/m^2,$ dl & d28) chemotherapy. Between Aug. 1993 and Nov. 1994, 62 patients entered this study; $6(10\%)$ had advanced stage IIIa and $56(90\%)$ had IIIb disease including 11 with pleural effusion and 10 with supraclavicular metastases. Among 62 patients, $48(77\%)$ completed planned therapy. Fourteen patients refused further treatment during chemoradiotherapy. Of 46 patients evaluable for response, $34(74\%)$ showed major response including $10(22\%)$ with complete and $24(52\%)$ with partial responses. Of 48 patients evaluable for toxicity, $13(27\%)$ showed grade IV hematologic toxicity but treatment delay did not exceed 5 days Two patients died of sepsis during chemoradiotherapy. Severe weight loss(more than $10\%)$ occurred in 9 patients$(19\%)$ during treatment. Nine patients$(19\%)$ developed radiation pneumonitis Six of these patients had grade 1 (mild) Pneumonitis with radiographic changes within the treatment fields Three other patients had grade 11 Pneumonitis, but none of these patients had continuous symptoms after steroid treatment. Concurrent chemoradiotherapy for patients with advanced NSCLC was well tolerated with acceptable toxicity and achieved higher response rates than the first study, but rather low compliance $rate(77\%)$ in this study is worrisome. We need to improve nutritional support during treatment and to use G-CSF to improve leukopenia and if necessary. supportive care will be given as in patients, Longer follow-up and larger sample size is needed to observe survival advantage.

• Tuberculosis and Respiratory Diseases
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• v.49 no.5
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• pp.601-613
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• 2000

Background : Idiopathic pulmonary fibrosis (IPF) is a fatal progressive fibrous disease of the lung of unknown etiology. Recently it has been classified into several distinct entities on the basis of pathologic and clinical characteristics, ie : usual interstitial pneumonia (UIP), desquamative interstitial pneumonia (DIP), acute interstitial pneumonia (AIP), bronchiolitis obliterans with organizing pneumonia (BOOP), and nonspecific interstitial pneumonia (NSIP). IPF is now applied only for UIP, which has the worst prognosis. The previous reports of 3-5 year median survival appears to be overoptimistic because other types with better prognosis like NSIP or BOOP might have been included. Therefore, this study was performed to determine the clinical course and the prognostic factors of UIP as diagnosed by surgical lung biopsy. Methods : The subjects were 72 UIP patients (age $58.2{\pm}11.6$ years, M : F=45 : 27, median follow up period : 18.1 months (0.7-103.6) diagnosed by surgical lung biopsy at the Asan Medical Center (68 patients) and the Paik Hospital in Seoul (4 patients). Clinical scores (level of dyspnea : 1-20 points), radiologic score (honeycombing : HC score 0-5 points, ground glass : GG score 0-5 points), and physiologic scores (FVC : 1-12 points, $FEV_1$ : 0-3 points, TLC : 0-10 points, $D_{LCO)$ : 0-5 points, $AaDO_2$ : 0-10 points) were summed into a total CRP score. Results : 1) The one year survival rate was 78.3%, while the rate for three year survival was 58.1%, and the median survival period was 42.5months. 2) Short term (1 year) prognosis : The patients who died within one year of diagnosis (14 patients) had the higher initial total CRP score ($28.6{\pm}8.3$ vs. $16.6{\pm}9.7$) than those who lived longer than one year (46 patients). The difference in the total CRP score was attributed to the symptom score ($8.4{\pm}2.1$ vs. $5.7{\pm}3.9$) and the physiologic score ($15.7{\pm}7.1$ vs. $6.7{\pm}5.7$) including FVC, $D_{LCO)$ and $AaDO_2$. 3) Long-term (3year) prognosis : The total CRP score ($12.2{\pm}6.7$ vs. $28.7{\pm}7.9$ : including symptom score, FVC, $D_{LCO)$ and $AaDO_2$) at the time of diagnosis were also different for the long-term survivors and those who lived less than 3 years. 4) Cox regression analysis showed $D_{LCO)$ (${\geq}$60%) (Hazard ratio : 4.56, 95% CI : 2.30-16.04) was the independent prognostic factors of UIP (P<0.05). Conclusion : These results suggest that $D_{LCO)$ at the time of diagnosis seem to be a prognostic markers of biopsy-proven UIP.

