Age and sex differences in the management of ischaemic heart disease

Objective

To investigate age and sex differences in the utilisation of hospital services for ischaemic heart disease.

Design

Analysis of routine mortality data and hospital activity data.

Setting

South West Thames Regional Health Authority.

Subjects

Residents of the South West Thames Regional Health Authority who in 1991 either died from ischaemic heart disease or were admitted to an NHS hospital in England and Wales with a main diagnosis of ischaemic heart disease.

Main outcome measures

Ratio of consultant episodes to deaths from ischaemic heart disease (as a proxymeasure of the utilisation of hospital care), and the percentages of consultant episodes in which further investigation (angiography or catheterisation) or revascularisation treatment (coronary artery bypass grafting or angioplasty) were carried out.

Results

The ratio of episodes to deaths was similar in men and women (odds ratio for men vs. women 0.96, 95% confidence intervals 0.90 to 1.03). The percentage of episodes in which further investigation was carried out was higher in men than women (odds ratio for men vs. women 1.46, 95% confidence intervals 1.25 to 1.70) as was the percentage of episodes in which revascularisation treatment was carried out (odds ratio for men vs. women 1.46, 95% confidence intervals 1.20 to 1.77). The ratio of episodes to deaths, the percentage of episodes in which further investigation was carried out, and the percentage of episodes in which revascularisation treatment was carried out all declined with age (all p values <0.001).

Conclusions

Women with ischaemic heart disease are as likely as men to be admitted to hospital, but afteradmission are less likely to undergo further investigation and revascularisation treatment. Elderly patients with ischaemic heart disease are less likely than younger patients to be admitted to hospital; after admission, they are also less likely to undergo further investigation and revascularisation treatment. Further research is needed to determine whether these age and sex differences in the use of hospital services are clinically justified.     

Congenital pulmonary atresia with ventricular septal defect: angiographic and surgical correlates

Of 181 patients with severe congenital pulmonary atresia and ventricular septal defect or "type IV truncus" (an obsolete term), all but 11% had true central pulmonary arteries. These arteries were demonstrable by large serial biplane angiograms using multiple selective injections into collateral vessels, frequent photographic subtraction, and occasional pulmonary vein-wedge angiograms. These techniques are extremely important for accurate diagnosis and in planning corrective or palliative surgery, which was done in 77% of patients with pulmonary arteries.     

地高辛抗血清对老龄大鼠心肌缺氧复氧损伤影响的体外实验

目的:观察内洋地黄素水平在老龄大鼠心肌细胞缺氧复氧损伤中的变化以及地高辛抗血清的保护作用。方法:实验于2005-04/05在皖南医学院病理生理教研室完成。取10只24月龄和10只6月龄雄性普通级SD大鼠,分别制备青年和老龄大鼠心肌细胞匀浆,老龄和成年大鼠为两大组,每组分为7小组,即每只大鼠心肌随机分到各小组中,共计14小组,每组10支试管。正常对照组:给予CO2和O2的混合气体(1∶19)通气40min;缺氧复氧组:CO2,O2,N2混合气体(5∶4∶91)通气20min后换成CO2和O2的混合气体(1∶19)通气20min;阴性对照组:同缺氧复氧组,但于再给氧前加入0.1mL的非特异性灭活兔血清;地高辛抗血清组:同缺氧复氧组,但于再给氧前加入0.1mL的非特异性地高辛抗血清(分别为1∶90000,60000,30000,10000)。观察大鼠心肌细胞钠-钾-三磷酸腺苷酶活性和线粒体内钙聚集程度,分析其剂量-效应关系。结果:①缺氧复氧时,青年组和老龄组大鼠心肌分泌内洋地黄素均显著升高,但老龄组显著低于青年组[(0.081±0.03),(0.153±0.06);(0.074±0.04),(0.125±0.05)ng/g;P<0.05]。②缺氧复氧时,老龄组与青年组心肌细胞钠-钾-三磷酸腺苷酶活性显著受抑制[(0.239±0.015),(0.778±0.050);(0.350±0.047),(0.836±0.044)μkat/g;P<0.05],老龄组与青年组相比,其抑制效应显著增强(P<0.05)。③缺氧复氧时,老龄组线粒体内钙与青年组比较明显增强[(0.082±0.011),(0.495±0.095);(0.075±0.008),(0.412±0.084)mmol/L,P<0.05]。④老龄组和青年组相比,地高辛抗血清呈剂量依赖性的恢复钠-钾-三磷酸腺苷酶活性(r=0.695,0.797,n=5,P<0.05),减轻线粒体内钙聚集(r=-0.565,-0.649,n=5,P<0.05);经直线回归分析发现,老龄鼠回归系数大于青年组(酶活性抑制K=1.50,0.94,线粒体内钙K=-7.43,-6.46)。结论:心肌细胞缺氧复氧时,老龄鼠损伤较青年大鼠更显著,其机制与老龄大鼠心肌细胞钠-钾-三磷酸腺苷酶对内洋地黄素敏感性增加有关,地高辛抗血清对老龄大鼠心肌细胞缺氧复氧保护作用更有效。     

