A case of refractory disseminated subcutaneous abscess with intrahousehold transmission by a USA300-LV-like strain of PVL-positive community-acquired MRSA clone.

A 44-year-old man with hypertension and dyslipidemia presented with pain in the buttocks. The patient was diagnosed with perianal ischiorectal fossa abscesses and cellulitis. He was subsequently diagnosed with a perineal subcutaneous abscess after a week, a right lower leg impetigo after a month, right periorchitis, a scrotal abscess, and Fournier's gangrene after two months. The patient was treated with various antimicrobials and underwent incisional drainage. Methicillin-resistant Staphylococcus aureus (MRSA) was detected in all draining specimens. Her daughter and son, who lived with the patient, presented with subcutaneous abscesses caused by MRSA. Suspecting repeated infections and household infections by virulent types of MRSA, such as PVL-positive strains, we performed genetic analyses of his and his son's strains. The results showed that the genotype and toxin gene profiles [ST8/t008/SCCmec type IVc/Panton-Valentine leucocidin (PVL) (+)/arginine catabolic mobile element (ACME) (-)] of both strains matched. single nucleotide polymorphism (SNP) analysis confirmed genetic homology between the two, concluding that home transmission by the same clone had occurred. In addition, the strain in this case differed from USA300 [ST8/t008/SCCmec type IVa/PVL (+) ACME (+)], which is a PVL-positive MRSA worldwide, including Japan, and its genetic profile matches that of USA300-LV, which is detected mainly in South America. Furthermore, SNP analysis showed that this strain is similar to USA300-LV/J (derived from USA300-LV) detected on Ishigaki Island, Okinawa Prefecture, Japan. This is the first report of refractory infections and household transmission of USA300-LV/J. Therefore, it is necessary to closely monitor both the USA300 and the USA300-LV.

Noninvasive positive pressure ventilation for treating acute asthmatic attacks in three pregnant women with dyspnea and hypoxemia.

In our case reports, we mentioned about the utility of NPPV therapy in addition to standard pharmacologic therapy for acute asthma exacerbations in pregnant women with dyspnea and hypoxemia compared with that of oxygen therapy alone. Careful patient selection and clinicians' NPPV experience are crucial in optimizing patient outcomes.

A rare case of congenital bronchoesophageal fistula in an adult.

INTRODUCTION: When congenital bronchoesophageal fistulas exist without atresia of the esophagus, the diagnosis can be delayed, although symptoms may occur early following fistula development. Therefore, while they are usually found in infants, they can be extremely rarely found in adults. We herein report a rare case of bronchoesophageal fistula without atresia in an adult. CASE: An 69-year-old male presented to the outpatient clinic with a decades-long history of cough with expectoration immediately after taking food, especially liquids. Computed tomograph, esophagoscopy, and esophagography revealed the fistulous communication between the mid-esophagus and right lower lobe bronchus, with consolidation in the right lower lobe. We performed right lower lobectomy with the closure and excision of the fistula. The histopathology of the fistula revealed the mucosa to be lined by stratified squamous epithelium. There was no evidence of inflammation, granuloma, or carcinoma. CONCLUSION: In conclusion, despite the benign nature of this malformation, if left untreated, it can cause long-term debilitating respiratory symptoms associated with the fistula. Therefore, the diagnosis should be considered in the evaluation of recurrent lung infection.

Clinical features of three cases with pulmonary alveolar proteinosis secondary to myelodysplastic syndrome developed during the course of Behçet's disease.

We have previously reported that myelodysplastic syndrome (MDS) is the most common underlying disease in cases of secondary pulmonary alveolar proteinosis (PAP). Here, we present 3 MDS cases in which PAP developed during the course of Behçet's disease (BD). All patients carried trisomy 8 in the bone marrow. Chest HRCT scans showed variable distribution of ground glass opacities, but none of the scans showed so called "crazy paving appearance". Two patients with intestinal BD who underwent potent immunosuppressive therapy died of sepsis. These findings demonstrate that PAP secondary to MDS may be occasionally associated with BD.

Legionella pneumonia caused by Legionella pneumophila serogroup 2: second case report in Japan.

