Level of Fecal Calprotectin Correlates With Severity of Small Bowel Crohn's Disease, Measured by Balloon-assisted Enteroscopy and Computed Tomography Enterography.

BACKGROUND & AIMS: Previous studies have not found a correlation between fecal level of calprotectin and small bowel Crohn's disease (CD). However, these studies evaluated patients mainly by ileocolonoscopy, which views up to only the terminal ileum rather than entire small intestine. We investigated whether level of fecal calprotectin (FC) is a marker of active CD of the small bowel, identified by balloon-assisted enteroscopy and computed tomography enterography (CTE). METHODS: We performed a prospective study of 123 patients with CD (35 with ileitis, 72 with ileocolitis, and 16 with colitis) evaluated by balloon-assisted enteroscopy from May 2012 through July 2015 at Toho University Sakura Medical Centre in Japan. Patients with strictures detected by balloon-assisted enteroscopy were evaluated by CTE (n = 17). Fecal samples were collected from each patient, and levels of calprotectin were measured; patient demographic variables and medical history were also collected. We developed a CTE scoring system for disease severity that was based on bowel wall thickness, mural hyperenhancement, and engorged vasa recta. The association between level of FC and simple endoscopic index for CD score or CTE was evaluated by using Spearman rank correlation coefficient. RESULTS: Level of FC correlated with the simple endoscopic index for CD score (r = 0.6362, P < .0001), even in patients with only active disease of the small intestine (r = 0.6594, P = .0005). In the 17 patients with strictures that could not be passed with the enteroscope, CTE detected all lesions beyond the strictures as well as areas in the distal side of the strictures. Level of FC correlated with CTE score in these patients (r = 0.4018, P = .0011, n = 63). In receiver operating characteristic analyses, the FC cutoff value for mucosal healing was 215 µg/g; this cutoff value identified patients with healing with 82.8% sensitivity, 71.4% specificity, positive predictive value of 74.3%, negative predictive value of 80.6%, odds ratio of 12.0, and area under the receiver operating characteristic curve value of 0.81. CONCLUSIONS: A combination of measurement of level of FC and CTE appears to be effective for monitoring CD activity in patients with small intestinal CD, including patients with strictures that cannot be passed by conventional endoscopy.

Biological markers, lifestyles and metabolic syndrome in workers.

OBJECTIVE: The association between metabolic syndrome (MetS) and biological inflammatory or anti-coagulant markers were clarified in combination with lifestyle factors. PATIENTS AND METHODS: The target subjects were 5102 working men without metabolic diseases, aged 30-60 years old. The authors measured the serum levels of high-sensitivity C-reactive protein (CRP), uric acid and plasma fibrinogen as potential key biomarkers of MetS. RESULTS: Mean values of uric acid, log-transformed serum CRP and plasma fibrinogen increased significantly as the number of components of MetS increased after adjustment for age. Multivariate analysis revealed significant associations between the presence of MetS and age, habitual exercise, not current smoking, the log-transformed value of serum CRP and serum uric acid, with odds ratios (ORs) of 1.03 (95% confidence interval (CI): 1.02-1.04; p<0.001), 0.77 (95% CI: 0.65-0.90; p<0.01), 0.82 (95% CI: 0.70-0.96; p<0.05), 3.2 (95% CI: 2.6-3.9; p<0.001) and 1.5 (95% CI: 1.4-1.6; p<0.001), respectively for the presence of MetS. CONCLUSION: Elevated serum level of CRP, uric acid, not habitual exercise and current smoking were associated with MetS in this cross-sectional study.

Effect of smoking prevention education using improved tobacco smoke collection method.

