• Tuberculosis and Respiratory Diseases
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• v.42 no.3
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• pp.361-369
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• 1995

Background: A number of different weaning techniques can be employed such as spontaneous breathing trial, Intermittent mandatory ventilation(IMV) or Pressure support ventilation(PSV). However, the conclusive data indicating the superiority of one technique over another have not been published. Usually, a conventional spontaneous breathing trial is undertaken by supplying humidified $O_2$ through T-shaped adaptor connected to endotracheal tube or tracheostomy tube. In Korea, T-tube trial is not popular because the high-flow oxygen system is not always available. Also, the timing of extubation is not conclusive and depends on clinical experiences. It is known that to withdraw the endotracheal tube after weaning is far better than to go through any period. The tube produces varying degrees of resistance depending on its internal diameter and the flow rates encountered. The purpose of present study is to evaluate the effectiveness of weaning and extubation following a 60 minutes spontaneous breathing trial with simple oxygen supply through the endotracheal tube. Methods: We analyzed the result of weaning and extubation following a 60 minutes spontaneous breathing trial with simple oxygen supply through the endotracheal tube in 18 subjects from June, 1993 to June, 1994. They consisted of 9 males and 9 females. The duration of mechanical ventilation was from 38 hours to 341 hours(mean: $105.9{\pm}83.4$ hours). In all cases, the cause of ventilator dependency should be identified and precipitating factors should be corrected. The weaning trial was done when the patient became alert and arterial $O_2$ tension was adequate($PaO_2$ > 55mmHg) with an inspired oxygen fraction of 40%. We conducted a careful physical examination when the patient was breathing spontaneously through the endotracheal tube. Failure of weaning trial was signaled by cyanosis, sweating, paradoxical respiration, intercostal recession. Weaning failure was defined as the need for mechanical ventilation within 48 hours. Results: In 19 weaning trials of 18 patients, successful weaning and extubation was possible in 16/19(84.2 %). During the trial of spontaneous breathing for 60 minutes through the endotracheal tube, the patients who could wean developed slight increase in respiratory rates but significant changes of arterial blood gas values were not noted. But, the patients who failed weaning trial showed the marked increase in respiratory rates without significant changes of arterial blood gas values. Conclusion: The result of present study indicates that weaning from mechanical ventilation following a 60 minutes spontaneous breathing with $O_2$ supply through the endotracheal tube is a simple and effective method. Extubation can be done at the same time of successful weaning except for endobronchial toilet or airway protection.

• Tuberculosis and Respiratory Diseases
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• v.44 no.5
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• pp.1094-1104
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• 1997

Background : Spontaneous pneumothoraces(SP) are divided into primary spontaneous pneumothoraces (PSP) which develop in healthy individuals without underlying pulmonary disorders and secondary spontaneous pneumothoraces(SSP) which occur in those who have underlying disorders such as tuberculosis or chronic obstructive lung diseases. Yet there is no established standard therapeutic approach to this disorder, i.e., from the spectrum of noninvasive treatment such as clinical observation with or without oxygen therapy, to aggressively invasive thoracoscopic bullectomy or open thoracotomy. Although chest tube thoracostomy has been most widely used, the patients should overcome pain in the initiation of tube insertion or during indwelling it potential infection and subcutaneous emphysema. Thus smaller-caliber tube has been challenged for the treatment of pneumothorax. Previously, we studied the therapeutic efficacy of 8 French catheter for spontaneous pneumothorax. But there has been few data for effectiveness of small-caliber catheterization in comparison with that of chest tube. In this study, we intended to observe the long-term effectiveness of 8 French catheter for the treatment of spontaneous pneumothoraces in comparison with that of chest tube thoracostomy. Method : From January, 1990 to January, 1996, sixty two patients with spontaneous pneumothoraces treated at Chung-Ang University Hospital were reviewed retrospectively. The patients were sub-divided into a group treated with 8 French catheter(n=23) and the other one with chest tube insertion(n=39). The clinical data were reviewed(age, sex, underlying pulmonary disorders, past history of pneumothorax, size of pneumothorax, follow-up period). And therapeutic effect of two groups was compared by treatment duration(duration of indwelling catheter or tube), treatment-associated complications and recurrence rate. Results : The follow-up period(median) of 8 French catheter group and chest tube group was 28 and 22 months, which had no statistical significance. Ther was no statistically significant difference of clinical characteristics between two groups with SP, PSP, SSP. The indwelling time of 8 French catheter group was $6.2{\pm}3.8$ days, which was significantly shorter than that of chest tube group in SP, $9.1{\pm}7.5$ days(p=0.047). In comparison of treatment-related complication in PSP, 8 French catheter group as 6.25% of complication showed lower tendency than the other group as 23.8% (p=0.041 ; one-tailed, p=0.053; two-tailed). The recurrence rate in each group of SP was 17.4%, 10.3%, which did not show any statistically significant difference. Conclusion : Treatment with 8 French catheter resulted in shorter indwelling time in sponteous pneumothorax, and lower incidence of treatment-related complication in primary spontaneous pneumothorax. And the recurrence rate in each of treatment group showed no statistically significant difference. So, we can recommend the 8 French small-caliber catheter for the initial therapy for spontaneous pneumothorax for the replacement of conventional chest tube thoracostomy. But further prospective study with more subjects of spontaneous pneumothorax will be needed for the evaluation of effectiveness of 8 French cateter.

