Frailty Checkup Supporters' Intentions to Participate in Human-Resource Development and Training Activities.

BACKGROUND: Frailty prevention is one of social prescriptions for an aging society. That requires community level intervention. OBJECTIVES: This study examined frailty checkup supporters' (FCSs') intentions to engage in human-resource development and training activities (i.e., leadership activities) and related factors. DESIGN: Cross-sectional study. SETTING: Three municipalities in suburban area, Eastern Japan. PARTICIPANTS: Forty-five of 59 FCSs completed anonymous self-administered questionnaires. MEASUREMENTS: Questionnaire sought information regarding their sociodemographic data, their perceptions and experiences of FCS activities, and their intentions to participate in human-resource development and training activities. Participants were divided into a high intention (HI) and low intention group (LI). The two groups were compared using quantitative and qualitative data. RESULTS: Eleven FCSs reported intending to engage in leader-related activities. Factors associated with FCSs' intentions were finding FCS activities rewarding and the willingness to continue performing FCS activities. The participants who changed their daily activities (p = .041) and perceptions regarding contributing to the community (p = .018) showed significantly higher intention than LI participants. Free description about the changes in perceptions and lifestyles as a consequence of participating in FCS activities were analyzed qualitatively. FCSs who changed their daily activities and perspectives about contributing to the community described positive changes in both the groups. Meanwhile, FCSs who did not change their daily activities and perspectives about contributing to the community described their reason only in the LI group. CONCLUSIONS: The results might encourage FCSs to participate in training and guidance activities, as they have positive experiences and receive recognition obtained through participation in such activities.

Lung cancer in chronic hypersensitivity pneumonitis.

BACKGROUND: So far, the association of lung cancer with chronic hypersensitivity pneumonitis (CHP) has not been studied. OBJECTIVE: We examined the prevalence and revealed clinical features of lung cancer in CHP. METHODS: We retrospectively reviewed the medical records from 1994 through 2005 and identified 11 patients (15 lesions) with lung cancer among 104 patients with CHP. Their clinical features and histopathological findings were analyzed. RESULTS: Ten men and 1 woman with a median age of 68.9 years were included. All patients had a smoking history. The most prevalent histopathological type of lung cancer was squamous cell carcinoma (53%), and all tumors were located in the peripheral region of the lung. Four patients suffered from lung cancer after the diagnosis of CHP and 1 patient had lung cancer before the diagnosis of CHP. The histological pattern of CHP showed a predominantly usual interstitial pneumonia-like lesion. Tumors were located adjacent to honeycombing in 7 (47%) of 15 lesions, bullae in 4 (27%) lesions, and relatively normal lung in 4 lesions. CONCLUSIONS: Since the prevalence of lung cancer in CHP seems to be high (10.6%) as seen in idiopathic pulmonary fibrosis, physicians should be aware of the possible complication of lung cancer in CHP.

Prior nonhip limb fracture predicts subsequent hip fracture in institutionalized elderly people.

SUMMARY: This 1-year cohort study of nursing home residents revealed that historical fractures of upper limbs or nonhip lower limbs were associated with hip fracture (hazard ratio = 2.14), independent of activities of daily living (ADL), mobility, dementia, weight, and type of nursing home. Prior nonhip fractures are useful for predicting of hip fracture in institutional settings. INTRODUCTION: The aim of this study was to evaluate the utility of fracture history for the prediction of hip fracture in nursing home residents. METHODS: This was a cohort study with a 1-year follow-up. Subjects were 8,905 residents of nursing homes in Niigata, Japan (mean age, 84.3 years). Fracture histories were obtained from nursing home medical records. ADL levels were assessed by caregivers. Hip fracture diagnosis was based on hospital medical records. RESULTS: Subjects had fracture histories of upper limbs (5.0%), hip (14.0%), and nonhip lower limbs (4.6%). Among historical single fractures, only prior nonhip lower limbs significantly predicted subsequent fracture (adjusted hazard ratio, 2.43; 95% confidence interval (CI), 1.30-4.57). The stepwise method selected the best model, in which a combined historical fracture at upper limbs or nonhip lower limbs (adjusted hazard ratio, 2.14; 95% CI, 1.30-3.52), dependence, ADL levels, mobility, dementia, weight, and type of nursing home independently predicted subsequent hip fracture. CONCLUSIONS: A fracture history at upper or nonhip lower limbs, in combination with other known risk factors, is useful for the prediction of future hip fracture in institutional settings.

