Faculty Bibliography

We report on the adaptation and evaluation of a previously developed patient-centered instrument that we call the Quality of End-of-life care and Satisfaction with Treatment (QUEST) scale. In a separate group of 30 inpatients, test-retest reliability for QUEST items ranged from 63% agreement (kappa = 0.43) to 93% agreement (kappa = 0.86) and construct validity was evidenced by correlations with a somewhat related satisfaction scale ranging from 0.38 to 0.47. QUEST was then administered to 206 consecutive medical inpatients (or their surrogates) with DNR orders and to a comparison group of 51 medical inpatients without DNR orders at 2 academic medical centers. Among these main study patients, internal consistency was reflected by Cronbach alphas of 0.88 to 0.93. QUEST scores showed modest inverse correlations with severity of symptoms, but were uncorrelated with severity of illness, anxiety, or depression, suggesting an appropriate relationship to symptom control but divergence of the underlying construct from degree of physical illness or affective state. QUEST scores were lower for patients with DNR orders compared to those without DNR orders (P = 0.02 to 0.06). Surrogate ratings of satisfaction and quality were uncorrelated with patient ratings. Although preliminary, these findings suggest that QUEST may be useful in assessing quality and satisfaction with the care rendered by physicians and nurses to hospitalized patients at the end of life.

A large battery of anti-CD23 mAb were compared for their epitope specificities and for their abilities to alter both IgE binding to cell-associated CD23 and IgE production in vitro in response to three sets of stimulants. The nine mAb tested can be divided into four families which define four antigenic epitopes (A-D) of CD23. Of these four families, two bind antigenic sites, (A and D) that appear to lie outside the IgE ligand binding site and two bind sites (B and C) that appear to be located within or close to this site, as determined by the abilities of appropriate mAb to alter IgE binding to CD23. The effects that these mAb had on IgE secretion by normal peripheral blood mononuclear cells (PBMNC) varied depending on the stimulant employed to induce IgE production. Interactions with epitope A, which was found to lie outside the ligand binding site and to be made more accessible by binding of mAb to other epitopes, had different effects on IgE production than interactions with the other epitopes. Indeed, mAb binding to this epitope lead to as much as a 10 fold enhancement in IgE biosynthesis induced by IL-4 alone or by IL-4 + hydrocortisone whereas interactions at the other sites resulted in almost complete inhibition of IgE production. In addition, mAb reactive with epitopes B and C had minimal effects on IgE production induced by IL-4 + anti-CD40 mAb whereas interactions at epitope A consistently enhanced IgE production. Finally, no apparent direct correlation was found between the ability of individual anti-CD23 mAb to alter IgE binding to cell-associated CD23 and their ability to modulate IgE production by PBMNC. These studies suggest that IgE binding to cell-associated CD23 does not have a major role in the de novo synthesis of IgE that involves CD23 interactions. In addition, the different effects that binding to epitope A vs B or C have on IgE synthesis suggest that molecular interactions between distinct portions of the CD23 molecule and other cell surface molecules expressed on the same B cell or adjacent communicating cells may lead to divergent cellular effects on IgE production. Finally these studies imply that only epitope A is involved in the generation of an IgE response through the CD40 pathway