Yasuhito Higashiyama

Nagasaki University Hospital, Nagasaki, Nagasaki, Japan

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Publications (71)113.06 Total impact

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    ABSTRACT: In the autumn two patients with general malaise were consecutively admitted to the department of internal medicine of our hospital in the northern region of Nagasaki Prefecture. Since both patients were engaged in rice farm work and showed conjunctival suffusion and pain of the gastrocnemius muscle, leptospirosis was suspected. The first patient required temporary hemodialysis for renal dysfunction, whereas liver dysfunction developed in the second patient. The disease was remitted by antimicrobial agents. A diagnosis of leptospirosis was made serologically in both patients. Leptospirosis should be considered as a differential diagnosis when a patient engaged in farm work in the autumn has typical symptoms, and an early initiation of treatment after onset is important.
    Internal Medicine 01/2010; 49(12):1143-7. · 0.97 Impact Factor
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    ABSTRACT: A novel, rapid, and noninvasive test (ODK0501) to detect Streptococcus pneumoniae antigen was evaluated in a Japanese multicenter study. ODK0501 uses polyclonal antibodies to detect C polysaccharide of S. pneumoniae from sputum samples by an immunochromatographic assay. The utility of ODK0501 was evaluated for 161 adult patients with lower respiratory tract infection between March 2006 and March 2007. Bacterial culture and identification, real-time PCR, and ODK0501 assays were performed on sputum samples, and the Binax Now Streptococcus pneumoniae antigen test was performed using urine samples obtained from the same patients. The performances of all tests were compared based on the results of bacterial culture and identification. The sensitivity and specificity of ODK0501 were 89.1% (49/55 samples) and 95.3% (101/106 samples), respectively. We then compared the Binax Now Streptococcus pneumoniae antigen test with ODK0501 using samples from 142 patients. The sensitivities of ODK0501 and the Binax Now S. pneumoniae antigen test were 90.0% (45/50 samples) and 62.0% (31/50 samples), respectively (P = 0.002). The relative quantity of S. pneumoniae in expectorated sputum was calculated using real-time PCR and indicated that the possibility of false-positive results for ODK0501 due to indigenous S. pneumoniae was low. The positive and negative concordance rates of ODK0501 and Binax Now were 96.8% (30/31 samples) and 21.1% (4/19 samples), respectively. Binax Now was less capable of detecting S. pneumoniae antigen among patients with underlying chronic obstructive pulmonary disease. In conclusion, ODK0501 is noninvasive, rapid, and an accurate tool for diagnosing respiratory infection caused by S. pneumoniae.
    Clinical and vaccine Immunology: CVI 04/2009; 16(5):672-8. · 2.60 Impact Factor
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    ABSTRACT: To evaluate the clinical usefulness of piperacillin (4 g/day) therapy for community-acquired pneumonia compared to sulbactam/ampicillin (6 g/day). A randomized prospective clinical study was conducted in patients with mild to severe community-acquired bacterial pneumonia. The overall clinical efficiency of piperacillin therapy (4 g/day) in these patients (41/53=77.4%) was comparable to that of sulbactam/ampicillin therapy (6 g/day: efficiency rate: 33/49=67.3%), when each therapy was administered intravenously for 3-7 days. With regards to clinical efficiency based on disease severity, bacteriological efficiency, improvement in chest X-ray findings and adverse reactions, the two therapies were comparable, even though we found more efficiency for patients who had underlying diseases and there were also cost benefits in piperacillin therapy, compared with sulbactam/ampicillin therapy The results suggested that piperacillin therapy has good efficiency and tolerability and that it may be highly effective, even in cases of pneumonia with underlying diseases. This regimen may thus serve as a first line treatment of community-acquired pneumonia.
