Efficacy and safety of multitarget therapy with cyclophosphamide and tacrolimus for lupus nephritis: a prospective, single-arm, single-centre, open label pilot study in Japan.

Background Pulsed cyclophosphamide or mycophenolate mofetil for lupus nephritis has limited efficacy. We previously reported a case of mixed-class IV + V lupus nephritis successfully treated with cyclophosphamide and tacrolimus. This study assessed the efficacy and safety of multitarget therapy with cyclophosphamide and tacrolimus for the treatment of lupus nephritis. Methods In a prospective, single-arm, open label pilot study, we recruited 15 patients aged 18-64 years with active lupus nephritis who met the American College of Rheumatology criteria for a diagnosis of systemic lupus erythematosus (1997). The treatment protocol was a starting dose of prednisolone of 0.6-1.0 mg/kg/day for 2 weeks and then tapered to a maintenance dose, intravenous cyclophosphamide (500 mg biweekly for 3 months) and tacrolimus (3.0 mg/day). Tacrolimus was continued as maintenance therapy. Complete remission was defined as a spot urine protein/creatinine ratio of < 0.5 g/gCr with no active urine casts and a serum creatinine level that was either normal or within 30% of a previously abnormal baseline level. We retrospectively compared results for the study patients with those of 18 historical controls conventionally treated with cyclophosphamide and prednisolone. Results At baseline, the mean patient age was 41.5 ± 14.6 years (male:female ratio 2:13), urine protein/creatinine ratio 3.9 ± 2.3 g/gCr and serum creatinine 84.6 ± 34.6 µmol/L. Lupus nephritis classifications included classes IV ( n = 8), III + V ( n = 1), IV + V ( n = 5) and unclassified ( n = 1). Eleven patients completed the treatment protocol and four withdrew. At 6 months, 12 of 15 (80.0%) had achieved complete remission using intention-to-treat analysis, significantly more than historical controls (seven of 18 patients, 38.9%). A transient increase in serum creatinine and gastric symptoms occurred in three cases. One patient withdrew due to cytomegalovirus antigenemia and severe diabetes, and one patient died of thrombotic microangiopathy. Conclusions Multitarget therapy with cyclophosphamide and tacrolimus can be a therapeutic option for lupus nephritis. Clinical trials registration Combination therapy of tacrolimus and intravenous cyclophosphamide for remission induction of lupus nephritis, UMIN: 000004893, URL: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000005830&language=E . Date of registration: 18 January 2011.

COMPARISON OF PERSONAL DOSE EQUIVALENT Hp(10) IN 137CS RADIATION BETWEEN THE PRIMARY STANDARDS LABORATORIES OF JAPAN AND AUSTRALIA USING BeO OSL PERSONAL DOSEMETERS.

A comparison of personal dose equivalent Hp(10) for 137Cs radiation was conducted between the primary standards laboratories of Japan and Australia. A set of 120 commercially available passive BeO OSL dosemeters were used (Dosimetrics GmbH, Munich). The aim was to investigate the precision which could be obtained with this technique, and to confirm the personal dose equivalent delivery methods in each standards laboratory. A dose of 5 mSv was delivered to 40 dosemeters in each country, and 40 dosemeters were used as controls. The result of the comparison was a ratio of Hp(10) in Japan to Australia of 1.006 with a combined standard uncertainty of 3.2%. The statistical uncertainty was 0.32% indicating that passive dosemeters can be used for comparisons of high precision.

Cooperation between accessory cells and T lymphocytes in patients with tuberculous pleurisy.

We studied interleukin 1 (IL-1) activity of pleural fluid macrophages and peripheral blood monocytes obtained from ten patients with tuberculous pleurisy and ten patients with malignant pleurisy, using purified protein derivative (PPD) as a stimulating agent. Tuberculous pleural fluid macrophages and peripheral blood monocytes tended to produce higher IL-1 activity than malignant pleural fluid macrophages and blood monocytes and showed significantly more IL-1 activity than healthy control monocytes. However, no significant difference in IL-1 activity was observed between tuberculous pleural macrophages and blood monocytes. With the cooperation of these accessory cells, pleural fluid T lymphocytes in patients with tuberculous pleurisy showed a significant level of interleukin 2 (IL-2) activity in the presence of PPD. Tuberculous pleural fluid macrophages promoted greater IL-2 production than blood monocytes from either tuberculous pleural fluid or blood T lymphocytes despite relative equivalence in measured IL-1 production. Combination of tuberculous pleural fluid macrophages and pleural fluid T lymphocytes was the most effective for increasing IL-2 activity when compared with other combinations. These results suggest that tuberculous pleural fluid macrophages and T lymphocytes may contribute to the immunopathogenesis of tuberculosis at a local site of disease.

