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Biomedical subjects

K Tomono

Publications and source records attributed to K Tomono.

At least 55 records · Page 3Linked to original sources

In-vitro and in-vivo activities of SCH56592 against Cryptococcus neoformans.

The in-vitro and in-vivo activities of SCH56592, a triazole antifungal agent, against Cryptococcus neoformans were studied. MIC(90)s for 16 strains of C. neoformans measured by microdilution method (NCCLS M27-A) were 1 mg/L of SCH56592, 16 mg/L of fluconazole, 32 mg/L of flucytosine, and 0.5 mg/L of amphotericin B. In a murine model of pulmonary cryptococcosis, 10 mg/kg of SCH56592 was more effective than fluconazole. The fungal burden of the lung of animals treated with SCH56592 was significantly reduced (7.40 +/- 0.21 log(10) cfu/g), as compared with fluconazole (7.77 +/- 0.07 log(10) cfu/g) and control (7.79 +/- 0.1 log(10) cfu/g) (P < 0.01). For C. neoformans-infected mice following 7 days treatment with 10 mg/kg of SCH56592 there was a higher concentration in lung (3.36 +/- 0.62 ng/ml) than in plasma (2.16 +/- 0.86 ng/mL), and this was maintained for 12 h after administration.

Animals↗

[A case of pulmonary cryptococcosis with lung cancer in a pulmonary lobe].

A 63-year old female was admitted because of an abnormal shadow on chest X-ray film. Chest CT showed a nodular shadow in the right S6 and a patchy shadow in the right S10. Right lower lobectomy was performed under a diagnosis of lung cancer made by TBLB in the right S6. Pathological examination of the resected lung revealed papillary adenocarcinoma in the right S6 and numerous cryptococci in the right S10. No cryptococcal infection was found in the resected lymph nodes.

Adenocarcinoma, Papillary↗

[The booster phenomenon in two-step tuberculin testing of employees in a community hospital].

A study was made to clarify to what degree the booster phenomenon was present when the employees in a community hospital in Japan received two-step tuberculin testing (PPD). Of the seventy-five employees, most of all BCG-vaccinated subjects, twenty-three showed strongly positive of more than 30 mm of induration at the first test (PPD/T1), and the remaining fifty-two subjects received a second (PPD/T2) after 2 weeks. The second PPD showed a marked increase in reactivity, sixteen subjects newly became strongly positive and six of eight who were initially PPD negative (< 10 mm) were converted positive, and the mean reaction size changed from 14.7 +/- 5.6 mm (PPD/T1) to 31.5 +/- 15.5 mm (PPD/T2). The degree of boosting, measured by the change in millimeters induration size between PPD/T1 and PPD/T2 (PPD/T2-PPD/T1), was correlated with neither the size of PPD/T1 nor the age of the study participants, and was not associated with the difference of the position in the hospital. Thus, we could not explain the factor why such a marked boosting was observed in this study. However, these results indicated that the two-step tuberculin testing is an essential means of distinguishing new tuberculous infection from booster phenomenon. We agree with the current recommendation for routine two-step testing of new employees in the hospital.

Adult↗

In vitro and in vivo activities of NS-718, a new lipid nanosphere incorporating amphotericin B, against Aspergillus fumigatus.

We evaluated the in vitro and in vivo potencies of a new lipid nanosphere that incorporates amphotericin B (AmB), NS-718, against Aspergillus fumigatus. The in vitro activity of NS-718 (the MIC at which 90% of strains are inhibited [MIC90], 0.25 microgram/ml) against 18 isolates of A. fumigatus was similar to that of deoxycholate AmB (D-AmB; Fungizone; MIC90, 0.25 microgram/ml), but NS-718 was more potent than liposomal AmB (L-AmB; AmBi-some; MIC90, 1.0 microgram/ml). The in vivo efficacy of NS-718 in a rat model of invasive pulmonary aspergillosis was compared with those of D-AmB and L-AmB. A low dose (1 mg/kg of body weight) of L-AmB was ineffective (survival rate, 0%), although equivalent doses of D-AmB and NS-718 were more effective (survival rate, 17%). However, a higher dose of NS-718 (3 mg/kg) was more effective (survival rate, 100%) than equivalent doses of D-AmB and L-AmB (survival rate, 0%). To explain these differences, pharmacokinetic studies showed higher concentrations of AmB in the plasma of rats treated with NS-718 than in the plasma of those treated with D-AmB. Our results suggest that NS-718, a new preparation of AmB, is a promising antifungal agent with activity against pulmonary aspergillosis.

