Biomedical subjects
Publications and source records attributed to M Kaku.
We describe the first known case of pneumonia caused by a mucoid Stenotrophomonas maltophilia (Xanthomonas maltophilia) strain in a patient with bronchiectasis. The patient was admitted because of mild hemoptysis and productive cough with infiltrative shadow in the right lower lung field on chest X ray. The clinical symptoms were mild, and treatment with minocycline was effective.
The direct detection of Bacteroides fragilis from clinical specimens was examined by using the PCR method for amplifying a specific fragment of the glutamine synthetase gene from B. fragilis. By this method, all five B. fragilis strains tested were detected, but DNAs from anaerobic bacteria of 24 other species tested, from aerobic bacteria of 12 species tested, and from human leukocytes were not amplified. Using the nested PCR method, we were able to detect as little as one bacterial cell or 100 fg of chromosomal DNA of B. fragilis. A total of 39 clinical specimens, which consisted of 19 bronchial aspirates, 10 percutaneous lung aspirates, 2 transtracheal aspirates, 6 pleural fluid specimens, and 2 pus specimens, were tested. All four culture-positive samples, of which two were bronchial aspirates, one was pleural fluid, and one was pus, were positive by PCR. Among 35 culture-negative samples, 2 bronchial aspirates were positive by PCR. One was from a patient whose two previous samples were positive by both culture and PCR. It had been submitted for culture several hours after collection, and clindamycin had been administered to the patient before collection of the specimen. The other bronchial aspirate positive by PCR was from a pneumonia patient who had also been administered clindamycin. We believe that B. fragilis was present in these two specimens but that either it was dead, it was below the level detectable by culture, or the process of anaerobic culture was unsuccessful. Thus, the PCR method may be considered useful for the sensitive and rapid detection of anaerobes in clinical specimens.
We examined retrospectively the pattern of respiratory infection in 579 patients with lung cancer admitted to Nagasaki University Hospital during the past 15 years. A total of 139 patients (24.0%) developed respiratory infection. The rates of pulmonary infection associated with large (36.2%) and small cell carcinomas (33.6%) were significantly higher than those with squamous cell carcinoma (26.0%) and adenocarcinoma (17.3%). Advanced stages of lung cancer were associated with higher complication rates (stage I: 6.3%, stage II: 15.9%, stage III: 27.9%, and stage IV: 33.8%). Deceased patients showed a significantly higher rate of pulmonary infection than alive patients during the period of investigation. Isolated organisms in excess of 10(7) cfu/ml in sputum or 10(4) cfu/ml in bronchial aspirate were mainly gram-negative bacteria (68.8%), such as Haemophilus influenzae, Klebsiella pneumoniae, Enterobacter cloacae, Acinetobacter sp. and Pseudomonas aeruginosa. The number of patients infected with gram-positive bacteria increased markedly after 1982. Our results suggest that a successful control of pulmonary infection associated with lung cancer is important in improving the prognosis of lung malignancy.
Twenty-eight patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were clinically studied for the effectiveness of the time-difference combination use of netilmicin (NTL) and minocycline (MINO). The patients were treated with NTL 100 mg and two hours later, with MINO 100 mg intravenously, twice daily, in the morning and evening for 14 days. Of 26 patients, MRSA was eradicated in 16 (61.5%), decreased in one, and unchanged in nine. Superinfections occurred with Serratia marcescens and Pseudomonas aeruginosa in two patients. The clinical efficacies were assessed in two patients with septicemia, 16 with pneumonia, and eight with chronic bronchitis. The obtained results were excellent in four patients, good in 15, fair in six, and poor in one patient. The rate of effectiveness was 73.1% (19/26). The overall clinical effectiveness judged by the committee was good in 19, fair in five, and poor in two patients. The efficacy rate was also 73.1% (19/26). Coagulase type II of MRSA was found in 23 patients, and coagulase type III in three patients, with overall clinical efficacy rates of 73.9% (17/23) and 66.7% (2/3), respectively. A side effect of eruption was observed in one patient, and its incidence was 3.6% (1/28). Abnormal laboratory test results were observed in 16 patients (57.1%), including abnormal liver function in 14 patients, abnormal kidney function in three, and increased eosinophils in three. Laboratory abnormalities occurred twelve of 16 bedridden patients, and this rate was higher than that in non bedridden patients. However, these abnormalities were all mild, transient, and immediately recovered after the treatment. In conclusion, the time-difference combination therapy using NTL and MINO was effective in the treatment of MRSA infections.
