bluuebunny/crossref_metadata_2025 huggingface dataset:
Endothelin B Receptor-Mediated Protection Against Anoxia–Reoxygenation Injury in Perfused Rat Liver: Nitric Oxide-Dependent and -Independent Mechanisms
Authors: Taniai Hisashi , Suematsu Makoto , Suzuki Tsuneharu , Norimizu Shinji , Hori Rio , Ishimura Yuzuru , Nimura Yuji
Published: August 2002

This study aimed to investigate the roles of endothelin (ET) receptors in biliary dysfunction and cell injury in postischemic livers. Rat livers perfused with oxygenated Krebs–Henseleit solution were exposed to reoxygenation following 20–minute hypoxia. The anoxic perfusion decreased bile output and reduced cyclic guanosine monophosphate (cGMP) contents, an index of nitric oxide (NO) generation. Upon reoxygenation, the decreased bile was not fully recovered, and the resistance increased biphasically: an early transient spike accompanied by an elevated release of ET–1 and a rise accompanied by a cGMP elevation in the later period. The initial vasoconstriction appeared to be mediated by both ETA and ETB receptors, as judged by inhibitory effects of their antagonists, BQ–485 and BQ-788, respectively, while the late elevation of the resistance was not attenuated by these reagents, but rather enhanced by the ETB blockade. The BQ–788 treatment attenuated the reoxygenation–induced cGMP elevation and induced bile acid-dependent choleresis. However, such a change upon the ETB blockade coincided with dissociation of a recovery of phospholipids and aggravation of cell injury. The BQ–788-elicited deterioration of reoxygenation–elicited changes was attenuated by NO supplement with S–nitroso–N–acetyl penicillamine. N
ω–Nitro–l–arginine methyl ester, an NO synthase inhibitor, mimicked biliary changes elicited by the ETB blockade but without causing notable cell injury. Under these circumstances, coadministration of clotrimazole, an inhibitor of cytochrome P450 mono–oxygenases, elicited the injury comparable with that observed under the ETB blockade. These results suggest that ETB–mediated signaling limits excessive bile acid excretion and plays a protective role against reoxygenation injury through mechanisms involving both NO–dependent and –independent processes.
Lamivudine Treatment Can Overcome Cytotoxic T–Cell Hyporesponsiveness in Chronic Hepatitis B: New Perspectives for Immune Therapy
Authors: Boni Carolina , Penna Amalia , Ogg Graham S. , Bertoletti Antonio , Pilli Massimo , Cavallo Cristina , Cavalli Albertina , Urbani Simona , Boehme Richard , Panebianco Ruggero , Fiaccadori Franco , Ferrari Carlo
Published: August 2002

The hepatitis B virus (HBV) cytotoxic T lymphocyte (CTL) response in patients with chronic HBV infection is generally weak or totally undetectable. This inability to mount protective CTL responses is believed to be a crucial determinant of viral persistence, and its correction represents an important objective of immune therapies for chronic hepatitis B. However, amplification of CTL responses in vivo may be ineffective if HBV–specific CD8 cells are either absent or nonresponsive to exogenous stimulation. In this study, we asked whether antiviral treatments able to inhibit viral replication and to reduce viral and antigen load can successfully reconstitute CTL responses creating the appropriate conditions for their therapeutic stimulation. For this purpose, the HBV–specific CTL response before and during lamivudine therapy was studied longitudinally in 6 HLA–A2-positive patients with HBeAg+ chronic hepatitis B. Both HBV–specific cytotoxic T cell activity measured by chromium release assay on peptide stimulation in vitro and CD8+ T cell frequency measured ex vivo by HLA–A2/peptide tetramer staining were significantly augmented by lamivudine therapy. This enhancement followed the reconstitution of CD4 reactivity and the decline of viral load induced by therapy. Our study shows that lamivudine treatment in chronic hepatitis B can restore CTL reactivity, making CTL susceptible to exogenous stimulation. This effect may enhance the probability that T cell–based immune therapies delivered after lamivudine treatment can successfully reconstitute a protective CTL response able to cure chronic HBV infection. (Hepatology 2001;33:963–971.)
Rna Expression in the Early Characterization of Hepatotoxicants in Wistar Rats by High–Density Dna Microarrays
Authors: Bulera Steven J. , Eddy Susan M. , Ferguson Erika , Jatkoe Timothy A. , Reindel James F. , Bleavins Michael R. , De La Iglesia Felix A.
Published: August 2002

High–density microarrays are useful tools to study gene expression for the purpose of characterizing functional tissue changes in response to the action of drugs and chemicals. To test whether high–density expression data can identify mechanisms of toxicity and to identify an unknown sample through its RNA expression pattern, groups of male Wistar rats were administered 6 hepatotoxicants. The compounds chosen for this study were microcystin–LR (MLR), phenobarbital (PB), lipopolysaccharide (LPS), carbon tetrachloride (CT), thioacetamide (THA), and cyproterone acetate (CPA). These hepatotoxicants are known to induce adverse liver effects through different mechanisms. Liver mRNA was isolated and used to generate biotinylated cRNA for hybridization to a custom 1,600-rat gene DNA microarray. Treatment correlation matrices analyzed hybridization data from a hepatotoxicant–blinded sample, with gene expression coefficients (GEC) evaluated by means of hierarchical cluster analysis and visual representation as dendrograms. The experimental liver toxicity from the different treatments was confirmed by means of concurrent histopathology, liver enzymes, and bilirubin assays. This toxico genomic analysis identified multiple genes and groups of genes that were affected by the hepatotoxicants on study, indicating that high–density microarray expression data are useful to identify groups of genes involved in toxicity. In addition, the mRNA expression profile of an unidentified sample can be accurately identified when compared with the expression profiles resident in the data set. This study supports the use of gene expression-profiling technology to determine or to predict toxic liver effects. (Hepatology 2001;33:1239–1258.)
Morphologic and Functional Characterization of Caveolae in Rat Liver Hepatocytes
Authors: Calvo Maria , Tebar Francesc , Lopez-Iglesias Carmen , Enrich Carlos
Published: August 2002

