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Obstetrician & Gynecologist (OB/GYN)
43 years of experience
Accepting new patients

Credentials

Education ?

Medical School Score Rankings
The University of Texas Southwestern (1969)
  •  
Top 25%

Awards & Distinctions ?

Awards  
Patients' Choice Award (2008 - 2011)
Associations
American Board of Obstetrics and Gynecology

Affiliations ?

Dr. Wood is affiliated with 10 hospitals.

Hospital Affiliations

Score

Rankings

  • Texas Health Harris Methodist Hospital Southwest Fort Worth
    6100 Harris Pkwy, Fort Worth, TX 76132
    •  
    Top 25%
  • Harris Methodist H E B
    1600 Hospital Pkwy, Bedford, TX 76022
    •  
    Top 25%
  • Texas Health Arlington Memorial Hospital
    800 W Randol Mill Rd, Arlington, TX 76012
    •  
    Top 50%
  • Texas Health Harris Methodist Hospital Azle
    108 Denver Trl, Azle, TX 76020
    •  
    Top 50%
  • Texas Health Presbyterian Hospital Of Dallas
    8200 Walnut Hill Ln, Dallas, TX 75231
    •  
    Top 50%
  • Usmd Surgical Hospital Of Arlington
    801 W Interstate 20, Arlington, TX 76017
    •  
  • Harris Continued Care Hospital
    1301 Pennsylvania Ave, Fort Worth, TX 76104
  • Arlington Mem
  • Usmd
  • TX Health Arlington
  • Publications & Research

    Dr. Wood has contributed to 132 publications.
    Title Speciation of Oxaliplatin Adducts with Dna Nucleotides.
    Date January 2012
    Journal Metallomics : Integrated Biometal Science
    Excerpt

    This paper describes a set of fast and selective high performance liquid chromatography (HPLC) methods coupled to electro-spray ionisation linear ion trap mass spectrometry (ESI-MS), sector-field inductively coupled plasma mass spectrometry (SF-ICP-MS) and UV detection for in vitro studies of the bifunctional adducts of oxaliplatin with mono-nucleotides, di-nucleotides and cellular DNA. The stationary phases and the optimised conditions used for each separation are discussed. Interaction of oxaliplatin with A and G mono-nucleotides resulted in the formation of five bifunctional platinum diaminocyclohexane (DACHPt) adducts. These were two isomers of the A-DACHPt-A and A-DACHPt-G adducts, and one G-DACHPt-G adduct, as confirmed by MS/MS spectra obtained by collision induced dissociation. These adducts were also characterised by UV absorption data and SF-ICP-MS elemental (195)Pt and (31)P signals. Further, interaction of oxaliplatin with AG and GG di-nucleotides resulted in the formation of three adducts: DACHPt-GG and two isomers of the DACHPt-AG adduct, as confirmed by ESI-MS and the complementary data obtained by UV and SF-ICP-MS. Finally, a very sensitive LC-ICP-MS method for the quantification of oxaliplatin GG intra-strand adducts (DACHPt-GG) was developed and used for monitoring the in vitro formation and repair of these adducts in human colorectal cancer cells. The method detection limit was 0.14 ppb Pt which was equivalent to 0.22 Pt adduct per 10(6) nucleotides based on a 10 μg DNA sample. This detection limit makes this method suitable for in vivo assessment of DACHPt-GG adducts in patients undergoing oxaliplatin chemotherapy.

    Title Efficacy of Liquid Spray Decontaminants for Inactivation of Bacillus Anthracis Spores on Building and Outdoor Materials.
    Date July 2011
    Journal Journal of Applied Microbiology
    Excerpt

    To obtain data on the efficacy of various liquid and foam decontamination technologies to inactivate Bacillus anthracis Ames and Bacillus subtilis spores on building and outdoor materials.

    Title 'getting Back to Real Living': A Qualitative Study of the Process of Community Reintegration After Stroke.
    Date March 2011
    Journal Clinical Rehabilitation
    Excerpt

    To examine the process of community reintegration over the first year following stroke, from the patient's perspective.

