Quantitative lymphatic vessel trait analysis suggests Vcam1 as candidate modifier gene of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic debilitating disease resulting from a complex interaction of multiple genetic factors with the environment. To identify modifier genes of IBD, we used an F2 intercross of IBD-resistant C57BL/6J-Il10(-/-) mice and IBD-susceptible C3H/HeJBir-Il10(-/-) (C3Bir-Il10(-/-)) mice. We found a prominent involvement of lymphatic vessels in IBD and applied a scoring system to quantify lymphatic vascular changes. Quantitative trait locus (QTL) analyses revealed a large-effect QTL on chromosome 3, mapping to an interval of 43.6 Mbp. This candidate interval was narrowed by fine mapping to 22 Mbp, and candidate genes were analyzed by a systems genetics approach that included quantitative gene expression profiling, search for functional polymorphisms, and haplotype block analysis. We identified vascular adhesion molecule 1 (Vcam1) as a candidate modifier gene in the interleukin 10-deficient mouse model of IBD. Importantly, VCAM1 protein levels were increased in susceptible C3H/HeJ mice, compared with C57BL/6J mice; systemic blockade of VCAM1 in C3Bir-Il10(-/-) mice reduced their inflammatory lymphatic vessel changes. These results indicate that genetically determined expression differences of VCAM1 are associated with susceptibility to colon inflammation, which is accompanied by extensive lymphatic vessel changes. VCAM1 is, therefore, a promising therapeutic target for IBD.

Two distinct mutations in gyrA lead to ciprofloxacin and nalidixic acid resistance in Campylobacter coli and Campylobacter jejuni isolated from chickens and beef cattle.

AIMS: The aim of this study was to identify point mutations in the gyrA quinolone resistance determining region (QRDR) of Campylobacter coli (n = 27) and Campylobacter jejuni (n = 26) that confer nalidixic acid (NAL) resistance without conferring resistance to ciprofloxacin (CIP). METHODS AND RESULTS: Point mutations in the QRDR of gyrA from C. coli and C. jejuni isolates were identified by direct sequencing. All isolates (n = 14) with minimum inhibitory concentrations (MICs) >or=4 microg ml(-1) for CIP and >or=32 microg ml(-1) for NAL possessed a missense mutation leading to substitution of Ile for Thr at codon 86. Three isolates with a missense mutation leading to a Thr86Ala substitution had MICs <4 mug ml(-1) for CIP and >or=32 microg ml(-1) for NAL. CONCLUSIONS: These data confirm previous findings that Thr86Ile mutations confer resistance to both CIP and NAL. However, resistance to NAL alone was conferred by a single Thr86Ala mutation. SIGNIFICANCE AND IMPACT OF THE STUDY: Resistance to NAL alone arises independently from CIP resistance. In addition, the role of other previously described point mutations in quinolone resistance is discussed.

Sequence analysis of two cryptic plasmids from an agricultural isolate of Campylobacter coli.

As part of a study identifying plasmids in Campylobacter, we isolated and sequenced two novel cryptic plasmids from an agricultural isolate of Campylobacter coli. The larger of the two plasmids, p3384, is 3316 bp in length and has a G+C content of 31.18%. A typical origin of replication consisting of five iterons was observed directly upstream of the first of three putative ORFs. The smaller plasmid, p3386, is 2426 bp in length and has a G+C content of 26.22%. Of the three putative ORFs detected on p3386, one shared homology with a putative protein from Campylobacter upsaliensis. The unique sequence of p3386 makes it attractive for further study concerning the evolutionary relationship of this plasmid to other Campylobacter plasmids, and to other Campylobacter isolates.

The influence of an organizational pain management policy on nurses' pain management practices.

