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.
Lee, Jae Seung;Chung, Joo Won;Koh, Yunsuck;Lim, Chae-Man;Jung, Young Joo;Oh, Youn Mok;Shim, Tae Sun;Lee, Sang Do;Kim, Woo Sung;Kim, Dong-Soon;Kim, Won Dong;Hong, Sang-Bum
Tuberculosis and Respiratory Diseases
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v.59
no.5
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pp.522-529
/
2005
Background : Several national societies have published guidelines for empirical antimicrobial therapy in patients with severe community-acquired pneumonia (SCAP). This study investigated the etiologies of SCAP in the Asan Medical Center and assessed the relationship between the initial empirical antimicrobial regimen and 30 day mortality rate. Method : retrospective analysis was performed on patients with SCAP admitted to the ICU between March 2002 and February 2004 in the Asan Medical Center. The basic demographic data, bacteriologic study results and initial antimicrobial regimen were examined for all patients. The clinical outcomes including the ICU length of stay, the ICU mortality rate, and 30 days mortality rates were assessed by the initial antimicrobial regimen. Results : One hundred sixteen consecutive patients were admitted to the ICU (mean age 66.5 years, 81.9 % male, 30 days mortality 28.4 %). The microbiologic diagnosis was established in 58 patients (50 %). The most common pathogens were S. pneumoniae (n=12), P. aeruginosae (n=9), K. pneumonia (n=9) and S. aureus (n=8). The initial empirical antimicrobial regimens were classified as: ${\beta}$-lactam plus macrolide; ${\beta}$-lactam plus fluoroquinolone; anti-Pseudomonal ${\beta}$-lactam plus fluoroquinolone; Aminoglycoside combination regimen; ${\beta}$-lactam plus clindamycin; and ${\beta}$-lactam alone. There were no statistical significant differences in the 30-day mortality rate according to the initial antimicrobial regimen (p = 0.682). Multivariate analysis revealed that acute renal failure, acute respiratory distress syndrome and K. pneumonae were independent risk factors related to the 30 day mortality rate. Conclusion : S. pneumoniae, P. aeruginosae, K. pneumonia and S. aureus were the most common causative pathogens in patients with SCAP and K. pneumoniae was an independent risk factor for 30 day mortality. The initial antimicrobial regimen was not associated with the 30-day mortality.
Lee, Kum Joo;Yun, Soo Young;Lee, Ran;Hean, Jae Ho;Jung, Ghee Young;Park, Jin Hee;Park, Young Sun
Clinical and Experimental Pediatrics
/
v.45
no.5
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pp.596-602
/
2002
Purpose : The purpose of this study was to analyze the association of peripheral neutrophil count with the development of respiratory failure in preterm infants. Methods : A retrospective study was conducted from January 1993 to December 1999 on 44 preterm infants, who were admitted to the neonatal intensive care unit of St. Francisco hospital. Preterm infants(birth weight 500 to 1,350 gm) who had a complete blood count obtained within 2 hours after delivery. Patients in the lowest of neutrophil count(early neutropenia, < $1.0{\times}10^9/L$) were compared with patients in the remaining group. Results : Low neutrophil count were transient in early neutropenia group. The concentration the circulating neutrophil count rose from $0.85{\pm}0.11{\times}10^9/L$ at average of 2 hours after delivery to $5.3{\pm}2.7{\times}10^9/L$ at 24 hours after delivery in the early neutropenia group and from $3.6{\pm}1.6{\times}10^9/L$ to $5.8{\pm}3.2{\times}10^9/L$ in the non-neutropenia group during the same time period. Compare to the non-neutropenia group, the neutropenia group had a lower birth weight($1,046.50{\pm}180.76gm$ Vs $1,156.70{\pm}124.99gm$), a lower Apgar score(1 min : $3.41{\pm}1.18$ Vs $4.30{\pm}1.46$, 5 min : $5.41{\pm}0.87$ Vs $6.15{\pm}0.95$), and a higher incidence of bronchopulmonary dysplasia(27.27% Vs 7.0%). Patients who had early neutropenia were more likely to require mechanical ventilation, supplemental oxygen and hospital stay. Also, main effect factors for the two groups were birth weight(Odds ratio=5.457, 95% CI=1.551-27.525), initial peripheral blood white cells(odds ratio=8.308, 95% CI=2.054-52.699), and bronchopulmonary dysplasia(odds ratio=0.099, 95% CI=0.017-0.397). Conclusion : A low count of neutrophil in the systemic circulation of premature infants within 2 hours of birth is associated with more severe respiratory distress.
