大象传媒

Locally administered antibiotics for prophylaxis against surgical wound infection: An in vivo study

Seth R. Yarboro, BS, Elyse J. Baum, BS, Laurence E. Dahners, MD

This study investigated the relative efficacy of various methods of antibiotic delivery for the prevention of surgical wound infections. Currently, the standard of surgical infection prophylaxis consists of perioperative systemic antibiotics. We hypothesized that sustained release of local antibiotics inside the wound cavity by a drug delivery system (DDS) would be more effective than systemically administered antibiotics. Using a rat model, we inoculated a surgical wound in the quadriceps musculature with 8.0 x 10⁵ CFU of Staphylococcus aureus (ATCC 29523), then administered one of seven treatments. There were 10 rats in each of the groups, consisting of: control (no treatment), bacitracin irrigation, calcium sulfate flakes, systemic gentamicin, local aqueous gentamicin, local gentamicin loaded calcium sulfate flakes, and a combination of local gentamicin loaded calcium sulfate and systemic gentamicin. To further evaluate a trend, the systemic gentamicin and local gentamicin solution groups were extended to include 25 and 27 rats, respectively. At 48 hours post surgery, the wounds were quantitatively cultured. The control, bacitracin irrigation and plain calcium sulfate groups had very high bacterial counts and high mortality rates while the gentamicin treatment groups had low bacterial counts and full survivorship. Local gentamicin was significantly more effective than systemic gentamicin. Refuting our hypothesis, the gentamicin loaded calcium sulfate flakes did not result in significantly lower bacteria counts than the systemic gentamicin. However, simple local gentamicin solution injected directly into the closed wound did result in significantly lower levels of bacteria than the systemic gentamicin. We believe that a high initial concentration of the locally applied antibiotic inside the wound effectively kills bacteria present in the wound cavity where systemic antibiotics have poor penetration, suggesting that this method of antibiotic administration may be a desirable adjunct for the prophylaxis of infection in surgical wounds.

Evolution of the Surgical Management of Neonatal Ovarian Cysts: Laparoscopic-Assisted Trans-umbilical Extra-corporeal Cystectomy (LATEC)

Lucy Schenkman¹, J.Duncan Phillips¹, Timothy Weiner¹

¹Department of Surgery

University of North Carolina, Chapel Hill, NC

听Background: Since its first detailed description in 1995, laparoscopic management of neonatal ovarian cysts has typically required multiple incisions, specialized equipment, and advanced laparoscopic skills. After some initial frustration with neonatal laparoscopy, we developed a simplified single-incision, Laparoscopic-Assisted, Trans-umbilical, Extra-corporeal Cystectomy (LATEC).

Objectives: This study reviews our experience with this technique and compares outcomes to those of our other surgically-managed neonatal ovarian cyst patients.
Methods: Retrospective record review of 20 patients treated surgically between 1992 and 2006. Student’s t-tests and ANOVA were used for comparisons (p<0.05=significant).
Results: Means: age 11 dys, weight 3.7 kg, cyst diameter 5.0 cm. 19 patients were diagnosed prenatally, at mean gestational age 33 wks. 12 of 20 (60%) had torsed cysts (1 bilateral). 3 of 13 torsed cysts (23%) were less than 4 cm diameter (range 2.9-3.5 cm). Laparotomies were transverse lower abdominal incisions. Laparoscopic operations used 2 incisions (3 patients) or 3 incisions (2 patients). LATEC involved trans-umbilical laparoscopy, complete cyst aspiration, and then cyst evisceration through the umbilicus for either ovarian cystectomy (simple cysts) or salpingo-oophorectomy (torsed cysts). Laparoscopic patients had similar time to feeds, length of stay (LOS), and postop narcotic requirements when compared to laparotomy patients (p=NS) but a high complication rate. LATEC patients had shorter surgical times (45.6 min versus 83.0 min)*, more rapid advancement to full enteral feedings (20.5 hrs versus 38.7 hrs)*, and shorter lengths of hospital stay (30.9 hrs versus 53.3 hrs)* when compared to traditional laparoscopy (*p<0.05). LATEC had equal ovarian preservation (100% of ovaries with simple cysts) to traditional laparoscopy. There were no major complications in the LATEC patients, and cosmetic results with LATEC were excellent.
Conclusions: Both laparoscopic and “open” approaches have low morbidity and rapid recovery. LATEC is a relatively simple procedure which combines laparoscopy and traditional extra-corporeal surgery and appears to offer improved outcomes, with a single incision.

Role of Myosin-X in the Formation and Function of Microvilli

Department of Cell and Molecular Physiology, 大象传媒-Chapel Hill

听听听听听听听听听听听 Myosin-X is an actin-based motor involved in intercellular transport. It has recently been shown that myosin-X is essential for filopodial formation and localizes to the tips of filopodia while exhibiting bidirectional movement along its length. This study investigates the role of myosin-X in a similar construct, microvilli. Microvilli are slender extensions composed of a core of actin filaments which is responsible for absorption and secretion by intestinal epithelial cells in the small intestine. As myosin-X is plays a necessary role in filopodia, we question whether myosin-X behaves similarly in microvilli, specifically, in its localization and its function in the formation and maintenance of the microvilli.

听听听听听听听听听听听 We utilized the Caco-2 construct, a human colon carcinoma cell line which most closely resembles human intestinal epithelial cells in structure and function. Localization of endogenous myosin-X was determined by epifluorescence staining over a two-week time course and viewed with confocal microscopy. Also, the quantity of myosin-X over the time course was determined by western blot. Over-expression of myosin-X was carried out through transient transfection of the Caco-2 cells with GFP-labeled myosin-X and was viewed with confocal microscopy.

听听听听听听听听听听听 Analysis of endogenous myosin-X in Caco-2 cells showed that myosin-X in cells in the non-polarized state (0-5 days) localizes to the tips of filopodia-like villous structures (immature microvilli). As the cells mature and became polarized (5-13 days), myosin-X then localizes all along the microvilli and concentrates in vesicles within the cell cytoplasm. Over-expression of myosin-X in mature Caco-2 cells shows decreased polarization and a less developed brush border. This suggests that myosin-X plays a role in the formation of microvilli at the filopodia-like stage (0-5 days) and in maintenance of polarization of microvilli in the mature stage (5-13 days). Further data will be elucidated through viral knock-down and expression of myosin-X in Caco-2 cells.

Anti-estrogen mediated enhancement of ATP-mediated ASL secretion in cystic fibrosis

听Russell Stackhouse, Robert Tarran¹, and Mark Clunes

¹Department of Cellular and Molecular Physiology

Cystic fibrosis airways exhibit a decreased airway surface liquid (ASL) height due to a lack of fluid secretion. This results in reduced mucus clearance and an impaired innate immunity leading to bacterial infections and destruction of the airways.听It has been shown that the estrogen receptor antagonist tamoxifen (TXN) can potentiate ATP-mediated ASL secretion, which is signaled via changes in intracellular calcium, which may be therapeutically beneficial for CF patients. Our aim was to evaluate whether other anti-estrogens were more efficacious than tamoxifen in stimulating increases in intracellular Ca²⁺. JME cells, derived from a CF patient, were stained for intracellular Ca²⁺ and measured by epifluorescent microscopy.听TXN, ICI 182,780 (a pure anti-estrogen), and 4-hydroxytamoixfen (4-HT; the major metabolite of TXN) were applied to the cells in the presence of ATP to create dose response curves.听BHK cells, that do not express 飦� or 飦� isoforms of the estrogen receptor, were also treated with TXN.听TXN showed significant potentiation of the calcium response to ATP in cells that express estrogen receptors.听Neither ICI_182,780 nor 4-HT showed potentiation of the calcium response in these same cells.听When tamoxifen was added to BHK cells that do not exhibit estrogen receptors 飦� or 飦� the same level of potentiation of the calcium response to ATP was witnessed.听The lack of potentiation by ICI_182,780 and 4-HT indicates that TXN鈥檚 potentiation of the Ca²⁺ response to ATP is mediated in some other way than the classical ER.听听 The same response seen in the BHK cells that do not exhibit the ER further supports this conclusion.听Further research should be performed to better elicit TXN鈥檚 mode of potentiation on the intracellular Ca²⁺ response to ATP.

Proyecto Puentes de Salud (Project Health Bridges): The relationship of economic migration and HIV risk factors in Rural Mexico.

Ian J Nelligan^1,2, Amanda L Rollins^1,2, Allan D Nanney^1,2, 听Trista D Snyder^1,2, Pamela Y Frasier MA, MSPH, PhD¹, Alfred Reid MS¹, Bron Skinner PhD¹, Daniel Reuland MD², Mauricio G Cohen MD³

¹Department of Family Medicine, Department of Internal Medicine², Department of Cardiology³

Several well recognized studies have defined risk factors for HIV transmission among male economic migrants in NC and the US, however, there remains a deficit in primary research of HIV risk among the partners of economic migrants in rural Mexico. A convenience sample of 169 participants, recruited from six rural communities in Guanajuato, Mexico were offered free HIV testing using the Oraquick庐 Advance鈩� Rapid HIV-1/2 Antibody Test and counseled about risk factors and reduction strategies for HIV by bilingual investigators. A counselor-conducted survey was used to assess extent economic migration impacted the rick of acquiring HIV. Additionally, self-administered HIV knowledge survey was used to assess the basic and advanced knowledge of HIV and risk reduction. Women comprised 85.8% of those tested.听Aproximately 90% of participants neither migrated nor used condoms routinely; however, those who used condoms regularly were 4.6 times more likely to have migrated. Those who migrated were 48 times more likely to have sex with a commercial sex worker and 67% never or almost never used condoms with them.听Risk of HIV transmission is high in this population while condom was very low.听Those that migrated to the US were much more likely to engage in high risk behavior. Participants that never left Mexico have risk derived from transnational migration between communities with a steep gradient of HIV incidence.

Introduction: A collaborative Duke/大象传媒 study in Durham, NC revealed that 46% of single Hispanic men, and 42% men living apart from their wives, had intercourse with sex workers within the last year. While increased risk factors for HIV transmission among male economic migrants in NC and the US have been established in several studies, there is a lack of information about HIV risk among the spouses of economic migrants in rural Mexico. Using a preliminary HIV risk assessment survey, we selected six rural communities near Juventino Rosas (JR), Guanajuato, Mexico with estimated 66% or more of the working men migrating to the US and a large number coming to the South. JR was chosen because of the Sister City and Sister Church relationships with Carrboro, NC and the Catholic Church of Chapel Hill, NC. Identical screenings are planned in Orange and Chatham Counties, NC.

Methods: A convenience sample of 169 participants, recruited from six rural communities in Guanajuato, Mexico during June and July of 2006, were (1) offered free HIV testing using the Oraquick庐 Advance鈩� Rapid HIV-1/2 Antibody Test听and (2) counseled about risk factors and reduction for HIV by bilingual investigators. The participant was then offered the free, confidential HIV screening. All participated in a counselor-conducted survey to assess economic migration defined as 鈥渕igration to the US to live or work for 1 month or more鈥� and risk of acquiring HIV. A self-administered HIV knowledge survey was used to assess the basic and advanced knowledge of HIV and risk reduction of 34 individuals in one community. Networks were set up with local doctors to provide care in positive test situations.

Results: Using Oraquick庐 Advance鈩� Rapid HIV-1/2 Antibody Test, 169 people were tested for HIV, 0.0% were positive. 169 individuals participated in our study. Women comprised 85.8% of those tested and 11% of those sampled had been to the US.

Analysis of the HIV risk survey showed that aproximately 90% of participants neither migrated nor used condoms routinely; however, those who used condoms regularly were 4.6 times more likely to have migrated. Of those screened, participants who migrated were 17 times more likely to have had more than one sexual partner.听Those who migrated were 48 times more likely to have sex with a commercial sex worker and 67% never or almost never used condoms with them. 61% of those that have migrated had sex with a commercial sex worker compared with 3% that had not migrated.听

Discussion: While incidence of HIV was not found, the risk of HIV transmission is high in this population. Condom use in this population was very low.听Those that migrated to the US were much more likely to engage in high risk behavior including multiple sexual partners, little condom use and sex with commercial sex workers.听Those that never left Mexico had little risk as a group but many had one life time partner that introduced risk.听The investigation was limited by being a convenience sample of those attracted to a health fair setting and the under-representation of male participants due to the fact that the vast majority was in the US at the time. HIV knowledge was very limited. Data analysis is ongoing.听

Impact of a 12 Week School-Based Intervention on

Nutrition and Physical Activity Knowledge, Attitudes, and Behaviors

Improving Meals and Physical Activity in Children and Teens (IMPACT)

Natalie Muth¹, Avik Chatterjee¹, Donna Williams³, Kori Flower²

¹School of Medicine and ²Department of Pediatrics, University of North Carolina, Chapel Hill, NC;³Orange County Schools, North Carolina

Poor nutrition and inactivity are widespread and contribute to the epidemic problem of childhood overweight.听This study examines the effectiveness of a pilot program to improve nutrition and activity in 4^th graders and teens in a rural North Carolina community.听The Improving Meals and Physical Activity in Children and Teens (IMPACT) school-based curriculum used a train-the-trainer model to encourage increased activity and healthier nutrition.听Six medical students taught nine teens (ages 16-17) recruited from one high school the IMPACT curriculum and leadership skills during a 15-hour training program.听Four 4^th grade classes at a neighboring school were randomized to receive the IMPACT curriculum delivered by the medical students and teens over 12 weeks (2 classrooms, 38 students) versus standard curriculum (2 classrooms, 37 students).听Outcomes were assessed using pre-intervention and follow-up survey and BMI measures. 听The hypothesis is the teens and 4th grade intervention groups will increase (1) nutrition and physical activity knowledge and attitudes; (2) daily fruit, vegetable, whole grain, and dairy product consumption; and (3) amount of physical activity.听Results indicate that 4^th graders in the intervention group significantly increased fruit and vegetable intake (p<0.05), knowledge of food group to eat the most servings (p<0.01), and recommended number of servings of fruits and vegetables to eat daily (p<0.01).听The number of teens lost to follow up prohibited analysis of teen outcomes.听If disseminated more widely, the IMPACT curriculum could support healthy nutrition and activity in high school and elementary school settings.