A 46-year-old female was admitted to our hospital on December 1991 for further examination of an abnormal shadow on chest X-ray. A huge mass in the upper mediastinum and a thin-walled cavitary lesion in the right upper lobe were found by chest radiography and computed tomography. On March 2, 1992, surgical resection was performed with pathological diagnosis of thymoma for the mediastinal mass and pulmonary cryptococcosis for the cavitary lesion. Although ATL cells were not found in the peripheral blood, anti-HTLV-1 antibody was found to be positive. Natural killer cell activity was lower than normal control and other tests of humoral and cell-mediated immunity were normal. Histological examination of the specimens obtained from the thymoma revealed lymphocytic predominance without atypical cells such as ATL cells, but with integration of HTLV-1 proviral DNA. There seemed to be a causal relationship between HTLV-1 carrier state and thymoma. Since there are no reported cases of HTLV-1 carrier associated with pulmonary cryptococcosis and thymoma, we report the first case with a review of the literature.
We developed the rapid detection and identification method of mycobacteria, involving amplification of mycobacterial 16S rRNA gene by nested PCR and identification of M. tuberculosis complex or M. avium-intracellulare complex (MAC) by hybridization protection assay (HPA) using the acridinium-ester (AE) labeled DNA probe. The specificity of the nested PCR combined with DNA probe test was excellent in terms of detection of mycobacterial organisms and identification of M. tuberculosis or MAC. The detection limits of the present method were 10 fg DNA for M. tuberculosis, and 100 fg DNA for MAC, respectively. We further investigated on the optimum temperature for hybridization in HPA with AE labeled DNA probe because there was the difference in the mode of DNA-RNA hybridization from that of DNA-DNA hybridization. In our method, the optimum temperature of hybridization was estimated as 55 +/- 1 degrees C. In preliminary experiments on two clinical cases, we practically detected and identified M. tuberculosis and MAC in clinical specimens, such as sputa, by using this newly devised method. We concluded that this method is useful for rapid detection and identification of M. tuberculosis and MAC in clinical specimens.
We evaluated the efficacy of combined therapy of arbekacin (ABK) and imipenem/cilastatin (IPM/CS) against infections by methicillin-resistant Staphylococcus aureus (MRSA). The MICs of ampicillin, cefmetazole, cefotiam, cefuzonam, flomoxef, fosfomycin, ofloxacin, minocycline, ABK and IPM/CS against clinically isolated strains of MRSA were examined. Almost all strains of MRSA were resistant to these antibiotics except ABK. Furthermore, combination of ABK and IPM/CS showed smaller MICs than that of ABK or IPM/CS alone. All fractional inhibitory concentration indices (FIC indices) of ABK plus IPM/CS were lower than 0.75. The efficacy rate of combined therapy of ABK and IPM/CS in 22 patients with MRSA infections (15 patients with pneumonia, 3 patients with chronic bronchitis, 2 patients with sepsis, a patient with subcutaneous abscess and a patient with DPB) was 68%. And no patients had adverse reactions. Six (27%) of 22 strains of MRSA were eradicated. Significant correlations were found between bacteriological effect and severity of disease, and between serum albumin level and clinical effect.
A 30-year-old female was admitted to our hospital for further investigation of infertility. The menstrual culture and polymerase chain reaction (PCR) of the endometrial tissue for detection of Mycobacterium tuberculosis were both positive. The pelvic CT scan and hysterosalpingography showed a slightly expanded uterus and irregularity of the endometrium. Barium enema and pyelography showed no abnormality. Since these data established a diagnosis of early primary endometrial tuberculosis, the combined therapy of three antituberculous agents was commenced. Menstrual smear, culture and PCR for M. tuberculosis were examined monthly throughout the therapy. The mycobacterial culture became negative soon after the start of therapy, followed by a negative PCR result 3 months later. We conclude that PCR is useful for the rapid detection of M. tuberculosis not only in pulmonary but also in endometrial tuberculosis.