A 56-year-old man with a 3-day history of a chilly sensation and general fatigue presented to a hospital in his neighborhood. He was diagnosed as having pneumonia and immediately treated with intravenous ceftriaxone sodium, but his respiratory condition deteriorated and he developed symptoms of restlessness. Although Legionella urinary antigen detection tests were negative, his clinical course suggested Legionella pneumonia. After his treatment was changed to intravenous ciprofloxacin and oral clarithromycin, his general condition gradually improved. Later, Legionella pneumophila serogroup 2 was isolated from a bronchoalveolar lavage specimen. This was considered to be the causative organism. In our literature search, this was only the second case of Legionella pneumonia caused by Legionella pneumophila serogroup 2 in Japan.

[Usefulness of support during treatment by alignment with health centers and DOT during hospitalization].

OBJECTIVES: To evaluate the effectiveness of patient support by alignment with public health centers and DOT during hospitalization, on treatment completion of tuberculosis patients. SUBJECTS: Four hundred seventy-seven patients (male 344, female 133) newly admitted from July 1, 2002 to June 30, 2003 to our hospital were enrolled in the study. METHOD: The patients were divided into two groups: one comprised of the patients who were discussed in the conference held by the hospital staffs and the regional public health center staffs about the necessity of support for continuing treatment regularly after discharge from our hospital (Conference (+) group; N=306), and the other who were not discussed in the conference (Conference (-) group; N=171). The Conference (+) group was further divided into two groups: One comprised of the patients who were regarded to need support after discharge (Support (+) group; N=106), and the other no need of support after discharge (Support (-) group; N=200). The patients' characteristics and backgrounds were compared between the Conference (+) and the Conference (-) groups, and between the Support (+) and the Support (-) groups. The rate of treatment completion and of default were compared between the Conference (+) and the Conference (-) group, and between the Support (+) and the Support (-) group. They were also compared between the patients with and without DOT for a month during hospitalization, and between the patients who were treated for the first time (new case) and those who had been treated previously (retreated case) or who had been treated when they were admitted to our hospital and continued treatment after admission (continuous cases). RESULTS: There is no significant differences in patients' characteristics and backgrounds between the Conference (+) and Conference (-) groups, but the ratios of male, sputum-culture positivity, far advanced lesions on chest X-ray, hypoalbuminemia, and disemployment were higher in Support (+) group than in Support (-) group. The overall (N=477) treatment outcomes were as follows: cured (defined by sputum-culture negativity at completion of chemotherapy) 300 (62.9%), completed (defined by no sputum data at completion of chemotherapy) 90 (18.9%), failed 5 (1.0%), defaulted 6 (1.3%), transfer out 6 (1.3%) and death 70 (14.7%). Therefore, the ratio of treatment success (defined by cured+completed) was 390/477 (81.8%). Because of more died cases in Conference (-) groups, treatment success rate was significantly higher in the Conference (+) groups than in the Conference (-) groups. There were no significant differences in the rate of treatment success and of default between the Support (+) and the Support (-) groups, but no defaulter case was seen in the Support (+) group. There were no differences in the rate of treatment success and of default between the groups with and without DOT for a month during hospitalization. There were no differences in the rate of treatment success and of default between the groups with the retreated and continuously treated cases and the new cases. CONSIDERATIONS: Treatment success rate was excellent in our study. DOT for a month during hospitalization didn't affect the improvement of treatment success after discharge, partly because the education on tuberculosis treatment was sufficiently done for most patients during hospitalization and a nurse made a telephone call to the patient who didn't attend the outpatient department of the hospital. CONCLUSIONS: To hold conference with regional public health center is effective for completion of tuberculosis treatment.

[Pulmonary nontuberculous mycobacteriosis in patients with lung cancer].

OBJECTIVES: To clarify the clinical features of the coexisting lung cancer and nontuberculous mycobacteriosis of the lung. MATERIALS AND METHODS: We analyzed clinical data on 11 admitted cases of coexisting lung cancer and pulmonary non-tuberculous mycobacteriosis at National Organization Tokyo Hospital during the period from 1997 to 2002. RESULTS: There were 10 men and 1 woman, with a mean age of 66 years. Five of 11 patients had underlying pulmonary disorders, such as healed tuberculosis and lung cyst. Histological types of lung cancer were squamous cell carcinoma in 4, adenocarcinoma and small cell carcinoma in 3 each, and 8 out of 11 cases were in stages III to IV. We classified the 11 cases into 2 groups: (1) lung cancer concurrently detected with mycobacteriosis (8 cases) and (2) lung cancer sequentially detected during the follow-up of mycobacteriosis (3 cases). Lung cancers in the latter group were in relatively early stages and all patients of this group received resection of the cancer, while most of lung cancers in the concurrent group were in far-advanced, and palliative and/or supportive treatment for lung cancer were frequently selected. The strains of mycobacteria were as follows: M. avium complex (6 cases) and M. kansasii (5 cases). The incidence of lung cancer among patients with nontuberculous mycobacteriosis was 2.5 percent (2 percent of M. avium complex diseases patients and 8.2 percent of M. kansasii disease patients), while the incidence of nontuberculous mycobacteriosis in untreated lung cancer patients was 1.4 percent. Analysis of anatomical relationship between lung cancer and non-tuberculous mycobacteriosis revealed that the two diseases located in the same lung in 8 cases, and also in the same lobe in 4 out of the 8 cases. Outcome of treatment for nontuberculous mycobacteriosis was good especially in patients with M. kansasii disease, and it seemed that coexisting nontuberculous mycobacteriosis did not influence on the prognosis of lung cancer patients. CONCLUSION: In the management of lung cancer, physicians should consider the possibility of coexisting pulmonary non-tuberculous mycobacteriosis, as well as coexisting pulmonary tuberculosis.