Caveolae are small pits on the plasma membrane found in several, if not all, differentiated cells. They are involved in potocytosis, endocytosis, transcytosis, membrane trafficking, and signal transduction. Although caveolin has recently been identified in subcellular fractions from rat liver there is no clear–cut morphologic evidence for the presence of prototypical caveolae on the surface of hepatocytes. In this study the presence of caveolae at the cell surface of hepatocytes was directly shown by rapid–freeze, deep–etching electron microscopy. Moreover, combined deep–etching and immunogold techniques revealed caveolin in caveolae of the dorsal membrane of primary culture hepatocytes. Using reagents that perturb membrane cholesterol and interfere with endocytosis through the caveolae, a caveolae–dependent internalization of cholera toxin B and retinol–binding protein by hepatocytes in primary culture was shown. Finally, immunocytochemical analysis of caveolin in nonparenchymal cells of the rat liver showed its presence in Kupffer and stellate cells, however no caveolin could be detected in endothelial cells. (Hepatology 2001;33:1259–1269.)
Autoimmune Regulator Aire: Evidence for Genetic Differences Between Autoimmune Hepatitis and Hepatitis As Part of the Autoimmune Polyglandular Syndrome Type 1
Authors: Vogel Arndt , Liermann Heike , Harms Andrea , Strassburg Christian P. , Manns Michael P. , Obermayer-Straub Petra
Published: August 2002

The mechanisms driving the immune–mediated destruction of hepatic tissues in autoimmune hepatitis (AIH) are unknown. Recently the autoimmune regulator (AIRE), a gene associated with the development of the autoimmune polyglandular syndrome type 1 (APS–1), was cloned. About 15% to 20% of APS–1 patients develop hepatitis. However, the role of AIRE mutations in AIH, primary sclerosing cholangitis (PSC), and primary biliary cirrhosis (PBC) is not known. To address this issue patients with AIH (n = 94), PSC (n = 60), and PBC (n = 30) were analyzed for the presence of mutations in exons 6, 8, and 10 of AIRE by single stranded conformation polymorphism and sequence analysis. Autoantibody patterns of patients with defects in AIRE were analyzed by indirect immunofluorescence, enzyme–linked immunosorbent assay and Western blot. Heterozygous mutations of AIRE were identified in 3 patients: a patient with PBC and a patient with AIH type 1 carried a R257X mutation, and a patient with AIH type 2, diabetes mellitus type 1 (IDDM), thyroid disease, and atrophic gastritis carried a G305S mutation in the first PHD ring finger domain of the AIRE protein. None of the 3 patients with a defective AIRE allele showed autoantibodies, which are known to associate with APS–1. These findings show a differential genetic association of autoimmune liver diseases and hepatitis in APS–1. The subgroup of patients with heterozygous mutations in AIRE does not represent patients with an incomplete APS–1 syndrome. However, the Aire gene defect showed that genes involved in the induction of immunologic tolerance provide candidates for etiologic factors in autoimmune liver diseases.
Immunogenicity of Hepatitis A Vaccination in Decompensated Cirrhotic Patients
Authors: Arguedas Miguel R. , Johnson Anita , Eloubeidi Mohamad A. , Fallon Michael B.
Published: August 2002

Hepatitis A virus (HAV) vaccination is recommended in chronic liver disease because of an increased morbidity and mortality associated with HAV superinfection. However, data regarding the efficacy of HAV vaccination in patients with advanced chronic liver disease is limited. We assessed the efficacy of a standard HAV vaccination schedule in decompensated chronic liver disease in comparison with compensated disease and defined clinical predictors associated with seroconversion. Eighty–four anti–HAV antibody-negative patients, 49 with compensated liver disease, and 35 with decompensated disease were enrolled. Seroconversion was measured by qualitative and quantitative anti–HAV antibody measurements 1 month after each vaccine dose, and univariate/multivariate analysis was performed to define clinical predictors associated with seroconversion. One month after the primary dose, 71.4% of patients with compensated liver disease had detectable anti–HAV antibody compared with 37.1% with decompensated liver disease (P < .05). One month after the booster dose, 98% of compensated patients seroconverted compared with 65.7% with decompensated disease (P < .05). The median serum antibody concentration in compensated liver disease was 76.4 mIU/mL at month 1 and 327.91 mIU/mL at month 7 compared with 20.0 mIU/mL and 102.57 mIU/mL, respectively, in decompensated disease. On multivariate analysis, Child–Pugh class was the only factor predicting response to vaccination. Seroconversion after HAV vaccination was significantly less common in decompensated liver disease and the presence of advanced disease (Child–Pugh class B/C) predicted a lower response rate. These findings indicate that the response to HAV vaccination in chronic liver disease is optimal when targeted to patients before the development of hepatic decompensation.
A Dominant Hepatitis B Virus Population Defective in Virus Secretion Because of Several S–Gene Mutations From A Patient With Fulminant Hepatitis
Authors: Kalinina Tatyana , Riu Anna , Fischer Lutz , Will Hans , Sterneck Martina
Published: August 2002

