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Biomedical subjects

Edward Schwarz

Publications and source records attributed to Edward Schwarz.

5 recordsLinked to original sources

COX-2 has a critical role during incorporation of structural bone allografts.

Nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit cyclooxygenase (COX) activity, reduced pain and are commonly used in patients with skeletal injury. In this article we will also present data to show that selective COX-2 inhibitor delays allograft healing and incorporation. In contrast, local delivery of prostaglandin E2 (PGE2) enhanced bone formation at cortical bone graft junction. A 4-mm mid-diaphyseal segmental femoral defect was created and then repaired by frozen bone allograft of the same size. A 22-gauge metal pin was placed in the intramedullary cavity to stabilize the bone graft. Healing was evaluated weekly by X ray and by a semiquantitative histomorphometric analysis at 5 weeks postsurgery. Celecoxib (25 mg/kg/day) and Ketorolac (4 mg/kg/day) were administered daily for 2 weeks or 5 weeks. PGE2 was infused locally at a dose of 800 nmol/kg per day via osmotic minipump for 4 weeks. Inhibition of cyclooxygenase by daily administration of the Celecoxib or Ketorolac for 5 weeks reduced new bone ingrowth by about 60% (P < 0.05). The percentage of bony bridging in both drug-treated groups was significantly decreased at 5 weeks. Temporal administration of Celecoxib for 2 weeks also significantly reduced bone formation by 45% and withdrawal of the Celecoxib only led to slight recovery of bone formation at the graft side. In contrast to the inhibitory effects of NSAIDS, PGE2 infusion at the cortical bone junction increased bone formation by about twofold. These results demonstrated that COX-2 is essential for bone allograft incorporation. Furthermore, our data support the notion that COX-2-dependent PGE2 produced at the early stage of bone healing is prerequisite for efficient skeletal repair.

Animals↗

Evaluation and development of potentially better practices to prevent chronic lung disease and reduce lung injury in neonates.

OBJECTIVE: Despite increased knowledge and improving technology, chronic lung disease (CLD) rates in extremely low birth weight infants have remained constant for 20 years. One reason for this is an ineffective translation of research-proven improvements into practice. The Neonatal Intensive Care Quality Improvement Collaborative Year 2000 (NIC/Q 2000) was created to provide participating nurseries the tools necessary to effect change. The objective of this study was to develop and implement a process that uses quality improvement techniques to collaboratively improve CLD rates. METHODS: Nine member hospitals of the NIC/Q 2000 collaborative formed a focus group aiming to decrease CLD rates. The focus group established goals and outcome measures, created a list of potentially better practices (PBPs) based on available literature, benchmarked and performed site visits, encouraged individual site implementation of PBPs, developed a database, and measured outcomes. RESULTS: The goal "decrease CLD rates in extremely low birth weight infants" was established. Nine PBPs were identified, and 57 PBPs were implemented by the 9 participating sites. Twelve site visits were conducted, and a 435-patient database of infants with a mean birth weight of 789 g was established. CONCLUSIONS: Collaborative use of quality improvement techniques resulted in creation of a logical, efficient, and effective process to improve CLD rates. Group creation of PBPs, based on literature review and reinforced with site visits, internal data analysis, and improved individual site outcomes, resulted in accelerated and effective change, unlikely to occur if attempted outside of the collaborative.

Benchmarking↗

Implementing potentially better practices to reduce lung injury in neonates.

OBJECTIVE: Adherence to basic quality improvement principles enhances the implementation of potentially better practices (PBPs) and requires extensive planning and education. Even after PBPs have been identified and acknowledged as desirable, effective implementation of these practices does not occur easily. The objective of this study was to identify and assess implementation strategies that facilitate quality improvements in the respiratory care of extremely low birth weight infants. METHODS: The 9 members of the Neonatal Intensive Care Quality Improvement Collaborative Year 2000 Reducing Lung Injury focus group identified 9 PBPs in a evidence-based manner to decrease chronic lung disease in extremely low birth weight newborns. Each site implemented several or all PBPs based on a site-specific selection process. Each site was asked to submit 1 or more examples of experiences that highlighted effective implementation strategies. This article reports these examples and emphasizes the principles on which they are based. RESULTS: The 9 participating institutions implemented a total of 57 PBPs (range: 1-9; median: 5). Including previous implementation, the 9 participating institutions implemented a total of 70 of a possible 81 PBPs before or during the study period (range: 5-9; median: 8). We report 7 approaches that facilitated PBP implementation: information availability, feedback, perseverance, collaboration, imitation, recognition of implementation complexity, and tracking of process indicators. CONCLUSIONS: Quality improvement efforts are enhanced by identifying and then implementing PBPs. In our experience, implementation of these PBPs can be difficult. Implementation strategies, such as those identified in this article, can improve the chances that quality improvement efforts will be effective.

