Perelman School of Medicine

Perelman School of Medicine's mission is to advance knowledge and improve health through research, patient care, and the education of trainees in an inclusive culture that embraces diversity, fosters innovation, stimulates critical thinking, supports lifelong learning, and sustains our legacy of excellence.

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  • Publication
    Epidemiology of Methicillin‐Resistant Staphylococcus aureus Bacteremia in Gaborone, Botswana
    (2009-08-01) Wood, Sarah; Shah, Samir S; Bafana, Maragaret; Ratner, Adam J; Meaney, Peter A; Malefho, Kolaatamo C.S; Steenhoff, Andrew P
    This cross‐sectional study at a tertiary‐care hospital in Botswana from 2000 to 2007 was performed to determine the epidemiologic characteristics of Staphylococcus aureus bacteremia. We identified a high prevalence (11.2% of bacteremia cases) of methicillin‐resistant S. aureus (MRSA) bacteremia. MRSA isolates had higher proportions of resistance to commonly used antimicrobials than did methicillin‐susceptible isolates, emphasizing the need to revise empiric prescribing practices in Botswana.
  • Publication
    Perceived Effectiveness of Acupuncture: Findings From the National Health Interview Survey
    (2008-12-01) LaRiccia, Patrick J; McMurphy, Suzanne; Gallo, Joseph J; Xie, Daiwei; Branas, Charles
    Background: Knowledge of perceived benefit from acupuncture treatment is important to predict who is using acupuncture, to inform physicians of the possible benefits of acupuncture, to determine where rigorous research should be focused, and to help policy makers predict future demand. Objectives: To determine the proportions of survey respondents who reported perceived effectiveness of acupuncture treatment for specific conditions; and to determine the association of specified demographic variables with perceived effectiveness. Design, Setting, and Participants: Publicly available data from 31,044 noninstitutionalized US adults who participated in the 2002 National Health Interview Survey, a cross-sectional in-home computer-assisted interview. Outcome Measures: The proportions of participants reporting “any help” and “great help” for perceived effectiveness across conditions treated and per condition treated; and the association of the subgroups within age, sex, and body mass index (BMI), along with the subgroups Asian race and Chinese ethnicity, with “any help” of acupuncture treatment across conditions treated. Results: Of the 1,274 respondents who reported having consulted an acupuncturist, 329 had used acupuncture in the last 12 months; 276 had used acupuncture to treat a specific condition. A total of 86% of respondents reported being helped by acupuncture, while 45% reported being greatly helped across conditions treated. In an examination of specific conditions treated, the range for “any help” was 98% to 67%, and 98% to 7% in the “great help” outcome. Older age and obesity were negatively associated with perceived effectiveness statistically but not clinically. Asian race and Chinese ethnicity were not statistically significantly associated with perceived effectiveness. Conclusions: Acupuncture is perceived to be effective by most respondents who used it to treat a specific condition. Older age and obesity are negatively associated with perceived effectiveness, but not at a clinically significant level. A larger sample of Asian and Chinese subgroups is needed to determine if there is an association of these subgroups with perceived benefit.
  • Publication
    Baby Schema in Infant Faces Induces Cuteness Perception and Motivation for Caretaking in Adults
    (2009-03-01) Glocker, Melanie L; Langleben, Daniel D; Ruparel, Kosha; Loughead, James W; Gur, Ruben C; Sachser, Norbert
    Ethologist Konrad Lorenz proposed that baby schema (‘Kindchenschema’) is a set of infantile physical features such as the large head, round face and big eyes that is perceived as cute and motivates caretaking behavior in other individuals, with the evolutionary function of enhancing offspring survival. Previous work on this fundamental concept was restricted to schematic baby representations or correlative approaches. Here, we experimentally tested the effects of baby schema on the perception of cuteness and the motivation for caretaking using photographs of infant faces. Employing quantitative techniques, we parametrically manipulated the baby schema content to produce infant faces with high (e.g. round face and high forehead), and low (e. g. narrow face and low forehead) baby schema features that retained all the characteristics of a photographic portrait. Undergraduate students (n = 122) rated these infants’ cuteness and their motivation to take care of them. The high baby schema infants were rated as more cute and elicited stronger motivation for caretaking than the unmanipulated and the low baby schema infants. This is the first experimental proof of the baby schema effects in actual infant faces. Our findings indicate that the baby schema response is a critical function of human social cognition that may be the basis of caregiving and have implications for infant–caretaker interactions.