There is increasing evidence that certain pathogenic hepatitis B virus (HBV) variants may play a role in the pathogenesis of fulminant hepatitis (FHB). Recently, we isolated from a patient with fulminant recurrent hepatitis B after liver transplantation variants with enhanced replication competence and a possible defect in viral particle secretion. Both viral features may have contributed to the severity of the disease. The aim of this study was to prove the secretion defect of these variants, to analyze the consequences, and to identify the responsible viral mutations. The variant genomes and appropriate wild–type/variant hybrid genomes were functionally characterized after transfection in human hepatoma cells. Two cloned genomes and the polymerase chain reaction (PCR)–amplified mixture of full–length genomes showed a block in viral particle secretion. This was caused by a combination of amino acid changes in the S–protein including the mutation G145R frequently emerging after hyperimmunoglobulin treatment. The mutations induced retention of the surface proteins in an endoplasmic reticulum (ER)–like compartment, but no intracellular accumulation. These data provide evidence for the in vivo existence of a dominant HBV population with a severe defect in viral particle secretion caused by mutations in the S–gene. This viral phenotype in combination with the enhanced replication competence may have contributed to the fulminant clinical course of the infection.
Hepatitis C Virus-Like Particles Induce Virus–Specific Humoral and Cellular Immune Responses in Mice
Authors: Lechmann Martin , Murata Kazumoto , Satoi Jujin , Vergalla John , Baumert Thomas F. , Liang Jake T.
Published: August 2002

We have recently described the production of hepatitis C virus-like particles (HCV–LPs) in insect cells that resemble the putative virions. Here we evaluate the humoral and cellular immunogenicity of the virus–like particles with or without viral p7 protein, a small viral polypeptide that resides between the structural and nonstructural regions of the HCV polyprotein and whose function has not been defined. Immunized BALB/c mice developed high titers of anti–E2 antibodies and virus–specific cellular immune responses including cytotoxic T lymphocytes and T helper responses with gamma interferon production. The virus–like particles without p7 generated a higher cellular immune response with a more TH1 profile than the particles with p7. Immunization of heat–denatured particles resulted in substantially lower humoral and cellular responses, suggesting that the immunogenicity is strongly dependent on particle formation. Administration of CpG oligonucleotide or cationic lipid 3β–[N–(N',N'–dimethylaminoethane)carbamoyl]cholesterol (DC–Chol), two potent adjuvants, did not significantly enhance the immunogenicity of HCV–LPs. Our results indicate that HCV–LPs can induce humoral and cellular immune responses and offer a promising approach to vaccine development.
Hydrogen Peroxide Mediates Vascular Cell Adhesion Molecule–1 Expression From Interleukin–18-Activated Hepatic Sinusoidal Endothelium: Implications for Circulating Cancer Cell Arrest in the Murine Liver
Authors: Mendoza Lorea , Carrascal Teresa , De Luca Marco , Fuentes Angela M. , Salado Clarisa , Blanco Jerónimo , Vidal-Vanaclocha Fernando
Published: August 2002

The mechanism of intrasinusoidal arrest of circulating cancer cells, which is a critical step in liver metastasis, appears to be facilitated by tumor–derived proinflammatory factors that increase sinusoidal cell adhesion receptors for cancer cells. However, how this prometastatic microenvironment is up–regulated remains unknown. Using intrasplenically injected B16 melanoma (B16M) cells, we show that the expression of vascular cell adhesion molecule–1 (VCAM–1) significantly increased in hepatic sinusoidal endothelium (HSE) cells over physiologic baseline within the first 24 hours of metastatic cancer cell infiltration in the liver. This correlated with increased in vitro adhesion of B16M cells to HSE cells isolated from B16M cell-injected mice. In vivo VCAM–1 blockade with specific antibodies before B16M cell injection decreased sinusoidal retention of luciferase–transfected B16M cells by 85%, and metastasis development by 75%, indicating that VCAM–1 expression on tumor–activated HSE cells had a prometastatic contribution. Because VCAM–1 expression is oxidative stress-inducible, recombinant catalase was in vivo administered, resulting in a complete abrogation of both VCAM–1 expression and B16M cell adhesion increases in HSE cells isolated from B16M cell-injected mice. Catalase also abrogated the proadhesive response of HSE cells to B16M–conditioned medium (B16M–CM) in vitro, although this did not affect the concomitant release of major proinflammatory cytokines by HSE cells. HSE cells treated with B16M–CM released interleukin (IL)–18 via tumor necrosis factor–α (TNF–α)-dependent IL–1β in vitro. In turn, H2O2 production from B16M–CM-treated HSE cells was regulated by IL–18. Thus, liver–infiltrating B16M cells activated their adhesion to HSE through a sequential process involving TNF–α-dependent IL–1β, which induced IL–18 to up–regulate VCAM–1 via H2O2. The pivotal position of H2O2 was further supported by the fact that incubation of HSE cells with nontoxic concentrations of H2O2 directly enhanced VCAM–1-dependent B16M cell adhesion in vitro without proinflammatory cytokine mediation, which emphasizes the key role of oxidative stress in the pathogenesis of liver inflammation and metastasis.
A comparative study of antibody expressions in primary biliary cirrhosis and autoimmune cholangitis using phage display
Authors: Ikuno Nobuhiro , Scealy Marita , Davies Janet M. , Whittingham Senga F. , Omagari Katsuhisa , Mackay Ian R. , Rowley Merrill J.
Published: August 2002

