Phenotypic and Genotypic Analysis of Anti-Tuberculosis Drug Resistance in Mycobacterium tuberculosis Isolates in Myanmar

BACKGROUND: Tuberculosis (TB) is one of the most serious health problems in Myanmar. Because TB drug resistance is associated with genetic mutation(s) relevant to responses to each drug, genotypic methods for detecting these mutations have been proposed to overcome the limitations of classic phenotypic drug susceptibility testing (DST). We explored the current estimates of drug-resistant TB and evaluated the usefulness of genotypic DST in Myanmar. METHODS: We determined the drug susceptibility of Mycobacterium tuberculosis isolated from sputum smear-positive patients with newly diagnosed pulmonary TB at two main TB centers in Myanmar during 2013 by using conventional phenotypic DST and the GenoType MTBDRplus assay (Hain Lifescience, Germany). Discrepant results were confirmed by sequencing the genes relevant to each type of resistance (rpoB for rifampicin; katG and inhA for isoniazid). RESULTS: Of 191 isolates, phenotypic DST showed that 27.7% (n=53) were resistant to at least one first-line drug and 20.9% (n=40) were resistant to two or more, including 18.3% (n=35) multidrug-resistant TB (MDR-TB) strains. Monoresistant strains accounted for 6.8% (n=13) of the samples. Genotypic assay of 189 isolates showed 17.5% (n=33) MDR-TB and 5.3% (n=10) isoniazid-monoresistant strains. Genotypic susceptibility results were 99.5% (n=188) concordant and agreed almost perfectly with phenotypic DST (kappa=0.99; 95% confidence interval 0.96-1.01). CONCLUSIONS: The results highlight the burden of TB drug resistance and prove the usefulness of the genotypic DST in Myanmar.

Clinical Courses of Cavitary Lesions in Pulmonary Tuberculosis / 결핵

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 40mm in their size, and 83.8% were less than 6mm 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 though to affect ot 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.

Pulmonary Resection for Multidrug-Resistant Tuberculosis / 대한흉부외과학회지

BACKGROUND: Treatment outcome with only chemotherapy for multi-drug resistant tuberculosis is usually considered not to be satisfactory. However, the combined therapy of chemotherapy with surgical treatment has been producing higher sputum AFB negative conversion and longer survival rates, and this treatment strategy is expected to be a set-up for the patients with multi-drug resistant tuberculosis. MATERIAL AND METHOD: A retrospective review was performed with the medical records and laboratory findings in 49 patients with multi-drug resistant tuberculosis of 130 patients who underwent pulmonary resection for pulmonary tuberculosis between January 1995 and December 1999 at National Masan Tuberculosis Hospital. RESULT: A mean number of the resistant drugs was 4.5 with a mean age of 35 years. Cavitary lesions on plain chest x-ray were shown in 43 patients of 49(87.8%). Thirty one had positive sputum cultures preoperatively(63.3%). Operative techniques were as follows; 12 pneumonectomies, 28 lobectomies, 7 lobectomies with segmentectomies or wedge resections, one wedge resection and a cavernoplasty. Sputum AFB negative conversion rate was 93.5 % with continuous postoperative chemotherapy. There was no death after operation. Air leakage over a week, postoperative bleeding and wound disruption were developed as postoperative complications. CONCLUSION: We experienced the higher effectiveness of postoperative chemotherapy with pulmonary resection on multi-drug resistant tuberculosis. Although there are several different ideas about operative indications, postoperative drug regimens and length of postoperative medications, pulmonary resection should be considered actively as a effective combination measure with chemotherapy to give a treatment for multi-drug resistant pulmonary tuberculosis.

Evaluation of an ELISA kit for the Serodiagnosis of Pulmonary Tuberculosis by Using Mixed Antigens of Mycobacterium Tuberculosis / 결핵

