Medicine and Health Sciences Commons^™

Are Roadside Pedestrian Injury Patterns Predictable In A Densely Populated, Urban Setting?, Niels D. Martin, Daniel J. Grabo, Lili Tang, Jacqueline Sullivan, Kris R. Kaulback, Michael S. Weinstein, Gary A. Lindenbaum, Murray J. Cohen

Department of Surgery Faculty Papers

BACKGROUND: Roadside pedestrian injuries represent a significant portion of trauma team activations, especially at urban trauma centers. Patient demographics and severity of injury vary greatly in this patient population. Herein, we hypothesize that injury patterns may be predictable, especially with respect to age.

MATERIALS AND METHODS: All patients with roadside pedestrian injuries evaluated at our urban, level one trauma center from January 2006 through December 2008 were retrospectively reviewed. Data were collected from the institutional trauma registry. Age was used as an independent variable and compared with injury type, substance abuse, discharge setting, and mortality.

RESULTS: There were 226 roadside …

The Importance Of Examining Movements Within The Us Health Caresystem: Sequential Logit Modeling, Chioun Lee, Stephanie L L. Ayers, Jennie Jacobs Kronenfeld, Jemima A. Frimpong, Patrick A. Rivers, Sam S. Kim

Dartmouth Scholarship

Utilization of specialty care may not be a discrete, isolated behavior but rather, a behavior of sequential movements within the health care system. Although patients may often visit their primary care physician and receive a referral before utilizing specialty care, prior studies have underestimated the importance of accounting for these sequential movements. The sample included 6,772 adults aged 18 years and older who participated in the 2001 Survey on Disparities in Quality of Care, sponsored by the Commonwealth Fund. A sequential logit model was used to account for movement in all stages of utilization: use of any health services (i.e., …

Efficacy Of Morning-Only Compared With Split-Dose Polyethylene Glycol Electrolyte Solution For Afternoon Colonoscopy: A Randomized Controlled Single-Blind Study., Rebecca Matro, Md, Anastasia Shnitser, Md, Maya Spodik, Md, Constantine Daskalakis, Sc.D, Leo Katz, Md, Alexandra Murtha, Ba, David Kastenberg, Md

Division of Internal Medicine Faculty Papers & Presentations

OBJECTIVES: Administering a purgative close to the time of colonoscopy is optimal for cleansing. The aim of this study was to compare the efficacy and tolerability of morning-only (AM-only) polyethylene glycol electrolyte solution (PEG-ELS) to split-dose (PM/AM) PEG-ELS for afternoon colonoscopy.

METHODS: This was a single-center, prospective, randomized, investigator-blinded, non-inferiority study comparing AM-only to PM/AM PEG-ELS for afternoon outpatient colonoscopy. The primary end point was whole colon prep adequacy. Tolerance and polyp detection were secondary outcomes.

RESULTS: Overall, 125 patients were randomized and 9 withdrew without taking any prep. Of 116 analyzed, 62 received AM-only prep and 54 received PM/AM …

Differences In Discharge Medication After Acute Myocardial Infarction In Patients With Hmo And Fee-For-Service Medical Insurance, Danny Mccormick, Jerry Gurwitz, Judith Savageau, Jorge Yarzebski, Joel Gore, Robert Goldberg

Jorge L. Yarzebski

OBJECTIVE: To assess the impact of fee-for-service (FFS) versus HMO medical insurance coverage on receipt of aspirin, beta-blockers, and calcium channel blockers at the time of hospital discharge following an acute myocardial infarction. DESIGN: Prospective, population-based study. SETTING: All 16 community and tertiary care hospitals in the metropolitan area of Worcester, Massachusetts. PATIENTS: The study population consisted of patients under 65 years of age hospitalized with a validated acute myocardial infarction in all hospitals in the Worcester (Massachusetts) Standard Metropolitan Statistical Area (1990 census estimate, 437,000) during 1986, 1988, 1990, 1991, and 1993. MEASUREMENTS AND MAIN RESULTS: After adjustment for …