    Internal Medicine 02/2009; 48(1):49-55. · 0.97 Impact Factor
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    ABSTRACT: Biofilms play an important role in the establishment of chronic infection caused by Pseudomonas aeruginosa. It has been suggested that membrane vesicles (MVs) are released into the surrounding medium during normal growth and might supply the bacterial extracellular DNA that is required for early biofilm formation, as MVs released from the bacterial outer membrane are suspected to be the source of extracellular DNA. MVs possess lipopolysaccharide (LPS), extracellular DNA, and several hydrolytic enzymes. It is well known that the quorum-sensing (QS) system is important in controlling virulence factors in P. aeruginosa and biofilm formation. In the current study, we investigated extracellular LPS and DNA in the supernatants of culture solutions from PAO1, the wild-type P. aeruginosa, and those of QS mutants. As compared to that of las QS mutants, the amount of LPS and DNA released was significantly higher in PAO1 and in las QS mutants complemented with N-(3-oxododecanoyl) homoserine lactone. Our study indicated that the QS is among the regulators involved in the release of extracellular DNA and LPS. It is possible that these extracellular components are supplied from MVs. Investigation of the mechanism of biofilm formation is of particular interest, as it may be useful for designing treatments for severe P. aeruginosa infection.
    Japanese journal of infectious diseases 10/2008; 61(5):375-8. · 1.51 Impact Factor
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    ABSTRACT: Accumulating evidence has suggested the involvement of HTLV-1 in the inflammatory lesions of various organs, including the lung. However, the causal relationship between HTLV-1 and inflammatory responses in the organs remains to be elucidated. In order to evaluate the expression of HTLV-1 and its effects in the lung, we examined the expression of mRNA for the HTLV-1 tax/rex gene in fresh bronchoalveolar lavage cells (BALC) and peripheral blood mononuclear cells (PBMC) of 23 seropositive individuals, including six patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), by use of an improved method of reverse transcription-polymerase chain reaction (RT-PCR). The tax/rex mRNA was more frequently detected in BALC than in PBMC. All the HAM/TSP patients and eight of 17 carriers without neurological symptoms showed the expression of tax/rex mRNA in the BALC. IgM class antibodies to HTLV-1 were preferentially detected in sera of the tax/rex mRNA-positive individuals. The detection of tax/rex mRNA correlated closely with the presence of lymphocytosis accompanied by an elevated proportion of IL-2 receptor-bearing T cells in the BALC. Our findings indicate the crucial role of viral expression in the inflammatory response in the lung in HTLV-1-infected individuals.
    Clinical & Experimental Immunology 01/2008; 96(2):193-201. · 3.41 Impact Factor
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    ABSTRACT: The recommended treatments for Mycobacterium avium complex (MAC) infectious disease are combination regimens of clarithromycin (CLR) or azithromycin with ethambutol and rifamycin. However, these chemotherapy regimens are sometimes unsuccessful. Recently developed antimicrobial agents, such as newer fluoroquinolones (FQs) containing C-8 methoxy quinolone (moxifloxacin [MXF] and gatifloxacin [GAT]), are expected to be novel antimycobacterial agents. Here, we evaluated the in vitro and in vivo antimycobacterial activities of three FQs (MXF, GAT, and levofloxacin) and CLR against clinically isolated MAC strains. Subsequently, the in vitro and in vivo synergic activities of FQ-CLR combinations against MAC strains were investigated. CLR and the individual FQs alone showed promising activity against MAC strains in vitro, and the bacterial counts in organs (lungs, liver, and spleen) of MAC-infected mice treated with single agents were significantly reduced compared to control mice. CLR showed the best anti-MAC effect in vivo. When the three FQs were individually combined with CLR in vitro, mild antagonism was observed for 53 to 57% of the tested isolates. Moreover, mice were infected with MAC strains showing mild antagonism for FQ-CLR combinations in vitro, and the anti-MAC effects of the FQ-CLR combinations were evaluated by counting the viable bacteria in their organs and by histopathological examination after 28 days of treatment. Several FQ-CLR combinations exhibited bacterial counts in organs significantly higher than those in mice treated with CLR alone. Our results indicate that the activity of CLR is occasionally attenuated by combination with an FQ both in vitro and in vivo and that this effect seems to be MAC strain dependent. Careful combination chemotherapy using these agents against MAC infectious disease may be required.
