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Biomedical subjects

M Kaku

Publications and source records attributed to M Kaku.

At least 109 records · Page 6Linked to original sources

Clinical evaluation of catheter-related fungemia and bacteremia.

Forty-four patients with catheter-related infection admitted to Hokusho Central Hospital between 1985 and 1991 were studied retrospectively. The rate of catheter-related fungemia or bacteremia to all corresponding cases of fungemia and bacteremia increased from 7.7% in 1985 to 28.8% in 1991. The isolated pathogens were Candida parapsilosis (8 strains), Candida tropicalis (6 strains), methicillin-resistant Staphylococcus aureus (MRSA) (6 strains), methicillin-sensitive S. aureus (MSSA) (5 strains) and Streptococcus epidermidis (3 strains). Bacteremia occurred after catheterization of the femoral vein for a mean duration of 37 days. The period was significantly shorter than that after catheterization of the subclavian vein (56 days). The major isolates from the subclavian vein were Candida spp. (14/17, 82.4%), followed by MRSA (1/17, 5.9%) and MSSA (1/17, 5.9%), while isolates from the femoral vein were Candida spp. (6/16, 37.5%), MRSA (5/16, 31.3%) and MSSA (3/16, 20.8%). Catheter removal alone did not improve the clinical condition, particularly in MRSA bacteremia; the combination of antimicrobial therapy and removal of the catheter was necessary for a better prognosis.

Aged↗

Infections in patients with liver cirrhosis and hepatocellular carcinoma.

Infections in immunocompromised hosts have been an important clinical problem. Patients with liver cirrhosis and/or hepatocellular carcinoma are at a high risk of infection due to multiple factors. Five hundred and two patients admitted with liver cirrhosis and/or hepatocellular carcinoma were evaluated for infection. The infection rate was not influenced by the etiology of hepatic diseases or the presence of hepatocellular carcinoma, however, it increased with the advance of clinical stages of liver cirrhosis and hepatoma. The respiratory tract and urinary tract were the most common sites of infection, being involved in 50% and 28% of cases, respectively. The major pathogens of respiratory tract infection were S. aureus, H. influenzae, and P. aeruginosa. Gram-negative bacteria was the common isolate from sputum and urine, and S. aureus was also common in gram-positive bacteria. The infection rate was high in patients who died although infections could rarely be implicated as the direct cause of death. These findings should be a guide for the clinicians in treating patients with liver cirrhosis and/or hepatocellular carcinoma who exhibit signs of infection.

Carcinoma, Hepatocellular↗

[A rapid susceptibility test of Mycobacterium tuberculosis using hybridization protection assay].

The conventional drug susceptibility tests of Mycobacterium tuberculosis are time-consuming and usually require 2 to 4 weeks to obtain final results. In this study, we attempted to develop a novel method for rapid detection of drug-resistant M. tuberculosis using hybridization protection assay (HPA). Clinically isolated strains of M. tuberculosis including seven isoniazid (INH) susceptible strains and six resistant strains were used. The organisms grown on Ogawa egg medium were inoculated into Middlebrook 7H9 broth and cultured at 37 degrees C for one week. Then, the inoculum of each strain was prepared as a tenfold dilution of bacterial suspension at McFarland No. 0.5. The inocula were mixed with INH solutions to yield final concentrations of 0.1 and 1.0 micrograms/ml, and the resulting bacterial suspensions with or without test drug were cultured on the swaying plate at 37 degrees C for up to 5 days. At intervals, 50 microliters of each sample was withdrawn and subjected to the protocol of the HPA using acridinium-ester (AE) labeled DNA probe, and then the relative light unit (RLU) was read in a luminometer. In the case of the susceptible strains, a significant difference in the mode of increase in RLU ratio (% of RLU on day x/RLU on day 0) was observed between the INH-treated and drug-free control sets within three days of cultivation, while no such differences were seen in the case of the resistant strains.(ABSTRACT TRUNCATED AT 250 WORDS)

Acridines↗

The Eiken Latex test for detection of a cryptococcal antigen in cryptococcosis. Comparison with a monoclonal antibody-based latex agglutination test, Pastorex Cryptococcus.

A latex agglutination test for cryptococcal antigen, the Eiken Latex test (Eiken, Tokyo, Japan), was compared with a monoclonal antibody-based agglutination assay, Pastorex Cryptococcus (Diagnostics Pasteur, Marneur-la-Coquette, France). In a murine model of disseminated cryptococcosis, the kinetics of the antigen titers by the Eiken Latex were similar to those by the Pastorex Cryptococcus, but sensitivity was much higher. In HIV-negative patients with pulmonary cryptococcosis, a cryptococcal antigen was detected in 6 of 10 patients by the Eiken Latex test and in only 3 of those patients by the Pastorex Cryptococcus. The results indicate that the Eiken Latex is more sensitive for the detection of the cryptococcal antigen, even in non-disseminated cryptococcosis. The sensitivity and specificity of the Eiken Latex were examined using 195 sera from 25 patients with pulmonary cryptococcosis and 170 patients with non-cryptococcosis. The cutoff value of > or = 1:8 showed a sensitivity of 76% (19/25) and a specificity of 98.9% (168/170).