• Tuberculosis and Respiratory Diseases
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• v.44 no.5
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• pp.1114-1124
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• 1997

Background : Endothelin(ET) is a very potent vasoconstrictive peptide produced by endothelial cells of pulmonary artery. The endothelin level was increased in plasma of primary pulmonary hypertension and acute pulmonary thromboembolism and it was suggested that the endothelin might do a critical role in the cardiopulmonary dysfunction in these two conditions. But the exact mechanism of increase of ET has not been known. In these two conditions, platelet activation and thrombosis are the main pathophysiologic findings. So there is a possibility that the platelet might stimulate endothelin secretion from endothelial cells. Therefore, we performed this study to evaluate the role of platelet and its mediators on endothelin production in bovine pulmonary artery endothelial(BPAE) cells. Method : Bovine pulmonary artery endothelial cells, ATCC certified cell line 209, were cultured and treated with human platelets($10^6{\sim}10^8/ml$), thrombin (0.1~10u/ml), TGF-${\beta}1$(1~100uM), serotonin(1~100uM), and endotoxin(1ug/ml) in a final volume of 500ul for 18 hours. Levels of ir(immunoreactive)-ET in each conditioned medium were measured by a radioimmunoassay specific for ET. Result : The increase of ir-ET levels was platelet number and time dependent over 18 hours. When washed human platelets were added($10^8/ml$), the ir-ET levels were significantly higher than that of control(p<0.05) at 8 and 18 hours after culture. Subthreshold concentration of platelets($10^7/ml$) coincubated with endotoxin(1ug/ml) or subthreshold dose of thrombin(0.1u/ml) stimulated ir-ET secretion from BPAE cells significantly(p<0.05) compared with control. Thrombin(1ug/ml, 10ug/ml) and TGF-${\beta}1$(100pM, 1000pM) significantly increased ir-ET secretion from BP AE cells(p<0.05) compared with control, but serotoin(1~100uM) and endotoxin(1ug/ml) did not stimulate the ir-ET secretion. Conclusions : Platelets stimulate endothelin secretion from bovine pulmonary artery endothelial cells. The mechanism of increase of endothelin secretion seems to be a stimulation by platelet itself or by mediators, such as TGF-${\beta}1$, secreted from activated platelets. And, in this study, the priming effect of platelets on endothelin secretion from BPAE cells could be another possibility.

