Medicine and Health Sciences Commons^™

A Novel Runx2 Missense Mutation Predicted To Disrupt Dna Binding Causes Cleidocranial Dysplasia In A Large Chinese Family With Hyperplastic Nails, Shaohua Tang, Qiyu Xu, Xueqin Xu, Jicheng Du, Xuemei Yang, Yusheng Jiang, Xiaoqin Wang, Nancy Speck, Taosheng Huang

Dartmouth Scholarship

Background: Cleidocranial dysplasia (CCD) is a dominantly inherited disease characterized by hypoplastic or absent clavicles, large fontanels, dental dysplasia, and delayed skeletal development. The purpose of this study is to investigate the genetic basis of Chinese family with CCD.

Methods: Here, a large Chinese family with CCD and hyperplastic nails was recruited. The clinical features displayed a significant intrafamilial variation. We sequenced the coding region of the RUNX2 gene for the mutation and phenotype analysis.

Results: The family carries a c.T407C (p.L136P) mutation in the DNA- and CBFβ-binding Runt domain of RUNX2. Based on the crystal structure, we predict this …

Short-Wavelength Light Sensitivity Of Circadian, Pupillary, And Visual Awareness In Humans Lacking An Outer Retina, Farhan H. Zaidi, Joseph T. Hull, Stuart N. Peirson, Katharina Wulff, Daniel Aeschbach, Joshua J. Gooley, George C. Brainard, Kevin Gregory-Evans, Joseph F. Rizzo Iii, Charles A. Czeisler, Russell G. Foster, Merrick J. Moseley, Steven W. Lockley

Department of Neurology Faculty Papers

As the ear has dual functions for audition and balance, the eye has a dual role in detecting light for a wide range of behavioral and physiological functions separate from sight. These responses are driven primarily by stimulation of photosensitive retinal ganglion cells (pRGCs) that are most sensitive to short-wavelength ( approximately 480 nm) blue light and remain functional in the absence of rods and cones. We examined the spectral sensitivity of non-image-forming responses in two profoundly blind subjects lacking functional rods and cones (one male, 56 yr old; one female, 87 yr old). In the male subject, we found …

Illusory Predictors: Generalizability Of Findings In Cocaine Treatment Retention Research, Angela L Stotts, Marc E Mooney, Shelly L Sayre, Meredith Novy, Joy M Schmitz, John Grabowski

Journal Articles

Treatment retention is of paramount importance in cocaine treatment research as treatment completion rates are often 50% or less. Failure to retain cocaine patients in treatment has both significant research and clinical implications. In this paper we qualitatively and quantitatively demonstrate the inconsistency found across analyses of retention predictors in order to highlight the problem. First, a qualitative review of the published literature was undertaken to identify the frequency of predictors studied and their relations to treatment retention. Second, an empirical demonstration of predictor stability was conducted by testing a common set of variables across three similar 12-week cocaine clinical …

Comparison Of Eight Prosthetic Aortic Valves In A Cadaver Model., Benjamin A. Youdelman, Hitoshi Hirose, Harsh Jain, J Yasha Kresh, John W.C. Entwistle, Andrew S. Wechsler

Department of Surgery Faculty Papers

OBJECTIVES: Proper valve selection is critical to ensure appropriate valve replacement for patients, because implantation of a small valve might place the patient at risk for persistent gradients. Labeled valve size is not the same as millimeter measure of prosthetic valve diameters or the annulus into which it will fit. Studies that use the labeled valve size in lieu of actual measured diameter in millimeters to compare different valves might be misleading. Using human cadaver hearts, we sized the aortic annulus with 8 commonly used prosthetic aortic valve sizers and compared the valves using geometric orifice area. This novel method …

Modulation Of Tgf-Beta Signaling By Proinflammatory Cytokines In Articular Chondrocytes., Jorge A. Roman-Blas, David G. Stokes, Sergio A. Jimenez