PURPOSE/OBJECTIVES: To examine the influence of a formal organizational pain management policy on nurses' pain management practices. DESIGN: Descriptive correlational. SETTING: Tertiary-care medical center. SAMPLE: 91 nurses providing direct patient care on five study units during a 72-hour study period. METHODS: Off-going nurses completed three self-administered questionnaires one-half hour before the end of each eight-hour work shift. Opioid administration data also were collected. Data were analyzed using correlational, t test, chi-square, and analysis of variance analyses and descriptive statistics. MAIN RESEARCH VARIABLES: Nurses' knowledge of the healthcare organization's chronic pain management policy; nurses' knowledge of pain and pain management; nurses' perceived accountability for pain management activities; the ratio of actual amounts of opioid analgesics administered compared with maximum amounts ordered. FINDINGS: Nurses' knowledge of pain management and their perceived accountability for pain management were significantly related to knowledge of the organization's chronic pain management policy. Correlations were lower than expected, based on theoretical relationships proposed in the open system study framework. CONCLUSIONS: Further research is needed to explore the influence of a high-quality pain management policy on nursing practice and clinical pain management. IMPLICATIONS FOR NURSING PRACTICE: Better understanding of the influence of organizational policy could lead to much needed improvements in pain management.

Application of HEDIS measures within a Veterans Affairs medical center.

OBJECTIVE: To pilot test 3 HEDIS performance measures--beta-blocker treatment after a heart attack, ambulatory follow-up after hospitalization for mental illness, and cervical cancer screening--within a Veterans Affairs (VA) medical center. STUDY DESIGN: Retrospective review of administrative data. For 1 performance measure (beta-blocker treatment after a heart attack), a medical record review was performed for purposes of data validation. METHODS: The eligibility criteria differed by the performance measure. Eligible populations for the first, second, and third performance measures, respectively, were: (1) patients aged 35 years or older who were hospitalized and discharged alive with a primary diagnosis of acute myocardial infarction in calendar year 1996; (2) patients hospitalized for treatment of selected mental health disorders in fiscal year 1997; and (3) female patients aged 21 to 64 years enrolled in VA primary care clinics during fiscal years 1995-1997. We collected data in accordance with HEDIS 3.0 specifications for administrative data. RESULTS: With few or no modifications to the HEDIS specifications, we successfully adapted the HEDIS performance measures to the VA setting. We found that, in some areas, VA performance compared favorably to or exceeded that of the private sector. We also identified opportunities for quality improvement. CONCLUSIONS: HEDIS performance measures can be applied within the VA system, both as a means of quantifying performance and as a tool for improving the quality of care. Adopting HEDIS measures would provide additional value to VA medical centers by allowing them to compare their performance with that of private-sector providers.

Quality Enhancement Research Initiative in stroke: prevention, treatment, and rehabilitation.

Stroke is the third leading cause of death and a leading cause of adult disability in the United States. Both within and outside of the Veterans Health Administration (VHA), the lack of a systematic approach to stroke prevention and treatment may have contributed to reduced rates of compliance with recommended practices and increased rates of stroke. Gaps in the knowledge base inhibit a systematic approach to high-quality care within the veteran population. Initial recommendations for closing those gaps are proposed. In some cases (eg, systematic anticoagulation management), the VHA is perceived as a leader in applied research; therefore, a systematic national policy for implementing these clinics may significantly reduce stroke rates. In other areas (eg, carotid endarterectomy), databases exist that would help advance quality and outcomes, but short-term studies are necessary to establish their utility. To promote strategic improvement in prevention, treatment, and rehabilitation for veterans who may be at risk or have had a stroke, specific objectives are proposed to (1) identify best practices for the effective delivery of long-term anticoagulation and enhance veterans' access to these services, (2) develop risk-adjusted models for the surgical preventive procedure carotid endarterectomy to understand facility variation in outcomes so practices can be improved, (3) define a systematic acute stroke management system so that high-quality stroke-related care can be generalizable to a variety of VHA settings, and (4) assess the impact of poststroke rehabilitation on risk adjustment and the location of outcomes so as to facilitate the implementation of best rehabilitation practices.