• Tuberculosis and Respiratory Diseases
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• v.54 no.1
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• pp.45-56
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• 2003

Background : Mycobacterium abscessus is the most common respiratory pathogen in rapidly growing mycobacteria and is resistant to all of the first-line antituberculosis drugs. This report describes the clinical and radiographic characteristics in patients with pulmonary disease caused by M. abscessus. Materials and Methods : Twelve patients with pulmonary disease caused by M. abscessus who fulfilled the 1997 American Thoracic Society diagnostic criteria for a nontuberculous mycobacterial pulmonary infection were observed over a five-and-a-half year period. The clinical characteristics and chest radiographic findings were analyzed, retrospectively. Results : The patients were predominantly female(11/12, 92%) and nonsmokers(12/12, 100%). Coughing (10/12, 83%), sputum(10/12, 83%) and hemoptysis(10/12, 83%) were the common symptoms and they had prolonged periods from the onset of symptoms to the diagnosis of their disease(median 6.5 years). Eleven (92%) patients had a previous history of being treated for pulmonary tuberculosis. The sputum specimens were acid-fast bacilli smear-positive in all patients. All patients were administered antituberculosis drugs. Six (50%) patients were treated with second-line antituberculosis drugs on account of persistent smear-positive sputum specimens. The chest radiographs showed that reticulonodular opacities(11/12, 92%) were the most common pattern of abnormality, followed by cavitary lesions(5/12, 42%). The computed tomography findings suggested bronchiolitis from the centrilobular nodules with a tree-in-bud appearances(9/10, 90%) and bronchiectasis (9/10, 90%) were the most common, followed by well-defined nodules smaller than 10-mm in diameter(7/10, 70%). Conclusions : M. abscessus pulmonary disease should be recognized as a cause of chronic mycobacterial lung disease, and respiratory isolates should be assessed carefully.

• Tuberculosis and Respiratory Diseases
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• v.54 no.4
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• pp.403-414
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• 2003

Background : Proteasome inhibitors can promote either cell survival or programmed cell death, depending on both the specific type and proliferative status of the cell. However, it is not well known whether inhibition of proteasome activity is related to apoptosis in lung cancer cells. In addition, the exact mechanisms responsible for apoptosis induced by proteasome inhibition are not well understood. In the present study, we have examined the effect of proteasome inhibition on lung cancer cells and tried to test the mechanisms that may be associated with the apoptosis of these cells. Methods : We examined the effect of proteasome inhibition with MG132 or PS-341 on cell survival in A549 and NCI-H157 lung cancer cells using MTT assay, and analyzed the cleavage of PARP by Western blot analysis to find evidence of apoptosis. Next, we evaluated the activation of caspase 3 by Western blot analysis and the activity of JNK by immunocomplex kinase assay. We also examined the changes in anti-apoptotic pathways like ERK and cIAP1 by Western blot analysis after inhibition of proteasome function. Results : We demonstrated that MG132 reduced cell survival by inducing apoptosis in A549 and NCI-H157 cells. Proteasome inhibition with MG132 or PS-341 was associated with activation of caspase 3 and JNK, reduced expression of activated ERK, and downregulation of cIAP1. Conclusion : Apoptosis induced by proteasome inhibition may be associated with the activation of pro-apoptotic pathways like caspase 3 and JNK and the inactivation of anti-apoptotic pathways in lung cancer cells.

• Tuberculosis and Respiratory Diseases
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• v.66 no.4
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• pp.324-328
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• 2009

The syndrome of inappropriate secretion of the antidiuretic hormone (SIADH) is a well recognized paraneoplastic phenomenon related to impaired water excretion, and can result in dilutional hyponatremia as well as central nervous system symptoms. It is characterized by a decrease in plasma osmolarity with inappropriately concentrated urine. The causes of SIADH are associated with pulmonary and endocrine disorders, central nervous system diseases, and malignancies, including lung cancer. The other causes of SIADH include some drugs, particularly chemotherapy agents. Anticancer drugs, such as cisplatin, vincristine, and cyclophosphamide are well known causes of SIADH but the mechanisms are unclear. Recently, we encountered a patient with advanced non-small cell lung cancer who suffered from general weakness and altered mentality after an intravenous carboplatin and gemcitabine combination.