A method for direct incorporation of radiolabeled cholesteryl ester into human plasma low-density-lipoproteins: preparation of tracer substrate for cholesteryl ester transfer reaction between lipoproteins.

[14C]Cholesteryl ester was directly incorporated into human plasma low-density lipoproteins (LDL) for the purpose of preparing a tracer substrate for investigation of the cholesteryl ester transfer reaction between plasma lipoproteins. The radiolabeled cholesteryl oleate was sonicated with egg phosphatidylcholine to form cholesteryl ester-containing liposomes. The liposomes were incubated with plasma fraction of density greater than 1.006 at 37 degrees C in the presence of dithionitrobenzoic acid. When the distribution of the radiolabeled cholesteryl ester was equilibrated among liposomes and lipoprotein fractions, the mixture was applied to an affinity chromatography column of dextran sulfate-cellulose (LA01) (Arteriosclerosis 4, 276-282). LDL was eluted by increasing the NaCl concentration and was finally isolated as a floating fraction by ultracentrifugation at a solvent density of 1.063 (adjusted with NaCl). The chemical composition, electrophoretic mobility and density of the labeled LDL were consistent with those of the native LDL. Radioactivity in this preparation was present exclusively in cholesteryl ester. Apolipoprotein B100 was preserved intact throughout the procedure. When the rate of cholesteryl ester transfer was measured between LDL and high-density lipoproteins by using this labeled LDL, the kinetics was consistent with the equilibrium transfer model, but the apparent rate measured was slightly higher than that measured with the labeled LDL prepared by the method using the intrinsic cholesterol esterification reaction of plasma.

Rate of cholesteryl ester transfer between high and low density lipoproteins in human serum and a case with decreased transfer rate in association with hyperalphalipoproteinemia.

The rate of cholesteryl ester transfer between intrinsic high and low density lipoproteins (HDL and LDL) was measured in human serum in the absence of lecithin:cholesterol acyltransferase (LCAT) and very low density lipoproteins. The rate was calculated according to the equilibrium transfer model between the two lipoprotein cholesteryl ester pools. The average rate of the transfer was 213 +/- 95 nmol/h/ml (mean +/- S.E.) for all 20 normal and 13 hyperlipoproteinemic subjects. The transfer rate in individual serum was higher by several times than the cholesterol esterification rate, showing that cholesteryl ester generated by LCAT on HDL is promptly distributed among various lipoprotein subclasses. The rate of cholesteryl ester transfer in the serum was significantly proportional to the product of intrinsic HDL and LDL concentrations, a possible indicator of the frequency of collision between these lipoproteins, for the range of physiological lipoprotein concentrations. Among the subjects analyzed was a patient with remarkable hyperalphalipoproteinemia accompanied by hypertriglyceridemia, who showed a very low rate of cholesteryl ester transfer in relation to his LDL and HDL concentrations. Compositional analysis of lipoprotein lipids of the patients also supported the possibility of impaired neutral lipids transfer activity among lipoproteins in the blood.

Effects of murine lysozyme on lipopolysaccharide-induced biological activities.

We have demonstrated that egg-white lysozyme (EW-LZM) bound to lipopolysaccharide (LPS), reduced the lethal toxicity and the biological activity of LPS. In this study, the interaction of LPS with murine lysozyme (M-LZM) and the modulation of biological activities were investigated. M-LZM was prepared from the culture supernatant of the murine macrophage cell line RAW264.7 by ion-exchange and gel filtration chromatographies and dialysis. Two types of M-LZM, murine M lysozyme (MM-LZM) and murine P lysozyme (MP-LZM), were purified from the supernatant. The enzymatic activities of both MM-LZM and MP-LZM were inhibited by LPS and their effects were affected by the temperature and the ionic strength. TNF-alpha production from RAW264.7 by LPS was inhibited by mixing with MM-LZM and MP-LZM. MP-LZM inhibited TNF-alpha production stronger than MM-LZM. Considering these facts, we suggested that M-LZM, like EW-LZM, make a complex with LPS to reduce the toxicity of LPS together with inhibiting the enzymatic activity.