Primary biliary cirrhosis (PBC) and autoimmune cholangitis (AIC) are serologic expressions of an autoimmune liver disease affecting biliary ductular cells. Previously we screened a phage-displayed random peptide library with polyclonal IgG from 2 Australian patients with PBC and derived peptides that identified a single conformational (discontinuous) epitope in the inner lipoyl domain of the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2), the characteristic autoantigen in PBC. Here we have used phage display to investigate the reactivity of PBC sera from 2 ethnically and geographically distinct populations, Japanese and Australian, and the 2 serologic expressions, PBC and AIC. Random 7-mer and 12-mer peptide libraries were biopanned with IgG from 3 Japanese patients with PBC and 3 with AIC who did not have anti-PDC-E2. The phage clones (phagotopes) obtained were tested by capture enzyme-linked immunosorbent assay (ELISA) for reactivity with affinity-purified anti-PDC-E2, and compared with those obtained from Australian patients with PBC. Peptide sequences of the derived phagotopes and sequences derived by biopanning with irrelevant antisera were aligned to develop a guide tree based on physicochemical similarity. Both Australian and Japanese PBC-derived phagotopes were distributed in branches of the guide tree that contained the peptide sequences MH and FV previously identified as part of an immunodominant conformational epitope of PDC-E2, indicating that epitope selection was not influenced by the racial origin of the PBC sera. Biopanning with either PBC or AIC-derived IgG yielded phagotopes that reacted with anti-PDC-E2 by capture ELISA, further establishing that there is a similar autoimmune targeting in PBC and AIC. (Hepatology 2001;34:478-486.)
Sternal Bone Biopsy in Standing Horses
Authors: Désévaux C. , Laverty S. , Doizé B
Published: August 2002

Objective—To develop a technique for sternal bone biopsy in standing horses.

Study Design—Experimental study.

Animals—Five adult horses.

Methods—Horses were restrained in a standing stocks and sedated. The sternal biopsy site, identified by ultrasonographic examination, was clipped and prepared for aseptic surgery and infiltrated with local anesthetic. An electric bone biopsy drill (Osteocore; Institut Straumann AG, CH‐4437, Waldenburg, Switzerland)), which yielded 4‐mm‐diameter bone specimens, was used to obtain sternal biopsies through a small skin incision. Sections (7 μm) of the bone specimens were stained with toluidine blue and Goldner's green trichrome and observed microscopically to determine suitability for histological and histomorphometric evaluation.

Results—The most suitable sternal biopsy site was at the 4th or 5th sternebra. The surgical procedure was easy to perform and well tolerated by the horses, and adequate samples were obtained on the first attempt. The only complications were incisional edema in all horses and wound drainage in 1 horse.

Conclusions—Sternal bone biopsy may be successfully performed in standing horses, and the technique described in this report yields architecturally intact bone specimens.

Clinical Relevance—The sternum is an accessible site for cancellous bone biopsy specimens in standing horses.
Long‐Term Results of Bovine Mandibular Fractures Involving the Molar Teeth
Authors: Reif Ullrich , Lischer Christoph J. , Steiner Adrian , Flüuckiger Mark A. , Auer Jörg A.
Published: August 2002

Objective— To evaluate postoperative complications and long‐term outcome of simple mandibular fractures involving the molar teeth in cattle.

Animal Population— Seventeen cattle with mandibular fractures involving the molar teeth with disruption of the occlusal surface.

Methods— Treatment consisted of application of AO/ASIF‐Pinless External Fixators (Synthes, Paoli, PA) in 14 cows, interdental wire stabilization in 1 cow, and conservative treatment in 2 cows. Long‐term outcome was determined by telephone contact with the owners, and whenever possible, cows were reevaluated by physical, intraoral, and radiographic examination of the fracture site.

Results— Loosening of the fixation device (4 cattle) and bone sequestration (11 cattle) were the most commonly encountered complications. Oral incontinence during rumination was a minor complication in 1 cow. The mean (± SD) time the cattle were in production was 26 (± 14) months, with 10 cows still alive at follow‐up examination; 9 cows were reevaluated. On intraoral examination there was a step in the occlusal surface at the level of the healed fracture site in 3 cows, wave and shear mouth formation in 3 cows, and enamel point formation in 1 cow. Radiographically, all the reevaluated fractures had healed, and there were no signs of tooth root infection.

Conclusions— Complications during healing were bone sequestration and loosening of the fixator. None of the cows was removed from production because of fracture‐associated complications, but decreased milk yield occurred in 2 cows. Tooth abnormalities developed in 6 cows, but function of the mandible was not altered.

Clinical Relevance— Mandible fractures involving the molar teeth carry a good prognosis for return to normal function. Radiographic follow‐up is necessary to detect bone sequestration.
The Effects of a Hemoglobin‐Based Oxygen Carrier (HBOC‐301) on Left Ventricular Systolic Function in Anesthetized Dogs
Authors: Muir William W. , De Morais Autran Helio S. , Constable Peter D.
Published: August 2002

Objective— To evaluate the effects of a hemoglobin‐based oxygen carrier (HBOC‐301) on left ventricular preload, afterload, contractility, and ventriculo‐arterial coupling in anesthetized dogs.

