• The Korean Society of Law and Medicine
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• v.17 no.1
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• pp.299-346
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• 2016

There were also various decisions made in medical area in 2015. In the case that an inmate in a sanatorium was injured due to the reason which can be attributable to the sanatorium and the social welfare foundation that operates the sanatorium request treatment of the patient, the court set the standard of fixation of a party in medical contract. In the case that the family of the patient who was declared brain dead required withdrawal of meaningless life sustaining treatment but the hospital rejected and continued the treatment, the court made a decision regarding chargeable fee for such treatment. When it comes to the eye brightening operation which received measure of suspension from the Ministry of Health and Welfare for the first time in February, 2011, because of uncertainty of its safety, the court did not accept the illegality of such operation itself, however, ordered compensation of the whole damage based on the violation of liability for explanation, which is the omission of explanation about the fact that the cost-effectiveness is not sure as it is still in clinical test stage. There were numerous cases that courts actively acknowledged malpractices; in the cases of paresis syndrome after back surgery, quite a few malpractices during the surgery were acknowledged by the court and in the case of nosocomial infection, hospital's negligence to cause such nosocomial infection was acknowledged by the court. There was a decision which acknowledged malpractice by distinguishing the duty of installation of emergency equipment according to the Emergency Medical Service Act and duty of emergency measure in emergency situations, and a decision which acknowledged negligence of a hospital if the hospital did not take appropriate measures, although it was a very rare disease. In connection with the scope of compensation for damage, there were decisions which comply with substantive truth such as; a court applied different labor ability loss rate as the labor ability loss rate decreased after result of reappraisal of physical ability in appeal compared to the one in the first trial, and a court acknowledged lower labor ability loss rate than the result of appraisal of physical ability considering the condition of a patient, etc. In the event of any damage caused by malpractice, in regard to whether there is a limitation on liability in fee charge after such medical malpractice, the court rejected the hospital's claim for setoff saying that if the hospital only continued treatments to cure the patient or prevent aggravation of disease, the hospital cannot charge Medical bills to the patient. In regard to the provision of the Medical Law that prohibit medical advertisement which was not reviewed preliminarily and punish the violation of such, a decision of unconstitutionality was made as it is a precensorship by an administrative agency as the deliberative bodies such as Korean Medical Association, etc. cannot be denied to be considered as administrative bodies. When it comes to the issue whether PRP treatment, which is commonly performed clinically, should be considered as legally determined uninsured treatment, the court made it clear that legally determined uninsured treatment should not be decided by theoretical possibility or actual implementation but should be acknowledged its medical safety and effectiveness and included in medical care or legally determined uninsured treatment. Moreover, court acknowledged the illegality of investigation method or process in the administrative litigation regarding evaluation of suitability of sanatorium, however, denied the compensation liability or restitution of unjust enrichment of the Health Insurance Review & Assessment Service and the National Health Insurance Corporation as the evaluation agents did not cause such violation intentionally or negligently. We hope there will be more decisions which are closer to substantive truth through clear legal principles in respect of variously arisen issues in the future.

• Journal of Sasang Constitutional Medicine
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• v.11 no.2
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• pp.1-26
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• 1999