Fracture incidence in nursing homes in Japan.

UNLABELLED: We conducted the first study to determine fracture incidence in institutionalized elderly people in East Asia. Fracture incidence was generally higher than in the general population but was not for all fracture types. Specific fracture prevention strategies for institutionalized people are needed. Ethnic differences in fracture incidence are also discussed. INTRODUCTION: The aim of this study was to determine the incidence of fractures in nursing homes in Japan, where fracture is becoming an increasingly problematic health issue. METHODS: We conducted a cohort study with a 1-year follow-up. Subjects were 8,905 residents (average age, 84.3 years) in nursing homes. Caregivers assessed activities of daily living levels using Barthel's index, and we collected demographic data of each resident. Fracture diagnosis was based on medical records from the hospitals where patients were admitted. RESULTS: Incidence of hip fracture was 14.9 per 1,000 person-years for women and 9.7 for men. Incidence of forearm and upper-arm fractures was 1.9 and 5.1 for women and 0.5 and 2.1 for men, respectively. Hip and upper-arm fracture rates were higher than in the general population, but forearm fracture rates were lower. Hazard ratio of fracture incidence in totally dependent to partially dependent or independent subjects was 0.14 (95%CI 0.05-0.33) for hip fracture and 0.34 (95%CI 0.23-0.50) for all fractures. CONCLUSIONS: Fracture incidence in institutionalized elderly people is generally higher but is not higher for all types of fractures than the general population. In addition, totally dependent persons had a much lower risk of hip fracture.

A phase I study of TS-1 plus carboplatin in patients with advanced non-small-cell lung cancer.

TS-1 is a novel oral anticancer agent comprised of tegafur, a prodrug of 5- flurouracil, and two modulators. A phase i study of tS-1 plus carboplatin combination therapy was conducted to determine the maximum tolerated dose (MTD), recommended dose (RD), and dose limiting toxicities (DLT) in advanced non-small-cell lung cancer (NSClC). TS-1 was given orally at a dose of 80 mg/m(2)/day for 2 weeks, followed by a 2-week rest. Carboplatin was given intravenously on day 8 at a dose of 4.0, 5.0, 6.0 area under the curve (AUC) values. Fifteen patients with advanced NSClC were analyzed. the grade 3-4 toxicities observed during the first cycle were febrile neutropenia (6%), anemia (6%), anorexia (6%), and diarrhea (6%). these toxicities were reversible and manageable. The MTD for carboplatin was evaluated to be more than 6.0 AUC values, as one of six patients developed Dlt at this dose. the RD for carboplatin was estimated as 6.0 AUC values. Objective responses were seen in five patients (response rate 33%).

Expression profile of early lung adenocarcinoma: identification of MRP3 as a molecular marker for early progression.

Early lung adenocarcinoma is well-recognized as a small-sized non-invasive adenocarcinoma or localized non-mucinous bronchioloalveolar carcinoma (LNMBAC); however, the molecular events associated with these early lesions are not clear. To determine the genes involved in tumorigenesis at the early stage of lung adenocarcinoma, we compared the mRNA expression profiles of LNMBAC and normal lungs with an oligonucleotide array. Immunohistochemical analyses were performed to confirm the expression of detected genes. We identified 183 differentially expressed genes, of which 15 were up-regulated and 168 down-regulated. Among them, most up-regulated genes, such as AQP3 and Claudin-4, were expressed in both adenocarcinoma cells and type II alveolar pneumocytes, corresponding to the histological similarity between these cell types. However, multidrug resistant protein 3 (MRP3) was only expressed on tumour cell membranes and not in type II alveolar pneumocytes, as confirmed by immunohistochemistry. Moreover, the number of MRP3-positive cells significantly increased from AAH (the precursor lesion of lung adenocarcinoma) to LNMBAC. We conclude that MRP3 could be a novel molecular marker for LNMBAC, whose expression increases during the early progression of tumourigenesis.

