Tissue Doppler imaging a new prognosticator for cardiovascular diseases

Tissue Doppler imaging (TDI) is evolving as a useful echocardiographic tool for quantitative assessment of left ventricular (LV) systolic and diastolic function. Recent studies have explored the prognostic role of TDI-derived parameters in major cardiac diseases, such as heart failure, acute myocardial infarction, and hypertension. In these conditions, myocardial mitral annular or basal segmental (Sm) systolic and early diastolic (Ea or Em) velocities have been shown to predict mortality or cardiovascular events. In particular, those with reduced Sm or Em values of <3 cm/s have a very poor prognosis. In heart failure and after myocardial infarction, noninvasive assessment of LV diastolic pressure by transmitral to mitral annular early diastolic velocity ratio (E/Ea or E/Em) is a strong prognosticator, especially when E/Ea is > or =15. In addition, systolic intraventricular dyssynchrony measured by segmental analysis of myocardial velocities is another independent predictor of adverse clinical outcome in heart failure subjects, even when the QRS duration is normal. In heart failure patients who received cardiac resynchronization therapy, the presence of systolic dyssynchrony at baseline is associated with favorable LV remodeling, which in turn predicts a favorable long-term clinical outcome. Finally, TDI and derived deformation parameters improve prognostic assessment during dobutamine stress echocardiography. A high mean Sm value in the basal segments of patients with suspected coronary artery disease is associated with lower mortality rate or myocardial infarction and is superior to the wall motion score.     

Carcinogenicity studies of 1,4-dioxane administered in drinking-water to rats and mice for 2 years

The carcinogenicity of 1,4-dioxane was examined by giving groups of 50 F344/DuCrj rats and 50 Crj:BDF₁ mice of each sex 1,4-dioxane in the drinking-water for 2 years. The concentrations of 1,4-dioxane were 0 (control), 200, 1000 and 5000 ppm (wt./wt.) for rats and 0, 500, 2000 and 8000 ppm for mice. The highest dose levels did not exceed the maximum tolerated dose. In the rat, there was significant induction of nasal squamous cell carcinomas in females and hepatocellular adenomas and carcinomas in males and females, peritoneal mesotheliomas in males, and mammary gland adenomas in females. In the mouse, there was significant induction of hepatocellular tumors in males and females. Two nasal tumors occurring in the 8000 ppm-dosed groups were spontaneously rare and, thus, were attributed to 1,4-dioxane exposure. The present studies provided clear evidence of carcinogenicity in rats and mice. Lifetime cancer risk of humans exposed to 1,4-dioxane through drinking-water was quantitatively estimated with a non-threshold approach by application of a linearized multistage model to dose–carcinogenic response relationships, in addition to a threshold approach for estimation of the tolerable daily intake using no-observed- or lowest-observed-adverse-effect levels of the carcinogenic responses and uncertainty factors.     

Minireview on the toxicity of dietary acrylamide.

Acrylamide is a commodity chemical with many industrial and laboratory uses. It is also formed from carbohydrate and amino acid containing food by heating (primarily in fried potato products, bread, coffee). Neurotoxicity was detected as the primary toxic effect after occupational exposure. In rats and mice AA is toxic for reproduction and development and to male germ cells, is genotoxic through a reactive metabolite, glycidamide, and carcinogenic to several organs. Epidemiological studies did not point to an association between either occupational or dietary exposure and an excess of cancer incidence. Health risks of the general population are based on an average exposure to 1 microg/kg bw/day increasing for high consumers to 4 microg/kg bw/day. For average consumers a margin of exposure of 200 for neurotoxicity can be regarded as sufficiently protective. However, a margin of 300 for carcinogenic risks appears not sufficient when applying a precautionary principle. This is also illustrated when the benchmark dose lower confidence limit for cancer is divided by an uncertainty factor of 300, which arrives at a tolerable daily intake of 1 microg/kg bw/day, and thus is in the range of average consumption. Further measures to minimize acrylamide formation in food should therefore be explored to reduce human exposure.     