Bradykinin B1 and B2 receptors both have protective roles in renal ischemia-reperfusion injury

Robert W. McGarrah, Masao Kakoki, Hyung-Suk Kim and Oliver Smithies

Department of Pathology and Laboratory Medicine

Ischemic events such as stroke, myocardial infarction and acute renal failure are well-known and devastating complications in patients with hypertension, diabetes and atherosclerosis.听Moreover, damage incurred during ischemia/reperfusion (I/R) of transplanted allografts directly impacts short-term and long-term graft outcomes.听Angiotensin-I converting enzyme inhibitors (ACEIs), in addition to their beneficial effect on chronic cardiac remodeling after ischemia, have been demonstrated to prevent acute injury caused by I/R in the heart, lung, liver and kidneys.听Studies indicate that this protective effect is due mainly to activation of the bradykinin-nitric oxide (NO) cascade rather than suppression of angiotensin II formation.听Indeed, angiotensin receptor blockers are much less effective than ACEIs in protecting against I/R injury and bradykinin receptor antagonists and NO synthase inhibitors attenuate the protective effects of ACEIs.听There are conflicting results, however, regarding the exact role of bradykinin receptor stimulation in I/R injury and some studies suggest that stimulation of the bradykinin B1 and bradykinin B2 receptors may have opposite effects from each other in this situation.

We used mice lacking either the bradykinin B2 receptor gene (Bdkrb2^-/-) or both the bradykinin B1 and B2 receptor genes (Bdkrb1^-/-Bdkrb2^-/-) to further investigate the role of the bradykinin receptors in renal I/R injury.听After 30-minutes of bilateral renal occlusion and 24-hours of reperfusion, mortality rates, renal histological and functional changes, 8-OHdG levels in total DNA (a marker of oxidative DNA modification), mitochondrial DNA deletions, the number of TUNEL-positive cells, and mRNA levels of transforming growth factor 尾1 and endothelin-1 in the kidneys of Bdkrb1^-/-Bdkrb2^-/- mice were significantly more enhanced than in Bdkrb2^-/- or wildtype mice.听Therefore, both the bradykinin B1 and B2 receptors play an important protective role in reducing DNA damage, apoptosis, morphological and functional kidney changes, and mortality during renal I/R injury.

of Six Rural Honduran Communities Served

by the 大象传媒 Honduran Health Alliance

¹Department of Family Medicine, ²Department of Nutrition

University of North Carolina, Chapel Hill

Honduras is one of the poorest Latin American countries with over 68% of its residents classified as at or below the poverty level.听Honduras also suffers from increased rates of insufficient food intake, protein malnutrition, low birth weight, and stunted growth. The situation is even worse in rural communities.听The 大象传媒 Honduran Health Alliance (HHA) exists in an effort to improve the health status of rural Honduran families.听The purpose of this study was to determine the target population鈥檚 health and nutrition status based on a variety of factors including background conditions; community conditions; living, working and social conditions; and individual lifestyle factors. The community needs assessment was conducted in four stages: a literature review, a focus group meeting with four of the Honduran lay health advisors, focus groups with community members who attend the educational Charlas (focused health discussions led by the Honduran Health Alliance medical students), and 24 hour dietary recall and BMI measurements.听Results indicate that women studied maintain a healthy weight, eat an unvaried diet low in fruits and vegetables, and have a stronger desire to eat more fresh produce and a more varied diet but feel they have limited access to those foods. The HHA is in a unique position to help community members develop creative solutions to improve dietary intake including modifying educational teaching and collaborating with community members on creating sustainable projects such as a community garden.

Clinical Characteristics and Prognostic Factors of

Lauren Paton¹; Jonathan R. Salahshour^1,2; Aram Kim^1,2 and Craig Barrett¹, Toan T. Huynh¹; Britt Christmas¹, Ronald Sing¹

¹Department of General Surgery

Carolinas Medical Center, Charlotte, NC

University of North Carolina, Chapel Hill, NC

Appropriate empiric antimicrobial therapies against life-threatening bacterial infections such as meningitis, pneumonia, and sepsis has been shown to decrease morbidity and mortality as compared to therapies strictly based on a definitive culture diagnosis. The decision to cover select virulent and/or common organisms is a dynamic process that involves re-evaluation of the patient population and the infectious organisms responsible. Stenotrophomonas maltophilia is a multidrug-resistant, gram-negative rod which causes nosocomial infections in immunocompromised patients and patients who are subjected to invasive devices such as catheters or endotracheal tube. Currently, Stenotrophomonas maltophilia infections are not included in empiric treatment coverage for pneumonia and sepsis for the patient population susceptible. To analyze the effects of empiric therapy on the clinical outcome of Stenotrophomonas maltophilia infections, all surgical patients at the Carolinas Medical Center from May 2003 to July 2005 treated for Stenotrophomonas maltophilia infections were retrospectively reviewed. Patient demographics, length of stay (LOS), concomitant infections, antibiotic susceptibilities and mortality was analyzed with standard statistical testing with a confidence interval of p<0.05. The study identified eighty-two patients (37 females/ 45 males) with an mean age of 54.6 years (range; 12-92). Mean LOS was 38.1 days (range; 2-120) with a mean ICU-LOS 29.3 days (range; 0-114 days). Overall mortality was 26.8%. The most common Stenotrophomonas maltophilia infections were pneumonia (68%) and bacteremia (11%). Thirty-three patients (40%) had a past medical history significant for COPD or asthma. The diagnosis of Stenotrophomonas maltophilia was made on average hospital day number 17 (range; 0-86). Forty-seven patients (57%) had received antibiotics for other infectious etiologies prior to Stenotrophomonas maltophilia infection. Fifty-nine patients (72%) had empiric treatment that required a change in antibiotic therapy based on sensitivity results. Patients requiring antibiotic changes based on sensitivities did not have worse outcomes (p=0.64) however those with the diagnosis made early in their hospital course within 2 weeks (p=0.05) had significantly better outcomes. Though Stenotrophomonas maltophilia infections seemed to occur in patients treated for prior infections including ventilator associated pneumonia, empiric treatment against Stenotrophomonas maltophilia did not correlate with improved clinical outcomes. At this point, we do not recommend that Stenotrophomonas maltophilia be included in empiric antibiotic coverage.

A Comparison of Fixation Methods for Acromioclavicular Joint Separation: A Biomechanical Study

Michael Hromadka, BS ¹, Laurence Dahners, MD^2,3, Paul Weinhold, PhD³

¹School of Medicine, ²Department of Orthopaedics, and听³ Department of Biomedical Engineering听University of North Carolina, Chapel Hill, NC

Proyecto Puentes de Salud (Project Health Bridges): The relationship of economic migration and HIV risk factors in Rural Mexico.

Amanda L Rollins^1,2, Ian J Nelligan^1,2, Allan D Nanney^1,2,听Trista D Snyder^1,2, Pamela Y Frasier MA, MSPH, PhD¹, Alfred Reid MS¹, Bron Skinner PhD¹, Daniel Reuland MD², Mauricio G Cohen MD³

¹Department of Family Medicine, Department of Internal Medicine², Department of Cardiology³

While increased risk factors for HIV transmission among male economic migrants in NC and the US have been established in several studies, there is a lack of information about HIV risk among the spouses of economic migrants in rural Mexico.听A convenience sample of 169 participants, recruited from six rural communities in Guanajuato, Mexico were offered free HIV testing using the Oraquick庐 Advance鈩� Rapid HIV-1/2 Antibody Test and counseled about risk factors and reduction for HIV by bilingual investigators. All participated in a counselor-conducted survey to assess economic migration defined as 鈥渕igration to the US to live or work for 1 month or more鈥� and risk of acquiring HIV. A self-administered HIV knowledge survey was used to assess the basic and advanced knowledge of HIV and risk reduction to some participants. 0.0% were positive. Women comprised 85.8% of those tested.听Aproximately 90% of participants neither migrated nor used condoms routinely; however, those who used condoms regularly were 4.6 times more likely to have migrated. Those who migrated were 48 times more likely to have sex with a commercial sex worker and 67% never or almost never used condoms with them.听Risk of HIV transmission is high in this population. Condom use in this population was very low.听Those that migrated to the US were much more likely to engage in high risk behavior.听Those that never left Mexico had little risk as a group but many had sexual partners that introduced risk.听Overall, HIV knowledge was very limited.

听听听听 The effects of recombinant Fc (rFc) on passive transfer mouse models of bullous pemphigoid, pemphigus foliaceous and pemphigus vulgaris

听听听听 Bullous pemphigoid (BP), pemphigus foliaceus (PF) and pemphigus vulgaris (PV) are autoimmune skin blistering diseases, each with its own characteristic pathophysiology.听Pemphigoid exhibits subepidermal blisters, infiltration by inflammatory cells as well as an accumulation of IgG autoantibodies at the basement membrane zone (1). Pemphigus, on the other hand, progresses through intraepidermal blisters as a result of epidermis specific antibodies (2).听One form of treatment that has shown considerable promise for patients with other autoimmune disorders has been intravenous IgG (IVIG) (3).听However, IVIG as a therapy for the above blistering diseases has yet to be fully evaluated.听Because of its effectiveness in reducing the manifestations of BP, PF and PV in mice models, more work is being done with respect to this therapy鈥檚 mechanism of action.听Based on recent work in this area, this study seeks to examine the efficacy of a recombinant protein that makes use of a specific domain within the IgG molecule-the Fc domain.听It is our hope that through the use of this specific domain of the immunoglobulin, an efficacy equivalent to that of IVIG in terms of disease reduction will be achieved as demonstrated through these same in vivo models.听

Screen for miRNAs that Regulate Apoptosis in Primary Neurons

Adam J Kole¹, Michelle I Smith² and Mohanish Deshmukh²

¹MD/PhD Program, ²Department of Cell and Developmental Biology

Apoptosis, or programmed cell death, is an evolutionarily conserved process by which cells die in a regulated manner. Apoptosis is important both in development and in homeostasis by removing cells that are superfluous, no longer useful, or harmful for the organism. The deregulation of cell death has many pathological consequences. MicroRNAs (miRNAs) are a newly discovered family of evolutionarily conserved regulatory RNAs. miRNAs are short, non-coding RNAs that are processed into double-stranded RNA structures and regulate gene expression by binding to complementary mRNAs, inhibiting their translation. Several miRNAs have been identified in Drosophila that are potent inhibitors of cell death by blocking translation of apoptotic proteins.

These findings prompted us to investigate whether expression of miRNAs is modulated in mammalian primary neurons undergoing apoptosis. Since miRNAs are involved in the regulation of expression of a wide range of genes, it was hypothesized that miRNAs do in fact regulate neuronal apoptosis. The specific aims to test this hypothesis were:

鈥�听听听听听听听听听 To culture murine primary cerebellar granule neurons (CGNs).

鈥�听听听听听听听听听 To induce apoptosis in primary CGNs.

鈥�听听听听听听听听听 To purify RNA from CGNs and confirm the activation of apoptosis by measuring increased levels of known pro-apoptotic factors.

鈥�听听听听听听听听听 To profile miRNA expression by hybridizing total CGN RNA with a custom microarray containing the complements to murine miRNAs.

Effect of AMPK Activation on Insulin-Like Growth Factor-I Signaling in Vascular Smooth Muscle Cells

Adrienne Turner Duffield, David R. Clemmons

University of North Carolina, Chapel Hill, NC

Effect of language task difficulty on cortical activation in normally developing pediatric subjects

¹A Pendyal, ²MM Berl, ³EK Ritzl, ^2,5L Rosenberger, ²DA Weber, & ^4,5WD Gaillard

¹University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA

²Department of Neuropsychology, Children鈥檚 National Medical Center, Washington, DC, USA

³Department of Neurology, The Johns Hopkins Hospital, Baltimore, MD, USA

⁴Department of Neurology, Children鈥檚 National Medical Center, Washington, DC, USA

⁵Epilepsy Research Branch, NINDS, NIH, Bethesda, MD, USA

Background: fMRI is a non-invasive technique used to examine the neural correlates of language, working memory, and attention in normal controls. Objective: Using fMRI, to determine the changes in activation patterns that arise from an increase in language task difficulty within normally developing children. Previous studies involving adult subjects have suggested that an increase in language task difficulty may result in increased cortical activation in key Brodmann areas. Methods: We studied 19 normal, healthy, right-handed volunteers (12 male, 7 female, aged 7.25-12.58 years). We used whole-brain 3T fMRI (EPI BOLD), and employed a boxcar design that consisted of multiple runs (of varying difficulty) of an auditory category decision task. We measured in-scanner behavioral performance, including accuracy and reaction time. Data were analyzed using SPM2; individual t-contrast maps were generated, displaying differences in activation between medium and hard runs for each subject. Group 鈥渉ard minus medium鈥� results were then displayed as a single-sample t-test. Results: Average true positive accuracy among subjects was 83% for the medium task level and 72% for the hard task level; average reaction times for medium and hard task levels were 1085 and 1187 milliseconds, respectively. As expected, we observed a main effect of matched task level and age on accuracy and reaction time. The single-sample t-test (p=.005, uncorrected) revealed significant activation in the right anterior cingulate region (AntCing, Z=4.07), left inferior frontal gyrus (IFG, Z=3.57), and left superior temporal gyrus (STG, Z=3.23). Conclusions: In normally developing pediatric subjects, an increase in language task difficulty results in increased recruitment of cortical areas. Left-hemisphere activation of IFG and STG may reflect additional activation of traditional language areas, as well as the hard level鈥檚 additional working memory and language processing demands. Similarly, Right AntCing activation may reflect greater attentional or motivational demands in the hard version of the auditory category decision task.