Study Design— A prospective experimental study.

Animals— Seven adult male dogs weighing 2.3 to 2.7 kg.

Methods— The study was performed on intact, closed‐chest, chloralose‐anesthetized dogs. Heart rate, left ventricular end‐systolic and end‐diastolic volume and pressure, cardiac output, stroke volume, blood resistivity, mean arterial pressure (MAP), dP/dtmax, end‐systolic elastance (Ees), systemic vascular resistance (SVR), effective arterial elastance (Ea), left ventricular‐arterial coupling (Ees/Ea), and myocardial oxygen consumption (MVo2) were determined during a 90‐minute infusion of 30 mL/kg (20 mL/kg/h) of HBOC‐301 and for 90 minutes thereafter.

Results— The administration of HBOC‐301 significantly decreased packed cell volume, blood resistivity, heart rate, cardiac output, and dP/dtmax and significantly increased left ventricular end‐diastolic and end‐systolic pressure, MAP, and SVR. The Ea, Ees, Ees/Ea, and MVo2 did not change.

Conclusions— HBOC‐301 produced insignificant changes in load independent indexes of cardiac performance (Ees, Ea, Ees/Ea) in anesthetized dogs. The collective directional changes in these variables, however, in conjunction with significant increases in SVR were most likely responsible for a decrease in cardiac output. Increases in SVR and the volume load (30 mL/kg) contributed to increases in left ventricular end‐diastolic pressure.

Clinical Relevance— HBOC‐301 infusion should be monitored and administered cautiously to dogs with poor ventricular function.
One Percent Sodium Carboxymethylcellulose Prevents Experimentally Induced abdominal Adhesions in Horses
Authors: Hay William P. , Mueller P.O. Eric , Harmon Barry , Amoroso Lisa
Published: August 2002

Objective—To evaluate the efficacy of 1% sodium carboxymethylcellulose (SCMC) for prevention of experimentally induced abdominal adhesions in horses.

Study Design—Prospective, controlled, experimental study.

Animal Population—Twelve healthy adult horses

Methods—The effect of 1% SCMC on adhesion formation was evaluated in 12 healthy horses by using an established model of serosal trauma to induce intraabdominal adhesions. After ventral median celiotomy, 2 separate areas of the jejunum were abraded, and three 2–0 chromic gut sutures were placed in each abraded area. Jejunal resection and end‐to‐end anastomosis was performed at 2 sites distant to the abrasion sites. In treated horses (n= 6), 2 L of 1% SCMC was applied to the intestine before and after intestinal manipulation. In control horses (n= 6), 2 L of saline solution were applied to the intestine before and after surgical manipulation. All horses were euthanatized 10 days after surgery, and the abdominal cavity was evaluated for adhesion formation. The frequency of intraabdominal adhesions between groups was compared with a chi‐square test. Statistical significance was set atP< .05.

Results—All control horses had intraabdominal adhesions. Fibrous adhesions were associated with both jejunal abrasion sites in 5 control horses. Fibrous adhesions were also associated with 1 or both jejunal anastomotic sites in 5 control horses. Only 1 treated horse developed adhesions at the jejunal abrasion sites, and no adhesions were present at the anastomotic sites in the treated horses. There were significantly fewer adhesions in the SCMC treatment group compared with the control group (P< .05).

Conclusion—In this experimental model, application of 1% SCMC reduced the frequency of intraabdominal adhesions at areas of serosal abrasion and at jejunal anastomotic sites.

Clinical Relevance—In horses at an increased risk for developing intraabdominal adhesions after intestinal surgery, the use of 1% SCMC during celiotomy may decrease the frequency of adhesion formation.
An In Vitro Biomechanical Comparison of Interlocking Nail Constructs and Double Plating for Fixation of Diaphyseal Femur Fractures in Immature Horses
Authors: Radcliffe Rolfe M. , Lopez Mandi J. , Turner Tracy A. , Watkins Jeffrey P. , Radcliffe Catherine H. , Markel Mark D.
Published: August 2002

Objective—To compare the biomechanical properties of intact immature horse femurs and 3 stabilization methods in ostectomized femurs.

Animal or Sample Population—Eighteen pairs of femurs from immature horses aged 1 to 15 months, and weighing 68 to 236 kg.

Methods—Thirty‐four immature horse femurs were randomly assigned to 1 of 5 test groups: 1) interlocking intramedullary nail (IIN) (n = 6); 2) IIN with a cranial dynamic compression plate (I/DCP) (n = 6); 3) 2 dynamic compression plates (2DCP) (n = 8); 4) intact femurs tested to failure in lateromedial (LM) bending (n = 6); and 5) intact femurs tested to failure in caudocranial (CaCr) bending (n = 8). Mid‐diaphyseal ostectomies (1 cm) were performed in all fixation constructs. Biomechanical testing consisted of 4 nondestructive tests: CaCr bending, LM bending, compression, and torsion, followed by bending to failure. All groups were tested to failure in LM bending with the exception of 1 group of intact femurs tested to failure in CaCr bending. Stiffness and failure properties were compared among groups.