OBJECTIVE: To verify the effect of smoking prevention education for nursing students using the improved tobacco smoke collection method. METHODS: The improved tobacco smoke collection method allows mainstream smoke and sidestream smoke from a cigarette to be separately extracted using a closed system. After collection, we performed gas measurement using a gas detection tube and the Schiff reagent method. We provided a lecture incorporating the experimental method for an experimental group (42 students), but only the lecture without the method for a control group (43 students). We surveyed the changes in The Kano Test for Social Dependence (KTSND) scores before and after the lecture and one month later. RESULTS: In the experimental group, the total scores of the KTSND were 10.2 ± 5.0 (mean ± standard deviation) before the lecture, 5.8 ± 4.1 after the lecture, and 6.9 ± 4.8 one month later. On the other hand, the scores were 10.7 ± 5.7, 7.5 ± 5.8, and 9.7 ± 5.5 in the control group before, after, and one month after the lecture, respectively. It is considered that the students understood "smoking is harmful to health" since this gas analysis method can be used to check for harmful gases visually. CONCLUSION: Result of this study suggest that this experimental method is useful for educating nursing students on the harmful effects of smoking.

Depressive state and subsequent weight gain in workers: A 4-year follow-up study.

OBJECTIVE: It has been suggested that the presence of a depressive state is a predictor of increase of the body weight. However, to precisely understand the nature of this relationship, the data should be controlled for other factors that can also be associated with weight gain. METHODS AND PARTICIPANTS: To test the hypothesis that the presence of a depressive state is associated with future weight gain, a 4-year prospective occupation-based cohort study was conducted in male adult workers (N=1730) at a railway company. Following the initial screening, follow-up information was obtained via a legally required annual health examination. The presence of a depressive state was identified using the Zung Self-Rating Depression Scale (SDS). The weight of each participant was measured to the nearest kilogram. Multiple logistic regression analysis was used to test the association between the depressive state and a weight gain of 4 kg or more over the 4-year study period after controlling for potentially confounding variables such as the age, smoking status, alcohol intake status, and physical activity. RESULTS: A weight gain of 4 kg or more over the 4-year study period was significantly associated with the depressive state, even after controlling for confounding variables (p< 0.05). Short-term longitudinal analysis also revealed an association between the depressive state and subsequent increase of the body weight. CONCLUSION: Since the depressive state was demonstrated to be an important risk factor for increase of the body weight, further research on depression should be conducted with a view to providing effective health education.

Relation of smoking status to serum levels of N-terminal pro-brain natriuretic peptide in middle-aged men without overt cardiovascular disease.

Cigarette smoking impairs arterial function and promotes atherosclerosis. However, whether smoking status is associated with cardiac overload has not yet been fully examined, particularly from an epidemiologic viewpoint. The present study examined the relation of smoking status to serum levels of N-terminal pro-brain natriuretic peptide (NT-pro-BNP), a marker of cardiac overload, in middle-aged men without overt cardiovascular disease. Serum NT-pro-BNP levels were measured in a work-site based population of 969 men (mean age 44 ± 6 years) who did not have any history or presence of cardiovascular disease. Smoking status was evaluated by self-reported questionnaire. Four hundred fifty-nine, 222, and 288 subjects were never, former, and current smokers, respectively. NT-pro-BNP levels were significantly higher in current smokers (21.7 ± 2.3 pg/ml) than in never smokers (17.9 ± 2.1 pg/ml, p <0.001). This significant difference was maintained even after adjusting for age, obesity, heart rate, hypertension, dyslipidemia, impaired fasting glucose/diabetes mellitus, left ventricular hypertrophy, estimated glomerular filtration rate, high-sensitivity C-reactive protein, alcohol consumption, and regular exercise. Current smokers had an increased odds ratio (3.04, 95% confidence interval 1.64 to 5.61, p <0.001) for elevated NT-pro-BNP (>54.5 pg/ml) compared to never smokers, even after adjusting for the studied variables. In contrast, former smokers did not show a significantly increased odds ratio for elevated NT-pro-BNP. NT-pro-BNP levels showed a weak, but significant negative correlation with duration of smoking cessation (partial r = -0.15, p = 0.034) in former smokers. In conclusion, these results suggest that cigarette smoking increases cardiac overload, whereas smoking cessation ameliorates these conditions.

Significance of the 100-point scale to evaluate perceived tobacco dependence.