Background : The signal pathways and their precise roles for acute respiratory distress syndrome caused by endotoxin (ETX) has not been established. Since there has been several in vitro experiments suggesting that activation of protein kinase C (PKC) pathway may be responsible for endotoxin-induced inflammatory reaction, we performed in vivo experiments in the rats with the hypothesis that PKC-inhibition can effectively prevent endotoxin-induced acute lung injury. Methods : We studied the role of PKC in ETX-induced ALI using PKC inhibitor (staurosporine, STP) in the rat Specific pathogen free male Sprague-Dawley weighted from 165 to 270g were used for the study. Animals were divided into the normal control (NC)-, vehicle control (VC)-, ETX-, PMA (phorbolmyristateacetate)-, STP+PMA-, and STP+ETX-group. PMA (50mg/kg) or ETX (7mg/kg) was instilled through polyethylen catheter after aseptic tracheostomy with and without STP (0.2mg/kg)-pretreatment STP was injected via tail vein 30min before intratracheal injection (IT) of PMA or ETX. Bronchoalveolar lavage (BAL) was done 3-or 6-hrs after IT of PMA or ETX respectively, to measure protein concentration, total and differential cell counts. Results : The results were as follows. The protein concentrations in BALF in the PMA- and ETX-group were very higher than that of VC-group (p<0.001). When animals were pretreated with STP, the %reduction of the protein concentration in BALF was $64.8{\pm}8.5$ and $30.4{\pm}2.5%$ in the STP+PMA- and STP+ETX-group, respectively (p = 0.028). There was no difference in the total cell counts between the PMA-and VC-group (p = 0.26). However the ETX-group showed markedly increased total cell counts as compared to the VC- (p = 0.003) and PMA-group (p = 0.0027), respectively. The total cell counts in BALF were not changed after pretreatment with STP compared to the PMA- (p = 0.22) and ETX-group (p = 0.46). The percentage of PMN, but not alveolar macrophage, was significantly elevated in the PMA-, and ETX-group. Especially in the ETX-group, the percentage of PMN was 17 times higher than that of PMA (p < 0.001). The differential cell counts was not different between the PMA and STP+PMA On the contrary the STP+ETX-group showed decreased percentage of PMN (p = 0.016). There was no significant relationship between the protein concentration and the total or differential cell counts in each group. Conclusion : Pretreatment with PKC-inhibitor (staurosporine) partially but significantly inhibited ETX-induced ALI.
Background : Heat-treated cells are known to be protected from lysis by TNF, which is considered to play a central role in the pathogenesis of sepsis-induced acute lung injury. The objective of the study was to investigate the effect of heat shock response by heat-pretreatment on the acute lung injury of the rats induced by intratracheally administered TNF-$\alpha$, Methods : We intratracheally instilled either saline or TNF (R&D, 500ng) with and without heat pretreatment in Sprague-Dawley rats weighing 250~350 g. The heated rats were raised their rectal temperature to $41^{\circ}C$ and was maintained thereafter for 13 minutes at 18 h before intratracheal administration of saline or TNF. After 5 h of intratracheal treatment, lung leak, lung myeloperoxidase activity (MPO) and heat shock proteins were measured in rats. Lung leak index was defined as counts per minute of $I^{25}$ in the right lung divided by counts per minutes of $I^{25}$ in 1.0 ml of blood. All data are expressed as means ${\pm}$SE. Results : There is no difference in acute lung leak index ($0.099{\pm}0.024$ vs $0.123{\pm}0.005$) among the rats given saline intratracheally with and without heat pretreatment, but MPO activity showed a decreased tendency in heat-pretreated rats ($4.58{\pm}0.79\;U/g$) compared with heat-unpretreated rats ($7.32{\pm}0.97\;U/g$) (P=0.064). Rats administered TNF intratracheally with heat-pretreatment had decreased lung leak index ($0.137{\pm}0.012$) and lung MPO activity ($5.51{\pm}1.04\;U/g$) compared with those of heat-unpretreated and TNF-administered rats ($0.186{\pm}0.016$, $14.34{\pm}1.22\;U/g$) (P<0.05 in each). There were no significant difference of lung leak index and MPO activity between TNF-treated rats with heat-pretreatment and saline-treated rats with and without heat-pretreatment. Conclusion : The heat shock response attenuated neutrophil recruitment and acute lung leak induced by intratracheal instillation of TNF-in rats.
