A hypertensive response to exercise is associated with transient ischemic dilation on myocardial perfusion SPECT imaging.

BACKGROUND: A hypertensive response to exercise (HRE) is associated with false-positive stress echocardiograms and myocardial perfusion single photon emission computed tomography (myocardial perfusion imaging [MPI]) defects even in the absence of coronary artery disease (CAD). Transient ischemic dilation (TID) of the left ventricle on stress MPI is a marker of severe CAD and future cardiac events. This study evaluated the association between an HRE and TID. METHODS AND RESULTS: Blinded quantitative TID assessment was performed in 125 patients who had an HRE and a summed stress score (SSS) of less than 4, as well as 125 control patients with an SSS of less than 4 and without an HRE matched for age, gender, and resting systolic blood pressure. Cardiac comorbidities, pretest Framingham risk, and exercise results were recorded. TID was defined as a stress-to-rest volume ratio of 1.22 or greater. An HRE was associated with a high prevalence of TID and significantly more TID than no HRE (25.6% vs 11.2%; odds ratio, 3.00 [95% confidence interval, 1.41-6.38]). TID was more prevalent even in subgroups with a low pretest probability CAD, including those without diabetes mellitus or angina. On conditional logistic regression analysis, an HRE was found to be independently associated with TID after consideration of other clinical and exercise MPI variables (odds ratio, 2.72 [95% confidence interval, 1.01-7.31]). CONCLUSION: An HRE is associated with a high prevalence of TID in patients without other significant perfusion defects, possibly as a result of global subendocardial ischemia induced by the HRE.     

Cerebral lipid deposition in aged apolipoprotein-E-deficient mice.

To assess the influence of age and diet on cerebral pathology in mice lacking apolipoprotein E (apoE), four male apoE knockout mice (epsilon -/-), and five male wild-type (epsilon +/+) littermate controls were placed on a high-fat/high-cholesterol diet for 7 weeks beginning at 17 months of age. All four aged knockout mice developed xanthomatous lesions in the brain consisting mostly of crystalline cholesterol clefts, lipid globules, and foam cells. Smaller xanthomas were confined mainly to the choroid plexus and ventral fornix in the roof of the third ventricle, occasionally extending subpially along the choroidal fissure and into the adjacent parenchyma. More advanced xanthomas disrupted adjoining neural tissue in the fornix, hippocampus, and dorsal diencephalon; in one case, over 60% of one telencephalic hemisphere, including nearly the entire neocortex, was obliterated by the lesion. No xanthomas were observed in aged wild-type controls fed the high-fat/high-cholesterol diet. Brains from 42 additional animals, fed only conventional chow, were examined; 3 of 15 aged (15- to 23-month-old) apoE knockout mice developed small choroidal xanthomas. In contrast, no lesions were observed in five young (2- to 4-month-old) apoE knockout mice or in any wild-type controls between the ages of 2 and 23 months. Our findings indicate that disorders of lipid metabolism can induce significant pathological changes in the central nervous system of aged apoE knockout mice, particularly those on a high-fat/high-cholesterol diet. It may be fruitful to seek potential interactions between genetic factors and diet in modulating the risk of Alzheimer's disease and other neurodegenerative disorders in aged humans.     

石杉碱甲类似物的研究II.N-甲基吡啶酮石杉碱甲类似物的合成

石杉碱甲(1)是从中草药石杉属植物千层塔(Lycopodium serratum Thunb.)中分得的一种高效可逆的乙酰胆碱酯酶抑制剂,临床试验证实它对早老性痴呆症有显著疗效。本文报道N-甲基吡啶酮石杉碱甲类似物2和3的合成。2-甲氧基-5-甲氧羰基-11-亚甲基-5,9-甲撑环辛-7-烯并吡啶(9)在乙腈中用三甲基氯硅烷和碘化钠选择性脱保护以定量的产率得吡啶酮10,再用甲醇钠和碘甲烷甲基化得N-甲基吡啶酮11,11经碱性水解,Curtius重排和氨基的脱保护得N-甲基吡啶酮石杉碱甲类似物2。通过类似的途径从中间体2-甲氧基-5-甲氧羰基-7-甲基-11-酮-5,9-甲撑环辛-7-烯并吡啶(14)合成了类似物3。类似物2和3的乙酰胆碱酯酶抑制活性均低于天然石杉碱甲。     

Etiology and treatment of acquired coagulopathies in the critically ill patient

Summary Excessive bleeding frequently complicates the care of critically-ill patients. Except in the case of trauma or in patients with known coagulopathies (e.g., hemophilia), the bleeding is generally not directly related to the illness that results in admission to the intensive care unit. In general, the causes of the bleeding can be divided into 3 categories: consumptive coagulopathies (e.g., DIC), bleeding related to ``hepatic issues' (i.e., liver dysfunction, vitamin K deficiency), and iatrogenic causes. This review will discuss the more common causes of bleeding in the critically-ill patient and outline diagnostic and treatment approaches for these patients. New experimental data linking activation of the coagulation and inflammatory systems with the development of multisystem organ failure is briefly discussed. Received: 8 November 1996 Accepted: 18 November 1996     

Sex ratio in relation to fathers'' occupations.

OBJECTIVE: To investigate whether the sex ratio of children varies between fathers of different occupations. METHODS: The sex ratio (the ratio of the number of boys to the number of girls at birth) was calculated in relation to paternal occupation in the cohort of all 253,433 live births in Cumbria, north west England, from 1950-89. Exact binomial confidence intervals were used to estimate whether the sex ratio in each occupational category was significantly different from that for the rest of the cohort. RESULTS: There were fewer occupational categories with significantly different sex ratios at the 5% level than expected by chance alone, assuming the same binomial distribution of sexes at birth within each paternal occupation. CONCLUSIONS: Significant variation of the sex ratio with fathers' occupations was not found. There is some evidence that the sex ratio shows less variance than expected under a binomial model which assumes independence of the sex of each child; a possible explanation of this may be parental preference for limiting family size after children of both sexes have been born or some other factor which results in children within a family being more likely to be of both sexes rather than the same sex.