Results—The 2DCP‐femur construct had greater structural stiffness in nondestructive bending than the IIN‐femur construct in either LM or CaCr bending, and the I/DCP‐femur construct in LM bending. Only the I/DCP and 2DCP fixations were similar to intact bone in nondestructive‐bending tests. In addition, the 2DCP‐femur construct had greater structural and gap torsional stiffness than the I/DCP‐femur construct, and greater gap torsional stiffness than the IIN‐femur construct. However, all of the fixation methods tested, including the 2DCP‐femur construct, had lower structural stiffness in torsional loading compared with intact bone. No significant differences in structural stiffness were found between intact bones and femur constructs tested nondestructively in compression. In resistance to LM bending to failure, the 2DCP‐femur construct was superior to the IIN‐femur construct, yet similar to the I/DCP‐femur construct. Also, evaluation of yield and failure loads revealed no significant differences between intact bone and any of the femur constructs tested to failure in LM bending.

Conclusions—In general, the 2DCP‐femur construct provided superior strength and stiffness compared with the IIN and I/DCP‐femur constructs under bending and torsion.

Clinical Relevance—Double plating of diaphyseal comminuted femoral fractures in immature horses may be the best method of repair, because in general, it provides the greatest strength and stiffness in bending and torsion.
An in vitro biomechanical study of bone plate and interlocking nail in a canine diaphyseal femoral fracture model
Authors: Bernarde Antoine , Diop Amadou , Maurel Nathalie , Viguier Eric
Published: August 2002

Objective—To compare the structural properties and the interfragmentary motion in ostectomized canine femurs stabilized with either an 8‐mm interlocking nail system (IN) or a 10‐hole dynamic compression broad plate (DCP).

Animal or Sample Population—Ten pairs of adult canine femurs with a 25‐mm mid‐diaphyseal gap.

Methods—Bone specimens were divided into 2 groups (10 femurs each). Left femurs were stabilized with a DCP and 8 bicortical screws; right femurs were stabilized with an IN and 3 screws. Mechanical tests were performed in eccentric axial loading and in craniocaudal bending. The testing was first conducted nondestructively and then until breakage. Structural properties, ie, stiffness, yield limits, and failure limits, were determined. Interfragmentary motion was measured during nondestructive tests with the use of an optoelectronic device. Axial, transverse, and rotational motions were calculated. Mean values of stiffness, yield and failure limits, and axial and shear motions for each fixation method were compared using a pairedttest within each group (P< .05).

Results—Mean (±SD) values of stiffness and failure limit were significantly higher for IN constructs than for DCP constructs in compression, while there was little difference in the results between each tested group in bending. Mean yield load values were significantly higher for IN than for DCP specimens in compression as well as in bending. The axial‐motion analysis revealed significant differences between IN and DCP groups during bending tests only. The highest score of transverse motion at the gap was recorded during bending tests, and was higher for DCP than for IN specimens. There were insignificant differences between the two groups with regard to rotation around the diaphyseal axis.

Conclusions and Clinical Relevance—Structural properties and interfragmentary shear motion analysis demonstrated a much higher rigidity in the IN‐bone than in the DCP‐bone constructs.
Arthroscopic Anatomy of the Equine Temporomandibular Joint
Authors: May Kimberly A. , Moll H. David , Howard Rick D. , Pleasant R. Scott , Gregg John M.
Published: August 2002

Objective—To develop an arthroscopic approach to, and describe the arthroscopic anatomy of, the equine temporomandibular joint (TMJ).

Study Design—Cadaveric study, after which the technique was tested in horses.

Animals or Sample Population—Ten cadaveric equine heads and 5 normal horses (age, 5–13 years; weight, 425–545 kg).

Methods—Specimens or horses were positioned in right lateral recumbency. After fluid distention of the TMJ, arthroscopic portals were made in the dorsal compartment over the most prominent portion of the joint outpouching (caudodorsal approach) and in rostral and intermediate locations. The joint was explored and photographed. Positional changes in the mandible were made to determine if observation of the joint could be improved. Instrument portals were created to assess the feasibility of surgical arthroscopy. Cadaveric heads were dissected to assess iatrogenic damage, whereas experimental horses were observed for postoperative complications for 30 days.

Results—A caudodorsal arthroscopic approach provided the best evaluation of the dorsal compartment of the TMJ. The approach allowed observation of the rostral and caudal synovial pouches and the lateral aspect of the joint including the articular disc. Examination of the medial aspect of the joint was limited to the most rostral and caudal aspects. Access to the lateral aspect of the ventral compartment of the TMJ was precluded by the position of the transverse facial artery and vein. In specimens, iatrogenic damage was minimal and limited to the articular fibrocartilage, articular disc, and penetration of the parotid salivary gland. If the latter also occurred in horses, no adverse effects were noted. In horses, mild fluid extravasation occurred and resolved within 1 day. All horses ate normally after surgery but had periarticular swelling and mild pain upon palpation of the TMJ for 2 days.

Conclusions—A caudodorsal arthroscopic approach to the TMJ allowed adequate observation of the lateral aspect of the dorsal compartment of the joint. Access to the ventral compartment was precluded by the location of the transverse facial artery and vein.

Clinical Relevance—Conditions affecting the lateral and caudal aspects of the dorsal compartment of the TMJ should be visible by arthroscopy.
An Evaluation of Combined Immunosuppression with MNA 715 and Microemulsified Cyclosporine on Renal Allograft Rejection in Mismatched Mongrel Dogs
Authors: Kyles Andrew E. , Gregory Clare R. , Griffey Stephen M. , Jackson Joshua , Bernsteen Lynda , Morris Randall E.
Published: August 2002

Objective—To evaluate a combination of MNA 715 and microemulsifed cyclosporine for the prevention of renal allograft rejection in mismatched mongrel dogs.