Department of Medicine Faculty Papers

OBJECTIVE: The normal structure and function of articular cartilage are the result of a precisely balanced interaction between anabolic and catabolic processes. The transforming growth factor-beta (TGF-beta) family of growth factors generally exerts an anabolic or repair response; in contrast, proinflammatory cytokines such as interleukin 1 beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) exert a strong catabolic effect. Recent evidence has shown that IL-1beta, and TNF-alpha, and the TGF-beta signaling pathways share an antagonistic relationship. The aim of this study was to determine whether the modulation of the response of articular chondrocytes to TGF-beta by IL-1beta or TNF-alpha signaling pathways …

Nonsexual Transmission Of Anogenital Warts In Children: A Retrospective Analysis, Valerie Jones, Shawn J. Smith, Hatim A. Omar

Pediatrics Faculty Publications

The purpose was to evaluate the prevalence of sexual abuse in patients who were referred to a pediatric gynecologist for evaluation based on the clinical findings of anogenital warts. A retrospective analysis was performed on 131 patients between the ages 6 month and 9 years referred to a pediatric gynecologist after the finding of anogenital warts by a clinical provider, parent or caregiver. A complete physical examination under colposcopy by a the same, trained pediatric gynecologist was completed, and a complete medical and family history including maternal and sibling history for evidence of Human Papillomavirus (HPV) and anogenital warts. The …

Obesity And Diabetes In Vulnerable Populations: Reflection On Proximal And Distal Causes, Lucy M. Candib

Lucy M. Candib

Around the world obesity and diabetes are climbing to epidemic proportion, even in countries previously characterized by scarcity. Likewise, people from low-income and minority communities, as well as immigrants from the developing world, increasingly visit physicians in North America with obesity, metabolic syndrome, or diabetes. Explanations limited to lifestyle factors such as diet and exercise are inadequate to explain the universality of what can be called a syndemic, a complex and widespread phenomenon in population health produced by multiple reinforcing conditions. Underlying the problem are complex factors-genetic, physiological, psychological, familial, social, economic, and political-coalescing to overdetermine these conditions. These interacting …

Adaptive Radiotherapy Planning On Decreasing Gross Tumor Volumes As Seen On Megavoltage Computed Tomography Images., Curtis Woodford, Slav Yartsev, R. Dar, Glenn Bauman, Jacob Van Dyk

Oncology Publications

PURPOSE: To evaluate gross tumor volume (GTV) changes for patients with non-small-cell lung cancer by using daily megavoltage (MV) computed tomography (CT) studies acquired before each treatment fraction on helical tomotherapy and to relate the potential benefit of adaptive image-guided radiotherapy to changes in GTV.

METHODS AND MATERIALS: Seventeen patients were prescribed 30 fractions of radiotherapy on helical tomotherapy for non-small-cell lung cancer at London Regional Cancer Program from Dec 2005 to March 2007. The GTV was contoured on the daily MVCT studies of each patient. Adapted plans were created using merged MVCT-kilovoltage CT image sets to investigate the advantages …

Is A 3-Mm Intrafractional Margin Sufficient For Daily Image-Guided Intensity-Modulated Radiation Therapy Of Prostate Cancer?, Adam D Melancon, Jennifer C O'Daniel, Lifei Zhang, Rajat J Kudchadker, Deborah A Kuban, Andrew K Lee, Rex M Cheung, Renaud De Crevoisier, Susan L Tucker, Wayne D Newhauser, Radhe Mohan, Lei Dong

Journal Articles

PURPOSE: To determine whether a 3-mm isotropic target margin adequately covers the prostate and seminal vesicles (SVs) during administration of an intensity-modulated radiation therapy (IMRT) treatment fraction, assuming that daily image-guided setup is performed just before each fraction.

