Brain protection for cerebral aneurysm surgery

The modern management of patients undergoing surgery for intracranial aneurysm often includes temporary periods of cerebral ischemia to minimize the risks final dissection and clipping or to allow vascular reconstruction. This article reviews the concepts of ischemic thresholds and examines the effects of the physiologic variables that may affect outcome from an ischemic episode. The protective agents presently available and the agents in development that may limit the extent of ischemic injury are reviewed extensively as well.     

Fibromuscular dysplasia of the internal carotid artery associated with alpha1-antitrypsin deficiency

OBJECTIVE: A deficiency of alpha1-antitrypsin has been implicated in the development of various disorders affecting medium-sized arteries, including intracranial aneurysms, cervicocephalic arterial dissections, and fibromuscular dysplasia (FMD). We performed alpha1-antitrypsin phenotyping in three consecutive patients who underwent bypass surgery for FMD of the extracranial internal carotid artery to test the hypothesis that alpha1-antitrypsin deficiency is a genetic risk factor for the development of FMD. METHODS: The study population consisted of three women (aged 37, 49, and 53 years, respectively) who had bilateral internal carotid artery stenosis caused by FMD. The indications for surgery included ocular or cerebral ischemic symptoms in two patients and progressive stenosis in one patient. The diagnosis of FMD was confirmed by histological examination of the resected segment of artery. The alpha1-antitrypsin phenotype was determined by isoelectric focusing in polyacrylamide gels. RESULTS: Two of the three patients had a heterozygous alpha1-antitrypsin deficiency (PiMZ phenotype). Pathological examination of the resected arterial segment showed typical medial FMD with focal intimal fibroplasia in both patients with the PiMZ phenotype. CONCLUSION: These findings suggest that a heterozygous alpha1-antitrypsin deficiency may be a genetic risk factor for the development of FMD of the internal carotid artery.     

Spruce budworm elastase precipitates Bacillus thuringiensis delta-endotoxin by specifically recognizing the C-terminal region

A gut juice protein from Choristoneura fumiferana (spruce budworm) larvae that precipitates certain delta-endotoxins shows a unique specificity for the C-terminal amino acid sequence. Using homolog scanning mutants, we have identified a contiguous region of the Cry1Aa toxin which interacts with the 75-kDa toxin precipitating protein (TPP-75)' resulting in precipitation. The contiguous region from Cry1Aa can be transferred to Cry1Ac and results in an identical precipitation reaction. The precipitation reaction occurs rapidly and is unique in that the ratio of precipitating protein to toxin is low (estimated at 0.01), unlike antibody-antigen reactions which exhibit mole ratios close to 1. TPP-75 has been characterized as an elastase-like serine protease. We have taken advantage of this serine protease character and incorporated a radiolabel using an irreversible inhibitor. The radiolabel has allowed us to show the coincidence of the catalytically-inhibited TPP-75 with the toxin in a blotting assay and to follow the degradation of TPP-75 during storage. TPP-75 represents the first evidence that gut juice proteins may selectively attenuate the activity of delta-endotoxins, prior to binding to putative receptors on susceptible cells. TPP-75 should be evaluated as a possible resistance mechanism for those larvae that do not exhibit a receptor-based resistance.     

Modelling internal migration in Kenya: an econometric analysis with limited data

"In this paper the determinants of internal migration in Kenya are analyzed on the basis of a human capital model. Explanatory variables included in the specification are both economic (wage rates and employment rates) and noneconomic (for example, population density and educational attainment). Also incorporated are variables which reflect intervening opportunities.... The econometric results show that destination variables are important determinants of internal migration, as is distance between the districts. Further, the variables for the intervening opportunities add significantly to the explanatory power of the model."