Amir H. Khandani^1,5, Alexander W. Rich³, Bahjat F. Qaqish^4,5, Leonard A. Parker^2,5,

Marijana Ivanovic¹, William H. McCartney^1,5

¹Sections of Nuclear Medicine, ²Thoracic Radiology, Department of Radiology, ³MD Program, 大象传媒, ⁴Department of Biostatistics, 大象传媒 School of Public Health, ⁵Multidisciplinary

University of North Carolina, Chapel Hill, NC

AIMS: To evaluate the sensitivity of FDG PET in malignant lung nodules based on the visual interpretation of attenuation corrected images, non-attenuation corrected images, and based on SUV. METHODS: 62 lung nodules in 54 patients with preoperative FDG PET were included. Nodules with more intensity that normal lung or the mediastinum on non-attenuation corrected and attenuation corrected images, respectively, were considered positive for malignancy. In evaluation based on SUV, an SUV>2.5 was considered positive for malignancy. RESULTS: 61/62 (98%) nodules were correctly identified as malignant on non-attenuation corrected images. In comparison, only 36 (58%) were positive on attenuation corrected images, and only 38 were positive based on an SUV>2.5. The probability of missing a malignant nodule based on attenuation-corrected images or on SUV correlated negatively with nodule size. CONCLUSIONS: Non-attenuation corrected images are more sensitive than attenuation corrected images or SUV in detecting malignant lung nodules. Thus, non-attenuation corrected images should be used in future studies evaluating the sensitivity and specificity of FDG PET in diagnosing malignancy in lung nodules of indeterminate origin.听听听听

Gene Expression Profile of Hematopoietic Stem Cells During Regeneration

Hematopoietic stem cells (HSC) are able to proliferate and regenerate rapidly in response to damage of the hematopoietic compartment.听To better understand the regulatory mechanisms that govern this response at the molecular level, we treated mice with the chemotherapeutic drug cyclophosphamide (Cy) and the cytokine granulocyte colony-stimulating factor (GCSF).听Treatment with Cy results in the loss of actively cycling progenitor cells in the bone marrow, followed by rapid proliferation and regeneration of HSCs.听When Cy is combined with GCSF, a synergistic increase in proliferation is observed.听Using the Cy/GCSF model, a microarray analysis was performed.听The microarray analysis was a four-arm study in which HSCs derived from untreated mice were compared to those derived from mice treated with Cy alone, GSCF alone, or a combination of the two drugs.听Gene expression profiles were created for each of the three experimental groups based on differential gene expression compared to the untreated group.听Nearly 75% of all genes differentially expressed in this experiment are uniquely attributable to the combined Cy/GCSF treatment.听Real-time PCR provided confirmation of several differentially expressed genes, including a novel gene in the HSC regenerative process.听Gene ontologies of the differentially expressed genes vary widely but intracellular and membrane structural proteins, metabolic activity, and cellular physiological processes account for nearly 45% of the differentially expressed genes.听Finally, this study suggests that the drugs induce distinct expression profiles when administered individually and in combination.

Early Experience with da Vinci Robot-Assisted Nissen Fundoplication in Pediatric Surgery

¹School of Medicine, ²Department of Pediatric Surgery

University of North Carolina, Chapel Hill, NC

Traditional non-robotic laparoscopic Nissen fundoplication (LNF) is a well described surgical solution to gastroesophageal reflux disease (GERD) in adults as well as children.听The da Vinci Robotic Surgery System enhances LNF surgery with a three-dimensional view into the patient, wrist-like instruments, tremor filtration, and motion scaling.听This study is a report of our early experience with this system to perform LNF in infants and small children.听Goals were to investigate the intra and post-operative feasibility of da Vinci robot-assisted LNF in pediatric surgery and examine the difference in operating room costs for robotic versus standard LNF.听From April 2005 through June 2006, fifteen children (5 months to 15 years) suffering from GERD unresponsive to non-operative therapy underwent LNF using the da Vinci Robotic Surgery System.听All cases were reviewed retrospectively for demographic, intra and post-operative content.听Total cost per robotic LNF was compiled and compared with non-robotic norms at our institution.听Surgery time from first incision to time of dressing, averaged 167 min (98 to 250 min), and included robot docking time.听Mean surgery operating time for fundoplication alone was 138 min (n=6) and with gastrostomy tube 187 min. (n=7).听Following surgery, the mean time to discharge was 60 hours (n=14).听There were no intra-operative complications or surgical mortalities.听Operating room costs with the da Vinci robot averaged $1,609 more, and necessitated 40 min. less room time to complete than conventional LNF.听These preliminary results of our series suggest that the da Vinci robot helps overcome the inherent challenges of performing LNF in children; benefiting the patient with decreased anesthetic exposure and the institution with shorter procedure times.听Based on the intra-operative and short term follow-up data that was available at the time of this study, da Vinci robot-assisted LNF appears to be an effective alternative to conventional laparoscopy.

Sodium at 24 Hours of Life in Very Low Birth Weight Newborns: Does it Correlate with Dehydration?

Very low birth weight infants, or VLBW infants, have particular physiological challenges in regulating fluids and electrolytes, especially around the time of birth.听Physicians often follow serum sodiums of VLBW infants to identify dehydration and manage fluids and electrolytes accordingly.听However, currently there is little data to endorse this practice as a clinically useful technique.听The purpose of this study is to explore the efficacy of this practice by providing quantitative data.听A retrospective chart review was performed on all inborn neonates at 大象传媒 Hospitals in 2004 weighing less than 1500g at the time of birth.听Demographic data as well as data concerning fluid and salt administration, weight change, and serum sodium levels in the first 24 hours of life was collected and analyzed.听Of the infants included in the study (n=127), only 5 infants (3.9%) were found to have dehydration in the first 24 hours of life and of those subjects, only 3 of the 5 infants had abnormally high serum sodium levels.听In contrast, 23 infants (18.1%) in the study suffered from hypernatremia, or a serum sodium measuring greater than 145 mEq/L.听This result suggests that hypernatremia is not a marker of dehydration.听There is, however, a very strong inverse linear relationship between percent weight change in the first 24-hours and serum sodium levels (p<5.99*10^-7), as well as a clear correlation between percent weight change and the total amount of sodium administered during the first 24 hours of life (p<3.52*10^-4). The take home message for physicians is that there is a complex interplay between fluid administration practices, sodium administration (either intentionally or non-intentionally administered), and serum sodium values that all need to be carefully balanced in order to avoid the pathological condition of dehydration.听听

Predicting Patterns of Heterotopic Ossification in Burn Patients

A.N. Hardy¹, K.P. Kolappa¹, M. Kidd³, B. Cairns², C.S. Hultman², E.G. Loboa⁴, and J.A. van Aalst²

¹大象传媒 Chapel Hill School of Medicine; ²Department of Surgery, 大象传媒 Chapel Hill; ³Department of Surgery,

University of Oklahoma; ⁴Joint Department of Biomedical Engineering, NC State University and

大象传媒 Chapel Hill

Commonalities and Gender in the Patient-Physician Interaction

Cherri Hobgood^1,2, Morgan Lasater, Ashley Davis¹, Mari-Wells Hedgpeth¹

¹Medical School Office of Educational Development, ²Department of Emergency Medicine

University of North Carolina, Chapel Hill, NC

Background:听Empathy is an essential component of the patient physician interaction in order for the physician to build rapport with the patient.听The concept of 鈥渃ommonality鈥� is an aspect of empathy where similar world views/life experiences of the patient and physician helps them understand each other and effectively communicate.听In this study a commonality is defined as an interaction between a patient and physician where either the patient or physician initiates a personal story, idea or thought in one of several categories.听Then, depending on the topic, a response that completes this type of interaction may be to share something new about the subject, provide new information, or give an opinion.听听听

Aims:听Determine if differences in occurrences of commonalities between patient and physician during the patient interview change as a function of the treating ED physician gender.

Methods:听Data were collected in 大象传媒-CH Emergency Department between the hours of 8 am and 2 am daily.听Patient-physician interactions were observed and commonality occurrences were recorded.听Then, surveys were administered to patient and physician participants.

Results:听Mean number of commonalities for interactions between female physicians-female patients was the greatest at 0.87 with significance of 0.01 and the next highest was for male physician-male patients at 0.58 with significance of 0.46.听There was so significant difference when looking only at patient gender or only at physician gender.

Time Dependent Reduction of iNOS Protein and Downregulation of mRNA in Primary Cultured Hepatic Progenitor Cells

Babar Fiza^*, Natasha Wright^搂, and David Gerber^搂

^*University of North Carolina School of Medicine, Chapel Hill, NC

^搂Department of Transplant Surgery, University of North Carolina, Chapel Hill, NC

Pediatric HIV Clinic Chart Audit: Determining

Bradley C Fetzer¹, Mina Hosseinipour², Irving Hoffman³

¹大象传媒 School of Medicine, ²大象传媒 Project, Malawi, ³Department of Infectious Disease

University of North Carolina, Chapel Hill, NC

Studies performed on HIV positive adults in Malawi, where over 15% of the population is estimated to be HIV positive, have been beneficial towards prolonging life, improving clinical care, and improving delivery of Anti-retroviral Therapy (ART).听Few studies exist for HIV positive children in the hopes of achieving such aims.听The goals of this study are to determine predictors of mortality in children on ART who attend the Pediatric HIV Clinic in Kamuzu Central Hospital in Lilongwe, Malawi. We conducted a retrospective chart review of all children who had started ART between x date and May 2006.听Variables included basic demographics, clinical presentation, WHO HIV Staging, and treatment relating to HIV and their outcome as of June 2006.听Descriptive statistics and bivariate analysis was performed to evaluate associations according to vital status.听Cox proportional hazard modeling was performed to identify independent predictors of mortality.听258 children started ART.听51% were female, 7% were under 18 months, 26% were 18 months to 5 years, and 54% were >5 years of age.听Most were WHO stage 3 or 4. (55% and 36%, respectively).听41 died, 216 were alive, 1 transferred听. The mean survival time was 7.90+- 0.18 months. On multivariate analysis, factors associated with mortality included Ill at Presentation (HR 2.7 80% CI 1.51, 10.450, Weight Loss (HR 4.0, 80% CI 1.5 10.50), and age <18 months (HR 4.62 80% CI 2.3, 9.2).听Most (83%) of the death occurred in the first 3 months of treatment.听Early mortality among children starting ART is most associated with illness at time of presentation and being <18months.听Evaluation of infants and children, prior to illness, will likely result in improved outcomes.听Early diagnosis of infected infants using DNA testing or p24 antigen testing may allow early initiation of ART in infants at higher risk of death.

The Role of Cell-Associated VEGF Isoforms on the Transmigration of Choroidal Endothelial Cells Across the Retinal Pigment Epithelium

B. King, P. Geisen, J.R. McColm, L. Peterson, M.E. Hartnett

Department of Ophthalmology, School of Medicine

Purpose:听In age-related macular degeneration (AMD), choroidal neovascularization (CNV) is often preceded by the migration of choroidal endothelial cells (CECs) across the retinal pigment epithelium (RPE). The aim of this study was to investigate the role of VEGF isoforms in CEC transmigration when contact is made with RPE.

Methods:听For hypoxia studies, ARPE were exposed to 24 hours of 1% O2. Controls remained in 21% O2. mRNA concentration was determined by real time RT-PCR and protein determined by Western blot. To determine the change in VEGF189 protein expression when CECs made contact with ARPE, ARPE were plated on the undersides of transwell inserts (contacting) or in the wells of a 6-well dish (noncontacting). CECs were plated in the inserts. For the transmigration study, ARPE were incubated in CellTracker Red and plated onto the underside of inserts. After 72 hours, primary human CECs incubated in CellTracker Green were plated into each insert. Then, after 24, 48, or 72 hours, inserts were transferred to a new well and trypsinized. Green cells taken from the well were counted on a hemocytometer to determine the number of transmigrated CECs.