MATERIALS AND METHODS: In-room computed tomographic (CT) scans were acquired immediately before and after a daily treatment fraction in 46 patients with prostate cancer. An eight-field IMRT plan was designed using the pre-fraction CT with a 3-mm margin and subsequently recalculated on the post-fraction CT. For convenience of comparison, dose plans were scaled to full course of treatment (75.6 Gy). Dose coverage …

The Activity Of Azithromycin Against Leishmania (Viannia) Braziliensis And Leishmania (Leishmania) Amazonensis In The Golden Hamster Model., Angel Sinagra, Concepción Luna, David Abraham, Maria Del Carmen Iannella, Adelina Riarte, Alejandro J. Krolewiecki

Department of Microbiology and Immunology Faculty Papers

New therapeutic alternatives against leishmaniasis remain a priority. The activity of azithromycin against Leishmania (Leishmania) major has been previously demonstrated. Different responses among species of Leishmania make species-specific drug screening necessary. The activity of azithromycin against Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis was evaluated in golden hamsters infected through footpad injections of metacyclic promastigotes, and compared with untreated controls and animals treated with meglumine antimoniate. Footpad thickness, lesion cultures and dissemination sites were analyzed. Treatment of golden hamsters with oral azithromycin at 450mg/kg had no activity against infections with Leishmania (Leishmania) amazonensis. For infections due to Leishmania (Viannia) braziliensis, …

The Relationship Between The Field-Shifting Phenomenon And Representational Coherence Of Place Cells In Ca1 And Ca3 In A Cue-Altered Environment, Inah Lee, James J Knierim

Journal Articles

Subfields of the hippocampus display differential dynamics in processing a spatial environment, especially when changes are introduced to the environment. Specifically, when familiar cues in the environment are spatially rearranged, place cells in the CA3 subfield tend to rotate with a particular set of cues (e.g., proximal cues), maintaining a coherent spatial representation. Place cells in CA1, in contrast, display discordant behaviors (e.g., rotating with different sets of cues or remapping) in the same condition. In addition, on average, CA3 place cells shift their firing locations (measured by the center of mass, or COM) backward over time when the animal …

Rhabdomyolysis After Laparoscopic Nephrectomy., Deborah T. Glassman, William G. Merriam, Edouard J. Trabulsi, Dolores Byrne, Leonard Gomella

Department of Urology Faculty Papers

BACKGROUND AND OBJECTIVES: Laparoscopic renal surgery has become a widely applied technique in recent years. The development of postoperative rhabdomyolysis is a known but rare complication of laparoscopic renal surgery. Herein, 4 cases of rhabdomyolysis and a review of the literature are presented with respect to pathogenesis, treatment, and prevention of this dire complication. METHODS: A retrospective review of over 600 laparoscopic renal operations over the past 8 years was performed. All cases of postoperative rhabdomyolysis were identified. A Medline search was performed to find articles related to the development of postoperative rhabdomyolysis. Cases of rhabdomyolysis developing after laparoscopic renal …

Human Parietal "Reach Region" Primarily Encodes Intrinsic Visual Direction, Not Extrinsic Movement Direction, In A Visual Motor Dissociation Task., Juan Fernandez-Ruiz, Herbert C Goltz, Joseph F X Desouza, Tutis Vilis, J Douglas Crawford

Brain and Mind Institute Researchers' Publications

Posterior parietal cortex (PPC) participates in the planning of visuospatial behaviors, including reach movements, in gaze-centered coordinates. It is not known if these representations encode the visual goal in retinal coordinates, or the movement direction relative to gaze. Here, by dissociating the intrinsic retinal stimulus from the extrinsic direction of movement, we show that PPC employs a visual code. Using delayed pointing and event-related functional magnetic resonance imaging, we identified a cluster of PPC regions whose activity was topographically (contralaterally) related to the direction of the planned movement. We then switched the normal visual-motor spatial relationship by adapting subjects to …

Effects Of Atomoxetine On Growth In Children With Attention-Deficit/Hyperactivity Disorder Following Up To Five Years Of Treatment., Thomas J. Spencer, Christopher J. Kratochvil, R. Bart Sangal, Keith E. Saylor, Charles E. Bailey, David W. Dunn, Daniel A. Geller, Charles D. Casat, Robert S. Lipetz, Rakesh Jain, Jeffrey H. Newcorn, Dustin D. Ruff, Peter D. Feldman, Amanda J. Furr, Albert J. Allen

Journal Articles: Psychiatry

OBJECTIVE: To examine the effects on growth of long-term pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD), we present findings from an ongoing 5-year study of the efficacy and safety of treatment with atomoxetine.

