[The present status of nontuberculous (atypical) mycobacterial infections].
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Biomedical subjects
Publications and source records attributed to R Amitani.
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To investigate the morphological changes of local eosinophils in the lungs, we observed the ultrastructure of eosinophils in bronchoalveolar lavage fluid (BALF) from patients with eosinophilic pneumonia. We also measured the BALF concentration of eosinophil cationic protein (ECP) as an index of the activation of eosinophils. The eosinophils in BALF from patients with eosinophilic pneumonia showed various ultrastructural changes compared to eosinophils in BALF of the control patient. Changes included degranulation or disintegration of specific granules, cytoplasmic vacuolation, increased lipid droplets and the appearance of Charcot-Leiden crystals. These changes of BALF eosinophils were more prominent than those of peripheral blood eosinophils. ECP concentration (mean +/- SD) in BALF from patients with eosinophilic pneumonia was 12.2 +/- 7.78 micrograms/l which was significantly higher than the concentrations in patients with bronchial asthma not during an attack (1.36 +/- 2.08 micrograms/l) and in healthy control subjects (2.14 +/- 4.62 micrograms/l). These results suggest that local eosinophils in the lungs are activated and degranulated by various stimuli and undergo structural degeneration in eosinophilic pneumonia.
Chronic cough may be the sole presenting manifestation of bronchial asthma (reference 3; Corrao et al, 1979), and "cough variant asthma (CVA)" has been used to categorize such patients. In order to clarify the clinical picture of CVA, we evaluated the clinical history, laboratory data, sputum cytology and pulmonary function in 14 subjects (5 males and 9 females, aged 14 to 65 years) compatible with the following diagnostic criteria: (1) chronic cough persistent for more than 8 weeks, (2) no wheeze nor dyspnea, (3) no rales, (4) no past history of asthma, (5) bronchial hyperreactivity to methacholine proven by Takishima's method (reference 13), (6) effectiveness of bronchodilators against cough, (7) normal chest X-ray film, (8) afebrile and negative CRP, (9) absence of sinusitis and postnasal drip, or if present, they are proved not to be responsible for the cough, and (10) no other causes of cough such as heart disease, prescription of ACE inhibitors, current smoking. The results were as follows. 1) Many of the subjects were atopic, with positive skin tests to one or more common allergens in 10 subjects, elevated serum IgE in 4 subjects, and past history and family history of atopy in 4 and 7 subjects, respectively. 2) Respiratory infection preceded the onset of CVA in 3 subjects. 3) Cough was generally nocturnal, but 2 subjects coughed only in the daytime. 4) FEV1.0% was decreased (less than 70%) in only 2 subjects, whereas V25 was decreased (less than 80% of predicted value) in 11 out of 12 evaluable subjects, which suggested peripheral airway obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)
Twenty-two patients were diagnosed as coexisting active pulmonary tuberculosis and lung cancer during last ten years until 1989. They were nineteen men and three women and their age ranged from 61 to 84 years with a mean age of 71.3. Six patients had history of tuberculosis, three had undergone gastrectomy and four patients were complicated with diabetes mellitus. Histological types of lung cancer were epidermoid cell carcinoma in 13, adenocarcinoma in 3, large cell carcinoma in 2, and small cell carcinoma in 4 and clinical stages were "stage I" in 2, "stage II" in 2, "stage IIIA" in 5, "stage IIIB" in 4 and "stage IV" in 7, except 2 patients after surgical treatment. Localizations of lesions of cancer and tuberculosis were in the same lobes in 6, in ipsilateral lung in 6, and in contralateral lung in 6, except 4 cases, whose lesion of tuberculosis was not detectable roentgenologically and all cancers of "same lobe" cases were peripheral origins. Although, the prognosis was poor, which reflects the prognosis of lung cancer as a whole, the efficacy of anti-tuberculous chemotherapy was as good as patients without lung cancer. We mainly discussed the diagnostic points to detect the coexistence of lung cancer and pulmonary tuberculosis at early stage.