BACKGROUND: Recently, serologic techniques for tuberculosis have been developed and some of them, which are focusing on detection of serum antibodies mainly directed against specific 38-kDa Mycobacterium tuberculosis, have already been introduced into the market. In this study, diagnostic significance of a new serologic test(ELISA kit) for pulmonary tuberculosis was evaluated. METHODS: Serologic test with newly developed ELISA kit was performed upon 474 individuals, who include 333 active pulmonary tuberculosis patients, 80 healthy cases, and 61 tuberculosis contact cases. This serologic test was based on the ELISA technique and designed to detect antibodies to mixed complex antigens including 38-kDa, which were developed by Erume Biotech Co.,Seoul.Active pulmonary tuberculosis was diagnosed by sputum AFB smear and culture methods. RESULTS: The seropositivities using this ELISA kit were 82.1% and 73.6% in smear-positive and negative groups among active pulmonary tuberculosis, respectively. And, it also showed that seronegativities were 97.5% and 85.2% in healthy and contact groups, respectively. As a whole, the results of our study suing the ELISA kit as a diagnostic methiod for pulmonary tuberculosis showed 80.0% sensitivity for active pulmonary tuberculosis, 97.5% specificity, 96.1% positive predictive value, and 65.0% negative predictive value when the prevalence of tuberculosis in the samples was 60.1%. CONCLUSION: Our results reveal that the detection of antibody its reaction with 38-kDa antigen of M.tuberculosis is not sufficient to be accepted as single diagnostic method for pulmonary tuberculosis. However, they suggest that ELISA kit may be considered as an adjunctive test to standard diagnostic techniques of pulmonary tuberculosis.

The Length of postoperative antituberculous therapy in patients with pulmonary tuberculosis / 결핵

BACKGROUND: The length of postoperative drug therapy remains controversial in pulmonary tuberculosis. We analyzed our experiences to determine the postoperative duration of chemotherapy after resection. METHODS: A retrospective review was performed in 66 of 95 patients that underwent pulmonary resection for pulmonary tuberculosis between January 1993 and December 1998. We compared the relapse rates according to the length of postoperative chemotherapy in each group, classified by the results of sputum AFB culture before the surgery, the number of resistant durgs, the number of prior treatment and the division of anti-TB drugs used postoperatively. RESULTS: Fifty three of 66(80.3%) were men and 13(19.7%) were women with a median age of 33.5 years(range, 16 to 63). The mean lengths of the pre-and post-operative chemotherapies were 4.9 months, and 12.9 months respectively. Five of 66 patients(7.6%) relapsed during the mean period of follow up(39.7 months). In the group less than three times of the prior treatment, there were two relapses(20%) in Ed-the highlight above-rephrase 10 patients that were medicated for 6 months or less, and one relapse in 43 patients(2.3%) that took medicine for more than 6 months(p=0.03). In the group using second-line drugs postoperatively, there was one relapse(25%) in four patients that were medicated for 12 months or less. No patient in a total of 17 that received medicine for more than 12 months relapsed(p=0.03). CONCLUSION: We recommend that patients with the prior treatment less than three times should be treated for more than 6 months after resection and patients using the second-line drugs postoperatively should be medicated for more than 12 months.

Diagnostic Significance of the Serologic Test Using Multiple Antigens of Mycobacterium Tuberculosis by ELISA / 결핵

BACKGROUND: Diagnosis by smear and/or cultures of the Mycobacterium tuberculosis from body fluid or biopsy specimen is "Gold standard". However the sensitivity of the direct microscopy is relatively l ow and culture of mycobacteria is time consuming. Despite an explosion in the techniques of rapid identification of mycobacteria by molecular genetic means, it is laborious and expensive and then rapid, inexpensive serodiagnosis is interested in diagnosis of tuberculosis. But sensitivity and specificity of known serologic antigen is not full sufficient level and then new antigen develop and combination cocktails of new develped antigens by ELISA are needed. METHOD: To compare the efficacy of different mycobacterial specific antigen and to assess the applicability of the combination of several different antigens in the diagnosis of tuberculosis, five ELISA tests derived 14KDa, 16KDa, 19KDa, 23KDa, 38KDa were evaluated in 57 active pulmonary patient and 24 inactive post-therapy follow up patient and 48 normal control. RESULTS: The optical densities of ELISA test with 14KDa, 16KDa, 19KDa, 23KDa, 38KDa were significantly higher in active tuberculosis cases than in normal control(P<0.001, P<0.001, P<0.027, P<0.001, P<0.001) and those with 16KDa, 38KDa were significant higher in active tuberculosis cases than in inactive post-therapy follow up cases(P<0.01, P<0.001) and those of 14KDa, 16KDa, 23KDa, 38KDa were significant higher in inactive post-therapy follow up cases than in normal control(P<0.008, P<0.01, P<0.006, P<0.001). The sensitivity of 14KDa, 16KDa, 19KDa, 23KDa, 38KDa in active pulmonary patient cases was 42.1%, 43.9%, 15.8%, 28.0%, 70.2%, respectively and the specificity of 14KDa, 16KDa, 19KDa, 23KDa, 38KDa in active pulmonary patient cases was 95.8%, 95.8%, 91.7%, 89.6%, 93.8%, respectively. The sensitivity and specificity of combination 38KDa with 16KDa was 87% and 93.7%. CONCLUSION: The sensitivity andspecificity of new antigens for serodiagnosis of the tuberculosis still remains limited at around 70%, which makes its a poor diagnostic tool for disease confirmation. A combination of cocktail antigens provided by cut-off value adjustment for serodiagnosis of tuberculosis some improved diagnostic yield than single antigen serologic test.