(1-3)-beta-D-Glucan (beta-glucan) is a major structural component of fungi. The G test is a direct method to detect beta-glucan using fractionated (1-3)-beta-D-glucan-sensitive component, factor G, eluted from the limulus lysate. Previously, we reported that the G test is a more sensitive method than the mannan detection assay for the serological diagnosis of Candida infection. In this study, we discuss beta-glucanemia in patients with pulmonary aspergillosis and cryptococcosis. The concentration of beta-glucan was less than 10 pg/ml in 9 of 10 cases of pulmonary cryptococcosis, except for one case receiving hemodialysis (16.5 pg/ml). beta-Glucan increased in 3 cases of invasive pulmonary aspergillosis (27-937 pg/ml). Galactomannan antigen was positive in all of those cases. In 8 cases of aspergilloma, which showed fungus ball on roentgenogram, the mean concentration of beta-glucan was 67.1 +/- 92.7 pg/ml. Two of 8 cases were positive for galactomannan antigen. One of three cases of PAIC (productive aspergilloma on the inner wall of a cavity) and one case of chronic necrotizing pulmonary aspergillosis showed slightly increased levels of beta-glucan and positive results of galactomannan antigen test.
The incidence of methicillin resistant Staphylococcus aureus and penicillin resistant Streptococcus pneumoniae have been increasing in Japan. These resistant strains produce toxins and extracellular enzymes working as virulence factors of infection. Some of these toxins and extracellular enzymes are introduced here. The difference of virulence between MRSA and MSSA is not clear but some of MRSA strains are known to produce new type cytotoxins. The difference of virulence factors between penicillin resistant S. pneumoniae and penicillin sensitive S. pneumoniae were not observed.
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Two different kits for the detection of serum cryptococcal antigen in patients with pulmonary cryptococcosis were evaluated. The Eiken test (the Eiken Co., Tokyo), which uses pronase for pretreatment of serum, was compared with the Crypto-LA test (International Biological Laboratories, Cranbury, NJ), which did not use pronase prior to testing. Cryptococcal antigen was detected in 21 of 23 patients (91%) with the Eiken test and in only 10 of 23 patients (43%) with the Crypto-LA test (p < 0.01 by McNemar test). However, the sensitivity of two tests was identical without use of pronase, as both tests could detect as little as 10(4) cells/ml of Cryptococcus neoformans and 10 ng/ml of capsular polysaccharide of C. neoformans. In those serum specimens for which both tests were positive, titers were much higher for the Eiken test, but there was a statistically significant correlation between the two tests (coefficient correlation 0.79, p < 0.01). Cryptococcal antigen titer levels measured by the Eiken test correlated well with clinical courses. There was one false-positive reaction among 82 sera of non-cryptococcal patients. Pronase enhanced the sensitivity of the Eiken test, which appeared to be useful in patients with pulmonary cryptococcal disease, and its use may prevent unneeded lung biopsies.
Clearance of various bacteria isolated from portal and systemic blood of mice was evaluated and compared. All portal blood strains, including Escherichia coli and enterococci were eliminated more rapidly from the circulation than were strains isolated from systemic blood, including Pseudomonas aeruginosa. With mannose-type lectin, mannose or fucose residues that mediated lectinophagocytosis were detected on the surfaces of most portal strains by agglutination tests. Blood clearance of Esch. coli H21 was inhibited by prior injection of mannose into mice, suggesting that the clearance of this strain was mediated by mannose-type lectin on the surface of tissue macrophages. However, no inhibition of clearance of any other strains was observed by the injection of mannose, galactose, or fucose into mice, nor by pre-incubation of bacteria with mannose. Blood clearance of some portal strains was significantly faster in CBA/J mice than in CBA/N mice with B cell immune deficiency, indicating that immunoglobulin was involved in their clearance. Among portal strains only enterococci showed high cell-surface hydrophobicity. These data suggest that initial bacteria blood clearance may be critical in determining whether latent portal bacteraemia progresses to systemic bacteraemia and that the rapid clearance of most strains is multifactorial.
Mice that had been treated with cyclophosphamide and ampicillin were fed with Pseudomonas aeruginosa. These procedures induced an endogenous septicaemia under conditions mimicking the pathophysiology of the disease in man. This model was used to compare the mortality rates in mice infected with P. aeruginosa isolates from various clinical sources. Mortality rates in mice given isolates from blood cultures had a broad range (0-100%), but the mean rate was significantly higher than with isolates from other infection sites. Moreover, blood isolates persisted in the intestines of mice after oral inoculation, whereas most isolates from other sources were gradually eliminated. Most P. aeruginosa isolates from blood culture produced significantly higher levels of exotoxin A and total proteases than isolates from other infection sites. Amongst the blood isolates, all but one of the lethal strains produced large quantities of exotoxin A or total proteases or both. Taken together, the results suggest that the ability of P. aeruginosa to adhere to the intestinal tract and to produce high levels of exo-enzymes may contribute to the development of fatal septicaemia.