This paper was written in order to understand each constitutional symptoms and diseases with two aspects. The first was to trace the courses to accomplish constitutional symptoms and diseases from that of oriented medicine through "Dongyi Bogam" and the original writing such as "Shanghanlun". The second was to analyze the constitutional diseases with Lee Je-ma's own recognition on human being and the society which was based on the "Dongyi Suse Bowon". The original concepts of 'The Interior Disease' and 'The Exterior Disease' were based on the Nature and the Emotion, the Environmental Frames and the Human Affairs, the Ears Eyes Nose Mouth and the Lung Spleen Liver Kidney. The exterior disease were caused by the abilities of ears to listen, eyes to see, nose to smell, and mouth to taste on the environmental frames which were related one's recognition to society. The interior diseases were caused by the abilities of lung to study, spleen to ask, liver to think, kidney to judge on human affairs which were related the relationship between me and others. So the titles of constitutional diseases were named by these views on his first writing of "Dongyi Suse Bowon" in 1894. So the titles of Taeyangin diseases, 'The lumbar Vertebae Disease Induced by Exopathogen' and 'The Small Intestine Disease Induced by Endopathogen' were still remained as the first writing. But the titles of constitutional diseases were rewritten such as present titles in 1900. In order to express pathology and mechanism of constitutional diseases exactly, he rewrote titles which contained the manifestation sites of diseases, and the symptoms of febrile and cold, and the different congenital formations of organs. The exterior diseases and interior diseases had three characteristics. The first was that the exterior disease injured by the nature which had a tendency to progress slowly and the interior disease injured by the emotion which had a tendency to progress rapidly. The second was not that the interior disease and the exterior disease were separated, but that one influenced the other and these were revealed as a disease together when the diseases continued for a long time. The third was that even though the disease caught together it was included the beginning disease. The symptoms in ordinary times was the origin and clue to recognize the constitutional symptoms and diseases. It enabled to establish the constitutional medicine which treated by different ways according to constitution. It had two characteristics which were different from the Traditional Chinese Medicine in appearance of diseases. The first was that the disease was progressed to the next step from the symptoms in ordinary times. The second was that each constitution had different symptoms which were due to symptoms in ordinary times under the same disease, The third was the manifestation of disease were different from symptoms in ordinary times in the same constitution. But the most important thing was that Lee Je-ma recognized these symptoms in ordinary times as four categories and he presented constitutional symptoms and constitutional disease. The four categories were the method to recognize the human being and the diseases for him As the symptoms and diseases of Sasang Constitutional Medicine were compared to Traditional Chinese Medicine, the constitutional diseases of "Dongyi Suse Bowon" could be classified into two groups. The first group was the unique diseases and symptoms, which were not in the Traditional Chinese Medicine, and which were established by the Lee Je-ma. These contained the diseases of taeyangin, the exterior disease of taeumin, the exterior disease of soyangin. The second group used the unique methods to treat disease, which were not in Traditional Chinese Medicine, and which were established by Lee Je-ma. This contained the interior disease of taeumin, the delirium diseases from the MangYin of soyangin, the treatment to help the Yang-Qi ascend and to supplement the ql In the exterior disease of soeumin. Especially, the diseases of taeyangin and taeumin which were caused by the metabolism disorders of Qi-Yack(氣液) were the great achievement to establish constitutional symptoms and diseases. The discourse of taeyangin diseases presented his original thought to recognize the symptoms and diseases through the Shin Gi Hyul Jeong(神氣血精) and the Qi-Yack, the discourse of taeumin diseases presented the disperse of Qi-Yack through the forward and backward of sweat, the discourse of soyangin disease presented the sweat of hand and feet which was manifested that yin-qi of spleen descended to yin qi of kidney, and the bowel movement which was manifested that yang qi of large intestine ascend to head, face and four extremities, the discourse of soeumin disease presented the Jueyin syndrome without the abdominal pain and diarrhea as the exterior disease and made importance to the nervous mind And the classification of exterior diseases and interior diseases were not due to the pharmacology but due to the symptoms and diseases according to the constitution.

• Tuberculosis and Respiratory Diseases
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• v.40 no.1
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• pp.6-15
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• 1993

Background: Positive end, expiratory pressure (PEEP) has become one of the standard therapies for adult respiratory distress syndrome (ARDS). Total static compliance has been proposed as a guide to determine the size of PEEP ('best PEEP') which is of unproven clinical benefit and remains controversial. Besides increasing functional residual capacity and thus improving oxygenation, PEEP stimulate prostacyclin secretion and was proposed for the treatment of acute pulmonary embolism. But little is known about the effect of PEEP on hemodynamic and gas exchange disturbances in acute pulmonary embolism. Methods: To study the validity of total static compliance as a predictor of 'best PEEP' in ARDS and acute pulmonary embolism, experimental ARDS was induced in mongrel dog with oleic acid and acute pulmonary embolism with autologous blood clot. Then hemodynamic and gas exchange parameters were measured with serial increment of PEEP. Results:In ARDS group, total static compliance and oxygen transport were maximal at 5 cm$H_2O$, and decreased thereafter (p<0.05). With increment of PEEP, arterial oxygen tension ($PaO_2$) and arterial carbon dioxide tension ($PaCO_2$) increased and cardiac output and physiological shunt decreased. In pulmonary embolism group, total static compliance, oxygen transport, physiological shunt and cardiac output decreased and $PaO_2$ and $PaCO_2$ increased with increment of PEEP (p<0.05). Comparing the change induced by increment of PEEP by 1 cm$H_2O$ in ARDS group with that in pulmonary embolism group, there was no significant difference between two groups except cardiac output which decreased more in pulmonary embolism group (p<0.05). In ARDS group, oxygen transport and total static compliance increased after PEEP application, and total static compliance was maximal at the PEEP level where oxygen transport was maximal. However in pulmonary embolism group, oxygen transport and total static compliance decreased after application of PEEP. There was significant correlation between change of total static compliance and change of oxygen transport in both groups. Conclusion: In both ARDS and acute pulmonary embolism, it can be concluded that total static compliance is useful as a predictor of 'best PEEP'.