BACKGROUND: Smoking cessation is one of the primary targets for risk reduction of atherosclerotic cardiovascular disease. It also leads to the prevention of workers' illness or disability. Validation of a 100-point scale to evaluate perceived tobacco dependence was conducted using a 10-item questionnaire (the Tobacco Dependence Screener; TDS), a 6-item questionnaire (Fagerstrom Test for Nicotine Dependence; FTND), and determining the salivary levels of cotinine at Japanese workplaces. METHODS: A total of 1023 male smokers completed the TDS and FTND and scored themselves on the 100-point scale for tobacco dependence (Study 1). Of the subjects participating in Study 1, 282 male smokers from one workplace presented saliva samples, and the salivary nicotine and cotinine levels were determined by high-performance liquid chromatography (Study 2). After conducting principal axis factor analysis, multiple regression analysis was employed to clarify the association between the score on the 100-point scale for perceived tobacco dependence and several factors such as age, the TDS score, the FTND score, and the salivary cotinine level. RESULTS: The mean age for the subjects was 40.3 years. The mean salivary cotinine level was 235.4 ng/ml, and it increased significantly with increase in the number of cigarettes smoked per day. Cronbach's alpha coefficients for the TDS and FTND were 0.77 and 0.64, respectively. A ROC analysis indicated a cutoff point for the score on the 100-point scale of 61, which yielded a positive result on the TDS ( 5) with 65.7% sensitivity and 70.0% specificity. When FTND 4 was adopted as the gold standard, the sensitivity and specificity became 68.7% and 73.2%, respectively. Three factors were extracted by principal axis factor analysis, explaining 42% of the total variation. Multiple regression analysis revealed that the score on the 100-point scale for evaluating tobacco dependence was positively associated with the TDS and FTND scores, and negatively associated with the age. The adjusted multiple correlation coefficient was 0.262. CONCLUSIONS: The 100-point scale, which is a simple and easy tool to evaluate tobacco dependence, must be used in combination with other tobacco dependence questionnaires such as TDS and FTND and also the salivary cotinine level as a biological marker of tobacco exposure to conduct multi-dimensional education to promote smoking cessation.

A cross-sectional study on the shift work and metabolic syndrome in Japanese male workers.

INTRODUCTION: Shift work has been reported to be associated with an increase in the metabolic syndrome (MetS). To clarify the association between the type of shift work and the risk of MetS, a cross-sectional field survey was conducted after adjusting for age and lifestyle factors. METHODS: The subjects were 3007 Japanese males, aged 34-64 years old, who were employees (1700 day and 1307 shift workers) of a car-manufacturing company. The standard Japanese criteria for the diagnosis of MetS was used. Age, smoking habit, drinking habit, sleeping habit and exercise habit were used as the independent variables. RESULTS: The prevalence of MetS in the day workers, two-shift workers, and three-shift workers were 13.8% (234/1700), 10.7% (120/1125) and 17.6% (32/182), respectively. There was a significant difference in the prevalence between the two-shift workers and the day workers. Estimation of the odds ratios (95% confidence intervals) of age, two-shift work and habitual exercise for MetS were 1.03 (1.01-1.04), 0.77 (0.61-0.98) and 0.64 (0.51-0.81), respectively. CONCLUSION: Two-shift work was associated with lower risk of MetS, which is not in accordance with past reports. This finding should therefore be re-analysed, including investigation of the job content in each group.

Insulin resistance, as expressed by HOMA-R, is strongly determined by waist circumference or body mass index among Japanese working men.

OBJECTIVE: This study was intended to identify significant determinant factors of insulin resistance. METHODS: Insulin resistance was assessed using the homeostasis model assessment for insulin resistance (HOMA-R) and was calculated as "Fasting plasma glucose × Fasting serum insulin)/405". The target subjects were 3008 working men. The serum lipid profiles, uric acid level, insulin level, plasma glucose level, hemoglobin A1C level, and blood pressure, in addition to the waist circumference or body mass index, were also measured. A stepwise multiple regression analysis was performed using log-transformed values of HOMA-R as the dependent variable. RESULTS: The standardized regression coefficient for waist circumference was about six times larger than that for hemoglobin A1c (0.45 and 0.08, respectively). The standardized regression coefficients for the other factors were 0.15 for diastolic blood pressure, 0.10 for the low-density lipoprotein cholesterol level, -0.06 for age, -0.04 for habitual exercise, 0.14 for no habitual drinking, and 0.07 for no smoking. When body mass index was substituted for waist circumference, almost the same results were obtained. The adverse effects of no smoking and no habitual drinking on the HOMA-R score might be explained, at least in part, by the relation of these factors with obesity. Regular exercise had a protective effect on lowering insulin resistance. CONCLUSIONS: A close relation exists between obesity-related indices (waist circumference and body mass index) and insulin resistance, independent of age and other vascular risk factors in Japanese working men.

