Comparison between unattended automated office blood pressure and conventional office blood pressure under the environment of health checkup among Japanese general population.

Unattended automated office blood pressure (AOBP) measurement has been endorsed as the preferred in-office measurement modality in recent Canadian and American clinical practice guidelines. However, the difference between AOBP and conventional office blood pressure (CBP) under the environment of a health checkup remains unclear. We aimed to identify the clinical significance of AOBP as compared to CBP under the environment of a health checkup. There were 491 participants (333 females, mean age of 62.5 years) who were at least 20 years old, including 179 participants who were previously diagnosed with hypertension. Mean AOBPs were 131.8 ± 20.9/76.6 ± 11.7 mm Hg, and CBPs were 135.6 ± 21.6/77.3 ± 11.5 mm Hg. There was a difference of 3.9 mm Hg in systolic blood pressure (SBP) and 0.8 mm Hg in diastolic BP between AOBP and CBP. In all participants, SBP and pulse pressure, as well as the white coat effect (WCE), increased with age. The cutoff value used was 140/90 mm Hg for CBP and 135/85 mm Hg for AOBP, and the prevalence of WCE and masked hypertension effect (MHE) was 12.4% and 14.1%, respectively. Even in a health checkup environment of the general population, there was a difference between the AOBP and CBP, and the WCE was observed more strongly in the elderly with a history of hypertension, suggesting that a combination of AOBP with CBP may be useful in detecting WCE and MHE in all clinical scenarios including health checkups, and help solve the "hypertension paradox" not only in Japan but in all over the world.

Respiratory function in healthy ever-smokers is impaired by smoking habits in a dose-dependent manner.

BACKGROUND: There is limited information about the respiratory function of ever-smokers without lung disorders. We sought to assess the effects of smoking habits on respiratory function in subjects without lung disorders. METHODS: Subjects were recruited from among patients without any evidence of respiratory disorders who visited rural primary care clinics. Each participant was asked to answer a questionnaire that included questions smoking history. Their forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were measured. RESULTS: We analyzed 802 subjects (364 men and 438 women). The means of the lambda-mu-sigma method derived z-score of FEV1 (zFEV1) both in current-smokers and ex-smokers were lower than that in never-smokers. The mean zFEV1 in the ever-smokers with more than 30 pack-years of smoking history were lower than that in the ever-smokers with less smoking history. Univariate analysis showed that there were significant negative correlations between pack-years and zFEV1 both in the ex-smokers and current-smokers. There was no significant correlation between the duration of smoking cessation and zFEV1 in the ex-smokers. CONCLUSIONS: Our data suggests that respiratory function in healthy ever-smokers is decreased based on smoking habits in a dose-dependent manner. Even after a long period of smoking cessation, the decreased respiratory function seems to be maintained in ex-smokers.

Evaluation of a Quantitative Serological Assay for Diagnosing Chronic Pulmonary Aspergillosis.

The purpose of this study was to evaluate the clinical utility of a quantitative Aspergillus IgG assay for diagnosing chronic pulmonary aspergillosis. We examined Aspergillus-specific IgG levels in patients who met the following criteria: (i) chronic (duration of >3 months) pulmonary or systemic symptoms, (ii) radiological evidence of a progressive (over months or years) pulmonary lesion with surrounding inflammation, and (iii) no major discernible immunocompromising factors. Anti-Aspergillus IgG serum levels were retrospectively analyzed according to defined classifications. Mean Aspergillus IgG levels were significantly higher in the proven group than those in the possible and control groups (P < 0.01). Receiver operating characteristic curve analysis revealed that the Aspergillus IgG cutoff value for diagnosing proven cases was 50 mg of antigen-specific antibodies/liter (area under the curve, 0.94; sensitivity, 0.98; specificity, 0.84). The sensitivity and specificity for diagnosing proven cases using this cutoff were 0.77 and 0.78, respectively. The positive rates of Aspergillus IgG in the proven and possible groups were 97.9% and 39.2%, respectively, whereas that of the control group was 6.6%. The quantitative Aspergillus IgG assay offers reliable sensitivity and specificity for diagnosing chronic pulmonary aspergillosis and may be an alternative to the conventional precipitin test.

Conifer-Derived Monoterpenes and Forest Walking.

Conifer and broadleaf trees emit volatile organic compounds in the summer. The major components of these emissions are volatile monoterpenes. Using solid phase microextraction fiber as the adsorbant, monoterpenes were successfully detected and identified in forest air samples. Gas chromatography/mass chromatogram of monoterpenes in the atmosphere of a conifer forest and that of serum from subjects who were walking in a forest were found to be similar each other. The amounts of α-pinene in the subjects became several folds higher after forest walking. The results indicate that monoterpenes in the atmosphere of conifer forests are transferred to and accumulate in subjects by inhalation while they are exposed to this type of environment.