Agglutination Tests↗

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↗

In-vitro and in-vivo activity of a new quinolone AM-1155 against Mycoplasma pneumoniae.

We investigated the in-vitro and in-vivo activity of a new quinolone AM-1155 against Mycoplasma pneumoniae, and compared it with ofloxacin, ciprofloxacin, lomefloxacin, tosufloxacin, erythromycin and minocycline. AM-1155 was the most potent agent in vitro of the quinolones tested. Its pre-treatment minimal inhibitory concentrations for 90% of the 41 strains (MIC90) was 0.06 mg/L. In contrast, pre-treatment MIC90 values for ofloxacin, ciprofloxacin, lomefloxacin, tosufloxacin, erythromycin, and minocycline were 1, 1, 2, 0.5, 0.0156, and 0.5 mg/L, respectively. Post-treatments MIC90s, which may reflect mycoplasmacidal potency, of AM-1155, ofloxacin, ciprofloxacin, lomefloxacin, tosufloxacin, erythromycin and minocycline were 0.125, 1, 2, 4, 0.5, 0.125 and 4 mg/L, respectively. In-vitro activities of antimicrobial agents were assessed in an experimental pulmonary infection model in Syrian golden hamsters. AM-1155 was the most effective agent among five antimicrobial agents (AM-1155, ofloxacin, tosufloxacin, erythromycin, minocycline) tested in terms of reduction in viable M. pneumoniae cells and in reducing macroscopic lung lesions. These results suggest that AM-1155 will be a useful antimicrobial agent for the treatment of M. pneumoniae infections.

Animals↗

Detection of antibody-coated bacteria in expectorated sputum for diagnosis of lower respiratory infections.

We evaluated antibody-coated bacteria (ACB) in expectorated sputum to discriminate contaminating or colonizing organisms from true pathogens. We examined 60 expectorated sputum samples from 51 patients with lower respiratory infections (chronic obstructive pulmonary disease 25, pneumonia 20, purulent tracheobronchitis 6). All samples were examined with quantitative culture and immunofluorescent demonstration of ACB. From the results of quantitative culture, we divided specimens into pathogen-isolated and pathogen-free samples. Among pathogen-isolated samples, in which we isolated accepted pathogenic organisms at > or = 10(7) colony-forming units per ml, 16 of 23 samples were ACB-positive (69.5%). In contrast, among pathogen-free samples, in which we isolated accepted pathogens at < 10(7) colony forming units per ml or only upper respiratory flora, only 3 of 37 samples were ACB-positive (8.1%). The ACB-positive rate was significantly higher in pathogen-isolated than in pathogen-free samples (P < 0.001). Consequently, detecting ACB in expectorated sputum shows good potential as another criterion for distinguishing contaminating or colonizing organisms from true pathogens.

Adult↗

Influence of molecular sizes of Cryptococcus neoformans capsular polysaccharide on phagocytosis.

The role of capsular polysaccharides (CPS) of Cryptococcus neoformans in phagocytosis by murine alveolar macrophages was investigated in four strains of C. neoformans serotype A, YC-11, YC-5, YC-27 and YC-13. Phagocytosis rates increased markedly after adding 10% mouse serum, compared to fetal calf serum. The reverse relation between capsular thickness of C. neoformans and phagocytosis by alveolar macrophages was observed except in YC-27, which had thin capsules and high virulence. The phagocytosis rate in mice serum was 17.3% in YC-11 (capsule thickness 2.8-3.5 microns), 39.8% in YC-5 (capsule size 0.8-1.5 microns), 20.3% in YC-27 (capsule size 0.6-1.1 microns), and 62.8% in YC-13 (capsule not detected microscopically). The CPS of YC-11, YC-5, and YC-27 analyzed by gel-filtration using CL-2B showed high molecular fractions near the void volume. However, the CPS of YC-13 showed only low molecular fractions. The widely eluted CPS of YC-11 was separated into 3 fractions and each fraction was added in the phagocytosis assay of YC-13. Phagocytosis was markedly suppressed particularly by the addition of a higher molecular fraction. These results suggest that phagocytosis of C. neoformans by alveolar macrophages is influenced by the molecular sizes of the CPS.