Study design—Randomized, experimental study.

Animals—Fourteen female mismatched mongrel dogs.

Methods—Heterotopic renal transplantation and bilateral nephrectomy were performed in each dog. Dogs were randomly assigned to receive either MNA 715 and cyclosporine (n = 8) or cyclosporine alone (n = 6). Dogs were killed at 100 days after transplantation or when plasma creatinine exceeded 7 mg/dL.

Results—In the cyclosporine and MNA 715 group: 4 dogs survived to 100 days with normal plasma creatinine concentrations; 2 dogs with intestinal intussusceptions were killed at 5 and 8 days, 1 dog with a wound infection and sepsis was killed at 14 days, and 1 dog with a serum creatinine concentration >7 mg/dL was killed at 51 days postoperatively. In the cyclosporine‐alone group: 3 dogs with acute rejection were killed at 6 to 9 days and 3 dogs survived to 100 days. In dogs treated with cyclosporine and MNA 715, survival to histologically confirmed acute rejection was significantly longer (P= .044) and the degree of mononuclear cell infiltration was significantly reduced (P= .040), compared with dogs treated with cyclosporine alone.

Conclusions—MNA 715 combined with cyclosporine prolonged allograft survival and reduced the severity of histologic rejection in a clinically relevant renal transplant model.

Clinical relevance—An immunosuppressive regimen consisting of MNA715 and microemulsified cyclosporine may be effective in preventing allograft rejection in canine renal transplant patients.
Assessing Skeletal Muscle Glucose Metabolism With Positron Emission Tomography
Authors: Kelley David E. , Price Julie C. , Cobelli Claudio
Published: August 2002

Insulin has a marked effect to stimulate the transport and metabolism of glucose in skeletal muscle in healthy individuals, whereas an impaired response, termed insulin resistance, is a major risk factor for diabetes mellitus and other metabolic diseases. Studies of the molecular physiology of insulin action in skeletal muscle indicate that a principal loci of control resides within the proximal steps of glucose transport and phosphorylation. Deoxyglucose, the metabolism of which is limited to these proximal steps, is widely used for in vitro studies of insulin action on glucose transport. The technologies of PET imaging provide a unique opportunity to carry out similar studies in vivo in human skeletal muscle. In this instance, a short‐lived positron labeled tracer, [18F] FDG, can be given at sufficiently high specific activity to image not only glucose uptake, but by dynamic PET imaging, by monitoring the time course of [18F] FDG tissue activity, data can be generated to examine the kinetics of glucose transport and phosphorylation. The experimental procedures of this approach, including an overview of the mathematical modeling, are described in this review, along with some of the key findings of the initial applications of PET for the study of glucose metabolism in human skeletal muscle.
Siting a hazardous waste facility: the tangled web of risk communication
Authors: Beder Sharon , Shortland Michael
Published: August 2002

In 1990, the Australian government tried to establish a national hazardous waste incinerator in rural New South Wales. This paper considers the debates over the risks associated with hazardous waste incineration that emerged and the symbolic portrayal of technology implicit in these debates. Risk communications associated with technologies convey a message about how technological systems are shaped, implemented and operated. In this case, government officials succumbed to the temptation to employ an idealistic model of technology in an attempt to gain community acceptance for the proposed incinerator. They depicted incinerator technology as predictable and controllable, and separable from the social context. Opponents reacted by employing a `worse case' model; they represented incinerator technology as unreliable, uncertain and uncontrollable. Neither side deliberately lied: each put forward a view of technology that furthered its own goals. The polarized positions that resulted are not uncommon in technological controversies, and environmental groups are often branded as alarmist on this account. But there is some evidence in this case study that messages of reassurance also communicate insincerity and leave proponents of a technology vulnerable to having their claims easily deconstructed by the opposition.
Should we attempt to eradicate disability?
Authors: Harris John
Published: August 2002

This paper addresses two very important questions about the ethics of dealing with disability, namely: is it morally wrong to attempt to eradicate disability? and does such an attempt constitute discrimination against the disabled? The attempts to answer these two very general questions involve distinguishing two prior questions: is it wrong to prefer a non-disabled person to a disabled one, and is it wrong to prefer to produce (or even to prefer to be) a non-disabled individual rather than a disabled one? The paper argues that not only is it not wrong, but indeed it is right to prefer to produce a non-disabled individual rather than a disabled one where there is a genuine choice. It argues that the exercise of such a choice is morally defensible and does not constitute discrimination against those with disability, although the contrary is often asserted. The paper concludes that attempts to eradicate disability are not the same as attempts to eradicate the disabled, even where these attempts constitute preferring not to create new individuals with disability.
Newspaper coverage of maverick science: creating controversy through balancing
Authors: Dearing James W.
Published: August 2002

How do journalists portray the ideas of maverick scientists to the general public? Are mavericks portrayed as credible scientific sources? Do the stories written by journalists function to merely translate maverick theories for nonscientific audiences, or do they more often transform those maverick theories into the realm of scientific controversies? This study hypothesized answers to these questions by analysing how journalists wrote about three maverick theories: (1) a 1990 earthquake prediction, (2) an alternative theory about the cause of AIDS, and (3) cold fusion. A content analysis of 393 news articles in 26 US newspapers and a mailed survey of the journalists who wrote those stories suggest that scientific theories which are believed to be credible by a minority of scientists may be lent credibility in mass media stories, even though the journalists themselves thought that the maverick scientists lacked credibility. Implications for the communication of risk through the mass media are discussed.
Reporters, news sources, and scientific intervention: the New Madrid earthquake prediction
Authors: Smith Conrad
Published: August 2002