甲苯二异氰酸酯诱发的小鼠肺内炎症细胞c-myc的表达

目的　观察吸入甲苯二异氰酸酯 (TDI)诱发的小鼠肺损伤和TDI引起的肺内炎症细胞c myc的表达变化。方法　将 30只小鼠均分为 5组 (4个实验组 ,1个对照组 ) ,4个实验组在空气中TDI浓度为(4 30± 0 6 0 )mg/m3 时 ,分别吸入 1,2 ,3,4周 ,实验结束后常规留取肺标本并进行快速冰冻切片 ,免疫组织化学方法检测c myc在肺内的表达。结果　吸入TDI 2周后开始 ,小鼠肺泡腔内炎症细胞增加 ,主要为淋巴细胞及巨噬细胞渗出 ;随着吸入TDI时间的延长 ,肺泡腔内炎症细胞浸润进一步增加 ,肺间质出现明显纤维化 ;吸入TDI 1～ 4周后 ,各实验组小鼠气道上皮细胞、血管内皮细胞及肺内炎症细胞c myc表达均逐渐增多。结论　吸入TDI可引起小鼠肺内炎症细胞出游 ,增加气道上皮细胞、血管内皮细胞及肺内炎症细胞c myc的表达     

Accelerated loss of FEV- in polyurethane production workers: a four-year prospective study

A four-year longitudinal study of ventilatory function in polyurethane-foam production workers exposed to toluene diisocyanate (TDI) revealed a dose-response relationship between average exposure to TDI and change in forced expiratory volume per second (FEV-1). Workers with mean exposure in excess of 0.0035 ppm showed a greater rate of decline of FEV-1 over the four-year period than that expected from aging. Factors other than TDI exposure (sex, smoking history, history of atopy) do not account for the loss. The current threshold limit value (TLV) for exposure to TDI in industry (0.02 ppm) does not protect workers from accelerated impairment of ventilatory capacity.     

Increased left atrial volume index is an independent predictor of raised serum natriuretic peptide in patients with suspected heart failure but normal left ventricular ejection fraction: Implication for diagnosis of diastolic heart failure

BACKGROUND: Left atrial volume index (LAVI) is increasingly recognised as a relatively load-independent marker of left ventricular (LV) filling pressures. We assessed the capacity of LAVI to predict LV diastolic dysfunction in comparison with N-terminal pro B-type natriuretic peptide (NTproBNP) in patients with suspected heart failure and a normal ejection fraction (EF). METHODS: 137 patients with suspected heart failure (HF), referred from the community for echocardiography, prospectively underwent Doppler echocardiography, LAVI and NTproBNP estimation. Raised LAVI and reduced LV systolic function were defined as >26 ml/m2 and LV EF <50% respectively. RESULTS: Of 137 patients, 21 were excluded (2 with significant mitral valve disease and 19 with atrial fibrillation). Of the remaining 116 subjects, 92 showed normal LV systolic function. The univariate predictors of serum log NTproBNP were age (p < 0.001), LA dimension (p = 0.001), LAVI (p < 0.001), A wave (p = 0.001), E:A (p = 0.07) and septal wall thickness (p = 0.004). However on multivariate analysis, LAVI was found to be the most consistent and significant predictor of NTproBNP. The area under the curve of the receiver operating characteristic (ROC) curve for NTproBNP in detecting patients with LVEF > or = 50% and LAVI >26 ml/m2 was 0.81 (p < 0.0001) and for patients with LAVI > 26 ml/m2 with and without LVEF > or = 50% was 0.82 (p < 0.0001). CONCLUSION: This data confirms that LAVI on resting echocardiography, specifically in patients with suspected HF and normal LV systolic function is a powerful independent predictor of LV diastolic dysfunction as predicted by serum NTproBNP. In a population with a high suspicion of diastolic heart failure, LAVI may significantly contribute to diagnostic precision.     