• Journal of Chest Surgery
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• v.38 no.7 s.252
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• pp.483-488
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• 2005

Aortic valve-sparing procedures could reduce valve-related morbidity, but may increase operative risks; therefore, these procedures could not be performed routinely. We attempted to find out the early results while focusing on the operative risks associated with these procedures in our hospital. Material and Method: From May 1996 to July 2003, 26 patients underwent these procedures including 15 patients with Marfan syndrome and 1 patient with Behcet disease. There were 17 men and 9 women with mean age of $37.9\pm19.2$ years (range: 6 months-74 years). Ten patients had ascending aortic dissection, 18 patients had more than moderate degree of aortic valve insufficiency (AI). Two types of valve-sparing procedures were performed: valve reimplantation in 14 and root remodeling in 12 patients. Associated procedures were performed as follows: aortic valve plasty in 6, mitral valve plasty in 5, hemi-arch replacement in 4, total arch replacement in 2, coronary artery bypass surgery in 1 and Maze procedure in 1 patient(s). Result: In four patients, valve-sparing procedures were converted to Bentall procedures during operation. Including these patients, there was no operative deaths, 3 patients underwent re-operation due to bleeding, 1 patient had permanent pacemaker. The median duration of ICU stay was 45.5 hours, the median duration of hospital stay was 10.5 days. In 22 patients excluding 4 converted patients, intraoperative transesophageal echocardiogram (TEE) showed less than mild degree of AI in all except one who had not received intra-operative TEE in the beginning and showed moderate degree of AI at discharge. The mean duration of follow-up was $21.2\pm27.4$ months. All patients were alive except one who died during other departmental surgery. In 3 patients, more than moderate degree of AI was recurred, but there were no reoperation. Conclusion: Aortic valve-sparing procedures could be performed relatively safely in selected patients who had annuloaortic ectasia.

• Journal of Chest Surgery
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• v.36 no.8
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• pp.545-558
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• 2003

Adult respiratory distress syndrome (ARDS) is of particular interest because of its severity of the associated lung injury and its high mortality. However, the pathophysiologies of ARDS in infant and childhood groups are still not well clarified inspite of many previous investigations. To investigate the time course of pathophysiology of ARDS in infant and childhood groups, this study was designed with experimental endotoxin-induced ARDS model using young rabbits (8 week-old). Material and Method: Rabbits were divided into the control group (n=8) and the endotoxin-treated group (n=32). The endotoxin group was subdivided into 4 groups by the sampling times as 3, 6, 12 and 24 hr-groups (G- $E_{3,6,12,24,}$ each n=8). The experimental ARDS was made by a bolus injection of endotoxin (Escherichia coli serotype 055 : B5, 0.50 mg/kg) via rabbit ear vein. For evaluation of the hematologic and inflammatory markers, and superoxide dismutase (SOD) concentrations, the blood samples were taken from the heart. The bronchoalveolar lavage fluid (BALF) were obtained for analysis of the leukocytes and protein concentration. With biopsy of the lung, histopathologic changes of the lung were also evaluated. Result: In the endotoxin groups, significant leukopenia (owing to pancytopenia) occurred in 3 and 6-hr groups, which was followed by significant leukocytosis (owing to neutrophilia) in the 12 and 24-hr groups (p<0.05). Serum levels of tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and interleukin-1 $\beta$ (IL-1 $\beta$) in the endotoxin groups were higher than those of control group (p<0.05). Serum levels of superoxide dismutase (SOD) of G- $E_{3}$ and G- $E_{6}$ were higher than those of control group, whereas those of G- $E_{12}$ were lower than those of control groups (p<0.05). Total leukocyte counts and protein con-centrations in BALF were significantly elevated in the endotoxin groups compared to the control group (p < 0.05). The hemorrhagic pattern of BALF showed occurred in the endotoxin groups. The endotoxin groups (in G- $E_{6}$) had severe infiltration of inflammatory cells (lymphocyte and monocyte) in the pulmonary interstitium and parenchyma, migrations of neutrophil and eosinophil into alveolar spaces and interstitial widening, which are the evidences of acute lung injury. In the endotoxin groups, there were significant positive correlations between the BALF findings and the immunologic markers (TNF-$\alpha$, IL-1$\beta$, SOD) (p<0.05). Conclusion: Severe acute lung injury occurred in all the endotoxin-treated rabbits. The pathophysiologic findings were so progressive until 6-hr by time dependant pattern, and then recovered slowly, Variable hematologic, immuno-logic, and pathologic factors were well correlated in the development and progression of endoxin-induced lung injury. The pathophysiologic responses were sensitive and rapid in young rabbit Young rabbit seemed to be a useful experimental animal model for infant and childhood groups.roups.