The epidermal growth factor receptor mediates allergic airway remodelling in the rat.

The chronicity of bronchial asthma is attributed to persistent airway inflammation and to a variety of structural changes, or remodelling, that includes smooth muscle and goblet cell hyperplasia. To investigate the mechanisms of airway remodelling, the current authors used an established allergen (ovalbumin; OVA)-driven rodent model (the Brown Norway rat). Brown Norway rats were sensitised to OVA and challenged three times at 5-day intervals to evoke airway remodelling. The effects of an epidermal growth factor (EGF) receptor inhibitor, AG1478, and a cysteinyl leukotriene-1 receptor antagonist, montelukast, on epithelial and airway smooth muscle (ASM) cell proliferation in vivo in response to repeated OVA challenge were tested. Three challenges with leukotriene (LT)D(4) were given, to examine their effects on remodelling with and without AG1478 pretreatment. OVA challenges caused ASM hyperplasia, with an increase in mass, epithelial cell proliferation and goblet cell proliferation. AG1478 prevented the changes, as did montelukast. Multiple OVA challenges increased heparin-binding EGF-like growth factor but not EGF expression by airway epithelium. LTD(4) reproduced the changes in remodelling induced by OVA and this was blocked by AG1478. Allergen-induced airway epithelial and airway smooth muscle remodelling is mediated by cysteinyl leukotrienes via the cysteinyl leukotriene-1 receptor with downstream effects on the epidermal growth factor receptor axis.

Pathogenesis of cBFL in common with IPF? Correlation of IP-10/TARC ratio with histological patterns.

BACKGROUND: A Th1 predominant immune response has been shown in acute hypersensitivity pneumonitis. Predominance of Th2 appears to favour the development of pulmonary fibrosis through the profibrotic process and has been described as crucial in the progression of idiopathic pulmonary fibrosis. Chronic bird fancier's lung (cBFL) can present with a histological pattern of usual interstitial pneumonia (UIP)-like lesions. Little is known about the Th1/Th2 balance in the pathogenesis of cBFL. METHODS: To evaluate the relevance of Th1-type chemokines (interferon-inducible protein, IP-10) and Th2-type chemokines (thymus- and activation-regulated chemokine, TARC) and their receptors (CXCR3 and CCR4) to the histological patterns of cBFL, 40 patients with cBFL who underwent surgical lung biopsies, 12 with acute BFL (aBFL) and 10 healthy volunteers were analysed. IP-10 and TARC levels in serum and bronchoalveolar lavage (BAL) fluid were measured by ELISA. Immunohistochemistry for CXCR3 and CCR4 was performed on surgical lung specimens. RESULTS: The ratio of TARC to IP-10 in the serum of patients with UIP-like lesions was significantly higher than in patients with cNSIP/OP-like lesions, aBFL and healthy volunteers. The ratio of CCR4 to CXCR3 in patients with UIP-like lesions was significantly higher than in those with cNSIP/OP-like lesions and fNSIP-like lesions. The ratio of CCR4-positive to CXCR3-positive cells correlated with the ratio of TARC to IP-10 in serum. CONCLUSIONS: A Th2 predominant immune response may play an important role in the development of UIP-like lesions, as already observed in idiopathic pulmonary fibrosis. A Th1 predominance may play a role in the development of cNSIP/OP-like lesions in cBFL.

Maturational changes in skin color of Japanese newborn infants.