Background : In patients with severe chronic lung diseases even a small pneumothorax can result in life-threatening respiratory distress. It is important to treat the attack by chest tube drainage until the lung expands. Pneumothorax with a persistent air leak that does not resolve under prolonged tube thoracostomy suction is usually treated by open operation to excise or oversew a bulla or cluster of blebs to stop the air leak. Pleurodesis by the instillation of chemical agents is used for the patient who has persistent air leak and is not good candidate for surgical treatment. When the primary trial of pleurodesis with common agent fails, it is uncertain which agent should be used f or stopping the air leak by pleurodesis. It is well known that inappropriate drainage of hemothorax results in severe pleural adhesion and thickening. Based on this idea, some reports described a successful treatment with autologous blood instillation for pneumothorax patients with or without residual pleural space. We tried pleurodesis with autologous bood for pneumothorax with persistent air leak and then we evaluated the efficacy and safety. Methods : Fifteen patients who had persistent air leak in the pneumothorax complicated from the severe chronic lung disease were enrolled. They were not good candidates for surgical treatment and doxycycline pleurodesis failed to stop up their air leaks. We used a mixture of autologous blood and 50% dextrose for pleurodesis. Effect and complications were assessed by clinical out∞me, chest radiography and pulmonary function tests. Results : The mean duration of air leak was 18.4${\pm}$6.16 days before ABP (autologous blood and dextrose pleurodesis) and $5.2{\pm}1.68$ days after ABP. The mean severity of pain was $2.3{\pm}0.70$ for DP(doxycycline pleurodesis) and $1.7{\pm}0.59$ for ABDP (p<0.05). There was no other complication except mild fever. Pleural adhesion grade was a mean of $0.6{\pm}0.63$. The mean dyspnea scale was $1.7{\pm}0.46$ before pneumothrax and $2.0{\pm}0.59$ after ABDP (p>0.05). The mean $FEV_1$ was $1.47{\pm}1.01$ before pneumothorax and $1.44{\pm}1.00$ after ABDP (p>0.05). Except in 1 patient, 14 patients had no recurrent pneumothorax. Conclusion : Autologous blood pleurodesis (ABP) was successful for treatment of persistent air leak in the pneumothorax. It was easy and inexpensive and involved less pain than doxycycline pleurodesis. It did not cause complications and severe pleural adhesion. We report that ABP can be considered as a useful treatment for persistent air leak in the pneumothorax complicated from the severe chronic lung disease.
Kim, Ho Cheol;Cho, Dae Hyun;Kang, Gyoung Woo;Park, Dong Jun;Lee, Jong Deok;Hwang, Young Sil
Tuberculosis and Respiratory Diseases
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v.56
no.3
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pp.280-288
/
2004
Background : Lung protective strategies, using low tidal volume in ARDS, improve survival rate in ARDS. However, low tidal volume ventilation may promote alveolar de-recruitment. Therefore, alveolar recruitment is necessary to maintain arterial oxygenation and to prevent repetitive opening and closure of collapsed alveoli in lung protective strategies. There has been a recent report describing improvement in arterial oxygenation with use of recruitment maneuver. However, impact of recruitment on outcome of ARDS is unknown. We evaluated whether short-term survival difference existed in patients with ARDS, who were performed alveolar recruitment maneuver(ARM) and prone position, according to response of alveolar recruitment or not. Methods : All patients who were diagnosed with ADRS and received mechanical ventilation were included. ARM were sustained inflation($35-45cmH_2O$ CPAP for 30-40 sec.) or increasing level of PEEP. If these methods were ineffective, alveolar recruitment with prone position was done for at least 10 hours. $P_aO_2/FiO_2$(P/F) ratio was determined before and at 0.5 and 2 hours after ARM. We defined a responder if the P/F ratio was increased over 50% of baseline value. We compared 10-days and 30-days survival rate between responders and non-responders. Results : 20 patients(M:F=12:8, $63{\pm}14age$) were included. Among them, 12 patients were responders and 8 patients were non-responders. In responders, P/F ratio was increased from $92{\pm}25mmHg$ to $244{\pm}85mmHg$. In non-responders, P/F ratio increased from $138{\pm}37mmHg$ to $163{\pm}60mmHg$. Among non-responders, P/F ratio was improved over 50% in 2 patients after prone position. Overall, 14 patients were responders after ARM and prone position. The 10-days and 30-days survival rate in responders was significantly higher than in non-responders(86%, 57% in responders and 33%, 0% in non-responders)(p<0.05). There was no significant difference between responders and non-responders in age($71{\pm}11$, $60{\pm}14$), lung injury score($2.8{\pm}0.2$, $2.9{\pm}0.45$), simplified acute physiology score(SAPS) II ($35{\pm}4.6$, $34{\pm}5.7$), positive end-positive pressure level($15.6{\pm}1.9cmH_2O$, $14.5{\pm}2.1cmH_2O$). Conclusion : ARM may improve arterial oxygenation in some patients with ARDS. These responders in patients with ARDS showed significant higher 10-days and 30-days survival rate than non-responders patients with alveolar recruitment.
