Mortality risk attributable to atrial fibrillation in middle-aged and elderly people in the Japanese general population: nineteen-year follow-up in NIPPON DATA80.

BACKGROUND: The extent to which atrial fibrillation (AF) contributes to mortality in the Japanese general population has not been clarified. METHODS AND RESULTS: A randomly sampled general population from all over Japan (4,154 men, 5,329 women; age > or =30 years) was enrolled. Single electrocardiogram recordings were taken in the baseline survey. Stroke death, cardiovascular deaths and all-cause deaths during the subsequent 19 years were analyzed by the presence of AF at baseline. Cox's regression analysis was carried out to estimate the hazard ratios (HRs) of each cause of death attributable to AF after adjusting for other risk factors. Prevalence of AF was 0.64% in the study. The observed person-years were 162,980 among persons without AF and 699 among persons with AF. There were 1,919 deaths. Multivariate adjusted HRs for stroke death, cardiovascular death and all-cause death were 2.69, 2.76 and 1.88, respectively (p<0.05). These HRs were 14.7, 9.63 and 4.00 among persons aged 64 years or younger (p<0.05). CONCLUSION: AF affects stroke mortality, cardiovascular mortality and all-cause mortality in the Japanese general population. Careful attention should be paid to persons with AF in order to prevent future cardiovascular events.     

Diabetes and life expectancy among Japanese - NIPPON DATA80

Life expectancy (LE) among the Japanese population with or without diabetes mellitus was estimated. LE in 40-year old men and women was 41.1 and 47.5 years in those without diabetes and 32.3 and 40.9 years in those with diabetes. The LE of 40-year old men and women with diabetes was 8.8 and 6.6 years shorter than in those without diabetes. Diabetes mellitus leads to a decrease in LE. The presence of impaired glucose tolerance also affected LE inversely.     

Activation of c-Jun N-terminal kinase in non-cancerous liver tissue predicts a high risk of recurrence after hepatic resection for hepatocellular carcinoma

Aim: Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer deaths worldwide. Hepatic resection is the mainstay of curative treatment for early stage HCC. Although c‐Jun N‐terminal kinase (JNK) activation contributes to hepatocyte proliferation and HCC development in mice, the extent of involvement of JNK in human HCC development is unknown. The aim of this study is to assess the predictive value of JNK for postoperative recurrence in HCC. Methods: From April 2005 to March 2008, 159 patients underwent curative resection for HCC. From the 159 patients, 20 patients each matched for age, gender and etiology were registered as three groups: (i) without recurrence (no recurrence group), (ii) with recurrence within one year after surgery (early recurrence group), and (iii) with recurrence at one year or more after surgery (late recurrence group) (a cross‐sectional control study). We investigated factors contributing to postoperative early and late phase recurrence. Results: Multivariate analysis using a Logistic regression model showed that JNK activity in non‐cancerous liver tissue was correlated with postoperative late recurrence. (P = 0.02, odds ratio; 5.79, 95% confidence interval [CI]; 1.33–25.36). Conclusions: JNK activity in non‐cancerous liver tissue is considered as a reliable predictive biomarker for post‐operative recurrence in HCC.     

Effects of stress‐shielding on the dynamic viscoelasticity and ordering of the collagen fibers in rabbit Achilles tendon

We investigated the effects of stress‐shielding on both viscoelastic properties and microstructure of collagen fibers in the Achilles tendon by proton double‐quantum filtered (¹H‐DQF) NMR spectroscopy. The right hind‐limbs of 20 Japanese white rabbits were immobilized for 4 weeks in a cast with the ankle in plantarflexion. Dynamic viscoelasticity of the Achilles tendons was measured using a viscoelastic spectrometer. Proton DQF NMR signals were analyzed to determine the residual dipolar coupling of bound water molecules in the Achilles tendons. Both the dynamic storage modulus (E′) and dynamic loss modulus (E″) decreased significantly in the Achilles tendons of the stress‐shielding group. The results of the ¹H‐DQF NMR examination demonstrated significantly reduced residual dipolar coupling in the Achilles tendons of this same group. The disorientation of collagen fibers by stress‐shielding should contribute to degradation of the dynamic storage and loss moduli. The alterations of the collagen fiber orientation that contributed to the function of tendinous tissue can be evaluated by performing an analysis of ¹H DQF NMR spectroscopy. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1708–1712, 2013     