[Thoracic malignancies in patients with chronic tuberculous empyema].

OBJECTIVES: To clarify features of thoracic malignancies occurred in patients with chronic tuberculous empyema. MATERIALS AND METHODS: We analyzed clinicopathological data of 15 patients with thoracic malignancies who had chronic tuberculous empyema, encountered at Tokyo National Hospital during the period from 1977 to 2002. RESULTS: There were 13 men and 2 women, with a mean age of 67 years. Most of all (13/15) patients had history of surgery for tuberculosis including artificial pneumothorax (9 cases). Malignancies consisted of pyothorax-associated lymphoma (PAL; 9 cases), lung cancer (4 cases), malignant fibrous histiocytoma (1 case), and angiosarcoma (1 case). There were no differences in background factors between PAL patients and the other patients. Common symptoms were chest pain (10 cases), fever (7 cases), and bloody sputum (4 cases) and it seemed that these symptoms were more evident in patients with PAL than in patients with other diseases. Plain chest X-ray films often failed to detect the tumor, and the diagnosis was often obtained by sputum cytology, bronchofiberscopy, transcutaneous biopsy, and resection with support of CT and/or MRI films. On radiographs, all tumors located in empyema cavities or around empyema walls, and a pulmonary mass adjacent to the empyema wall was characteristic of lung cancer. PAL showed certainly good outcome; 40% 5-year survival rate with resection or chemoradiotherapy. On the other hand, all of lung cancer cases were diagnosed at stage III, and had poor outcome, and the remaining patients with the other malignancies also had poor outcome. CONCLUSION: Clinicians should keep in mind occurrence of several thoracic malignancies during the follow-up of patients with chronic tuberculous empyema.

[Leukopenia due to anti-tuberculous chemotherapy including rifampicin and isoniazid].