Health Insurance Coverage And Outcome Following Acute Myocardial Infarction. A Community-Wide Perspective, Silvia Kreindel, Ronald Rosetti, Robert Goldberg, Judith Savageau, Jorge Yarzebski, Joel Gore, Arthur Russo, Carol Bigelow

Jorge L. Yarzebski

BACKGROUND: Several studies have suggested that type of medical insurance coverage is associated with hospital utilization rates and receipt of selected diagnostic or treatment approaches. To our knowledge no studies, however, have examined the relation between medical insurance coverage and short-term outcomes following acute myocardial infarction (AMI) from a multihospital, community-wide perspective. OBJECTIVE: To examine the association between medical insurance coverage and in-hospital case-fatality rates as well as length of hospital stay following AMI. METHODS: The study sample consisted of 3735 residents of the Worcester, Mass, metropolitan area hospitalized with validated AMI during 1986, 1988, 1990, 1991, and 1993 at …

Human Papillomavirus And Survival Of Patients With Oropharyngeal Cancer., K Kian Ang, Jonathan Harris, Richard Wheeler, Randal Weber, David I Rosenthal, Phuc Felix Nguyen-Tân, William H Westra, Christine H Chung, Richard C Jordan, Charles Lu, Harold Kim, Rita S. Axelrod, Md, C Craig Silverman, Kevin P Redmond, Maura L Gillison

Jefferson Hospital Staff Papers and Presentations

BACKGROUND: Oropharyngeal squamous-cell carcinomas caused by human papillomavirus (HPV) are associated with favorable survival, but the independent prognostic significance of tumor HPV status remains unknown.

METHODS: We performed a retrospective analysis of the association between tumor HPV status and survival among patients with stage III or IV oropharyngeal squamous-cell carcinoma who were enrolled in a randomized trial comparing accelerated-fractionation radiotherapy (with acceleration by means of concomitant boost radiotherapy) with standard-fractionation radiotherapy, each combined with cisplatin therapy, in patients with squamous-cell carcinoma of the head and neck. Proportional-hazards models were used to compare the risk of death among patients with HPV-positive …

Postoperative Complications Of Powered Intracapsular Tonsillectomy And Monopolar Electrocautery Tonsillectomy In Teens Versus Adults., Douglas R Johnston, Michael Gaslin, Maurits Boon, Edmund Pribitkin, David Rosen

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVES: This study was performed to determine whether teens have different rates of posttonsillectomy hemorrhage, admission for dehydration, or recurrent tonsillitis compared to adults. Specifically, these parameters were compared within two groups: patients who underwent powered intracapsular tonsillectomy (PIT) and those who underwent monopolar electrocautery tonsillectomy (MET).

METHODS: In a retrospective review of 579 patients at least 12 years of age from January 2000 to July 2006 in a tertiary referral center, outcome measures of reoperation for hemorrhage, readmission or emergency room visit for dehydration, and postoperative tonsillitis were compared for 200 patients 12 to 19 years of age and …

A Randomized Comparison Of Online And Paper Mood Charts For People With Bipolar Disorder., Daniel Z Lieberman, Tammas F Kelly, Lanny Douglas, Frederick K Goodwin

Psychiatry and Behavioral Sciences Faculty Publications

BACKGROUND: Longitudinal mood instability is the essential feature of bipolar disorder, however most rating scales are cross sectional in nature, and focus on acute symptoms. By contrast, the NIMH Life Chart Methodology (LCM) characterizes in detail the severity, duration, and frequency of mood episodes. Adherence to daily rating, however, tends to be low. In this study an online version of the LCM, designed to enhance adherence, was compared to the standard paper version.

METHODS: Patients from a mood disorders specialty clinic were randomized to the standard LCM or an online, open-source adaptation. The online version used hypertext links embedded in …

Tubercular Pancreatic Abscess Presenting As Fever And Cystic Pancreatic Lesion With Endoscopic Management., Jonathan M. Fenkel, Maya Spodik, Bheema S. Singu, Anthony Infantolino, Sandeep P. Deshmukh, David E. Loren

Division of Gastroenterology and Hepatology Faculty Papers

Isolated pancreatic tuberculosis is a rare presentation of tubercular infection. There are few reported cases of pancreatic tuberculosis diagnosed by endoscopic ultrasound with fine-needle aspiration (EUS FNA), though EUS is often used in the evaluation of pancreatic cystic lesions. We present a case of a tubercular pancreatic abscess presenting as a cystic lesion in a patient with undiagnosed immunodeficiency. The abscess was aspirated by EUS FNA and treated with endoscopic drainage and anti-mycobacterial medications.

