Biomedical subjects

K Mitsutake

Publications and source records attributed to K Mitsutake.

At least 37 records · Page 2Linked to original sources

PubMed1994

In vitro and in vivo antifungal activities of liposomal amphotericin B, and amphotericin B lipid complex.

The in vitro and in vivo antifungal activities of liposomal amphotericin B (L-AMPH) and amphotericin B lipid complex (ABLC), which is composed of amphotericin B and the phospholipids dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol, were compared with those of conventional amphotericin B (Fungizone, AMPH). The acute intravenous toxicity was markedly lower in BALB/c mice; 50% lethal doses (LD50s) were 2.75 mg/kg in AMPH, 32.9 mg/kg in L-AMPH and > 75 mg/kg in ABLC. In vitro antifungal activities against Candida albicans, C. parapsilosis, C. tropicalis, C. glabrata, and C. krusei were evaluated by the agar plate dilution method. The activities were unchanged against C. albicans, but MICs increased more than four fold in 18 of the 20 strains other than C. albicans in L-AMPH and in 9 of the 20 in ABLC. L-AMPH and ABLC were as efficacious as AMPH in the treatment of mice infected with C. albicans, and at a dose of 0.5 and 1.0 mg/kg of body weight, ABLC was more efficacious on survival A ten-times larger dose (10 mg/kg) of L-AMPH and ABLC was administered to mice with 100% survival, suggesting improved tolerability as compared to amphotericin B.

Amphotericin B↗

PubMed1994

[Evaluation of (1-3)-beta-D-glucan in aspergillosis and cryptococcosis].

(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.

Adult↗

PubMed1993

High detection rates of cryptococcal antigen in pulmonary cryptococcosis by Eiken latex agglutination test with pronase pretreatment.

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.

Adult↗

PubMed1993

An evaluation of serodiagnostic tests in patients with candidemia: beta-glucan, mannan, candida antigen by Cand-Tec and D-arabinitol.

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.

Adolescent↗

PubMed1993

[Treatment of experimental invasive pulmonary aspergillosis in rats with liposomal amphotericin B].

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.

Amphotericin B↗

PubMed1993

Efficacy of intravenous itraconazole against experimental pulmonary aspergillosis.

The efficacy of intravenous itraconazole solubilized in hydroxypropyl-beta-cyclodextrin was assessed in a rat model of Aspergillus fumigatus pneumonia. Immunosuppressed rats were infected by intratracheal inoculation of A. fumigatus conidia. Intravenous administration of various doses of itraconazole was started immediately after infection and continued once a day for 7 days. A 10-mg dose of intravenous itraconazole per kg was as effective on survival as 1 mg of amphotericin B per kg daily (a survival rate of 100% in 28 days), while treatment with 1 mg/kg did not increase the survival rate. The 50% lethal dose of intravenous itraconazole given to immunosuppressed and uninfected rats for 7 days was 24.5 mg/kg/day. A microbiological assay to estimate accumulation in tissue after five daily intravenous administrations of itraconazole at 10 mg/kg showed that itraconazole and its active metabolites were present in the lungs for at least 6 h, reaching the MIC as previously described (B. Dupont and E. Drouchet, Rev. Infect. Dis. 9(Suppl. 1):71-76, 1987; A. Espinel-Ingroff, S. Shadomy, and R. J. Gebhart, Antimicrob. Agents Chemother. 26:5-9, 1984). Intravenous itraconazole was considered to be worth evaluating in clinical trials of aspergillosis.

Animals↗

PubMed1993

[Pulmonary cryptococcosis treated by combination therapy of fluconazole plus flucytosine].

