Hideki Takahashi

Tokyo Metropolitan Geriatric Medical Center, Edo, Tōkyō, Japan

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Publications (22)36.07 Total impact

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    ABSTRACT: Nursing and healthcare-associated pneumonia (NHCAP) is a modified category of healthcare-associated pneumonia adjusted for the healthcare system of Japan. The clinical characteristics and risk factors for mortality have not been well characterized in elderly patients with NHCAP. We retrospectively investigated 960 consecutive patients aged ≥65 years admitted for pneumonia. Baseline characteristics, severity, pathogen distribution, outcomes and risk factors for mortality were compared between patients with community-acquired pneumonia (CAP) and those with NHCAP. The applicability of age, dehydration, respiratory failure, orientation disturbance, and low BP (A-DROP) score, a standard severity index for CAP in Japan, was also evaluated in NHCAP. The study participants consisted of 373 patients (38.8%) with CAP and 587 (61.2%) with NHCAP. The patients with NHCAP were older and had poorer performance status (PS) and more comorbidities than those with CAP. The frequency of potentially drug-resistant (PDR) pathogens and in-hospital mortality were found in 10 (2.7%) and 17 patients (4.6%) with CAP, and 60 (10.2%) and 83 patients (14.1%) with NHCAP, respectively (P < 0.0001). The incidences of PDR pathogens and mortality were not significantly different among the criteria for NHCAP. The higher mortality was associated with PS, comorbidity with Charlson Comorbidity Index ≥3, and the coexistence of congestive heart failure, chronic kidney disease and malignancy. A-DROP score was poor at predicting mortality in most patients with NHCAP. The current criteria for NHCAP seem to be appropriate for differentiating patients with poor outcomes from community-acquired pneumonia patients. It is essential to assess individual underlying conditions, such as PS and comorbidity, when caring for patients with NHCAP. Geriatr Gerontol Int 2013; ●●: ●●-●●.
    Geriatrics & Gerontology International 07/2013;
  • Mari Sasaki, Hideaki Mochizuki, Hideki Takahashi
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    ABSTRACT: A 26-year-old man visited our clinic because of a persistent cough. Although his chest roentgenography showed no abnormalities, a sputum culture revealed a positive result for Mycobacterium tuberculosis. Computed tomography (CT) prior to antituberculous chemotherapy demonstrated an esophagomediastinal fistula with subcarinal lymphadenopathy. One week after the treatment, he complained of a severe cough exacerbated by swallowing liquid. The development of a bronchoesophageal fistula (BEF) was suggested by esophagoscopy, and was confirmed by CT and bronchoscopy. The present case was unique because the process of BEF development could be followed by CT, and the BEF developed in an immunocompetent patient with relatively mild pulmonary tuberculosis.
    Internal Medicine 01/2013; 52(7):795-9. · 0.97 Impact Factor
  • Hideaki Mochizuki, Yuta Nanjo, Hideki Takahashi
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    ABSTRACT: Background:  Inhaled long-acting β2-agonists (LABA) are often poorly adhered to by elderly patients with chronic obstructive pulmonary disease (COPD). We hypothesized that older age and compromised cognitive function might contribute to poor adherence to inhaled medications among COPD patients, and that transdermally delivered medications could improve adherence, exercise tolerance and quality of life (QOL). Objective:  To compare adherence and effects on health outcomes between transdermal and inhaled LABA. Methods:  A total of 44 treatment-naïve, elderly Japanese patients with moderate-to-severe COPD were treated with a transdermal tulobuterol patch (TP; 2 mg, once a day) or inhaled salmeterol (50 µg, twice a day) in a randomized crossover manner. The primary outcomes were adherence to the LABA medications and changes in QOL measured by the St George's Respiratory Questionnaire. Secondary outcomes were changes in 6-min walk distance (6MWD) and spirometric values. Results:  The overall adherence rate was 90.3 ± 1.6% for TP and 75.5 ± 2.9% for salmeterol (P < 0.001). Adherence to salmeterol was correlated with age and Mini-Mental State Examination (MMSE) score (P < 0.05 and P < 0.01, respectively), although that to TP was relatively constant regardless of age and MMSE score. 6MWD and QOL were significantly improved from baseline after TP, but not after salmeterol treatment (P < 0.05). Similar degrees of increase in spirometric values occurred after treatment with TP and salmeterol. Conclusions:  Adherence levels were higher overall with TP than with inhaled salmeterol, and more stable across age groups and MMSE levels. TP might be a favorable treatment option for COPD patients with poor adherence to an inhaled LABA. Geriatr Gerontol Int 2012; ••: ••-••.
