CD8 T Cells Are Required for the Formation of Ectopic Germinal Centers in Rheumatoid Synovitis

The assembly of inflammatory lesions in rheumatoid arthritis is highly regulated and typically leads to the formation of lymphoid follicles with germinal center (GC) reactions. We used microdissection of such extranodal follicles to analyze the colonizing T cells. Although the repertoire of follicular T cells was diverse, a subset of T cell receptor (TCR) sequences was detected in multiple independent follicles and not in interfollicular zones, suggesting recognition of a common antigen. Unexpectedly, the majority of shared TCR sequences were from CD8 T cells that were highly enriched in the synovium and present in low numbers in the periphery. To examine their role in extranodal GC reactions, CD8 T cells were depleted in human synovium-SCID mouse chimeras. Depletion of synovial CD8 T cells caused disintegration of the GC-containing follicles. In the absence of CD8 T cells, follicular dendritic cells disappeared, production of lymphotoxin-α1β2 markedly decreased, and immunoglobulin (Ig) secretion ceased. Immunohistochemical studies demonstrated that these CD8 T cells accumulated at the edge of the mantle zone. Besides their unique localization, they were characterized by the production of interferon (IFN)-γ, lack of the pore-forming enzyme perforin, and expression of CD40 ligand. Perifollicular IFN-γ+ CD8 T cells were rare in secondary lymphoid tissues but accounted for the majority of IFN-γ+ cells in synovial infiltrates. We propose that CD8+ T cells regulate the structural integrity and functional activity of GCs in ectopic lymphoid follicles

Variation in physicians' definitions of the competent parent and other barriers to guideline adherence: the case of pediatric minor head injury management

A lack of consensus regarding the definition of even an everyday term can affect physician adherence to clinical guidelines using that term. We demonstrate this by taking, as an illustrative case, the American Academy of Pediatrics' minor head injury (MHI) management guidelines, which generally recommend at-home observation by a "competent" parent (or the equivalent). The recommendation assumes consensus among physicians as to what parental competence comprises. We systematically examined this assumption. Physicians associated with Children's Hospital, San Diego were mailed a survey asking them to freely list terms defining parental competence. Independent variables were: physician gender, training, specialty, practice location, patient age mix, years in practice, and number of MHI cases seen per year. Dependent variables were: free-list content and length, ease and style of competence decision-making style (e.g., independent or collaborative), familiarity with the guidelines, and likelihood of ordering a computed tomography (CT) scan. Of 112 respondents, 34 (30%) were "not at all" or only "slightly" familiar with the guidelines; 23% (21/112) "frequently" or "sometimes" ordered CTs when the guidelines did not support this. Surgeons were more likely to order discretionary CTs. Office-based, pediatric-trained, and female physicians each found it significantly easier than their counterparts to determine which parents were, in their opinion, competent. Men reported using "objective" criteria significantly less frequently than women. A total of 64 discrete criteria were listed. Individual lists contained an average of 6.5 items. Surgeon's lists were significantly shorter than those of medical physicians. Seven sub-domains of competence were identified. Parental competence is not a unitary construct interpreted similarly by all physicians. Subgroups with distinct models may exist; training and specialization may be key variables. To decrease MHI management variation, guidelines should specify parental competence factors to be considered; they may need to be tailored to different physician subgroups.Decision making Guidelines Brain injuries Computed tomography Pediatrics Child health Physician-patient relations USA

Between 'desperation' and disability rights: a narrative analysis of complementary/alternative medicine use by parents for children with Down syndrome

This paper presents a narrative analysis of complementary/alternative medicine (CAM) use by parents for children with Down syndrome (DS), based on interviews conducted with thirty families. Critics often presume that CAM use for children with developmental disabilities reflects parental desperation in the face of limited biomedical options. Integrating insights from anthropological studies of CAM with narrative analyses in disability studies, we constructively complicate this interpretation in two ways. First, we suggest that the appeal of CAM may lie in its discursive consonance with the broader narrative strategies through which parents construct alternatives to conventional definitions of DS as a condition with a fixed, universal, and essentially pathological course. Second, we submit that the process of seeking and evaluating information about CAM is consonant with how parents construct their identities as 'good' parents through describing their roles as committed advocates and service coordinators for their children. In these ways, CAM can be conceptualized as a new discursive resource that parents engage in their culturally and historically specific efforts to articulate the essential human rights of their children, and to assert the moral soundness of their own parenthood. These findings provide a new conceptualization of parents' motives for choosing CAM, thereby posing new questions for further research about CAM use for developmental disabilities.Complementary/alternative medicine Down syndrome Narrative analysis Disability studies Consumerism USA