Association of smoking status, insulin resistance, body mass index, and metabolic syndrome in workers: A 1-year follow-up study.

OBJECTIVE: We performed a 1-year follow-up study to determine the effects of smoking status and insulin resistance on the prevalence of metabolic syndrome. METHODS: This study included 2136 workers without metabolic syndrome at baseline who were followed for 1 year. The subjects were divided into four categories of smoking and work history, respectively. Insulin resistance was evaluated using the homeostasis model assessment for insulin resistance (HOMA-R). RESULTS: The prevalence of metabolic syndrome after 1 year was 6.3%. A multiple logistic regression analysis showed that the current smokers category versus the non-smokers category, a 0.1-point increase in the HOMA-R score, a 1-point increase in the uric acid level, age, and body mass index were significantly correlated with increased odds for metabolic syndrome, yielding odds ratios (95% confidence intervals) of 1.61 (1.09-2.39), 1.14 (1.04-1.25), 1.31 (1.12-1.54), and 1.06 (1.03-1.09), and 1.23 (1.15-1.31), respectively. CONCLUSIONS: Current smoking, insulin resistance, uric acid level, and age contributed positively to the prevalence of metabolic syndrome. In contrast, smoking cessation within 1 year and work history did not contribute to metabolic syndrome.

[Evaluation of new saliva collection device for determination of salivary cotinine, cortisol, dehydroepiandrosterone and testosterone concentrations].

OBJECTIVES: This study was conducted to examine the effectiveness of a new salivary collection device (psi10 mm x 25 mm) made of polypropylene and polyethylene polymers (Salisoft((R))). METHOD: Experiment 1; We measured the absorption capacity of the new device by two methods. Next, we examined whether the device affected the pH of 0.1 M NaHCO(3) solution (pH 8.7) and 0.1 M sodium phosphate buffer solution (pH 6.0). Experiment 2; We compared three saliva collection methods: by passive drool, using a cotton device (Salivette((R))), and using the new device. Saliva samples were collected from twelve men (average age, 31.5 +/- 17.1 years). Saliva samples were assayed for cotinine, cortisol, dehydroepiandrosterone, and testosterone concentrations by enzyme immunoassay, and the pH of saliva samples were measured. RESULTS: After this device was put in the mouth for one minute, 1.28 +/- 0.13 mL (mean +/- SD, N = 6) of saliva samples were obtained. The mean pHs of saliva samples collected using Salisoft((R)) and by passive drool did not differ significantly, whereas that of saliva samples collected with Salivette((R)) was significantly low. Saliva samples collected with Salisoft((R)) and those obtained by passive drool did not show significant differences in the concentrations of cotinine, cortisol, dehydroepiandrosterone, and testosterone. Moreover, significant positive correlations were noted between the concentrations in saliva samples collected with Salisoft((R)) and those in saliva samples collected by passive drool. CONCLUSION: This new device was shown to be suitable for saliva collection for the determination of the concentrations of cotinine and some steroids by enzyme immunoassay.

Healthy lifestyles are associated with higher levels of perforin, granulysin and granzymes A/B-expressing cells in peripheral blood lymphocytes.