    Geriatrics & Gerontology International 07/2012;
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    ABSTRACT: Τhat β2-adrenergic receptor (β2AR) haplotypes may play a key role in clinical response to β2-agonists and haplotype Cys-19Gly16Gln27 (CysGlyGln) is reported to be associated with desensitization of β2AR to β-agonists in lymphocytes isolated from patients with asthma and septic shock. We sought to determine whether haplotypic variation of the β2AR affects the functional outcomes of long-acting β2-agonist (LABA) treatment for chronic obstructive pulmonary disease (COPD) when used as monotherapy. Treatment-naïve patients with COPD (n = 36) were prospectively treated with two kinds of LABA--inhaled salmeterol and transdermal tulobuterol patch--for 12 weeks in crossover study, and changes in pulmonary function data and 6-minute walk distance (6 MWD) were compared between groups stratified by the CysGlyGln. Frequencies of haplotype and diplotype for the CysGlyGln were 0.51 and 0.36, respectively. The individuals homozygous for CysGlyGln showed less improvement in FEV(1), %FEF(25-75 %), and IC/TLC than those with 0 or 1 copy of CysGlyGln after treatment with both LABAs despite initial bronchodilator responses to albuterol being similar in these groups. The response in these parameters was not significantly different between two types of LABA. Overall changes in 6 MWD in individuals with 2 copies of CysGlyGln versus 0 or 1 copy for salmeterol were 2.8 and 11 m, and for tulobuterol were -1.3 and 16 m, respectively. Homozygous haplotype for the CysGlyGln of β2AR may be associated with susceptibility to desensitization to LABA in patients with COPD.
    Beiträge zur Klinik der Tuberkulose 04/2012; 190(4):411-7. · 2.06 Impact Factor
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    ABSTRACT: An 84-year-old man was admitted with paresis of the right lower limb. Hemorrhagic lesions were demonstrated in the left frontoparietal lobe and cerebellum by cranial computed tomography (CT) and magnetic resonance imaging (MRI). Chest CT revealed an ill-defined mass measuring 4 x 6 cm in the left lower lobe of the lung, although bronchoscopic examination failed to obtain pathological diagnosis. Clinical diagnosis of primary lung cancer with multiple brain metastases was made, and he underwent whole brain radiotherapy. The pulmonary and cerebral lesions mimicked abscesses during his clinical course, and he died of respiratory failure due to bilateral pneumonia three months after admission. Autopsy revealed that both the pulmonary and brain lesions were malignant melanomas, but no other melanoma lesions could be identified despite meticulous investigation. Although malignant melanoma with an unknown primary site is rare in Japan, careful evaluation of the CT and MRI findings might be the key to correct diagnosis in this case.
    Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 06/2011; 49(6):472-7.