METHODS: North American patients, 6-17 years old at study entry (N = 1,312) and with Diagnostic and Statistical Manual of Mental Disorders,4th edition (DSM-IV) ADHD, were studied under open-label atomoxetine treatment. Sixty-one were studied up to 5 years.

RESULTS: After 1 month's treatment, patients weighed less than expected from their starting percentiles relative to population norms, with a maximum shortfall at 15 months and a return to expected …

Microvascular Endothelial Cells Express A Phosphatidylserine Receptor: A Functionally Active Receptor For Phosphatidylserine-Positive Erythrocytes, Yamaja Setty, Suhita Gayen Betal

Department of Pediatrics Faculty Papers

Phosphatidylserine (PS)-positive erythrocytes adhere to endothelium and subendothelial matrix components. While thrombospondin mediates these inter-actions, it is unknown whether PS-associated erythrocyte-endothelial adhesion occurs in the absence of plasma ligands. Using ionophore-treated PS-expressing control HbAA erythrocytes, we demonstrate that PS-positive erythrocytes adhered to human lung microendothelial cells in the absence of plasma ligands, that this adhesion was enhanced following endothelial activation with IL-1alpha, TNF-alpha, LPS, hypoxia, and heme, and that this adhesive interaction was selective to erythrocyte PS. We next explored whether microendothelial cells express an adhesion receptor that recognizes cell surface-expressed PS (PSR) similar to that expressed on activated macrophages. …

Western Diet, But Not High Fat Diet, Causes Derangements Of Fatty Acid Metabolism And Contractile Dysfunction In The Heart Of Wistar Rats, Christopher R Wilson, Mai K Tran, Katrina L Salazar, Martin E Young, Heinrich Taegtmeyer

Journal Articles

Obesity and diabetes are associated with increased fatty acid availability in excess of muscle fatty acid oxidation capacity. This mismatch is implicated in the pathogenesis of cardiac contractile dysfunction and also in the development of skeletal-muscle insulin resistance. We tested the hypothesis that 'Western' and high fat diets differentially cause maladaptation of cardiac- and skeletal-muscle fatty acid oxidation, resulting in cardiac contractile dysfunction. Wistar rats were fed on low fat, 'Western' or high fat (10, 45 or 60% calories from fat respectively) diet for acute (1 day to 1 week), short (4-8 weeks), intermediate (16-24 weeks) or long (32-48 weeks) …

Teaching Case: Headache Stigmata, Michael Marmura, Seymour Solomon

Department of Neurology Faculty Papers

A 38-year-old man with past medical history of hypertension and obesity presented to our clinic for evaluation of severe headaches and multiple episodes of discoloration of the forehead on the same side as the headache.

Human Collagen Krox Up-Regulates Type I Collagen Expression In Normal And Scleroderma Fibroblasts Through Interaction With Sp1 And Sp3 Transcription Factors., Magdalini Kypriotou, Gallic Beauchef, Christos Chadjichristos, Russell Widom, Emmanuelle Renard, Sergio A. Jimenez, Joseph Korn, François-Xavier Maquart, Thierry Oddos, Otto Von Stetten, Jean-Pierre Pujol, Philippe Galéra

Department of Medicine Faculty Papers

Despite several investigations, the transcriptional mechanisms that regulate the expression of both type I collagen genes (COL1A1 and COL1A2) in either physiological or pathological situations, such as scleroderma, are not completely known. We have investigated the role of hc-Krox transcription factor on type I collagen expression by human dermal fibroblasts. hc-Krox exerted a stimulating effect on type I collagen protein synthesis and enhanced the corresponding mRNA steady-state levels of COL1A1 and COL1A2 in foreskin fibroblasts (FF), adult normal fibroblasts (ANF), and scleroderma fibroblasts (SF). Forced hc-Krox expression was found to up-regulate COL1A1 transcription through a -112/-61-bp sequence in FF, ANF, …