Now, it is a stylized fact that a small number of technology firms such as Apple, Alphabet, Microsoft, Amazon, Facebook and a few others have become larger and dominant players in an industry. Coupled with the rise of these leading firms, we have also observed that a large number of young firms have become an acquisition target in their early IPO stages. This indeed results in a sharp decline in the number of new entries in public exchanges although a series of policy reforms have been promulgated to foster competition through an increase in new entries. Given the observed industry trend in recent decades, a number of studies have reported increased concentration in most developed countries. However, it is less understood as to what caused an increase in industry concentration. In this paper, we uncover the mechanisms by which industries have become concentrated over the last decades by tracing the changes in industry concentration associated with a firm's status change in its early IPO stages. To this end, we put emphasis on the case in which firms are acquired shortly after they went public. Especially, with the transition to digital-based economies, it is imperative for incumbent firms to adapt and keep pace with new ICT and related intelligent systems. For instance, after the acquisition of a young firm equipped with AI-based solutions, an incumbent firm may better respond to a change in customer taste and preference by integrating acquired AI solutions and analytics skills into multiple business processes. Accordingly, it is not unusual for young ICT firms become an attractive acquisition target. To examine the role of M&As involved with young firms in reshaping the level of industry concentration, we identify a firm's status in early post-IPO stages over the sample periods spanning from 1990 to 2016 as follows: i) being delisted, ii) being standalone firms and iii) being acquired. According to our analysis, firms that have conducted IPO since 2000s have been acquired by incumbent firms at a relatively quicker time than those that did IPO in previous generations. We also show a greater acquisition rate for IPO firms in the ICT sector compared with their counterparts in other sectors. Our results based on multinomial logit models suggest that a large number of IPO firms have been acquired in their early post-IPO lives despite their financial soundness. Specifically, we show that IPO firms are likely to be acquired rather than be delisted due to financial distress in early IPO stages when they are more profitable, more mature or less leveraged. For those IPO firms with venture capital backup have also become an acquisition target more frequently. As a larger number of firms are acquired shortly after their IPO, our results show increased concentration. While providing limited evidence on the impact of large incumbent firms in explaining the change in industry concentration, our results show that the large firms' effect on industry concentration are pronounced in the ICT sector. This result possibly captures the current trend that a few tech giants such as Alphabet, Apple and Facebook continue to increase their market share. In addition, compared with the acquisitions of non-ICT firms, the concentration impact of IPO firms in early stages becomes larger when ICT firms are acquired as a target. Our study makes new contributions. To our best knowledge, this is one of a few studies that link a firm's post-IPO status to associated changes in industry concentration. Although some studies have addressed concentration issues, their primary focus was on market power or proprietary software. Contrast to earlier studies, we are able to uncover the mechanism by which industries have become concentrated by placing emphasis on M&As involving young IPO firms. Interestingly, the concentration impact of IPO firm acquisitions are magnified when a large incumbent firms are involved as an acquirer. This leads us to infer the underlying reasons as to why industries have become more concentrated with a favor of large firms in recent decades. Overall, our study sheds new light on the literature by providing a plausible explanation as to why industries have become concentrated.