• Tuberculosis and Respiratory Diseases
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• v.48 no.2
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• pp.180-190
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• 2000

Background: Genomic instability, which is manifested by the replication error(RER) phenotype, has been proposed for the promotion of genetic alterations necessary for carcinogenesis. Merlo et al. reported frequent microsatellite instability in primary small cell lung cancers. However, Kim et al. found that instability occurred in only 1% of the loci tested and did not resemble the replication error-positive phenotype. The significance of microsatellite instability in the tumorigenesis of small cell lung cancer as well as the relationship between microsatellite instability and its clinical prognosis was investigated in our study. Methods: Fifteen primary small cell lung cancers were chosen for this study. The DNAs extracted from paraffin-embedded tissue blocks with primary tumor and corresponding control tissue were investigated. Forty microsatellite markers on chromosome 1p, 2p, 3p, 5q, 6p, 6q, 9p, 9q, 13q, and 17p were used in the microsatellite analysis. Results: Thirteen(86.7%) of 15 tumors exhibited LOH in at least one of the tested microsatellite markers. Three of 13 tumors exhibiting LOH lost a larger area in chromosome 9p. LOH was shown in 72.7% on chromosome 2p, 40% on 3p, 50% on 5q, 46.7% on 9p, 69.2% on 13q, and 66.7% on 17p(Table 1). Nine(60%) of 15 tumors exhibited shifted bands in at least one of the tested microsatellite markers. Nine cases exhibiting shifted bands showed altered loci ranging 2.5~52.5%(mean $9.4%\pm16.19$)(Table 2). Shifted bands occurred in 5.7% (34 of 600) of the loci tested(Table 2). Nine cases with shifted bands exhibited LOH ranging between 0~83.3%, and the median survival duration of those cases was 35 weeks. Six cases without shifted bands exhibited LOH ranging between 0~83.3%, and the median survival duration of those cases was 73 weeks. There was no significant difference between median survival durations of the two groups(p=0.4712). Conclusion: Microsatellite instability as well as the inactivation of several tumor suppressor genes may play important roles in the development and progression process of tumors. However, the relationship between microsatellite instability and its clinical prognosis in primary small cell lung cancer could not be established.

• Tuberculosis and Respiratory Diseases
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• v.43 no.4
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• pp.600-612
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• 1996

Background : Recent studies deported that untreated patients with obstructive sleep apnea syndrome had high long-term mortality rates, and cardiovascular complications of these patients clad a major effect on mortality. Several data indicates that obstructive sheep apnea syndrome contributes to the development of diurnal systemic hypertension. But the pathophysiological mechanism of the development of systemic hypertension in these patients is still uncertain. This study was performed to evaluate the possible role of sympathetic nervous system activity for the development of systemic hypertension in patients with obstructive sleep apnea syndrome. Method : 35 patients with obstructive sleep apnea syndrome(OSAS) and 13 Control subjects(control) were included in this study. 21 patients of OSAS were normotensives(OSAS-NBP), and 14 patients of OSAS were hypertensives(OSAS-HBP). Full night polysomnography was undertaken to all subjects. We measured plasma norepinephrine(NE) and epinephrine(EP) concentrations during waking and sleep, using high performance liquid chromatography, in all patients and control subjects. Results : In OSAS, OSAS-NBP and control, plasma NE and EP concentrations during sleep were lowed than during waking(p<0.01). But, in OSAS-HBP, these was no difference between during waking and sleep. Plasma NE concentrations during sleep of OSAS, OSAS-NBP and OSAS-HBP were higher than Control(p<0.05). In OSAS-HBP, daytime systolic blood pressure correlated with plasma NE concentration during sleep(r=0.7415, p<0.01), arid correlated inversely with mean arterial oxygen saturation(r=-0.6465, p<0.05) or arterial oxygen saturation nadir(r=-0.6) 14, p<0.05) during sleep. Conclusion : The sympathetic activity during sleep of obstructive sleep apnea syndrome patients was higher than control subjects. In obstructive sleep apnea syndrome patients with systemic hypertension, there was no diurnal variation of sympathetic activity, and there was correlation between daytime systolic blood pressure and sympathetic activity during sleep. These data suggests that chronic hyperactivity of sympathetic nervous system may contribute to the development of diurnal systemic hypertension in patients with obstructive sleep apnea syndrome.