• Journal of the Korean Institute of Traditional Landscape Architecture
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• v.36 no.3
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• pp.115-127
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• 2018

This study was attempted to find out the value of cultural assets through the clear diagnosis and prescription of the dead and weakness factors of the Population of Retusa Fringe Trees in Pyeongji-ri, Jinan(Natural Monument No. 214), The results are as follows. First, Since the designation of 13 natural monuments in 1968, since 1973, many years have passed since then. In particular, despite the removal of some of the buried soil during the maintenance process, such as retreating from the fence of the primary school after 2010, Second, The first and third surviving tree of the designated trees also have many branches that are dead, the leaves are dull, and the amount of leaves is small. vitality of tree is 'extremely bad', and the first branch has already been faded by a large number of branches, and the amount of leaves is considerably low this year, so that only two flowers are bloomed. The second is also in a 'bad'state, with small leaves, low leaf density, and deformed water. The largest number 1 in the world is added to the concern that the s coverd oil is assumed to be paddy soils. Third, It is found that the composition ratio of silt is high because it is known as '[silty loam(SiL)]'. In addition, the pH of the northern soil at pH 1 was 6.6, which was significantly different from that of the other soil. In addition, the organic matter content was higher than the appropriate range, which is considered to reflect the result of continuous application for protection management. Fourth, It is considered that the root cause of failure and growth of Jinan pyeongji-ri Population of Retusa Fringe Trees group is chronic syndrome of serious menstrual deterioration due to covered soil. This can also be attributed to the newly planted succession and to some of the deaths. Fifthly, It is urgent to gradually remove the subsoil part, which is estimated to be the cause of the initial damage. Above all, it is almost impossible to remove the coverd soil after grasping the details of the soil, such as clayey soil, which is buried in the rootstock. After removal of the coverd soil, a pestle is installed to improve the respiration of the roots and the ground with Masato. And the dead 4th dead wood and the 5th and 6th dead wood are the best, and the lower layer vegetation is mown. The viable neck should be removed from the upper surface, and the bark defect should undergo surgery and induce the development of blindness by vestibule below the growth point. Sixth, The underground roots should be identified to prepare a method to improve the decompression of the root and the respiration of the soil. It is induced by the shortening of rotten roots by tracing the first half of the rootstock to induce the generation of new roots. Seventh, We try mulching to suppress weed occurrence, trampling pressure, and soil moisturizing effect. In addition, consideration should be given to the fertilization of the foliar fertilizer, the injection of the nutrients, and the soil management of the inorganic fertilizer for the continuous nutrition supply. Future monitoring and forecasting plans should be developed to check for changes continuously.

• Tuberculosis and Respiratory Diseases
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• v.41 no.4
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• pp.379-388
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• 1994