Splenic lymphoma with villous lymphocytes involves B cells with extensively mutated Ig heavy chain variable region genes

Splenic lymphoma with villous lymphocytes (SLVL) is a recently defined subgroup of chronic B-cell lymphoproliferative diseases. The characteristic morphology of the tumor cells, together with phenotypic and cytogenetic findings, indicate that it is a distinct entity, but the nature of the cell or origin and its relationship to other low- grade lymphomas is unclear. For B-cell tumors, analysis of the variable region heavy chain (VH) genes used to encode the clonal Ig has shown marked differences between histologic categories, both in gene usage and extent of somatic mutation. An investigation of VH genes used in five typical cases of SLVL has shown somatic hypermutation from germline sequences in all cases, indicating that the cell of origin has been exposed to the hypermutation mechanism. However, no clonal heterogeneity was detectable, demonstrating that the tumor cell does not accumulate further mutations. These characteristics are similar to those found in mature postfollicular B cells, such as plasma cells. The distribution of mutations leading to replacement amino acids differed among the cases, with three of five cases showing clear evidence for antigen selection.     

Cancer‐associated somatic DICER1 hotspot mutations cause defective miRNA processing and reverse‐strand expression bias to predominantly mature 3p strands through loss of 5p strand cleavage

Our group recently described recurrent somatic mutations of the miRNA processing gene DICER1 in non‐epithelial ovarian cancer. Mutations appeared to be clustered around each of four critical metal‐binding residues in the RNase IIIB domain of DICER1. This domain is responsible for cleavage of the 3′ end of the 5p miRNA strand of a pre‐mRNA hairpin. To investigate the effects of these cancer‐associated 'hotspot' mutations, we engineered mouse DICER1‐deficient ES cells to express wild‐type and an allelic series of the mutant DICER1 variants. Global miRNA and mRNA profiles from cells carrying the metal‐binding site mutations were compared to each other and to wild‐type DICER1. The miRNA and mRNA profiles generated through the expression of the hotspot mutations were virtually identical, and the DICER1 hotspot mutation‐carrying cells were distinct from both wild‐type and DICER1‐deficient cells. Further, miRNA profiles showed that mutant DICER1 results in a dramatic loss in processing of mature 5p miRNA strands but were still able to create 3p strand miRNAs. Messenger RNA (mRNA) profile changes were consistent with the loss of 5p strand miRNAs and showed enriched expression for predicted targets of the lost 5p‐derived miRNAs. We therefore conclude that cancer‐associated somatic hotspot mutations of DICER1, affecting any one of four metal‐binding residues in the RNase IIIB domain, are functionally equivalent with respect to miRNA processing and are hypomorphic alleles, yielding a global loss in processing of mature 5p strand miRNA. We further propose that this resulting 3p strand bias in mature miRNA expression likely underpins the oncogenic potential of these hotspot mutations. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.