Defective Dna Base Excision Repair In Brain From Individuals With Alzheimer's Disease And Amnestic Mild Cognitive Impairment, Lior Weissman, Dong-Gyu Jo, Martin M. Sørensen, Nadja C. De Souza-Pinto, William R. Markesbery, Mark P. Mattson, Vilhelm A. Bohr

Pathology and Laboratory Medicine Faculty Publications

Oxidative stress is thought to play a role in the pathogenesis of Alzheimer's disease (AD) and increased oxidative DNA damage has been observed in brain tissue from AD patients. Base excision repair (BER) is the primary DNA repair pathway for small base modifications such as alkylation, deamination and oxidation. In this study, we have investigated alterations in the BER capacity in brains of AD patients. We employed a set of functional assays to measure BER activities in brain tissue from short post-mortem interval autopsies of 10 sporadic AD patients and 10 age-matched controls. BER activities were also measured in brain …

Polymorphisms In Nucleotide Excision Repair Genes, Arsenic Exposure, And Non-Melanoma Skin Cancer In New Hampshire, Katie M. Applebaum, Margaret R. Karagas, David J. Hunter, Paul J. Catalano, Steven H. Byler, Steve Morris, Heather H. Nelson

Dartmouth Scholarship

Background:

Arsenic exposure may alter the efficiency of DNA repair. UV damage is specifically repaired by nucleotide excision repair (NER), and common genetic variants in NER may increase risk for non-melanoma skin cancer (NMSC).

Objective:

We tested whether polymorphisms in the NER genes XPA (A23G) and XPD (Asp312Asn and Lys751Gln) modify the association between arsenic and NMSC.

Methods:

Incident cases of basal and squamous cell carcinoma (BCC and SCC, respectively) were identified through a network of dermatologists and pathology laboratories across New Hampshire. Population-based controls were frequency matched to cases on age and sex. Arsenic exposure was assessed in toenail …

Comparison Of Eight Prosthetic Aortic Valves In A Cadaver Model, Benjamin A. Youdelman, Hitoshi Hirose, Harsh Jain, J. Yasha Kresh, John W.C. Entwhistle Iii, Andrew S. Wechsler

Department of Surgery Faculty Papers

OBJECTIVES: Proper valve selection is critical to ensure appropriate valve replacement for patients, because implantation of a small valve might place the patient at risk for persistent gradients. Labeled valve size is not the same as millimeter measure of prosthetic valve diameters or the annulus into which it will fit. Studies that use the labeled valve size in lieu of actual measured diameter in millimeters to compare different valves might be misleading. Using human cadaver hearts, we sized the aortic annulus with 8 commonly used prosthetic aortic valve sizers and compared the valves using geometric orifice area. This novel method …

Epstein-Barr Virus Infection Of Langerhans Cell Precursors As A Mechanism Of Oral Epithelial Entry, Persistence, And Reactivation., Dennis M. Walling, Autumn J. Ray, Joan E. Nichols, Catherine M. Flaitz, C. Mark Nichols

Journal Articles

Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus associated with many malignant and nonmalignant human diseases. Life-long latent EBV persistence occurs in blood-borne B lymphocytes, while EBV intermittently productively replicates in mucosal epithelia. Although several models have previously been proposed, the mechanism of EBV transition between these two reservoirs of infection has not been determined. In this study, we present the first evidence demonstrating that EBV latently infects a unique subset of blood-borne mononuclear cells that are direct precursors to Langerhans cells and that EBV both latently and productively infects oral epithelium-resident cells that are likely Langerhans cells. These data …

Relationships Between Scores On The Jefferson Scale Of Physician Empathy, Patient Perceptions Of Physician Empathy, And Humanistic Approaches To Patient Care: A Validity Study., Karen M. Glaser, Fred W. Markham, Herbert M. Adler, Patrick R. Mcmanus, Mohammadreza Hojat

Department of Psychiatry and Human Behavior Faculty Papers

BACKGROUND: Empathy is the backbone of a positive physician-patient relationship. Physician empathy and the patient's awareness of the physician's empathic concern can lead to a more positive clinical outcome.