Clinical Finding of MDR Tuberculosis and Frequency of MOTT / 결핵

BACKGROUND: The frequency of MOTT has risen as the prevalence of tuberculosis has been declining. Our country has been also. The most of MOTT was resistant to the major anti-tuberculous drugs. METHOD: To compare clinical characteristics and frequencies of MDR tuverculosis with MOTT, the author studied 65 patients showing AFB culture positive with sputum. The data were collected from 176 patients who had been admitted at the National Masan Tuberculosis Hospital from May to June, 1997 to April, 1998. RESULTS: The frequency of MDR tuberculosis was 43.1% and that of MOTT was 9.2%. Among 65 isolated my-cobacteria, 3 cases were M. intracellulare, 2 cases were M. fortuitum, and 1 case was unidentified MOTT. The most frequent age group in 65 culture positive patients was 4th decade and the mean age was 44. The mean age was 61 in MOTT and 42 in M. tuberculosis and bad significant difference(p<0.01). The numbers with past history of treatment were 2.3 in MDR tuberculosis and 1.7 in non-MDR tuberculosis and had significant difference(p<0.05). At the time of admisson, the most frequent regiment for the theatment of MDR tuberculosis was 24 months regimen(85.7%) with the 2nd line anti-tuberculosis drugs. For non-MDR tuberculosis, 9 or 12 months regimen (72.9%) with the 1st line anti-tuberculosis drugs and had significant difference(p<0.01). At the time of admission, the symptom of weight loss was shown in 84.7% of M. tuberculosis and 50.0% in MOTT and there was significant difference(p<0.05) between them. All of the MOTT were identified to be resistant against INH and PAS. Drug resistane rates to INH, OFX(p<0.01) and PAS(p<0.05) in MOTT were higher than in MDR. All of three M. intracellulare strains were resistant to INH, RFP, PAS and OFX. All of two M. fortuitum strains were resistant to most anti-tuberculosis drugs. And the other MOTT was resistant to INH, EMB and PAS. CONCLUSION: MOTT was more common in elderly patients than M. tuberculosis. MOTT cases should be considered to be the probability of multiple drug resistance and treatment failure during the 1st treatment because they showed more resistance to anti-tuberculosis drugs than M. tuberculosis cases. Therefore, there should be more careful investigations for clinical characteristics, natural history of disease, and efficient management for MOTT.

Pulmonary Resection in the Treatment of Multidrug-Resistant Tuberculosis / 결핵

BACKGROUND: Recent outbreaks of pulmonary disease due to drug-resistant strains of Mycobacterium Tuber-culosis have resulted in significant morbidity and mortality in patients worldwide. We reviewed our experience to evaluate the effects of pulmonary resection on the managenent of multidrug-resistant tuberculosis. METHOD: A retrospective review was performed of 41 patients undergoing pulmonary resection for multidrug-resistant tuberculosis between January 1993 and December 1997. We divided these into 3 groups according to the radiologic findigs : (1) patients who have reasonably localized lesion ( Localized Lesion Group ; LLG) (2) patients who have cavitary lesion after pulmonary resection on chest roentgenogram (Remained Cavity Group : RCG). (3) patients who have Remained infiltrative lesions postoperatively (Remained infiltrative group : RIG). We evaluated the negative conversion rate after resection and overall response rate of the groups. Then they were compared with the results of the chemotherapy on the multidrug-resistant tuberculosis which has been outcome by Goble et al. Goble et al reported that negative conversion rate was 65% and overall response rate, 56% over a mean period of 5.1 months. RESULTS: Seventy five point six percent were men and 24.4% woment with a median age of 31 years (range, 16 to 60 years). Although the patients were treated preoperatively with multidrug regimens in an effort to reduce the mycobacterial burden, 22 of 41 were still sputum culture positive at the time of surgery. 20 of 22 patients (90.9%, p<0.01) responded which is defined as negative sputum cultures within 2 months postoperative. Of 26 patients with the sufficient follow up data, 19 have Remained sputum culture negative for a mean duration of 25.7 months (73.1%, p<0.05). The bulk of the disease was manifest in one lung, but lesser amounts of contralateral disease were demonstrated in 15, consisted of 8 in RIG and 7 in RCG, of 41. 12 of 12 patients (100%, p<0.01) who were sputum positive at the time of surgery in LLG converted successfully. 14 of 15 patients (93.3%, p<0.05) with the follow up have completed treatment and not relapsed for a mean period of 25.7 months. The mean length of postoperative drug therapy off LLG was 12.2 months. In RIG, postoperative negative conversion rate was 83.3% which was not significant statistically. There was a statistical significance in overall response rate (100%, p<0.05) of RIG for a mean period of 24.4 months with a mean length of postoperative chemotherapy, 11.8 months. In RCG a statistically lower overall response rate (14.3%, p<0.01) has been revealed for a mean duration of follow up, 24.2 months. A negative conversion rate of RCG was 75% which was not significant statistically. CONCLUSION: Surgery plays an important role in the management of patients with multidrug-resistant Mycobacterium tuberculosis infection. Aggressive pulmonary resection should be performed for resistant Mycobacterium tuberculosis infection to avoid treatment failture or relapse. Especially all cavitary lesions on preoperative chest roentgenogram should be resected completely. If all them could not be resected perfectly, you should not open the thorax.