Hypertension In Children And Adolescents: Epidemiology And Natural History., Bonita Falkner

Department of Medicine Faculty Papers

Primary hypertension is detectable in children and adolescents and, as in adults, is associated with a positive family history of hypertension, obesity, and life-style factors. Owing to the well-established childhood obesity epidemic, the population prevalence of high blood pressure (BP) in the young is increasing. Hypertension in childhood is commonly associated with other cardiovascular risk factors as well as obesity. Although death and cardiovascular disability do not occur in hypertensive children, intermediate markers of target organ damage, such as left ventricular hypertrophy, thickening of the carotid vessel wall, retinal vascular changes, and even subtle cognitive changes, are detectable in children …

Anti-Hiv Activity In Cervical-Vaginal Secretions From Hiv-Positive And -Negative Women Correlate With Innate Antimicrobial Levels And Igg Antibodies, Mimi Ghosh, John V. Fahey, Zheng Shen, Timothy Lahey, Susan Cu-Uvin, Zhijin Wu, Kenneth Mayer, Peter F. Wright, John C. Kappes, Christina Ochsenbauer, Charles R. Wira

Dartmouth Scholarship

Background: We investigated the impact of antimicrobials in cervicovaginal lavage (CVL) from HIV(+) and HIV(2) women on target cell infection with HIV. Since female reproductive tract (FRT) secretions contain a spectrum of antimicrobials, we hypothesized that CVL from healthy HIV(+) and (2) women inhibit HIV infection.

Methodology/Principal Findings: CVL from 32 HIV(+) healthy women with high CD4 counts and 15 healthy HIV(2) women were collected by gently washing the cervicovaginal area with 10 ml of sterile normal saline. Following centrifugation, anti- HIV activity in CVL was determined by incubating CVL with HIV prior to addition to TZM-bl cells. Antimicrobials and …

Splenic Infarction: An Update On William Osler's Observations., Yaacov R Lawrence, Ma Mbbs Mrcp, Russell Pokroy, Mb Bch, Daniel Berlowitz, Mb Bch, Dvora Aharoni, Md, Daniel Hain, Md, Gabriel S Breuer, Md

Department of Radiation Oncology Faculty Papers

BACKGROUND: Osler taught that splenic infarction presents with left upper abdominal quadrant pain, tenderness and swelling accompanied by a peritoneal friction rub. Splenic infarction is classically associated with bacterial endocarditis and sickle cell disease.

OBJECTIVES: To describe the contemporary experience of splenic infarction.

METHODS: We conducted a chart review of inpatients diagnosed with splenic infarction in a Jerusalem hospital between 1990 and 2003.

RESULTS: We identified 26 cases with a mean age of 52 years. Common causes were hematologic malignancy (six cases) and intracardiac thrombus (five cases). Only three cases were associated with bacterial endocarditis. In 21 cases the splenic …

In-Theater Peritoneal Dialysis For Combat-Related Renal Failure, Joseph S. Pina, Soraya Moghadam, Howard M. Cushner, Greg J. Beilman, Vivian C. Mcalister

Surgery Publications

BACKGROUND: Complications of renal failure may prevent timely evacuation of injured soldiers. Conventional renal replacement therapy is not available in forward surgical units. METHODS: Records of in-theater improvised peritoneal dialysis (IPD) in level III hospitals or forward surgical units in Iraq or Afghanistan were reviewed to determine the following: cause of renal failure and associated injuries; type of dialysate, peritoneal access, and exchange technique; and patient outcome. These data were used to propose method for IPD using commonly available materials. RESULTS: IPD is described in four patients. Abdominal or chest drains were used with either improvised dextrose-electrolyte solution or commercial …