Results:听Exposure to 1% O2 conditions induced increased expression of VEGF mRNA for all three isoforms compared to 21% O2 (5.60, 8.68 and 10.01 fold increase for VEGF121, 165, 189, respectively). VEGF189 protein expression was higher in ARPE grown in contact with CECs than in ARPE grown in noncontacting coculture (0.479 vs 0.328 pixel density). Transmigration of CECs was increased in contacting culture vs. solo CEC culture (2091 cells/0.33 cm2 vs 270 cells/0.33 cm2 p = 0.016).

Background: Patient behaviors such as smoking, unhealthy diet and low physical activity have been shown to directly contribute to chronic diseases like diabetes and heart disease. Stopping unhealthy behaviors reduces the incidence of both the diseases and their complications. The process of modifying an unhealthy behavior works best with both patient willingness and physician assistance.

Aims: The project sought to find relationships between chronic disease diagnosis and both patient willingness to change and physician intervention.

Methods: Patients were recruited at non-acute visits to six primary care practices across NC. Upon completing a waiting room computer survey, those patients identified as having at least one risky health behavior were enrolled. A follow up telephone interview gathered further information about the patient and their encounter with the doctor.

Results: The preliminary data (n=108) showed no significant relationship between a chronic disease diagnosis and patient being in the 鈥渁ctive鈥� stage of behavior change. Physicians, on the other hand, appeared to have their behavior influenced by patient chronic disease status. Multiple chronic diseases showed statistically significant relationships with physician intervention at p<.10 (a more rigorous standard will be applied when to the updated data used for the poster presentation).听The consistent trend, observed for nearly all conditions, was for physicians to be less likely to counsel chronic disease patients about unhealthy behaviors but to be more likely to provide printed information and to refer to community resources.

Discussion: The initial data suggests that while physicians focus time and energy on unhealthy behaviors in their patients with chronic disease, the patients themselves may not be as aware of the link between behavior and disease. The increased rate of printed materials and referrals given to chronic disease patients suggests that physicians target aggressive interventions toward certain persons with chronic illness.

Association between Uterine Artery Resistance and Low Birth Weight

Catherine Varner¹, Amy Herring¹, John Thorp²

¹ Department of Obstetrics and Gynecology; ² Department of Biostatistics, School of Public Health

Ultrasound is a key component in the evaluation of pregnancy.听With improving technology, the ability to evaluate uterine artery blood flow parameters may predict adverse birth outcomes, including low birth weight.听OBJECTIVE:听This study investigated the relationship between high-resistance uterine artery waveforms in pregnancy and birth weight.听METHODS:听Uterine artery Doppler recordings were obtained between 15 and 20 weeks gestation and subsequently between 24 and 29 weeks in a cohort of women who attended prenatal care clinics in central North Carolina (n= 870).听Doppler waveforms were evaluated by a blinded reviewer for the presence of an early diastolic notch, representing a failure of circulatory accommodation in pregnancy and a sign of high resistance blood flow.听RESULTS:听The mean birth weight of infants of women with any notching detected (any artery, any visit) was 150 g less than women who had no notching (p=0.001).听The mean birth weight of infants of women with notching at both 15-20 weeks and 24-29 weeks was 160 g less than infants of women with notching present at 15-20 weeks, but resolved by 24-29 weeks (p=0.01).听The largest discrepancy in birth weights occurred between women who had bilateral notching at 24-29 weeks as compared to women with no notching at either visit [3053.3 g vs. 3339 g; p=0.001].听CONCLUSIONS: 听These findings indicate arterial notching is associated with low birth weight infants, and this association is most pronounced when notching is present at both time points in pregnancy.听This information may be of value in increasing our understanding of the pathophysiology of growth restriction in pregnancy and may identify at risk pregnancies warranting closer surveillance.听

Development of Novel Biosensors to Determine the Balance between Activation of Different Rho GTPase isoforms in Malignant Breast Cancers

Christopher Welch, Louis Hodgson, and Klaus Hahn

Validating the Mini-Cog as a Screener for Mild Cognitive Impairment in the Primary Care Setting

James J. Lah^1,2, Nelson Kyle Steenland^1,3, Courtney Melton¹

¹Alzheimer鈥檚 Disease Research Center, ²Center for Neurodegenerative Disease, and ^听3Department of Environmental and Occupational Health

Mild Cognitive Impairment is a public health concern because studies of MCI subjects have shown significantly higher annual conversion rates to dementia than cognitively normal individuals.听Therefore, identifying those with MCI allows for initiation of treatment in the earliest stages of cognitive decline, which has been shown to provide more benefit in delaying the progression of the dementia.听There are several challenges faced in the Primary Care Setting that make screening for cognitive decline difficult, and research has shown poor MCI detection rates in these settings.听The goal of this project is to validate the Mini-Cog combined with the Functional Assessment Questionnaire (FAQ) as an efficient means of screening for MCI in the primary care setting.听Three-by-three tables comparing 鈥済old standard鈥� diagnosis (made by a neurologist) vs. predicted diagnosis by Mini-Cog and FAQ scores were evaluated for accuracy and kappa statistics.听The preliminary analysis includes 158 subjects.听The Mini-Cog and FAQ combination accurately predicted 126 of the 158 diagnoses made by the neurologists, for an accuracy rate of 80%.Weighted Kappa=0.78.听The study is still underway and conclusions are pending.

Aging and Arterial Changes in the Cerebrovascular Tree

Eric Hintz, Elizabeth Bullitt, Mark Van Horn, and Donglin Zeng

听University of North Carolina, Chapel Hill, NC 27599

Functional and histological changes in the cerebrovasculature associated with aging have been well documented.听These changes include a decline in cerebral blood flow and both decreased density and ultrastructural degradation of capillaries.听However, changes in the macrovascular tree, such as number and size of radiographically-discernible arteries, have not received equivalent attention.听We address this deficit using novel software to analyze magnetic resonance angiogram (MRA) derived images in forty healthy volunteers.听Subjects fit into one of two age brackets, 18-29 or 60+, each of which were equally divided by sex.听Head-only MRA images were acquired in standardized fashion, yielding images containing 512 x 512 x 120 voxels acquired at 0.5 x 0.5 x 0.8 mm³.听Automatic vessel extraction, performed by previously-created software, yielded text files containing coordinates and diameter for each vessel at a density of ten data points per voxel.听听 Our program calculated the total number of arteries in each brain and, for each vessel, determined average diameter.听Based on diameter, arteries were categorized into one of 20 equisized bins ranging in size from 0.257 to 3.073 cm, with bin 1 containing the smallest vessels and bin 20 containing the largest.听We found that, compared to the younger group, the brains of older subjects contained fewer arteries (265.65 v 341.75; p = 0.0016).听Older subjects were more likely to have vessels in the large-diameter bins; statistically significant differences were noted in bins 4-7, 10, and a conglomerate containing bins 11-20.听Furthermore, despite having fewer vessels overall, the older subjects had over twice as many arteries in bins 11-20 as the younger subjects (124 v 59 vessels).听Younger subjects, on the other hand, were more likely to have vessels in bins 1 and 2.听Together, this data suggests that normal aging is associated with a pruning of the vascular tree and a compensatory dilatation of the remaining vessels.听This finding raises important questions about the role of macrovascular insufficiency in pathologic conditions more prevalent in older patients such as dementia and ischemic stroke.

Hann-Hsiang Chao¹ and Charles Perou^2,3

¹School of Medicine, University of North Carolina at Chapel Hill, ^听2Department of Genetics, University of North Carolina at Chapel Hill, ³Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill

Background and aims:听Patients who develop basal-like breast cancer have been shown to have higher mortality rates than the other breast cancer subtypes, and tend to be largely unresponsive to most current forms of therapy.听The basal-like breast cancers are known to be a type of basal cell carcinoma.听Smoothened (Smo)is a proto-oncogene in the Hedgehog and Wnt signaling pathways, both of which play important roles in development, proliferation and differentiation.听Overexpression of mutant Smoothened has been associated with the development of basal cell carcinomas.听大象传媒 patient data revealed certain mutations (V270I and D25G) in the Smo protein in patients with basal鈥搇ike tumors.听The aim of this study was to assess whether the V270I and D25G mutations were germline variants or somatic mutations and to determine the significance of the changes in the Smo gene.

Methods:听The Smo full-length cDNA was cloned into the pBABE.puro expression vector.听Site-directed mutagenesis was used to generate the Smo mutations of interest, V270I and D25G.听The three Smo clones, along with the corresponding empty vector, were transfected into the SUM102 cell line.听SUM102 was chosen because it is a basal epithelial cell line with low endogenous Smo expression.听mRNA was isolated from the transfected cell lines, amplified and labeled, and microarray analysis was performed to create gene expression profiles.听Significance Analysis of Microarrays (SAM) was carried out to determine significant gene expression changes caused by Smo overexpression.

Results:听Smo expression was confirmed to be increased in all of the Smo transfected cell lines.听A 2-class SAM showed that there was in a change in gene expression profiles when Smo was overexpressed versus the empty control.听In addition, sequencing of a normal breast tissue sample from a patient revealed that the V270I change was present in normal as well as in the tumor sample.

Conclusions:听Smo transfected SUM102 lines had increased Smo mRNA levels.听Overexpression of Smo results in changes in the gene expression profile.听The presence of the V270I mutation in a normal sample suggests that this change may be a germline variant.

Evaluation of Safety and Efficacy of an Insulin Infusion Algorithm

MR=maintenance rate; IR=insulin infusion rate; ROD=rate of descent of blood glucose; MR_csne = MR_{cross step next estimate}

Several clinical trials have shown that when patients with hyperglycemia were treated with insulin infusion, there was improvement of patient outcomes.听The rigorous control of hyperglycemia reduced morbidity, mortality and hospitalization time for inpatients.听The purpose of an insulin infusion protocol is to improve blood glucose control in hospitalized patients without the risk of substantial hypoglycemia.听It would be an improvement if an insulin infusion algorithm could predict insulin requirements proactively rather than reactively for better glycemic control.听It is known that both directional and rate changes of blood glucose influence the rate determination of insulin infusion. The purpose of the current study is to assess safety and efficacy of an Insulin Infusion algorithm of IRB 04-MED-358 protocol to estimate maintenance insulin requirements.

Evaluable timepoints from 27 historical runs among trauma service patients were used to determine intervals of blood glucose stability based on the criteria set for the current study to help the consistency of the data analysis. Mean IRnext, historical during each interval of stability was determined.听Values of MRcsne just before stable intervals were calculated according to the new algorithm:

听MRcsne= (IRprevious ) / {1 + [(RODprevious * 24hr) / (1800 mg/dL)]听听

A total of 30 stable intervals were determined for the analysis.听Data analysis revealed that there was a linear relationship between values of mean IRnext, historical during stable intervals and MRcsne just before the stable intervals.听Strong correlation was observed between the values, R2=0.884, p<0.05.

The study showed that hypothetical MRcsne values were systematically higher than mean IRnext, historical. Although the overestimation of mean IR on stable interval was made by MRcsne, the strong correlation between the two sets of values suggest efficacy and safety of the new programmable algorithm compared with the paper protocol used in the patient care.

John Hartmann¹,Theodore Garland, Jr.², Daniel Pomp¹, and Gloria Munoz¹

¹University of North Carolina, Department of Nutrition, Chapel Hill, NC 27599, USA

²Department of Zoology, 430 Lincoln Drive, University of Wisconsin, Madison, WI 53706 -1381, USA

BACKGROUND: A collaborative project is currently being carried out to elucidate key mechanisms of locomotor adaptation and the physiological limits of selection.听Selective breeding for high voluntary wheel running in mice has resulted in multiple lines that run an average of three times more per day than control lines.听A key discovery of this selective breeding is the 鈥渕ini-muscle鈥� allele that has been favored and has gone to fixation in one of the high-running lines (S3).听This autosomal recessive gene causes a 50% reduction in hindlimb muscle mass while doubling mass-specific aerobic capacity and altering contractile characteristics in ways that are hypothesized to enhance endurance running and the energetic efficiency of locomotion, but compromising sprinting abilities.听My research goals consisted of identifying the chromosome harboring the putative mini-muscle locus, mapping it to a 3-5 cM region, and identifying possible candidate genes.听METHODS: The mapping was performed through microsatellite marker analysis on a population of mice resulting from a backcross of S3 x C57 F1 to S3, resulting in a population with 50% affected mice.听An initial genome-wide scan was done across selected backcross mice (N=54) to identify the chromosome harboring the mini-muscle gene.听This was followed with fine mapping, which utilized the entire backcross population (N=404) to localize the gene to a manageable region.听RESULTS: The genome-wide scan revealed that both of the two microsatellite markers run on CHR11 were significantly linked to the gene of interest (p<0.005).听Fine mapping placed the gene in a final region of 2.634 Mb (67.455 Mb to 70.089 Mb) on CHR11. CONCLUSIONS: Further research may pinpoint the causal mutation, which may prove to be an important model for understanding basic muscle growth and development.听Two candidate genes in this region were sequenced (SOX15 and CHRNB1), but the causal mutation has not been found.听

Proliferative subpopulations in partially differentiated embryonic stem cells:听Characteristics and engraftment efficiency within the liver parenchyma.