BACKGROUND/OBJECTIVE: The skin color of newborn infants is subjectively observed to change, depending upon their gestational age. We evaluated the relationship between neonatal skin color and gestational age by employing an objective method. METHODS: Using a tristimulus photocolorimeter, L*, a*, and b* were examined as the parameters of skin color in Japanese newborn infants (Commission Internationale de l'Eclairage L*a*b* color space). The following items were examined: (1) the reproducibility of the measurements; (2) the time course of the values during the first 24 h after birth, and (3) the relationship with the gestational age. The gestational age of these infants had been determined by measuring their crown-rump length during fetal periods. RESULTS: Reliability and validity of the measurements were satisfactory for all parameters. However, a* and b* fluctuated widely during the first 24 h. By contrast, L* was stable between 3 and 24 h after birth. L* measured during these periods directly correlated with the gestational age (r=0.843, p<0.0001). CONCLUSIONS: Because L* represents lightness or darkness, our results suggest that the skin color changes from black to white with maturation. L* may be a helpful parameter for the evaluation of the gestational age of newborn infants.

Chronic bird fancier's lung: histopathological and clinical correlation. An application of the 2002 ATS/ERS consensus classification of the idiopathic interstitial pneumonias.

BACKGROUND: Chronic bird fancier's lung (BFL) has often been misdiagnosed as one of the idiopathic interstitial pneumonias (IIPs). METHODS: To define the clinical and pathological characteristics of chronic BFL, 26 patients with chronic BFL from whom a surgical lung biopsy specimen was taken between October 1992 and June 2001 were evaluated. The histopathological characteristics of the surgical lung biopsy specimens were examined and correlations between the histopathology and clinical characteristics were analysed. The quality of chronic inflammatory and fibrotic changes was expressed according to the 2002 ATS/ERS consensus classification of IIPs. RESULTS: Two patients were diagnosed as having bronchiolitis obliterans organising pneumonia (BOOP)-like lesions, five as having cellular non-specific interstitial pneumonia (NSIP)-like lesions, and eight as having fibrotic NSIP-like lesions. The other 11 patients were considered to have usual interstitial pneumonia (UIP)-like lesions because of the temporal heterogeneous appearances of the fibrotic changes. However, fibrosis in these patients had developed in centrilobular as well as perilobular areas, suggestive of hypersensitivity pneumonitis. Nineteen patients (73.1%) had multinucleated giant cells, often with cholesterol clefts, while only five patients (19.2%) had granulomas. Patients with BOOP-like or cellular NSIP-like lesions tended to have recurrent acute episodes, whereas patients with UIP-like lesions had an insidious onset. Patients with BOOP-like or cellular NSIP-like lesions had a more favourable outcome than those with fibrotic NSIP-like and UIP-like lesions. CONCLUSIONS: The qualities of chronic inflammatory and fibrotic lesions vary significantly among patients with chronic BFL but correlate with clinical features and prognosis.

Physical characteristics of low and medium energy collimators for 123I imaging and simultaneous dual-isotope imaging.

Septal penetration of high energy photons may degrade 123I images obtained with a low energy collimator. We evaluated the physical characteristics of a low energy, high resolution (LEHR) collimator, special LEHR (SLEHR) collimator, and medium energy collimator for 123I studies. The cross-talk of 99mTc and 123I into the 201Tl window was also examined. Sensitivity and spatial resolution were measured with each collimator. Point sources of 99mTc and 123I were imaged at various source-collimator distances using multiple energy windows, and the effects of collimator choice on energy spectrum and spatial distribution of photopeak counts were assessed. For 99mTc, both sensitivity and resolution were similar with the low energy collimators, and higher sensitivity and lower resolution were observed with the medium energy collimator. For 123I, the full width at tenth maximum was larger for 123I than for 99mTc when using the LEHR collimator. Acquisitions with multiple energy windows revealed severe degradation due to septal penetration in imaging 123I with the LEHR collimator, especially at short distances. The degradation was reduced with the SLEHR collimator and further with the medium energy collimator. In both 99mTc and 123I imaging, cross-talk into the 201Tl window was larger at shorter distances and the largest with the LEHR collimator. In conclusion, variation in collimator geometry causes differences in the effect of septal penetration on 123I images and in cross-talk into the 201Tl window. The SLEHR collimator may be suitable for use in high resolution 123I imaging and simultaneous 99mTc/201Tl imaging. Use of the medium energy collimator appears to be preferable in quantitative 123I studies.