Basal Insulin Requirements On Continuous Subcutaneous Insulin Infusion During The First 12 Months After Diagnosis Of Type 1 Diabetes Mellitus., Neesha Ramchandani, Mary Kristine Ellis, Shobhit Jain, Sonal Bhandari, Henry Anhalt, Noel K. Maclaren, Svetlana Ten

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: While the endogenous first-phase insulin response has disappeared by the time of diagnosis of type 1 diabetes mellitus (T1DM), anecdotal evidence suggests that these patients can continue to have a second-phase insulin response during the first 12 months after diagnosis. We hypothesized that patients who are started on continuous subcutaneous insulin infusion (CSII) at the time of diagnosis of T1DM would have a lower basal insulin requirement than the 40-60% usually expected.

METHODS: We analyzed 38 patients with T1DM, age 9.9 +/- 6.4 years, 71% male, who were started on CSII within the first month of diagnosis.

RESULTS: Average …

Aberrations In Post-Trauma Monocyte (Mo) Subpopulation: Role In Septic Shock Syndrome, Carol Miller-Graziano, Gyongyi Szabo, Karen Kodys, Katherine Griffey

Gyongyi Szabo

Appearance of increased proportions of monocytes bearing the 72kd(FcRI) receptor for IgG correlated to aberrant monocyte (MO) functions, depressed immune functions, and poor clinical outcome. The trauma patients' FcRI+ MO subpopulation produced the majority of their elevated IL-6, TNF alpha, TGF beta, and PGE2. IgG stimulation of patients' MO through FcRI not only stimulated TNF alpha, IL-6, and PGE2 levels, but also greatly augmented the levels of these monokines produced after subsequent bacterial challenge. Post-trauma increased IL-6 levels can lead to polyclonal B-cell activation and high levels of circulating, nonspecific IgG as seen in trauma patients. This nonspecific IgG triggers …

Dibutyryl-Camp Modulation Of Receptor Expression And Antigen Presentation Capacity In Monocyte Subpopulations, Gyongyi Szabo, Karen Kodys, Carol Miller-Graziano

Gyongyi Szabo

Monocyte phenotype heterogeneity is often associated with functional differences between the distinguished Mphi subpopulations. We have previously demonstrated that the Mphi subpopulation separated and stimulated by rosetting Mphi via the Type I Fc gamma R (CD64) are poor antigen presenting cells but can be induced to greater production of TNF alpha, IL-6 and PGE2 than the Fc gamma RI- Mphi population. Here we demonstrate that the Fc gamma RI- Mphi represent the major antigen presenting Mphi population and that APC capacity of the FcRI- Mphi can be further increased by elevating intracellular cAMP levels. Treatment of the Fc gamma RI+ …

Role Of Elevated Monocyte Transforming Growth Factor Beta (Tgf Beta) Production In Posttrauma Immunosuppression, Carol Miller-Graziano, Gyongyi Szabo, Katherine Griffey, Bela Mehta, Karen Kodys, Donna Catalano

Gyongyi Szabo

We previously reported that increased production of prostaglandin E2 by monocytes is a pivotal mechanism in posttrauma immunopathology. Here we characterize monocyte levels of transforming growth factor beta and examine the effects of elevated transforming growth factor beta on prostaglandin E2 release by patients' monocytes. Trauma patients' and normals' monocyte supernates (+/- stimulation with muramyl dipeptide) were acid treated and assayed for transforming growth factor beta using the mink lung-cell bioassay. Alternatively, human transforming growth factor beta was added to patients' and normals' monocytes and prostaglandin E2 production assayed. Significantly elevated transforming growth factor beta levels (median = 181.7 pmol/10(6) …

Reduced Alloreactive T-Cell Activation After Alcohol Intake Is Due To Impaired Monocyte Accessory Cell Function And Correlates With Elevated Il-10, Il-13, And Decreased Ifngamma Levels, Gyongyi Szabo, Pranoti Mandrekar, Angela Dolganiuc, Donna Catalano, Karen Kodys

