Wade Davis

In Search of the Best Peritoneal Adhesion Model: Comparison of Different Techniques in a Rat Model

BACKGROUND Adhesion-related complications after abdominal surgery result in significant morbidity and costs. Results from animal studies investigating prevention or treatment of adhesions are limited due to lack of consistency in existing animal models. The aim of this study was to compare quality and quantity of adhesions in four different models and to find the best model. MATERIALS AND METHODS This study was approved by the University of Missouri Animal Care and Use Committee (ACUC). Forty female rats were randomly assigned to four different groups of 10 animals each. Adhesion created was performed utilizing the four techniques: Group 1 - parietal peritoneum excision (PPE), Group 2 - parietal peritoneum abrasion (PPA), Group 3 - peritoneal button creation (PBC), and Group 4 - cecal abrasion (CA). Rats were allowed to recover and necropsy was performed on postoperative d 14. Adhesions were scored by an established quantitative and qualitative scoring systems. The midline incision served as the control in each animal. RESULTS The four groups were not equal with respect to both quantity score (P<0.001) and quality score (P=0.042). The PBC group had the highest quantity of adhesions. The highest quality of adhesion was seen in the PPE group. A multivariate analysis carried out to quantify the performance of each model clearly demonstrated that PBC exhibited the best results in terms of both quantity and quality. CONCLUSIONS The button technique (PBC) is most consistent and reproducible technique for an intra-abdominal adhesion model. This model can help in the study and development of substances to prevent adhesion formation in the future.

A Review of Verbal Order Policies in Acute Care Hospitals

BACKGROUND Although verbal and telephone orders (VOs) are commonly used in the patient care process, there has been little examination of the strategies and tactics used to ensure their appropriate use or how to ensure that they are accurately communicated, correctly understood, initially documented, and subsequently transcribed into the medical record and ultimately carried out as intended. A systematic review was conducted of hospital verbal and telephone order policies in acute care settings. METHODS A stratified random sample of hospital verbal and telephone order policy documents were abstracted from critical access, rural, rural referral, and urban hospitals located in Iowa and Missouri and from academic medical centers from across the United States. FINDINGS Substantial differences were found across 40 acute care settings in terms of who is authorized to give (including nonlicensed personnel) and take VOs and in terms of time allowed for the prescriber to cosign the VO. When a nonphysician or other licensed prescriber was allowed to communicate VOs, there was no discussion of the process to review the VO before it was communicated in turn to the hospital personnel receiving the order. Policies within several of the same hospitals were inconsistent in terms of the periods specified for prescriber cosignature. Few hospitals required authentication of the identity of the person making telephone VOs, nor the use of practices to improve communication reliability. CONCLUSION Careful review and updating of hospital VO policies is necessary to ensure that they are internally consistent and optimize patient safety. The implementation of computerized medical records and ordering systems can reduce but not eliminate the need for VOs.

Algorithmic Discovery of Methylation "Hot Spots" in DNA from Lymphoma Patients

Summary The computational aspects of the problem in this paper involve, firstly, selective mapping of methylated DNA clones according to methylation level and, secondly, extracting motif information from all the mapped elements in the absence of prior probability distribution. Our novel implementation of algorithms to map and maximize expectation in this setting has generated data that appear to be distinct for each lymphoma subtype examined. A “clone” represents a polymerase chain reaction (PCR) product (on average ~500 bp) which belongs to a microarray of 8544 such sequences preserving CpG-rich islands (CGIs) [1]. Accumulating evidence indicates that cancers including lymphomas demonstrate hypermethylation of CGIs “silencing” an increasing number of tumor suppressor (TS) genes which can lead to tumorigenesis. Availability Algorithms are available on request from the authors Contact papageorgioc@health.missouri.edu Supplementary Information available on page 453.

