• Tuberculosis and Respiratory Diseases
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• v.65 no.2
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• pp.116-120
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• 2008

Rifampin is one of the first line drugs for treating tuberculosis, but it might be associated with serious adverse effects, including renal failure. We report here on a case of a 57-year-old patient who developed Henoch-$Sh{\ddot{o}}nlein$ purpura during antituberculosis therapy that included rifampin. The patient converted to negative on the AFB smear for tuberculosis two weeks after the initial administration of antituberculosis medication. After treatment for 60 days, this patient was diagnosed with Henoch-$Sh{\ddot{o}}nlein$ purpura by the purpura lesion on the lower legs, the leukocytoclastic vasculitis, the renal impairment and the pathological examination. After stopping rifampin, the skin lesions disappeared in about 10 days and his renal function gradually improved. This case study showed that Henoch-$Sh{\ddot{o}}nlein$ purpura can be caused by rifampin during antituberculosis therapy and we recommend that the use of rifampin should be restrained when clinical symptoms of Henoch-$Sh{\ddot{o}}nlein$ purpura are observed.

• Tuberculosis and Respiratory Diseases
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• v.52 no.4
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• pp.411-418
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• 2002

Pulmonary alveolar proteinosis(PAP) is a disorder in which an insoluble, proteinaceous material, rich in phospholipids, is deposited in the alveoli and bronchioles. The deficiency in the clearance and degradation of the intra-alveolar phospholipoproteinaceous material in PAP most likely represents a dysfunction of the type II pneumocytes. Although the pathogenesis and causative treatment of PAP is unclear a whole lung bronchopulmonary lavage is a relatively safe and effective treatment. Here we experienced a case of pulmonary alveolar proteinosis in a 62 year old female patient who had pulmonary tuberculosis approximately 20 years ago. She complained of aggravated dyspnea and chronic cough, and presented fine inspiratory crackles at both lung fields, diffuse ground glass opacity with some area of consolidation and smooth interlobular septal thickenings in both upper, right middled lobes, and a portion of right lower lobe. Optical microscopy of the lung tissue obtained by and open lung biopsy revealed many granulomas containing acid-fast smear positive bacilli and diffuse homogeneous PAS-positive fluid in the alveolar space. Immunohistochemical stain showed surfactant. A in the alveolar space. Antituberculosis drugs with bronchoalveolar lavage were used to treat the disease. Thereafter she showed improvement in her symptoms and a partial improvement in the chest X-ray and HRCT findings. We present a case of PAP associated with pulmonary tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.60 no.3
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• pp.353-356
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• 2006

Acute transverse myelitis (TM) is a neurological syndrome caused by inflammation of the spinal cord. TM is rare but is frequently caused by viral or bacterial infections. TM caused by tuberculosis (TB) is extremely rare and there are no reports of TM caused by multidrug-resistant TB (MDR-TB). We report a case of acute TM due to MDR-TB in a 40-year-old man. The patient had been diagnosed with pulmonary TB and was started on the first-line anti-TB treatment. However, the chest radiographic findings were aggravated and neurological symptoms such as weakness in both lower extremities, sensory changes, and voiding difficulty were newly developed. The T2-weighted magnetic resonance image of the spine showed diffusely increased signal intensity in the spinal cord, particularly at the lower cervical and upper thoracic levels, without any definite evidence of myeloradicular compression, which is consistent with a diagnosis of TM. A drug susceptibility test revealed MDR and second-line anti-TB drugs were prescribed. The chest radiographic findings showed improvement after treatment, the mycobacterial culture converted to negative, the MRI findings improved, and there was partial improvement in the low extremity weakness. The patient has been prescribing second-line anti-TB medications for 14 months.

• Tuberculosis and Respiratory Diseases
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• v.59 no.3
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• pp.266-271
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• 2005

Background : Ethambutol(EMB) is one of the first-line drugs included in short-course anti-tuberculosis therapy. The point mutations in embB gene have been speculated to be associated EMB resistance. However, detection of embB mutations at these positions have been observed in both EMB-susceptible isolates; thus, it remains controversial whether these mutations are associated with EMB resistance Methods : The 36 M. tuberculosis isolates were selected from clinical isolates which tested susceptible to EMB and resistant to at least one drug. DNA extracted from the isolates was analyzed by amplifying embB gene. The PCR products were purified and directly sequenced. We reviewed the history of past drug susceptibility test results. Results : Out of 36 EMB-susceptible strains, 3 strains (8.3%) had a mutation in codon 306 or 406 of the embB gene. These three strains had at least isoniazid resistance. They grew at 1.0 mcg/ml of EMB in Lowenstein-Jensen media. The patients of the strains were continuously smear-positive for over 3 years despite taking TB therapy. One strain had been EMB-resistant in past drug susceptibility tests. Conclusion : EMB-susceptible strains containing embB mutation may be caused by decreased viability in vitro test not by itself.