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    ABSTRACT: The optimal treatment for patients older than 80 years with small cell lung cancer (SCLC) is unknown. A retrospective chart review was conducted for 45 patients aged 80 years or older with SCLC, and therapeutic indices and toxicities of anticancer treatment were compared with those of 38 patients aged 70 to 79 years. Subgroup analyses according to the levels of performance status (PS) and comorbidity were also performed. Twenty-four (53%) of the 45 patients underwent combination chemotherapy and/or thoracic radiotherapy, which resulted in significant survival benefit compared with those left untreated (p < 0.01). The main reasons for not administrating anticancer treatments were advanced age (>85 years), poor PS, and severe comorbidities. The average total chemotherapy dose delivered was 60% of the intended protocol dose. Median survival time and 1-year survival of the treated patients were 13.0 months and 57% for limited disease and 10.3 months and 40% for extensive disease, respectively. Despite a lower chemotherapy dose being administered, survival indices were similar to those of patients aged 70 to 79 years. Survival benefit was observed even in the treated patients with PS 2 to 3 or a moderate degree of comorbidity compared with those left untreated. The frequency of grade 3 to 4 hematologic toxicities was not significantly different between the two age groups. The standard chemotherapy regimen with or without thoracic radiotherapy seems to be feasible for patients older than 80 years with SCLC, even for those with PS 2 to 3 and/or moderate comorbidity, although frequent dose adjustment is necessary.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 07/2010; 5(7):1081-7. · 4.55 Impact Factor
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    ABSTRACT: We report an 81-year-old man and a 65-year-old woman with a solitary pulmonary nodule (SPN) due to infection with non-tuberculous mycobacteria (NTM). In each case, the nodule showed a high (18)F-fluorodeoxyglucose (FDG) uptake with the maximum standardized uptake values (SUV) of 13.2 and 4.8 on positron emission tomography (PET) imaging, respectively. Both cases required partial lung resection for confirmation of the histological diagnosis. A review of six reported patients with SPN due to NTM infections showed that the SUV of FDG was more than 4.0 in the nodules of all cases. Positive results on FDG-PET should be interpreted cautiously when evaluating SPN, especially in patients having predisposing factors for NTM infections.
    Geriatrics & Gerontology International 07/2010; 10(3):251-4.
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    ABSTRACT: Clinical variables and laboratory data were compared to elucidate the risk factors associated with the development of ARDS among elderly patients with community-acquired pneumonia (CAP). The predictors for ARDS appeared to differ from the determinants of severity of CAP. ARDS developed less frequently among patients aged>or=85 years. The incidence of and risk factors for ARDS among elderly patients with community-acquired pneumonia (CAP) have not been well characterized. The clinical details of 221 consecutive patients aged>or=65 years, who were admitted with CAP during the period April 2006 to June 2008, were investigated by review of patient charts. Clinical variables and laboratory data at admission for CAP were compared between patients with and without ARDS. Eighteen patients (8.1%) developed ARDS 1-5 days after admission. The mortality rate was 44% in patients with ARDS and 10.3% in those without ARDS (P<0.001). The incidence of ARDS was 8.5-20% among patients aged<85 years and 1.1% in patients aged>or=85 years (P<0.001), while overall mortality rates were not significantly different among the age groups. Predictors for the development of ARDS included higher serum levels of CRP and glucose, lower PaO2/fraction of inspired O2 (FiO2), PaCO2 and HCO3-, and the presence of systemic inflammatory response syndrome at admission. ARDS developed less frequently among patients with pneumonia associated with oropharyngeal aspiration (AP). Multivariate analysis indicated that lower age, serum glucose, pre-existence of systemic inflammatory response syndrome and non-oropharyngeal AP were significant risk factors for ARDS. The Pneumonia Severity Index and confusion, urea, respiratory rate, blood pressure, age>or=65 score were not correlated with the incidence of ARDS. Predictors for ARDS appeared to differ from the determinants of severity of CAP in the elderly. ARDS developed less frequently in patients aged>or=85 years and in those with oropharyngeal AP. It is important to identify subjects at high risk for ARDS upon admission and to observe them closely.