A Comparative Study of Effect of Secondary Anti-tuberculosis Drugs in the Retreatment of Pulmonary Tuberculosis / 결핵

BACKGROUND: In the management of patients whose primary chemotherapy has failed, careful assessment is essential. It is important to find out as accurate a chemotherapy history as possible. Preferably it should contain the drugs which has never used before. The purpose of present study is establishment of retreatment regimen for pulmonary tuberculosis. The present report concerns the results of retreatment of pulmonary tuberculosis patients treated at National Masan Tubersulosis Hospital. METHOD: Retrospective cohort study was made 104 drug-resistant pulmonary tuberculosis patients who were treated by five regimens between Jan. 1994 and Now. 1996. All the patients taken medicine for second anti-tuberculosis regimens for the first time. We separated the patients by three groups(Group l : OFX+PTA+CS+PAS+Aminoglycoside, Group ll : PZA+PTA+CS+PAS+Aminoglycoside, Group lll : PZA+OFX+PTA+PAS+Aminoglycoside). RESULTS: The age distribution was most frequent in fourth decade(36patients, 34.6%) and the mean age was 42.6 year. The sex distribution was most frequent in the males(81patients, 85.7%). There was 31 patients(29.8%) with combined diseaes, 18 patients with complication and 24 patients(27.9%) with family history. Primary chemotherapy regaimens were HERAZ(S or K) in 48 patients (46.2%), HER(S or K) in 41 patients (39.4%) and others in 15 patients(14.4%). Result of drug sensivivity test showed that the resistance to INH and RFP is in 68 patients(65.4%), RFP is in 12 patients(11.5%), INH s in 3 patients(2.9%) and all sensitive to INH and RFP is 3 patients(2.9%). The clinical symptoms on admission were coughing(89.4%), sputum(69.2%), dyspenea on exertion(37.5%), weight loss(33.7%) blood tinged sputum (15.4%) and otheres. The extent of disease on the radiograph was far-advanced in 73 patients (70.2%), moderate in 28 patients(26.9%) and minimal in 3 patients(2.8%). The side effects for drugs were gastrointestinal troubles in 31 patients(29.8%), arthralgai in 22 patients(21.2%), skin rash in 12 patients(11.5%) and others. The negative conversion rate on sputum AFB smear was 85.6%(87.5% in Group l, 80% in Group ll and 90.5% in Group lll). The average negative conversion time on sputum was 4 month(4.0 month in Group l, 4.6 month in Group ll and 3.0 month in Group III). CONCLUSION: In the retreatment of pulmonary tuberculosis, ofloxacin is useful drug for the patients who are not available to use PZA and combination of PZA and OFX can be use effectively substively substituting for CS.

Clinical Study of Pulmonary Tuberculosis for Admitted Patients at National Masan Tuberculosis Hospital / 결핵