Synthesis of branched cyclomaltooligosaccharide carboxylic acids (cyclodextrin carboxylic acids) by microbial oxidation.

Novel branched cyclomaltooligosaccharide carboxylic acid (cyclodextrin carboxylic acid) derivatives were synthesized by microbial oxidation using Pseudogluconobacter saccharoketogenes to oxidize five types of branched cyclodextrins, including maltosyl beta-cyclodextrin (maltosyl-beta-CyD). For each novel cyclodextrin carboxylic acid derivative synthesized, the hydroxymethyl group of the terminal glucose residue in the branched part of the molecule was regiospecifically oxidized to a carboxyl group to give the corresponding uronic acid. In addition, the physicochemical properties of cyclomaltoheptaosyl-(6-->1)-alpha-D-glucopyranosyl-(4-->1)-alpha-D-glucopyranosiduronic acid (GUG-beta-CyD) (1) and its sodium salt were studied more extensively, as these compounds are most likely to have a practical application.

Four Japanese cases of episodic angioedema with eosinophilia.

Here we describe four young Japanese women aged 25-33 years, whose clinical findings are characterized by episodic angioedema, marked leukocytosis with eosinophilia, benign course with spontaneous remission or low-dose prednisolone treatment. The recognized causes of eosinophilia, such as allergy, parasite, and collagen diseases, and the causes of edema, such as heart, kidney, and liver diseases, were ruled out. The findings in these patients are very similar to those reported as episodic angioedema with eosinophilia, which is clearly distinct from the so-called hypereosinophilic syndrome. We suggest that this syndrome is not rare, and should be widely recognized as a new clinical entity for accurate and prompt diagnosis.

Diagnosis and management of endobronchial tuberculosis.

We examined the records of sixty-one patients (17 males and 44 females) with endobronchial tuberculosis (EBTB). Smear tests of acid-fast bacilli were positive in 42 cases and cultures of tubercle bacilli (TB) were positive in 57. The main findings of chest roentgenogram on admission were as follows: no abnormal findings in 8, atelectasis in 30, infiltration in 25, and cavitary lesions in 6. The localization and cross-sectional extension of lesions confirmed bronchoscopically were as follows: trachea in 15, with 3 circular lesions (CLs). Right (R-) main bronchus in 19 with 11 CLs, left (L-) main bronchus in 18 with 11 of CLs, R-truncus intermedius in 14 with 6 of CLs, R-upper lobar bronchus (UB) in 17 with 12 CLs, R-middle lobar bronchus in 14 with 11 of CLs, R-lower lobar bronchus (LB) in 6 with 2 CLs, L-UB in 10 with 7 CLs and L-LB in 3 with 2 CLs. All cases were treated by combination chemotherapy with isoniazid, rifampicin, streptomycin and/or ethambutol and the rate of negative conversion of TB was good, but most of circular lesions resulted in severe bronchial stenosis or complete obstruction during and after chemotherapy, and no improvement was seen in any of the atelectasis cases at the cessation of chemotherapy. We discuss the points of early diagnosis and management of EBTB.

[A clinical study of pulmonary cryptococcosis. The Study Group of Respiratory Mycosis in Kyoto].

During the 7 years from 1990, thirty-two patients (20 in male and 12 in female, mean age; 53 years old) were diagnosed as having pulmonary cryptococcosis. To clarify the essential points for early diagnosis of pulmonary cryptococcosis, we reviewed the clinical records and chest images. Three patients had a past history of pulmonary tuberculosis and eleven patients had underlying disorders such as malignancy, chronic pulmonary diseases and so on, but no HIV infection, which would affect this disease. Eighteen patients did not have any past history nor complications. The symptoms such as cough, sputum, chest pain and fever were generally of low-grade, 14 patients had no symptom at diagnosis. Except of some patients with severe infections and severe underlying disorders, laboratory findings such as inflamatory and nutritious markers were almost within near the normal range. On plain chest X-ray films the distribution of lesions was almost in proprtion to the volume of the lobes. The multifocal nudular and/or infitrative shadows wer observed in about 2/3 cases and single lesion in about 1/3. The width of lesions were minimal except of one case with interstitial pneumonia and two cases with multifocal segmental pneumonia. The cavity lesions were observed in 7 cases and hilar lymphadenopathy in 3 cases. On CT images, the lesions were almost located in the outer zone, the lesions which were adjacent to the pleura were observed in 15 cases. Cavitary lesions were almost smooth in edge and ubiquitous, the walls were also thick. The peripheral air-bronchogram in the nodular/infitrative shadows were observed in three cases. Pulmonary cryptococcosis is air-borne and almost a chronic infection except in AIDS patients, so careful planning for examination is essential with considerations of the characteristics of clinical and imaging features of this infection.