OBJECTIVES: To examine the incidence rate by age and gender of leukopenia caused by chemotherapy including rifampicin (RFP) and isoniazid (INH), and to study the relationships between the leukopenia and the hepatic side effect or other haematological disorders such as thrombocytopenia. SUBJECTS: Out of the tuberculosis patients who were admitted to our hospital in 1987-88, 1991-92, and 1996-2000, 1,525 patients (1,153 men, 372 women) were chosen for our study who had the white blood cell counts (WBC) in the peripheral blood more than 3,000/mm3 before chemotherapy, and underwent haematologic examination at least twice within 3 months after starting chemotherapy. METHODS: The definition of leukopenia was as follows: 1) WBC became less than 3,000/mm3 during chemotherapy for patients with pre-treatment WBC more than 4,000/mm3, or 2) WBC decreased more than 1,000/mm3 in patients with pre-treatment WBC between 3,000 and 4,000/mm3. The incidence rates of leukopenia by age, gender, and regimens of chemotherapy were calculated. The case-control study was done between the control and the leukopenia groups excluding patients suffered from agranulocytosis to clarify the hematological and biochemical characteristics of the leukopenia group. The control patients were chosen in the following way. For each patient with leukopenia, a patient with the same admission year, same gender, same regimen of chemotherapy, and the nearest age was chosen as a control patient. The changes in counts of white blood cell, granulocyte, and platelet, in hemoglobin concentration, and in hepatic enzyme levels before and during chemotherapy were compared between the leukopenia and the control groups. Thrombocytopenia was defined as platelet count less than 15 x 10(4)/mm3 and hepatic dysfunction as either asparate aminotransferase (AST) higher than 31 IU/l or alanine aminotransferase (ALT) higher than 34 IU/l. RESULTS: (1) Incidence rate of leukopenia The leukopenia appeared in 36 patients (14 men, 22 women), two (one man, one woman) of whom showed agranulocytosis. The incidence rate was 1.2% (14/1,153) for men and 5.9% (22/372) for women. The incidence rate of women was higher than that of men in the age groups between 20 to 79 y.o., but no difference was seen in the age groups elder than 80 y.o. There were no differences in the incidence rate among groups treated with HRE (E: ethambutol), HRS (S: streptomycin), and HREZ (Z: pyrazinamide). The chemotherapy was continued in 30 patients after the appearance of leukopenia, and the natural recovery from leukopenia was seen in 19 patients, while the leukopenic state lasted during the chemotherapy in the remaining 11 patients. In two patients who exhibited agranulocytosis all drugs were discontinued. In the remaining 4 patients one or more drugs were discontinued. (2) Case-control study between leukopenia (N = 34) and the control (N = 34) groups There were no differences in age, sputum culture positivity on admission, degree of roentgenographic extent of the disease, ratio of cavity formation, and quantity of daily doses between the two groups. There was also no difference between the days until leukopenia appeared after starting chemotherapy (47.6 +/- 29.5 days) in the leukopenia group, and the days until WBC count became minimum within 3 months after starting chemotherapy (41.7 +/- 21.0 days) in the control group. The negativity of tuberculin skin testing was higher in the leukopenia group [7/14 (50%)] than in the control group [1/10 (10%)], however, the difference was statistically not significant due to rather small size of cases. Before the starting chemotherapy, the counts of WBC (7,230 +/- 1,530 vs 5,500 +/- 1,510/mm3, p < 0.001), neutrophil (5,230 +/- 1,450 vs 4,320 +/- 1,620/mm3, p < 0.05), lymphocyte (1,440 +/- 830 vs 830 +/- 440/mm3, p < 0.001) and platelet (34.9 +/- 12.2 vs 24.1 +/- 6.4 x 10(4)/mm3, p < 0.001) in the peripheral blood and the globulin level (3.71 +/- 0.61 vs 3.35 +/- 0.61 g/dl, p < 0.05) in the serum were significantly higher in the control group than in the leukopenia group. The decrements in the counts of WBC and granulocyte during chemotherapy were larger in the leukopenia group than in the control group (delta WBC: 2,880 +/- 1,530 vs 1,910 +/- 1,520/mm3, and delta Neut: 2,840 +/- 1,510 vs 1,820 +/- 1,380/mm3, p = 0.01, respectively), but the counts of lymphocyte were similar in both groups. The platelet counts also decreased in both groups, but to the mid-normal level in the control group, and to the lowest normal level in the leukopenia group, in which 15 out of 34 patients (44%) showed thrombocytopenia. The levels in the serum of hepatic enzymes such as AST, ALT, and gamma-GTP (gamma-glutamyl aminotransferase) increased during chemotherapy in the leukopenia group, while decreased in the control group, and the facts indicate that in the former not only bone marrow cells but also hepatic cells were impaired by anti-tuberculosis drugs. CONSIDERATIONS: Leukopenia may occur in the course of treatment with anti-tuberculosis drugs, but it is not necessary to stop the chemotherapy immediately, because the WBC count recovers spontaneously or remains under stable leukopenic state during chemotherapy in most cases. But when leukopenia appears, the peripheral blood counts must be checked cautiously, and the chemotherapy should be stopped if the WBC count progressively decreases. The patients who showed leukopenia due to anti-tuberculosis drugs may have had weaker natural and acquired (cell-mediated) immunologic response to tuberculosis infection, and more vulnerable bone marrow cells and hepatic cells to anti-tuberculosis drugs than the control.

[Agranulocytosis due to anti-tuberculosis drugs including isoniazid (INH) and rifampicin (RFP)--a report of four cases and review of the literature].