The efficacy of the combination therapy of fluconazole plus flucytosine against pulmonary cryptococcosis was investigated. The minimal inhibitory concentrations of antifungal agents were measured by growth inhibition on Yeast-morphology agar plates, and the fractional inhibitory concentration index of each antifungal combination were calculated by checker-board titration. Eight of Cryptococcus neoformans clinical isolates showed sensitivity for AMPH, 5-FC, MCZ and ITZ. C. neoformans showed resistance against FLCZ. The combination of FLCZ plus 5-FC showed synergistic effect against C. neoformans. Three cases of pulmonary cryptococcosis were treated by combination therapy of fluconazole plus flucytosine. After treatment, C. neoformans isolates were eradicated and the chest X-ray improved remarkably. The combination therapy of fluconazole plus flucytosine was effective for the treatment of pulmonary cryptococcosis.

Aged↗

PubMed1993

[A case of pulmonary aspergilloma successfully treated with combination therapy of intracavitary injection of amphotericin B and intravenous administration of urinastatin].

A 57-year-old man with pulmonary tuberculosis underwent left upper lobectomy in 1984. In 1987, chest X-ray showed a fungus ball, and Aspergillus species was isolated from sputum. He was treated by intracavitary injection of amphotericin B (AMPH) in June, 1992. However, no change was observed in the chest CT scan after a total dose of 1,000 mg of AMPH. Combination therapy of intravenous administration of 100,000 units of urinastatin and intracavitary injection of AMPH resulted in complete disappearance of the fungus ball on chest CT scan. This report describes case of pulmonary aspergilloma successfully treated with the combination of AMPH and urinastatin.

Amphotericin B↗

PubMed1993

[Incidence of fungal isolation in clinical specimens from the respiratory tract].

The incidence of fungal isolation in 711 clinical specimens from the respiratory tract was investigated in 159 patients with pulmonary diseases. Fungi were isolated from 14/19 pharynx swab samples, 246/342 sputum samples, 34/147 bronchial aspirate samples, 18/97 bronchial lavage samples, 4/17 transbronchial lung biopsy samples, and 5/60 plugged catheter brush samples. Contamination by fungi in normal flora was prevented by using an aseptic procedure for sampling specimens from the respiratory tract. The isolation rate of Candida spp. from sputum was 70.0% (C. albicans: 151 strains, C. glabrata: 43 strains, C. tropicalis: 25 strains, C. lusitaniae: 4 strains, C. krusei: 3 strains, C. guilliermondii: 3 strains and C. paraspilosis: 1 strain). The isolation rates of C. neoformans and A. fumigatus from sputum were 6.4% and 8.8%, respectively. Isolated fungi from bronchial aspirate included 12 strains of C. albicans, 6 strains of C. tropicalis, 5 strains of A. fumigatus and 2 strains of C. neoformans. Isolated fungi from bronchial aspirate revealed 6 strains of C. albicans, 2 strains of C. glabrata, 1 strain of C. neoformans and 6 strains of A. fumigatus. The isolation rates of fungi from sputum obtained from patients with pulmonary aspergilloma and cryptococcosis were 66.5% and 50.0%, respectively. The isolation rate of fungi from sputum of patients with underlying diseases was higher than that of patients with no underlying disease.

Adolescent↗

PubMed1992

G test, a new direct method for diagnosis of Candida infection: comparison with assays for beta-glucan and mannan antigen in a rabbit model of systemic candidiasis.

An indirect method to measure beta-glucan, a major structural component of yeast cell walls, is available, but has the disadvantage of requiring the combined use of two assays. Recent reports describe the fungal index, which measures the difference between the conventional limulus test, in which factors C and G react with endotoxin and beta-glucan, and a new endotoxin-specific test, in which only factor C reacts with endotoxin. The G test was developed as a direct method to measure beta-glucan, and contains only factor G reacting with beta-glucan alone. In this study, the G test was examined in sera of rabbits with experimental systemic candidiasis, and compared with the fungal index and mannan assay. The G test showed positive in all rabbits with systemic candidiasis faster and with higher titers than with the fungal index. Three rabbits with fulminant systemic candidiasis showed higher levels of reactivity with the G test and the fungal index than two rabbits with mild reactions. Mannan was positive by at least one serum in four of five rabbits by the latex agglutination test, and there was a good correlation between these assays. The G test is a good serodiagnostic method for the detection of candidiasis.