Gyongyi Szabo

BACKGROUND: Immunosuppression associated with chronic alcohol use is characterized by reduced antigen-specific T-cell response and impaired delayed type hypersensitivity. Increasing evidence suggests in chronic alcohol consumption models that reduced antigen-specific T-cell proliferation is due to insufficient accessory cell function. Accessory cell function, a critical step in recognition of viral antigens, is reduced in chronic hepatitis C. The severity of hepatitis C is increased by alcohol consumption. Thus, we investigated the effects of alcohol consumption on accessory cell activity of monocytes in supporting alloreactive T-cell proliferation. METHODS: Alloreactive T-cell proliferation was evaluated in a one-way mixed lymphocyte reaction (MLR). Mononuclear cells …

Elevated Tumor Necrosis Factor Alpha Production Concomitant To Elevated Prostaglandin E2 Production By Trauma Patients' Monocytes, Thomas Takayama, Carol Miller-Graziano, Gyongyi Szabo

Gyongyi Szabo

The level of tumor necrosis factor alpha (TNF alpha), a monokine implicated in mediating septic shock, is elevated in the blood of some patients with sepsis. Monocytes from 11 trauma patients and 11 burn patients were suboptimally stimulated with interferon gamma and muramyl dipeptide, an analogue of bacterial wall products. The patients with sepsis showed significantly greater total TNF alpha levels (secreted in combination with cell-associated) 3 days before septic episodes, as compared with normal controls (32.38 to 2231.76 ng/10(6) monocytes per milliliter, median = 121.03 ng/10(6) monocytes per milliliter; normal control: 0.00 to 18.20 ng/10(6) monocytes per milliliter, median …

Regulation Of Human Monocyte Functions By Acute Ethanol Treatment: Decreased Tumor Necrosis Factor-Alpha, Interleukin-1 Beta And Elevated Interleukin-10, And Transforming Growth Factor-Beta Production, Gyongyi Szabo, Pranoti Mandrekar, Linda Girouard, Donna Catalano

Gyongyi Szabo

We and others have previously shown that even acute ethanol exposure has the capacity to modulate immune functions, particularly monocyte functions. Herein, we tested the hypothesis that acute ethanol treatment inhibits inflammatory, while increasing inhibitory cytokine production in human blood monocytes that, in turn, could contribute to the overall immune abnormalities seen after alcohol use. Our data show that in vitro treatment of blood monocytes with a physiologically relevant dose of alcohol (25 mM) results in significantly decreased induction of tumor necrosis factor-alpha (TNF alpha) and interleukin (IL)-1 beta by bacterial stimulation of either Gram-positive [staphylococcal enterotoxin B (SEB), 1 …

Monocytes, Alcohol Use, And Altered Immunity, Gyongyi Szabo

Gyongyi Szabo

The immunomodulatory capacity of acute, moderate alcohol consumption was investigated in this study in nonalcoholic volunteers after 2 ml of vodka/kg body weight of alcohol consumption. There was a significant, transient increase in interleukin-12 and interferon-gamma (IFNgamma) levels in whole blood samples collected 4 hr after alcohol consumption in response to an ex vivo bacterial challenge with lipopolysaccharide (p < 0.02). However, decreased IFNgamma levels were produced by mononuclear cells collected later after alcohol consumption (16 hr), suggesting that acute alcohol consumption has a biphasic effect on IFNgamma inducibility. Furthermore, isolated blood monocytes collected 16 hr after alcohol consumption showed significantly …

Mechanisms Of Altered Monocyte Prostaglandin E2 Production In Severely Injured Patients, Carol Miller-Graziano, Mitchell Fink, Jia-Yan Wu, Gyongyi Szabo, Karen Kodys

Gyongyi Szabo

Monocytes from immunosuppressed trauma (11 patients) and burn (12 patients) patients stimulated with muramyl dipeptide, a potent prostaglandin E2 (PGE2) secretagogue, showed twofold greater PGE2 production compared with normal controls or immunocompetent patients. Monocyte plasminogen activator production was markedly depressed and inversely correlated to patients' monocyte hyper PGE2 production. Levels of the PGE2-producing monocyte subset (selected as high-affinity Fc+ receptors) were progressively elevated after injury in immunosuppressed patients, reaching 65% to 80% of the total monocyte population (39% for normal controls). Although early T-suppressor (Ts) lymphocytes did not augment monocyte PGE2 secretion, Ts lymphocytes that appeared late (greater than 12 …