A method for measuring mouse respiratory allergic reaction to low-dose chemical exposure to allergens: An environmental chemical of uncertain allergenicity,a typical contact allergen and a non-sensitizing irritant

Our aim was to improve a method for detecting respiratory hypersensitivity by testing three confirmed respiratory allergens (trimellitic anhydride [TMA], phthalic anhydride [PA] and toluene diisocyanate [TDI]), an environmental chemical of uncertain allergenicity (2,4-d-butyl [DB]), a confirmed contact allergen (2,4-dinitrochlorobenzene [DNCB]) and a standard irritant (sodium dodecyl sulfate [SDS]). BALB/c mice were topically sensitized (nine times in 3 weeks) with these chemicals, then challenged via the trachea. One day post-challenge, samples were taken from the mice to assay for total immunoglobulin (IgE and IgG₁) levels in serum and bronchoalveolar lavage fluid (BALF); differential cell counts and cytokine/chemokine levels in BALF; lymphocyte counts and surface antigen expression on B-cells within lung-associated lymph nodes (LNs); ex situ cytokine production by cells from these LNs; and gene expression in BALF (CCR3) and LNs (CCR4, STAT6 and GATA-3). The three confirmed respiratory allergens and DB induced immune response characteristic of immediate-type respiratory reactions, as evidenced by increased total IgE and IgG₁ levels; influx of eosinophils, neutrophils, chemokines and cytokines in BALF; increased surface antigen expression on B-cells in LNs; increased Th2 cytokine production in LNs; and increased respiratory allergy-related gene expression in both BALF and LNs. In contrast, DNCB and SDS treatments yielded, at most, insignificant increases in all respiratory allergic parameters. Thus, the protocol was equally suitable for use with an environmental chemical of unknown allergenicity and for typical respiratory allergens. Since the protocol differentiated respiratory allergens from contact allergens and irritants, it may be useful for detecting respiratory allergy related to environmental chemicals.     

Functional iron deficiency and diastolic function in heart failure with preserved ejection fraction

Background

Functional iron deficiency (FID) is an independent risk factor for poor outcome in advanced heart failure with reduced EF, but its role in heart failure with preserved EF (HFPEF) remains unclear. We aimed to investigate the impact of FID on cardiac performance determined by pressure–volume loop analysis in HFPEF.

Methods

26 HFPEF patients who showed an increase in LV stiffness by pressure–volume (PV) loop analysis obtained by conductance-catheterization, performed exercise testing, echocardiographic examination including tissue Doppler and determination of iron metabolism: serum iron, ferritin and transferrin saturation. HFPEF patients who provided ferritin < 100 μg/l or ferritin of 100–299 μg/l in combination with transferrin saturation < 20% were defined as having FID. In 14 patients the expression of transferrin receptor was determined from available endomyocardial biopsies.

Results

Fifteen out of 26 HFPEF patients showed FID without anemia. Compared to control subjects and HFPEF patients without FID, HFPEF patients with FID showed an up-regulation of the myocardial transferrin receptor expression (p < 0.05). No differences between HFPEF patients with and without iron deficiency were found in heart dimensions, systolic and diastolic function obtained by PV-loop and echocardiography analysis. According to the linear regression analysis, LV stiffness was correlated with peak oxygen uptake (r = − 0.636, p < 0.001) but not with the ferritin level or transferrin saturation. No relation was found between FID and exercise capacity. The association of LV stiffness with exercise performance was independent from the level of iron deficiency.

Conclusion

In non-anemic HFPEF patients, cardiac dysfunction and impaired exercise capacity occur independently of FID.     

评价结合组织多普勒（TDI）的Tei指数检测胎儿先天性心脏病早期心功能变化的价值

目的 探讨结合组织多普勒的Tei指数在评价胎儿先天性心脏病左心功能早期变化的价值.方法 选择经常规产前超声检查发现胎儿心脏结构或心律有异常的孕妇27例,以30例胎儿心脏结构或心律正常者为对照组.在常规胎儿超声心动图切面测量胎儿左室舒张末期内径及收缩末期内径（LVDd、LVDs）、左室射血分数（LVEF％）、左室缩短率（FS％）,应用组织多普勒于心尖五腔心切面测得Tei指数[Tei指数=（ICT＋IRT）/ET=（a-b）/b].对各组的EF、FS及Tei指数进行分析.结果 对照组胎儿的LVDd、LVDs、EF、FS及Tei指数没有明显变化;先心组EF％、FS％轻度减低,但是没有明显统计学意义;与对照组相比,先心组LVDd、LVDs没有明显统计学意义,而Tei指数相对于对照组则明显增高（P＜0.01）.结论 结合组织多普勒的Tei指数能早期敏感检测胎儿早期心脏功能的变化,为评估胎儿先天性心脏病早期心功能改变提供了客观依据.