[Tuberculin skin test of patients with active pulmonary tuberculosis and non-tuberculous pulmonary diseases].

The maximum diameter of redness of tuberculin skin test (PPD) was studied in patients with active pulmonary tuberculosis (TB) (257 cases) and with various non-tuberculous pulmonary disorders (Non-TB) (328 cases). Negative rate of PPD (maximum diameter under 9 mm) was 9.3% in patients of TB; 6.5% in patients without underlying disorders and 16.3% with underlying disorders, which may affect the break-down of tuberculosis. In patients with miliary tuberculosis, the negative rate was high and PPD reaction became weaker in advanced patients and patients with pleurisy. High age, hypoalbminemia and lymphocytepenia in peripheral blood were the factors influencing the negative conversion of PPD skin test. In Non-TB patients, positive rate of PPD was similar between patients with and without past history of tuberculosis and the rate of patients with maximum redness over 35mm were about 10%, regardless of sex, age and disorders. But there was a difference in the positive rates of PPD between male and female; the positive rate of PPD skin test was highest in male with lung cancer, and there was a difference in the positive rate of PPD between the age groups in male, but there was no difference in females regardless of age with or without lung cancer.

[An outbreak of pulmonary tuberculosis in the dormitory of construction labors suspected to have been due to exogenous reinfection].

We report an outbreak of pulmonary tuberculosis (TB) in a dormitory of construction labors, and this outbreak is suspected to have been caused by exogenous reinfection, based on the restriction fragment length polymorphism (RFLP) analysis and other findings. After a patient entered our hospital with active TB, 12 new other patients were discovered by contacts examination. These patients lived together in the same dormitory. They were all male and single, and were aged from 43 to 63 years old. Except one patient (No. 3) previously treated for TB for three months about 2 years ago and was suspected to be the index case of this outbreak, 12 other patients did not have a medical history of TB. The bacilli cultured from 11 patients (No. 1-11) were tested by RFLP analysis, three patterns were identified, and the fingerprints from 9 patients (No. 1-9) were identical, and the patterns of incomplete resistance of some antituberculous drugs were quite similar between No. 1-9 and No. 12 and between No. 10 and No. 13, respectively. The locations of the main lesions of TB on chest X-ray pictures were the apico-posterior segments of bilateral upper lobes. No signs suspected to indicate primary tuberculosis were detected. Considering the rate of tuberculous infection in Japan among the middle age and above as well as the identical RFLP results, most of patients in this outbreak except the index case No. 3 were suspected to have TB due to the exogenous reinfection.

[A case of primary tuberculosis, with subpleural infiltrative shadow, hilar lymphadenopathy perforated into bronchus, causing tuberculous pneumonia].

A 47-year-old asymptomatic female was referred to our outpatient department with pulmonary infiltration in the left S6. PPD skin test revealed 12 x 11 mm redness. The infiltration disappeared without treatment. Hilar lymphadenopathy appeared 2 months after the first visit. In 6 months after the first visit, the hilar lymphadenopathy disappeared without treatment, but infiltration appeared in the left S6 (different site to that of the first visit). A repeated PPD revealed 47 x 40 mm redness and 20 x 15 mm induration. Bronchoscopy revealed a polipoid lesion at the orifice of left B6, MTD (Mycobacterium tuberculosis direct test) was positive from the bronchial washing of left B6. She was diagnosed as tuberculosis based on the courses and radiographic appearances. After antituberculous chemotherapy, the pulmonary infiltration and the polipoid lesion at the orifice of left B6 improved.

[Two cases of elderly people diagnosed with acute tuberculous pneumonia possibly succeeded by the perforation of lymph nodes in the bronchus].