Polymorphonuclear Functions In Patients With Mixed Connective Tissue Disease, E. Bodolay, Katalin Lukacs, G. Frendl, Gyongyi Szabo, G. Arato, Gyula Szegedi

Gyongyi Szabo

Polymorphonuclear leukocytes (PMNs) from 29 patients with mixed connective tissue disease (MCTD) were studied "in vitro" for their phagocytic and chemotactic function as well as for granulocyte alkaline phosphatase (GAP) activity. Fc-receptor expression detected by EA-rosette formation was comparable to the control. Yeast-phagocytosis, C3b-receptor mediated phagocytosis and chemotaxis of PMNs, however, significantly decreased in MCTD. At the same time, photometric measure of alkaline phosphatase activity indicated a nearly two fold increase in PMNs from patients with MCTD. Although no correlation was found between PMN functions and the activity of the disease, PMN disorders may play a role in pathogenesis of …

Acute Alcohol Consumption Attenuates Interleukin-8 (Il-8) And Monocyte Chemoattractant Peptide-1 (Mcp-1) Induction In Response To Ex Vivo Stimulation, Gyongyi Szabo, Sangeeta Chavan, Pranoti Mandrekar, Donna Catalano

Gyongyi Szabo

No abstract provided.

Monocyte Functions In Patients With Mixed Connective Tissue Disease, E. Bodolay, Katalin Lukacs, Gyongyi Szabo, G. Frendl, T. Ben, Gyula Szegedi

Gyongyi Szabo

The authors investigated the number and functions of peripheral blood monocytes in patients with mixed connective tissue disease. Moderate monocytopenia was detected in the active stage of the disease. There was a close correlation between the sensitized sheep red blood cell binding capacity of monocytes and the elevated levels of circulating immune complexes. The yeast phagocytosis of monocytes and the chemotactic activity were normal in patients with mixed connective tissue disease. C3b receptor mediated phagocytosis of monocytes decreased in the active and inactive stages of the disease. This study suggests that the decreased function of C3b receptors of monocytes is …

Acute Ethanol Consumption Synergizes With Trauma To Increase Monocyte Tumor Necrosis Factor Alpha Production Late Postinjury, Gyongyi Szabo, Pranoti Mandrekar, Bikash Verma, Ann Isaac, Donna Catalano

Gyongyi Szabo

The hypothesis that acute ethanol uptake plus trauma can synergize to increase immunosuppression was tested. We found that, unlike non-alcohol-exposed patients, patients with acute alcohol use prior to trauma have a transient decrease in monocyte tumor necrosis factor alpha (TNF alpha) production during the very early postinjury (0-3 days) period. However, TNF alpha production by these alcohol-exposed patients' monocytes (M0) became hyperelevated late postinjury (> 9 days). Consequently, these massively elevated M0 TNF alpha levels can contribute to posttrauma immunosuppression after acute alcohol use. We also demonstrate that normal monocyte activation with the superantigen, Staphylococcus enterotoxin B (SEB), results in …

Regulation Of Monocyte Interleukin-12 Production By Acute Alcohol: A Role For Inhibition By Interleukin-10, Linda Girouard, Pranoti Mandrekar, Donna Catalano, Gyongyi Szabo

Gyongyi Szabo

Acute ethanol treatment results in decreased antigen presentation capacity (Th1-type immunity) and elevated interleukin IL-10 (Th2 cytokine) production in human monocytes. Monocytes can contribute to both Th1 (IL-12) and Th2 (IL-10) immune responses via production of IL-12 and IL-10, respectively. Thus, we tested the hypothesis that acute alcohol treatment might affect Th1/Th2 immune balance by altering monocyte production of IL-12 and IL-10. Neither acute ethanol treatment alone (25 to 100 mM) nor its combination with a bacterial challenge Staphylococcal enterotoxin B (SEB) induced IL-12 production in isolated blood monocytes. In contrast, the same physiological alcohol concentrations increased monocyte IL-10 levels, …