OBJECTIVE: Although the prevalence of pulmonary tuberculosis has decreased progressively after the national control program for tuberculosis began, nowadays the number of MDRTB is increasing seriously. MDRTB tends to be poor responsive to current antituberculosis regimens. It is mainly due to poor compliance, high rate of side reaction of secondary drugs, and limitation in number of available drugs. The purpose of present study is to evaluate the clinical features of pulmonary tuberculosis patients admitted in one national tuberculosis hospital and to expose the problems pertaining to current remedies, to increase the treatment efficacy for pulmonary tuberculosis including MDRTB in the end. METHOD: Retrospective analysis of 336 pulmonary tuberculosis patients admitted in National Masan Tuberculosis Hospital was done. Contents of analysis were patients profile, the first diagnosed time and medical institutes, family history, residence, previous treatment history, chief complaints at the time of admission, lesion site on chest X-ray film, combined deseases, side reaction to antibuberculosis drugs, used drugs before admission and the results of drug sensitivity test. RESULTS: The ratio between male and female was 4:1. Age showed relatively even distribution from 3rd to 6 th decades. 64.6% of the patients was diagnosed at public health center. Weight loss was the most common complaint at admission. Bilateral lesions on chest X-ray films were 59.8%. 1 30patients had combined desease, of which DM was the most common(37.7%). 95patients had family history, of which parents were the most common(41.7%). According to the time of first diagnosis, 31 patients were diagnosed before 1980, and after then the number of patients was increased by degrees Residence overwhelmed in pusan and gyung-nam province. 258 patients got previous treatment history, of which 112 patients(43.4%) had more than 3 times and only 133 patients(51.6%) got regular medication. 97 patients used more than other 3 drugs in addition to INH, EMB, RFP and PZA before admission. 154 patients were informed with the results of drug sensitivity test. of which 77 patients had resistance to more than 5 drugs. Gastrointestinal problem was the most common in side reaction to drugs. CONCLUSION: In the case of weigt loss of unknown cause, tuberculosis should be suspected. In first treatment, sufficient and satisfactory explanation for tuberculosis is necessary and treatment period should not be stict to 6 month-short term therapy. In retreatment, new drugs should not be added to used drugs enen though drug sensitivity restlts show sensitivity to some of them. Proper time for surgical intervention should not be delayed.

Analysis of Causes for Primary Treatment Failure of Pulmonary Tuberculosis / 결핵

BACKGROUND: Nowadays drug resistant tuberculosis is making problems in the treatment of pulmonary tuberculosis and its number is increasing. Several reasons for this are considered including irregular medication, poor drug compliance and wrong regimens. But there are treatment failure cases in spite of regular medication with short-term standard regimens. We reviewed clinical data of 50 patients to find out possible causes of this. METHODS: Subject of this study was 50 patients who failed in the primary treatment of pulmonary tuberculosis in spite of regular medication with short-term standard regimens. All of them were under treatment with secondary regimens in National Masan Tuberculosis Hospital on Oct. 1996. The patient's records were analyzed retrospectively and direct interviews with patients were done. RESULTS: There were relatively more patients in the age of 20th. Male overwhelmed in number. There were smoking in 22 patients and drinking in 24 patients during medication. 17(34%) patients had family history of tuberculosis. Public health center was the most common site for the initial diagnosis among medical institutes. 42 patients had subjective symptoms for pulmonary tuberculosis. 38 patients got sufficient explanation from medical institute about tuberculosis and medication courses. 24 patients had bilateral lesions on chest X-ray film and 43 patients had cavitary lesions. 29 patients had past history for pulmonary tuberculosis with regular medication. The results of drug sensitivity test showed resistance in 41 patients of whom we could get the results CONCLUISON: Main cause of treatment failure of pulmonary tuberculosis in spite of regular medication with short-term standard regimens was drug resistance. Several factors were considered to be related to high prevalence of drug resistance, including age of 20th, male, family history for tuberculosis, bilateral lesions or remaining cavitary lesion on chest X-ray film.

Clinical Evaluation of Surgical Resection on Pulmonary Tuberculosis: Multiple Drug Resistent Pulmonary Tuberculosis / 대한흉부외과학회지

A clinical study of 71 cases of pulmonary tuberculosis that had had surgical resection during the period of 7 years and 6months from January 1989 to June 1996 in National Masan Tuberculosis Hospital. The results were as follows : 1. The ratio of male to female was 3.7 : 1 and in the age incidence the fourth decade was 22%, the third decade 15%. 2. Although medical treatment was performed for more than 3 to 6 months, preoperatively the conversion failure rate of positive sputum to negative state was 66.2%(47 cases). Of the failure cases, multiple-drug-resistant(MDR) patients were 41 cases(87.2%). 3. In MDR group, preoperatively conversion failure rate was 71.9%. 4. From the view of indication for lung resection on the radiographic finding, cavitary lesions were 43 cases(60.6%), destroyed lung lesions were 24 cases(33.8%). 5. The incidence of postoperative complication was 28.2%(20 cases). All cases were MDR group and the most common of complication was tuberculosis spreading. 6. In bilateral lesion, incidence of postoperative tuberculosis spreading was 25%(7 cases). Of the 7 cases, there was the cavitary lesion in 6 cases(86.7%). 7. Total conversion rate of AFB positive sputum to negative state related to resectional sugery was 76.6% and in MDR group conversion rate of AFB positive sputum to negative state was 73.2%. Conversion rate of MDR group with bilateral lesion was the lowest(60%). Conversion rate of drug-sensitivity group was 100% regardeless of lesions site. In conclusion, despite of long-standing medical treatment, it is difficult to converse sputum-positive to negative state in multiple-drug resistance patients and that increases postoperative complications such as tuberculosis relapse as a lack of appropriate drugs postoperatively. Postoperative conversion rate of sputum-positive to negative state was decreased in multiple-drug resistance patients. Because multiple-drug resistance patients have increased due to several factors in Korea, it is important to prevent spreading of multiple-drug resistnce patients through the aggressive operative treatment. When the first medical therapy is fail or drug-resistance is found, operative treatment should be considered with the secondary medical therapy. The operation should be aggressively attempted even though at first medical treatment if indicated.