Animals↗

PubMed1992

[Limulus test (factor G) and polysaccharides from fungus].

Picogram quantifies per ml of endotoxin showed a positive limulus test. The concentration more than ten pg/ml of curdlan ((1-3)-beta-D-glucan) was also positive to a conventional limulus test, which contains a factor G. One nanogram per ml of CM-curdlan was positive, but higher concentration of 10 pg/ml of CM-curdlan decreased its optical density of the conventional limulus test. More than one hundred ng/ml of mannan from Saccharomyces cerevisiae did not react with factor G. However, a culture supernatant of Saccharomyces cerevisiae activated factor G. This result suggested that beta-glucan activated factor G. In addition, culture supernatant of Aspergillus fumigatus, Rhodotorula rubra, Candida parapsilosis, Candida tropicalis, Candida krusei also activated factor G, but Cryptococcus neoformans did not activate it.

Antimicrobial Cationic Peptides↗

PubMed1992

[Antigen detection in the murine models of systemic candidiasis].

We compared two latex agglutination tests for serum candidal antigen in murine models of systemic infection and gastrointestinal colonization. In the intravascular-infection model, mannan detection test was positive at 2 hours after inoculation, but Cand-Tec was less sensitive than mannan detection test in this model. In the gastrointestinal colonization model followed by systemic infection in neutropenic mice, the mannan antigen test became positive after 3 weeks of colonization with increased number of Candida of the stool, and Cand-Tec became positive after 5 weeks in neutropenic mice.

Animals↗

PubMed1992

[Four cases of respiratory tract infections caused by Corynebacterium pseudodiphtheriticum].

Four cases of respiratory tract infections caused by Corynebacterium pseudodiphtheriticum were reported. The first two patients developed pneumonia with Corynebacterium pseudodiphtheriticum during steroid therapy used against their underlying diseases. The other two patients had acute exacerbation of chronic pulmonary diseases caused by C. pseudodiphtheriticum. These four patients improved by antibiotic therapy. Though nondiphtheria corynebacteria are regarded as "normal flora" when they are isolated from sputum, they should be recognized as potential pathogens.

Aged↗

PubMed1992

Prevalence of HTLV-I antibody in pulmonary cryptococcosis.

A retrospective study was done to determine the prevalence of anti-HTLV-I antibodies in patients with pulmonary cryptococcosis. None of the 19 patients with pulmonary cryptococcosis had underlying immunodeficiency. Anti-HTLV-I antibody was present in 6 (32%) of 19 patients with pulmonary cryptococcosis, a significantly higher prevalence than found in patients with bronchial asthma (4 (7%) of 58) (p less than 0.01, chi-square test). No statistical difference was noted when anti-HTLV-I antibody seropositivity was compared to that of patients with pulmonary tuberculosis (16% (17/105)), lung cancer (17% (22/129)) and pneumonia (9% (6/64)). A reduced cellular immunity as shown by lymphopenia, the CD4/CD8 ratio, and purified protein derivative skin test was found in only 1 (5%) of 19, 2 (12%) of 17, and 6 (33%) of 18 patients, respectively. These results do not explain the susceptibility to pulmonary cryptococcosis in HTLV-I carriers. This is the first report of high prevalence of pulmonary cryptococcosis in HTLV-I carriers and it raises the question whether HTLV-I carriers are more susceptible to opportunistic infections and other malignancies probably due to subtle immunological abnormalities.

Adolescent↗

PubMed1992

Combination of conventional and endotoxin-specific limulus tests for measurement of polysaccharides in sera of rabbits with experimental systemic candidiasis.