Double-blind, placebo-controlled clinical trial with a rho-kinase inhibitor in pulmonary arterial hypertension.

BACKGROUND: We have previously demonstrated that long-term inhibition of Rho-kinase ameliorates pulmonary arterial hypertension (PAH) in animal models. In the present study, we examined the clinical effects of mid-term oral treatment with an extended release formulation of AT-877 (fasudil hydrochloride), a specific Rho-kinase inhibitor (AT-877ER) on PAH. METHODS AND RESULTS: 23 PAH patients were treated with either placebo (10/2 females/males, 51 ± 16 years, idiopathic PAH (IPAH) in 6, PAH associated with connective tissue disease (CTD-PAH) in 3, PAH with congenital heart disease (CHD-PAH) in 2, and portal PAH in 1) or AT-877ER (6/5 females/males, 47 ± 14 years, IPAH in 2, CTD-PAH in 5, and CHD-PAH in 4); 3 patients were excluded. We performed a 6-min walk test and right heart catheterization in the remaining 20 patients, before and 3 months after the treatment (placebo n=11, AT-877ER n=9). Although there were no significant differences between the 2 groups for the 6-min walk distance, pulmonary hemodynamics tended to be improved in the AT-877ER group, especially the prevalence of improved cardiac index from baseline, which was significantly higher in the AT-877ER than in the placebo group. In the AT-877ER group, serum levels of hydroxyfasudil, an active metabolite of AT-877ER tended to correlate with improvements in the cardiac index and mean pulmonary artery pressure. CONCLUSIONS: Mid-term treatment with oral AT-877ER showed additional improvement in pulmonary hemodynamics in patients with PAH.

[The add-on effect of omalizumab on patients with uncontrolled bronchial asthma].

A high-dose administration of inhaled corticosteroid is effective in the majority of patients with bronchial asthma, but is often difficult to attain sufficient control in certain subsets of patients. Omalizumab has recently emerged as a promising drug for bronchial asthma. To assess its add-on effect we administered omalizumab to patients with uncontrolled atopic asthma for more than 16 weeks and gave them questionnaires. The study population comprised 9 patients with frequent asthmatic symptoms despite the administration of high-dose inhaled corticosteroid and other disease controllers. We scored disease control using the Asthma Health Questionnaire-33-Japan and the Asthma Control Test, and evaluated the frequencies of short-acting beta2-agonist use for rescue and drip infusion of theophyllines and/or systemic steroids in a retrospective fashion. Asthmatic scores were significantly improved after 16 weeks of omalizumab therapy. The frequencies of reliever use and drip infusion were also decreased. These trends were present even in patients in whom no aeroallergen-specific IgE antibodies were detected. No statistically significant side effects were observed. Our study confirmed the add-on effect of omalizumab based on evaluation by simple questionnaires. Further studies are needed to clarify whether omalizumab therapy is suitable for patients without specific IgE antibodies.

[Comparison between predicted equations obtained by standard Japanese values and present predicted equations for vital capacity and forced expiratory volume in one second].

Until recently, predicted values of vital capacity (VC) and forced expiratory volume in one second (FEV1) have been calculated with Baldwin's equation (VC-B) and Berglund's equation (FEV1-B) respectively, in Japan. Due to several problems using these equations, new prediction equations of VC (VC-J) and FEV1 (FEV1-J), which were created using data from healthy Japanese, were provided by the Japanese Respiratory Society in 2001. In the present study, we studied the validity of these prediction equations. Also, we compared the outcomes of patients who match respiratory handicap "indexes" with VC-B and VC-J. The subjects were all adult patients whose respiratory function was tested in Asahikawa Medical College Hospital between 1998 and 2006. Cases which were diagnosed as contractive respiratory disorder increased approximately 2-fold when %VC was calculated with VC-J compared with VC-B. Grade 4 or higher respiratory handicap scores increased 20% if the index was calculated with VC-J compared with VC-B. There was no significant difference in mortality between the respiratory handicap grade 3 scores calculated with VC-J and VC-B. Also, there was no significant difference in mortality between grade 4 respiratory handicap scores calculated with VC-J and VC-B. These findings suggest that the prediction equations using Japanese data increase the number of predicted respiratory disorders, and those additional cases have the same prognoses as those cases diagnosed with the former criteria.