Benchmarking↗

Continuous bladder infusion methods for studying voiding function in the ambulatory mouse.

OBJECTIVES: To develop a method for chronic cannulation of the mouse bladder that would enable repeated intravesical drug delivery and measurement of voiding patterns in unrestrained mice under controlled infusion conditions. METHODS: Fifteen female mice were anesthetized with halothane and implanted with a 3F polyurethane bladder catheter. The catheter exited from the back through mesh and a polysulfone button into a spring coil that protected the catheter and tethered the mouse. A counterbalanced swivel and infusion pump permitted unencumbered mobility during continuous intravesical perfusion. RESULTS: Patent catheterization was consistently achieved for at least 5 weeks. The voiding patterns produced with an infusion pump were stable not only within a study session but also during the course of several weeks. The catheters remained patent but eventually withdrew from the bladder in 9 mice, at which point the mice were killed. The mesh eventually emerged from the skin in 4 animals without evidence of infection and was associated with catheter leakage at the level of mesh exposure. The subcutaneous placement of the mesh and tether assembly adequately transferred torque to the swivel without catheter obstruction. One mouse died unexpectedly during anesthesia; another was killed 1 week after catheter implantation because of an intraperitoneal leak. No bladder stones were identified. The results of the urine cultures were inconclusive. CONCLUSIONS: Continuous, patent catheterization of the murine bladder can be achieved consistently for a period of 5 weeks. When used in combination with counterbalanced swivel assemblies and electronic balance technology, these methods permit prolonged evaluation of micturition patterns in the awake, ambulatory mouse.

Administration, Intravesical↗

Microarray analyses of peripheral blood cells identifies unique gene expression signature in psoriatic arthritis.

Psoriatic arthritis (PsA) is a chronic and erosive form of arthritis of unknown cause. We aimed to characterize the PsA phenotype using gene expression profiling and comparing it with healthy control subjects and patients rheumatoid arthritis (RA). Peripheral blood cells (PBCs) of 19 patients with active PsA and 19 age- and sex-matched control subjects were used in the analyses of PsA, with blood samples collected in PaxGene tubes. A significant alteration in the pattern of expression of 313 genes was noted in the PBCs of PsA patients on Affymetrix U133A arrays: 257 genes were expressed at reduced levels in PsA, and 56 genes were expressed at increased levels, compared with controls. Downregulated genes tended to cluster to certain chromosomal regions, including those containing the psoriasis susceptibility loci PSORS1 and PSORS2. Among the genes with the most significantly reduced expression were those involved in downregulation or suppression of innate and acquired immune responses, such as SIGIRR, STAT3, SHP1, IKBKB, IL-11RA, and TCF7, suggesting inappropriate control that favors proin-flammatory responses. Several members of the MAPK signaling pathway and tumor suppressor genes showed reduced expression. Three proinflammatory genes--S100A8, S100A12, and thioredoxin--showed increased expression. Logistic regression and recursive partitioning analysis determined that one gene, nucleoporin 62 kDa, could correctly classify all controls and 94.7% of the PsA patients. Using a dataset of 48 RA samples for comparison, the combination of two genes, MAP3K3 followed by CACNA1S, was enough to correctly classify all RA and PsA patients. Thus, PBC gene expression profiling identified a gene expression signature that differentiated PsA from RA, and PsA from controls. Several novel genes were differentially expressed in PsA and may prove to be diagnostic biomarkers or serve as new targets for the development of therapies.

Adult↗