The serodiagnostic tests, beta-glucan, mannan, candida antigen by Cand-Tec, and D-arabinitol were evaluated in 10 patients with candidemia, 14 patients with suspected fungemia, and 10 healthy persons. By blood culture or lysis centrifugation, C. albicans was isolated from 5 patients, C. parapsilosis from 4, and C. tropicalis from 1 patient; no organisms were isolated from the 14 patients with suspected fungemia or the 10 healthy subjects. Beta-glucan was measured by the difference between two chromogenic limulus tests (Endotoxin test-D and Endospecy), which was more than 60 pg/ml in 7 of 9 (78%) candidemic patients and 1 of 12 (8%) patients with suspected fungemia. Mannan was positive in 6 of 10 (60%) candidemic patients and 1 of 13 (8%) patients with suspected fungemia. Both antigens were very sensitive and highly specific for candidemia. However, the Cand-Tec assay was less specific, because titers of more than 4 were observed in 5 of 14 (34%) patients with suspected fungemia. D-Arabinitol was the least sensitive, because a D-arabinitol/creatinine ratio greater than 2.0 mumol/mg was observed in only 2 of 7 (29%) candidemic patients. The titers of serodiagnostic tests decreased after successful treatment with an anti-fungal agent. Our results show that the combined use of the assays in necessary for accurate serological diagnosis of candidemia.
Liposomal amphotericin B was evaluated for toxicity, pharmacokinetic properties and therapeutic efficacy in invasive pulmonary aspergillosis in Sprague-Dawley rats. The protective effect of liposomes against the toxicity induced by repeated amphotericin B infusions was observed in a survival study of rats, thereby allowing higher dosages to be administered. Pharmacokinetic studies showed that liposomes led to high levels of amphotericin B in the spleen and liver. Drug levels in the lung were higher at ten minutes after intravenous injection of liposomal amphotericin B at 20 mg/kg than of free amphotericin B at 1.5 mg/kg. Efficacy was assessed in rats treated with cortisone acetate, fed a low-protein diet and infected transtracheally with 8 x 10(4) Aspergillus fumigatus spores to cause fetal pneumonia and pulmonary bleeding. Dosages of 20 or 4 mg/kg of liposomal amphotericin B, or 1.5 mg/kg of free amphotericin B were administered intravenously to rats once daily for 8 days. Control rats received saline. Twenty mg/kg of liposomal amphotericin B was as effective on survival rate as 1.5 mg/kg of free amphotericin B. However, 4 mg/kg of liposomal amphotericin B was less effective than 1.5 mg/kg of free amphotericin B, prolonging the mean survival time of rats treated with saline, which showed elevation of galactomannan antigen titers of Aspergillus fumigatus in sera and invasive proliferation or mycelia with bleeding in histopathological sections of the lung. We conclude that liposomal amphotericin B reduces toxicity of the drug, thereby increasing the concentration of the drug in the lung by high-dose administration, but decreases the efficacy of the drug in experimental pulmonary aspergillosis.
At Hokusho Central Hospital, we studied the isolation rate of methicillin-resistant Staphylococcus aureus (MRSA) from 1985 to 1989; respiratory infection with MRSA, in 1989; and sepsis of MRSA, from 1988 to 1989. The isolation rate of MRSA from sputum increased from 0% in 1985 to 65.4% in 1989. MRSA was isolated mainly from elderly patients in a geriatric ward, with 55 of 67 strains (82%) being isolated from these patients in 1989. MIC80 of isolated MRSA strains was 0.01 microgram/ml to rifampicin, 0.02 microgram/ml to mynomycine, 3.13 micrograms/ml to vancomycin, 12.5 micrograms/ml to ofloxacin and 100 micrograms/ml to imipenem in 1989. One-third of the 60 isolated cases showed respiratory infections including 10 cases of pneumonia and 10 sepsis patients and 11 blood samples in 1988 and 1989, especially 92.9% of S. aureus isolated in 1989 was MRSA. Four of the 6 patients with respiratory infections of MRSA and 1 of the 3 patients with MRSA sepsis were treated successfully by a combination therapy of imipenem/cilastatin and cefazolin.