Animals↗

[Coexisting respiratory tract infection and bacteremia or sepsis caused by the same bacterium].

We experienced 12 patients who were suffering from bacteremia or sepsis and pneumonia or lung abscess coincidently caused by the same bacterium, during the 8 years from 1985 to 1992 a Hokusyo Central Hospital. All of them has some underlying diseases, and the average age was 73.6 years old. In ten out of 12 patients bacteremia or sepsis preceded the respiratory tract infection, and in 7 cases indwelling intravenous catheter was thought to be the port of entry of the bacteria. Respiratory tract infections were composed of pneumonia in 8 cases and lung abscess in 4 cases. Methicillin resistant Staphylococcus aureus (MRSA) was detected in 4 cases, Methicillin sensitive Staphylococcus aureus (MRSA), Klebsiella pneumoniae and Pseudomonas aeruginosa were in 2 cases respectively, Citrobacter freundii and Methicillin resistant Staphylococcus spp. were in one cases respectively. Eight out of 12 cases died in spite of current antibiotics therapy, suggesting poor prognosis.

Aged↗

[Three cases of Pasteurella multocida infection in the respiratory tract].

Pasteurella multocida (P. multocida) is well recognized as "normal flora" in the upper respiratory tract of cats, dogs and other animals. Recently, various infections due to P. multocida in human have been noted as pulmonary infections in the patients with chronic pulmonary diseases as well as skin abscesses or septicemia after an animal bite or scratch. We report here three cases of respiratory tract infections caused by P. multocida. The first two patients had acute exacerbation of bronchiectasis caused by P. multocida and the other patients with pulmonary emphysema developed pneumonia. These three patients improved by antibiotic therapy. In Japan, P. multocida respiratory tract infection is rare, but it may become more common in the future. Therefore, it seems to be important to take this pathogen into consideration in the management of chronic lung disease.

Adult↗

[A case of brain abscess associated with enterococcal endocarditis].

Enterococcal infections involving the central nervous system are uncommon clinical entities. A 74-year-old male was admitted to our hospital on November 3, 1991 for high fever. Nuchal rigidity was observed at neurological examination. All four blood cultures yielded E. faecalis. The MIC value of ABPC against the isolated E. faecalis was 0.25 microgram/ml. Vegetation on the mitral valve and mitral regurgitation were revealed by an echocardiogram. Enhanced CT scan showed low density area with ring enhancement in the right basal ganglia and a CSF examination suggested bacterial meningitis. He became better after ABPC 8 g/day was intravenously administered. Then the vegetation on the mitral valve and the brain abscess disappeared. He was discharged with no complications. We reported a rare case of brain abscess associated with enterococcal endocarditis.

Aged↗

[Clinical investigation of obstructive pneumonia with lung cancer].

Nineteen episodes (18 patients) of obstructive pneumonia occurring in 247 patients with lung cancer were clinically examined, and the following findings were obtained. 1) All 18 patients were male smokers, with an average of 64 years. 2) Body temperatures stood above 37 degrees C in 95% of the 19 episodes. Leukocytosis was detected in 41%, and neutrophilia was observed in 69%. CRP values were positive in all episodes. 3) The frequency of obstructive pneumonia according to the site of lung cancer was 13.2% in proximal tumors and 1.7% in peripheral tumors. Pathologically, the frequency was 5.2% in adenocarcinomas 7.6% in squamous cell carcinomas, 15.6% in small cell carcinomas and 9.1% in large cell carcinomas. Squamous cell carcinomas even in Stage I led to obstructive pneumonia at the rate of 13.0%. In contrast, higher frequency was observed in adenocarcinomas in Stage II or later and small cell carcinomas in Stage IIIB or later. 4) Obstructive pneumonia was detected at the time of discovery of lung cancer in 48% of the 18 patients, and during treatment and in the terminal stage in 26% respectively. 5) Chest X-ray examinations showed that 42% of the pneumonia cases were lobar pneumonia and 11% had pleural effusion. 6) In expectorated sputum, 50% of bacteria isolated were gram-negative, 10% were gram-positive and 40% were unknown. 7) Most of the bacteria isolated from expectorated sputum showed a good susceptibility to antimicrobial agents, but those proved clinically ineffective. 8) The prognosis of obstructive pneumonia was significantly affected by performance status and levels of total protein and choline-esterase.

Aged↗

Effects of antifungal agent combinations administered simultaneously and sequentially against Aspergillus fumigatus.

