MHC class II beta sequence diversity in the deer mouse (Peromyscus maniculatus): implications for models of balancing selection.

We studied population polymorphism at a major histocompatibility complex (MHC) class II beta gene in the deer mouse (Peromyscus maniculatus). We found that: (i) a single population of P. maniculatus has significantly higher levels of DNA and protein sequence diversity than worldwide samples from homologous genes in other taxa, including humans and mice; and (ii) the genealogy of allelic sequences in P. maniculatus deviates significantly from theoretical expectation under a model of symmetric balancing selection, in that alleles are relatively more divergent than expected. We suggest that the observation of high levels of pairwise allelic sequence divergence and deviation of the genealogy from theoretical expectation in P. maniculatus together provide support for a divergent allele advantage model for the maintenance of MHC polymorphism.

Clinical evaluation units: a research agenda.

A new model for evaluating quality rests on the tripod of outcomes research, practice pattern analysis, and the tenets of continuous quality improvement. The hospital-based locus for this tripod could be clinical evaluation units. This article describes the conceptual framework, study design, and research challenges associated with an ongoing project whose purpose is to assess the current status of these clinical evaluation units in academic medical centers nationwide.

Overview: public accountability of hospitals regarding quality.

In this overview, the guest editors highlight some of the issues concerning the accountability of hospitals regarding quality, as raised by these articles. They then raise additional critical questions yet to be addressed.

Cost accounting supports clinical evaluations.

This article describes how a hospital cost accounting system was used to evaluate the financial impact of the use of a new and expensive drug at a 700-bed academic medical center.

Relationship between practice guidelines, formulary management, and pharmacoeconomic studies.

Pharmacy and therapeutics committees can use pharmacoeconomic and outcome studies as tools to evaluate and implement clinical guidelines for patient care. Results of studies help optimize the clinical effects and control the costs of drug therapy. Such data also assist in positioning products in competitive environments. A four-part classification of research studies is offered as an aid to strategic research planning.

Managing outcomes: the perspective of the players.

Outcomes management is most deeply rooted in clinical issues that interrelate concerns about quality with cost effectiveness of care. This is ground-breaking activity from many perspectives. Researchers must work more closely with clinicians and decision makers than ever before. Hospital executives must contend with many new external data demands and determine how to operationalize outcomes management programs within their institutions. There are new roles for clinician executives who act as change agents within health care organizations, while data on outcomes of care can lead to increased bargaining power among purchasers of services. In this article we discuss the major implications this new focus on managing outcomes is having on researchers, hospital executives, clinicians, and the purchasers of health care services.

Beta-lactam resistance in Nocardia brasiliensis is mediated by beta-lactamase and reversed in the presence of clavulanic acid.

Forty clinical isolates and the type strain of Nocardia brasiliensis were screened for susceptibility to 20 beta-lactams. Isolates exhibited a single pattern of resistance, with large zones of inhibition by disk diffusion and low MICs by broth and agar dilutions only to cefotaxime, ceftriaxone, ceftizoxime, Augmentin, and Timentin. All strains produced beta-lactamase, with five different enzyme patterns by isoelectric focusing. Despite the differences in their isoelectric points, the enzymes had the same substrate profiles, with equivalent activity against penicillin, ampicillin, cefamandole, cephalothin, and cephalordine. In an in vitro assay, the enzymes were highly susceptible to clavulanic acid. The MIC50 and MIC90 for the combination of amoxicillin and clavulanic acid (Augmentin) was 2 and 4 micrograms/ml, respectively, compared with 16 micrograms/ml for both values for amoxicillin alone. These studies suggest that beta-lactamase is the major mechanism of beta-lactam resistance in this species and that Augmentin is the first oral beta-lactam with good potential for treating infections due to N. brasiliensis.