    Antimicrobial Agents and Chemotherapy 12/2007; 51(11):4071-6. · 4.57 Impact Factor
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    ABSTRACT: Over the course of 11 years (1993-2003) we encountered 5 cases of pulmonary nontuberculous mycobacterium (NTM) involving a solitary pulmonary nodule. In this report we analyze the chest computed tomography (CT) of these patients, the utility of bronchoscope and transthoracic fine-needle aspiration techniques, the mycobacterium species involved, and treatment results. Four of the 5 NTM cases were due to infection with M. avium and one was due to infection with M. intracellulare. The characteristic findings of the chest CTs were as follows: A solitary nodule was present just under the pleura. No definite distribution pattern was evident. Some cases had agglutinated nodules or fine calcifications. Although fiberoptic bronchoscopy was not used as a diagnostic tool in all 5 NTM cases and histological samples did not contain granulomas, we determined the presence of NTM and we also verified that no cancer cells were present in any of the 5 NTM patients, using transthoracic fine-needle aspiration. Four out of the 5 NTM patients were treated only with drug therapy and they displayed clinical improvement. We resected a solitary nodule in one of the 5 NTM patients because of slow response to drug therapy. We conclude that the solitary pulmonary nodule of NTM is often due to M. avium and that transthoracic fine-needle aspiration is an easy and effective method of detecting NTM.
    Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 10/2007; 45(9):655-60.
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    ABSTRACT: A 79-year-old woman was admitted to the Department of Orthopedics Surgery for treatment of osteoarthritis in her knee. Multiple pulmonary nodular lesions were found on preoperative chest x-ray film screening. Metastatic lung tumor was suspected, but no tumorous lesions were detected in other organs. CT guided lung biopsy was performed. Histopathological examination revealed amyloid consisting of homogenous eosinophilic materials. No amyloid deposits were detected in other organs, so we diagnosed localized nodular pulmonary amyloidosis. She was subsequently given a diagnosis of primary Sjögren syndrome. We believe that such a case of multiple nodular pulmonary amyloidosis with Sjögren syndrome is rare, and the case showed interesting radiological findings, such as mimicking metastatic lung tumor.
    Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 05/2007; 45(4):356-60.
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    ABSTRACT: To determine the differences in the clinical features of bacterial pneumonia patients between patients co-infected with influenza virus or not co-infected. Fifteen adult patients with bacterial pneumonia (7 men and 8 women) who also tested positive for influenza virus antigen were compared with those with bacterial pneumonia alone (n=28). Complications with chronic lung diseases were more frequently found in bacterial pneumonia patients with influenza virus infection, compared with those who had bacteria pneumonia alone. Statistical differences were also found in body temperature, and heart rates between the two groups. CRP levels, chest X-ray infiltrates and the severity of pneumonia, as determined using the criteria of the Japan Respiratory Society (JRS) and/or the Infectious Diseases Society of America (IDSA), were also significantly worse in patients of bacterial pneumonia infected with influenza virus, than in those who had bacterial pneumonia alone. The severity of pneumonia in patients co-infected with influenza virus and bacteria was significantly higher than in those infected with bacteria alone. These data suggested that the influenza virus infection enhanced the bacterial pneumonia. Further study of the pathogenesis of the synergic interaction between influenza virus and bacteria is warranted.
    Internal Medicine 02/2007; 46(13):953-8. · 0.97 Impact Factor
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    ABSTRACT: We wished to assess the clinical differences between beta-lactamase-negative, ampicillin-sensitive and beta-lactamase-negative, ampicillin-resistant Haemophilus influenzae pneumonia. The medical records of 118 patients with H. influenzae pneumonia admitted between March 1998 and March 2003 to Nagasaki University Hospital and affiliated institutions were reviewed. In line with CLSI (Clinical and Laboratory Standards Institute) criteria, we classified H. influenzae according to sensitivity to ampicillin as follows: S (sensitive), minimum inhibitory concentration (MIC) =1; I (intermediate sensitivity), MIC =2; R (resistant), MIC =4. We defined the R strains as the BLNAR group and the S and I strains as the non-BLNAR group. We measured the patient's background, Pneumonia Severity Index (PSI), drug sensitivity of H. influenzae, and evaluation of antibiotic choices. There were no significant clinical differences between the beta-lactamase-negative, ampicillin-susceptible and the beta-lactamase-negative, ampicillin-resistant groups. However, BLNAR pneumonia was more prominent in the younger than the older patients. This study should provide useful information for understanding the clinical characteristics of BLNAR pneumonia.