MATERIAL/METHODS: The Jefferson Scale of Physician Empathy (JSPE) was completed by 36 physicians in the Family Medicine residency program at Thomas Jefferson University Hospital, and 90 patients evaluated these physicians by completing the Jefferson Scale of Patient Perceptions of Physician Empathy (JSPPPE), and a survey about physicians' humanistic approaches to patient care.

RESULTS: A statistically significant correlation was found between scores of the JSPE and JSPPPE (r=0.48, p

CONCLUSIONS: These findings …

Walking Age Does Not Explain Term Versus Preterm Difference In Bone Geometry, Haifa Abou Samra, Bonny Specker

Ethel Austin Martin Program Publications

OBJECTIVE: To elucidate the relationship between bone geometry and onset of walking in former term and preterm children.
STUDY DESIGN: We conducted a cross-sectional study of 128 preschool children aged 3 to 5 years who underwent peripheral quantitative computerized tomography measures of bone size at the distal tibia. Linear models were developed, stratifying by sex, to determine whether bone differences between children born term and preterm were caused by differences in walking age.
RESULTS: Children with a history of preterm birth walked later than children born at term (12.4 +/- 0.5 versus 10.9 +/- 0.2 months; P = .004); however, …

Pp2cdelta (Ppm1d, Wip1), An Endogenous Inhibitor Of P38 Mapk, Is Regulated Along With Trp53 And Cdkn2a Following P38 Mapk Inhibition During Mouse Preimplantation Development., Jenny A Hickson, Barry Fong, Patricia H Watson, Andrew J Watson

Obstetrics & Gynaecology Publications

Preimplantation embryos utilize mitogen-activated protein kinase signaling (MAPK) pathways to relay signals from the external environment to prepare appropriate responses and adaptations to a changing milieu. It is therefore important to investigate how MAPK pathways are regulated during preimplantation development. This study was conducted to investigate whether PP2Cdelta (Ppm1d, WIP1) is expressed during mouse preimplantation development and to determine the influences of p38 MAPK inhibition on expression of Trp53 (p53), Ppm1d, (WIP1), and Cdkn2a (p16) during mouse preimplantation development. Our results indicate that Trp53, Ppm1d, and Cdkn2a mRNAs and TRP53 and PP2Cdelta proteins are expressed throughout mouse preimplantation development. Treatment …

Neural Reprogramming In Retinal Degeneration, Robert E Marc, Bryan W Jones, James R Anderson, Krista Kinard, David W Marshak, John H Wilson, Theodore Wensel, Robert J Lucas

Journal Articles

PURPOSE: Early visual defects in degenerative diseases such as retinitis pigmentosa (RP) may arise from phased remodeling of the neural retina. The authors sought to explore the functional expression of ionotropic (iGluR) and group 3, type 6 metabotropic (mGluR6) glutamate receptors in late-stage photoreceptor degeneration.

METHODS: Excitation mapping with organic cations and computational molecular phenotyping were used to determine whether retinal neurons displayed functional glutamate receptor signaling in rodent models of retinal degeneration and a sample of human RP.

RESULTS: After photoreceptor loss in rodent models of RP, bipolar cells lose mGluR6 and iGluR glutamate-activated currents, whereas amacrine and ganglion …

Survival After Bidirectional Cavopulmonary Anastomosis: Analysis Of Preoperative Risk Factors., Mark A. Scheurer, Elizabeth G Hill, Nagavardhan Vasuki, Scott Maurer, Eric M. Graham, Varsha Bandisode, Girish S. Shirali, Andrew M. Atz, Scott M. Bradley

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Prognostic factors for survival after bidirectional cavopulmonary anastomosis for functionally single ventricle are not well defined. We analyzed preoperative hemodynamic and echocardiographic data to determine risk factors for death or transplantation at least 1 year after bidirectional cavopulmonary anastomosis.

