Naohiko Hamaguchi

Comparative Evaluation of Serum Markers in Pulmonary Sarcoidosis

BACKGROUND Although several serum markers have shown their ability to reflect lymphocytic alveolitis and disease progression in pulmonary sarcoidosis, to our knowledge no prior study has made comparative evaluations of these markers. METHODS Forty-three patients with pulmonary sarcoidosis were enrolled. BAL fluid (BALF) cells were analyzed, and serum levels of serum amyloid A (SAA), soluble interleukin 2 receptor (sIL-2R), lysozyme, angiotensin-converting enzyme (ACE), and the mucin-like, high-molecular-weight glycoprotein KL-6 were measured at disease presentation. Clinical data, including chest radiographs, were collected at presentation and during follow-ups. Univariate and multivariate analyses were used to identify markers best predictive of increased parenchymal infiltration. RESULTS Significantly higher serum levels of sIL-2R, lysozyme, and KL-6 were found in patients with parenchymal infiltration compared with those without parenchymal infiltration. The numbers of total cells and lymphocytes in BALF were significantly higher in patients with parenchymal infiltration. Serum levels of sIL-2R, lysozyme, and KL-6 were significantly correlated with the numbers of total cells, lymphocytes, and CD4(+) T lymphocytes in BALF. At the cutoff levels determined by receiver operating characteristic curves, sIL-2R, lysozyme, KL-6 serum levels, and the number of BAL lymphocytes showed significant correlations with increased parenchymal infiltrations by univariate analysis. However, multivariate analysis revealed that only KL-6 was a predictor of increased parenchymal infiltration. CONCLUSION Our results suggest that initial serum sIL-2R, lysozyme, and KL-6 levels may reflect lymphocytic alveolitis in pulmonary sarcoidosis. Furthermore, initial serum KL-6 tends to associate with increased parenchymal infiltration in pulmonary sarcoidosis.

In vitro and in vivo therapeutic efficacy of the PPAR‐γ agonist troglitazone in combination with cisplatin against malignant pleural mesothelioma cell growth

Malignant pleural mesothelioma (MPM), an aggressive and refractory tumor type, is increasing in frequency throughout the world. Peroxisome proliferator activated receptor‐γ (PPAR‐γ) agonists have anticancer activity against several cancer cell lines in vitro and in vivo. However, there have been no reports that PPAR‐γ agonists induce growth inhibition of MPM cell lines. In this study, we investigated the inhibitory effect of a PPAR‐γ agonist in combination with an anticancer agent on MPM cell growth in vitro and in vivo. We examined the therapeutic efficacy of the PPAR‐γ agonist troglitazone (TGZ) in combination with cisplatin against a human MPM cell line, both in vitro and orthotopically inoculated into severe combined immunodeficient (SCID) mice. Troglitazone (TGZ) alone inhibited MPM cell growth in vitro in a dose‐dependent manner via induction of G1 cell cycle arrest and apoptosis. The combination of TGZ and cisplatin showed an additive inhibitory effect on MPM cell growth compared to treatment with either individual drug. Treatment with 500 mg/kg or 1000 mg/kg TGZ effectively inhibited the production of thoracic tumors and pleural effusion in EHMES‐10 cell‐bearing SCID mice. Moreover, treatment with 500 mg/kg TGZ in combination with 3 mg/kg cisplatin more effectively prolonged survival compared to treatment with either individual drug. These results suggest that TGZ in combination with cisplatin may become a novel therapy for MPM. (Cancer Sci 2010)

Antitussive effect of bakumondoto a fixed kampo medicine (six herbal components) for treatment of post-infectious prolonged cough: controlled clinical pilot study with 19 patients.

Bakumondoto (TJ-29) is a traditional herbal medicine that has been used in Japan for the treatment of bronchitis, bronchial asthma, and cough. This study investigated the effect of TJ-29 for the treatment of post-infectious prolonged cough. We performed a multicenter randomized controlled trial treating patients without (group A, n=11) or with TJ-29 (group B, n=8) for a total of 2 weeks using a beta 2 stimulant as the basal agent. Efficacy and safety were compared by a cough diary, VAS and sleeping questionnaire. At 4 and 5 days after treatment, the cough score of group B showed significant improvement compared with group A, demonstrating an early antitussive effect. At the assessment 2 weeks after treatment start, both groups showed similar levels of improvement in the cough score. No significant difference was observed in the VAS and the sleeping questionnaire items. In conclusion, oral TJ-29 administration could be useful and safe for the treatment of post-infectious prolonged cough.

Antitumor activity of MEK and PI3K inhibitors against malignant pleural mesothelioma cells in vitro and in vivo

Malignant pleural mesothelioma (MPM) is an aggressive malignancy for which there is no approved targeted therapy. We examined the therapeutic efficacy of the mitogen-activated protein kinase kinase (MEK) and phosphatidylinositol 3-kinase (PI3K) inhibitors against human MPM cell lines both in vitro and orthotopically inoculated into severe combined immunodeficient (SCID) mice. In addition, the molecular mechanisms of these agents were confirmed in vitro and in vivo. The MEK or the PI3K inhibitor suppressed MPM cell growth in vitro in a dose-dependent manner via induction of G1 cell cycle arrest and apoptosis. In addition, combined use of the MEK and PI3K inhibitors showed an additive or synergistic inhibitory effect on MPM cell growth compared to treatment with either individual drug. Treatment with MEK or PI3K inhibitor suppressed the production of thoracic tumors and pleural effusion and prolonged the survival time of EHMES-10 cell-bearing SCID mice. The combination therapy more effectively prolonged the survival time compared to treatment with either individual drug. Immunohistochemical and western blot analysis of thoracic tumors suggested that these agents induced cell cycle arrest, apoptosis and inhibition of tumor angiogenesis. Our results suggest that a combination of MEK and PI3K inhibitors is a promising therapeutic strategy for MPM.