  • Publication
    The D0 Domain of KIR3D Acts as a Major Histocompatibility Complex Class I Binding Enhancer
    (2002-10-07) Khakoo, Salim I; Geller, Ron; Shin, Sunny; Jenkins, Jomaquai A; Parham, Peter
    In contrast to the KIR2D:HLA-C interaction, little is known of KIR3DL1's interaction with HLA-B or the role of D0, the domain not present in KIR2D. Differences in the strength and specificity for major histocompatibility complex class I of KIR3DL1 and its common chimpanzee homologue Pt-KIR3DL1/2 were exploited to address these questions. Domain-swap, deletion, and site-directed mutants of KIR3DL1 were analyzed for HLA-B binding using a novel, positively signaling cell–cell binding assay. Natural ‘deletion’ of residues 50 and 51 from its D0 domain causes Pt-KIR3DL1/2 to bind Bw4+ HLA-B allotypes more avidly than does KIR3DL1. Deletion of these residues from KIR3DL1, or their substitution for alanine, enhanced binding of Bw4+ HLA-B. None of 15 different point mutations in D0 abrogated KIR3DL1 binding to Bw4+ HLA-B. In contrast point mutations in the D1 and D2 domains of KIR3DL1, made from knowledge of KIR2D:HLA-C interactions, disrupted binding to Bw4+ HLA-B. The results are consistent with a model in which D1 and D2 make the principal contacts between KIR3DL1 and HLA-B while D0 acts through a different mechanism to enhance the interaction. This modulatory role for D0 is compatible with natural loss of expression of the D0 domain, a repeated event in the evolution of functional KIR genes.
  • Publication
    Type IV Secretion-Dependent Activation of Host MAP Kinases Induces an Increased Proinflammatory Cytokine Response to Legionella pneumophila
    (2008-11-28) Shin, Sunny; Case, Christopher L; Archer, Kristina A; Nogueira, Catarina V; Kobayashi, Koichi S; Flavell, Richard A; Roy, Craig R; Zamboni, Dario S
    The immune system must discriminate between pathogenic and nonpathogenic microbes in order to initiate an appropriate response. Toll-like receptors (TLRs) detect microbial components common to both pathogenic and nonpathogenic bacteria, whereas Nod-like receptors (NLRs) sense microbial components introduced into the host cytosol by the specialized secretion systems or pore-forming toxins of bacterial pathogens. The host signaling pathways that respond to bacterial secretion systems remain poorly understood. Infection with the pathogen Legionella pneumophila, which utilizes a type IV secretion system (T4SS), induced an increased proinflammatory cytokine response compared to avirulent bacteria in which the T4SS was inactivated. This enhanced response involved NF-κB activation by TLR signaling as well as Nod1 and Nod2 detection of type IV secretion. Furthermore, a TLR- and RIP2-independent pathway leading to p38 and SAPK/JNK MAPK activation was found to play an equally important role in the host response to virulent L. pneumophila. Activation of this MAPK pathway was T4SS-dependent and coordinated with TLR signaling to mount a robust proinflammatory cytokine response to virulent L. pneumophila. These findings define a previously uncharacterized host response to bacterial type IV secretion that activates MAPK signaling and demonstrate that coincident detection of multiple bacterial components enables immune discrimination between virulent and avirulent bacteria.
  • Publication
    The Representation of Parts and Wholes in Face-selective Cortex
    (2008-05-01) Harris, Alison; Aguirre, Geoffrey Karl
    Although face perception is often characterized as depending on holistic, rather than part-based, processing, there is behavioral evidence for independent representations of face parts. Recent work has linked ‘‘face-selective’’ regions defined with functional magnetic resonance imaging (fMRI) to holistic processing, but the response of these areas to face parts remains unclear. Here we examine part-based versus holistic processing in ‘‘face-selective’’ visual areas using face stimuli manipulated in binocular disparity to appear either behind or in front of a set of stripes [Nakayama, K., Shimojo, S., & Silverman, G. H. Stereoscopic depth: Its relation to image segmentation, grouping, and the recognition of occluded objects. Perception, 18, 55–68, 1989]. While the first case will be ‘‘filled in’’ by the visual system and perceived holistically, we demonstrate behaviorally that the latter cannot be completed amodally, and thus is perceived as parts. Using these stimuli in fMRI, we found significant responses to both depth manipulations in inferior occipital gyrus and middle fusiform gyrus (MFG) ‘‘faceselective’’ regions, suggesting that neural populations in these areas encode both parts and wholes. In comparison, applying these depth manipulations to control stimuli (alphanumeric characters) elicited much smaller signal changes within faceselective regions, indicating that the part-based representation for faces is separate from that for objects. The combined adaptation data also showed an interaction of depth and familiarity within the right MFG, with greater adaptation in the back (holistic) condition relative to parts for familiar but not unfamiliar faces. Together, these data indicate that face-selective regions of occipito-temporal cortex engage in both part-based and holistic processing. The relative recruitment of such representations may be additionally influenced by external factors such as familiarity.