• Tuberculosis and Respiratory Diseases
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• v.75 no.1
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• pp.9-17
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• 2013

Background: In cancer cells, autophagy is generally induced as a pro-survival mechanism in response to treatment-associated genotoxic and metabolic stress. Thus, concurrent autophagy inhibition can be expected to have a synergistic effect with chemotherapy on cancer cell death. Monensin, a polyether antibiotic, is known as an autophagy inhibitor, which interferes with the fusion of autophagosome and lysosome. There have been a few reports of its effect in combination with anticancer drugs. We performed this study to investigate whether erlotinib, an epidermal growth factor receptor inhibitor, or rapamycin, an mammalian target of rapamycin (mTOR) inhibitor, is effective in combination therapy with monensin in non-small cell lung cancer cells. Methods: NCI-H1299 cells were treated with rapamycin or erlotinib, with or without monensin pretreatment, and then subjected to growth inhibition assay, apoptosis analysis by flow cytometry, and cell cycle analysis on the basis of the DNA contents histogram. Finally, a Western blot analysis was done to examine the changes of proteins related to apoptosis and cell cycle control. Results: Monensin synergistically increases growth inhibition and apoptosis induced by rapamycin or erlotinib. The number of cells in the sub-$G_1$ phase increases noticeably after the combination treatment. Increase of proapoptotic proteins, including bax, cleaved caspase 3, and cleaved poly(ADP-ribose) polymerase, and decrease of anti-apoptotic proteins, bcl-2 and bcl-xL, are augmented by the combination treatment with monensin. The promoters of cell cycle progression, notch3 and skp2, decrease and p21, a cyclin-dependent kinase inhibitor, accumulates within the cell during this process. Conclusion: Our findings suggest that concurrent autophagy inhibition could have a role in lung cancer treatment.

• Tuberculosis and Respiratory Diseases
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• v.56 no.2
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• pp.169-177
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• 2004

Background : Cyclooxygenase is the main target enzyme for the nonsteroidal anti inflammatory drugs (NSAIDs) that have been shown to suppress carcinogenesis in both experimental models and epidemiological studies. COX-2 plays an important role in solid tumor growth, invasiveness and angiogenesis, through, in part, the synthesis of prostaglandins, such as prostaglandin E2 (PGE2). In this study, the prognostic significance of an increase in COX-2 expression in lung cancer samples was evaluated. Material and Methods : The expression of COX-2, by immunohistochemistry, was studied in paraffin-embedded tumor blocks obtained from 84 patients(male 67, female 17, with a mean age of 63, ranging from 34 to 84 years) who had undergone surgery at Wonkwang University Hospital, between 1997 and 2002. For the evaluation of the relationships between COX-2 expression, and the clinical stage, metastasis to lymph nodes and survival, those cases showing the respective antigen expression in >10% of the tumor cells were considered positive. Result : Of the 84 patients, 61 (73%) exhibited more than 10% COX-2 immunoreactivities in the tumor and normal cells, whereas the remaining 23 showed no increase in the expression of COX-2. There was no significant relationship between the increased expression of COX-2 and the disease stage(p=0.1002) or cell type(p=0.152). The median survival was longer for the patients with a negative, compared to positive, COX-2 expression(36 compared to 24 months, p<0.05). The two year-survival rate was also higher in the patients with a negative COX-2 expression (78%) than those with a positive expression (47%, Kaplan-Meier, Log Rank, p < 0.05). Conclusion : The median survival was longer in the patients with a negative, compared to positive, COX-2 expression was longer than those with positive COX-2, having undergone complete resection due to primary non-small cell lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.338-348
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• 1997

Background : Endotoxin, the component of outermembrane of gram negative organism, plays an important role in the initiation and amplification of inflammatory reaction by its effects on inflammatory cells. Until recently, there have been continuing efforts to delinate the mechanisms of the signal trasduction pathway of endotoxin stimuli on inflammatory cells. By uncovering the mechanisms of signal transduction pathway of endotoxin stimuli, we can expect to have tools to control the excessive inflammatory responses which sometimes may be fatal to the involved host. It was generally accepted that endotoxin exerts its inflammatory effects through inflammatory cytokines that are produced by endotoxin-stimulated inflammatory cells and there were some reports on the importance of protein kinase C and protein tyrosine kinase activation in the production of inflammatory cytokines by endotoxin So we evaluated the effect of pretreatment of protein kinase C inhibitors (H7, Staurosporin) and protein tyrosine kinase inhibitors(Herbimycin, Genistein) on the endotoxin-stimulated cytokines(IL-8 & TNF-$\alpha$) mRNA expression. Method : Peripheral blood monocytes were isolated from healthy volunteers by Ficoll-Hypaque density gradient method and purified by adhesion to 60mm Petri dishes. Endotoxin(LPS 100ng/ml) was added to each dishes except one control dish, and each endotoxin-stimulated dishes was preincubated with H7, Staurosporin(protein kinase C inhibitor), Herbimycin or Genistein(protein tyrosine kinase inhibitor) respectively except one dish. Four hours later the endotoxin stimulation, total RNA was extracted and Northern blot analysis for IL-8 mRNA and TNF-$\alpha$ mRNA was done. Result : Endotoxin stimulation increased the expression of IL-8 mRNA and TNF-$\alpha$ mRNA expression in human peripheral blood monocyte as expected and the stimulatory effect of endotoxin on TNF-$\alpha$ mRNA expression was inhibited by protein kinase C inhibitors(H7, Staurosporin) and protein tyrosine kinase inhibitors (Herbimycin, Genistein). The inhibitory effect of each drugs was increased with increasing concentration. The stimulatory effect of endotoxin on IL-8 mRNA was also inhibited by H7 and protein tyrosine kinase inhibitors (Herbimycin, Genistein) dose-dependently but not by Staurosporin. Conclusion : Protein kinase C and protein tyrosine kinase are involved in the endotoxin induced signal transduction pathway in human peripheral blood monocyte.