We experienced 4 cases of agranulocytosis due to anti-tuberculosis drugs (rifampicin [RFP], isoniazid [INH], ethambutol [EB], streptomycin [SM] or pyrazinamide [PZA]) among some 6,400 tuberculosis patients who underwent chemotherapy over the past 20 years from 1981 to 2002 in our hospital, and the incidence rate of agranulocytosis was estimated at 0.06%. The 4 cases of agranulocytosis were as follows. CASE 1: A 51-year-old woman with right chest pain and fever was admitted to our hospital on Jan 4, 2001. The white blood cell (WBC) count was 5,200/microliter. The tubercle bacilli were cultured in her sputum. The treatment with INH 0.3, RFP 0.45, EB 0.75, PZA 1.2 g/day, allopurinol and teprenone was started on Jan 13. Pyrazinamide and allopurinol were stopped because of hyper-uric acidemia on Feb 7. Agranulocytosis and eosinophilia (WBC 1,300 [Neut 1%, Ly 57%, Eos 35%]) developed on Feb 13. All drugs were withdrawn and G-CSF drug nartograstim 100 micrograms was injected subcutaneously for 3 days. The WBC recovered to normal level and she was thereafter treated with INH, EB and Levofloxacin (LVFX) without any further trouble. Agranulocytosis in this case was supposed to be due to RFP. CASE 2: A 66-year-old man who had had nephrotic syndrome and hypothyroidism and has been treated with prednisolone 10 mg/day was admitted to our hospital on Aug 9, 2000 because of miliary tuberculosis. The tubercle bacilli were cultured in his sputum and the treatment with INH 0.3, RFP 0.45, and EB 0.75 g/day were started on Aug 10, but it was withdrawn on Aug 17 because of general skin eruption. After re-starting treatment with EB and INH on Aug 24, RFP was added in small dosage (0.05 g) on Oct 12, but agranulomatosis (WBC 2,300/microliter [Neut 2%]) developed on Nov 21, and all drugs were withdrawn again. The G-CSF drug filgrastim was used once subcutaneously, and WBC recovered immediately. He was thereafter treated with INH, EB, LVFX successfully. Agranulocytosis was supposed to be due to RFP. CASE 3: A 60-year-old woman without symptoms had abnormal chest roentgenograph, and consulted with our hospital on Aug 26, 2002. The broncho-alveolar lavage fluid was smear and culture-negative, but PCR-TB positive, and the case was diagnosed as pulmonary tuberculosis. Treatment with INH 0.3, RFP 0.45, EB 0.75, PZA 1.2 g/day, alloprinol 300 mg and rebamipide 300 mg/day was started on Sept. 5, 2002. Late in September, she complained of appetite loss. The laboratory data on Oct 3 revealed WBC 900/microliter (Neut 1%, Ly 94%), aspartate aminotransferase (AST) 199 IU/l, and alanine aminotransferase (ALT) 253 IU/l, showing agranulocytosis and drug-induced hepatitis. The chemotherapy was immediately withdrawn and she was admitted to our hospital on the next day. Glycyrrhizin derivative (SNMC) 40 ml was injected for 5 days, and WBC recovered, and AST and ALT also became normal. CASE 4: A 60-year-old man was admitted to our hospital on March 11, 1981 because pulmonary tuberculosis had recurred. He had been treated with SM, PAS and INH in 1973 for pulmonary tuberculosis. On admission examination of blood count and blood chemistry were normal. Treatment with RFP, INH and SM was started on March 11. He stopped out from the hospital on April 17, but in a few days he returned back with sore throat, lower lip swelling and gingival bleeding. Blood cell count on April 24 showed pancytopenia with RBC 226, Hb 7.5, WBC 800 (Ly 96%, Eos 4%) and Plt 10,000/microliter. The bone-marrow showed NCC (nuceated cell count) of 5,500, and megakaryocyte 0. Thereafter ground glass appearance shadows were seen on the whole lung field, and he died May 26. Autopsy showed generalized aspergillosis. It was strongly suspected that either of RFP, INH or SM was responsible for his pancytopenia. We collected another 10 cases of agranulocytosis due to anti-tuberculosis drugs in the world wide literature, and found men/women ratio 5/8 (in one case gender was not known), the duration of chemotherapy before appearance of agranulocytosis 1-3 months, no change in the lymphocyte count of the peripheral blood, and the accompanying of another allergic signs such as skin eruption, blood eosinophilia or drug-induced hepatitis in some cases, and these findings suggest that the mechanism of agranulocytosis due to anti-tuberculosis drugs was allergic in nature.

[Characteristics and treatment outcomes of INH-resistant or RFP-resistant tuberculosis].