High incidence of chromosomal abnormalities at 1p36 and 9p21 in early-stage central type squamous cell carcinoma and squamous dysplasia of bronchus detected by autofluorescence bronchoscopy.

Heavy smokers with central type squamous cell carcinoma (SCC) frequently have multiple cancerous lesions in the bronchus. Autofluorescence bronchoscopy (AFB) is useful in the detection of early bronchogenic cancer and dysplastic lesions. We investigated the loss of heterozygosity (LOH) and microsatellite instability (MSI) and expression of four proteins in 13 early stage SCC (early SCC) and 9 squamous dysplasia detected by AFB and 19 cases of surgically resected invasive SCC (invasive SCC). In early SCC and squamous dysplasia, LOH/MSI of chromosome 1p36 was found in 62 and 33%, respectively, and of 9p21 in 54 and 63%, respectively. TAp73 expression of early SCC and squamous dysplasia was lower than that of normal bronchial epithelium, and p16 expression was not detectable in these lesions. These results suggested that the genetic abnormalities had already developed in the early stage of carcinogenesis of SCC, including squamous dysplasia. The AFB system was able to reveal abnormal autofluorescence in these precancerous lesions, including squamous dysplasia.

[Evaluation of galactomannan antigen and beta-D-glucan value for diagnosis of chronic necrotizing pulmomary aspergillosis].

In order to establish the reliable cut-off value of galactomannan (GM) antigen as well as that for beta-D-glucan for CNPA diagnosis, we conducted the following study. From 2001 to 2008, in a total of 1511 patients we measured GM and anti-aspergillus antibody simultaneously. These patients had chronic pulmonary disease including old tuberculosis, nontuberculous mycobacteriosis, COPD, and had bullous lung, interstitial lung disease or were suspected to have suspected to have interstitial lung disease. We designated cases as probable CNPA when the sample represented a positive anti-aspergillus antibody. We then analyzed the sensitivity and specificity according to various GM antigen values. When using the GM antigen cut-off value at 0.5, the sensitivity and specificity for CNPA were 63.4% and 68.6% respectively. Using 1.0 for cut-off value resulted in the better specificity for CNPA diagnosis. Similar analysis was performed on beta-D-glucan for CNPA diagnosis. When using D-glucan cut-off value as 20 pg/ml, the sensitivity and specificity for CNPA. These results indicate that the cut-off value of serological examination for infectious disease should be considered by the type of disease.

Administration of VEGF receptor tyrosine kinase inhibitor increases VEGF production causing angiogenesis in human small-cell lung cancer xenografts.

Angiogenesis is mediated mainly by vascular endothelial growth factor (VEGF), and VEGF causes rapid growth in cancers, including human small-cell lung cancer (SCLC). The anti-angiogenic strategy of treating cancer using VEGF receptor (VEGFR) inhibition is currently of great interest. We tested the effects of the VEGFR2 tyrosine kinase inhibitor (TKI) vandetanib on the proliferation of two kinds of SCLC cell lines: SBC-1 cells, with detectable VEGFR2 expression and MS-1-L cells, without detectable VEGFR2 expression. To evaluate the anti-tumor and anti-angiogenic effects of vandetanib in vivo, we grafted SBC-1 and MS-1-L cells into mice. After a 3-week treatment, we measured the tumor size and histologically evaluated necrosis and apoptosis using H&E and TUNEL staining, respectively. The microvessels in the xenografts were also quantified by immunostaining of CD31. Vandetanib did not affect the proliferation of SBC-1 cells, but stimulated the growth of MS-1-L cells. In the SCLC xenograft model, vandetanib inhibited growth and tumor angiogenesis in a dose-dependent manner in SBC-1 xenografts. Vandetanib inhibited the growth of MS-1-L xenografts at a low dose (<12.5 mg/kg/day), but it did not affect tumor size or change microvessel counts at a higher dose. Interestingly, secretion of VEGF increased significantly in the MS-1-L cell line in the presence of a high dose of vandetanib in vitro. The effects of vandetanib on tumor angiogenesis were different in SBC-1 and MS-1-L cell lines. Production of angiogenic factors such as VEGF by the tumor potentially stimulates tumor angiogenesis and results in the acquisition of resistance to VEGFR TKI.

Renal abscess with Morganella morganii complicating leukemoid reaction.

We report a case of leukemoid reaction (LR) complicating renal abscess caused by Morganella morganii infection in an 80-year-old man. On administration, laboratory tests revealed white blood cell count of 76160 /microL and C reactive protein 3.09 mg/dL. Although chronic myeloid leukemia was suspected, bcr/abl fusion transcript was not observed. Contrast enhanced computer tomography imaging of the abdomen showed abscess in the right kidney. M. morganii was detected repeatedly in material of liquid from the abscess and arterial blood culture. To our knowledge, this is the first case of M. morganii infection complicating LR.