Young's syndrome is characterized by azoospermia due to bilateral epididymal obstruction associated with chronic sinobronchial disease. We report two Japanese cases of Young's syndrome who were treated with microsurgical epididymovasostomy. The histopathology of the caput epididymis showed an obstruction at the most distal region of the ductuli efferentes. The incidence of Young's syndrome in patients with obstructive azoospermia was much lower for mongoloids than for Caucasians.
It has been suggested that proteinase enzymes could play an important role in the pathogenesis of chronic bronchial infections including bronchiectasis and cystic fibrosis (CF). Because Pseudomonas aeruginosa frequently colonizes the respiratory tract in bronchiectasis and CF, we examined the in vitro effects of human neutrophil elastase (HNE) and proteinase enzymes produced by P. aeruginosa (elastase: PE; alkaline proteinase: PAP) on the ciliary beat frequency (CBF) and ultrastructure of human nasal ciliated respiratory epithelium. HNE (500 micrograms/ml) progressively reduced CBF and caused marked epithelial disruption; lower concentrations (100 and 20 micrograms/ml) also caused epithelial disruption but without slowing CBF. The effects of HNE (500 micrograms/ml) were completely abolished by adding alpha 1-antitrypsin (5 mg/ml). There was no synergy between HNE and pyocyanin, a product of P. aeruginosa which slows CBF. PE in phosphate-buffered saline also caused epithelial disruption without slowing CBF; however, PE in medium containing divalent metal ions caused CBF slowing as well as epithelial disruption at 100 micrograms/ml. PAP (500 micrograms/ml) had almost no effect on ciliated epithelium. The effects of HNE and PE on nasal and bronchial epithelium obtained from the same patient were similar. Light and transmission electron microscopy revealed that HNE and PE were cytotoxic and caused detachment of epithelial cells from neighboring cells and the basement membrane. There was cytoplasmic blebbing of the cell surface and mitochondrial damage; however, no increase of abnormalities in the ultrastructure of cilia on living cells was seen. These results support the hypothesis that HNE and PE contribute to the delayed mucociliary clearance and epithelial damage that is observed in patients with chronic bronchial infection.
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It is widely accepted that the impairment of tracheobronchial clearance (TBC) are closely related to the development and the progression of chronic bronchial infections. We investigated TBC in patients with chronic bronchial infections (bronchiectasis; 11 cases, diffuse panbronchiolitis; 9 cases and primary ciliary dyskinesia; 3 cases) and also in 6 healthy subjects by a radioactive aerosol (99mTc-human serum albumin, 4.4 +/- 1.4 microns in diameter) inhalation scintigraphy with cough control in order to elucidate the relationships between impaired TBC and chronic bronchial infections. All subjects were not current smokers. After 4-minutes inhalation of radioactive aerosols (tidal volume: 500 ml x 20/min.), radioactivities in whole right lung were measured every 20 seconds for 2 hours serially and then measured at the time of 6 and 24 hours after inhalation. Immediately after the serial recording for 2 hours, single photon emission computed tomography (SPECT) was performed to assess the deposition pattern of radioactive aerosols. During the first 2 hours, all the subjects were instructed to avoid coughing as much as possible to evaluate the mucociliary clearance without cough effect. And then the subjects were allowed to cough between 2 and 24 hours after inhalation. All radiation counts were corrected for background radiation and physical decay of 99mTc. Because it is considered that the deposited aerosols are eliminated much more slowly in alveoli (biological half life: several months) than in airways (biological half life: several hours), the radioactivity remaining at the time of 24 hours was defined as alveolar deposition (ALV). Initial bronchial deposition (Br0) was defined as initial whole lung deposition (L0) minus ALV. We evaluated the TBC with following parameters; 1) Br0/L0 (%):ratio of initial bronchial deposition to initial lung (bronchial and alveolar) deposition. 