• Tuberculosis and Respiratory Diseases
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• v.49 no.5
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• pp.624-632
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• 2000

Background : Home ventilation can decrease hospital-acquired infection, increase physical activity, improve nutritional status, enhance quality of life, and reduce medical costs. The number of patient using home ventilators has been increasing, particularly in Europe and United States. Although the number of patients with home ventilation has been increasing in Korea, the current status of these patients is not well known. This study was undertaken to obtain basic information upon these patients in addition to evaluating any problems related to patients' home care in our country. Methods : A register of 92 patients with home ventilators in Seoul and Kyunggi Province were obtained from commercial ventilator supply companies. The patients were contacted by phone and 29 of them accepted our visit. Information concerning education about home care before discharge, equipment cost, and problems related to home care were documented. The mode and preset variables of the home ventilator were checked; tidal volume (TV), peak airway pressure, and oxygen saturation were measured. Results : There were 26 males (90%) and their mean age was 48.0 (${\pm}20.1$) years. The underlying diseases were : 21 neuromuscular disorders, 2 spinal cord injuries, 6 chronic lung diseases. Among the caregivers, spouses (n=14) predominated. Education for home care before discharge was performed primarily by intensive care unit nurses and the education for ventilator management by commercial companies. Twenty-five of the 29 patients had tracheostomies. Volume targeted type (VTT ; n=20, 69%) was more frequently used than the pressure targeted type (PTT). Twenty-three of the 29 patients purchased a ventilator privately, which cost 7,450,000 (${\pm}$3,290,000) won for a PTT, and 14,280.000 (${\pm}$3,130,000) won for a VTT. Total cost for the equipment was 11,430,000 (${\pm}$634,000) won. The average cost required for home care per month was 1,120,000 (${\pm}$1,360, 000) won. Conclusion : The commonest underlying disease of the patients was neuromuscular disease. The VTT ventilator was primarily used with tracheostomy. Patients and their families considered the financial difficulties associated with purchasing and maintaining equipment for home care an urgent problem. Some patients were aided by a visiting nurse, however most patients were neglected and left without professional medical supervision.

• Tuberculosis and Respiratory Diseases
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• v.47 no.3
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• pp.321-330
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• 1999

Background : Early diagnosis and proper antibiotic treatment are very important in the management of ventilator-associated pneumonia (VAP) because of its high mortality. Bronchoscopy with a protected specimen brush (PSB) has been considered the standard method to isolate the causative organisms of VAP. However, this method burdens consumer economically to purchase a PSB. Another useful method for the diagnosis of VAP is quantitative cultures of aspirated specimens through bronchoscopic bronchoalveolar lavage (BAL), for which the infusion of more than 120 m1 of saline has been recommended for adequate sampling of a pulmonary segment. However, occasionally it leads to deterioration of the patient's condition. We studied the diagnostic efficacy of minibronchoalveolar lavage (miniBAL), which retrieves only 25 ml of BAL fluid, in the isolation of causative organisms of VAP. Methods: We included 38 consecutive patients (41 cases) suspected of having VAP on the basis of clinical evidence, who had received antibiotics before the bronchoscopy. The two diagnostic techniques of PSB and miniBAL, which were performed one after another at the same pulmonary segment, 'were compared prospectively. The cut-off values for quantitative cultures to define causative bacteria of VAP were more than $10^3$ colony-forming units (cfu)/ml for PSB and more than $10^4$ cfu/ml for BAL. Results: The amount of instilled normal saline required to retrieve 25 ml of BAL fluid was $93{\pm}32 ml$ (mean${\pm}$SD). The detection rate of causative agents was 46.3% (19/41) with PSB and 43.9% (18/41) with miniBAL. The concordance rate of PSB and miniBAL in the bacterial culture was 85.4% (35/41). Although arterial blood oxygen saturation dropped significantly (p<0.05) during ($92{\pm}10%$) and 10 min after ($95{\pm}3%$) miniBAL compared with the baseline ($97{\pm}3%$), all except 3 cases were within normal ranges. The significantly elevated heart rate during ($l25{\pm}24$/min, p<0.05) miniBAL compared with the baseline ($1l1{\pm}22$/min) recovered again in 10 min after ($111{\pm}26$/min) miniBAL. Transient hypotension was developed during the procedure in two cases. The procedure was stopped in one case due to atrial flutter. Conclusion: MiniBAL is a safe and effective technique to detect the causative organisms of VAP.