    Respirology 02/2010; 15(2):319-25. · 2.78 Impact Factor
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    ABSTRACT: A 69-year-old woman with a right cervical lymphadenopathy presented with an adenocarcinoma on excisional biopsy. Computed tomography (CT) scans and a positron emission tomography scan demonstrated that the tumor was localized in the right paratracheal and cervical region. A clinical diagnosis of lung cancer arising from an unknown primary site was made based on the radiologic and immunohistochemical findings. Serial CT scans showed a growing nodule in the left apex from pinpoint size to 1 cm in diameter after several months, which was defined as the primary site at autopsy. The finding of a clinically occult lung cancer directly spreading to the contralateral mediastinal and cervical nodes by skipping ipsilateral hilar and mediastinal nodes is rare.
    Clinical Lung Cancer 08/2009; 10(4):249-51. · 2.04 Impact Factor
  • Journal of the American Geriatrics Society 06/2009; 57(5):919-20. · 3.98 Impact Factor
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    ABSTRACT: Little is known about the aetiology and clinical characteristics of COPD among people who have never smoked. A case-control study was conducted to describe the potential risk factors for clinically significant COPD among smokers and people who had never smoked. Medical record reviews and scoring of high-resolution computed tomography (HRCT) findings were performed in patients with clinically significant COPD (defined as having post-bronchodilator FEV(1)/FVC < 0.7 and FEV(1) < 60% of the predicted values). Pathological analyses were performed in some patients following autopsy. Among the 9493 subjects screened, 424 (4.5%) were diagnosed with clinically significant COPD. Forty-nine (11.6% of clinically significant COPD) were never smokers (NSCOPD), and a comparative group of 98 smoking patients with COPD was randomly selected (SMCOPD). NSCOPD was characterized by predominantly female sex (87.8%) and a high prevalence of physician-diagnosed asthma (61.2%). Similar levels of reduction in %FEV(1) and %FEF(25-75%) were found in NSCOPD and SMCOPD, but there were higher %DL(CO) values and fewer low attenuation areas on HRCT in NSCOPD. More than half of the NSCOPD patients without a history of asthma had features of asthma. More than one-third of NSCOPD patients with an asthma history had never had a severe attack. At autopsy, both NSCOPD and SMCOPD showed wall thickening and inflammatory cell infiltration in small airways, and the number of CD4(+)-T cells was increased in NSCOPD. In elderly Japanese, COPD among never smokers is largely attributable to asthma. Airflow limitation in NSCOPD results from small airway disease (airway predominant phenotype) rather than parenchymal destruction (emphysematous phenotype).
    Respirology 05/2009; 14(4):529-36. · 2.78 Impact Factor
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    ABSTRACT: A 69-year-old man was diagnosed as having syndrome of inappropriate secretion of antidiuretic hormone (SIADH) (serum sodium: 113 mEq/L) 13 days after a right upper lobectomy due to squamous cell carcinoma of the lung (pT1N0M0, stage IA) whereas the preoperative serum sodium level was nearly normal. He had undergone pleurodesis by instillation of OK432 at 2 and 5 days after surgery for prolonged air leakage. Since other possible causes of SIADH, such as residue of lung cancer, pulmonary infections, brain disorders, or known causative drugs were ruled out, the SIADH in this patient was likely associated with pleurodesis by the use of OK-432. A review of similar cases reported suggests that it is important to be aware of the possibility of severe hyponatremia due to SIADH after chemical pleurodesis.
    Internal Medicine 02/2009; 48(12):1069-71. · 0.97 Impact Factor
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    Circulation Research - CIRC RES. 01/2009; 104(10).
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    ABSTRACT: We report a case of bucillamine-induced interstitial pneumonia accompanied by severe hypoxemia in an 83-year-old woman who had rheumatoid arthritis. Respiratory failure worsened even after withdrawal of bucillamine and administration of high-dose corticosteroids, and mechanical ventilation was required. A review of 15 cases with bucillamine-induced pulmonary injury suggests that advanced age may be associated with the development of severe interstitial pneumonia. Bucillamine can cause corticosteroid-resistant and life-threatening lung injury, especially in the elderly.