• Tuberculosis and Respiratory Diseases
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• v.56 no.5
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• pp.465-484
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• 2004

Background : Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) inhibits the proliferation of non-small cell lung cancer (NSCLC) cells by inducing apoptosis. Methods : In this study, we investigated whether hypermethylation of IGFBP-3 promoter play an important role in the loss of IGFBP-3 expression in NSCLC. We also studied the mechanisms that mediate the silencing of IGFBP-3 expression in the cell lines which have hypermethylated IGFBP-3 promoter. Results : The IGFBP-3 promoter has hypermethylation in 7 of 15 (46.7%) NSCLC cell lines and 16 (69.7%) of 23, 7 (77.8%) of 9, 4 (80%) of 5, 4 (66.7 %) of 6, and 6 (100%) of 6 tumor specimens from patients with stage I, II, IIIA, IIIB, and IV NSCLC, respectively. The methylation status correlated with the level of protein and mRNA in NSCLC cell lines. Expression of IGFBP-3 was restored by the demethylating agent 5'-aza-2'-deoxycytidine (5'-aza-dC) in a subset of NSCLC cell lines. The Sp-1/ Sp-3 binding element in the IGFBP-3 promoter, important for promoter activity, was methylated in the NSCLC cell lines which have reduced IGFBP-3 expression and the methylation of this element suppressed the binding of the Sp-1 transcription factor. A ChIP assay showed that the methylation status of the IGFBP-3 promoter influenced the binding of Sp-1, methyl-CpG binding protein-2 (MeCP2), and histone deacetylase (HDAC) to Sp-1/Sp-3 binding element, which were reversed by by 5'-aza-dC. In vitro methylation of the IGFBP-3 promoter containing the Sp-1/Sp-3 binding element significantly reduced promoter activity, which was further suppressed by the overexpression of MeCP2. This reduction in activity was rescued by 5'-aza-dC. Conclusion : These findings indicate that hypermethylation of the IGFBP-3 promoter is one mechanism by which IGFBP-3 expression is silenced and MeCP2, with recruitment of HDAC, may play a role in silencing of IGFBP-3 expression. The frequency of this abnormality is also associated with advanced stages among the patients with NSCLC, suggesting that IGFBP-3 plays an important role in lung carcinogenesis/progression and that the promoter methylation status of IGFBP-3 may be a marker for early molecular detection and/or for monitoring chemoprevention efforts.

• Childhood Kidney Diseases
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• v.4 no.1
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• pp.17-24
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• 2000

Purpose: MCNS is found in approximately $85\%$ of the idiopathic nephrotic syndrome in children and shows good prognosis with initial steroid therapy. However in FSGS, there is poor prognosis with initial therapy and shows higher rate of progression to chronic renal failure and relapse after kindney transplantation. We have experienced 8 patients who were diagnosed as MCNS on initial renal biopsy and then progressed to FSGS on follow-up biopsy. So we have investigated their clinical course and risk factors for transition of MCNS to FSGS. Methods: We conducted a retrospective study with a review of histopathologic findings and clinical manifestations of 296 cases of MCNS and FSGS that were diagnosed from January 1988 to May 1999. We classified them into 3 groups according to the histopathologic finding; MCNS, FSGS, MCNS progressed to FSGS in follow-up biopsy. Results: The number of children was 296 cases comprising 241 cases($81.4\%$) showing MCNS, 8 cases($2.7\%$) transition group, 47 cases($15.9\%$) FSGS. The mean onset age was $6.0{\pm}2.6$years in MCNS, transition group $8.3{\pm}2.3$years, FSGS $7.2{\pm4.3$years, and the gender (M:F) ratio was 3.7:1 in MCNS, 3:1 in transition group, 1.8:1 in FSGS. Comparing the presence of initial hematuria, hypertension,24 hour urine protein, serum albumin, serum creatinine, there were significant difference between the transition group and the FSGS group in the following points; 24hour urine protein $684:342mg/m^2/hr$(P<0.05), serum albumin 1.92: 2.47g/dL(P<0.05), serum cholesterol 494:343mg/dL(P<0.05). Refractoriness to steroid therapy was 13.3$\%$ in MCNS. $12.5\%$ in transition group, $29.6\%$ in FSGS; significantly higher in FSGS(P<0.05). Immunosuppressant therapy was performed in $58.5\%$ of MCNS, $100\%$ in transition group, $80.8\%$ in FSGS; transition group showed significantly higher .ate(P<0.05) comparing with MCNS. Mean number of relapse and duration from onset to first relapse showed no significance difference between these groups. Conclusion: 249 patients with MCNS have been followed and $3.2\%$ (8 patients) of them has shown change in pathologic diagnosis from MCNS to FSCS. The risk factor for transition could not be found. Our results point to the need for a follow-up biopsy to certify the possibility of transition to FSCS in some MCNS cases with refractory cases to steroid therepy, frequent relapsing cases, or in case of no remission in spite of vigorous immunosuppressant therapy.