BACKGROUND: As an effective regimen for isoniazid-resistant but rifampicin-susceptible tuberculosis (INHr-TB), the use of a 6-month three or four-drug treatment regimen including refampicin (or rifampin) and pyrazinamide has been recommended by many experts of the world. On the other hand, treatment regimen for rifampicin-resistant but isoniazide-susceptible tuberculosis (RFPr-TB) has not been well established because of the small number of such patients. In Japan the standard regimen has not been established even for INHr-TB, and the treatment has been done by each physician on the empirical bases. OBJECTIVES: To determine the adequate therapy of INH-resistant TB or RFP-resistant TB. DESIGN: Retrospective cohort study. SUBJECTIVES: Hundred and eleven INHr-TB patients (4.9%) and 5 RFPr-TB patients (0.2%) out of 2252 new smear-positive tuberculosis patients who were admitted to our hospital from 1994 to 1998. RESULTS: Patients with previous tuberculosis history was found in 35 of 111 INHr-TB (31.5%) patients, of which 13 (37.1%) were re-treated within 3 years. On the other hand 146 patients (21.1%) of all new culture-positive tuberculosis patients (N = 690) treated in our hospital from 1997 to 1999 had the previous tuberculosis history of which only 8 patients (5.5%) were retreated within 3 years while 115 patients relapsed more than 10 years after the onset of previous tuberculosis history. The frequency of recurrence within 3 years after the onset of previous tuberculosis history was, significantly higher (p < 0.0001) in cases of INHr-TB (13/111 [11.7%]) than in cases of newly registered ones (8/690 [1.2%]), and the fact indicates that the incidence of tuberculosis recurrence was higher in INHr-TB patients than in pan-sensitive TB patients when the previous treatment was discontinued or insufficiently implemented. The resistance pattern of the INHr-strains were as follows. INH alone 40 (36.0%), SM-resistant 47 (42.3%), TH resistant 19 (17.1%), EB-resistant 18 (16.2%), KM-resistant 6 (5.4%), and others 3 (2.7%). Therefore the mean number (+/- SD) of resistant drugs excluding INH was 1.4 +/- 0.7. Eighteen out of 71 (25.4%) strains with low grade INH-resistance (0.1 microgram/ml complete resistance) had also TH-resistance, while only one out of 40 (2.5%) strains with high grade INH-resistance (1 microgram/ml resistance) was resistant to TH (p = 0.005). Of 111 INHr-TB patients, 9 patients (8.1%) discontinued treatment by themselves, 17 patients (15.3%) admitted to another hospital, and 17 patients (15.3%) died. The patients who died (age [M +/- SD] 66.4 +/- 14.0 yrs) were older than those who were alive (48.7 +/- 17.8, p < 0.001), and were too seriously ill to accept sufficient chemotherapy, and therefore their deaths were not considered to be related to INH resistance. The treatment outcomes of the remaining 68 patients who were followed in our hospital were summarized as follows. 1) Treatment failure occurred in 3 patients, of whom 2 patients could not be treated with full dose rifampicin in the initial phase of treatment because of side effects to liver or accompanying idiopathic thrombocytepenic purpura (ITP). Two out of these 3 patients developed multi-drug resistant tuberculosis (MDR-TB). Success rate of treatment was 65/68 (95.6%). 2) Alterations of regimens after knowing INHr-TB were done in 41 of 65 patients (63.0%) with treatment success in all cases. The susceptible drugs used were 65 (100%) for RFP, 62 (95.4%) for EB, 23 (35.4%) for PZA, 26 (40.0%) for SM, 32 (49.2%) for new quinolone (NQ). 3) The sputum culture conversion rates two months after starting chemotherapy with (N = 16) and without (N = 52) PZA were 13/16 (81.3%) and 31/52 (59.6%), respectively. 4) After the completion of treatment, relapse occurred in 4 patients during follow-up period (1-39 months). The recurrence occurred in 3 out of 20 patients (15%) treated with INH and two susceptible drugs, none out of 13 with three susceptible drugs (0%), 1 out of 20 with INH and three susceptible drugs (5%), and none out of 11 with more than 4 susceptible drugs (0%), and the fact indicates that there was no significant advantage to add INH of usual dose to the regimens. 5) The durations of treatment were not less than 9 months except one case. When 3 or more susceptible drugs were used, the recurrence rate in the group of treatment duration 9-12 months was 0/12 and that in the group of treatment duration more than 12 months was 1/33. Even in the groups without PZA in the initial 2 months of treatment, the recurrence rate in the group of treatment duration 9-12 month was 0/8, and that in the group of treatment duration more than 12 months was 0/22. The fact indicates that 12 months therapy was sufficient irrespective of the use of PZA. 6) One of 5 RFPr-TB patients discontinued treatment by himself. Remaining 4 patients were treated by 4.5 +/- 0.5 susceptible drugs including INH for more than 20 months (21.7 +/- 2.8 months) after sputum culture conversion with the successful result of treatment and no relapses during the followup period for 3-60 months. CONCLUSION: For INHr-TB, even when PZA can't be used because of adverse effects or resistance, 3 or 4 susceptible drugs regimens including RFP for 12 months were effective. For RFPr-TB, the treatment with 4 or more susceptible drugs for 20 months after sputum culture conversion might be adequate.

