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.     

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.     

Effect of physiotherapy on sickness absence in industry: a comparative study.

A cross-sectional comparative study was carried out in two chemical manufacturing plants in order to ascertain the effect of an occupational physiotherapy service on absence attributed to sickness. There was no overall effect on total sickness absence rates in this study, but a possible reduction in short-term sickness absence was noted. Changes in management attitudes to absence attributed to sickness at the comparison site caused a significant reduction in short-term absences. It is concluded that physiotherapy in an occupational setting has little effect on sickness absence compared to management attitudes, but the unquantifiable benefits, such as increased employee mobility, better industrial relations and employee morale may be significant benefits, worthy of further study.     

Leukocyte Depletion of Blood Cardioplegia Attenuates Reperfusion Injury

Background. Leukocytes are associated with myocardial injury during reperfusion after ischemia. Short periods of leukocyte depletion during reperfusion result in persistent attenuation of postischemic myocardial dysfunction.

Methods. Leukocyte depletion was examined in a canine model of regional myocardial ischemia and reperfusion. The extracorporeal circuit and cardioplegia circuits underwent leukocyte depletion by mechanical filtration. Animals were instrumented for baseline global function before 90-minute occlusion of the left anterior descending coronary artery. Global function during ischemia and at 5, 30, 60, and 90 minutes after a 60-minute cardioplegic arrest using continuous blood cardioplegia was assessed in leukocyte-depleted (n = 9) and control (n = 10) groups.

Results. No significant difference between groups was seen for systemic leukocyte counts, global function, or water content. Endothelial function was significantly protected as assessed by response to both calcium ionophore (endothelial-dependent, receptor-independent relaxation: leukocyte-depleted, 72% ± 19% of endothelin-induced constriction versus control, 46% ± 14%; p < 0.05) and acetylcholine (endothelial-dependent, receptor-dependent relaxation: leukocyte-depleted, 83% ± 11% versus control, 44% ± 15%; p < 0.05).

Conclusions. Leukocyte-mediated endothelial reperfusion injury can be attenuated by leukocyte depletion during reperfusion.