Jonathan Haywood, Montserrat Caballero, Mai Nguyen, Suzanne Lyman and Jeff H. Fair

Department of Surgery 鈥� The University of North Carolina at Chapel Hill

Embryonic stem (ES) cells are pluripotent cells with capability to differentiate into cell types from the three germ layers, making them excellent candidates for cell replacement therapies. Although they represent probably one of the best therapeutic tools for many common diseases, there are still a lot of problems associated with their potential, such as lack of function, teratoma formation, and allograft rejection (1-4).听Recently, in our lab, partially differentiated mouse ES cells have proved to engraft into the liver and reverse the hemophilia defect in a FIX knockout mouse model (5).听Although the teratoma ratio in those experiments was low (6.2%), the risk is still present.听The aim of this specific project was to characterize two subpopulations based on their expression of the tyrosine kinase growth factor receptor CD117 (c-kit), a proliferation marker present in some adult stem cells. Mouse ES cells were grown and differentiated in the presence of acidic fibroblast growth factor (FGF), and then sorted using magnetic beads on the basis of CD117 expression. The gene expression of positive and negative subpopulations was analyzed by qRT-PCR. Each population was then injected into the liver parenchyma of wild type mice to determine engraftment efficiency as well as teratoma formation rates. Gene expression analysis showed that endodermal markers are highly expressed in the CD117 positive fraction. The in vivo experiments showed that while CD117 positive cells induced teratoma formation in very high rates, the CD117 negative fraction did not engraft at all.听The CD117 positive fraction is linked to a very high rate of teratoma formation, although the high levels endodermal markers would make them good candidates for robust engraftment. On the other hand the negative fraction does not engraft at all. Further subfractioning of the CD117 positive population is needed in order to select the population with high endodermal markers that would engraft without inducing teratoma formation.

Failure of Dexmedetomidine (DM) to Facilitate Extubation in a Trauma Intensive Care Unit (TICU)

Lauren Paton¹, Craig Barrett¹, Jonathan Salahshour^1,2, Aram Kim^1,2, Britt Christmas¹, David G. Jacobs¹, and Ronald Sing¹

¹Surgery, F.H. Sammy Ross Jr. Trauma Center, Carolinas Medical Center, Charlotte, NC, USA

²University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA

Introduction: Dexmedetomidine (DM), a selective alpha-2 adrenergic agonist that exhibits sedative, analgesic, anxiolytic, and sympatholytic effects to facilitate extubation. Present FDA recommendations allow DM administration for less than 24 hours with the dose less than 0.7 mcg/kg/hr. We retrospectively evaluated the use of DM to facilitate extubation for patients in the TICU.

Hypothesis: DM does not facilitate successful weaning and extubation from mechanical ventilation.

Methods: After IRB approval, TICU patients from January 2003 to June 2006 who received DM were retrospectively reviewed. Data collected included demographics, length of stay (LOS), days requiring mechanical ventilation, and number of hours receiving DM prior to weaning and extubation from mechanical ventilation.

Results: Sixty-six patients (55 males: 11 females) with a mean age of 41 years (range; 17-79) received DM while requiring mechanical ventilation. Average ICU LOS was 21.4 days (range; 1-54). Intravenous infusion of DM commenced at 0.4 to 0.7 mcg/kg/hr with a loading dose of 0.4 mcg. Background sedation and analgesia with propofol, benzodiazepines, and opiates were discontinued or reduced as tolerated. DM infusion was titrated between 0.2 and 1.9 with an average maximum dose of 0.83 mcg/kg/hr to maintain a stable cardiopulmonary response and modified Ramsay Sedation Score between 2 and 4. Only thirty patients (45.5%) were successfully extubated with the average time on DM till extubation being 58.9 hours requiring on average 0.91 mcg/kg/hr of DM. Only 4 patients (6%) were extubated within 24 hours of therapy and on less than 0.7 mcg/kg/hr. Average duration of therapy of DM was 74.9 hours (range; 1-302).

Whole Globe Enucleation Versus In Situ Corneal Excision:

A Retrospective Study of Tissue Trauma

Joseph Hoyle¹, W. Craig Fowler^2,3, and Mark Soper³

¹School of Medicine ²Department of Ophthalmology, and ³North Carolina Eye Bank

Purpose: To examine whether an enucleation (EN), followed by controlled laboratory excision, is a superior technique compared with a bedside in situ excision (IS) to minimize damage of corneal donor tissue before use in penetrating keratoplasty (PK) transplant surgery.

Background: Several small studies have suggested that the IS protocol is associated with increased tissue trauma and contamination.听Nevertheless, during the last decade, IS has become the standard protocol because of lower costs to eye banks and a reduced time from death to placement in preservative media.听

Results: Records of all 1026 tissues procured by North Carolina Eye Bank (NCEB) personnel in 1998 were studied, and procurement protocols for 727 tissues were compared.听Tissue exclusions were made because tissues were not used for PK (291), biomicroscopy data was not available (4), or the corneas were from infants (4).听Analyses included endothelial cell density (ECD) and two retrospective tissue grades, assigned by the NCEB medical director, based on the cornea tissue evaluation forms originally completed by Certified Eye Bank Technicians (CEBT).听One grade, the initial grade, was based on evaluation made shortly after excision of the cornea.听The second grade, the final grade, was based on evaluation made usually twenty-hours later.听We found significantly better ECD (3% of mean) and initial grade (41% of mean) for the EN protocol.听There was no significant difference in final grade between the two protocols.

Conclusion:听Our results support previous findings of increased tissue trauma associated with the IS protocol.听The EN protocol may provide surgeons with improved tissue quality, although the tissue appears to recover.

Sodium-Calcium Exchange in HIV Neuropathogenesis

Department of Neurology, University of North Carolina, Chapel Hill, NC

Human Immunodeficiency Virus (HIV) rapidly penetrates into and infects the central nervous system (CNS).听Although neurons are not infected, cognitive-motor deficits and neuronal loss are a significant consequence.听The interaction of HIV with macrophages and microglia in the nervous system is thought to produce neurotoxic factors that are a primary cause of the neurological dysfunction.听One of the proposed effects of the neurotoxic factors is dysfunction of the sodium-calcium exchanger (NCX).听The NCX is responsible for the high capacity clearance of calcium from the cytosol using the sodium gradient to exchange sodium for calcium.听Previous data suggest that decreased NCX function is a principle cause of the loss of calcium homeostasis following exposure to a variety of HIV-associated toxins, but the cause of the NCX dysfunction is unknown.听We hypothesize that proteases such as metalloproteinases (MMPs) and calpain, released or activated during inflammation, may be responsible for the damage to NCX.听NCX damage subsequently results in a loss of calcium homeostasis in neurons, neurological impairments and ultimately neuronal loss.听To study this, an in vitro analysis was performed to examine calcium uptake into 鈥渋nside-out鈥� membrane vesicles prepared from rat or cat neural tissue and treated with medium obtained from monocyte derived macrophages (MDM) and metalloproteinases (MMPs).听The radioisotope Calcium-45 was used to measure the amount of calcium influx into the membrane vesicles.听Kinetics of NCX activity was examined, and MAP-2 staining of rat neuronal cultures was used to characterize the toxicity of MDM medium before and after treatment with the HIV envelope protein gp120.听The results showed that neurons exposed to the MDM medium exhibit acute increases in intracellular calcium followed by more gradual long-term changes.听Kinetic analysis to estimate the vesicular uptake of ⁴⁵Ca revealed that treatment of the membrane vesicles with MMPs and MDM led to a decrease in Vmax.听A significant decrease in Map-2 staining intensity was also seen after treatment of rat primary neuronal cultures with MDM medium, post treatment with gp120.听All of these results suggest that the NCX was damaged by factors released from the MDM that was treated with gp120.听This damage to NCX is likely a common cause of neuronal dysfunction in response to inflammation.

Synaptogenesis and Synaptic Elimination Across Development in Mouse Frontal Cortex

Karissa L. Gable, Chistina Grobin, Swarooparani Vadlamudi, John H. Gilmore, L. Fredrik Jarskog

Schizophrenia Research Center, Dept. of Psychiatry, University of North Carolina 鈥� Chapel Hill, Chapel Hill, NC

Background听Schizophrenia is believed to be a neurodevelopmental disorder that involves both genetic and environmental causes.听Aberrant synaptic change, specifically during synaptic pruning in adolescence, is a possible mechanistic theory for the development of schizophrenia.

Aims听Characterization of cortical synaptic changes in a mouse model measuring both dendritic spine density and pre-and post-synaptic protein changes will give a thorough indication of normal development.听听听

Methods听Mouse brain tissue that has been previously homogenized will be used in Western blot to assess protein levels of synaptophysin and spinophilin.听Thy1 transgenic YFP mouse brain tissue will be coronally cut, mounted and imaged to assess dendritic spine density in the cingulate and hippocampal region using the Neurolucida imaging system.

Results听Western blots showed evidence of a significant decrease in excitatory spinophilin across development, which then reached a plateau at 70 days.听The synaptophysin protein, which is a marker for both excitatory and inhibitory synapses increased across development.听Dendritic spine density is still in the process of measurement and analysis.

Discussion听It was expected that synaptophysin would peak at adolescence and then decrease over development as has previously been shown in human tissue.听The synaptophysin increase in mice could be explained in conjuction with the spinophilin results.听In consideration of the fact that synaptophisin is a marker for all synapses, whereas spinophilin represents only excitatory synapses, the results of a decrease in excitatory synapses could represent a possible increase in inhibitory synapses.听This would be consistent with recent work done with electron microscopy.听The dendritic spine density analysis will be helpful in futher elucidating an explanation of the results.听听听

The Oxygen Dependent Regulation of ASB4 by FIH

Kevin R Smith¹, J E Ferguson, III^1,2, and Cam Patterson^1,2,3,4

¹Carolina Cardiovascular Biology Center, ²Department of Pharmacology, ³Department of Medicine and ⁴Department of Cell and Developmental Biology

University of North Carolina, Chapel Hill, NC

听听听听听听听听听听听 Angiogenesis has importance in embryonic development and pathologic states in adult humans.听The main regulator of angiogenesis is oxygen tension, which is indicated in the post-translational modification of the transcription factor, hypoxia-inducible factor-1伪 (HIF-1伪).听Under normoxic conditions, HIF-1伪 is hydroxylated at proline residues and an asparagine residue by prolyl hydroxylases and factor inhibiting HIF (FIH), respectively.听This hydroxylation leads to a decrease in the stability and activity of HIF-1伪, blocking the transcription of genes involved in glycolysis and angiogenesis, which are upregulated in response to hypoxia.听Importantly, post-translational modification can occur at a faster rate than transcriptional regulation.听Until recently, FIH was believed to only hydroxylate HIF-1伪 and its homologue HIF-2伪.听There is now new evidence that FIH has additional substrates for hydroxylation.听Ankyrin repeat and SOCS-box protein-4 (ASB4) is a nine ankyrin repeat containing protein with a C terminus SOCS box that recruits the ubiquitin machinery leading to substrate protein degradation.听ASB4 shows a narrow time frame of embryonic expression in cells of endothelial lineage, during which time the primitive vascular plexus is undergoing remodeling.听We show that ASB4 binds to FIH through an EVN motif and mass spectroscopy is used to show that asparagine-246 in the EVN motif of ASB4 is hydroxylated by FIH in a manner similar to HIF-1伪.听The hydroxylation of ASB4 appears to show that hypoxia has a broader mechanism of controlling vascular development than simply transcriptional regulation.听Therefore, it is likely that ASB4 functions to degrade a yet unknown substrate whose function is critical in the hypoxia regulated vascular development, and whose cellular levels require careful titration.听Angiogenesis is important in disease states such as the formation of tumor vasculature, diabetic retinopathy, and ischemic heart disease.听Therefore, we hope our results may lead to the identification of novel therapeutic targets for these diseases.

Regional Change in Brain Morphometry in Schizophrenia Associated with Short Term Antipsychotic Treatment.

Khary Carew¹, Stacy Greeter¹ and Robert McClure, MD²

¹ School of Medicine, ²Department of Psychiatry

University of North Carolina, Chapel Hill, NC

Role of NF-魏B in osteoblastic differentiation, an implication of diabetic inflammatory disorder in bone healing

Lan Chi Tran₁, Justin Barbaro₂, Lyndon Cooper_2,3, and Sompop Bencharit_2,3,4

_颅1School of Medicine, ₂School of Dentistry, ₃Department of Prosthodontics, ₄Department of Pharmacology

University of North Carolina 鈥� Chapel Hill

Type II diabetes patients have increased levels of inflammation and cellular apoptosis which can be induced by tumor necrosis factor (TNF伪) signaling. The dysregulation of TNF伪 potentiates ^听inflammatory responses and induces apoptosis of matrix-producingcells. TNF伪 have been demonstrated to inhibit osteoblast differentiation via NF-魏B pathway. However, NF-魏B has also been shown to be implemented in the early process of osteogenesis. Interestingly, there is a concomitant upregulation of TNF伪 and I魏B伪, an inhibitor of NF-魏B. The precise role of NF-魏B and its inhibitor, I魏B伪, in the process of bone remodeling is still unclear. This study aims to elucidate the effects of NF-魏B-I魏B伪 interaction on osteogenic pathways. Human mesenchymal stem cells were transduced to overexpress I魏B伪 or NF-魏B, and then induced to differentiate into osteoblasts in vitro. For each line, the mRNA expression levels of several bone markers and cytokines were evaluated via Superarray^TM听Osteogenic analysis at timepoints 1, 3, and 7 days. The results from the gene array study will categorize osteogenic pathways that are upregulated by NF-魏B and I魏B伪.听Transduction of NF-魏B upregulates most genes involved in osteoblastic differentiation, which include ICAM1, MMP10, type 2A1 collagen, TNF伪 and BMPs. There are little changes however in the expression of these genes in the control group and the one transduced with I魏B伪..听On the contrary transduction of hMSCs with I魏B伪 downregulates several genes noticeably type 1A1 and 1A2 collagen and BMP6. These results imply that NF-魏B may regulate cellular adhesion, matrix formation, and mineralization of osteoblastic stem cells.