• Childhood Kidney Diseases
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• v.8 no.2
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• pp.186-194
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• 2004

Purpose: Membranoproliferative glomeulonephritis(MPGN) has been diagnosed in an increasing number of asymptomatic cases. These cases have been detected by school urinary screening test even though the total cases of MPGN show a decreasing trend. We have analyzed the clinical and pathological characteristics of children with MPGN according to the clinical manifestations at the time of disease presentation. Methods: A total of 18 patients who had been diagnosed with idiopathic MPGN by percutaneous renal biopsy from January 1990 to February 2004 were involved in our study. The patients were divided into 2 groups as the school urinary screening(A) group and the symptomatic(S) group according to the clinical manifestations at the time of disease presentation. Results: Out of the total 18 patients, 8(44.4%) were in the S group and 10(55.6%) were in the A group. The mean serum total protein, albumin and $C_3$ levels in the S group were significantly lower than those levels of the A group, respectively($4.9{\pm}1.2\;g/dL,\;vs\;7.0{\pm}0.5\;g/dL\;P=0.002,\;2.8{\pm}0.9\;g/dL\;vs.\;4.1{\pm}0.3\;g/dL\;P=0.002,\;63.9{\pm}36.4\;mg/dL\;vs.\;100.8{\pm}39.5\;g/dL\;P=0.041$). The mean total protein amount of 24 hour collected urine in the S group were significantly higher than that of the A group($3684.0{\pm}2601.3\;mg/m^2\;vs.\;559.4{\pm}4.6.9\;mg/m^2$, respectively, P=0.001). Hypocomplementemia was observed in 11(61.1%) out of 18 patients at the time of disease onset, 7(87.5%) in the S group and 4(40%) in the A group. However the hypocomplementemia was decreased in 6(33.3%) out of 18 patients at the time of final follow-up, 3(37.5%) in the S group and 3(30%) in the A group. According to the pathologic type, hypocomplementemia was observed 8 patients(61.5%) with type I disease, 1 patients (100%) with type II disease, 2 patients(50%) in type III disease at the disease onset, but 4 patients(30.8%) in type I disease, 1 patient(100%) in type II disease, 1 patient(33.3%) with type III disease at the time of last follow-up. The incidence of cellular crescent formation and tubular atropy. as observed on light microscopy, were higher in the S group compared to the A group. Mean grade of capillary wall thickening and, mesangial proliferation were significantly higher in the S group. Conclusion: MPGN, as diagnosed in patients with only asymptomatic urinary abnormalities, has been increasing, it is more frequent in asymptomatic patients than in patients with presenting symptoms. Our result suggests that MPGN should be considered in the renal biopsy diagnosis regardless of serum $C_3$ level when urinary abnormalities are found by school urinary screening test.