METHODS: Data for all patients who underwent bidirectional cavopulmonary anastomosis before 5 years of age at our institution from September 1995 through June 2005 were analyzed. Available preoperative echocardiograms and catheterizations were reviewed. Survivors were compared with those who died or underwent transplantation. Bivariable associations between demographic and clinical risk factors and survival status (alive without transplantation vs dead or …

Spontaneous Low-Frequency Fluctuations In The Bold Signal In Schizophrenic Patients: Anomalies In The Default Network, Robyn L Bluhm, Jodi Miller, Ruth A Lanius, Elizabeth A Osuch, Kristine Boksman, R W J Neufeld, Jean Theberge, Betsy Schaefer, Peter Williamson

Department of Medicine Publications

Spontaneous low-frequency fluctuations in the blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (MRI) signal have been shown to reflect neural synchrony between brain regions. A "default network" of spontaneous low-frequency fluctuations has been described in healthy volunteers during stimulus-independent thought. Negatively correlated with this network are regions activated during attention-demanding tasks. Both these networks involve brain regions and functions that have been linked with schizophrenia in previous research. The present study examined spontaneous slow fluctuations in the BOLD signal at rest, as measured by correlation with low-frequency oscillations in the posterior cingulate, in 17 schizophrenic patients, and 17 comparable …

Azithromycin In The Extremely Low Birth Weight Infant For The Prevention Of Bronchopulmonary Dysplasia: A Pilot Study, Hubert O. Ballard, Michael I. Anstead, Lori A. Shook

Pediatrics Faculty Publications

BACKGROUND: Azithromycin reduces the severity of illness in patients with inflammatory lung disease such as cystic fibrosis and diffuse panbronchiolitis. Bronchopulmonary dysplasia (BPD) is a pulmonary disorder which causes significant morbidity and mortality in premature infants. BPD is pathologically characterized by inflammation, fibrosis and impaired alveolar development. The purpose of this study was to obtain pilot data on the effectiveness and safety of prophylactic azithromycin in reducing the incidence and severity of BPD in an extremely low birth weight (< or = 1000 grams) population.

METHODS: Infants < or = 1000 g birth weight admitted to the University of Kentucky Neonatal Intensive Care Unit (level III, regional referral center) from 9/1/02-6/30/03 were eligible for this pilot study. The pilot study was double-blinded, randomized, and placebo-controlled. Infants were randomized to treatment or placebo within 12 hours of beginning mechanical ventilation (IMV) and within 72 hours of birth. The treatment group received azithromycin 10 mg/kg/day for 7 days followed by 5 mg/kg/day for the duration of the study. Azithromycin or placebo was continued until the infant no longer required IMV or supplemental oxygen, to a maximum of 6 weeks. Primary endpoints were incidence of BPD as defined by oxygen requirement at 36 weeks gestation, post-natal steroid use, days of IMV, and mortality. Data was analyzed by intention to treat using Chi-square and ANOVA.

RESULTS: A total of 43 extremely premature infants were enrolled in this pilot study. Mean gestational age and …

The Pharmacokinetics Of Taurolidine Metabolites In Healthy Volunteers., Li Gong, Howard E Greenberg, James L Perhach, Scott A Waldman, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Taurolidine is an experimental antibacterial and antiendotoxic compound whose clinical utility as an antitumor agent is being investigated in human clinical trials. Taurolidine in aqueous solution exists in equilibrium with taurultam. Taurultam is subsequently transformed to taurinamide. The pharmacokinetic profiles of these metabolites are not well established. In this study, 18 healthy volunteers were administered 5.0 g of taurolidine in 250 mL of 5% polyvinylpyrrolidone in water over 2, 1, or 0.5 hours by intravenous infusion in a parallel-group design. All subjects noted discomfort at the infusion site, although there were no serious adverse events. t(max) generally occurred at the …