    Modern Rheumatology 06/2008; 18(5):522-5. · 1.72 Impact Factor
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    ABSTRACT: Angiopoietins, newly discovered vascular-specific growth factors, and vascular endothelial growth factors (VEGF) play distinct and complementary roles in angiogenesis and vascular maturation. However, the exact roles of angiogenic factors in the adult pulmonary vasculature remain unclear. To elucidate possible roles of angiopoietins and VEGF in the development of hypoxic pulmonary hypertension (PH), changes in the expression of angiogenic factors were examined. The cellular distribution and expression of angiopoietins and their receptor Tie2 and VEGF were investigated by RT-PCR, immunoblot, and immunohistochemical methods in rat lung under normal and hypoxic conditions. During the development of PH with vascular remodeling characterized by a decrease in vessel density of intrapulmonary arteries, protein expression of angiopoietin-1 (Ang-1), Tie2, and VEGF significantly decreased in the pulmonary arteries, and Tie2 receptor was inactivated in the lung. The expression of angiopoietin-3 (Ang-3), an endogenous antagonist of Ang-1, significantly increased in the intima under hypoxic conditions. Since both Ang-1/Tie2 and VEGF promote angiogenesis and vascular survival, and play protective roles in the adaptation of microvascular changes during the onset of PH, the downregulation of both Ang-1/Tie2 and VEGF and upregulation of Ang-3 appear to be associated with vascular rarefaction and the development of hypoxic PH.
    Respiration 02/2008; 75(3):328-38. · 2.62 Impact Factor
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    ABSTRACT: The mechanism of endothelium-dependent vasodilator signaling involves three components such as nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factor (EDHF). Although EDHF is distinct from nitric oxide and prostacyclin, it requires activation of Ca(2+)-sensitive K(+) channels (K(Ca)) and cytochrome P(450) metabolites. However, the physiological role of EDHF in the pulmonary circulation is unclear. Thus, we tested if EDHF would regulate vascular tone in rat lungs of control and monocrotaline (MCT)-induced pulmonary hypertension. Inhibition of EDHF with a combination of K(Ca) blockers, charybdotoxin (50 nM) plus apamin (50 nM), increased baseline vascular tone in MCT-induced hypertensive lungs. Thapsigargin (TG; 100 nM), an inhibitor of Ca-ATPase, caused greater EDHF-mediated vasodilation in MCT-induced hypertensive lungs. TG-induced vasodilation was abolished with the charybdotoxin-apamin combination. Sulfaphenazole (10 muM), a cytochrome P(450) inhibitor, reduced the TG-induced vasodilation in MCT-induced hypertensive lungs. RT-PCR analysis exhibited an increase in K(Ca) mRNA in MCT-treated lungs. These results indicate the augmentation of tonic EDHF activity, at least in part, through the alteration in cytochrome P(450) metabolites and the upregulation of K(Ca) expression in MCT-induced pulmonary hypertension.
    Journal of Vascular Research 02/2007; 44(4):325-35. · 2.43 Impact Factor
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    ABSTRACT: We report a case of angiosarcoma complicated by bilateral massive bloody pleurisy (hematocrit of 7.2%) in an 83-year-old woman. An autopsy revealed hemorrhagic tumors infiltrating both the diaphragm and serosal surface of the peritoneum. Histological examination confirmed an anastomosing vascular channel pattern of the tumor cells with characteristic immunohistochemical findings for angiosarcoma, such as positive staining for vimentin, CD31, CD34, D2-40, and factor VIII-related antigen. The tumor was thought to have originated from a small vessel on the serosal surface of the duodenum. We also reviewed cases of hemothorax associated with angiosarcoma, which suggested that primary or metastatic pleural angiosarcoma should be considered a cause of spontaneous hemothorax, especially in patients with bilateral and/or intractable hemothorax.
    Internal Medicine 02/2007; 46(3):125-8. · 0.97 Impact Factor
  • Internal Medicine - INTERNAL MED. 01/2007; 46(3):125-128.