Amphotericin B↗

Comparison between PCR and detection of antigen in sera for diagnosis of pulmonary aspergillosis.

We evaluated the usefulness of PCR and antigen detection for the diagnosis of pulmonary aspergillosis. Forty-four serum samples from patients with pulmonary aspergillosis (33 with pulmonary aspergilloma, 4 with allergic bronchopulmonary aspergillosis, 4 with invasive pulmonary aspergillosis, and 3 with aspergillus pyothorax) were used in this study. PCR detection of Aspergillus DNA in serum samples was successful in 39 patients. Galactomannan antigen was detected by sandwich enzyme-linked immunosorbent assay in 25 patients and by latex agglutination test in 13 patients. Detection of Aspergillus DNA in serum samples by nested PCR had the highest sensitivity of the three methods tested for the diagnosis of pulmonary aspergillosis.

Antigens, Fungal↗

Effect of the opioid antagonist naloxone on the regional metabolic rate for glucose in the conscious rat brain.

The effect of naloxone, a potent and specific opioid antagonist, on cerebral glucose utilization was investigated in conscious rat. For quantitative evaluation of the functional activity in brain, the regional cerebral metabolic rate for glucose (rCMRglc) was measured by the double tracer technique, using [14C]2-deoxyglucose and [3H]3-o-methylglucose. Intravenous administration of naloxone significantly increased rCMRglc in the medulla and thalamus at a dose of 1 or 10 mg/kg, and in the cerebral cortex, midbrain and cerebellum at a dose of 10 mg/kg. Our findings strongly suggest that naloxone by itself affects the cerebral functional activity within 10 min of administration.

Animals↗

Invasive pulmonary aspergillosis diagnosed early by polymerase chain reaction assay.

We compared the usefulness of a polymerase chain reaction (PCR) assay for the early diagnosis of invasive pulmonary aspergillosis with the serodiagnosis of sufficient concentrations of galactomannan using the same serum samples. A patient was treated with prednisolone for the management of hepatitis. Computed tomography (CT) scan of the chest showed the nodular shadow with a cavity containing a clear fungus ball. DNA of Aspergillus spp. from a serum sample was detected and using the same serum sample, both latex agglutination and sandwich enzyme-linked immunosorbent assay (ELISA) of galactomannan were negative. PCR assay provides an early diagnosis of invasive pulmonary aspergillosis compared with ELISA of galactomannan.

Antibodies, Fungal↗

Evaluation of sandwich ELISA galactomannan test in samples of positive LA test and positive aspergillus antibody.

OBJECTIVE: The detection of circulating Aspergillus galactomannan antigen is a useful tool for serodiagnosis of aspergillosis. However, the latex agglutination test for the detection of galactomannan is not completely reliable due to it's low sensitivity. The sandwich ELISA was developed to achieve high sensitivity. MATERIALS: The sandwich immunocapture ELISA was evaluated by testing 56 sero-positive and 56 sero-negative samples of circulating galactomannan detected by LA test retrospectively. RESULTS: Sixty of the samples were positive for galactomannan as measured by sandwich ELISA. Fifteen samples out of 56 samples negative by LA test were positive by ELISA and 4 samples out of 56 samples positive by LA test were negative by ELISA. Among 47 serum samples positive for anti-Aspergillus antibody, 14 samples were positive by ELISA. CONCLUSION: In conclusion, galactomannan may be detected in more samples of by the new sandwich ELISA than by LA test.

Antibodies, Fungal↗

[The future of antifungal agents. Non azole antifungal agents].

We investigated the efficacy of non-azole antifungal agents. Long circulating immunoliposomal amphotericin B was potent in murine invasive pulmonary aspergillosis. The concentration of AMPH-B was still high in the lung after 6 hours of 34A-PEG-liposomal AMPH-B. Lipid nanosphere amphotericin B (NS-718) showed efficacy against pulmonary aspergillosis in rats and pulmonary cryptococcosis in mice. The renal toxicity of NS-718 was estimated to be lower than that of AMPH-B from the results of the toxicity study in the rat infusion model. FK 463, a novel (1,3)-beta-D-glucan synthase inhibitor, showed efficacy against azole-resistant Candida albicans in murine experimental disseminated candidiasis. FK463 could be a promising drug and the therapy of choice for azole resistant C. albicans infection.