[Comparative evaluation of the isothermal and chimeric primer-initiated amplification of nucleic acids (ICAN) and Roche Amplicor PCR and culture for detecting Mycobacterium tuberculosis complex in sputum samples].

We compared the ability of the newly developed ICAN MTB Detection Kit (TaKaRa Bio Inc.), which uses the Isothermal and Chimeric primer-initiated Amplification of Nucleic acid (ICAN), with that of COBAS Amplicor PCR System (Roche Diagnostics) to directly detect Mycobacterium tuberculosis complex (MTB) in sputum samples. A total of 142 sputum samples from 120 patients were examined in this study. The results were compared with those of acid-fast staining and MGIT liquid culture system (BD) following identification by the probe test (DDH Mycobacteria Kit). A total of 68 specimens were MGIT positive for MTB. In addition, 62 specimens were positive by the combination of staining and MGIT assay for MTB. When compared with that for MGIT, the sensitivity of each assay system was 88.2% for ICAN and 92.6% for COBAS Amplicor, respectively. The specificity of each assay system was 65.7% for ICAN and 62.7% for COBAS Amplicor, respectively. Coincidence between ICAN and COBAS Amplicor assay results was 96.3% (130 of 135 samples). No significant difference was observed between the results of the two assay methods. It is concluded that although both nucleic acid amplification methods are sensitive and specific for the detection of MTB in the respiratory specimens, ICAN system appeared to be more rapid (within 3.5 h from the specimen collection) than Amplicor system. The ICAN system will be useful in clinical laboratories for the rapid detection of MTB without specially programmed thermo-cycler.

[Secular increase in the incidence rate of drug-induced hepatitis due to anti-tuberculosis chemotherapy including isoniazid and rifampicin].

To investigate the secular change in the incidence rate of drug-induced hepatitis (DIH) due to anti-tuberculosis chemotherapy including isoniazid (INH) and rifampicin (RFP), but not including pyrazinamide (PZA), we retrospectively studied the incidence rates of DIH in patients treated with chemotherapy including INH and RFP in four periods 1980-83, 87-88, 91-92, and 1998-2000. The criteria for selection of the patients were as follows. 1. The serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured before, and one month (20-40 days) and 2 months (45-75 days) after starting anti-tuberculosis chemotherapy. When the serum AST and ALT were measured twice or more during period 20-40 days or 45-75 days after starting anti-tuberculosis chemotherapy, the data obtained nearest to 30 or 60 days after were chosen as those of one or two months after starting chemotherapy, respectively. 2. The serum AST and ALT were within normal range before starting anti-tuberculosis chemotherapy. The normal range of serum AST and ALT were < or = 40 K-A and < or = 35 K-A (in 1980-83) or < or = 31 IU/l and 34 IU/l (in 1987-2000), respectively. 3. Chronic active hepatitis and cirrhosis patients were excluded. 4. All alive after completion of anti-tuberculosis chemotherapy. The numbers of the subjects who fulfilled the above criteria were 113, 135, 128 and 154 in 1980-83, 1987-88, 1991-92 and 1998-2000, respectively. DIH was defined serologically by serum AST > or = 40 K-A and/or ALT > or = 35 K-A (in 1980-83), or AST > or = 40 IU/l and/or ALT > or = 40 IU/l (1987-2000). The DIH incidence rate of the subjects classified by the year of treatment and age were examined, and the contributions of the risk factors for DIH, such as age, sex, alcoholics, previous liver disease history, HBs ag positivity, anti-HCV ab positivity, and hypoalbuminenia were studied, and none except the age over 80 y.o. was found to be a risk factor to DIH, in our subjects. In patients with the age over 80 y.o., daily doses of antituberculosis drugs RFP, INH and ethambutol (EB) were significantly higher in patients with DIH than those without DIH, but body weight and serum albumin level were not significantly different between these two groups. There was no risk factor to DIH in our patients less than 80 y.o. and this could be explained by the above-mentioned criteria of study patients selection. To exclude the age dependence of the incidence rate of DIH in our subjects, the incidence rates of DIH were calculated in patients less than 80 y.o. by the period of treatment, and they were 10/111 (9.0%), 23/131 (17.6%), 26/123 (21.1%) and 32/117 (27.4%) in 1980-83, 87-88, 91-92, and 1998-2000, respectively. The secular increase of the incidence rate of DIH was statistically significant (p = 0.01). It is quite clear that this secular increase was not at all attributable to the above-mentioned risk factors. It is suspected that human liver has become more easily affected with INH and RFP in recent years. It is suggested that the new chemical compounds present in our increasingly complicated human milieu give heavier burdens on human liver, weaken the liver function, and enhance the capacity of INH and RFP to cause DIH.