OBJECTIVE: It is well documented that natural killer (NK) cells provide host defense against tumors and viruses. We previously showed that lifestyle affects human NK and LAK activities. In order to explore the underlying mechanism, we investigated the effect of lifestyle on intracellular perforin, granulysin, and granzymes A/B in peripheral blood lymphocytes (PBL). METHODS: 114 healthy male subjects, aged 20-59 years, from a large company in Osaka, Japan were selected with informed consent. The subjects were divided into groups reporting good, moderate, and poor lifestyles according to their responses on a questionnaire regarding eight health practices (cigarette smoking, alcohol consumption, sleeping hours, working hours, physical exercise, eating breakfast, balanced nutrition, and mental stress). Peripheral blood was taken, and numbers of NK, T, perforin, granulysin, and granzymes A/B-expressing cells in PBL were measured by flow cytometry. RESULTS: Subjects with good or moderate lifestyle showed significantly higher numbers of NK, and perforin, granulysin, and granzymes A/B-expressing cells and a significantly lower number of T cells in PBL than subjects with poor lifestyle. Among the eight health practices, cigarette smoking, physical exercise, eating breakfast, and balanced nutrition significantly affect the numbers of NK, T cells, perforin, granulysin, and/or granzymes A/B-expressing cells, and alcohol consumption significantly affects the number of granzyme A-expressing cells. On the other hand, mental stress, sleeping, and working hours had no effect on those parameters. CONCLUSIONS: Taken together, these findings indicate that poor lifestyle significantly decreases the numbers of NK, perforin, granulysin, and granzymes A/B-expressing cells in PBL.

[The trial of simple gas analysis of tobacco smoke that can be used for medical education].

OBJECTIVE: The purpose of this study was to check a simple sampling and easy gas analysis of tobacco smoke for effective tobacco intervention in medical education. METHODS: The mainstream of tobacco smoke was sampled by a syringe (50 ml) at five, ten and twenty seconds. The extracted mainstream was moved to a commercial PET bottle (2000 ml), and measured with gas detector tubes. The sidestream, which rises from the tip of the cigarette, was collected into a commercial PET bottle for a duration of 30 or 60 seconds. Formaldehyde, acetaldehyde, ammonia, hydrogen cyanide, and nitrogen oxides (NO, NO2) in the tobacco smoke were measured. Then, these gasses in the tobacco smoke of four brands of cigarettes were compared. This trial was conducted in third-year medical students, and the changes in attitudes to smokers and tobacco itself were investigated. RESULTS: The method of sampling 50 ml for 5 seconds produced the highest concentration of each gas in the mainstream. The gas concentration in the sidestream increased as the sampling time increased. The gas concentration in mainstream of "Lucia" was the highest of the used four brands, and the gas concentrations in the sidestream of "Mild Seven Prime" were higher than those of the other brands. Many medical students obtained knowledge about the toxicity of smoking by this experiment study. CONCLUSION: We studied a simple sampling method of tobacco smoke, and gas analysis with gas detector tubes. This method is recommended for tobacco education and intervention in medical education.

Hemolysis of erythrocytes by granulysin-derived peptides but not by granulysin.

Granulysin, a 9-kDa protein localized in human cytolytic T lymphocytes and natural killer cell granules, is cytolytic against tumors and microbes but not against red blood cells. Synthetic peptides corresponding to the central region of granulysin recapitulate the lytic activity of the intact molecule, and some peptides cause hemolysis of red blood cells. Peptides in which cysteine residues were replaced by serine maintain their activity against microbes but lose activity against human cells, suggesting their potential as antibiotics. Studies were undertaken to determine the mechanism of resistance of red blood cells to granulysin and sensitivity to a subset of granulysin-derived peptides. Granulysin lyses immature reticulocytes, which have mitochondria, but not red blood cells. Granulysin lyses U937 cells but not U937 cells lacking mitochondrial DNA and a functional respiratory chain (U937rho(o) degrees cells), further demonstrating the requirement of intact mitochondria for granulysin-mediated death. Peptide G8, which corresponds to helix 2/loop 2/helix 3, lyses red blood cells, while peptide G9, which is identical except that the cysteine residues were replaced by serine, does not lyse red blood cells. Granulysin peptide-induced hemolysis is markedly inhibited by an anion transporter inhibitor and by Na(+), K(+), and Ca(2+) channel blockers but not by Na(+)/K(+) pump, cotransport, or Cl(-) channel blockers. Although recombinant granulysin and G9 peptide do not induce hemolysis, they both competitively inhibit G8-induced hemolysis. The finding that some derivatives of granulysin are hemolytic may have important implications for the design of granulysin-based antimicrobial therapeutics.