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Articles 29191 - 29220 of 29360
Full-Text Articles in Entire DC Network
A Novel Polymorphism Of Fcgammariiia (Cd16) Alters Receptor Function And Predisposes To Autoimmune Disease, Jianming Wu, Jeffrey C. Edberg, Patricia B. Redecha, Vipin Bansal, Paul M. Guyre, Kimberly Coleman, Jane E. Salmon, Robert P. Kimberly
A Novel Polymorphism Of Fcgammariiia (Cd16) Alters Receptor Function And Predisposes To Autoimmune Disease, Jianming Wu, Jeffrey C. Edberg, Patricia B. Redecha, Vipin Bansal, Paul M. Guyre, Kimberly Coleman, Jane E. Salmon, Robert P. Kimberly
Dartmouth Scholarship
A novel polymorphism in the extracellular domain 2 (EC2) of FcgammaRIIIA affects ligand binding by natural killer (NK) cells and monocytes from genotyped homozygous normal donors independently of receptor expression. The nonconservative T to G substitution at nucleotide 559 predicts a change of phenylalanine (F) to valine (V) at amino acid position 176. Compared with F/F homozygotes, FcgammaRIIIa expressed on NK cells and monocytes in V/V homozygotes bound more IgG1 and IgG3 despite identical levels of receptor expression. In response to a standard aggregated human IgG stimulus, FcgammaRIIIa engagement on NK cells from V/V (high-binding) homozygotes led to a larger …
Intrinsic And Extrinsic Control Of Hemopoietic Stem Cell Numbers: Mapping Of A Stem Cell Gene, Gerald De Haan, Gary Van Zant
Intrinsic And Extrinsic Control Of Hemopoietic Stem Cell Numbers: Mapping Of A Stem Cell Gene, Gerald De Haan, Gary Van Zant
Markey Cancer Center Faculty Publications
We evaluated in vivo interactions between extrinsic (growth factor induced) and intrinsic (genetically determined) effectors of mouse primitive hemopoietic stem cell proliferation and numbers. Accordingly, stem cell frequency and cell cycle kinetics were assessed in eight strains of inbred mice using the cobblestone area–forming cell (CAFC) assay. A strong inverse correlation was observed between mouse lifespan and the number of autonomously cycling progenitors (CAFC day 7) in the femur. The population size of primitive stem cells (CAFC day 35) varied widely (up to sevenfold) among strains, unlike total CAFC day 7 numbers (cycling and quiescent), which were similar. Administration of …
Extraskeletal Mesenchymal Chondrosarcoma Of The Rectus Sheath., D B Johnson, W Breidahl, J S Newman, K Devaney, Alan M. Yahanda Md, Facs
Extraskeletal Mesenchymal Chondrosarcoma Of The Rectus Sheath., D B Johnson, W Breidahl, J S Newman, K Devaney, Alan M. Yahanda Md, Facs
PCI Publications and Projects
Mesenchymal chondrosarcomas (MSCs) are a rare form of chondrosarcoma which usually arise in bone. Extraskeletal chondrosarcomas constitute a minority (14-25%) of MSCs. We describe the imaging features of an extraskeletal mesenchymal chondrosarcoma that arose from the rectus abdominus muscle.