• Tuberculosis and Respiratory Diseases
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• v.57 no.1
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• pp.55-60
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• 2004

Anticonvulsant hypersensitivity syndrome (AHS) is an uncommon, but potentially fatal and mutilsystemic disorder that occurs after exposure to the arene oxide-producing anticonvulsants-carbamzepine, phenobarbital and phenytoin. The multisystemic reactions include fever, skin eruptions, lymphadenopathy, hematologic abnormality and hepatitis. The diagnosis of AHS is made by history of drug exposure and clinical course. No specific treatments are proved as benefit except discontinuing the offending drug and trying the steroids in some severe cases. We report a case of carbamazepine induced anticonvulsant hypersensitivity syndrome characterized by skin rash, eosinophilia, subcarinal lymphadenopathy and eosinophilic pneumonia. The patient was resolved completely after only discontinuing carbamazepine.

• Tuberculosis and Respiratory Diseases
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• v.52 no.3
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• pp.219-229
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• 2002

Background : Sepsis-induced acute lung injury (ALI) is caused by many cellular and humoral mediators induced by an endotoxin. Histamine, which is widely distributed in the lungs and has been considered as an important mediator of sepsis. It increases P-selectin expression on the endothelial cell surfaces and induces IL-8 secretion. Therefore, an endotoxin-induced histamine may be related to neutrophil-mediated ALI by inducing the migration and activation of neutrophils in the lung tissue. However, the role of endogenous histamine in endotoxin ALI has not been clarified. The purpose of this study was to investigate how endotoxin-induced ALI is influenced by endogenous histamine and to identify the possible mechanism of action. Materials and Methods : The study consisted of 4 groups using Sprague-Dawley rats : 1) control group, where the rats were infused intratracheally by normal saline, 2) an endotoxin group, where lipopolysaccharide (LPS) was administered intratracheally 3) the $H_2$ receptor antagonist-treated group ($H_2$ group) and 4) the $H_1$ receptor antagonist-treated group ($H_1$ group), where $H_2$-receptor blocker (ranitidine) and $H_1$-receptor blocker(pyrilamine) were co-treated intravenously with the intratracheal administration of an endotoxin. The lung leak index using $I^{125}$-BSA, the total protein and LDH concentration in the lung lavage fluid, myeloperoxidase(MPO) activity in the lung tissue, the pathologic score and the total number of neutrophils, TNF-$\alpha$, IL-$1{\beta}$ and IL-10 in lung lavage (BAL) fluid were measured in each group as the indices of lung injury. Results : Compared to the control group, the endotoxin group exhibited significant increases in all lung injury indices. Significant reductions in the endotoxin-mediated increases in lung leak index (p<0.05) were observed in both the $H_1$ and $H_2$ groups. In addition the total protein (p<0.05) and LDH concentration (p<0.05) in the BAL fluid were also lower in the $H_2$ group compared to the endotoxin group. However, there was no change in the MPO activity in the lung tissue, the pathologic score and the total number of neutrophils in the BAL fluid in both the $H_2$ and $H_1$ groups compared to the endotoxin group. The increases in TNF-$\alpha$ IL-$1{\beta}$ and IL-10 concentrations in the BAL fluid observed in the endotoxin group were not reduced in the $H_2$ and $H_1$ groups. Conclusion : Antihistamine attenuated the enhanced alveolar-capillary permeability induced by the endotoxin via the $H_2$ receptor. However the attenuating mechanism may not be related to the pathogenesis of neutrophil dependent lung injury.

• Journal of Yeungnam Medical Science
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• v.1 no.1
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• pp.49-58
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• 1984

