The natural history of asymptomatic carotid artery disease

PURPOSE: The purpose of this article is to determine the natural history of carotid artery disease among asymptomatic patients with cervical bruits or other risk factors for stroke and to study the value of duplex ultrasonography in predicting future neurologic events. METHODS: Two hundred forty-two asymptomatic, unoperated patients, referred for evaluation of asymptomatic carotid artery disease, were followed prospectively with duplex ultrasonography. RESULTS: Fifteen ischemic strokes (6.2%) and 20 transient ischemic attacks (TIA) (8.3%) occurred in 34 patients during a mean follow-up of 27.4 months. Annual stroke, TIA, and combined event rates were 2.7%, 3.6%, and 6.2%, respectively. Although patients with 80% to 99% lesions had a 20.6% annual event rate, most events occurred contralateral to these lesions; the vessel-specific annual event rate for 80% to 99% disease was 5.1%. Only one of 15 strokes occurred ipsilateral to an 80% to 99% stenosis. Echolucent plaques were associated with TIA and stroke (5.7% annual vessel event rate vs 2.4% for echogenic plaques, p = 0.03). Disease progression was highly correlated with TIA and stroke (p < 0.0001), but it usually occurred in association with rather than before ischemic events, thus proving more useful in explaining pathogenesis than in predicting future events. There was no association between aspirin use and TIA, but patients taking aspirin had a threefold higher annual stroke rate (1.6% vs 4.8%, p = 0.027). CONCLUSIONS: This study, while confirming significant risk for asymptomatic patients with critical stenosis or echolucent plaque, demonstrates the importance of contralateral disease and the absence of orderly progression from minimal disease through high-grade stenosis to symptomatic cerebral ischemia. TIA and stroke commonly occur in association with abrupt, unpredictable, quantum changes in carotid artery disease.     

Earth Rotation and Polar Motion: Measurements and Implications

Earth rotation and polar motion studies are embarking on a new era with the advent of highly accurate space geodetic techniques and the availability of global atmospheric angular momentum measurements. Space geodesy is opening new doors, answering old questions, and posing new ones. The angular momentum balance and the transfer of angular momentum between the solid Earth, atmosphere, and oceans are emerging as a problem of great scientific interest overlapping many areas, such as atmospheric science, oceanography, geodesy, and geodynamics. Here, the measurements of Earth rotation and polar motion (collectively referred to as Earth orientation) are described; the combination, smoothing, and intercomparison of these results from various techniques are presented. The calculation of atmospheric angular momentum (AAM) excitation functions are outlined; comparisons of the AAM excitation functions with variations in the length of day (LOD) and polar motion results are discussed. The associated geophysical implications (e.g., J2, 50-day oscillations) are stressed; anticipated advances and prospects for the future are high lighted.     

Apoptosis: molecular regulation of cell death

This article focuses on the few disorders that produce chronic cholestasis in infants and children. Cholestasis is defined, and a framework for thinking about pathophysiology is provided. Medical management is discussed in the context of the consequences and complications of chronic cholestasis. The limited differential for chronic cholestasis is discussed, and approaches to diagnosis and management of specific disorders are provided.     

Prevention of traffic accidents

To inform nursing professionals about their role in the prevention of traffic accidents, a grave health-related problem, is the purpose of this article. To begin with, factors which can deteriorate one's capacity to drive vehicles, and over which nursing professionals can intervene, will be presented. These factors include alcohol, other drugs, medicines, individual morbidity, the factor of aging and the use of security devices. A special reference will be made about widely used medicines. Finally the role that a nurse can fulfill will be explained. This role can be directed to various sections of the general public, be of varying natures, be exercised with greater or lesser ease, and lastly can have more or less effect upon those to whom it is destined.     

Oxidative damage and metabolic dysfunction in Huntington's disease: selective vulnerability of the basal ganglia

The etiology of the selective neuronal death that occurs in Huntington's disease (HD) is unknown. Several lines of evidence implicate the involvement of energetic defects and oxidative damage in the disease process, including a recent study that demonstrated an interaction between huntingtin protein and the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Using spectrophotometric assays in postmortem brain tissue, we found evidence of impaired oxidative phosphorylation enzyme activities restricted to the basal ganglia in HD brain, while enzyme activities were unaltered in three regions relatively spared by HD pathology (frontal cortex, parietal cortex, and cerebellum). Citrate synthase-corrected complex II-III activity was markedly reduced in both HD caudate (-29%) and putamen (-67%), and complex IV activity was reduced in HD putamen (-62%). Complex I and GAPDH activities were unaltered in all regions examined. We also measured levels of the oxidative damage product 8-hydroxydeoxyguanosine (OH8dG) in nuclear DNA, and superoxide dismutase (SOD) activity. OH8dG levels were significantly increased in HD caudate. Cytosolic SOD activity was slightly reduced in HD parietal cortex and cerebellum, whereas particulate SOD activity was unaltered in these regions. These results further support a role for metabolic dysfunction and oxidative damage in the pathogenesis of HD.     

Two independent internal ribosome entry sites are involved in translation initiation of vascular endothelial growth factor mRNA

The mRNA of vascular endothelial growth factor (VEGF), the major angiogenic growth factor, contains an unusually long (1,038 nucleotides) and structured 5' untranslated region (UTR). According to the classical translation initiation model of ribosome scanning, such a 5' UTR is expected to be a strong translation inhibitor. In vitro and bicistronic strategies were used to show that the VEGF mRNA translation was cap independent and occurred by an internal ribosome entry process. For the first time, we demonstrate that two independent internal ribosome entry sites (IRESs) are present in this 5' UTR. IRES A is located within the 300 nucleotides upstream from the AUG start codon. RNA secondary structure prediction and site-directed mutagenesis allowed the identification of a 49-nucleotide structural domain (D4) essential to IRES A activity. UV cross-linking experiments revealed that IRES A activity was correlated with binding of a 100-kDa protein to the D4 domain. IRES B is located in the first half of the 5' UTR. An element between nucleotides 379 and 483 is required for its activity. Immunoprecipitation experiments demonstrated that a main IRES B-bound protein was the polypyrimidine tract binding protein (PTB), a well-known regulator of picornavirus IRESs. However, we showed that binding of the PTB on IRES B does not seem to be correlated with its activity. Evidence is provided of an original cumulative effect of two IRESs, probably controlled by different factors, to promote an efficient initiation of translation at the same AUG codon.