Clinical Characteristics of Paradoxical Response to Chemotherapy in Pulmonary Tuberculosis / 결핵

BACKGROUND: The paradoxical response refers to an enlargement of old lesions or unexpected new ones during apparently adequate antituberculous therapy. This response has been reported in cases of intracranial tuberculoma, tuberculous lymphadenopathy, tuberculous pleurisy and pulmonary tuberculosis. However, there are few reports on its frequency and clinical characteristics. METHOD: This study enrolled 205 patients who were treated with first line antituberculous agents for more than 6 months. We retrospectively studied 155 patients with pulmonary tuberculosis and 57 patients with pleural tuberculosis (7 patients had both) from July 1998 to March 2000. The patients were divided into the paradoxical response group and the non-paradoxical group. The clinical characteristics of the paradoxical group were investigated. Statistical analysis was done with an independent sample T-test and Chi-squared test. RESULT: 29 of the 205 patients(14.1%) had paradoxical response. Among the 29 patients, there were 19 pulmonary tuberculosis, 8 tuberculous pleurisy(2 patients had both). Paradoxical response appeared 32 days (mean 35 days in pulmonary tuberculosis, mean 25 days in tuberculous pleurisy) after the beginning of chemotherapy. The duration to regress less than half of initial chest lesion was 114 days in pulmonary tuberculosis and 124 days in tuberculous pleurisy, respectively. Most common clinical manifestation of paradoxical response patients was coughing in both pulmonary tuberculosis and tuberculous pleurisy. Male sex, high blood WBC count and high level of pleural fluid LDH were related with paradoxical response. CONCLUSION: These findings suggest that presponse usually appears 1 month and disappears within 4 months after the beginning of anti-tuberculous chemotherapy. Paradoxical response was relatively correlated with male sex, high blood WBC count and high level of pleural fluid LDH.

A Case of aspergillus tracheobronchitis in non-immunocompromise patient / 결핵

The aspergillus tracheobronchitis is distinctive manifestation of invasive aspergillosis, in which infection is limited completely or predominantly to the tracheobronchial tree. It accounts for about 7 to 10 percent of cases of invasive disease. Grossly, such disease may take the mucosal exudate and obstruct partially the airway lumen or completely the occlusive mucous/fungus plugs. Microscopically, the superficial portion of the airway wall is acutely inflamed and contain fungal hyphae. However, infection is often limited to the mucosa. We report a case of aspergillus tracheobrochits in a 54 year-old man who presented cough, progressive dyspnea with wheezing, and mucus plug. Bronchoscopy showed mucosal exudate and plug.Bronchoscopic biopsy showed aspergillus hyphae and inflammation in the mucosa. He was successfully treated with itraconazole.

A Case of chronic necrotizing pulmonary aspergillosis with pulmonary artery aneurysm / 결핵

Pulmonary aspergillosis is classified as a saprophytic, allergic, and invasive disease. Chronic necrotizing pulmonary aspergillosis is categorized as an invasive pulmonary aspergillosis. Most invasive pulmonary aspergillosis have acute and toxic clinical features but chronic necrotizing pulmonary aspergillosis is characterized by a sub-acute infection, most commonly seen in patients with altered local defense system from preexisting pulmonary disease of in mild immunocompromised patients. Pulmonary artery aneurysm due to this infection is termed as a mycotic aneurysm, etiology of which are tuberculosis, syphilis, bacteria and fungus. We report a case chronic necrotizing pulmonary aspergillosis complicating pulmonary aneurysm is a 62 year-old man who was presented with cough, sputum, and fever. Chest radiographs showed a rapid, progressive cavitary lesion and pulmonary artery aneurysm. Angioinvastion of aspergillus was revealed by pathology after operative removal of left upper lobe containing the pulmonary artery aneurysm. He was treated with itraconazole.

Emergence of YMDD Motif Mutant Hepatitis B Virus during Short-erm Lamivudine Therapy / 대한간학회지

BACKGROUND/AIMS: The emergence of lamivudine-resistant mutant hepatitis B virus (HBV), with aminoacid substitution in the YMDD motif of DNA polymerase, has been reported in the long-term lamivudine use group. However there is no report about the emergence of mutant viruses during the short-term lamivudine therapy. The objective of this study was to investigate the emergence of YMDD mutant HBV during short-term lamivudine therapy. METHODS: We evaluated twenty-eight chronic hepatitis B patients who were HBeAg and HBV DNA positive and treated with lamivudine 100mg p.o. daily for 12 weeks. First, we investigated the emergence of YMDD mutants by nested polymerase chain reaction (PCR) method developed by Chayama et al in 19 patients who lost HBV DNA during lamivudine therapy but showed HBV DNA re-emergence 2 weeks after the end of therapy. Second, DNA subcloning and sequencing of HBV DNA polymerase including YMDD motif was undertaken in one patient's serial blood samples at 0, 8, 12 weeks to confirm the results of nested PCR. RESULTS: YMDD motif mutation was detected in 17(90%) out of 19 patients at the end of therapy and the type of mutations were YIDD only. At the end of therapy, mutant was predominant in 5 patients, both mutant and wild type were similar in proportion in 3 patients, and wild type was predominant in 9 patients. When we carried out nested PCR serially with samples of 0, 2, 4, 8, 12, 14 weeks after initiation of therapy in 5 patients who were mutant predominant at 12 weeks, YIDD mutant began to be detected from 2 weeks in 4 patients and from 4 weeks in one patient. However, rapid turnover from mutant to wild type happened after the end of therapy, so only wild type was detected in 3 patients and wild type became predominant in 2 patients at 2 weeks after the end of therapy. All the sequencing results of serial blood samples in one patient were consistent with nested PCR data. CONCLUSIONS: The presence of YMDD motif HBV polymerase mutant may be possible before administration of lamivudine in Korean chronic hepatitis B patients. Nested PCR assay would be an useful method to detect YMDD mutant.