    Scandinavian Journal of Infectious Diseases 02/2007; 39(6-7):521-4. · 1.71 Impact Factor
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    ABSTRACT: The 14-membered macrolides, such as clarithromycin (CAM) and erythromycin (EM), are effective against diffuse panbronchiolitis. However, there have been no studies on the effects of telithromycin (TEL) on chronic respiratory infection in vivo. In this study, we determined the effect of TEL on an experimental murine model of chronic respiratory infection caused by Pseudomonas aeruginosa with biofilm formation. TEL significantly reduced the number of viable bacteria but had no effect on the proliferation of lymphocytes. In contrast, CAM decreased the number of lymphocytes but had no effect on the number of viable bacteria in the lung. These results suggest that TEL and CAM have different effects on chronic respiratory infection caused by P. aeruginosa.
    Chemotherapy 02/2007; 53(1):10-3. · 2.07 Impact Factor
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    ABSTRACT: Nocardia is typically regarded as an opportunistic infection, with pulmonary nocardiosis frequently disseminated to organs hematogenous by, and nearly half of these cases resulting in complicated nocardia brain abscess. Disseminated nocardia has a dismal prognosis with high mortality, and should be checked for multiple organs including the brain when nocardiosis is diagnosed. We describe the successful treatment of nocardia brain abscesses in an immunocompetent older people with pneumoconiosis by combining trimethoprim-sulfamethoxazole and ciprofloxacin. Patients had no history of fever, headache, or respiratory symptoms such as cough, or sputum until the acute hemiplegia episode. Nocardia infection is not as rare as generally assumed and should be considered as a possibility in the elderly due to its high mortality.
    Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases 12/2006; 80(6):721-5.
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    ABSTRACT: In this study, the potency of DX-619, a novel des-fluoro(6)-quinolone agent, was compared with that of vancomycin (VCM) in a murine model of haematogenous bronchopneumonia infection caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-intermediate S. aureus (VISA). The minimum inhibitory concentrations (MICs) of DX-619 and VCM against MRSA were 0.03 microg/mL and 1.0 microg/mL, respectively, whilst the MICs against VISA were 0.125 microg/mL and 8.0 microg/mL, respectively. Treatment with DX-619 resulted in a significant decrease in the number of viable bacteria in the MRSA infection model (mean+/-standard error of the mean for control, VCM and DX-619 groups: 7.97+/-0.32, 7.19+/-0.33 and 2.91+/-0.60 log(10) colony-forming units/lung, respectively). For infection with VISA, mice were pre-treated with cyclophosphamide. The survival rate of mice treated with DX-619 (90% survival) was significantly higher than survival rates in the other two groups (45% both for VCM and control groups; P<0.05). Histopathological examination revealed that inflammatory changes in the DX-619-treated group were less marked than in the other two groups. The parameters in lung tissue for the area under the concentration-time curve/MIC ratio both for MRSA and VISA were higher in the DX-619 group than in the VCM group. Our results emphasise the potency of DX-619 against MRSA and VISA murine haematogenous pulmonary infection.