Background : In sleep apnea syndrome, arterial oxygen saturation($SaO_2$) decreases at a variable rate and to a variable degree for a given apneic period from patient to patient, and various kinds of cardiac arrythmia are known to occur. Factors supposed to affect arterial oxygen desaturation during apnea are duration of apnea, lung voulume at which apnea occurs, and oxygen consumption rate of the subject. The lung serves as preferential oxygen source during apnea, and there have been many reports related with the influence of lung volume on $SaO_2$ during apnea, but there are few, if any, studies about the influence of oxygen consumption rate of an individual on $SaO_2$ during breath holding or about the profile of arterial oxygen resaturation after breathing resumed. Methods : To investigate the changes of $SaO_2$ and heart rate(HR) during breath holding(BH) and rebreathing(RB) and to evaluate the physiologic factors responsible for the changes, lung volume measurements, and arterial blood gas analyses were performed in 17 healthy subjects. Nasal airflow by thermistor, $SaO_2$ by pulse oxymeter and ECG tracing were recorded on Polygraph(TA 4000, Gould, U.S.A.) during voluntary BH & RB at total lung capacity(TLC), at functional residual capacity(FRC) and at residual volume(RV), respectively, for the study subjects. Each subject's basal metabolic rate(BMR) was assumed on Harris-Benedict equation. Results: The time needed for $SaO_2$ to drop 2% from the basal level during breath holding(T2%) were $70.1{\pm}14.2$ sec(mean${\pm}$standard deviation) at TLC, $44.0{\pm}11.6$ sec at FRC, and $33.2{\pm}11.1$ sec at RV(TLC vs. FRC, p<0.05; FRC vs. RV, p<0.05). On rebreathing after $SaO_2$ decreased 2%, further decrement in $SaO_2$ was observed and it was significantly greater at RV($4.3{\pm}2.1%$) than at TLC($1.4{\pm}1.0%$)(p<0.05) or at FRC($1.9{\pm}1.4%$)(p<0.05). The time required for $SaO_2$ to return to the basal level after RB(Tr) at TLC was not significantly different from those at FRC or at RV. T2% had no significant correlation either with lung volumes or with BMR respectively. On the other hand, T2% had significant correlation with TLC/BMR(r=0.693, p<0.01) and FRC/BMR (r=0.615, p<0.025) but not with RV/BMR(r=0.227, p>0.05). The differences between maximal and minimal HR(${\Delta}HR$) during the BH-RB manuever were $27.5{\pm}9.2/min$ at TLC, $26.4{\pm}14.0/min$ at RV, and $19.1{\pm}6.0/min$ at FRC which was significantly smaller than those at TLC(p<0.05) or at RV(p<0.05). The mean difference of 5 p-p intervals before and after RB were $0.8{\pm}0.10$ sec and $0.72{\pm}0.09$ sec at TLC(p<0.001), $0.82{\pm}0.11$ sec and $0.73{\pm}0.09$ sec at FRC(p<0.025), and $0.77{\pm}0.09$ sec and $0.72{\pm}0.09$ sec at RV(p<0.05). Conclusion Healthy subjects showed arterial desaturation of various rates and extent during breath holding at different lung volumes. When breath held at lung volume greater than FRC, the rate of arterial desaturation significantly correlated with lung volume/basal metabolic rate, but when breath held at RV, the rate of arterial desaturation did not correlate linearly with RV/BMR. Sinus arrythmias occurred during breath holding and rebreathing manuever irrespective of the size of the lung volume at which breath holding started, and the amount of change was smallest when breath held at FRC and the change in vagal tone induced by alteration in respiratory movement might be the major responsible factor for the sinus arrythmia.

• Tuberculosis and Respiratory Diseases
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• v.54 no.2
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• pp.219-229
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• 2003