The differential diagnosis of atypical mycobacteriosis caused by atypical mycobacteria (with the exception of Mycobacterium tuberculosis, Mycobacterium bovis, and Mycobacterium leprae) which are widly distributed in soil and water, from pulmonary tuberculosis is possible only when atypical mycobacteria are isolated and identified. In this investigation, attempts were made to isolate atypical mycobacteria from persons registered as tuberculosis patients in the Anyang Health Center in Anyang City, Kyungki province, Korea. Biological and biochemical tests were performed for the atypical mycobacteria isolated from these patients, also retrospective analysis of clinical and X-ray findings of the patients with bacteriologically confirmed atypical mycobacteriosis were done. The results can be summarized as follows: 1. 103 strains of mycobacteria were isolated among 334 sputum samples from patients. 2. Among the isolated mycobacteria, 10 strains (9.7%) were found to be a atypical mycobacteria and 93 strains (90.3%) were tubercle bacilli of human type. 3. On the basis of Runyon's grouping of atypical mycobacteria, there were 3 strains (30.0 %) of scotochromogen and nonphotochromogen respectively, 4 strains (40.0%) of rapid grower, and no photochromogen. 4. By biochemical tests, 3 strains of scotochromogen were identified as Mycobacterium scrofulaceum (2 strains) and Mycobacterium szulgai (1 strain) 3 strains of nonphotochromogen were Mycobacterium avium-complex (2 strains) and Mycobacterium terriae (1 strain), and 4 strains of rapid grower were Mycobacterium fortuitum (3 strains) and Mycobacterium chelonei. 5. In drug sensitivity tests, all 10 strains isolated atypical mycobacteria showed resistance to various concentration of INH and SM and low concentration (10mcg, 40mcg and 50mcg) of EB, TH, and CS, and were sensitive to only high concentration (20mcg and 100mcg) of EB, TH, CS, and RFP. 6. In analysis of clical findings by the patients with bacteriologically confirmed atypical mycobacteriosis, it was found that clinical symptoms of these patients appeared not to be mild than those of patients with pulmonary tuberculosis. The patients with atypical mycobacteriosis had been treated for pulmonary tuberculosis for a long time and they showed no improvement.

• Tuberculosis and Respiratory Diseases
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• v.50 no.4
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• pp.484-492
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• 2001

Background : Pulmonary tuberculosis with a remaining cavitary lesion is considered to be a problem with the course of treatment. In particular, re-treatment cases tend to respond poorly to current anti-tuberculosis agents. Therefore the factors that are related with the poor closure of a cavitary lesion in pulmonary tuberculosis during treatment were evaluated. Methods : A retrospective review of the medical records and chest X -ray films of 68 patients who had chemotherapy for the pulmonary tuberculosis with cavitary lesions was made. All the patients had been followed up for more than 12 months at National Masan Tuberculosis Hospital as of Aug. 2000. Results : The male to female ratio was 3.9:1.72.4% of the patients were between 20 to 50 years of age. 66.2% of the cavitary lesions on the chest X-ray films were confined to the upper lung fields : 36.8% in the right upper lung field and 29.4% in the left upper lung field. 82.4% of the cavities were less than 40 mm in their size, and 83.8% were less than 6 mm thick. The cavitary lesions were closed in 48 cases and remained in 20 cases during a follow-up period of more than 12 months. The factors that are thought to affect to the outcomes of the cavities were age, past medication history, the number of unused drugs, and the number of sensitive drugs. Conclusion : In the treatment courses of pulmonary tuberculosis with cavitary lesions, the following factors are associated with less desirable outcome:an age over 45, a past medication history of more than 2 courses of treatment, The number of unused drugs not exceeding average 6 and the number of sensitive drugs not exceeding average 7.

• Tuberculosis and Respiratory Diseases
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• v.51 no.1
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• pp.25-34
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• 2001

Background : Inhaled glucocorticoids are the medical treatment of choice in asthma patients. Fluticasone propionate is one of the most effective inhaled corticosteroids and has been reported to have minimal effect on the hypothalamic-pituitary-adrenal axis at the recommended dose. However, reports of long-term trials characterizing their systemic safety with chronic use are rare. This study was designed to evaluate the long-term safety of inhaled fluticasone propionate to the hypothalamic-pituitary-adrenal axis. Method : This study was conducted on 21 patients to evaluate the adrenal response to rapid ACTH stimulation test after 6 months of treatment with fluticasone propionate from $200\;{\mu}g$ to $750\;{\mu}g$ daily. The serum cortisol levels was measured to assess its effect on the hypothalamic-pituitary-adrenal axis just prior to the injection, at 30 minutes and 60 minutes after an intramuscular injection of synthetic ACTH. Result : The mean dose of inhaled fluticasone propionate was $355\;{\mu}g$ per day(SD=$174\;{\mu}g$, range=$200\;{\mu}g$ to $750\;{\mu}g$). The mean serum cortisol levels of the patients was $11.0\;{\mu}g/d{\ell}$(SD=$6.4\;{\mu}g/d{\ell}$) prior to the injection, $20.0\;{\mu}g/d{\ell}$ (SD=$7.7\;{\mu}g/d{\ell}$) after 30 minutes, and $23.0\;{\mu}g/d{\ell}$(SD=$6.3\;{\mu}g/d{\ell}$) after 60 minutes. Sixteen patients of the 21 patients had a normal response(> $18\;{\mu}g/d{\ell}$), and 5 out of the 21 patients had serum cortisol levels below the normal range after the rapid ACTH stimulation test. Conclusion: Adrenal suppression occurred in 5 out of 21 patients with 6 months treatment with inhaled fluticasone propionate.