Mirizzi Syndrome Type Ii: Is Laparoscopic Cholecystectomy Justified?, D C Desai, R D Smink
Mirizzi Syndrome Type Ii: Is Laparoscopic Cholecystectomy Justified?, D C Desai, R D Smink
Department of Surgery Faculty Papers
Mirizzi syndrome type II is an uncommon cause of obstructive jaundice caused by an inflammatory response to an impacted gallstone in Hartmann's pouch or the cystic duct with a resultant cholecystocholedochal fistula. Two cases of Mirizzi syndrome type II are presented. Clinically only one patient had jaundice and endoscopic retrograde cholangiopancreatogram (ERCP) established a preoperative diagnosis of Mirizzi syndrome. The other patient's diagnosis of Mirizzi syndrome was made intraoperatively. It is important to properly identify the anatomy at the time of surgery to avoid compromising the common bile duct. Operative treatment of Mirizzi syndrome type II includes laparoscopic or open …
Auditory Filters Measured At Neighboring Center Frequencies, Marc A. Fagelson, C. A. Champlin
Auditory Filters Measured At Neighboring Center Frequencies, Marc A. Fagelson, C. A. Champlin
ETSU Faculty Works
Auditory filters were derived in 20 normal-hearing human listeners at center frequencies (CFs) of 913, 1095, 3651, and 4382 Hz using the roex (p,r) method. Comparisons were made between slopes of the filters' skirts at the neighboring CFs with filter output levels of 45 and 70 dB. The same comparisons were made with regard to filter equivalent rectangular bandwidth (ERB). In the 1000-Hz region, the low-frequency slopes (Pl) of filters centered at 913 and 1095 Hz were significantly correlated at both stimulus levels, while the high-frequency slopes (Pu) were similar only at the high test level. In the 4000-Hz region, …
Phosphorylation Regulates The Assembly Of Numa In A Mammalian Mitotic Extract, Alejandro Saredi, Louisa Howard, Duane A. Compton
Phosphorylation Regulates The Assembly Of Numa In A Mammalian Mitotic Extract, Alejandro Saredi, Louisa Howard, Duane A. Compton
Dartmouth Scholarship
NuMA is a 236 kDa nuclear protein that is required for the organization of the mitotic spindle. To determine how NuMA redistributes in the cell during mitosis, we have examined the behavior of NuMA in a mammalian mitotic extract under conditions conducive to the reassembly of interphase nuclei. NuMA is a soluble protein in mitotic extracts prepared from synchronized cultured cells, but forms insoluble structures when the extract becomes non-mitotic (as judged by the inactivation of cdc2/cyclin B kinase and the disappearance of mpm-2-reactive antigens). These NuMA-containing structures are irregularly shaped particles of 1–2 microm in diameter and their assembly …
Choosing Ignorance In The Manufacture Of Toxic Products , Wendy E. Wagner
Choosing Ignorance In The Manufacture Of Toxic Products , Wendy E. Wagner
Cornell Law Review
No abstract provided.
Section 8(C) Of The Proposed Restatement (Third) Of Torts: Is It Really What The Doctor Ordered , Jeffrey D. Winchester
Section 8(C) Of The Proposed Restatement (Third) Of Torts: Is It Really What The Doctor Ordered , Jeffrey D. Winchester
Cornell Law Review
No abstract provided.
Loss Of Dcc Expression And Glioma Progression., M Reyes-Mugica, K Rieger-Christ, H Ohgaki, B C Ekstrand, M Helie, G Kleinman, Alan M. Yahanda Md, Facs, E R Fearon, P Kleihues, M A Reale
Loss Of Dcc Expression And Glioma Progression., M Reyes-Mugica, K Rieger-Christ, H Ohgaki, B C Ekstrand, M Helie, G Kleinman, Alan M. Yahanda Md, Facs, E R Fearon, P Kleihues, M A Reale
PCI Publications and Projects
The deleted in colorectal cancer (DCC) gene, a candidate tumor suppressor gene on chromosome 18q21, encodes a neural cell adhesion molecule family protein that is most highly expressed in the nervous system. To address the hypothesis that DCC may play a role in glioma development and/or progression, we examined DCC expression by immunohistochemistry in 57 resected human astrocytic tumors. Overall, low-grade astrocytomas were predominantly DCC positive (15 of 16, or 94%), whereas high-grade tumors significantly less often expressed the DCC protein (27 of 41, or 66%; P = 0.03). We were able to directly assess the relationship between DCC expression …
Ifn-Gamma, Igif, And Iddm., Nora Sarvetnick
Ifn-Gamma, Igif, And Iddm., Nora Sarvetnick
Journal Articles: Regenerative Medicine
No abstract provided.