    International Journal of Antimicrobial Agents 09/2006; 28(3):212-6. · 4.42 Impact Factor
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    ABSTRACT: To clarify the discrepancy between increasing resistance and conservative clinical effects of macrolides on macrolide-resistant Streptococcus pneumoniae, the authors evaluated the effects of sub-minimum inhibitory concentrations of macrolides on pneumolysin. In vitro, S. pneumoniae was incubated with 1, 2 and 4 microg.mL(-1) of clarithromycin (CLR) and azithromycin (AZM) for 8 h. Western blot analysis and haemolytic assay were performed to examine the production and activities of pneumolysin. In vivo, mice were infected with S. pneumoniae intra-nasally and treated with CLR (40 or 200 mg.kg(-1) twice daily) or AZM (40 or 200 mg.kg(-1) once daily) orally for 7 days. After 72 h post-infection, western blot analysis was performed to examine pneumolysin production in lungs. Survival rates were observed for 10 days. In vitro, every concentration of macrolide inhibited pneumolysin production more than the control. CLR (2 and 4 microg.mL(-1)) and AZM (4 microg.mL(-1)) reduced the pneumolysin activities more than the control. In vivo, macrolides (200 mg.kg(-1)) reduced pneumolysin in murine lungs more than the control. CLR (40 and 200 mg.kg(-1)) and AZM (200 mg.kg(-1)) improved the survival rates more than the control. The study results show that sub-minimum inhibitory concentrations of macrolides reduced pneumolysin. This might be related to the effectiveness of macrolides against pneumonia caused by high-level macrolide-resistant Streptococcus pneumoniae. Further investigations are necessary to evaluate the effects of macrolides on macrolide-resistant Streptococcus pneumoniae.
    European Respiratory Journal 06/2006; 27(5):1020-5. · 6.36 Impact Factor
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    ABSTRACT: Mycobacterium nonchromogenicum is generally considered nonpathogenic. However, M. nonchromogenicum rarely causes human disease; particularly, pulmonary disease is extremely rare. The common finding of M. nonchromogenicum pulmonary infection on chest X-ray is a solitary cavity. The present report describes an unusual case of M. nonchromogenicum primary pulmonary infection showing multiple nodular shadows.
    Diagnostic Microbiology and Infectious Disease 05/2006; 54(4):311-4. · 2.26 Impact Factor
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    ABSTRACT: A 77 years old woman who had a bite with eschar on her left arm, was admitted to emergency ward in our hospital, because of high fever, severe malaise, skin eruption, and consciousness disturbance beginning 5 days previously. She was diagnosed as Japanese spotted fever by seropositive of Rickettsia japonica (R. japonica) antibody, and successfully treated with fluoroquinolone, after minocycline hydrochloride had been proven ineffective. R. japonica-specific DNA was detected by PCR from the tick: Haemaphysalis hystricis larvae collected from a mountainous location in Fukuoka, Japan where the patient had been bitten.
    Internal Medicine 02/2006; 45(22):1323-6. · 0.97 Impact Factor
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    ABSTRACT: To evaluate the clinical usefulness of sulbactam/ampicillin therapy for community-acquired pneumonia in the elderly. A randomized prospective clinical study was conducted in the elderly patients with moderate-to-severe community-acquired bacterial pneumonia. Overall clinical efficacy of sulbactam/ampicillin therapy (6 g/day) in these patients (efficacy rate: 91.4%) was comparable to that of imipenem/cilastatin therapy (1 g/day; efficacy rate: 87.5%), when each therapy was administered intravenously twice daily for 7-14 days. With regard to clinical efficacy based on disease severity, bacteriological efficacy, improvement of chest X-ray findings and adverse reactions, the two therapies were comparable. These results suggest that sulbactam/ampicillin therapy has excellent efficacy and tolerability and that it may be highly effective, even in severe cases of pneumonia. This regimen may thus serve as first-line treatment for the treatment of community-acquired pneumonia in elderly patients.
    Internal Medicine 02/2006; 45(17):995-9. · 0.97 Impact Factor
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    ABSTRACT: We studied the quorum sensing (QS) system and the related homoserine lactones (HSLs) observing Pseudomonas aeruginosa invasion using the epithelial cell monolayer penetration assay model. Compared to the PAO1 wild-type, the QS mutants, DeltalasI and DeltarhlI, were compromised in their capacity to invade. The decreased invasiveness of DeltarhlI was restored by adding 100 microM exogenous C(4)-HSL. However, the decreased invasiveness of an efflux mutant, DeltamexAB-oprM, was not restored in the presence of exogenous HSLs. The QS system partially plays a role in P. aeruginosa invasion; however, C(4)-HSL and 3-O-C(12)-HSL are not the essential determinants for invasiveness for P. aeruginosa.
