Nonurgent Emergency-Department Care: Analysis of Parent and Primary Physician Perspectives

OBJECTIVE: To better understand parental decisions to seek care for their children and physician perceptions of parents' decisions to seek nonurgent emergency-department care. PATIENTS AND METHODS: In-depth interviews of 26 parents of children and 20 primary care physicians of the same children presenting for nonurgent care at a children's hospital emergency department were completed. Parent accounts of events that preceded the emergency-department visit were coded and qualitatively analyzed for themes. Physician evaluations of the accounts of events and parental decisions were ascertained through interviews with primary care physicians, who also described their practice characteristics. The parent/physician analyses allowed for an investigation of all aspects of the child's care and were designed to reveal differences between parent and physician beliefs. RESULTS: Parents believed that they acted appropriately, and physicians approved of parents' decisions. Four main themes emerged: (1) immediate reassurance that their children are safe from harm is critical to parents' decisions; (2) primary care offices lack specific tests and treatments that parents and physicians believe may be necessary, regardless of whether they are actually needed; (3) discrepancies exist between physician and parent perceptions of adequate communication and access; and (4) nonurgent emergency-department visits are not perceived as a significant enough breach in continuity of care by physicians and parents to warrant any concern. CONCLUSIONS: When individual interviews were evaluated, neither parents nor primary care physicians saw nonurgent emergency-department visits as a significant enough problem to warrant any change in physician care practices or parent care-seeking behavior. </jats:sec

Selection of individual VH genes occurs at the pro-B to pre-B cell transition.

International audienceB cells are subjected to selection at multiple checkpoints during their development. The selection of Ab H chains is difficult to study because of the large diversity of the CDR3. To study the selection of individual Ab H chain V region genes (V(H)), we performed CDR3 spectratyping of ∼ 75-300 rearrangements per individual V(H) in C57BL6/J mice. We measured the fraction of rearrangements that were in-frame in B cell DNA. We demonstrate that individual V(H)s have different fractions of in-frame rearrangements (IF fractions) ranging from 10 to 90% and that these IF fractions are reproducible in different mice. For most V(H)s, the IF fraction in pro-B cells approximated 33% and then shifted to the nearly final (mature) B cell value by the cycling pre-B cell stage. The frequency of high in-frame (IF) V(H) usage increased in cycling pre-B cells compared with that in pro-B cells, whereas this did not occur for low IF V(H)s. The IF fraction did not shift as much in BCR-expressing B cells and was minimally affected by L chain usage for most V(H). High IF clan II/III V(H)s share more positively charged CDR2 sequences, whereas high IF clan I J558 CDR2 sequences are diverse. These data indicate that individual V(H)s are subjected to differential selection, that V(H) IF fraction is mainly established through pre-BCR-mediated selection, that it may operate differently in clan I versus II/III V(H)s, and that it has a lasting influence on the Ab repertoire

Alternative mechanisms of receptor editing in autoreactive B cells

Pathogenic anti-DNA antibodies expressed in systemic lupus erythematosis bind DNA mainly through electrostatic interactions between the positively charged Arg residues of the antibody complementarity determining region (CDR) and the negatively charged phosphate groups of DNA. The importance of Arg in CDR3 for DNA binding has been shown in mice with transgenes coding for anti-DNA VH regions; there is also a close correlation between arginines in CDR3 of antibodies and DNA binding. Codons for Arg can readily be formed by V(D)J rearrangement; thereby, antibodies that bind DNA are part of the preimmune repertoire. Anti-DNAs in healthy mice are regulated by receptor editing, a mechanism that replaces κ light (L) chains compatible with DNA binding with κ L chains that harbor aspartic residues. This negatively charged amino acid is thought to neutralize Arg sites in the VH. Editing by replacement is allowed at the κ locus, because the rearranged VJ is nested between unrearranged Vs and Js. However, neither λ nor heavy (H) chain loci are organized so as to allow such second rearrangements. In this study, we analyze regulation of anti-DNA H chains in mice that lack the κ locus, κ-/κ- mice. These mice show that the endogenous preimmune repertoire does indeed include a high frequency of antibodies with Arg in their CDR3s (putative anti-DNAs) and they are associated mainly with the editor L chain λx. The editing mechanisms in the case of λ-expressing B cells include L chain allelic inclusion and VH replacement