The Effect of Long-erm Lamivudine Therapy for Chronic Liver Disease due to Hepatitis B Virus / 대한간학회지

BACKGROUND/AIMS: We studied to evaluate the virological and biochemical responses to lamivudine and to detect YMDD mutants in patients who received long-erm lamivudine therapy. METHODS: We conducted a one-ear trial of lamivudine in 45 Korean patients with chronic liver disease due to hepatitis B virus. The patients were treated with a single oral average dose of 100 mg of lamivudine every day for 12 months. RESULTS: The suppression of serum HBV DNA was sustained in 77.8% of the patients and the normalization of serum ALT in 80%. The proportions of patients with HBeAg seroconversion were 25%. YMDD mutants were detected in 4 of 8 patients who showed sustained HBV DNA and serum ALT response (n=31) and in 3 of 8 patients who showed HBV DNA or serum ALT breakthrough (n=9). The response to lamivudine therapy in HBeAg-egative patients was excellent. CONCLUSION: Lamivudine therapy resulted in a significant virological and biochemical improvements and were well tolerated. But, YMDD mutants were detected during lamivudine therapy.

Sequence Analysis of 'a' Determinant in Two Patients with De Novo HBV Infection after Renal Transplantation / 대한간학회지

BACKGROUND/AIMS: HBV infection can be seen after organ transplantation. The presence of anti-Bs in serum means protection from HBV infection. If amino acids were mutated in 'a' determinant which was a common antigenic epitope of HBsAg, escape from humoral immunity can occur. Recently, in chronic HBV infected patients who received liver transplantation but reinfected by HBV, many authors reported mutations in 'a' determinant sequence. However, in renal transplantation, there were few reports about HBV infection and 'a' determinant mutation after transplantation. Therefore, we studied the incidence of HBV reinfection after renal transplantation and also tried to analyze 'a' determinant sequence in those patients. METHODS: We reviewed HBsAg-egative patients who received renal transplantation in our hospital, but turned HBsAg positive after transplantation. We selected two patients who were anti-Bs positive before transplantation but turned HBsAg positive after transplantation, and analyzed 'a' determinant of amino acid sequence of these patients. RESULTS: Among 1682 patients who were HBsAg negative before transplantation, 21 patients were turned HBsAg positive after transplantation. Among them, 6 patients were anti-Bs positive before transplantation. Sequence analysis of the 'a' determinant amino acid in two patients whose HBsAg turned positive after transplantation revealed no evidence of mutation in comparison with previously reported subtype 'a' determinant sequences. CONCLUSION: In renal transplantation, HBV could be reinfected in patients who had been anti-Bs positive before transplantation even without mutation in 'a' determinant region.

Relationship Between Airway Inflammation Assessed by Induced Sputum and Airway Hyperresponsiveness in Asthmatic Patient / 결핵

BACKGROUND: Airway inflammation and hyperresponsiveness are recognized as major characteristics of bronchial asthma. Airway inflammation has usually been assessed by invasive methods, e.g. BAL or bronchial biopsy, but recent studies proposed induced sputum as another reliable and non- invasive tool to investigate airway inflammation in asthmatic patients. Thus, the relationship between airway inflammation assessed by induced sputum and airway hyperresponsiveness was investigated in asthmatic patient. METHOD: Airway responsiveness was determined by the concentration that caused a 20% decrease in FEV1(PC20) after inhaling incremental concentrations of methacholine. The numbers of inflammatory cells and the concentration of eosinophilic cationic protein(ECP) were assessed in induced sputum obtained by inhalation of hypertonic saline(3%). RESULT: We analyzed sputum induced in 15 stable asthmatic patients. 1. The differential cell count(%) of macrophages, neutrophils, eosinophils and lymphocytes in induced sputum were 39.1 +/- 27.0%, 29.6 +/- 21.0%, 28.8 +/- 18.8%, 1.3 +/- 3.1% respectively. 2. The mean value of baseline FEV1 (Predicted) and ECP were 76.3 +/- 30.3% and 1,101 +/- 833 micro gram/L respectively. The geometric mean value of PC20 was 0.56mg/mL. 3. The relationships between the sputum eosinophil and ECP in induced sputum, and between sputum eosinophil and degree of airway responsiveness(PC20) were found be significantly correlated (r=0.81, p<0.05 and r=-0.78, p<0.05, respectively). 4. Sputum neutrophils and PC20 were not correlated to each other (r=0.11, p=0.69) and a significant negative correlation was found between ECP and baseline FEV1(predicted) (r=-0.62, p<0.05). CONCLUSION: The results of this study suggest that an induced sputum via a inhalation of hypertonic saline is useful to determine a patient's status of airway inflammation, and airway inflammation is one of the major causal factors in the development of bronchial hyperresponsiveness in asthmatic patients.