Inhibition Of Antigen-Presenting Cell Functions By Alcohol: Implications For Hepatitis C Virus Infection, Gyongyi Szabo, Angela Dolganiuc, Pranoti Mandrekar, Bernadette White

Gyongyi Szabo

The mechanisms of alcohol-induced immunosuppression include defects in innate and adaptive immune responses. Monocytes and dendritic cells (DCs) link innate and adaptive immune responses as they recognize viral antigens and induce antigen-specific T-cell activation. We investigated the effects of alcohol on antigen-presenting cell functions. Acute alcohol consumption by healthy volunteers (vodka, 2 ml/kg) resulted in significantly reduced antigen-presenting cell function of monocyte-derived DCs. Reduced allostimulatory capacity of DCs treated with alcohol in vitro correlated with decreased co-stimulatory molecule (B7.1 and B7.2) expression, as well as with reduced interleukin (IL)-12 and increased IL-10 concentrations, in mixed lymphocyte cultures. Dendritic cells recognize …

Regulation Of Monocyte Il-12 Production: Augmentation By Lymphocyte Contact And Acute Ethanol Treatment, Inhibition By Elevated Intracellular Camp, Gyongyi Szabo, Linda Girouard, Pranoti Mandrekar, Donna Catalano

Gyongyi Szabo

IL-12, a monocyte-derived cytokine, is pivotal in activation of cellular immune response and inflammation. Both inflammatory response and cellular immunity are impaired by acute ethanol consumption. Here, we found that in vitro acute ethanol treatment (25-100 mM) results in a dose-dependent and significant increase of IL-12 in IFN-gamma (100 U/ml) plus Staphylococcal enterotoxin B (SEB; 1 microg/ml) stimulated monocytes and mononuclear cells but not in unstimulated cells from non-alcoholic blood donors. There was significantly greater IL-12 production in the MNC population compared to isolated Mphi (P < 0.001). Prevention of monocyte surface contact with either purified T lymphocytes or monocyte-depleted MNC resulted in a significant, 65+/-20%, decrease in IL-12 production regardless of IFN-gamma, SEB or ethanol stimulation suggesting that Mphi T-cell surface contact provides an additional signal for IL-12 production. In addition to cell surface contact, soluble mediators, particularly IL-10 and PGE2 may regulate IL-12 production. The cyclooxygenase inhibitor, Indomethacin (10(-6)M), augmented both IL-12 and IL-10 levels in isolated monocytes and mononuclear cells whether induced by medium, SEB or SEB plus 25 mM ethanol suggesting that regulation of IL-12 production via the cyclooxygenase pathway is independent of IL-10. Finally, elevation of intracellular cAMP levels by dbcAMP treatment consistently inhibited IL-12 as well as IL-10 production in monocytes induced by IFN-gamma or IFN-gamma plus 25 mM ethanol. These data suggest that augmentation of monocyte IL-12 by acute ethanol is not mediated via the cAMP pathway.

Viral And Host Factors Induce Macrophage Activation And Loss Of Toll-Like Receptor Tolerance In Chronic Hcv Infection, Angela Dolganiuc, Oxana Norkina, Karen Kodys, Donna Catalano, Gennadiy Bakis, Christopher Marshall, Pranoti Mandrekar, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND and AIMS: Persistent inflammation contributes to progression of liver damage in chronic HCV (cHCV) infection. Repeated exposure to toll-like receptor (TLR) ligands results in tolerance, a protective mechanism aimed at limiting inflammation.

METHODS: Monocytes/macrophages were repeatedly stimulated via proinflammatory cytokine-inducing TLRs and evaluated for activation markers.

RESULTS: Unlike monocytes of controls or patients with nonalcoholic steatohepatitis, the monocytes of cHCV patients were hyperresponsive and failed to show homo- or heterotolerance to TLR ligands, manifested by elevated tumor necrosis factor (TNF)-alpha production. Serum levels of interferon (IFN)-gamma, endotoxin (TLR4 ligand), and HCV core protein (TLR2 ligand) were elevated in cHCV …