Color auto-fluorescence from cancer lesions: improved detection of central type lung cancer.

A fluorescence endoscopic system, PDS-2000, enabled observation of color auto-fluorescence from the human body. We performed a clinical study to determine whether color auto-fluorescence bronchoscopy using PDS-2000 improved the accuracy of central type lung cancer diagnosis, as compared to white light bronchoscopy. White light bronchoscopy followed by auto-fluorescence bronchoscopy was performed in 71 subjects with either bronchogenic cancer, previous lung cancer, bloody sputum or who were at a high risk of developing lung cancer. Findings of white light bronchoscopy and auto-fluorescence bronchoscopy were classified into three categories. Two hundred eighty-eight biopsy specimens were taken from all sites which were considered to be abnormal by white light bronchoscopy as well as by auto-fluorescence bronchoscopy. The pathological findings were classified into nine categories. The sensitivity of only white light bronchoscopy (WLB) regarding the detection of severe dysplasia and cancer was compared with that of only auto-fluorescence bronchoscopy (AFB) and that of WLB+AFB. We quantified color endoscopic fluorescence images and compared the red/green signal intensity ratio (R/G ratio) according to the pathological diagnosis. The pathological diagnosis was normal in 123, inflammation, hyperplasia or metaplasia in 120, mild or moderate dysplasia in 8, severe dysplasia in 14 and cancer in 23. The sensitivity of WLB, AFB and WLB+AFB regarding the detection of severe dysplasia or cancer was 54.1%, 81.1% and 89.2%, respectively. The R/G ratio was significantly increased in the areas with severe dysplasia and cancer.

Radiological findings of alveolar hydatid disease of the lung caused by Echinococcus multilocularis.

Alveolar hydatid disease is a highly malignant form of echinococcosis caused by the larvae of the cestode Echinococcus multilocularis. Alveolar hydatid disease always affects the liver and can metastasise to the lungs and brain. The case reports describe the radiological features of alveolar hydatid disease of the lung caused by E. multilocularis. Multiple nodules which varied in size and shape were seen on CXR, CT showed most nodules to be lobulated, well circumscribed and of varying shape. Multiple lobulated lesions located between two segments of the lung and of varying shape appear to be characteristic of pulmonary alveolar hydatid disease caused by E. multilocularis.

Doxapram stimulates the carotid body via a different mechanism than hypoxic chemotransduction.

To determine if doxapram stimulates the carotid body through the same mechanism as hypoxia, we compared the effects of doxapram and hypoxia on isolated-perfused carotid bodies in rabbits. Doxapram stimulated the carotid body in a dose-dependent manner. In Ca(2+)-free solution, neither doxapram nor hypoxia stimulated the carotid body. Although, doxapram had an additive effect on the carotid body chemosensory response to hypercapnia, a synergistic effect was not observed. Also, we investigated the various K(+) channel activators on the response to doxapram and hypoxia: pinacidil and levcromakalim as ATP-sensitive K(+) channel activators; NS-1619 as a Ca(2+)-sensitive K(+) channel activator; and halothane as a TASK-like background K(+) channel activator. The hypoxic response was partially reduced by halothane only, while pinacidil, levcromakalim and NS-1619 had no effect. Interestingly, the effect of doxapram was partially inhibited by NS-1619. Neither pinacidil nor levcromakalim affected the stimulatory effect of doxapram. We conclude that doxapram stimulates the carotid body via a different mechanism than hypoxic chemotransduction.

[Symptoms in asthmatics living in cold districts during winter].

Exposure to cold is known as a potential exacerbating factor in asthmatics. However, few studies have investigated severity of symptoms during daily life in winter for asthmatics living in northern Hokkaido, the coldest region in Japan. We sent questionnaires to 126 asthmatics living in northern Hokkaido, and obtained answers from 116 patients (52 males, 64 females). Breathing difficulties during cold-air exposure were reported by 62.1% of patients. Furthermore, 19.6% of patients had experienced the need for bronchodilators following cold-air-induced attacks. Limitations to daily life in winter caused by exacerbated asthmatic symptoms were recognized by 48.3% of patients. Asthmatic exacerbation was experienced by 30% of patients in summer (May to August), compared to >35% in winter (September to April). No significant differences in results were noted between atopic and non-atopic patients. Improvements in respiratory symptoms during winter are thus necessary for better quality of life in asthmatics living in cold districts.