• Childhood Kidney Diseases
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• v.5 no.1
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• pp.51-58
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• 2001

Purpose : Treatment of primary nocturnal enuresis (PNE) includs folk remedies and various treatments based on pathogenesis. We assessed the therapeutic effect of nocturnal water restrict ion as the primary treatment of PNE. Materials and methods : From October 1998 to June 1999, 41 children with PNE (>3 wet nights per week) who visited Ewha Womans University Mokdong hospital and who had good compliances to nocturnal water restriction for 2 months were included. Before and during nocturnal water restriction, daily fluid intake and urine volume were recorded for 2 days every 2 weeks. Responses to nocturnal water restriction were classified according to the decrease of wet nights as complete (>90$\%$), partial (50-90$\%$) and no (<50$\%$) response. Predictors such as age, sex, daytime voiding dysfunction, fluid intake, urine volume, maximum urine volume per void and fasting urine osmolality were evaluated. Results . The response rate to nocturnal water restriction fir 2 month was 82.9$\%$(34/41) [complete response 39.0$\%$(16/41), partial response : 43.9$\%$(18/41)]. The response rate to nocturnal water restriction was significantly higher in monosymptomatic PNE than polysymptomatic PNE and more effective in PNE with or nocturnal fluid intake, nocturnal urine volume, and maximum urine volume than lower nocturnal fluid intake, nocturnal urine volume and maximum urine volume per void (P<0.05). Nocturnal urine volume, maximum urine volume per void and luting urine osmolality after nocturnal water restriction has significantly increased higher in complete response and partial response group than in no response group (P<0.05). Conclusion : The nocturnal water restriction was effective in monosymptomatic PNE with nocturnal polydypsia, nocturnal polyuria and high bladder capacity. (J, Korean Soc Pediatr Nephrol 5 : 51- 8, 2001)

• Radiation Oncology Journal
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• v.28 no.1
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• pp.1-8
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• 2010

Purpose: This retrospective study was performed to evaluate the efficacy of radiation therapy (RT) and to investigate the prognostic factors for thymoma when treated with RT. Materials and Methods: We analyzed 21 patients with thymoma and also received RT from March 2002 to January 2008. The median follow-up time was 37 months (range, 3 to 89 months). The median patient age was 57 years (range, 24 to 77 years) and the gender ratio of males to females was 4：3. Of the 21 patients, complete resections (trans-sternal thymectomy) and R2 resections were performed in 14 and 1 patient, respectively. A biopsy was performed in 6 patients (28.7%). The WHO cell types in the 21 patients were as follows: 1 patient (4.8%) had type A, 10 patients (47.6%) had type B1-3, and 10 patients (47.6%) had type C. Based on Masaoka staging, 10 patients (47.6%) were stage II, 7 patients (33.3%) were stage III, and 4 patients (19.1%) were stage IVa. Three-dimensional RT was adminstered to the tumor volume (planned target volume), including the anterior mediastinum and the residual disease. The total RT dose ranged from 52.0 to 70.2 Gy (median dose, 54 Gy). Consistent with the WHO criteria, the response rate was only analyzed for the 6 patients who received a biopsy only. The prognostic factors analyzed for an estimate of survival included age, gender, tumor size, tumor pathology, Masaoka stage, the possibility of treatment by performing surgery, the presence of myasthenia gravis, and RT dose. Results: The 3-year overall survival rate (OS) and the progression free survival rate (PFS) were 80.7% and 78.2%, respectively. Among the 10 patients with WHO cell type C, 3 of 4 patients (75%) who underwent a complete resection and 3 of 6 patients (50%) who underwent a biopsy survived. Distant metastasis developed in 4 patients (19.1%). The overall response rate in the 6 patients who received biopsy only were as follows: partial remission in 4 patients (66.7%), stable disease in 1 patient (16.6%), and progressive disease in 1 patient (16.6%). Acute RTOG radiation pneumonitis occurred in 1 patient (4.8%), grade 2 occurred in 2 patients (9.5%), grade 3 occurred in 1 patient (4.8%), and grade 4 occurred in 1 patient (4.8%). A univariate analysis revealed that the significant prognostic factors for OS were age (${\geq}60$, 58.3%; <60, 100%; p=0.0194), pathology (WHO cell type A-B3, 100%; C, 58.3%; p=0.0194) and, whether the patient underwent surgery (yes, 93.3%; no, 50%; p=0.0096). Conclusion: For the 15 patients who received surgery, there was no local failure within the radiation field. In patients with WHO cell type C, surgical procedures could have resulted in a more favorable outcome than biopsy alone. We report here our clinical experience in 21 patients with thymoma who were treated by radiation therapy.