听听听听听听 Lateral aggregation in B尾A68T recombinant fibrinogen using a

听听听 cell-based system

听听听听听听 Lance Warren¹, Robert Campbell², Susan Lord², and Alisa Wolberg²

¹M.D. Candidate, ²Department of Pathology and Laboratory Medicine,

听听听听听听听听听听听听听听听听 University of North Carolina, Chapel Hill, NC, USA

Although very rare, patients with the B尾A68T fibrinogen mutation (Fibrinogen Naples) display a high incidence of thrombotic episodes. Despite this phenotype, in-vitro clotting assays have shown that the final clot structure for Fibrinogen Naples is similar to wild-type when the same concentration of thrombin is used. The goal of this project was to utilize a model system assay to simulate the in-vivo coagulation process to compare clot formation, the end clot structure, and thrombin generation at onset of clot formation between wild-type and B尾A68T fibrinogen. The model system is an assay that monitors clot formation in the presence of plasma concentrations of tissue-factor bearing monocytes, platelets, and blood clotting factors. The formation of clots was assayed within this model system for the mutant and WT fibrinogen utilizing a spectrophotometer that monitored changes in absorbance as a function of time. In addition, the formation of thrombin was assayed and used to determine the thrombin concentration at clot formation under each of the conditions. The end structure of the clots was then examined using scanning electron microscopy. The model system experiment was carried out three times over the course of the summer. For both WT and the B尾A68T fibrinogen, three conditions were assayed: normal, elevated prothrombin, and hemophilic. In all three of these conditions and for each of the three model system experiments, the final turbidity of the B尾A68T fibrinogen was lower than for wild-type. In addition, there was a trend of increased thrombin concentration at the onset of clot formation for the fibrinogen variant B尾A68T. The lower turbidity for the B尾A68T fibrinogen indicates thinner fibers and/or more tightly woven fibers which is consistent with the phenotype of increased thromboses in patients with this mutated fibrinogen. In addition, the onset of clot formation at a higher thrombin concentration may be the basis for the thinner fibers.

A Comparison of Fertility Correlates on the Guatemalan Agricultural Frontier

Laura P. Boschini

This thesis conducted a comparison of fertility correlates in a population located on the Guatemalan agricultural frontier. The primary goal was to compare the effects of four groups of factors theorized to affect fertility: sociodemographic environment, openness to contraceptive use, degree of partner interaction, and couples鈥� desired fertility. Respondents used in this study were from communities on the agricultural frontier in and around the Sierra del Lacand贸n National Park in Pet茅n, Guatemala. The analysis proceeded in two stages. A descriptive analysis using a series of means, medians, and ranges was first conducted to describe the study population. Five models using the different variable groups were then created and run using Poisson regressions. Model 1, the core model of traditionally-considered fertility determinants, contained only the sociodemographic variables. Each other variable group was then added individually to determine if that group improved the predictive value of the core model. Model 2 added the contraception variables. Model 3 added the partner interaction variables. Model 4 added the fertility desires variables. Model 5 contained all four groups of variables. The five models were then compared using a Bayesian information criterion. The population in question, a young, agricultural population of recently arrived migrants, possessed the high fertility and low prevalence of contraceptive use typical of an isolated frontier environment. A comparison of the five different regression models indicated that sociodemographic characteristics alone were most associated with fertility in this study population, followed by a combination of sociodemographic and partner interaction characteristics and by a combination of sociodemographic and fertility desires characteristics. Sociodemographic indicators seem to be most closely associated correlates of fertility in this population, although the strong showing of partner interaction and fertility desires variables may indicate close relationship that could not accurately measured in this study.

Predictive model for mediastinal lymph node status at the time of mediastinoscopy

¹大象传媒-Chapel Hill School of Medicine, ²Department of Cardiothoracic Surgery , ³Department of Radiology, and ⁴Lineberger Comprehensive Cancer Center

University of North Carolina, Chapel Hill, NC

Mediastinal lymph node (N2) positivity in non-small cell lung cancer (NSCLC) patients is suspected based on imaging such as CT or PET scan, with confirmation by mediastinoscopy.听However, the most accurate clinical information in predicting N2 status is controversial. We reviewed 147 candidates for NSCLC resection (2000-2005) who had clinical database information available and had undergone mediastinoscopy.听Using suspected clinical predictors of mediastinal metastasis available prior to mediastinoscopy, we constructed a predictive model of N2 status.听The largest N2 node short-axis diameter on CT was by far the most influential factor in the model.听Three other predictors for N2 node positivity were significant (p<0.05) in univariate analysis:听indistinct tumor borders and mediastinal invasion on CT, and mediastinal PET scan positivity.听However, all were less influential than N2 size on CT.听Using logistic regression, these factors can be used to predict probability of positive N2 biopsy in an individual patient.听The resulting diagnostic test had a ROC (receiver operator characteristic) area of 0.80 and optimal sensitivity-specificity pairing of 75% and 73%.听35% (51/147) of patients analyzed had at least one N2 node positive at mediastinoscopy.听39% (57/147) of patients had PET scan data available, and 82% (120/147) had CT data available.听Of available data in early-stage NSCLC patients, mediastinal lymph node size on CT scan was more important than PET scan or other CT scan findings in predicting probability of positive mediastinoscopy.听A predictive model is useful in more accurately determining need for invasive staging by mediastinoscopy.

The 鈥淎ltitude Enigma鈥� in Gastric Cancer in Central America

Lindsey Wilfley, Ricardo Dominguez, ², Chris Martin, Paris Heidt,¹ Douglas Morgan¹.

¹ Medicine, University of North Carolina, Chapel Hill, NC, United States and

² Medicine, Hospital Regional del Occidente, Santa Rosa de Copan, Honduras .

Background. Gastric cancer is the second-leading cause of cancer mortality worldwide, with significant geographic variability. Areas of high incidence include Asia and Latin America. Further variability has been observed between areas of high and low elevation, potentially between mountainous and coastal regions. This has been observed in Latin America in the mountainous areas of the Pacific rim, extending from Mexico to Chile. This may relate to the interplay of host genotypes, H. pylori infection, dietary, and environmental factors.

Our aim was to investigate the variability of gastric cancer incidence based upon municipality elevation in western Honduras. The mountainous region of western Honduras is identified as a region of high incidence of gastric cancer. The standardized annual incidence is 30 per 10⁵ (Males, 39; Females, 21; per 10⁵, 2001).

Methods. The Western Regional Hospital (WRH) gastric cancer registry was used to identify incident cases from western Honduras for 1996鈥�2005. Municipality of residence and origin were determined; the latter was used, as little mobility was noted in the population. Census data was obtained from the Honduras National Statistics Institute (INE, 2001). Standardized municipality-specific gastric cancer incidence rates were calculated. Elevations were obtained from Falling Rain Genomics, Inc. Linear regression was used to evaluate the relation between altitude and gastric cancer incidence.

Results. Municipality-specific gastric cancer incidence rates were calculated for 95 municipalities in western Honduras. Thirty-six principal municipalities were identified with rates ranging between 2.7 and 31.2 cases per annum per 100,000 population, combined for males and females. The mean elevation of the municipalities ranged 307 鈥� 1210 meters. Five high incidence municipalities, all at higher elevations, were identified with a combined annual incidence of at least 20 per 10⁵.

The regression analysis suggests a borderline positive linear relationship between municipality incidence and altitude (P = 0.065, F = 3.63). The correlation coefficient confirms altitude is not the dominant factor to explain intra-regional differences in gastric cancer incidence (R = 0.31, R² = 0.096).

Conclusions. Gastric cancer incidence had a borderline correlation with elevation within the mountainous region of western Honduras. The observed 鈥淎ltitude Enigma鈥� in gastric cancer in Latin America is multifactorial, and more complex than elevation alone. It may be related to differential risk factors between coastal and mountain populations, including genetic and dietary factors. Further investigation in Latin America is warranted.

Early Formation of the Optic Cup in Sox2 Hypomorphic/Null Mice

¹Department of Genetics, ²University of North Carolina Neuroscience Center, ³MD/PhD Program

University of North Carolina, Chapel Hill, NC

Haploid insufficiency due to mutations in SOX2, a transcription factor affecting differentiation and maintenance of identity of neural progenitor cell populations, accounts for approximately ten percent of human micropthalmia (small eye) and anopthalmia (absent eye). In Sox2 hypomorphic/null mice, a reduction in SOX2 levels to less than forty percent of normal results in variable micropthalmia, hypocellularity of the retina, underdeveloped lens, and absence or hyperplasia of the optic nerve. It is not known if the decrease in SOX2 in hypomorphic/null embryos causes these defects through the regulation of neural cell differentiation alone, or if structural development of the optic cup in early embryos is also affected. Morphological and molecular marker analyses were conducted on the developing optic cup in Sox2 hypomorphic/null embryos at E10. No difference in overall optic cup structure was seen in Sox2 hypomorphic embryos. Consistent with SOX2鈥檚 role as a factor affecting neural cell differentiation but not regionalization, changes were seen in neurogenic markers 尾-TubulinIII and SIX3, but not in RALDH2, a marker of regionalization in the developing eye. The results suggest that the morphogenic formation of the optic cup is not affected by a decrease in SOX2 levels.

NSAID Use and its Effects on Barrett Esophagus and Esophageal Adenocarcinoma

D. Locke Glenn III¹, Ryan D. Madanick¹, Joseph A. Galanko¹, Ginny Sharpless¹, Nicholas J. Shaheen¹

1.听Medicine, University of North Carolina, Chapel Hill, NC, USA

Gastroesophageal reflux disease (GERD) affects the lives of many American adults, and it can lead to a pre-cancerous metaplastic change in esophageal epithelium known as Barrett鈥檚 esophagus (BE).听Many therapies have been tested to treat BE, and one that has shown promise in the prevention of esophageal adenocarcinoma is non-steroidal anti-inflammatory drugs (NSAIDs). 听It is unclear, however, whether NSAIDs play a role in preventing the progression of GERD to BE, or from BE to adenocarcinoma.听We assessed the history of NSAID use among subjects with BE followed at 大象传媒 Hospitals.听BE was defined as the endoscopic finding of cephalad displacement of the squamocolumnar junction of the esophagus, with histologic confirmation of specialized intestinalized metaplasia on biopsies from the tubular esophagus.听听 NSAID exposure data was collected from patients via a standardized questionnaire, which assessed multiple over-the-counter and prescription NSAIDs.听Relative frequency of NSAID use was captured, as was the temporal period of use in the patients life.听Subjects were categorized in one of four categories describing their NSAID use:听鈥�never users,鈥� 鈥�current users,鈥� 鈥�former users,鈥� and 鈥�sporadic users.鈥澨�听听 Other covariates which might act as confounders of the associate between the use of NSAIDs and the presence of BE were also collected, including age, race, gender, smoking, and alcohol use.听Analysis was performed using Chi square and Fisher鈥檚 Exact test.听Multiple logistic regression was performed with cases/control status as the outcome variable, and NSAID use as the predictor variable, with covariates as described above.听P values of < 0.05 were considered significant.听Three hundred and sixty patients participated in the study.听The proportion of current NSAID users did not differ between cases and controls (43% vs. 44%).听听 Similarly, when grouping current and former users together, and comparing them to sporadic or never users, there was no significant difference between cases and controls (58% vs. 57%).听听 Despite the strong negative association between NSAID use and incidence of adenocarcinoma of the esophagus, our results suggest no relationship between NSAID use and Barrett鈥檚 esophagus.听听 Based on these results, one might surmise that NSAIDs may prevent the development of dysplasia in BE, but not the development of BE itself.

The Influence of Race and Sex on Patient Reported Pain Levels

¹Curriculum and Educational Development

University of North Carolina School of Medicine, Chapel Hill, NC

Protein C Pathway Abnormalities as Biomarkers of Hypercoagulability in SLE and APS

Lynn Howie,¹ Jon Solow,¹ and Robert A. S. Roubey¹

¹Thurston Arthritis Research Center, University of North Carolina at Chapel Hill

Purines in Exhaled Breath Condensate as a biomarker of Inflammation.

H. Matias Jasin1,Leonard Collins2,Gunnar Boysen2听,Charles R. Esther, Jr.3

1MS2, 2Biomarker Mass Spectrometry Facility, and

3Pediatric Pulmonology, University of North Carolina at Chapel Hill,

Chapel Hill, NC, USA.

Background:听Assessment of inflammation in the lung has been a challenging problem in patients with cystic fibrosis (CF).听Historically, lung inflammation has been measured by analysis of bronchoalveolar lavage fluid (BALF) attained through invasive bronchoscopies.听Exhaled breath condensate (EBC) is a relatively new, non-invasive technique for collecting dilute samples of airway surface liquid (ASL).听A highly positive correlation between neutrophil counts and purine levels in BAL samples has recently been shown.听This indicates that purines may serve as good markers for neutrophilic lung inflammation.