Background : The management of thoracic empyema and complicated parapneumonic effusion requires adequate antibiotics use and prompt drainage of infected pleural space. Tube thoracostomy for loculated empyema has low success rate and is also an invasive procedure with potential morbidity. Complications include hemothorax, perforation of intra-abdominal or intra-thoracic organs, diaphragmatic laceration, empyema, pulmonary edema, and Horner's syndrome. Given the potential morbidity of traditional chest tube insertion, use of the image-guided pigtail catheter drainage(PCD) of empyema has been employed. We retrospectively analyzed the medical records of patients with empyema or complicated parapneumonic effusion to determine the efficacy of percutaneous pigtail catheter drainage. Materials and Methods : 45 patients with complicated parapneumonic effusions or empyema were treated at Gil medical center from January 1998 to June, 1999. All were initially given PCD procedure and the following data were collected: clinical symptoms at the time of diagnosis, alcohol and smoking history, the characteristics of pleural effusion, radiologic findings (at the time of catheter insertion, removal and 1 month after catheter removal), the amount of effusion drained for initial 24 hours, the time from catheter insertion to removal and the use of surgical approach. Results : Male gender was more frequent (42 men vs. 3 women), the mean age of the study population was 52(range: 21~74) years. Empyema was found in 23 patients, complicated parapneumonic effusion in 22 patients. Four patients(three, parapneumonic effusion and one, with empyema) with PCD only treated, were cast off. Among the available patients, 36(80%) patients were treated with PCD only or PCD with urokinase. Among the 23 patients with empyema, surgical approach was required in five patients(27.1%, one required decortication, four open thoracostomy), one patient, treated with surgical procedure, died of sepsis. There was no significant difference of the duration of catheter insertion, the duration of hospital admission after catheter insertion and the mean amount of effusion drained for initial 24 hours between the patients with only PCD treated and the patients treated with PCD and urokinase. The duration of catheter insertion($9.4{\pm}5.25days$ vs. $19.2{\pm}9.42days$, p<0.05) and the duration of hospital admission after catheter insertion($15.9{\pm}10.45days$ vs. $38.6{\pm}11.46days$, p<0.01) of the patients with only PCD treated were more longer than those of the patients treated with surgical procedure after PCD. They were same between the patients treated with urokinase after PCD and the patients treated with surgical procedure after PCD($11.1{\pm}7.35days$ vs. $19.2{\pm}9.42days$, p<0.05, $17.5{\pm}9.17days$ vs. $38.6{\pm}11.46days$, p<0.01). In 16 patients(44.4%) with only PCD treated or PCD and urokinase treated, the amount of effusion at the time of catheter removal was decreased more than 75% and in 17 patients(47.2%) effusion decreased 50~75%. .In one patient effusion decreased 25~50%, in two patients effusion decreased less than 25%. One month after catheter removal, in 35 patients(97.2%, four patients were cast off), the amount of pleural effusion was successfully decreased more than 50%. There were no complications related to pigtail catheter insertion. Conclusion : In this study, PCD seemed to be an early efficacious procedure in treating the patients with complicated parapneumonic effusion or empyema without any serious procedure related complication.

• Tuberculosis and Respiratory Diseases
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• v.43 no.3
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• pp.308-322
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• 1996

Background : Neutrophils are considered to play critical roles in the development of acute respiratory distress syndrome. Histamine, which is distributed abundantly in lung tissue, increases the rolling of neutrophills via increase of P-selectin expression on the surface of endothelial cells and is known to have some interrelationships with IL-1, IL-8 and TNF-$\alpha$. We studied to investigate the effect of the histamine on the acute lung injury of the rats induced by intratracheal insufflation of TNF-$\alpha$ which has less potency to cause lung injury compared to IL-1 in rats. Methods : We intratracheally instilled saline or TNF(R&D, 500ng), IL-1(R&D, 50ng)or histamine of varius dose(1.1, 11 and $55\;{\mu}g/kg$) with and without TNF separately in Sprague-Dawley rats weighing 270-370 grams. We also intratracheally treated IL-1(50ng) along with histamine($55\;{\mu}g/kg$). In cases, there were synergistic effects induced by histamine on the parameters of TNF-induced acute lung injury, antihistamines(Sigma, mepyramine as a $H_1$ receptor blockade and ranitidine as a $H_2$ receptor blockade, 10 mg/kg in each)were co-administered intravenously to the rats treated TNF along with histamine($1.1\;{\mu}g/kg$) intratraeheally. Then after 5 h we measured lung lavage neutrophil numbers, lavage cytokine-induced neutrophil chemoattractants(CINC), lung myeloperoxidase activity(MPO) and lung leak. We also intratracheally insufflated TNF with/without histamine($11\;{\mu}g/kg$), then after 24 h measured lung leak in rats. Statistical analyses were done by Kruskal-Wallis nonparametric ANOVA test with Dunn's multiple comparison test or by Mann-Whitney U test. Results : We found that rats given TNF, histamine alone(11 and $55\;{\mu}g/kg$), and TNF with histamine(l.1, 11, and $55\;{\mu}g/kg$) intratracheally had increased (p<0.05) lung MPO activity compared with saline-treated control rats. TNF with histamine $11\;{\mu}g/kg$ had increased MPO activity (P=0.0251) compared with TNF-treated rats. TNF and TNF with histamine(1.1, 11, and $55\;{\mu}g/kg$) intratracheally had all increased (p<0.05) lung leak, lavage neutophil numbers and lavage CINC activities compared with saline. TNF with histamine $1.1\;{\mu}g/kg$ had increased (p=0.0367) lavage neutrophil numbers compared with TNF treated rats. But there were no additive effect of histamine with TNF compared with TNF alone in acute lung leak on 5 h and 24 h in rats. Treatment of rats with the $H_1$ and $H_2$ antagonists resulted in inhibitions of lavage neutrophil accumulations and lavage CINC activity elevations elicited by co-treated histamine in TNF-induced acute lung injury intratracheally in rats. We also found that rats given IL-1 along with histamine intratracheally did not have increase in lung leak compared with IL-1 treated rats. Conclusion : Histamine administered intratracheally did not have synergistic effects on TNF-induced acute lung leak inspite of additive effects on increase in MPO activity and lavage neutrophil numbers in rats. These observations suggest that instilling histamine intratracheally would not play synergistic roles in neutrophil-mediated acute lung injury in rats.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.360-378
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• 1997