Rapid Extraction of DNA using Ion Exchange Resin for Early Detection ofMycobacterium tuberculosis by the Polymerase Chain Reaction / 결핵

BACKGROUND: The extraction methods of DNA from clinical samples are the major obstacle to use the PCR(Polymerase Chain Reaction) in routine labortary for early detection of M. tuberculosis. We tried to improve the extraction method of DNA from sputum for establishment of the PCR in routine labortary by reducing the possibility of cross contamination and performing it easily and safely. METHODS: We used the InstaGene(TM) DNA extraction kit(BioRad Co.) using Chelex 100 ion exchange resin for preparation of DNA. We compared InstaGene method in 100 cases of sputum from proteinase K method which is known as the most commonly used method for DNA purification(Experiment 1). And we compared InstaGene method in 98 cases of sputum from Microwave method developed by a company in Korea(Experiment 2). In experiment 1, 245bps of IS6110 were amplified and then 188bps were amplified by nested PCR. In experiment 2, 536bps in primary PCR and 276bps in nested PCR were amplified and analysed by agarose gel electrophoresis and EtBr staining. RESULTS: When we chose AFB smear, culture, or AFB smear and culture as a standard test, PCR had low specificity and positive predictive value in both experiments. The InstaGene method has higher value in sensitivity and negative predictive value significantly than proteinase K method. The InstaGene method and the Microwave methods were similar in sensitivity, specificity, positive predictive value and negative predictive value.. CONCLUSION: Even though both methods had lower possibility of cross contamination, shorter time requrirement, simplicity, and economic advantages than Proteinase K method, the InstaGene method was a little simpler than the Microwave method. Therefore, in terms of usfulness in clinical application, the Instagene method seems to be the most useful method in DNA extraction for detection of M. tuberculosis using PCR. The reliability of this method will be clarified by further studies with enough clinical samples.

Clinical Courses of Cavitary Lesions in Pulmonary Tuberculosis / 결핵

OBJECTIVE: Cavitary lesion in pulmonary tuberculosis sometimes makes problems in the course of treatment. Especially, retreatment cases tend to respond poorly to current antituberculosis agents. So, authors tried to render a guideline for clinical approach toward cavitary lesions in pulmonary tuberculosis. METHODS: Retrospective analysis of 33 pulmonary tuberculosis patients with cavitary lesions was made. All the patients had got treatment at National Masan Tuberculosis Hospital from Jan. 1995 to Aug. 1995. RESULTS: The ratio between male and female was 10:1. Age distribution was 69.7% in 3rd and 4th decades. The locations of cavitary lesion were 60.6% in right upper lung field and 36.4% in left upper lung field. In the extent of disease, there were 12 cases(36.4%) in moderate advanced and 21 cases in far advanced. Cavitary lesions were closed in 5 cases and remained in 28 cases. In the cases of closed cavity, it was happened within 10.6+/-4.72 months after they took treatment, the size of cavity was 35.5 +/-17.1 in long diameter, 27.0+/-12.2 in short diameter and 4.6+/-2.1 mm in wall thickness. In the cases of remained cavity, the size of cavity was 31.9 +/-12.3 in long diameter, 21.0+/-9.8 in short diameter and 5.04+/-2.0 mm in wall thickness. In terms of negative conversion, it took 3.8 +/-2.17 months in the case of closed cavity but it was happened within 5 months for only 4 patients in the case of remained cavity. In the point of past medication history, there was none in closed cavities but there were none in 1 case, once in 3 cases, two times in 9 cases and more than three times in 13 cases among remained cavitary lesions. CONCLUSION: In the retreatment cases of pulmonary tuberculosis with cavitary lesions, they tend to respond poorly to current antituberculosis agents. So, if the lesions are localized, operative intervention may be a proper method as adjunctive treatment.