• Tuberculosis and Respiratory Diseases
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• v.59 no.2
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• pp.142-150
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• 2005

Background : Continuous growth stimulation by various factors, as well as chronic oxidative stress, may co-exist in many solid tumors, such as lung cancer. A new family of antioxidant proteins, the peroxiredoxins (Prxs), have been implicated in the regulation of many cellular processes, including cell proliferation, differentiation and apoptosis. However, a real pathophysiological significance of Prx proteins, especially in lung disease, has not been sufficiently defined. Therefore, this study was conducted to investigate the distribution and expression of various Prx isoforms in lung cancer and other pulmonary conditions. Method : Patients diagnosed with lung cancer, and who underwent surgery at the Ajou Medical Center, were enrolled. The expressions of Prxs, Thioredoxin (Trx) and Thioredoxin reductase (TR) were analyzed using proteomic techniques and the subcellular localization of Prx proteins was studied using immunohistochemistry on normal mouse lung tissue. Result : Immunohistochemical staining has shown the isoforms of Prx I, II, III and V are predominantly expressed in bronchial and alveolar lining epithelia, as well as in the alveolar macrophages of the normal mouse lung. The isoforms of Prx I and III, and thioredoxin were also found to be over-expressed in the lung cancer tissues compared to their paired normal lung controls. There was also an increased amount of the oxidized form of Prx I, as well as a putative truncated form of Prx III, in the lung cancer samples when analyzed using 2-dimensional electrophoresis. In addition, a 43 kDa intermediate molecular weight protein band, and other high molecular weight bands of over 20 kDa, recognized by the anti-Prx I antibody, were present in the tissue extracts of lung cancer patients on 1-Dimensional electrophoresis, which require further investigation. Conclusion : The over-expressions of Prx I and III, and Trx in human lung cancer tissue, as well as their possible chaperoning function, may represent an attempt by tumor cells to adjust to their microenvironment in a manner advantageous to their survival and proliferation, while maintaining their malignant potential.

• Tuberculosis and Respiratory Diseases
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• v.44 no.5
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• pp.1083-1093
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• 1997

Background : So far, there have been numerous reports on organ damage due to cryptococcosis, however, cases of lung localization have been infrequently reported. Recently pulmonary cryptococcosis has been reported more frequently than before due to enhanced diagnostic techniques and increased underlying diseases. Method : The author, therefore, analyzed the clinical manifestations of 5 cryptococcosis cases that we experienced at Hanyang University Hospital from 1985 to 1996 and 9 cases reported in Korea from 1984 and 1996 retrospectively. The following results were obtained. Results : Cryptococcosis occurred frequently over sixth decade and the male to female ratio was 3.6 : 1. Underlying diseases included acute rejection after kidney transplantation, rheumatoid arthritis, autoimmune hepatitis, diabetes mellitus and state of bilateral adrenalectomy. Remaining 8 cases had no evidence of an underlying disease. Because the symptoms were subacute & nonspecific, and not improved by conventional antibiotics, 6 patients of 14 pulmonary cryptococcosis patients were treated as pulmonary tuberculosis before correct diagnosis was made. There were three asymptomatic cases. According to the results of CXR, solitary alveolar consolidation was the most common finding(8 cases) followed by diffuse infiltration(5 cases). It also showed pleural effusion, hilar lymphadenopathy and cavity formation that was rarely reported in world literature. The diagnasis was made through fine needle aspiration biopsy in 10 cases, open thoracotomy in 2 cases, transbronchial lung biopsy in 1 case. and thoracentesis with pleural biopsy in 1 case. Only one case showed positive result in sputum stain and culture, serum latex agglutination test for cryptococcus neoformans. Treatment modalities were various such as fluconazole, amphotericin B, flucytosine, ketoconazole, surgery and it's combination. After 1990 year, there was a trend that fluconazole or ketoconazole are more used than other therapeutic modalities. Conclusion : Because the symptoms are subacute & nonspecific and not improved by conventional antibiotics, pulmonary cryptococcosis is likely to misdiagnosis as pulmonary tuberculosis in Korea. Because the diagnosic yield of sputum stain, culture and serologic test for pulmonary cryptococcosis is low, histologic diagnosis is need in most pulmonary cryptococcosis.