Serum cytokine levels in atopic dermatitis.

Elevated IgE responses and eosinophilia observed in patients with atopic dermatitis (AD) may reflect increased responses of type 2 T-helper (Th2) cytokines with a concomitant decrease in interferon-gamma (IFN-gamma) production. However, the cross-regulation of Th1/Th2 derivation and function in AD patients are incompletely characterized. Therefore, we investigated serum levels of several cytokines [interleukin (IL)-18, IL-12, IL-10, IL-2 and IFN-gamma] in patients with AD to assess their possible relationships to the severity of disease. Serum IL-18 levels in AD patients were significantly higher than those in healthy controls [207 pg/mL; 95% confidence interval (CI), 172-242 pg/mL vs. 144 pg/mL; 95% CI, 116-178 pg/mL; P = 0.026]. Those IL-18 levels significantly correlated with eosinophil counts and serum soluble IL-2 receptor (sIL-2R) levels, and showed a tendency to correlate with clinical severity scores and serum IgE levels. IL-2 levels showed a significantly inverse correlation with serum IgE levels, and IL-12 levels clearly correlated with IL-10 levels. These results suggest the value of serum IL-18 levels as a parameter of AD activity and may support a possible role for IL-18 in the pathogenesis of AD. The inverse correlation between IgE levels and IL-2 levels suggests that IgE production may be inhibited by IL-2 in patients with AD. Furthermore, the correlation of IL-12 levels with IL-10 levels may support the previous reports that show the induction of IL-10 production by human natural killer cells and/or T cells stimulated with IL-12 in vitro.

IL-12 and IL-18 synergistically induce the bactericidal activity of murine peritoneal cells against M. leprae.

We examined the effect of IL-12 and IL-18 on bactericidal activities of mouse peritoneal cell (PC) against Mycobacterium leprae (M. leprae). We demonstrated that IL-12 and IL-18 synergistically induced the NO-dependent bactericidal activity of PC by stimulating Natural Killer (NK) cells and T-cells through IFN-gamma production. IL-12 and IL-18 induced host cell death through NK-cells and T-cells. Therefore. IL-12 and IL-18 play an important role on direct killing of intracellular M. leprae and on indirect killing of them through inducing host cell death.

[The relation between the severity of bronchial asthma and the treatment points in children].

The treatment points and score for definition of the asthma severity were initially introduced in the guideline for pediatric asthma treatment and management on 1998. We studied the relationship between the severity of clinical symptoms for children with bronchial asthma and the treatment points from July 1998 to November 1999 in our hospital. One hundred twenty five patients (one to 15 years of age, 77 boys and 48 girls) were retrospectively investigated. The treatment points and scores were associated with the clinical symptom score. However, there was no relationship in some patients. In order to define the severity of bronchial asthma, we should investigate not only the severity in terms of the clinical symptoms; the number and degree of asthma attacks, but also the treatment points and score. Furthermore, we should pay attention to the seasonal variation of the treatment points.

[A case of Churg-Strauss syndrome in which positive rheumatoid factor and MPO-ANCA preceded the development of clinical symptoms of vasculitis].