Thrombolytic properties of staphylokinase

We evaluated the properties of recombinant staphylokinase in comparison with those of tissue-type plasminogen activator (t-PA) and streptokinase (SK). The presence of fibrin(ogen) fragment FCB-2 in the reaction mixture increased plasminogen activation by staphylokinase more than 20-fold. Such characteristics are similar to those of t-PA. On the other hand, SK was not affected by the presence of FCB-2. The thrombolytic properties of staphylokinase were studied in a system consisting of a radioactive human plasma clot (125I-fibrinogen-labeled) suspended in the circulating citrated plasma. Significant thrombolysis (50% in 3 hours) was obtained with 2 micrograms/mL of staphylokinase and 4.45 micrograms/mL t-PA, as compared with 12 micrograms/mL for SK. The relative molar potency of staphylokinase, calculated from the molecular weight, was about two times more effective than that of SK, but about half of that of t-PA. Systemic fibrinolytic activation and fibrinogen breakdown was not observed with staphylokinase or t-PA, but was observed with SK. The thrombolytic efficiency of staphylokinase, which was calculated as the ratio of the degree of thrombolysis/the degree of fibrinogenolysis, was about five times greater than that of SK, and about half of that of t-PA. These findings suggest that staphylokinase has higher specific thrombolytic properties and lesser fibrinogenolytic properties than those of SK.     

Vagally mediated acid hypersecretion and lesion formation in anesthetized rat under hypothermic conditions

The pathophysiological changes associated with hypothermia were investigated in the rat stomach under anesthetized conditions. The animal was placed in a styrene foam box and the core body temperature was kept between 24 and 36°C using a heat lamp and refrigerant pack. Lowering of body temperature (<30°C) produced acid hypersecretion and induced hemorrhagic lesions in the gastric mucosa; these responses reached the maximum at 28°C, and a significant relationship was found between acid output and lesion score. Hypothermia (28°C) also caused a marked increase of gastric contractile activity and mucosal blood flow (MBF), but the ratio of acid output to MBF became greater when compared to that obtained under normothermic conditions. These changes induced by hypothermia (28°C) were completely blocked by vagotomy and were significantly inhibited by atropine, hexamethonium, clonidine, or TRH antiserum. However, lowering body temperature did not significantly affect acid secretory, motility, and ulcerogenic responses induced by carbachol in the vagotomized rat, excluding local mechanisms (suppression of the inhibitory nerves) in the hypothermia-induced changes. We conclude that hypothermia alone stimulates vagally dependent acid secretion and motility, resulting in damage in the gastric mucosa. These changes may be centrally mediated by TRH, which is released in association with the thermogenic response to hypothermia.     

Specific alcoholic beverage and blood pressure in a middle-aged Japanese population: the High-risk and Population Strategy for Occupational Health Promotion (HIPOP-OHP) Study