Five major newspapers in the United States published only eight stories about a scientifically legitimate prediction of a 1989 earthquake that caused six billion dollars' damage. The same newspapers published 68 stories about an unscientific prediction of a 1990 earthquake that did not occur. This paper attempts to explain why the unscientific prediction received more scrutiny by examining the journalistic practices that determine what is newsworthy and who is interviewed. The paper also analyses the effectiveness of an organized effort by the scientific community to intervene in the journalistic process.
Social rationality, risk, and the right to know: information leveraging with the Toxics Release Inventory
Authors: Goshorn Kent
Published: August 2002

Citizens endangered by toxic wastes and airborne pollutants have long been disadvantaged by a lack of information about the nature and extent of pollution, and their own limited ability to interpret what technical risk data was available. As a grassroots movement demanding the `right to know' about toxic emissions in their neighbourhoods emerged in the USA, federal legislation and the Toxics Release Inventory (TRI) compelled certain facilities to document their yearly emissions of various chemicals, and made this information available to the general public through an online database. Publication of this relatively `raw' data successfully pressured industry to reduce emissions, but also raised predictable questions about the ability of `non-expert' public interest groups to interpret the data, even though in many cases industry itself was remarkably under-informed. This paper draws on Beck's notion of the `risk society' in exploring the tension that arises between narrow scientific rationality and more flexible `social' rationality in approaches to risk reduction, as information technologies open up public access to technical data. The TRI shows the potential for public information to upset traditional power relationships predicated on techno-scientific expertise and sustained by industrial privacy. A somewhat simplistic `rhetoric of numbers' (used by both sides) was at first fostered by the simple quantitative nature of the data, but concern about non-expert, `unscientific' use of such data is found to be premature, as skilled activists linked by computer networks become adept at interpreting the information while using it to point to critical yet untested assumptions underlying scientific risk assessment. Diversified usage and multiple, contested perspectives on the data upgrade its quality and can enhance the overall rationality of the industrial/social system in which risks are generated.
When scientists turn to the public: alternative routes in science communication
Authors: Bucchi Massimiano
Published: August 2002

This paper argues that both the traditional normative models and the more refined (`continuity') models of public communication of science fail to account adequately for cases of `deviation', i.e. those cases when scientists address the public directly by skipping the usual stages of scientific communication. It is hypothesized that most of such cases are related to crisis situations and to the definition of scientific boundaries. Therefore, at least two modalities of public communication of science should be distinguished: one is the routine, generally unproblematic itinerary of a scientific idea through the different levels of communication as presented by the continuity models; and the other is the dramatic (re)assessment of boundaries and professional competences in the public arena that is required by marginal situations. Continuity models need to be supplemented by a multilevel, multivariate model which enables us to explain this second modality and to understand in more detail the role that the level of public communication plays when such a modality is activated.
Reactions to information about genetic engineering: impact of source characteristics, perceived personal relevance, and persuasiveness
Authors: Frewer Lynn J. , Howard Chaya , Hedderley Duncan , Shepherd Richard
Published: August 2002

There is a need to develop effective communication strategies with the public about the risks and benefits of applied genetic engineering. The Elaboration Likelihood Model was used to systematically investigate the impact of source factors (trust) and the perceived personal relevance of information, including the persuasiveness of the information, on attitudes towards genetic engineering, and whether these factors resulted in more thoughts about genetic engineering. The results from 160 respondents indicated an interaction between source effects and persuasiveness. People tended to respond more to information low in persuasiveness if it was attributed to a highly trusted source, and more to information high in persuasiveness if it were from a source low in public trust. In this context, respondents tended to express concern about the technology. It was concluded that source characteristics are important determinants of public responses to information about genetic engineering.
Understanding understanding: a model for the public learning of radioactivity
Authors: Alsop Steve
Published: August 2002

While much of the work in the public understanding of science has focused on the public's appreciation of science and their familiarity with key scientific concepts, understanding the processes involved in learning science has largely been ignored. This article documents a study of how particular members of the public learn about radiation and radioactivity, and proposes a model to describe their learning—the Informal Conceptual Change Model [ICCM]. ICCM is a multidimensional framework that incorporates three theoretical dimensions—the cognitive, conative, and affective. The paper documents each of these dimensions, and then illustrates the model by drawing upon data collected in a case study. The emphasis of the analysis is on understanding how the members of the public living in an area with high levels of background radiation learn about the science of this potential health threat. The summarizing comments examine the need for a greater awareness of the complexities of informal learning.
Heat and hot air: influence of local temperature on journalists' coverage of global warming
Authors: Shanahan James , Good Jennifer
Published: August 2002

This study examines relationships between local temperature in two cities (New York and Washington, D.C.) and coverage of global climate change in their local newspapers (the Times and the Post). The results show that there are some relationships between local temperature and frequency of attention to climate issues, such that journalists are more likely to discuss climate during unusually warm periods. However, support for the hypotheses was only partial; the Post did not show confirming relationships. The discussion focuses on implications for public understanding of climate change.