A 52-year-old man in whom bronchial asthma had been diagnosed in 1995 was admitted for the treatment of Churg-Strauss syndrome in June 1997. Positive tests MPO-ANCA and rheumatoid factor preceded the symptoms of vasculitis for several months. A skin biopsy revealed infiltration of eosinophils in the vessel walls, and the diagnosis of Churg-Strauss syndrome was confirmed. After systemic administration of corticosteroids, the symptoms other than mononeuritis improved markedly, and his MPO-ANCA and rheumatoid factor became negative. Rheumatoid factor and MPO-ANCA may be useful for the early diagnosis of Churg-Strauss syndrome in patients with bronchial asthma in which a well-controlled disease develops into an intractable condition.

Antiproliferative effect of isopentenylated coumarins on several cancer cell lines.

33 coumarins, mainly the simple isopentenylated coumarins and derived pyrano- and furanocoumarins, were examined for their antiproliferative activity towards several cancer and normal human cell lines. The pyrano- and furanocoumarins showed strong activity against the cancer cell lines, whereas they had weak antiproliferative activity against the normal human cell lines. The decreasing rank order of potency was osthenone (10), clausarin (25), clausenidin (26), dentatin (24), nordentatin (23), imperatorin (29), seselin (27), xanthyletin (21), suberosin (17), phebalosin (8) and osthol (12). The structure-activity relationship established from the results revealed that the 1,1-dimethylallyl and isopentenyl groups have an important role for antiproliferative activity.

[Tissue platinum distribution and the effect following intra-arterial injection of cisplatin to metastatic liver cancer--a case report].

A 63-year-old male with advanced esophageal cancer was admitted to our hospital. He received neoadjuvant chemotherapy with intravenous cisplatin and fluorouracil (5-FU), and underwent resection of the esophagus and placement of a gastric tube. Two months later, multiple metastases appeared in the right lobe of the liver. Intermittent arterial infusion chemotherapy with cisplatin and 5-FU were performed. To selectively infuse the drugs into the right hepatic artery, the left hepatic artery was embolized. Treatment had a marked effect in the right lobe, but new lesions were subsequently discovered in the left lobe. The patient died of pleuritis 27 days after the end of cisplatin infusion and 12 months after surgery. In total, 465 mg of cisplatin and 20 mg of nedaplatin were administered. At autopsy, tissue samples were collected to measure the platinum concentration. The result showed the highest value to be in the right lobe, 4.8 times as high as that in the left lobe. It is suggested that the concentration of platinum in tissue is correlated with the anticancer effect of cisplatin to the tissue, despite of the traditional view that the tissue concentration and the effect are not related.

Calretinin promoter for suicide gene expression in malignant mesothelioma.

To achieve specific and efficient expression of transfected suicide gene in malignant mesothelioma cells, we explored the 5-flanking region (2.2 kb) of the calretinin gene as a tumor-specific promoter. RT-PCR analysis demonstrated the expression of calretinin mRNA in two human malignant mesothelioma cell lines (H2052 and 211 H). A reporting vector containing the calretinin promoter (pCAL-LUC) exhibited relatively high luciferase activity in these cell lines. After transfecting an expression vector containing the calretinin promoter-bound thymidine kinase gene (pCAL-TK) into the cells, we examined their sensitivity to ganciclovir (GCV). In the mesothelioma cell lines, the pCAL-TK transfected cells became about 100 times more sensitive to GCV than the parental cells. The calretinin promoter seems to be a promising candidate as a specific and efficient promoter in malignant mesothelioma.

The antiproliferative effect of coumarins on several cancer cell lines.

Twenty-one coumarins were examined for their antiproliferative activity towards several cancer cell lines, namely lung carcinoma (A549), melanin pigment producing mouse melanoma (B16 melanoma 4A5), human T-cell leukemia (CCRF-HSB-2), and human gastric cancer, lymph node metastasized (TGBC11TKB). The structure-activity relationship established from the results revealed that the 6,7-dihydroxy moiety had an important role for their antiproliferative activity. Analysis of cell cycle distribution indicated that esculetin-treated cells accumulated in the G1 (at 400 microM) or in S phase (at 100 microM).