The report is a study of the cases in which elderly people (83 years-old male and 81 years-old female) diagnosed has having acute tuberculous pneumonia possibly suffered from subsequent perforation of lymph nodes in the bronchus. Neither of the patients had a prior history of tuberculosis treatment. Both patients were admitted to the hospital after being diagnosed with pneumonia. After the administration of antibiotics, the symptoms of illness improved, but chest roentgenograms were taken failed to show improvement. The patients were then transferred to our hospital, because sputa smear tests for Mycobacteria (Ziehl-Neelsen stain) were performed, and the results were positive. Case I (male) was suspected of having endobronchial tuberculosis, since rhonchi was audible in the left-front upper chest during expiration when performing auscultation. A bronchoscopy was conducted at which time ulcer lesions on the left upper lobe of the bronchus and perforated lymph node of the upper bronchus were detected. Case II (female) was suspected of having lung cancer and a bronchoscopy was performed due to the findings of a chest roentgenogram taken after one month of chemotherapy. A perforated lymph node in right truncus intermedius was detected. In this report, we discussed the early diagnosis of tuberculous pneumonia and the perforation of caseous lymph nodes in the bronchus, which was the main cause of tuberculous pneumonia.

[A clinical study of causes of death from active pulmonary tuberculosis with chemotherapy].

We evaluated retrospectively the causes of death from active pulmonary tuberculosis by the review of records and chest radiograohs of 364 patients (male 282, female 82) with active pulmonary tuberculosis, who were admitted to our hospital during 1995 to 1998. 43 patients (male 33, female 10) were died under anti-tuberculous chemotherapy. 20 cases were tuberculous death; death from acute progression of tuberculosis without response to chemotherapy (acute progression group) in eight cases and death from debility in spite of partial response to chemotherapy (debility group) in eight cases. 23 cases were died from underlying diseases; death from malignant neoplasmas (malignant group) in nine cases and death from complication of bacterial pneumonia (pneumonia group) in seven cases. In acute progression group, the age (mean +/- SE) was 64.8 +/- 5.2 years old and the survival period from admission was 11.8 +/- 4.2 days. Five cases were laborer or unemployed. This group was characterized with far advanced diseases presenting extensive lung lesions complicated with DIC or hepatic dysfunction, low performance status (PS), severe malnutrition and lymphocytepenia. In debility group, the age was 70.8 +/- 3.9 years old and the survival period from admission was 254.6 +/- 90.7 days. Five cases were laborer or unemployed. This group was characterized with multiple underlying diseases, low PS, previous anti-tuberculous chemotherapy and resistance to INH and/or RFP. In malignant group, the age was 69.3 +/- 3.2 years old and the survival period from admission was 99.9 +/- 21.2 days. This group was characterized with relatively well nourished, relatively good PS in comparison with other groups, and lymphocytepenia. In pneumonia group, the age was 82.8 +/- 1.7 years old and the survival period from admission was 153.3 +/- 54.5 days. This group was characterized with remarkably advanced age, low PS related to underlying disorders of central nervous system. In the causes of death with active pulmonary tuberculosis under chemotherapy, inhomogenous groups were included. Extensive disease, low PS, malnutrition, lymphocytopenia, previous chemotherapy, resistance to INH and/or RFP, and poorer social circumstances seemed to be risk factors for tuberculous death. In contrast, underlying malignant nepolasma, lower PS, and far advanced age were seemed to be the risk factors for non-tuberculous death.

[A case of pulmonary tuberculosis complicated with intracranial tuberculous abscess].

A 75-year-old male was admitted to our hospital with complaints of fever and cough. Chest X-ray showed infiltrative shadows with cavity, and sputum smears were positive for acid-fast bacilli. About 2 months after the initiation of anti-tuberculous chemotherapy, suddenly generalized convulsion occurred. CT of the brain showed the solitary mass with the ring enhancement in the left subcortical area. About 4 weeks later, brain aspiration drainage was performed and pus was aspirated. He was diagnosed as intracranial tuberculous abscess. After the drainage, neurological symptoms disappeared completely and there were no recurrence of abscess. Attention should be called to the complication of intracranial tuberculosis, especially in cases worsened during anti-tuberculous chemotherapy.

[A case of tuberculous infection of emphysematous bulla in the superior segment of left lower lobe].