[Frequency of previous tuberculosis history in patients with and without active tuberculosis admitted to our hospital in 1980-83 and in 1997-99].

To study recurrence rate over a long period after recovery from previous tuberculosis history, we examined the frequency of previous tuberculosis history in patients who were admitted to our hospital in 1980-83 and in 1997-99 and the comparison was made between cases with and without culture-positive tuberculosis. The tuberculosis groups comprised of 297 patients in 1980-83 and 688 patients in 1997-99. The non-tuberculosis groups (control groups) comprised of 373 patients in 1980-83 and 1092 patients in 1997-99 with non-tuberculosis diseases other than the tuberculosis-related diseases such as non-tuberculosis mycobacteriosis, pulmonary aspergillosis, bronchiectasis, chronic bronchitis and tuberculosis sequelae. The patients with viral chronic hepatitis previously operated and transfused were also excluded as they might be operated because of pulmonary tuberculosis in the era of surgical treatment for tuberculosis. In both tuberculosis and control groups, they had previous tuberculosis history most frequently when they were twenties. In the control groups, the frequency of previous tuberculosis history among cases admitted in 1980-83 and were born in 1910-19, 20-29, 30-39, 40-49 were 15/84 (17.9%), 22/93 (23.7%), 11/77 (14.3%) and 3/43 (7.0%), respectively, and those admitted in 1997-99 were 11/70 (15.7%), 30/231 (13.0%), 28/288 (9.7%), and 10/230 (4.3%), respectively. In these 4 birth year groups, frequency of previous tuberculosis history among cases admitted in 1997-99 were significantly lower than that admitted in 1980-83 (p < 0.05, one-sided paired t-test), and the fact suggests that persons with tuberculosis history died earlier than those without it. In the tuberculosis groups, the frequencies of previous tuberculosis history among cases admitted in 1980-83 and were born in 1910-19, 20-29, 30-39 and 40-49 were 20/35 (57.1%), 31/58 (53.4%), 19/48 (39.6%), and 11/53 (20.8%), respectively, and those among cases admitted in 1997-99 were 30/99 (30.3%), 58/125 (46.4%), 22/102 (21.6%) and 17/136 (12.5%), respectively. The frequency of previous tuberculosis history among cases admitted in 1997-99 was significantly lower than that admitted in 1980-83 (p < 0.01) as was the case in the control groups. As recurrence within 5 years had occurred in only 4 out of 113 tuberculosis patients (3.5%) in the above-mentioned 4 birth year groups, almost all tuberculosis patients were assumed to have recovered completely from previous tuberculosis. Comparison between the recurrence rate from previous tuberculosis and the incidence rate from the remotely infected persons without previous tuberculosis history in the same birth year group can be done by calculating the prevalence of tuberculosis infection for each birth year group using a model of annual risk of tuberculosis infection appropriate for Japanese. The ratios between the recurrence rate from previous tuberculosis patients and the incidence rate from remotely infected persons without previous tuberculosis history were 4.71, 2.33, 1.78 and 1.11 in 1980-83 and 1.84, 3.99, 1.80 and 1.11 in 1997-99 for groups born in 1910-19, 20-29, 30-39 and 40-49, respectively. The ratio did not change systematically with time in these groups, indicating the recurrence rate did not change with time more than ten years after recovery from previous tuberculosis. The ratio was about 3 for groups born in 1910-19 and 20-29 and 1 for group born in 1940-49. Almost all patients born in 1940-49 could receive chemotherapy for tuberculosis in their twenties, while most of the patients born in 1910-29 could not. Therefore, the above-mentioned fact may reflect the recurrence rate of patients treated successfully with chemotherapy is almost the same as the incidence rate from remotely infected persons, while that the recurrence rate from previous tuberculosis patients spontaneously recovered is 3 times higher than the incidence rate from remotely infected persons.