• Tuberculosis and Respiratory Diseases
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• v.49 no.2
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• pp.149-161
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• 2000

Background : Residual pleural thickening (RPT) develops in about 50% of tuberculous pleurisy ($PL_{TB}$). Some reports have suggested that elevated TNF-$\alpha$ and impaired fibrinolysis could be the cause of RPT, but until now, the mechanism and predictors of RPT have not been well known. TGF-$\beta$ has been known to promote fibrogenesis and is increased in tuberculous pleural fluid (PF). $PL_{TB}$ and malignant pleurisy ($PL_{MAL}$) manifest lymphocyte-dominant exudative pleural effusion, and it has clinical implications in the differentiation of the two diseases based on the findings of pleural effusion. We performed this study to compare pleural fluid TNF-$\alpha$ TGF-$\beta$, and fibrinolytic parameters between $PL_{TB}$ and $PL_{MAL}$, and to find the predictors of RPT in $PL_{TB}$. Methods : Thirty-five $PL_{TB}$ and 14 $PL_{MAL}$ patients who were admitted to the Asan Medical Center from February 1997 to August 1999 were enrolled. All $PL_{TB}$ patients were prescribed a primary, short-course, anti-tuberculosis regimen. INF-$\alpha$ tissue plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI-1), plasminogen, $\alpha$2-antiplasmin, and D-dimer were measured in both PF and PB. TGF-$\beta$was measured only in PF. Clinical characteristics, TNF-$\alpha$ TGF-$\beta$ and fibrinolytic parameters were compared between patients with RPT less than 2 mm and patients with more than 2 mm of the thirty patients who completed the anti-tuberculosis treatment. Results : The levels of TNF-$\alpha$ tPA, PAI-1, plasminogen, $\alpha$2-antiplasmin, and D-dimer in PF were higher than those in peripheral blood (PB) in $PL_{TB}$, whereas only plasminogen, $\alpha$2-antiplasmin, and D-dimer were higher in PF than in PB in $PL_{MAL}$. Pleural fluid TNF-$\alpha$ TGF-$\beta$, PAI-1, plasminogen, $\alpha$2-antiplasmin were increased in $PL_{TB}$ compared with $PL_{MAL}$, but these factors did not show any further advantages over ADA in differentiation between $PL_{TB}$ and $PL_{MAL}$. TNF-$\alpha$ TGF-$\beta$ and fibrinolytic parameters did not show any differences between patients with RPT less than 2 mm and patients with RPT more than 2 mm. Conclusion : Our data suggest that TNF-$\alpha$, TGF-$\beta$ and fibrinolytic parameters may play some role for the development of RPT in $PL_{TB}$, but they failed to predict the occurrence of RPT in $PL_{TB}$. Also these parameters did not seem to have any advantages over ADA in differentiating between two diseases.

• Tuberculosis and Respiratory Diseases
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• v.46 no.3
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• pp.350-362
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• 1999