2) Br2/Br0 (%), Br6/Br0 (%):bronchial retention ratio; the ratio of bronchial deposition at the time of 2 and 6 hours after inhalation to initial bronchial deposition, respectively. 3) TMV (mm/min.):tracheal mucus velocity (rate of shift of radioactive bolus on tracheal mucosa), which was measured during the period of first 2 hours under prohibition of cough. The patients (23 cases) were divided into two groups with regards to cough control for the first two hours of the scintigraphy:cough-controlled group (19 cases) and cough-uncontrolled group (4 cases). The cough-controlled group was subdivided into two subgroups (group A and group B) according to Br0/L0:group A less than 47.9% (mean + SD of Br0/L0 in healthy control) less than or equal to group B.(ABSTRACT TRUNCATED AT 400 WORDS)
Therapeutic effects of new rifamycin derivatives, 3'-hydroxy-5'-(4-alkylpiperazinyl) benzoxazinorifamycins, KRM 1648, 1657, 1668, 1674 and 2312 (kindly supplied by Kanegafuchi Chem. Ind. Co. Japan), were evaluated on experimental tuberculosis and Mycobacterium avium complex infection in mice. I. Experimental tuberculosis in mice Male ddY mice were inoculated via tail vein with ca. 1 x 10(9) CFU of M. tuberculosis H37Rv suspended in 0.2 ml medium. Treatment of the mice with the new rifamycin derivatives or rifampicin (RFP: as a control drug) was performed by daily oral administration of 10 mg/kg of the drugs, starting at the 24th hour of infection and continuing until the 40th day of infection. Therapeutic effect of each drug was assessed by mortality of the treated mice. All control mice which did not receive any drug died within the 20th day (in Exp. 1) and the 22nd day (in Exp. 2) of infection, while 25% (in Exp. 1) and 40% (in Exp. 2) of RFP-treated mice and 100% (in Exp. 1 and 2) of mice treated with any of the KRMs survived on the 40th day of infection. II. Experimental M. avium complex infection in mice Female beige mice (8-12 weeks old) were inoculated via tail vein with ca. 1 x 10(8) CFU of M. avium complex strain 31F093T, a mouse-virulent strain, suspended in 0.2 ml medium. Treatment of the mice with each drug (daily oral administration of 20 mg/kg) was started 24 hours after the inoculation, and was continued throughout 12 weeks of infection.(ABSTRACT TRUNCATED AT 250 WORDS)
The in vitro anti-M. tuberculosis and anti-M. avium complex activities of five new rifamycin derivatives, KRM1648, KRM1657, KRM1668, KRM1674 and KRM2312, provided by Kanegafuchi Chem. Ind. Co. Japan were evaluated and compared with those of rifampicin (RFP) and rifabutin (RBU). Antimycobacterial activity was tested by broth dilution method using Kirchner's liquid medium supplemented with 10% bovine serum. The MICs 90 (micrograms/ml) of all five KRMs and RBU for 20 clinical isolates of M. tuberculosis were 0.035-0.07, whereas that of RFP was 1.25. The new rifamycin derivatives showed 16 to 32 times lower MICs than those of RFP against M. tuberculosis. All five KRMs inhibited 100% of 20 clinical isolates of M. avium complex at a concentration of 1.25 micrograms/ml, while only 35% and 10% of the strains were inhibited by the same concentration of RBU and RFP, respectively. The MICs 90 (micrograms/ml) for the strains tested were 0.07-0.3 for all five KRMs, and 5 and 40-80 for RBU and RFP, respectively. The new rifamycin derivatives were 16 times more active than RBU, which was 8 times more active than RFP. The new rifamycin derivatives were far more effective against M. tuberculosis in vitro than RFP, and their superiority to RBU which showed the effect superior to RFP was notable in in vitro anti-M. avium complex activities.