Where Do Elderly Veterans Obtain Care For Acute Myocardial Infarction: Department Of Veterans Affairs Or Medicare?, S M. Wright, J Daley, E S. Fisher, G E. Thibault
Where Do Elderly Veterans Obtain Care For Acute Myocardial Infarction: Department Of Veterans Affairs Or Medicare?, S M. Wright, J Daley, E S. Fisher, G E. Thibault
Dartmouth Scholarship
To examine Department of Veterans Affairs (VA) and Medicare hospitalizations for elderly veterans with acute myocardial infarction (AMI), their use of cardiac procedures in both systems, and patient mortality. DATA SOURCES: Merging of inpatient discharge abstracts obtained from VA Patient Treatment Files (PTF) and Medicare MedPAR Part A files. A retrospective cohort study of male veterans 65 years or older who were prior users of the VA medical system (veteran-users) and who were initially admitted to a VA or Medicare hospital with a primary diagnosis of AMI at some time from January 1, 1988 through December 31, 1990 (N = …
Fracture Of An Acetabular Component Inserted Without Cement: A Case Report, R T. Trousdale, D J. Berry, Joshua J. Jacobs, Jeremy L. Gilbert
Fracture Of An Acetabular Component Inserted Without Cement: A Case Report, R T. Trousdale, D J. Berry, Joshua J. Jacobs, Jeremy L. Gilbert
Biomedical and Chemical Engineering - All Scholarship
No abstract provided.
Computed Tomography In Staging Of Patients With Melanoma Metastatic To The Regional Nodes., T M Johnson, D J Fader, A E Chang, Alan M. Yahanda Md, Facs, J W Smith, K R Hamlet, V K Sondak
Computed Tomography In Staging Of Patients With Melanoma Metastatic To The Regional Nodes., T M Johnson, D J Fader, A E Chang, Alan M. Yahanda Md, Facs, J W Smith, K R Hamlet, V K Sondak
PCI Publications and Projects
BACKGROUND: This study addresses the yield and clinical impact of computed tomography (CT) imaging in otherwise asymptomatic patients with stage III melanoma metastatic to the regional nodes.
METHODS: The database from the University of Michigan Mutlidisciplinary Melanoma Clinic was reviewed and identified 127 asymptomatic patients with stage III melanoma (regional nodal disease) who received CT scans of the head, chest, abdomen, and/or pelvis. Scans were confirmed as true positive, false positive, and normal.
RESULTS: Four hundred twenty-six head and body CT scans were performed at the time of presentation of stage III disease. Twenty patients had a true-positive CT scan …
A Computerized Adaptive Testing System For Speech Discrimination Measurement: The Speech Sound Pattern Discrimination Test, Joseph Bochner, Wayne Garrison, Linda Palmer, Douglas Mackenzie, Amy Braveman
A Computerized Adaptive Testing System For Speech Discrimination Measurement: The Speech Sound Pattern Discrimination Test, Joseph Bochner, Wayne Garrison, Linda Palmer, Douglas Mackenzie, Amy Braveman
School of Education
A computerized, adaptive test-delivery system for the measurement of speech discrimination, the Speech Sound Pattern Discrimination Test, is described and evaluated. Using a modified discrimination task, the testing system draws on a pool of 130 items spanning a broad range of difficulty to estimate an examinee's location along an underlying continuum of speech processing ability, yet does not require the examinee to possess a high level of English language proficiency. The system is driven by a mathematical measurement model which selects only test items which are appropriate in difficulty level for a given examinee, thereby individualizing the testing experience. Test …
Cross-Talk Between Adherens Junctions And Desmosomes Depends On Plakoglobin, Jani E. Lewis, James K. Wahl Iii, Kristin M. Sass, Pamels J. Jensen, Pamela J. Johnson, Margaret J. Wheelock
Cross-Talk Between Adherens Junctions And Desmosomes Depends On Plakoglobin, Jani E. Lewis, James K. Wahl Iii, Kristin M. Sass, Pamels J. Jensen, Pamela J. Johnson, Margaret J. Wheelock
Biology
Squamous epithelial cells have both adherens junctions and desmosomes. The ability of these cells to organize the desmosomal proteins into a functional structure depends upon their ability first to organize an adherens junction. Since the adherens junction and the desmosome are separate structures with different molecular make up, it is not immediately obvious why formation of an adherens junction is a prerequisite for the formation of a desmosome. The adherens junction is composed of a transmembrane classical cadherin (E-cadherin and/or P-cadherin in squamous epithelial cells) linked to either β-catenin or plakoglobin, which is linked to α-catenin, which is linked to …
Re: Midpalmar Approach To The Carpal Tunnel: An Alternative To Endoscopic Release., Robert X. Murphy Jr, Md, Ms
Re: Midpalmar Approach To The Carpal Tunnel: An Alternative To Endoscopic Release., Robert X. Murphy Jr, Md, Ms
Department of Surgery
No abstract provided.
