In vitro flow based systems to study platelet function and thrombus formation: Recommendations for standardization: Communication from the SSC on Biorheology of the ISTH

Experimental videomicroscopic in vitro assays of thrombus formation based on blood perfusion are instrumental in a wide range of basic studies in thrombosis, screening for hereditary or acquired plateletrelated pathologies, and assessing the effectiveness of novel anti‐platelet therapies. Here, we discuss application of the broadly used “in vitro thrombosis model”: a frequently used assay to study the formation of 3D aggregates under flow, which involves perfusing anticoagulated whole blood over fibrillar collagen in a flow geometry of rectangular cross‐section, such as glass microcapillaries or parallel‐plate flow chambers. Major advantaged of this assay are simplicity and ability to reproduce the four main stages of platelet thrombus formation, i.e. platelet tethering, adhesion, activation and aggregation under a wide range of hemodynamic conditions. On the other hand, these devices represent, at best, simple reductive models of thrombosis. We also describe how blood flow assays can be used to study various aspects of platelet function on adhesive proteins and discuss the relevance of such flow models. Finally, we propose recommendations for standardization related to the use of this assay that cover collagen source, coating methods, micropatterning, sample composition, anticoagulation, choice of flow device, hemodynamic conditions, quantification challenges, variability, pre‐analytical conditions and other issues.     

A Dejerine-Sottas neuropathy family with a gene mapped on chromosome 8

The patient is a 55-year-old black male who belongs to a large family with 9 affected relatives with autosomal dominant Dejerine-Sottas neuropathy (DSN). Onset of his condition was at 2 years of age with steppage gait followed by severe progressive weakness, atrophy, and sensory loss of his legs and hands accompanied by areflexia and thoracolumbar kyphoscoliosis. The patient became wheelchair-confined at age 38. At around age 42, the left shoulder became dislocated and the humeral head underwent aseptic necrosis (Charcot joint). Nerve conduction studies showed absent motor and sensory responses for all major nerves tested. Genetic linkage suggested mapping of this DSN gene on chromosome 8qter. A younger brother with similar neurological findings also demonstrated Charcot joints with bone destruction of the joints of the fourth and fifth fingers. © 1996 John Wiley & Sons, Inc.     

Community-based research: barriers to recruitment of African Americans

The elimination of health disparities for African Americans requires culturally relevant, empirical knowledge, which in turn requires including African Americans in research studies. However, power-difference barriers and conceptual barriers continue to inhibit the recruitment of African Americans. The purpose of this article is to define and discuss certain barriers to the recruitment of African Americans into research studies and to present culturally and contextually sensitive strategies to overcoming these barriers. Power-difference barriers reflect unequal authority and often generate mistrust. Conceptual barriers reflect researchers' need for better understanding about African Americans. Effective strategies include collaboration with the community through a community advisory board and conducting community-based participatory action research. Also, integrating alternative conceptual frameworks with mainstream frameworks may reduce researchers' ideological assumptions about African Americans. To promote optimal recruitment of African Americans, researchers must be aware of power-difference barriers and conceptual barriers and move toward active collaboration with African American communities.     

MR imaging findings of retinal hemorrhage in a case of nonaccidental trauma

Retinal hemorrhage is a well-recognized manifestation of child abuse found in many babies with shaken baby syndrome. The presence of retinal hemorrhage is generally associated with more severe neurological damage and a worse clinical outcome. MR imaging findings of retinal hemorrhages are not well described in the pediatric literature. We present a 6-month-old boy with new-onset seizures, subdural hemorrhage and bilateral retinal hemorrhages that were detected by MRI and confirmed by indirect ophthalmoscopy. This case demonstrates the MR imaging findings of retinal hemorrhages and the importance of radiologists being able to recognize these specific imaging features.     

Effects of the immunoglobulin A1 protease on Neisseria gonorrhoeae trafficking across polarized T84 epithelial monolayers

We previously demonstrated that the Neisseria IgA1 protease cleaves LAMP1 (lysosome-associated membrane protein 1), a major integral membrane glycoprotein of lysosomes, thereby accelerating its degradation rate in infected A431 human epidermoid carcinoma cells and resulting in the alteration of lysosomes in these cells. In this study, we determined whether the IgA1 protease also affects the trafficking of Neisseria gonorrhoeae across polarized T84 epithelial monolayers. We report that N. gonorrhoeae infection of T84 monolayers, grown on a solid substrate or polarized on semiporous membranes, also results in IgA1 protease-mediated reduction of LAMP1. We demonstrate that iga mutants in two genetic backgrounds exited polarized T84 monolayers in fewer numbers than the corresponding wild-type strains. Finally, we present evidence that these mutants have a statistically significant and reproducible defect in their ability to traverse T84 monolayers. These results add to our previous data by showing that the IgA1 protease alters lysosomal content in polarized as well as unpolarized cells and by demonstrating a role for the protease in the traversal of epithelial barriers by N. gonorrhoeae.