• Tuberculosis and Respiratory Diseases
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• v.72 no.1
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• pp.44-49
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• 2012

Background: Multidrug-resistant tuberculosis (MDR-TB) is an increasing public health problem and poses a serious threat to global TB control. Fluoroquinolone (FQ) and aminoglycoside (AG) are essential anti-TB drugs for MDR-TB treatment. REBA MTB-FQ$^{(R)}$ and REBA MTB-KM$^{(R)}$ (M&D, Wonju, Korea) were evaluated for rapid detection of FQ and kanamycin (KM) resistance in MDR-TB clinical isolates. Methods: M. tuberculosis (n=67) were isolated and cultured from the sputum samples of MDR-TB patients for extracting DNA of the bacilli. Mutations in genes, gyrA and rrs, that have been known to be associated with resistance to FQ and KM were analyzed using both REBA MTB-FQ$^{(R)}$ and REBA MTB-KM$^{(R)}$, respectively. The isolates were also utilized for a conventional phenotypic drug susceptibility test (DST) as the gold standard of FQ and KM resistance. The molecular and phenotypic DST results were compared. Results: Sensitivity and specificity of REBA MTB-FQ$^{(R)}$ were 77 and 100%, respectively. Positive predictive value and negative predictive value of the assay were 100 and 95%, respectively, for FQ resistance. Sensitivity, specificity, positive predictive value and negative predictive value of REBA MTB-KM$^{(R)}$ for detecting KM resistance were 66%, 94%, 70%, and 95%, respectively. Conclusion: REBA MTB-FQ$^{(R)}$ and REBA MTB-KM$^{(R)}$ evaluated in this study showed excellent specificities as 100 and 94%, respectively. However, sensitivities of the assays were low. It is essential to increase sensitivity of the rapid drug resistance assays for appropriate MDR-TB treatment, suggesting further investigation to detect new or other mutation sites of the associated genes in M. tuberculosis is required.

• Tuberculosis and Respiratory Diseases
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• v.67 no.3
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• pp.221-225
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• 2009

Background: Pain is one of the most troublesome problems caused by malignancy. We evaluated the change in pain status according to observance of NCCN guidelines in lung cancer patients. Methods: Lung cancer patients complaining of pain at admission were examined. The pain was assessed with visual analogue scale (VAS) for 20 days and moderate-to-severe pain was defined as more than VAS level 3. The guideline observance was classified as high (more than 80%), medium (50~79%) and low (less than 50%). Results: Among the total 91 lung cancer patients with pain, 34 patients (37%) had moderate-to-severe pain. Their average VAS score at admission was 5.6. It decreased to 2.9 after a 20-day period of pain management. The time to reach a VAS less than 3 was 3 days in a high guideline observance group, while it took 6 days in a low observance group. In addition, the pain in the high observance group was controlled to less than 3 VAS level in 86% of patients, whereas only 25% of patients in the low observance group succeeded. Conclusion: Pain was more effectively controlled when the dose of drugs was modified according to NCCN guidelines in lung cancer patients indicating the importance of guideline observance in pain management.

• Tuberculosis and Respiratory Diseases
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• v.64 no.5
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• pp.341-346
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• 2008

Background: Recurrent pulmonary tuberculosis (TB) can be due to relapse of the original infecting strain or due to reinfection with a new strain of Mycobacterium tuberculosis. We investigated the clinical characteristics and efficacy of short-term treatment (6 months) in patients with recurrent pulmonary TB. Methods: Twenty-nine patients with recurrent pulmonary TB were compared with control patients who received primary treatment for pulmonary TB with respect to drug sensitivity and outcomes of treatment. Results: Most patients with recurrent pulmonary TB (25 cases, 86.2%) recurred more than 2 years after the completion of previous treatment. Twenty-three patients (82.1%) with recurrent pulmonary TB were sensitive to all anti-tuberculous drugs and a ratio was similar to the drug sensitivities observed in control patients. The outcomes of short-term treatment in patients with drug-sensitive TB were not significantly different between the two groups. Conclusion: Recurrent pulmonary TB in the study area was likely due to reinfection with new strains. Thus the short-term treatment of patients with drug-sensitive recurrent pulmonary TB may be successful.