The History Of The Present Illness As Treatment: Who's Listening, And Why Does It Matter?, Herbert M. Adler, Md, Phd
The History Of The Present Illness As Treatment: Who's Listening, And Why Does It Matter?, Herbert M. Adler, Md, Phd
Department of Family & Community Medicine Faculty Papers
BACKGROUND: The history of the present illness (HPI) is examined as a narrative communication that has the potential to be therapeutic.
METHODS: The general principles that influence the therapeutic potential of the HPI are induced from participant observation of personal experience and natural observations of conventional social interaction. These principles are corroborated by evidence from cross-cultural healing practices, clinical experience, and experimental psychology.
RESULTS: To facilitate a therapeutic HPI, the clinician should convey a sense of safety, sensitivity, affective competence, and cognitive competence. Furthermore, the effective clinician joins the patient in coprocessing the illness experience.
CONCLUSIONS: The (HPI) is not …
Training Examiners For A National Epidemiological Survey Of Oral Mucosal Lesions, R.B. Zain, I.A. Razak, N. Ikeda, T. Axã©Ll, M.C. Downer
Training Examiners For A National Epidemiological Survey Of Oral Mucosal Lesions, R.B. Zain, I.A. Razak, N. Ikeda, T. Axã©Ll, M.C. Downer
Pre-2000
Ensuring the validity and reliability of data collected in epidemiological surveys is an important consideration. The purpose of the present report is to describe a training and calibration programme for 16 examiners taking part in a national survey of oral mucosal lesions and to present an evaluation of the results. The programme included the distribution of a pictorial manual to participants and a series of lectures followed by three diagnostic sessions, two using slides and the last involving patients. At the final session, the trainees classified 88 per cent of 16 patients correctly in comparison with the definitive diagnoses of …
F(C)Gammari-Targeted Fusion Proteins Result In Efficient Presentation By Human Monocytes Of Antigenic And Antagonist T Cell Epitopes, Chunlei Liu, Joel Goldstein, Robert F. Graziano, Jia He, Jeremiah K. O'Shea, Yashwant Deo, Paul M. Guyre
F(C)Gammari-Targeted Fusion Proteins Result In Efficient Presentation By Human Monocytes Of Antigenic And Antagonist T Cell Epitopes, Chunlei Liu, Joel Goldstein, Robert F. Graziano, Jia He, Jeremiah K. O'Shea, Yashwant Deo, Paul M. Guyre
Dartmouth Scholarship
A major challenge for using native or modified T cell epitopes to induce or suppress immunity relates to poor localization of peptides to antigen presenting cells (APCs) in vivo. In this study, we demonstrate enhanced presentation of antigenic and antagonistic peptides by targeting them to the type I Fc receptor for IgG (F(c)gammaRI, CD64) on human monocytes. A Th epitope of tetanus toxoid, TT830, and the antagonistic peptide for TT830, TT833S, were genetically grafted into the constant region of the heavy chain of the humanized anti-CD64 mAb 22 and expressed as monovalent fusion proteins, Fab22-TT830 and Fab22-TT833S. These CD64-targeted peptides …
Glanzmann Thrombasthenia. Cooperation Between Sequence Variants In Cis During Splice Site Selection., Ying Jin, Harry C. Dietz, Robert A. Montgomery, William R. Bell, Iain Mcintosh, Barry Coller, Paul F. Bray
Glanzmann Thrombasthenia. Cooperation Between Sequence Variants In Cis During Splice Site Selection., Ying Jin, Harry C. Dietz, Robert A. Montgomery, William R. Bell, Iain Mcintosh, Barry Coller, Paul F. Bray
Cardeza Foundation for Hematologic Research