Comparative Study on the Regimens with Pyrazinamide orOfloxacin in the retreatment of pulmonary tuberculosis / 결핵

Objective: In the early short-term therapy of pulmonary tuberculosis, PZA is used for the first two months on 6EHRZ therapy but PZA is not effective in the case of long-term use PZA for retreatment in the sensitive relapse or acquired drug resistance for PZA. But in the endemic area as Korea, if we can't use PZA in the retreatment of pulmonary tuberculosis, we can't expect the success for retreatment of pulmonary tuberculosis, therefore we need new drugs substituting for PZA. In these days, 4-fluoroquinolone derivatives were investigated and only ofloxacin and ciprofloxacin of derivatives were known to be effective but the effectiveness was also not certain because the result was experimental or combined with other bacteriocidal drugs and datas on effectiveness of pulmonary tuberculosis were so little. Therefore these drugs should be use with other two or three strong-acting drugs in the last period of retreatment of pulmonary tuberculosis. The ofloxacin or ciprofloxacin is used in some area in Korea but randomly and needed more study. We did this study for proving the effectiveness of these drugs and establishment of retreatment regimen for pulmonary tuberculosis. Methods: Retrospective cohort study of 83 drug-resistant pulmonary tuberculosis patients at National Masan Tuberculosis Hospital from Jan. 1994 to dec. 1995 was made. All the patients taken medicine for 2nd anti-tuberculosis regimens for the first time. We separated the patients by two groups.(Group I: OFX+PTA+CS+PAS + Injection, Group II: PZA+PTA+CS+PAS+Injection). We compared the difference between two groups and tested the confidence limit about results after treatment by chi2-test and T-test. Results: 1. The age distribution was most frequent in fourth decade(29.2% in Group I, 37.1% in Group II) and the mean age was 43.9 year in Group I, and 39.0 year in Group II, but had no significant difference between two groups. The sex distribution was more frequent in the males(68.8% in Group I, 85.7% in Group II), but had no significant difference. 2. Family history was 29.2% in Group I, 28.6% in Group II, but had no significant difference. 3. In the respect of extent of disease, far-advanced state was 60.4% in Group I, 74.3% in Group II, but had no significant difference. 4. The side effects for drugs showed in 58.3% in Group I and 65.7% in Group II, and the gastrointestinal trouble showed 25.0% in Group I and arthralgia 34.3% in Group II predominantly respectively and had the significant difference(p<0.05). 5. The negative conversion rate on sputum AFB smear was 87.5% in Group I and 80.0% in Group II, but had no significant difference. But the negative conversion rate on sputum AFB culture was 83.3% in Group I and 57.1% in Group II and had the significant difference(p<0.05). 6. The success rate of treatment was 87.5% in Group I and 83.3% in Group II but had no significant difference. Conclusion: In the retreatment of pulmonary tuberculosis, ofloxacin is useful drug for the patients who are not available to use PZA and can be use effectively substituting for PZA.

Clinical Evaluation of Surgical Resection of Pulmonary Tuberculosis / 결핵

BACKGROUND: In spite of initial intensive and long-term chemotherapy for pulmonary tuberculosis, many problems remain in the treatment of the residual lesion. The role of surgical intervention for pulmonary tuberculosis is getting rid of such residual lesion of pulmonary tuberculosis to support the healing process and to induce bacteriologically negative conversion in the end. METHOD: We experienced 30 cases of pulmonary resection for pulmonary tuberculosis from Aug. 1994 through Apr. 1995 in National Masan Tuberculosis Hospital. We conducted retrospective study to analyze several variables for the cases. RESULTS: 1) The ratio between male and female was 4:l(male 24, female 6) and the age of peak incidence was in 3rd and 4th decades. 2) Indications for pulmonary resection in the radiographic findings were cavitary lesions of 19 cases(63.3%), destroyed one side of 8 cases(26.7%) and destroyed one lobe of 3 cases(10%). 3) 16 of 20 cases with unilateral lesions and all of 10 cases with bilateral lesions on chest X-ray films showed AFB positive on preoperative sputum smears. 14 cases(87.5%) of unilateral lesions and 9 cases(90%) of bilateral ones were converted into AFB negative postoperatively. Negative conversion rates of pneumonectomy and lobectomy cases were 100% and 85.7%, respectively. 4) Preoperative combined disease was 3 cases(10%) of DM and postoperative complications were 2 cases(6.7%) of dead space and no death. CONCLUSION: Chemotherapy only has some limitation in treatment of all tuberculosis. So, surgical intervention for pulmonary tuberculosis is an effective method as partner of chemotherapy.