Background : Severe acute lung injury(ALI), also known as the adult respiratory distress syndrome(ARDS), is a heterogenous nature of dynamic and explosive clinical synrome that exacts a mortality of approximately 50%. Endotoxin(ETX) is an abundant component of the outer membrane of gram-negative bacteria capable of inducing severe lung injury in gram-negative sepsis and gram-negative bacterial pneumonia, which are among the most common predisposing causes of ARDS. The influx of PMNs into airway tissue is a pathological hallmark of LPS-induced lung injury. And there is a substantial evidence suggesting that cytokines are important mediators of lung injury in gram-negative sepsis. However, the kinetics of phagocytes and cytokines by an exact time sequence and their respective pathogenic importance remain to be elucidated. This study was performed to investigate the role of phagocytes and proinflammatory cytokines in ETX-induced ALI through a time course of changes in the concentration of protein, $TNF{\alpha}$ and IL-6, and counts of total and its differential cells in BALF. The consecutive histologic findings were also evaluated. Method : The experimental animals, healthy male Sprague-Dawley, weighted $200{\pm}50g$, were divided into control- and ALI- group. ALI was induced by an intravenous administration of ETX, 5mg/kg. Above mentioned all parameters were examined at 0(control), 3, 6, 24, 72 h after administration of ETX. $TNF{\alpha}$ and IL-6 cone. in BALF were measured by a bioassay. Results : The protein concentration and total leukocyte count(TC) in BALF was significantly increased at 3h compared to controls(p < 0.05). The protein conc. was significantly elavated during observation period, but TC was significantly decreased at 72h(p < 0.05 vs. 24h). There was a close relationship between TC and protein cone. in BALF(r = 0.65, p < 0.001). The PMN and monocyte count was well correlated with TC in BALF, and the correlation of PMN(r = 0.97, p < 0.001) appeared to be more meaningful than that of monocyte(r = 0.61, p < 0.001). There was also a significant correlation between protein cone. and PMN or monocyte count in BALF(PMN vs. monocyte : r = 0.55, p < 0.005 vs. r = 0.64, p < 0.001). The count of monocyte was significantly elavated during observation period though a meaningful reduction of PMN count in BALF at 72h, this observation suggested that monocyte may, at least, partipate in the process of lung injury steadly. In this study, there was no relationship between IL-6 and $TNF{\alpha}$ cone., and $TNF{\alpha}$ but not IL-6 was correlated with TC(r = 0.61, p < 0.05) and monocyte(r = 0.67, p < 0.05) in BALF only at 3, 6h after ETX introduced. In particular, the IL-6 cone. increased earlier and rapidly peaked than $TNF{\alpha}$ cone. in BALF. In histologic findings, the cell counts of lung slices were increased from 3 to 72h(p < 0.001 vs. NC). Alveolar wall-thickness was increased from 6 to 24h(p < 0.001 vs. NC). There was a significant correlation between the cell counts of lung slices and alveolar wall-thickness(r= 0.61, p < 0.001). This result suggested that the cellular infiltrations might be followed by the alterations of interstitium, and the edematous change of alveolar wall might be most rapidly recovered to its normal condition in the process of repair. Conclusion : We concluded that although the role of PMN is partly certain in ETX-induced ALI, it is somewhat inadequate to its known major impact on ALL Alveolar macrophage and/or non-immune cells such as pulmonary endothelial or epithelial cells, may be more importantly contributed to the initiation and perpetual progression of ETX-induced ALI. The IL-6 in ETX-induced ALI was independent to $TNF{\alpha}$, measured by a bioassay in BALF. The early rise in IL-6 in BALF implies multiple origins of the IL-6.