We evaluated laboratory and radiological findings and examined tracheobronchial cilia by transmission electron microscopy in 9 patients with primary ciliary dyskinesia (PCD), in order to elucidate the clinical pictures of PCD and the relationship between PCD and diffuse panbronchiolitis (DPB) which was proposed as a new disease entity in Japan in 1969. The clinical pictures of our PCD patients were almost the same as that already described in several articles in Europe and North America; early onset of respiratory symptoms, high incidence of chronic sinusitis and otitis media exudative as well as infertility, continuous infections in the lower respiratory tracts (Hemophilus influenzae, Pseudomonas aeruginosa etc.). Tracheobronchial cilia obtained by brushing technique were immotile (6 out of 8 patients) or dyskinetic (2 out of 8 patients). Ultrastructural study of cilia revealed the lack of dynein arms in all patients: the lack of both outer and inner arms (4 patients), the lack of outer arms (2 patients), the lack of inner arms (2 patients). Chest X-ray films revealed situs inversus in six out of nine patients. According to the radiological findings (chest X-ray film, CT-scan, bronchogram), the patients were divided into three groups; I: localized bronchiectasis (5 patients), II: diffuse micronodular lesions without definite bronchiectasis (3 patients), III: diffuse micronodular lesions with bronchiectasis (1 patient). Two patients of the second group satisfied the clinical diagnostic criteria for DPB (Chest 83:63, 1983). In conclusion, PCD can cause a variety of respiratory tract lesions such as bronchiectasis, DPB and other types of peripheral airway disorders.
To determine the reason for the high incidence of nasal sinusitis in patients with cleft palate, the type of cleft, degree of nasal septal deviation, velopharyngeal function, and presence of pharyngeal flap were investigated in relation to nasal sinusitis. We also examined the relationship between the side of sinusitis and the cleft side in patients with unilateral cleft palate. Development of maxillary sinus, nasal mucociliary transport, and ciliary beating frequency of ciliated cells were also examined. The saccharin test indicated that nasal mucociliary transport was impaired. This impairment is believed to be one of the reasons for the high incidence of sinusitis in patients with cleft palate.
A case of multiple intracranial tuberculomas diagnosed by enhanced brain CT scan and MRI, which developed during the course of miliary tuberculosis under anti-tuberculous chemotherapy was experienced. Chemotherapy with an increased dose of each agent and corticosteroid was administered, and eventually intracranial tuberculomas nearly disappeared. After 1970, there have been 29 reported cases of intracranial tuberculomas in Japan, which were diagnosed by brain CT and treated with anti-tuberculous agents. Among them, 27 evaluable cases were classified into 3 groups. Group A: Intracranial tuberculomas were proved by CT before chemotherapy in 7 cases. Four of them enlarged during chemotherapy. Group B: During chemotherapy of tuberculous meningitis, neurological symptoms worsened or prolonged, and finally intracranial tuberculomas were found by CT in 9 cases. In 5 of them, after meningitis was improved by chemotherapy, neurological symptoms worsened and intracranial tuberculomas were found. Group C: During chemotherapy of pulmonary tuberculosis or miliary tuberculosis, neurological symptoms appeared and intracranial tuberculomas were found by CT in 11 cases (including our own case). Getting 3 groups together, intracranial tuberculomas seem to have worsened during chemotherapy in 24 out of 27 evaluable cases. In view of response to chemotherapy, these 24 cases can be divided into 2 categories: 1) non-responders to chemotherapy; 2) cases finally cured by chemotherapy ("transient worsening").(ABSTRACT TRUNCATED AT 250 WORDS)
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A case of spontaneous regression of multiple pulmonary metastases of transitional cell carcinoma is reported. Spontaneous regression of metastatic pulmonary lesions seldom occurs in transitional cell cancer, and only 3 such cases have been reported in the literature. A 42-year-old male with multiple pulmonary metastases which had regressed spontaneously for a significant period of time is herein reported. The lesions were shown to be transitional cell carcinoma, originating from the left renal pelvis. The serial immunological examinations suggest that the phenomenon might be attributed to the augmented immune response of the patient.
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