Tuberculin Skin Test and Plasma Prostaglandin E2 in Patients of New and Intractable Pulmonary Tuberculosis / 결핵

BACKGROUND: The cell-mediated immunity is needed for eradicating the tubercle bacilli. Prosta- glandin(PG), especially PG E2, is involved in cellular immunosuppression. It is known that the PG E2 is suppressed by indo- methacin. For using indomethacin as a immunomodulator of intractable pulmonary tuberculosis(Tbc) patients, we measured the tuberculin skin test(TST) and the plasma PG E2 levels. METHOD: The forty-eight inpatients with sputum positive acid-fast stain bacilli were classified into 6 groups according to antiTbc chemotherapy history(new and intractable cases), plain chest roetgenogram(minimal and far advanced cases), and TST reaction(nagative and positive cases). Except for one group(n=2; new, minimal, and negative cases of TST reaction) of the 6 groups, all subjects(n=46) were measured for the plasma PG E2 levels with radioimmunoassay. RESULTS: 1) There was no significiant difference in the plasma PG E2 levels among A group(far advanced and positive TST reaction cases, n=10, 11.22 +/-2.86 pg/ml), B group(minimal and negative TST reaction cases, n=9, 11.35 +/-2.20) and C group(far advanced and positive TST reaction cases, n=7, 11.11+/-2.30) in the new cases(p >0.05). 2) There was no significiant difference in the plasma PG E2 levels between positive(n=10, 9.25 +/- 2.21) and negative(n=10, 8.25 +/- 1.13) groups by TST in the intractable cases(p>0.05). 3) Comparing the plasma PG E2 levels between new(n=26, 11.35 +/-2.41) and intractable(n=20, 8.75 1.78) groups, the intractable group had significi- antly lower plasma PG E2 levels(p0.05). 5) There was no significiant difference in the plasma PG E2 levels between male(n=32, 10.07 +/- 2.44) and female(n=14, 10.56 +/-2.70)(p >0.05). 6) There was no significiant difference in the plasma PG E2 levels among 2nd(n=5, 10.21 +/-2.86), 3rd(n=9, 9.97+/-2.47), 4th(n=13, 11.35+/-2.33) and 5th(n=19, 9.57+/-2.48) decades(p>0.05). 7) There was no significiant correlation between the induration sizes of the TST and the plasma PG E2 levels(r=0.054, p>0.05). CONCLUSION: From the above results, the plasma PG E2 levels of intract- able group are not higher as the authors had expected. There was no significiant difference in the plasma PG E2 levels by the lesion sizes of plain chest roetgengram and the induration sizes of TST, so more study will be needed to use the indomethacin as a immunomodulator for intractable pulmonary thberculosis patients.

Chest radiographic changes after lobactomy and pneumonectomy

No abstract available.

A clinical review of the surgical treatment for pulmonary tuberculo- sis / 결핵

No abstract available.

Anthelmintic effect of amidental (Bay d 8815) against Ancylostoma duodenale infection

A new anthelmintic, amidantel(Bay d 8815), an acetylated p-amino-phenyl-acetamidine was tried in 140 patients with Ancylostoma duodenale and other helminth infections. In the first trial, each 16 cases in 64 patients with A. duodenale were treated with 3.0, 6.0 and 9.0 or 10.0 mg/kg body weight of amidantel including placebo control. Another 76 patients infected with hookworms and other helminths were treated with 5.0, 6.0 and 8.0 mg/kg body weight of amidantel in the second trial. In order to assess the efficacy and safety of the drug, follow-up examination by repeated and replicated examinations over three consecutive days were performed at 14 to 16 days and 28 to 30 days after treatment, And complete laboratory studies including ECG were carried out before and one day after the medication. In the results, it was confirmed that amidantel is very effective against A. duodenale as well as Ascaris lumbricoides. With regard to dosage, a single dose of 6.0 mg/kg body weight of amidantel was found to be the most effective and well tolerated than the other dosages employed. In a single dose of 6.0 mg/kg body weight the cure rates were 93.8 and 96.6 per cent for A. duodenale infection and 90.9 and 93.1 per cent for ascariasis in the first and second trials respectivley. Relatively significant activity was also observed against Necator americanus at the dosages employed, however it was not superior to other drugs currently use. No significant activity was noted against Trichuris trichiura. Side effects including headache, nausea, dizziness and abdominal discomfort were usually mild and transient. No significant changes attributable to therapy were observed in hematology, blood biochemistry and urinalysis as well as ECG.