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    ABSTRACT: Heterozygous mutations in the type II receptor for bone morphogenetic protein (BMPR-II) and dysfunction of BMPR-II have been implicated in patients with primary pulmonary hypertension (PH). To clarify the possible involvement of BMP and BMPR-II in the development of hypoxic PH, the expression of BMP-2, BMPR-II, and their downstream signals were investigated in rat lung under normal and hypoxic conditions by RT-PCR, immunoblot, and immunohistochemical methods. In rats under normal conditions, BMP-2 is localized in the endothelium of the pulmonary artery, whereas BMPR-II is abundantly expressed in the endothelium, smooth muscle cells, and adventitial fibroblasts. After 0.5 and 3 days of exposure to hypoxia, upregulation of BMP-2 was observed in the intrapulmonary arteries. The change was accompanied by activation of its downstream signaling, p38 MAPK, and Erk1/2 MAPK, and the apoptotic process, measured by caspase-3 activity and TdT-mediated dUTP nick end labeling-positive cells. In contrast, a significant decrease in the expression of BMPR-II and inactivation of p38 MAPK and caspase-3 were observed in the pulmonary vasculature after 7-21 days of hypoxia exposure. Because BMP-2 is known to inhibit proliferation of vascular smooth muscle cells and promote cellular apoptosis, disruption of BMP signaling pathway through downregulation of BMPR-II in chronic hypoxia may result in pulmonary vascular remodeling due to the failure of critical antiproliferative/differentiation programs in the pulmonary vasculature. These results suggest abrogation of BMP signaling may be a common molecular pathogenesis in the development of PH with various pathophysiological events, including primary and hypoxic PH.
    AJP Lung Cellular and Molecular Physiology 04/2006; 290(3):L450-8. · 3.52 Impact Factor
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    ABSTRACT: Pulmonary hypertension is characterized by high pulmonary blood pressure, vascular remodeling, and right ventricular hypertrophy. Although recent studies suggest that an imbalance between endothelial mediators on pulmonary vasculature may contribute to the development of pulmonary hypertension, the pathogenesis is not fully understood and the treatment of pulmonary hypertension is still unresolved. The purpose of this study was to investigate whether genistein, a phytoestrogen derived from soybean, would prevent the development of monocrotaline (MCT)-induced pulmonary hypertension in rats. Hemodynamic parameters of catheterized rats and morphological feature of lungs were evaluated among MCT-treated rats receiving or not receiving genistein. Furthermore, examination of expression in endothelial nitric oxide synthase and endothelin-1 peptide level was performed. Daily supplementation with either genistein (0.2 mg/kg) or vehicle was started 2 days prior to a single-dose injection of MCT (60 mg/kg). On day 28, rats underwent catheterization, and right ventricular hypertrophy and morphological features were assessed. Furthermore, endothelial nitric oxide synthase and endothelin-1 were examined by Western blot analysis and radioimmunoassay, respectively, in homogenated lungs. In rats that received daily supplementation of genistein, mean pulmonary arterial pressure was significantly reduced, whereas mean systemic arterial pressure and heart rate were unaltered compared with MCT control rats on day 28 after MCT injection. Right ventricular hypertrophy, medial wall thickness of pulmonary arteries corresponding to the terminal bronchioles, and the degree of neo-muscularization of more distal arteries were less severe in genistein-treated rats. Genistein supplementation improved MCT-induced downregulation of expression of endothelial nitric oxide synthase in the lungs. However, endothelin-1 peptide levels did not differ among all groups of lungs. We conclude that daily supplementation of genistein potently attenuates MCT-induced pulmonary hypertension, right ventricular hypertrophy, and pulmonary vascular remodeling in rats. The underlying mechanism responsible for this effect may be partly related to the restoration of a decreased expression of endothelial nitric oxide synthase.
    Respiration 02/2006; 73(1):105-12. · 2.62 Impact Factor