    Microbiology and Immunology 02/2006; 50(5):395-401. · 1.55 Impact Factor
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    ABSTRACT: DX-619 is a novel des-fluoro(6) quinolone with potent activity against gram-positive pathogens. The in vivo activity of DX-619 against Streptococcus pneumoniae was compared with those of fluoro(6) quinolones, sitafloxacin, and ciprofloxacin in a mouse model. Two strains of S. pneumoniae were used: a penicillin-sensitive S. pneumoniae (PSSP) strain and a penicillin-resistant S. pneumoniae (PRSP) strain. Furthermore, these strains showed intermediate susceptibilities to ciprofloxacin. In murine lung infections caused by PSSP, the 50% effective doses (ED50s) of DX-619, sitafloxacin, and ciprofloxacin were 9.15, 11.1, and 127.6 mg/kg of body weight, respectively. Against PRSP-mediated pneumonia in mice, the ED50s of DX-619, sitafloxacin, and ciprofloxacin were 0.69, 4.84, and 38.75 mg/kg, respectively. The mean +/- standard error of the mean viable bacterial counts in murine lungs infected with PSSP and treated with DX-619, sitafloxacin, ciprofloxacin (10 mg/kg twice daily), and saline (twice daily) were 1.75 +/- 0.06, 1.92 +/- 0.23, 6.48 +/- 0.28, and 7.57 +/- 0.13 log10 CFU/ml, respectively. Furthermore, the numbers of viable bacteria in lungs infected with PRSP and treated with the three agents and not treated (control) were 1.73 +/- 0.04, 2.28 +/- 0.17, 4.61 +/- 0.59, and 5.54 +/- 0.72 log10 CFU/ml, respectively. DX-619 and sitafloxacin significantly decreased the numbers of viable bacteria in the lungs compared to the numbers in the lungs of ciprofloxacin-treated and untreated mice. The pharmacokinetic parameter of the area under the concentration-time curve (AUC)/MIC ratio in the lungs for DX-619, sitafloxacin, and ciprofloxacin were 171.0, 21.92, and 1.22, respectively. The AUC/MIC ratio in the lungs was significantly higher for DX-619 than for sitafloxacin and ciprofloxacin. Our results suggest that DX-619 and sitafloxacin are potent against both PSSP and PRSP in our mouse pneumonia model.
    Antimicrobial Agents and Chemotherapy 02/2006; 50(1):121-5. · 4.57 Impact Factor
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    ABSTRACT: An 88-year old man was admitted to our hospital because of severe respiratory disturbance and fever, but no sputum. We found diffuse reticular shadow on chest X-ray, and detected influenza virus antigen from nasopharyngeal swab. Primary influenza pneumonia was suspected and oseltamivir was prescribed. Data were improved after adding steroid; however, hemoptysis appeared on day 9, and the patient died 2 days later. We suspected the recurrence of primary virus pneumonia with alveolar damage, but Staphylococcus aureus was cultured from the hemosputum after his death despite oral administration of antibiotics. Subsequent secondary bacterial pneumonia as well as severe primary influenza virus pneumonia was finally suspected in this case. It was a rare case that not only fulminant primary virus pneumonia but also different type of severe influenza pneumonia were found in one patient. We need to observe influenza patients carefully, even if antibiotics were administered
    01/2006;

Publication Stats

469 Citations
113.06 Total Impact Points

Institutions

  • 1991–2010
    • Nagasaki University Hospital
      Nagasaki, Nagasaki, Japan
  • 2009
    • Japanese Red Cross Nagasaki Genbaku Isahaya Hospital
      Isahara, Nagasaki, Japan
  • 2004–2009
    • Nagasaki University
      • • Department of Internal Medicine
      • • Department of Laboratory Medicine
      • • School of Medicine
      Nagasaki-shi, Nagasaki-ken, Japan
  • 2004–2007
    • University Hospital Medical Information Network
      Edo, Tōkyō, Japan