Factor G, the coagulation enzyme from limulus amebocytes, is activated by (1-->3)-beta-D-glucan but not by endotoxin. The endotoxin-specific limulus test, which is devoid of factor G, reacts only with endotoxin. However, the conventional limulus test which includes factors G and C, reacts with not only endotoxin but also with (1-->3)-beta-D-glucan. In this study, the culture supernatant of Candida albicans in RPMI medium activated the conventional limulus test, but not the endotoxin-specific limulus test. All five rabbits inoculated intravenously with Candida albicans (1.0 x 10(7) CFU/rabbit) showed increased levels of reactivity with the conventional limulus test, whereas no elevation in the levels of the endotoxin-specific limulus test was observed in the sera of any infected rabbits. Only one serum sample from rabbit No. 5 on day 8 showed a positive Cand-tectest. The difference in the titers of the two limulus tests was suggestive of a diagnosis of Candida infection.

Amino Acid Sequence↗

PubMed1992

Fatal pneumonia caused by Corynebacterium group JK after treatment of Staphylococcus aureus pneumonia.

A 76-year-old man who was admitted to the hospital because of chronic renal insufficiency and chronic hepatitis died of Corynebacterium group JK pneumonia, after showing a slight improvement by treatment of Staphylococcus aureus with sulbactam/cefoperazone and minocycline. Transtracheal aspiration (TTA) just before his death revealed numerous gram-positive bacilli phagocytized by many neutrophils and more than 10(8) colony forming units (CFU)/ml of Corynebacterium group JK. A drug susceptibility test showed Corynebacterium group JK was resistant to many antibiotics, with the exception of vancomycin and amikacin.

Aged↗

PubMed1991

[Clinical evaluation of serological antigen detection tests for candidemia].

The new serological tests for candidemia were evaluated. In nine cases of candidemia, fungal index (Endotoxin D-Endospecy) was 146.8 +/- 116.8 pg/ml and D-arabinitol/creatinine 1.10 +/- 1.04 mumol/mg. Fungal index was significantly (p less than 0.01) higher in candidemia than suspected infections. All candidemia were positive for Cand-Tec latex agglutination, but twelve of the sixteen cases of suspected infections were also positive. Mannan latex agglutination was very specific for candidemia. Four cases of candidemia was positive for Mannan latex agglutination and only one case was positive in suspected infections. Fungal index and D-arabinitol/creatinine was decreased after treatment of antifungal agents. In poor clinical efficacy case, these titer remained high even after treatment. These data suggested the usefulness of these serological tests for candidemia.

Adolescent↗

PubMed1991

[Bacteriological studies on pharyngeal and tracheal colonization in patients of operations and patients in ICU].

Bacterial colonization of the pharynx before and one week after operation, and contamination of the trachea during intubation in 7 patients who underwent operations were investigated. And bacterial colonization of pharynx, tracheas, and mechanical-ventilators in 7 ICU patients was investigated. Flora of palms of 10 ICU personnel was also examined: 1) Oral bacteria began to be found in the trachea several hours after intubation. 2) In oropharyngeal flora, one week after operation, Neisseria and anaerobes which belong to normal flora decreased because of antibiotics, but no new resistant bacteria appeared. 3) Although isolates from pharynx of preoperative patients were normal flora, those of ICU patients were Staphylococcus epidermidis, Enterococcus spp., gram-negative rods such as Pseudomonas aeruginosa, and yeast liked organisms etc, which were resistant to antibiotics. 4) From the trachea of intubated patients in ICU, oral bacteria were isolated. 5) Pseudomonas pickettii was isolated from the expiratory side of ventilator circuits in one patient, but it was not isolated from the patient. 6) From hands of ICU personnel, gram-positive bacteria such as coagulase negative staphylococci, Coryne bacterium spp. and Bacillus spp. were isolated. 7) One patient in ICU, who developed pneumonia due to resistant Bacteroides fragilis following oropharyngeal colonization, was reported. These studies suggested the importance of environmental control, careful selection of antibiotics, and attention to change of flora.

Aged↗