Aims:听Develop a method for detecting urea (a dilution marker), adenosine, AMP, and ATP in EBC samples using liquid chromatography/ tandem mass spectrometry (LC/MS/MS) and assess the differences between EBC purine levels in CF vs. non-CF controls.

Methods:听Optimization of the electrospray LC/MS/MS method was performed using purine standards injected directly into the MS/MS.听Trials were run to find the optimal buffer pH for ionizing and detecting purines.听Standard curves at optimal pH were produced for estimating EBC purine concentrations.听With a reliable method in place, EBC samples were collected from pediatric CF patients (n=9), asthma patients (n=3), and healthy controls (n=4). Levels of urea, adenosine, and AMP were measured using the optimized LC/MS/MS method.

Results:听We developed a method to reliably detect urea, AMP, and adenosine.听Our work showed that purines are best ionized in buffer systems near pH 8.5.听For ATP, however, these results did not translate to better detection in samples run with the LC column in place.听EBC results showed increased AMP/Ado ratios in the CF airway compared to control, though the result did not reach significance (p=0.057).

Conclusion:听This work is a first step in showing that AMP can be reliably detected in EBC听To further support these preliminary findings, larger cohorts need to be studied and further optimization of the method needs to be done to refine detection techniques for ATP.

Prostate cancer in men treated with testosterone replacement therapy

R. Matthew Coward, Jay Simhan, and Culley C. Carson III, MD

Department of Surgery, Division of Urologic Surgery

University of North Carolina School of Medicine, Chapel Hill, NC

Introduction and Objectives: Although the long-term effect of testosterone replacement therapy (TRT) is unclear, a theoretical increased risk of prostate cancer (CaP) is a primary concern in treating hypogonadism. We retrospectively reviewed hypogonadal men on TRT to evaluate the occurrence and disease progression of CaP, and further to analyze the dynamics of prostate-specific antigen (PSA), in this population. Methods: A total of 81 hypogonadal men, age 56.8 卤 11.5 (range 25-82), were followed for 33.8 卤 29.7 months after initiating TRT. Testosterone and PSA levels were assessed every 6-12 months. Results: Baseline PSA was 1.32 卤 0.98 ng/ml. Pre- and post-treatment (36 months) total testosterone was 241.1 卤 103.5 ng/dl and 379.8 卤 203.3 ng/dl (p=0.003), and free testosterone was 7.9 卤 5.3 ng/dl and 13.3 卤 7.2 ng/dl (p=0.015), respectively. Four men, age 54.5 卤 8.7, developed CaP an average 32.5 卤 7.9 (range 22-41) months after initiating TRT. Three men were diagnosed with Gleason 3+3 CaP and one with Gleason 3+4 CaP. Two men underwent radical prostatectomy with negative surgical margins and subsequent PSA nadirs <0.1 ng/ml. One patient elected external beam radiation therapy with a PSA nadir of 0.7 ng/ml. The fourth patient had not pursued therapy at the time of the study. There was an increase in PSA from baseline to 18 months of 1.8 (p=0.15), while the PSA from baseline increased by 3.2 (p=0.047) at 36 months. In men without CaP, the PSA did not increase significantly for 60 months. Conclusions: Although four hypogonadal men on TRT developed CaP, these cases were of moderate grade and were successfully treated. We recommend closely monitoring all men during the first three years and to consider a decrease in the threshold for prostate biopsy in those men who experience an increase in PSA from baseline over the same time period.

The Effects of the novel protein BARC on Breast Cancer Cells

Matthew Triplette¹

¹Department of Cancer Biology, Wake Forest University Health Sciences

BMP Antagonist Regulated in Cancer(BARC), may influence growth and progression of cancer cells in breast cancers as a BMP antagonist.听Bone Morphogenetic Proteins (BMPs) can contribute to cancer progression through the TGF-beta pathway, with increased BMP levels leading to increased, and potentially unregulated, cellular growth.听The objective of this study was to demonstrate that BARC has a significant effect on secreted levels of BMP-7 in breast cancer cell models, and determine if increased BARC, leading to downregulation of BMP-7, has a significant suppressive effect on breast cancer cell growth.听The first objective was accomplished through a P-Smad immunoblot, detecting the amount of R-Smad phosphorylated extracellularly by BMP-7 in the TGF-beta pathway.听听 Phosphorylated-Smad levels were compared in BARC and control groups after adding a standardized amount of BMP-7 and the particular treatment to ductal carcinoma (MCF7) cells.听To accomplish the second objective, BARC mRNA levels from cDNA samples were used to compare BARC in normal and tumor tissue, BARC cellular and extracellular protein levels were compared across the Weinberg breast cancer cell progression line using Western blot, and, utilizing tissue microarrays, normal and cancerous tissues from patients were probed with BARC and their images were compared by pixel intensity.听The P-Smad immunoblots of MCF7 cells demonstrated that BARC downregulates BMP-7 to a further degree in these cells than known antagonist Noggin, the BARC mRNA levels demonstrate a significant decrease in BARC in tumor versus normal tissues in 81.1% of the patients, and听the immunoblots of the Weinberg line demonstrate that the normal and low oncogene cells secrete significantly more BARC than cancerous cells.听This preliminary study on BARC鈥檚 effect on breast cancer cells illustrates that BARC does act as a significant BMP-7 antagonist in the extracellular environment of breast cells, and its level of secretion has a significant effect on breast cancer cell growth.

Commensal microflora promote post-surgical IBD and fibrosis: Meagan Hunt, Rachael Rigby, Brooks Scull, Micheal Helmrath and P. Kay Lund.

Introduction: Crohn鈥檚 disease (CD) is an incurable, chronic inflammatory bowel disease (IBD).听Fifty-80% of CD patients require bowel resection.听Recurrent inflammation and fibrosis lead to repeat surgery in 20-65% of patients. Ileo-cecal resection (ICR) predicts the highest risk. Commensal microflora appear to initiate and perpetuate IBD in humans and the IL-10 null model of IBD. We developed a model of ICR in IL-10 null mice to test the hypothesis that commensal microflora promote post-surgical IBD.听

Methods: IL-10 null mice received ICR, or control (sham surgery or no surgery) while germ free (GF) and disease free, or 3 weeks after bacterial colonization (CONV), when inflammation is established in cecum.听Animals were killed 28 days post-op. Small intestine (SI), neoterminal ileum/anastomosis (NTI), and colon, were scored histologically for inflammation and fibrosis. Post-surgical disease in SI and NTI was defined as scores higher than in mean CONV or GF controls.听听 Results: In 10/11 CONV-IL-10 null mice, ICR led to inflammation and fibrosis in SI (a site typically disease free) and NTI. ICR in GF-IL-10 null mice led to inflammation and fibrosis in 5/9 SI and 8/9 NTI, although mean disease scores were lower than in CONV-IL-10 null given ICR.听Negative bacterial cultures, and inflammation scores below 1 in colon and SI of GF-IL-10 sham or no surgery controls, while co-housed with GF-ICR mice, confirmed GF status after surgery.

Conclusions : ICR in IL-10 null mice provides a new animal model of post-surgical IBD in small intestine and neoterminal ileum, sites of post-surgical disease in human CD. Differences between GF and CONV after ICR demonstrate that commensal microflora promote more severe and frequent post-surgical disease. Inflammation and fibrosis in a significant number of GF-IL-10 null mice after ICR indicate that bacteria-independent factors also promote post-surgical IBD. Our model should prove valuable for future analyses of mechanisms and preventive therapies for post-surgical IBD.

Regulation of the Myocyte Enhancer Factor 2A (MEF2A) gene by microRNA-346

Nikhil Jariwala, Mariko Tatsuguchi and Da-Zhi Wang

Department of Cell and Developmental Biology

Carolina Cardiovascular Biology Center

The MEF2A gene is critical for muscle cell differentiation.听Although it is known that regulation of the MEF2A mRNA depends upon the 3鈥橴TR, the exact mechanism is not known.听Current research suggests that miRNAs may cause this regulation due to their propensity to down-regulate mRNA translation by binding to the 3鈥橴TR.听Theoretically, miR-346 should regulate MEF2A by reducing gene expression in a reporter assay.听While the strong seeding region of miR-346 suggests one particular binding site on the 3鈥橴TR, the data is unclear as to whether miR-346 actually binds to this site.听Future analysis with a Western Blot may help determine how miR-346 regulates gene expression.

Bayesian Clustering and GO Identity in Bone and Prostate Cancer Microarray Data

Omar Halawa^1,2,3, Debashis Ghosh ^2,3, Zhaohui Qin ^2,3

¹听University of North Carolina School of Medicine, Chapel Hill, North Carolina 27514. USA.

²听Bioinformatics Program, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.

³听Department of Biostatistics, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.

The Relationship Between Functional Health Literacy and Adherence to Emergency Room Discharge Instructions Among Spanish-Speaking Patients

University of North Carolina at Chapel Hill

CYCLOSPORINE DOES NOT PENETRATE, BUT ACCUMULATES AT HIGH CONCENTRATIONS WITHIN, DIFFERENTIATED HUMAN AIRWAY EPITHELIAL CELLS IN VITRO: POSSIBLE IMPLICATIONS FOR THE USE OF INHALED CYCLOSPORINE

Robert Aris, MD¹, Patrick McNeillie, BS¹, Olusegan Olusesi, BS¹, Sarah Thomas, BS¹, Mary Paine, MD², Catherine Hammett-Stabler, MD³ and Isabel Neuringer, MD¹.

¹Pulmonary and Critical Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, 27599; ²School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, 27599 and ³Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, 27599.

Purpose: Recently, inhaled cyclosporine has been shown to reduce mortality and BOS. We hypothesized that inhaled cyclosporine is absorbed through the respiratory epithelium to exert a local immunosuppressive effect. We studied the kinetics of this process using a tissue culture model.

Conclusions: Cyclosporin is very inefficiently absorbed by airway epithelial cells and, interestingly, accumulates within these cells at high concentrations in vitro. Inhaled cyclosporine may work, in part, by altering epithelial cell function.

Fractionation, Dose selection, and Response of Hepatic Metastases of Neuroendocrine TumorsAfter 90Y – Microsphere Brachytherapy

Patrick McNeillie, BS1, Andrew S. Kennedy, MD, FACRO1, William A. Dezarn, PhD1, Carroll Overton, MD2, Mary England, RN1, and Scott L. Sailer, MD1

1Radiation Oncology, Wake Radiology Oncology, Cary, NC, United States, 27511; 2Interventional Radiology, Wake Radiology , Raleigh, NC, United States, 27511

This is a retrospective review of patients from a single institution that received 90Y- microsphere therapy for neuroendocrine hepatic metastases. Physical, radiographic, biochemical, and clinical factors associated with treatment and response were examined, including serial Chromogranin A (CgA) and liver function tests. All patients were followed with laboratory and imaging studies at regular intervals until death, or censured if other therapy was given after Brachytherapy. Toxicities (acute and late) were recorded, and survival of the group determined. We present novel approaches in the use of 90Y – microspheres for unresectable liver metastases from a variety of neuroendocrine tumors. Standard use of microspheres is to apply once, typically to a single lobe, followed a month or so later with treatment of the other lobe. We have used them differently, implanting all the tumors during each treatment i.e. whole liver. A second and third treatment was given to gain control of large hepatic lesions.

Eighteen consecutive patients (10M, 8F) received 24 fractions.The median follow-up is 27 months (4-44 mo). All had receivedprior therapy, with 16/18 chemotherapy, 6 TACE, 2 RGA, and 2lobar resection. Carcinoid symptoms were present in 13 patients prior to treatment, with objective responses found in 16 (89%) by imaging and CgA. Median survival has not yet been reached with only 2 patients succumbing to metastatic disease.听There were no treatment related deaths; radiation induced liver ease, or veno-occlusive disease. Tumors included glucogonoma 1, atypical pulmonary 1, islet cell 1, insulinoma 2, and carcinoid from a small bowel primary 12, usually terminal ileum.

Complete Radiographic Response of Hepatic Metastasesfrom Small Cell Lung Cancer

Treated with 90Y-Microspheres

Patrick McNeillie, BS¹; Andrew Kennedy, MD²; Mary England, BS²; William A. Dezarn, PhD²

¹Pulmonary and Critical Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, 27599; ²Wake Radiology and Oncology Service, Cary, NC United States, 27511.

Microsphere brachytherapy has become an effective treatment for primary and metastatic cancer to the liver. It is a way of permanently implanting liver tumors with radiation utilizing the arterial blood supply. The selective nature of this approach is based on the anatomic fact that 80-100% of the blood supply to

metastatic tumors in the liver derived their arterial supply from the hepatic artery, while the normal liver is predominately feed by the portal venous system. The functional unit is a microsphere (diameter 25-35 microns) containing the therapeutic isotope Yttrium-90 (90Y) contained within a matrix of glass or resin. We report a single, but not uncommon, case of complete resolution of hepatic tumors from a single application of microspheres.

While the rate of cancer in Americans has steadily declined since 1999 the rate among individuals age 65 and older has remained fixed at 24.8 per 100,000. This statistic is worrisome as the relative age of Americans increases due to the mid-1900 baby boom, and predicts for an increase in the number of

patients in need of effective therapy for hepatic metastases from all solid tumors.听The current literature is limited in analyzing treatments of primary lung cancer with metastases to the liver. Nagashima published

a successful surgical series of liver tumors from lung cancer origin with some 5-year survivors. While surgical treatment may provide the best treatment for a very small select group of patients, Y-90 microspheres can provide a treatment option to a greater percentage of patients. For the current patient, it is possible that other local therapies could have been attempted, but microspheres have provided a significant benefit without surgical intervention, and without side effects.