The purpose of this study was to clarify the effects of popular Japanese alcoholic beverages on blood pressure. We performed a cross-sectional study on 4335 Japanese male workers using baseline data from an intervention study. We defined six groups according to the type of alcoholic beverage that provided two-thirds of the subject's total alcohol consumption: beer, sake (rice wine), shochu (traditional Japanese spirits), whiskey, wine and others. The partial regression coefficients of daily alcohol intake (1 drink=11.5 g of ethanol) to systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 0.87(P<0.001, standard error (s.e.)=0.09) and 0.77(P<0.001, s.e.=0.06), respectively. A comparison among the types of alcoholic beverages mainly consumed revealed significant differences in SBP and DBP. Both SBP and DBP were highest in the shochu group. However, an analysis of covariance adjusting for total alcohol consumption resulted in the disappearance of these differences. Although after adjustment for total alcohol consumption, the shochu group exhibited a significant positive association with 'high-normal blood pressure or greater' (odds ratio 1.43, 95% confidence interval 1.06-1.95) compared with the beer group, this significant relation disappeared after adjusting for the body mass index (BMI), urinary sodium and potassium excretion. The pressor effect, per se, of popular Japanese alcoholic beverages on blood pressure may not be different among the types of alcoholic beverages after adjusting for other lifestyle factors.     

Low-risk profile for cardiovascular disease and mortality in Japanese.

BACKGROUND: Some studies focusing on low-risk profiles for cardiovascular disease have been reported in Western countries. Yet, few reports have examined, with substantial longevity, the low-risk profile for cardiovascular disease in the Japanese population. This study examines whether having a favorable risk factor profile yields lower all-cause mortality and whether the proportion of those with a low-risk profile is larger in the Japanese population. METHODS AND RESULTS: A total of 8,339 men and women aged 30-69 years without a history of cardiovascular diseases for 19 years, who had participated in the 1980 National Survey on Circulatory Disorders after being randomly selected from throughout Japan, were followed. Low risk was defined as having all of the following baseline characteristics: blood pressure (BP) <120/80 mmHg; no antihypertensive medication; serum cholesterol 160-240 mg/dl (4.14-6.22 mmol/L); no history of diabetes; and non-smoker. The long-term mortality of the low-risk group was compared with that of others using the Cox proportional hazard model. The prevalence of low risk was 9.4% of all participants. The multivariate-adjusted hazard ratios for low-risk individuals compared with others were as follows: 0.33 (95% confidence intervals (CI), 0.15-0.74) for cardiovascular disease and 0.63 (95% CI, 0.46-0.88) for all-cause mortality. The most attributable risk factor for all-cause mortality was high BP (>or=120/80 mmHg). CONCLUSION: Japanese individuals with favorable cardiovascular disease risk profiles had lower mortality from cardiovascular disease and all-causes than those without.     

Improvement of pulmonary function and dyspnea by tiotropium in COPD patients using a transdermal beta(2)-agonist

BACKGROUND: A combination of bronchodilators may be effective in the treatment of chronic obstructive pulmonary disease (COPD). We examined the effect of adding a long-acting anti-cholinergic agent (tiotropium) to a transdermal-type beta(2)-agonist (tulobuterol) on dyspnea as well as pulmonary function. METHODS: In a multicentre, randomized, parallel design study, 60 COPD patients treated with the transdermal beta(2)-agonist tulobuterol were divided into a tiotropium added group (Tulo+Tio group, n=40) or transdermal beta(2)-agonist tulobuterol alone group (Tulo group, n=20), and then treated for 4 weeks after a 2 week run-in period. Pulmonary function and a dyspnea (Medical Research Council (MRC)) scale were assessed before and after the treatment. Daily peak expiratory flow (PEF) monitoring was also performed. RESULTS: After 4 weeks, the Tulo+Tio group showed a significant increase in pulmonary function compared with the Tulo group; DeltaFVC (0.31+/-0.06 L vs. 0.06+/-0.05 L, p< 0.01), DeltaFEV(1) (0.15+/-0.03 L vs. -0.02+/-0.02 L, p<0.0001), and DeltaPEF (41.0+/-5.1 L/min vs. 0.5+/-3.5 L/min, p<0.0001). The MRC dyspnea scale was also significantly improved in Tulo+Tio, but not in Tulo group. CONCLUSION: These results suggest that tiotropium caused a significant improvement in both pulmonary function and dyspnea in COPD patients already treated with the transdermal beta(2)-agonist tulobuterol.