Glanzmann thrombasthenia (GT), an autosomal recessive bleeding disorder, results from abnormalities in the platelet fibrinogen receptor, GP(IIb)-IIIa (integrin alpha(IIb)beta3). A patient with GT was identified as homozygous for a G-->A mutation 6 bp upstream of the GP(IIIa) exon 9 splice donor site. Patient platelet GP(IIIa) transcripts lacked exon 9 despite normal DNA sequence in all of the cis-acting sequences known to regulate splice site selection. In vitro analysis of transcripts generated from mini-gene constructs demonstrated that exon skipping occurred only when the G-->A mutation was cis to a polymorphism 116 bp upstream, providing precedence that two sequence variations …
Perception And Control Of Locomotion, John M. Flach
Perception And Control Of Locomotion, John M. Flach
Psychology Faculty Publications
Over the past four years we have been studying problems of control and coordination with funds from AFOSR. Work over the first three years has been reviewed in the final report for the original AFOSR award (Flach, 1996). This report reviews work for the last year of the ASSERT grant. This work has focused on perception and control of low altitude flight. Experimental work from two synthetic task environments is described in this report. The first environment involved descent to low altitude. The key independent variables were speed of forward motion and optical texture (dot, grid, splay, depression). Results showed …
Cloning Of Human Acetyl-Coa Carboxylase-Beta And Its Unique Features., Joohun Ha, Jung-Kee Lee, Kyung-Sup Kim, Lee A. Witters, Ki-Han Kim
Cloning Of Human Acetyl-Coa Carboxylase-Beta And Its Unique Features., Joohun Ha, Jung-Kee Lee, Kyung-Sup Kim, Lee A. Witters, Ki-Han Kim
Dartmouth Scholarship
Acetyl-CoA carboxylase, which has a molecular mass of 265 kDa (ACC-alpha), catalyzes the rate-limiting step in the biosynthesis of long-chain fatty acids. In this study we report the complete amino acid sequence and unique features of an isoform of ACC with a molecular mass of 275 kDa (ACC-beta), which is primarily expressed in heart and skeletal muscles. In these tissues, ACC-beta may be involved in the regulation of fatty acid oxidation, rather than fatty acid biosynthesis. ACC-beta contains an amino acid sequence at the N terminus which is about 200 amino acids long and may be uniquely related to the …
Opposing Motor Activities Are Required For The Organization Of The Mammalian Mitotic Spindle Pole, Tirso Gaglio, Alejandro Saredi, James B. Bingham, M Josh Hasbani, Steven R. Grill, Trina A. Schroer, Duane A. Compton
Opposing Motor Activities Are Required For The Organization Of The Mammalian Mitotic Spindle Pole, Tirso Gaglio, Alejandro Saredi, James B. Bingham, M Josh Hasbani, Steven R. Grill, Trina A. Schroer, Duane A. Compton
Dartmouth Scholarship
We use both in vitro and in vivo approaches to examine the roles of Eg5 (kinesin-related protein), cytoplasmic dynein, and dynactin in the organization of the microtubules and the localization of NuMA (Nu-clear protein that associates with the Mitotic Apparatus) at the polar ends of the mammalian mitotic spindle. Perturbation of the function of Eg5 through either immunodepletion from a cell free system for assembly of mitotic asters or antibody microinjection into cultured cells leads to organized astral microtubule arrays with expanded polar regions in which the minus ends of the microtubules emanate from a ring-like structure that contains NuMA. …
Moving Occupation Into Treatment: Clinical Interpretation Of "Legitimizing Occupational Therapy's Knowledge"., Janice P. Burke
Moving Occupation Into Treatment: Clinical Interpretation Of "Legitimizing Occupational Therapy's Knowledge"., Janice P. Burke
Department of Occupational Therapy Faculty Papers
No abstract provided.