Background: Acute Respiratory failure which is developed after extubation in the weaning process from mechanical ventilation is an important cause of weaning failure. Once it was developed, endotracheal reintubation has been done for respiratory support. Noninvasive Positive Pressure Ventilation (NIPPV) has been used in the management of acute or chronic respiratory failure, as an alternative to endotracheal intubation, using via nasal or facial mask. In this study, we evaluated the usefulness of NIPPV as an alternative method of reintubation in patients who developed acute respiratory failure after extubation. Method: We retrospectively analyzed thirty one patients(eighteen males and thirteen females, mean ages $63\pm13.2$ years) who were developed acute respiratory failure within forty eight hours after extubation, or were extubated unintentionally at medical intensive care unit(MICU) of Asan Medical Center. NIPPV was applied to the patients. Ventilatory mode of NIPPV, level of ventilatory support and inspiratory oxygen concentration were adjusted according to the patient condition and results of blood gas analysis by the attending doctors at MICU. NIPPV was completely weaned when the patients maintained stable clinical condition under 8 $cmH_2O$ of pressure support level. Weaning success was defined as maintenance of stable spontaneous breathing more than forty eight hours after discontinuation of NIPPV. Respiratory rate, heart rate, arterial blood gas analysis, level of pressure support, and level of PEEP were monitored just before extubation, at thirty minutes, six hours, twenty four hours after initiation of NIPPV. They were also measured at just before weaning from NIPPV in success group, and just before reintubation in failure group. Results: NIPPV was successfully applied to thirty-one patients of thirty-two trials and one patient could not tolerated NIPPV longer than thirty minutes. Endotracheal reintubation was successfully obviated in fourteen patients (45%) among them. There was no difference in age, sex, APACHE III score on admission at MICU, duration of intubation, interval from extubation to initiation of NIPPV, baseline heart rate, respiratory rate, arterial blood gas, and $PaO_2/FiO_2$ between the success and the failure group. Heart rate and respiration rate were significantly decreased with increase $SaO_2$ after thirty minutes of NIPPV in both groups(p<0.05). However, in the patients of failure group, heart rate and respiratory rate were increased again with decrease in $SaO_2$ leading to endotracheal reintubation. The success rate of NIPPV treatment was significantly higher in the patients with COPD compared to other diseases(62% vs 39%) (p=0.007). The causes of failure were deterioration of arterial blood gas without aggravation of underlying disease(n=9), aggravation of undelying disease(n=5), mask intolerance(n=2), and retained airway secretion(n=l). Conclusion: NIPPV would be a useful therapeutic alternative which can avoid reintubation in patient who developed acute respiratory failure after extubation.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.813-822
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• 1998

Background: Extubation is recommended to be performed at minimum pressure support (PSmin) during the pressure support ventilation (PSV). In field, physicians sometimes perform additional 1 hr T-piece trial to the patient at PSmin to reduce re-intubation risk. Although it provides confirmation of patient's breathing reserve, weaning could be delayed due to increased airway resistance by endotracheal tube. Methods: To investigate the effect of additional 1 hr T-piece trial on weaning outcome, a prospective study was done in consecutive 44 patients who had received mechanical ventilation more than 3 days. Respiratory mechanics, hemodymic, and gas exchange measurements were done and the level of PSmin was calculated using the equation (PSmin=peak inspiratory flow rate $\times$ total ventilatory system resistance) at the 15cm $H_2O$ of pressure support. At PSmin, the patients were randomized into intervention (additional 1 hr T-piece trial) and control (extubation at PSmin). The measurements were repeated at PSmm, during weaning process (in cases of intervention), and after extubation. The weaning success was defined as spontaneous breathing more than 48hr after extubation. In intervention group, failure to continue weaning process was also considered as weaning failure. Results: Thirty-six patients with 42 times weaning trial were satisfied to the protocol. Mean PSmin level was 7.6 (${\pm}1.9$)cm $H_2O$. There were no differences in total ventilation times (TVT), APACHE III score, nutritional indices, and respiratory mechanics at PSmin between 2 groups. The weaning success rate and re-intubation rate were not different between intervention group (55% and 18% in each) and control group (70% and 20% in each) at first weaning trial. Work of breathing, pressure time product, and tidal volume were aggravated during 1 hr T-piece trial compared to those of PSmin in intervention group ($10.4{\pm}1.25$ and $1.66{\pm}1.08$ J/L in work of breathing) ($191{\pm}232$ and $287{\pm}217$cm $H_2O$ s/m in pressure time product) ($0.33{\pm}0.09$ and $0.29{\pm}0.09$ L in tidal volume) (P<0.05 in each). As in whole, TVT, and tidal volume at PSmin were significantly different between the patients with weaning success ($246{\pm}195$ hr, $0.43{\pm}0.11$ L) and the those with weaning failure ($407{\pm}248$ hr, $0.35{\pm}0.10$L) (P<0.05 in each). Conclusion : There were no advantage to weaning outcome by addition of 1 hr T-piece trial compared to prompt extubation to the patient at PS min.

• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.128-139
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• 1998

Background: It is well known that various cytokines and growth factors secreted mainly from alveolar macrophages do the key role in the pathogenesis of IPF. But recently it has been known that structural cells like fibroblast can also release cytokines. So the phenotypic changes in fibroblasts of IPF may do a role in continuous progression of fibrosis. The aim of this study is to find out whether there is a change in the biologic properties of the lung fibroblasts of IPF. Subjects and Method: The study was done on 13 patients with IPF diagnosed by open or thoracoscopic lung biopsy and 7 control patients who underwent resectional surgery for lung cancer. Lung fibroblast cell lines (FB) were established by explant culture technique from the biopsy or resected specimen Result: Basal proliferation of the fibroblast of IPF(IFB) measured by BrdU uptake tended to be highter than control fibroblast(NFB) (0.212 0.107 vs $0.319{\pm}0.143$, p=0.0922), also there was no significant difference in proliferation after the stimulation with PDGF or 10% serum. On the contrary, the degree of inhibition in proliferation by PGE2 was significantly lower($33.0{\pm}13.1%$) in IFB than control($46.7{\pm}10.0%$, p=0.0429). The IFB secreted significantly higher amount of MCP-l($l574{\pm}1283$ pg/ml) spontaneously than NFB($243{\pm}100$ pg/ml) and also after the stimulation with TGF-$\beta$($3.23{\pm}1.31$ ng/ml vs $0.552{\pm}0.236$ ng/ml, p=0.0012). Similarly IL-8 and IL-6 seretion of IFB was significantly higher than NFB at basal state and with TGF-$beta$ stimulation. But after the maximal stimulation with IL-1,8, no significant difference in cytokine secretion was found between IFB and NFB. Conclusion : Above data suggest that the fibroblasts of IPF were phenotypically changed and these change may do a role in the pathogenesis of IPF.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.954-964
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• 1996

Background : The type of the infiltrating cells in al veolitis may be determined by the chemokines in the lesion. MIP-1 ${\alpha}$, a C-C type chemokine, stimulates proliferation and cytokine secretion from macrophages and induces early neutrophilic and later monocytic inflammation in vi vo. IL-8, a C-X-C type chemokine is known to attract neutrophils and T-lymphocytes. This study is performed to find out the relative role of two different chemokines in diffuse interstitial lung disease. Subject and Method : We measured the secretion of MIP- 1 ${\alpha}$ and IL-8 from alveolar macrophages(AM), and their level in BAL fluid of 26 patients with DILD (10 IPF, 4 collagen disease, 10 sarcoidosis, and 2 hypersensitivity pneumonitis) and 7 normal control. Result: IL-8 secretion was significantly increased in patients with DILD ($8.15{\pm}4.58$ ng/ml) than in normal ($1.10{\pm}0.93$ ng/ml, p=0.0003). Significant correlation was found between IL-8 secretion and total cell number in BAL fluid (r=0.484, p=0.0068), %(r=0.592, p=0.0004) and No. (r=0.516, p=0.0042) of lymphocyte, and % of AM (r=-0.505, 0.0032). MIP- 1 ${\alpha}$ secretion was also increased in DILD ($2.41{\pm}1.45$ ng/ml) compared to control ($0.63{\pm}0.30$ ng/ml, p=0.0031), and showed a tendency of correlation with total cell number (r=0.368, p=0.0456) and No. of alveolar macrophages (r=0.356, p=0.0579) in BAL fluid. The concentration of IL-8 in BAL fluid was significantly increased in the patients with DILD ($40.4{\pm}34.5$ pg/ml) compared to control ($3.90{\pm}2.47$ pg/ml, p=0.0094) and it showed a significant correlation with the total cell number (r=0.484, p=0.0068), %(r=-0.505, p=0.0032) of AM, and % (r=0.592, p=0.0004) and No. (r=0.516, p=0.0042) of lymphocyte in BAL fluid. But there was a no significant difference in MIP- 1 ${\alpha}$ concentration in BAL fluid between normal control group and the patients with DILD. Conclusion : From the above results, we concluded that AM of DILD releases increased amount of both IL-8 and MIP- 1 ${\alpha}$ but IL-8 has better correlation with the type of alveolitis.