Identification of a Van der Woude syndrome mutation in the cleft palate 1 mutant mouse.

Mutations in Interferon Regulatory Factor 6 (IRF6) have been identified in two human allelic syndromes with cleft lip and/or palate: Van der Woude (VWS) and Popliteal Pterygium syndromes (PPS). Furthermore, common IRF6 haplotypes and single nucleotide polymorphisms (SNP) alleles are strongly associated with nonsyndromic clefting defects in multiple ethnic populations. Mutations in the mouse often provide good models for the study of human diseases and developmental processes. We identified the cleft palate 1 (clft1) mouse mutant in a forward genetic screen for phenotypes modeling human congenital disease. In the clft1 mutant, we have identified a novel missense point mutation in the mouse Irf6 gene, which confers an amino acid alteration that has been found in a VWS family. Phenotypic comparison of clft1 mutants to previously reported Irf6 mutant alleles demonstrates the Irf6(clft1) allele is a hypomorphic allele. The cleft palate seen in these mutants appears to be due to abnormal adhesion between the palate and tongue. The Irf6(clft1) allele provides the first mouse model for the study of an etiologic IRF6 missense mutation observed in a human VWS family.

Cooperation and consensus in the outcomes movement.

The "outcomes movement" is based on the confluence of two streams of influence: the translation of clinical outcomes research to applied settings and managed care's interest in competition and accountability. Leadership of the movement is diffuse, yet outcomes practitioners recognize the need for greater collaboration and information exchange. Two recent efforts to establish an ongoing forum for outcomes cooperation led to four consensus-based goals for collaboration: to disseminate information, to standardize measurement methods, to inform public opinion and public policy, and to use outcomes information to improve the quality of care. Obstacles to further progress on these four goals include lack of resources, lack of organization, and lack of leadership. Options for addressing these obstacles are presented.

Outcomes assessment in clinical settings: a consensus statement on principles and best practices in project management.

BACKGROUND: The focus of this article is on health-related outcomes particularly reducing symptoms and improving health status. Public policy, purchaser demand, quality assurance/quality improvement, clinical research, and the computerized medical record have all fed the increasing interest in outcomes. "Outcomes assessment" refers to the measurement, monitoring, and feedback of outcomes. In implementing outcomes assessment, the bulk of the work is concentrated in managing individual projects. From May 1992 through March 1993, under a grant from the Functional Outcomes Program of the New England Medical Center (Boston), the directors of five major health outcomes assessment programs held a series of meetings to share their experiences in implementation. Principles and recommended best practices for project management are provided here. Implementing an outcomes project: Making a commitment to begin includes identifying a condition or procedure to investigate, assembling a project team, and naming a coordinator. Designing a project entails defining its purpose and scope, developing the measurement instruments, and establishing a logistical protocol for data collection. Managing the data entails collecting the data, entering the data into a database, maintaining quality control over the data, and storing the data. Using the data entails analyzing the data, providing feedback and interpretation to clinicians, and linking outcomes to the clinical process. CASE STUDY: For a typical outcomes project--total hip replacement--the sequence of activities in the project and the staffing and resources needed are all described.

"Bicycle test" of van Gelderen in diagnosis of intermittent cauda equina compression syndrome. Case report.

The authors describe a simple clinical adjunct to the routine neurological examination of patients with intermittent cauda equina compression syndrome. The "bicycle test" helps exclude intermittent claudication due to vascular insufficiency and frequently confirms the relationship of posture to radicular pain.