We report a case of tuberculous infection of emphysematous bulla, who is a 71-years-old male and ex-smoker. He had no past-history and had been treated for chronic obstructive pulmonary disease. At the periodical consultation on Sept 28 '95, abnormal shadow was found in left middle lung field on plain chest X-ray without any exacerbation of symptoms. Nearly alllaboratory tests on admission were within normal limit, except of slight elevation of inflammatory markers and slight hypoxemia. The Mantoux's skin test was positive. Roentogenologically, the air-fluid level was detected in the bulla of superior segment of left lower lobe. By percutaneous thoracentesis of the bulla under fluoloscopy and ultrasonic echo-guide, the fluid in the bulla was obtained. The fluid was exudate, the activities of ADA and LDH were elevated, but neutrophils were more dominant than lymphocytes in the fluid. The MTD test was positive, which amplifies rRNA of Mycobacterium tuberculosis (MTB), and MTB were cultered after four weeks from the fluid. However, MTB was not cultured from sputum and bronchial washing of left S6 via bronchoscope. After the administration of RFP, INH and EB, the fluid gradually disappeared with reduction of the size of bulla. We discussed the usefulness of the examination of the fluid in the bulla, especially the measurement of the activity of ADA and the MTD test for the confirmation of diagnosis as tuberculosis.

[A case of middle ear tuberculosis; PCR of the otorrhea was useful for the diagnosis].

A 26-year-old female was admitted to our hospital with complaints of fever, cough, otorrhea and otalgia and progressive hearing loss of her left ear. Smears of her sputum were positive for acid-fast bacilli. Smears of her otorrhea were negative for acid-fast bacilli but PCR of her otorrhea was positive. Chest X-ray showed infiltrative shadows with the cavity. She was diagnosed as middle ear tuberculosis associated with pulmonary tuberculosis. After anti-tuberculous chemotherapy, fever, cough, otorrhea and pain of her left ear were improved, but her hearing level was not improved. In the case of middle ear tuberculosis, it is necessary to make an early diagnosis and treatment. This is the first reported case in Japan in which PCR of the otorrhea is positive.

[Clinical evaluation on causes of death in patients with pulmonary tuberculosis during the past 3 years (1994 to 1996)].

We evaluated the cause of death in patients with pulmonary tuberculosis during the past 3 years (1994 to 1996). Of 502 tuberculous patients, 58 (11.6%) patients died. Most of them were aged or under poor nutritional conditions. Of 378 active tuberculous patients, 39 (10.3%) patients died (group A). Of 124 old tuberculous patients or cases with extensive sequelae of tuberculosis, 19 (23.4%) patients died (group B). In the group A, 15 patients died in spite of improvements in tuberculosis lesions. All the intubated patients with active tuberculosis died. In the group B, most of patients died of respiratory failure or pneumonia.

[A clinical study of non-tuberculous pulmonary mycobacteriosis].

We studied the clinical features of sixty-one patients with non-tuberculous pulmonary mycobacteriosis (NTM), who were newly diagnosed at five national hospitals in Kinki area during 1993. The study subjects were composed of 31 patients with M. avium complex (MAC) disease (20 males and 15 females), 21 with M. kansasii (MK) disease (19 males and 3 females), 2 males with M. szulgai (MS) disease and 2 females with M. chelonae (MC) disease. The rate of NTM to all culture proven mycobacteriosis was 20.2% and the rate of NTM to all culture proven, newly discovered mycobacteriosis was 18.2% and the rates were higher than Sakatani's report in 1994 (14% in 1991). The ratio of MK to MAC was 22:35, and the ratio of MK was higher than the report of Sakatani. The mean age of patients with MK was 57.9 in male and 76.7 in female, that with MAC was 71.0 in male and 70.1 in female, that with MS was 57.0 in male and that 72.5 with MC in female. The proportion of elderly patients was higher than the former reports in Japan, especially in female with MK. The main lesions on chest X-ray was found in bilateral S1, 2(S1+2), particularly in the cases with cavitary lesions, but right middle lobe and left lingular lobe were mainly affected in some patients with MAC and S6 was often affected in elderly patients with MK. The chemotherapy with isoniazid, rifampicin, ethambutol and/or streptomycin (or kanamycin) w as highly effective in case with MK and MS disease, the efficacy was similar to pulmonary tuberculosis. Some patients with MAC were treated with combination of anti-tuberculosis drugs and new quinolons and/or clarythromycin, but the efficacy was not yet revealed.