Pasteurella multocida pneumonia: Zoonotic transmission confirmed by molecular epidemiological analysis

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Bacterial tracheobronchitis. A rare cause of adult airway stenosis.

Bacterial tracheobronchitis is a rare cause of airway stenosis in adults. This report describes a 73‐year‐old woman with a recent history of polysialadenitis, who presented with severe airway obstruction due to infection and stenosis of tracheal and bronchial tissue. Tissue culture of the bronchial mucosa showed growth of methicillin resistant Staphylococcus epidermidis (MRSE). Sputum culture showed growth of MRSE, Pseudomonas aeruginosa, Enterobacter cloacae and Enterococcus faecalis; the same organisms were cultured from the salivary glands. Tracheostomy and antibiotic therapy were effective in controlling the disease.

Pulmonary tumor thrombotic microangiopathy associated with lung cancer

We describe a case of pulmonary tumor thrombotic microangiopathy (PTTM) associated with lung cancer. A 63-year-old woman, who had been treated for lung cancer, was admitted to our hospital because of progressive dyspnea. Chest CT films showed reticular shadows in the middle and left upper lobes, and echocardiography revealed severe pulmonary hypertension. Because drug induced pneumonitis and either pulmonary thromboembolism or pulmonary tumor embolism were suspected, corticosteroid and anti-coagulant therapy were administered. Despite these treatments, she died 50 days after admission. Postmortem examination revealed PTTM associated with lung cancer. PTTM should be considered in cancer patients who show progressive respiratory failure and pulmonary hypertension.

A Case of Pulmonary Hemorrhaging as a Fatal Complication of IgA Vasculitis

A 64-year-old man was admitted to our hospital for purpuric rash, joint pain, and a fever. He had earlier undergone a follow-up examination for interstitial lung disease. At the current visit, the diagnosis was immunoglobulin A (IgA) vasculitis, based on skin and renal biopsy findings. He developed sudden breathlessness and hemoptysis. Chest computed tomography revealed ground glass opacity in the right lower lung fields, suggesting pulmonary hemorrhaging associated with IgA vasculitis. Despite steroid and cyclophosphamide therapy, and plasma exchange, he died 52 days after admission. Early aggressive therapies may be recommended for old patients with IgA vasculitis who have an additional comorbidities.

Use of the forced-oscillation technique to estimate spirometry values

Purpose Spirometry is sometimes difficult to perform in elderly patients and in those with severe respiratory distress. The forced-oscillation technique (FOT) is a simple and noninvasive method of measuring respiratory impedance. The aim of this study was to determine if FOT data reflect spirometric indices. Patients and methods Patients underwent both FOT and spirometry procedures prior to inclusion in development (n=1,089) and validation (n=552) studies. Multivariate linear regression analysis was performed to identify FOT parameters predictive of vital capacity (VC), forced VC (FVC), and forced expiratory volume in 1 second (FEV1). A regression equation was used to calculate estimated VC, FVC, and FEV1. We then determined whether the estimated data reflected spirometric indices. Agreement between actual and estimated spirometry data was assessed by Bland–Altman analysis. Results Significant correlations were observed between actual and estimated VC, FVC, and FEV1 values (all r>0.8 and P<0.001). These results were deemed robust by a separate validation study (all r>0.8 and P<0.001). Bias between the actual data and estimated data for VC, FVC, and FEV1 in the development study was 0.007 L (95% limits of agreement [LOA] 0.907 and −0.893 L), −0.064 L (95% LOA 0.843 and −0.971 L), and −0.039 L (95% LOA 0.735 and −0.814 L), respectively. On the other hand, bias between the actual data and estimated data for VC, FVC, and FEV1 in the validation study was −0.201 L (95% LOA 0.62 and −1.022 L), −0.262 L (95% LOA 0.582 and −1.106 L), and −0.174 L (95% LOA 0.576 and −0.923 L), respectively, suggesting that the estimated data in the validation study did not have high accuracy. Conclusion Further studies are needed to generate more accurate regression equations for spirometric indices based on FOT measurements.

Outcome of intravascular stent in superior vena cava syndrome

Background: Superior vena cava (SVC) syndrome is one of the oncologic emergency. The patients under life-threatening conditions require urgent treatment such as chemotherapy, radiation therapy and stent placement. It has been reported that stent placement provide a palliative benefit. However, indication for treatment of stenting are not well defined. Objective: The aim of this study was to evaluate the outcome of intravascular stent in SVCsyndrome. Methods: The subjects consisted of 11 patients who were undergone stent placement in Matsuyama Red Cross Hospital between June 2010 and April 2013. Contrast enhanced CT was made in all patients. Stent placement was made with self-expanding stent. Results: All patients had lung cancer (5 in adenocarcinoma, 4 in small cell carcinoma and 2 in non-small lung cancer). Seven patients previously had received chemotherapy and /or radiation therapy. In all patients, correct positioning of stents was achieved. Their symptoms completely disappeared within 6.8 hours. The median survival time was 133 days (range, 31 to 573 days). Major side effects were not observed. Conclusion: In our study, stent placement dramatically improved symptoms and quality of life. Stenting increased the survival benefit, especially in patients with improved performance status.