Pancreatic Expression Of Interleukin-4 Abrogates Insulitis And Autoimmune Diabetes In Nonobese Diabetic (Nod) Mice., Regula Mueller, Troy Krahl, Nora Sarvetnick
Pancreatic Expression Of Interleukin-4 Abrogates Insulitis And Autoimmune Diabetes In Nonobese Diabetic (Nod) Mice., Regula Mueller, Troy Krahl, Nora Sarvetnick
Journal Articles: Regenerative Medicine
Diabetes in nonobese diabetic (NOD) mice is a T cell-dependent autoimmune disease. The destructive activities of autoreactive T cells have been shown to be tightly regulated by effector molecules. In particular, T helper (Th) 1 cytokines have been linked to diabetes pathogenesis, whereas Th2 cytokines and the cells that release them have been postulated to be protective from disease. To test this hypothesis, we generated transgenic NOD mice that express interleukin (IL) 4 in their pancreatic beta cells under the control of the human insulin promoter. We found that transgenic NOD-IL-4 mice, both females and males, were completely protected from …
Efficient Vasoactive Intestinal Polypeptide Hydrolyzing Autoantibody Light Chains Selected By Phage Display, Sonia Tyutyulkova, Qing-Sheng Gao, Austin Thompson, Stephen I. Rennard, Sudhir Paul
Efficient Vasoactive Intestinal Polypeptide Hydrolyzing Autoantibody Light Chains Selected By Phage Display, Sonia Tyutyulkova, Qing-Sheng Gao, Austin Thompson, Stephen I. Rennard, Sudhir Paul
Journal Articles: Pulmonary & Critical Care Med
An immunoglobulin light chain (L chain) library derived from the peripheral blood lymphocytes of a patient with asthma was cloned into a phagemid vector. Phage particles displaying L chains capable of binding vasoactive intestinal polypeptide (VIP) were isolated by affinity chromatography. Two VIP binding L chains were expressed in Escherichia coli in soluble form and purified to electrophoretic homogeneity by metal chelating and protein L affinity chromatography. Both L chains catalyzed the hydrolysis of [tyr10-125I]VIP substrate. The catalytic activity eluted at the molecular mass of the monomer form of the L chain (28 kDa) from a gel filtration column. The …
Cloning Of The Mammalian Type Ii Iodothyronine Deiodinase. A Selenoprotein Differentially Expressed And Regulated In Human And Rat Brain And Other Tissues., Walburga Croteau, Jennifer C. Davey, Valerie Anne Galton, Donald L. St Germain
Cloning Of The Mammalian Type Ii Iodothyronine Deiodinase. A Selenoprotein Differentially Expressed And Regulated In Human And Rat Brain And Other Tissues., Walburga Croteau, Jennifer C. Davey, Valerie Anne Galton, Donald L. St Germain
Dartmouth Scholarship
The deiodination of thyroid hormones in extrathyroidal tissues plays an important role in modulating thyroid hormone action. The type II deiodinase (DII) converts thyroxine to the active hormone 3,5,3'-triiodothyronine, and in the rat is expressed in the brain, pituitary gland, and brown adipose tissue (BAT). Complementary DNAs (cDNAs) for the types I and III deiodinases (DI and DIII, respectively) have been isolated and shown to code for selenoproteins. However, information concerning the structure of the mammalian DII remains limited, and the pattern of its expression in human tissues is undefined. We report herein the identification and characterization of rat and …
Measuring Hospital Use Without Claims: A Comparison Of Patient And Provider Reports., R E. Clark, S K. Ricketts, G J. Mchugo
Measuring Hospital Use Without Claims: A Comparison Of Patient And Provider Reports., R E. Clark, S K. Ricketts, G J. Mchugo
Dartmouth Scholarship
We compared the validity of hospital admission and length of stay reports from patients, outpatient providers, and hospitals, and we examined possible sources of error. Data were collected from people enrolled in a randomized trial of treatment for severe mental illness and substance use disorders, from community mental health centers (CMHCs), and from hospitals. Reports for each of the 74 study participants covered two-year time periods beginning and ending at various times between 1989 and 1993. We compared reports from the various sources and constructed a hybrid with data from all three sources. Using parametric and non-parametric statistics, we compared …
A Novel Iron-Regulated Metal Transporter From Plants Identified By Functional Expression In Yeast., David Eide, Margaret Broderius, Jeanette Fett, Mary Lou Guerinot
A Novel Iron-Regulated Metal Transporter From Plants Identified By Functional Expression In Yeast., David Eide, Margaret Broderius, Jeanette Fett, Mary Lou Guerinot
Dartmouth Scholarship
Iron is an essential nutrient for virtually all organisms. The IRT1 (iron-regulated transporter) gene of the plant Arabidopsis thaliana, encoding a probable Fe(II) transporter, was cloned by functional expression in a yeast strain defective for iron uptake. Yeast expressing IRT1 possess a novel Fe(II) uptake activity that is strongly inhibited by Cd. IRT1 is predicted to be an integral membrane protein with a metal-binding domain. Data base comparisons and Southern blot analysis indicated that IRT1 is a member of a gene family in Arabidopsis. Related sequences were also found in the genomes of rice, yeast, nematodes, and humans. In Arabidopsis, …
Complications, Untoward Events, And Reality., Geoffrey G. Hallock Md
Complications, Untoward Events, And Reality., Geoffrey G. Hallock Md
Department of Surgery
The only surgeons who do not have deal with complications are those who do not operate.1