Hepatic metastases from a bronchogenic carcinoma can be controlled with a single, well tolerated brachytherapy procedure with Y-90 microspheres. For a percentage of patients with liverpredominant

Visual Function after Minimally Invasive Pituitary Surgery (MIPS)

Kuruvilla R, Ewend MG¹, Senior BA², Givre SJ^3,4

¹Department of Neurosurgery, ² Otolaryngology, Head and Neck Surgery,听³Ophthalmology, and ⁴Neurology

Introduction: Preservation and restoration of vision are important goals for surgical removal of pituitary adenomas.听As compared with traditional, sublabial transsphenoidal (SLTS) pituitary surgery, endoscopic endonasal surgery (MIPS) is reported to have fewer complications and result in shorter hospital stays.听However, in order for MIPS to be accepted along side traditional approaches, visual outcomes following MIPS must be comparable to those from traditional surgery.听Methods: Retrospective review of patients undergoing MIPS who had ophthalmologic examination and, when possible, visual field testing (automated threshold or Goldman perimetry) before and after surgery.听Surgery was performed by a single team of surgeons.听Pre- and postoperative data were compared.听Automated threshold perimetry was scored using a system similar to that used in the Collaborative Initial Glaucoma Treatment Study.听Results: The duration between surgery and post-operative ophthalmologic examination ranged from 2 days to 35 months (mean 6.1 months).听Of the 35 eyes evaluated, initial post-operative visual acuity was unchanged in 17 (48%), better in 14 (40%), and worse in 4 (11%).听Initial post-operative visual field scores were unchanged in 7 (20%), better in 24 (69%), and worse in 4 (11%). Only two eyes showed a decrease in both visual acuity and field. Averaged across all eyes, the postoperative visual field score after MIPS was significantly improved as compared with the preoperative score.听There was no statistically significant inter-eye difference.听Conclusion: Multiple studies of visual outcomes after traditional SLTS pituitary surgery have shown favorable results with this technique.听The methods of visual field testing and visual field scoring in the current study are not directly comparable to previous studies of outcomes from traditional surgery.听However, the current preliminary data suggest that visual outcomes after MIPS are favorable as well.听This implies that MIPS is a reasonable alternative to tradition pituitary surgery.

Health Behaviors in Primary Care Patients at Risk for Diabetes

Xiaoci 鈥淪arah鈥� Guo, MSII, Katrina E Donahue¹, MD, MPH, Madeline Mitchell², MURP, Philip D. Sloane^1,2, MD, MPH

¹Department of Family Medicine, ² Cecil G. Sheps Center for Health Services Research

PURPOSE:听Poor health behaviors contribute to developing diabetes.听This study examines the relationship between patients鈥� risk for diabetes and their health behaviors, including nutrition, physical activity, smoking, and alcohol use to understand health habits of this population to effectively tailor office counseling.

METHODS:听Patients presenting for routine visits at six NC family practices were asked to fill out a computer survey.听Those identified as having one or more risky behavior were enrolled.听Study participants received a follow up telephone survey to obtain additional information regarding their health behaviors.听Health behaviors were compared among patients with 1) diabetes, 2) high risk for developing diabetes and 3) low risk.

RESULTS:听Currently, 109 patients are enrolled.听Patients with diabetes or at risk for diabetes are more likely to be smokers than those at low risk (28.6% vs 22% vs 16.1%).听Patients with diabetes or at high risk are more likely to get less than 5 servings of fruits and vegetables per day than those at low risk (53.6% vs 68.0% vs 21.0%).听Patients with diabetes or at risk for diabetes are more sedentary than those at low risk (42.9% vs 74% vs 22.6%).

The Role of the Serotonin 2A Receptor Subtype in Primary Auditory Cortex Layer II/III Pyramidal Neurons

Scott Daniels¹, Gregory Basura², MD, PhD, Deepti Rao³, Paul Manis⁴

¹ School of Medicine MD Candidate, ² Otolaryngology Resident, ³ Cell and Molecular Biology PhD Candidate, ⁴ Otolaryngology Department Chair

Supportedby the Otolaryngology Training Grant

University of North Carolina, Chapel Hill, NC

Comparative Accuracy of Oscillometric and Intra-aortic Blood Pressure Measurements In Patients Undergoing Routine Cardiac Catheterization.

Skand Bhatt¹, Robert Kelly MD², Rick Stouffer MD²

¹School of Medicine and Public Health, ²Department of Cardiology

University of North Carolina at Chapel Hill

Oscillometry is a common method of non-invasive blood pressure determination, but few studies have reported the accuracy of this technique compared to direct measurement. To assess the accuracy of oscillometry, non-invasive cuff pressures were measured at the brachial artery and compared with simultaneous direct aortic pressure measurements in 98 patients (32-84 years, mean 58.5 years, 55.1% males) undergoing routine cardiac catheterization. Oscillometry underestimated mean aortic systolic pressure by 7.4 mm Hg (p<0.0001) and overestimated mean aortic diastolic pressure by 5.2 mm Hg (p<0.0001). Clinically significant discrepancies, defined as greater than +/- 10.0 mm Hg difference, were observed in 49.0% of mean systolic measurements and 30.6% of mean diastolic measurements. In a subgroup analysis, mean pressure differences were significantly greater for women compared to men after adjusting for other known factors. The results suggest that clinically significant differences in systolic and diastolic pressure exist by the oscillometric technique, compared to direct measurements, and that the magnitude of difference may be greater among female patients.

Regional Change in Brain Morphometry in Schizophrenia Associated with Short Term Antipsychotic Treatment.

Stacy Greeter, ¹ Khary Carew, ¹ Robert McClure, M.D. ²

大象传媒-Chapel Hill School of Medicine,¹ Department of Psychiatry, 大象传媒²

ROLE OF MACROPHAGE ACCUMULATION AND ALTERED SIGNALING IN INNATE IMMUNE DYSF大象传媒TION LATE AFTER BURN INJURY

Stefan Mlot BS¹, Robert Maile PhD^1,2, and Bruce Cairns MD¹

The University of North Carolina at Chapel Hill

NC Jaycee Burn Center, Departments of ¹Surgery and ²Microbiology and Immunology

Heparin sodium salt does not promote collagen fibril sliding in rat tail tendons, in vitro.

Department of Orthopaedics, University of North Carolina, Chapel Hill, NC

Comparison of Functional MRI Activation Patterns between Mild Cognitive Impairment Subjects and Elderly Controls at Ultra-High Field Strength

Sriyesh Krishnan^1,2, Melissa Slavin^1,2,3, Thanh-Thu Tran^1,2,3,Lakshmi Murty^1,2, Anne Finefrock ³, P.Murali Doraiswamy³, Jeffrey Petrella¹

¹Department of Radiology, ²Brain Imaging and Analysis Center, and ³Department of Psychiatry

BACKGROUND: The Mild Cognitive Impairment (MCI) population represents a group of at-risk subjects who may have prodromal Alzheimer鈥檚 disease (AD).听Analysis of subtle functional brain activation changes in this population may yield information on patterns of neuronal dysfunction occurring prior to anatomical changes seen with conventional imaging techniques.听听听 OBJECTIVE: To assess differences in brain activation patterns between MCI subjects and normal controls using functional magnetic resonance imaging (fMRI) at ultra high field strength during a memory encoding and retrieval task.听听听 METHODS: Twenty-eight subjects were studied during a face-name memory encoding and retrieval task at 4T.听Novel and familiar face-name pairs were presented within a blocked design.听The MCI (9M/5F, mean 76.3 years, SD 6.1) and control (9M/5F, mean 72.7 years, SD 5.0) groups were compared using Statistical Parametric Mapping random effects ANCOVA, with age as the covariate.听Medial temporal lobe (MTL) and whole brain analyses were performed.听听听 RESULTS: Analysis during encoding revealed increased activation in the right precentral and fusiform gyri and left medial frontal gyrus in ONS subjects and increased MTL activation in the left hippocampus and parahippocampal gyrus in MCI subjects.听听 During retrieval, there were multiple areas of increased frontal activation in ONS subjects including bilateral insular cortex and left precentral gyrus.听A single cluster of increased activation in MCI subjects in the area of the left fusiform and middle occipital gyri was noted during retrieval.听听听 CONCLUSIONS:Differential fMRI activation patterns within MTL and frontal lobe structures are evident in MCIs in comparison to controls.听These differences may reflect early disruption of the neuronal networks of memory processing prior to neuroanatomical atrophy.听Analysis of differential fMRI activation could someday have a diagnostic role in the early detection of AD.

Effects of Couples Intervention on the Experience of Fatigue

Theresa Kallman¹, Donald Baucom^2,3, Tina Gremore^2,3, Nicole Pukay-Martin^2,3

¹ School of Medicine听² Department of Psychology ³ Lineberger Comprehensive Cancer Center

Fatigue is experienced by 60 to 90 percent of cancer patients, and thus represents a significant barrier to achieving a high quality of life.听Decreasing the physical side effects of breast cancer, in this case, fatigue, is an obtainable goal in the treatment of breast cancer patients.听Given the link between psychological factors and fatigue, psychosocial interventions for breast cancer patients are likely to impact the patient鈥檚 experience of disease positively.听The goal of the current investigation is to understand the mechanisms through which the CanThrive intervention contributes to lower levels of fatigue for women with breast cancer.听Measures of pain, fatigue, social support, marital satisfaction, psychological functioning, and cancer related well-being are assessed in the CanThrive study as part of the routine research assessment battery.听Baron and Kenny鈥檚 approach to assessing mediation was employed to examine potential mechanisms through which CanThrive affects fatigue.听It was found that the CanThrive intervention decreases fatigue and also decreases psychological distress.听It was then found that psychological distress accounts for partial mediation of the relationship between treatment group and fatigue. That is, CanThrive appears to decrease fatigue in part by decreasing psychological distress.听This study found that the CanThrive intervention decreases fatigue, even though fatigue is not directly targeted.听This is important because even though fatigue is medically induced, behavioral and psychosocial strategies can be effective additions to medical interventions for decreasing the experience of fatigue among women with breast cancer.听The results of this study show that the effect of CanThrive is not medicated by social support or relationship variables such as relationship adjustment, but rather is a result of decreasing individual psychological distress.听Moreover, CanThrive decreases women鈥檚 psychological distress which is related to their experience of fatigue.听听

Proyecto Puentes de Salud: An Exploration of Cardiovascular Health and Risk Factors in Rural Mexico

Allan D Nanney III⁵, Trista D Snyder⁵, Ian J Nelligan⁵, Amanda L

Rollins⁵, Katherine Zeman, Michael Clarke-Pearson, Pamela Y Frasier¹

PhD MA MSPH, Bron Skinner¹ PhD, Daniel Reuland³ MD,

Flavio Rojas⁴ PhD, Mauricio G Cohen² MD.

¹大象传媒 Department of Family Medicine, ²大象传媒 Department of Cardiology, ³大象传媒 Department of Medicine, ⁴大象传媒 Department of Biostatistics, ⁵大象传媒

University of North Carolina, Chapel Hill, NC

The 2000 NC census estimated a 1200% increase in Hispanic immigration to the Triangle area. A large proportion of the economic migrants come from rural Mexican communities, and little is known about their antecedent lifestyles and health risks and how these might contribute to their current health status. Therefore, Proyecto Puentes de Salud was initiated to determine cardiovascular risk factors of rural residents in Guanajuato, Mexico. Future studies will draw correlations between health and lifestyle risks of the US immigrant and rural Mexican populations, providing NC physicians with an all-encompassing view of Latino health. A convenience sample of 267 participants, recruited from six rural communities in Guanajuato during June and July of 2006, were (1) offered free screenings for cholesterol, fasting glucose, blood pressure, and obesity; (2) counseled about risk factors for cardiovascular diseases and diabetes; and (3) interviewed using a standardized questionnaire that included demographic information, past medical history, family history, dietary and lifestyle behaviors, and social and psychological health.267 participants (ages 20-85) were screened and interviewed.听Prevalence of hypertension (>140/90) was 29.96%, impaired fasting glucose (>100 mg/dL) was 25.02%.听Frequency of abnormal cholesterol and HDL was 19.85 % (>200 mg/dL) and 85.55% (<40 mg/dL men, <50mg/dL women), respectively.听Abdominal obesity rates were 73.03%. We detected a high prevalence of cardiovascular risk factors in rural Mexicans that warrants further investigation. In particular, we noticed an overwhelming presence of inadequate levels of HDL and abdominal obesity, placing this population at risk for The Metabolic Syndrome.听Lack of education on cardiovascular risk factors and healthy lifestyles seem to play a large role in perpetuating poor diet, limited exercise, and daily health choices. Additional educational instruction, with lifestyle modifications could rectify these risks; improving the health of Mexicans in their place of origin may have a ripple effect on the health of Latino immigrants we treat in our community. Also, understanding of this expanding patient population will give American physicians a head-start when treating and educating in the clinic. The study was limited by the under-representation of men in the research and by being a convenience sample.