  • Publication
    Tenofovir-Associated Nephrotoxicity in Two HIV-Infected Adolescent Males
    (2009-02-01) Wood, Sarah M; Shah, Samir S; Steenhoff, Andrew P; Meyers, Kevin E. C; Kaplan, Bernard S; Rutstein, Richard M
    We report two cases of tenofovir (TDF)-associated nephrotoxicity in perinatally HIV-infected adolescents. The first case, a 16-year-old African American male with an absolute CD4+ cell count of 314 cells/mm3, presented with an abrupt rise in serum creatinine leading to irreversible renal failure while on TDF-containing highly active antiretroviral therapy (HAART). While the patient had evidence of underlying kidney disease, the timing of his renal failure indicates that TDF played a central role. The second case, a 16-year-old African-American male with an absolute CD4+ cell count of 895 cells/mm3, presented with rickets and hypophosphatemia while receiving TDF-based HAART. To our knowledge, these cases represent the first reports of TDF-associated irreversible renal failure and rickets in pediatric patients. We believe these cases highlight important and potentially irreversible side effects of this agent and emphasize the need for further studies of the renal safety of TDF in pediatric patients.
  • Publication
    Nonresectable Hepatocellular Carcinoma: Long-term Toxicity in Patients Treated with Transarterial Chemoembolization - Single-Center Experience
    (2008-10-01) Buijs, Manon; Vossen, Josephina A; Frangakis, Constantine; Hong, Kelvin; Georgiades, Christos S; Chen, Yong; Liapi, Eleni; Geschwind, Jean-François H
    Purpose: To determine the toxicity profile of transarterial chemoembolization (TACE) at 6 months and 1 year after treatment in patients with hepatocellular carcinoma (HCC) in a standardized oncology protocol so that TACE could be compared with systemic chemotherapeutic regimens for liver cancer. Materials and Methods: The study was authorized by the institutional review board. Between January 2002 and January 2007, 190 patients (155 men, 35 women; median age, 65 years; age range, 18 – 84 years) with HCC who underwent TACE treatment were identified from a prospectively collected database. Clinical records of complete blood cell counts and chemical profiles at baseline and at 6 and 12 months after treatment were studied retrospectively. Toxicity was graded according to the common terminology criteria for adverse events (CTCAE). A transition (survival) analysis perspective was used to estimate the distribution of toxicity grades. Patient survival from the first TACE session was calculated with Kaplan-Meier analysis. Results: Grade 3 or 4 toxicity 6 and 12 months, respectively, after treatment included leukocytopenia (7% and 19%); anemia (9% and 19%); thromobocytopenia (13% and 23%); prolonged activated partial thromboplastin time (8% and 18%); elevated aspartate aminotransferase (15% and 18%), alanine aminotransferase (10% and 18%), and alkaline phosphatase (8% and 18%) levels; hypoalbuminemia (10% and 19%); hyperbilirubinemia (10% and 22%); and alopecia (18%). The cumulative survival rate was 58% at 1 year, 39% at 2 years, and 29% at 3 years. These toxicity rates were considerably lower than those reported after treatment with currently used systemic chemotherapeutic agents. Conclusion: Study results show that TACE has a favorable long-term toxicity profile in patients with HCC. Data clearly support the role of TACE in the treatment of patients with nonresectable HHC.
  • Publication
    Power in Voxel-based Lesion–Symptom Mapping
    (2007-07-01) Kimberg, Daniel Y.; Coslett, H. Branch; Schwartz, Myrna F.
    Lesion analysis in brain-injured populations complements what can be learned from functional neuroimaging. Voxelbased approaches to mapping lesion–behavior correlations in brain-injured populations are increasingly popular, and have the potential to leverage image analysis methods drawn from functional magnetic resonance imaging. However, power is a major concern for these studies, and is likely to vary regionally due to the distribution of lesion locations. Here, we outline general considerations for voxel-based methods, characterize the use of a nonparametric permutation test adapted from functional neuroimaging, and present methods for regional power analysis in lesion studies.
  • Publication
    Simultanagnosia: When a Rose Is Not Red
    (2008-01-01) Coslett, H. Branch; Lie, Grace
    Information regarding object identity (‘‘what’’) and spatial location (‘‘where/how to’’) is largely segregated in visual processing. Under most circumstances, however, object identity and location are linked. We report data from a simultanagnosic patient (K.E.) with bilateral posterior parietal infarcts who was unable to ‘‘see’’ more than one object in an array despite relatively preserved object processing and normal preattentive processing. K.E. also demonstrated a finding that has not, to our knowledge, been reported: He was unable to report more than one attribute of a single object. For example, he was unable to name the color of the ink in which words were written despite naming the word correctly. Several experiments demonstrated, however, that perceptual attributes that he was unable to report influenced his performance. We suggest that binding of object identity and location is a limited-capacity operation that is essential for conscious awareness for which the posterior parietal lobe is crucial.