The in vitro effects of antifungal agent combinations administered simultaneously and sequentially against 15 strains of Aspergillus fumigatus were tested by the yeast-malt broth method. The synergistic effect of the combination of amphotericin B (AMPH) and miconazole was observed in nine strains (60%). However, the combinations of AMPH and fluconazole, AMPH and ketoconazole, and AMPH and itraconazole administered simultaneously showed antagonistic effects against three (20%), five (34%), and four (26%) strains, respectively. The effects of combinations of azole antifungal agents administered simultaneously were indifferent or antagonistic against A. fumigatus. In experiments measuring the effects of sequentially administered antifungal agents, however, pretreatment with AMPH and then azole antifungal agents exhibited better in vitro efficacy than that found in experiments measuring the effects of simultaneously administered AMPH and azole compounds.

Antifungal Agents↗

Comparative in vitro exoenzyme-suppressing activities of azithromycin and other macrolide antibiotics against Pseudomonas aeruginosa.

The inhibitory effects of azithromycin (AZM), a new 15-membered macrolide antibiotic, on the production of exotoxin A, total protease, elastase, and phospholipase C by Pseudomonas aeruginosa were determined, and the virulence-suppressing effects of AZM were compared with those of erythromycin (EM), roxithromycin (RXM), and rokitamycin (RKM). The effect of exposure of P. aeruginosa PA103 or B16 in cultures to sub-MICs of these macrolide antibiotics on the production of exoenzymes was determined. AZM suppressed the in vitro production of extracellular and intracellular exotoxin A by P. aeruginosa PA103 more than did EM, even at a concentration of only 2 micrograms/ml. At concentrations of between 4 and 32 micrograms/ml, AZM also inhibited total protease, elastase, and phospholipase C production by P. aeruginosa B16 more than did EM, RXM, and RKM. AZM was effective in suppressing exotoxin A and total protease production through 24 h of incubation in the presence of drug at sub-MICs, but it had no significant effect on either the growth of P. aeruginosa or its total protein production. Moreover, at a concentration of 4 micrograms/ml, AZM suppressed exoenzyme production by other strains of P. aeruginosa more than did EM. These findings indicate that AZM, EM, RXM, and RKM each has an inhibitory effect on exoenzyme production separate from the antimicrobial effect and that, of these macrolides, AZM has the strongest virulence-suppressing effect.

ADP Ribose Transferases↗

In vitro and in vivo activities of sparfloxacin against Mycoplasma pneumoniae.

The in vitro and in vivo activities of sparfloxacin against Mycoplasma pneumoniae were compared with those of erythromycin, levofloxacin, ofloxacin, and minocycline. The MICs of sparfloxacin, erythromycin, levofloxacin, ofloxacin, and minocycline for 90% of the 43 M. pneumoniae strains tested were 0.063, 0.016, 0.5, 1, and 0.5 microgram/ml, respectively. In the experimental pulmonary M. pneumoniae infection model in Syrian golden hamsters, sparfloxacin was as effective as erythromycin when orally administered at 15 mg/kg twice daily for 5 days and more effective than erythromycin when orally administered at 10 mg/kg once daily for 5 days. Sparfloxacin was more effective than levofloxacin and ofloxacin in both dosing regimens. The peak concentrations of sparfloxacin in hamster sera after administration of single oral doses of 15 mg/kg were almost the same as those in human sera after administration of single oral doses of 200 mg (the usual clinical dose), and the half-life of sparfloxacin in hamster serum was shorter than that in human serum after administration of a single oral dose of 200 mg. These results suggest that sparfloxacin may be clinically useful for the treatment of M. pneumoniae infections.

Animals↗

In vitro and in vivo activities of macrolides against Mycoplasma pneumoniae.

We investigated the in vitro and in vivo activities of macrolides against Mycoplasma pneumoniae. In vitro MICs of azithromycin, erythromycin, clarithromycin, and roxithromycin were determined. Azithromycin was the most potent antimicrobial agent tested in vitro. Its MIC for 90% of the strains was 0.00024 micrograms/ml. MICs for 90% of the strains of erythromycin, clarithromycin, and roxithromycin were 0.0156, 0.0078, and 0.03125 micrograms/ml, respectively. In vivo activities were assessed in a pulmonary infection model with Syrian golden hamsters. We evaluated the in vivo effects on reduction of viable M. pneumoniae cell counts and on reduction of microscopic and macroscopic histopathologies for azithromycin, erythromycin, and clarithromycin given at 10 mg/kg once daily for 1 and 3 days and given at 15 mg/kg twice daily for 2.5 and 5 days. Azithromycin was significantly more effective than erythromycin or clarithromycin in the same regimens. Especially at 10 mg/kg once daily for 1 day, only azithromycin was significantly effective in the reduction of viable M. pneumoniae cells and histopathologies. These results show that azithromycin is more efficacious than the other drugs tested against M. pneumoniae pneumonia in hamsters. These data suggest that clinical studies of macrolides in human patients are warranted.

Animals↗