Lee, Jin Hwan;Cheon, Jin Sook;Choi, Young Sik;Kim, Ho Chan;Oh, Byoung Hoon
Korean Journal of Psychosomatic Medicine
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v.27
no.1
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pp.50-59
/
2019
Objectives : Many of the patients with type 2 diabetes are associated with sleep problems, and the rate of insomnia is known to be higher in the general population. The aims of this study were to know the frequency and clnical characteristics of insomnia, and related variables to insomnia in patients diagnosed with type 2 diabetes. Methods : For 99 patients from 18 to 80 years of age (65 males and 34 females) with type 2 diabetes, interviews were performed. Total sleep time and sleep latency was evaluated. Insomnia was evaluated using the Korean Version of the Insomnia Severity Index (ISI-K). Severity of depressive symptoms were evaluted using the Korean version of the Hamilton Depression Scale (K-HDRM). According to the cutoff score of 15.5 on the ISI-K, subjects were divided into the group of type 2 diabetics with insomnia (N=34) and those without insomnia (N=65) at first, and then statistically analyzed. Results : TInsomnia could be found in 34.34% of type 2 diabetics. Type 2 diabetics with insomnia had significantly more single or divorced (respectively 11.8%, p<0.05), higher total scores of the K-HDRS ($11.76{\pm}5.52$, p<0.001), shorter total sleep time ($5.35{\pm}2.00hours$, p<0.001), and longer sleep latency ($50.29{\pm}33.80minutes$, p<0.001). The all item scores of the ISI-K in type 2 diabetics with insomnia were significantly higher than those in type 2 diabetics without insomnia, that is, total ($18.38{\pm}2.69$), A1 (Initial insomnia) ($2.97{\pm}0.76$), A2 (Middle insomnia) ($3.06{\pm}0.69$), A3 (Terminal insomnia) ($2.76{\pm}0.61$), B (Satisfaction) ($3.18{\pm}0.72$), C (Interference) ($2.09{\pm}0.97$), D (Noticeability) ($2.12{\pm}1.09$) and E (Distress) ($2.21{\pm}0.81$) (respectively p<0.001). Variables associated with insomnia in type 2 diabetics were as following. Age had significant negative correlation with A3 items of the ISI-K (${\beta}=-0.241$, p<0.05). Total scores of the K-HDRS had significant positive correlation, while total sleep time had significant negative correlation with all items of the ISI-K (respectively p<0.05). Sleep latency had significant positive correlation with total,, A1, B and E item scores of the ISI-K (respectively p<0.05). Conclusions : Insomnia was found in about 1/3 of type 2 diabetics. According to the presence of insomnia, clinical characteristics including sleep quality as well as quantity seemed to be different. Because depression seemed to be correlated with insomnia, clinicians should pay attention to early detection and intervention of depression among type 2 diabetics.
Purpose: This is to evaluate the acute complication, resection rate, and tumor down-staging after pre-operative concurrent chemoradiotherapy for stage IIIA (N2) non-small cell lung cancer. Materials and Methods Fifteen patients with non-small cell lung cancer were enrolled in this study from May 1997 to June 1998 in Samsung Medical Center. The median age of the patients was 61 (range, 45~67) years and male to female ratio was 12:3. Pathologic types were squamous cell carcinoma (11) and adenocarcinoma (4). Pre-operative clinical tumor stages were cT1 in 2 patients, cT2 in T2, and cT3 in 1 and all were N2. Ten patients were proved to be N2 with mediastinoscopic biopsy and five had clinically evident mediastinal Iymph node metastases on the chest CT scans. Pre-operative radiation therapy field included the primary tumor, the ipsilateral hilum, and the mediastinum. Total radiation dose was 45 Gy over 5 weeks with daily dose of 1.8 Gy. Pre-operative concurrent chemotherapy consisted of two cycles of intravenous cis-Platin (100 mg/m$^{2}$) on day 1 and oral Etoposide (50 mg/m$^{2}$/day) on days 1 through 14 with 4 weeks' interval. Surgery was followed after the pre-operative re-evaluation including chest CT scan in 3 weeks of the completion of the concurrent chemoradiotherapy if there was no evidence of disease progression. Results : Full dose radiation therapy was administered to all the 15 patients. Planned two cycles of chemotherapy was completed in 11 patients and one cycle was given to four. One treatment related death of acute respiratory distress syndrome occurred In 15 days of surgery. Hospital admission was required in three patients including one with radiation pneumonitis and two with neutropenic fever. Hematologic complications and other acute complications including esophagitis were tolerable. Resection rate was 92.3% (12/l3) in 13 patients excluding two patients who refused surgery. Pleural seeding was found in one patient after thoracotomy and tumor resection was not feasible. Post-operative tumor stagings were pT0 in 3 patients, pTl in 6, and pT2 in 3. Lymph node status findings were pN0 in 8 patients, pN1 in 1, and pN2 in 3. Pathologic tumor down-staging was 61.5% (8/13) including complete response in three patients ($23.7%). Tumor stage was unchanged in four patients (30.8%) and progression was in one (7.7%). Conclusions : Pre-operative concurrent chemoradiotherapy for Stage IIIA (N2) non-small cell lung cancer demonstrated satisfactory results with no increased severe acute complications. This treatment shceme deserves more patinet accrual with long-term follow-up.
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