Prophylactic Greenfield filters: acute complications and long-term follow-up

The efficacy of prophylactic vena caval filters (VCF) in reducing morbidity and mortality from pulmonary embolism (PE) in high-risk trauma patients has been shown, but minimal follow-up data is currently available. VCFs were prophylactically placed in 110 patients between August 1991 and June 1995. There was an early VCF complication rate of 7%. Twenty-two patients died; the remaining 88 patients formed the basis for the follow-up study. Forty-five patients were located and interviewed by phone, and 30 of these patients (34%) returned for evaluation. The mean follow-up time was 18 months (range, 4-42 months). There was no incidence of caval thrombosis on follow-up. Eleven patients had physical findings, and duplex evidence consistent with postphlebitic syndrome. An additional three patients had evidence of old deep venous thrombosis (DVT) by duplex, but no significant symptomatology. VCF are effective in preventing PE related deaths and have few major complications. The long-term morbidity associated with posttraumatic venous thrombosis is significant. This morbidity is related not to PE or VCF, but to the underlying DVT. Improved strategies against DVT are necessary.     

Use of electroencephalography to detect Alzheimer''s disease in Down''s syndrome

Asthma is one of the most common chronic illnesses in childhood. Increases in hospitalization rates have occurred in several countries. The cumulative risk of asthma requiring medical attention was 11.7% for males and 7.0% for females aged 0-4 in Manitoba, Canada, for the cohort of children born in 1984/1985. The cumulative risk of hospitalization for males was nearly twice that of females (2.1% vs. 1.1%). Disease onset was most likely at age 1 year. The risk of rehospitalization or return physician visit for asthma increased significantly with the number of prior hospitalizations and physician visits, respectively, which may reflect both the persistence of asthma and the difficulty of developing an effective disease management strategy.     

Investigation of conformational specificity at GPIIb/IIIa: evaluation of conformationally constrained RGD peptides

RGD-containing proteins and peptides are known to bind to the platelet GPIIb/IIIa receptor and inhibit platelet aggregation. That a conformational component to the specificity exists is suggested by significantly lower activity of linear RGD analogs relative to closely related cyclic peptides and small proteins containing the RGD sequence. Recently, conformations for a suite of RGD containing cyclic peptides have been defined by NMR-based methods and, for one molecule, by X-ray diffraction. We report here the NMR-based conformational analysis of an additional cyclic peptide, cyclo(Pro-Arg-Gly-Asp-D-Pro-Gly), and compare the conformational variations in the suite of peptides and related analogs. Biological activity data for these peptides shows a preference of the platelet GPIIb/IIIa receptor for one conformation of the RGD sequence, but suggests its ability to bind a second, distinct conformation.     

Adding backbone to protein folding: why proteins are polypeptides

It is argued that the chemical nature of the polypeptide backbone is the central determinant of the three-dimensional structures of proteins. The requirement that buried polar groups form intramolecular hydrogen bonds limits the fold of the backbone to the well known units of secondary structure while the amino acid sequence chooses among the set of conformations available to the backbone. 'Sidechain-only' models, based for example on hydrophobicity patterns, fail to account for the properties of the backbone and thus will have difficulty capturing essential features of a folding pathway. This is evident from the incorrect predictions they make for the conformations of the limiting cases of all-hydrophobic or all-polar sequences.     

The role of eosinophils and neutrophils in helminth-induced keratitis

PURPOSE: Intrastromal injection of mice with antigens from the parasitic helminth that causes river blindness (Onchocerca volvulus) induces eosinophil recruitment to the corneal stroma at the time of maximum corneal opacification and neovascularization. The present study was conducted to examine the role of eosinophils and neutrophils in onchocercal keratitis in control C57Bl/6 mice and in interleukin-5 gene knockout (IL-5(-/-)) mice. METHODS: C57Bl/6 and IL-5(-/-) mice were immunized subcutaneously and injected intrastromally with soluble O. volvulus antigens. Mice were killed at various times thereafter. Development of keratitis was assessed by slit lamp examination, and inflammatory cells in the cornea were identified by immunohistochemistry. RESULTS: A biphasic recruitment of inflammatory cells was observed in C57Bl/6 mice; neutrophils predominated during the first 72 hours after intrastromal injection and subsequently declined, whereas eosinophil recruitment increased as time elapsed and comprised the majority (90%) of cells in the cornea by day 7. In contrast, neutrophils were the predominant inflammatory cells in IL-5(-/-) mice at early and late time points and were associated with extensive stromal damage and corneal opacification and neovascularization. Eosinophils were not detected in these mice at any time. CONCLUSIONS: In the absence of eosinophils, neutrophils can mediate keratitis induced by helminth antigens. Together with the early neutrophilic infiltrate in control animals, these observations indicate that neutrophils have an important role in onchocercal keratitis.