Amphotericin B↗

[A case of invasive aspergillosis in an amyloidosis patient].

A sixty-four-year-old male patient was admitted on 13 April 1995 with diagnosis of old pulmonary tuberculosis and pulmonary aspergilloma. He developed a tarry stool and frequent loose motion in early November 1995. Histopathological findings of endoscopic biopsy from the duodenum and colon were suggestive of secondary amyloidosis. In spite of antibiotic and steroid pulse, he developed shock, and massive infiltration shadow appeared in chest X-ray. The patient died on 29 December 1995. The postmortem examination in the specimens of the lung, heart, kidney, liver, and spleen revealed hyphae of Aspergillus sp. and in the specimens of the lung, kidney, spleen, esophagus, adrenal gland, and thyroid revealed amyloid. He was finally diagnosed as invasive aspergillosis with secondary amyloidosis.

Amyloidosis↗

[Itraconazole-induced hypokalemia in a patient with pulmonary aspergilloma].

An 80-year-old man was admitted to the hospital with a diagnosis of pulmonary aspergilloma. A new azole antifungal agent, D 0870, was administered to the patient for 7 days orally, and itraconazole (400 mg/day) was started on March 5, 1997. After 1 month of chemotherapy, facial and pretibial edema were observed and the patient's serum potassium concentration decreased to 2.5 mEq/l. A chest radiograph disclosed cardiomegaly with cardiac effusion and right pleural effusion on admission. The serum potassium concentration rose after the cessation of itraconazole therapy. The serum ITCZ concentration remained high for 2 weeks after admission. Although reports of hypopotassemia induced by ITCZ are rare, we concluded that blood concentrations should be monitored more carefully when treating pulmonary aspergilloma patients with high-dose regimens of ITCZ.

Aged↗

[The combination therapy of clarithromycin and sparfloxacin for pulmonary Mycobacterium gordonae infection].

Seventy years old woman had fever and hemosputum at May 1997. She was diagnosed as mycobacteriosis because of the positive acid fast bacilli smear from sputum. Mycobacterium gordonae was isolated from sputum, gastric juice, and bronchial aspirate. The combination therapy of isoniazid, rifampicin, ethambutol, and clarithromycin was administrated; however, M. gordonae was not eradicated from sputum. Sparfloxacin was administered instead of isoniazid based on the result of drug susceptibility test. The smear became negative and M. gordonae was eradicated from sputum one month after the initiation of treatment with the combination of clarithromycin and sparfloxacin.

Aged↗

[Susceptibilities of Enterococcus faecium, PRSP and MRSA to RP59500 and their correlations with those to other drugs].

Investigations on emergence of vancomycin-resistant Enterococcus faecium (VREF) which has recently been attracting attention, especially in the Western countries, have been conducted in Japan. A total of 1,239 isolates of E. faecium were collected from 19 institutions during the period of April 1995 and June 1996, in the purpose of evaluating susceptibilities to variety of antimicrobial agents, including RP59500 and vancomycin (VCM), and detecting vancomycin-resistant genes (van genes). Susceptibilities of penicillin-resistant Streptococcus pneumoniae (PRSP) and methicillin-resistant Staphylococcus aureus (MRSA) were also studied. As a result, 2 isolates of E. faecium were found to be moderately resistant to VCM showing MIC of 8 micrograms/ml though the final identification in species level and the detection of van genes by PCR method have not been completed. On the other hand there detected no MRSA nor PRSP showing moderately resistant or resistant to VCM. It was concluded that RP59500 and VCM possessed favorable activity against clinically isolated E. faecium, PRSP and MRSA. Among other species of enterococci, moderately resistant strains to VCM showing MIC of 8 micrograms/ml were detected; 10 isolates of E. gallinarum, 4 of E. casseliflavus and 2 of E. flavescens. In those isolates, vanC1 and vanC2 were detected by PCR, and vanB was also detected in a isolates of E. gallinarum simultaneously.

Anti-Bacterial Agents↗