The RNA-Binding Protein HuR Posttranscriptionally Regulates IL-2 Homeostasis and CD4+ Th2 Differentiation

Posttranscriptional gene regulation by RNA-binding proteins, such as HuR (elavl1), fine-tune gene expression in T cells, leading to powerful effects on immune responses. HuR can stabilize target mRNAs and/or promote translation by interacting with their 3′ untranslated region adenylate and uridylate–rich elements. It was previously demonstrated that HuR facilitates Th2 cytokine expression by mRNA stabilization. However, its effects upon IL-2 homeostasis and CD4+ Th2 differentiation are not as well understood. We found that optimal translation of Il2ra (CD25) required interaction of its mRNA with HuR. Conditional HuR knockout in CD4+ T cells resulted in loss of IL-2 homeostasis and defects in JAK–STAT signaling, Th2 differentiation, and cytokine production. HuR-knockout CD4+ T cells from OVA-immunized mice also failed to proliferate in response to Ag. These results demonstrate that HuR plays a pivotal role in maintaining normal IL-2 homeostasis and initiating CD4+ Th2 differentiation.

Access to musculoskeletal specialists and resources in free and charitable clinics: a survey of clinic directors.

To evaluate the capabilities and resources of free and charitable clinics in the United States to deliver musculoskeletal care to an indigent population.

Poster 218 The State of Musculoskeletal Care in Our Nation's Charitable Clinics: A Resource Inventory

The L tibial and L peroneal were WNL. Sensory NCS: The R tibial medial plantar nerve, b/l superficial peroneal showed no response. Of note, the superficial peroneal had technical difficulties secondary to a 60 Hz cycle which may have confounded the results. The L medial plantar showed nl peak latency and amplitude. The R sural displayed nl latency and amplitude. The L sural showed normal latency with decreased amplitude. The tibial H reflex was absent on the R, and normal on the L. Needle EMG: The R FDB (medial plantar S2,S1) and FDL displayed spontaneous activity with absent voluntary action potenials. The R medial gastroc (tibial S1, S2) showed increased insertional activity with normal amplitude but decreased interference pattern. The R anterior tibialis (Deep Peroneal L4,L5) showed normal electrical activity, except for decreased interference pattern. Discussion: Tibial nerve injury can result in weakened or absent plantar flexion and or impaired sensation over plantar aspect of the foot. The peroneal nerve has been the more commonly reported nerve injury following total knee athroplasty (TKA). Conclusions: This case report illustrates the possibility of isolated tibial nerve neuropathy after TRK.

Abstract 3271: The RNA binding protein HuR controls angiogenesis in triple negative breast cancer

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Due to the poor correlation between steady state mRNA levels and protein products, traditional microarray analysis may miss many genes which are regulated primarily at the level of mRNA stability and translation. Posttranscriptional gene regulation mediated by microRNAs and RNA binding proteins (RBPs) is being recognized as an important form of gene regulation. The elav (embryonic lethal abnormal vision) family of RBPs, are paraneoplastic antigens, over-expressed in a variety of malignancies, including breast cancer. Antibodies against elav family members are believed to be cancer-protective. The elav family binds to the AU-rich elements (AREs) found in the 3’ untranslated regions (UTRs) of many early-response genes, including proto-oncogenes and cell cycle regulators. HuR, the ubiquitously expressed family member, has been described to play a role in cancer progression by stabilizing and translationally up regulating expression of its target mRNAs. Elevated levels of cytoplasmic HuR directly correlate with increased invasiveness of malignancy and poor prognosis for many cancers, including those of the breast. HuR has been described to positively control the expression of multiple genes in the acquired capabilities model, such as VEGF and HIF1α. Hence, it has been suggested that HuR may serve as a tumor maintenance gene which allows for cancers to proliferate. Therefore, it is of interest to discover in vivo HuR targets, as these genes may play vital roles in transformed cells. We have developed methods called RNA immunoprecipitations applied to microarrays, RIP-Chip. We used RIP-Chip to identify distinct subsets of HuR associated mRNAs in MDA-MB-231 and MCF-7 breast cancer cell lines and validated several novel targets. To further investigate the role of HuR in triple negative breast cancer, we over expressed HuR in MDA-MB-231 cells, which results in accelerated growth and alterations in cell cycle kinetics. Surprisingly, when employed in orthotopic mouse models of cancer, HuR over expression significantly inhibited growth of triple negative tumors by 90%. Putative mechanisms appear to be anti-angiogenic, as HuR over expression increases anti-angiogenic factors, but surprisingly, also down regulates pro-angiogenic factors such as VEGF. These results are highly significant because they implicate HuR as a master regulator of angiogenesis in triple negative breast cancer tumor formation and suggest potentially novel treatment methods for this aggressive form of breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3271.