    Title The Future of Emergency Medicine.
    Date February 2011
    Journal Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine
    Title Transition in Yield and Azimuthal Shape Modification in Dihadron Correlations in Relativistic Heavy Ion Collisions.
    Date February 2011
    Journal Physical Review Letters
    Excerpt

    Hard-scattered parton probes produced in collisions of large nuclei indicate large partonic energy loss, possibly with collective produced-medium response to the lost energy. We present measurements of π^{0} trigger particles at transverse momenta p{T}{t}=4-12  GeV/c and associated charged hadrons (p{T}{a}=0.5-7  GeV/c) vs relative azimuthal angle Δϕ in Au+Au and p+p collisions at sqrt[s{NN}]=200  GeV. The Au+Au distribution at low p{T}{a}, whose shape has been interpreted as a medium effect, is modified for p{T}{t}<7  GeV/c. At higher p{T}{t}, the data are consistent with unmodified or very weakly modified shapes, even for the lowest measured p{T}{a}, which quantitatively challenges some medium response models. The associated yield of hadrons opposing the trigger particle in Au+Au relative to p+p (I{AA}) is suppressed at high p{T} (I{AA}≈0.35-0.5), but less than for inclusive suppression (R{AA}≈0.2).

    Title Microglial Activation in the Visual Pathway in Experimental Glaucoma: Spatiotemporal Characterization and Correlation with Axonal Injury.
    Date January 2011
    Journal Investigative Ophthalmology & Visual Science
    Excerpt

    Glia are the main cellular CNS elements initiating defense mechanisms against destructive influences and promoting regenerative processes. The aim of the current work was to characterize the microglial response within the visual pathway in a rat model of experimental glaucoma and to correlate the microglial response with the severity of axonal degeneration.

    Title Elliptic and Hexadecapole Flow of Charged Hadrons in Au+au Collisions at Sq.rt(s(nn))=200  gev.
    Date January 2011
    Journal Physical Review Letters
    Excerpt

    Differential measurements of the elliptic (v(2)) and hexadecapole (v(4)) Fourier flow coefficients are reported for charged hadrons as a function of transverse momentum (p(T)) and collision centrality or number of participant nucleons (N(part)) for Au+Au collisions at sq.rt(s(NN))=200  GeV. The v(2,4) measurements at pseudorapidity |η|≤0.35, obtained with four separate reaction-plane detectors positioned in the range 1.0<|η|<3.9, show good agreement, indicating the absence of significant Δη-dependent nonflow correlations. Sizable values for v(4)(p(T)) are observed with a ratio v(4)(p(T),N(part))/v(2)(2)(p(T),N(part))≈0.8 for 50≲N(part)≲200, which is compatible with the combined effects of a finite viscosity and initial eccentricity fluctuations. For N(part)≳200 this ratio increases up to 1.7 in the most central collisions.

    Title Environmental Persistence of a Highly Pathogenic Avian Influenza (h5n1) Virus.
    Date January 2011
    Journal Environmental Science & Technology
    Excerpt

    Human cases of disease caused by highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype are rare, yet characterized with a mortality rate of approximately 60%. Tests were conducted to determine the environmental persistence of an HPAI (H5N1) virus on four materials (glass, wood, galvanized metal, and topsoil) that could act as fomites or harbor the virus. Test coupons were inoculated with the virus and exposed to one of five environmental conditions that included changes in temperature, relative humidity, and simulated sunlight. At time periods up to 13 days, the virus was extracted from each coupon, and quantified via cytopathic effects on Madin-Darby canine kidney cells. The virus was most persistent under the low temperature condition, with less than 1 log reduction on glass and steel after 13 days at low relative humidity. Thus, at these conditions, the virus would be expected to persist appreciably beyond 13 days.

    Title Properties of Procoagulant Platelets: Defining and Characterizing the Subpopulation Binding a Functional Prothrombinase.
    Date December 2010
    Journal Arteriosclerosis, Thrombosis, and Vascular Biology
    Excerpt

    The goal of this study was to define and characterize the subpopulation of platelets capable of regulating the functional interactions of factors Va (FVa) and Xa (FXa) on the thrombin-activated platelet surface.

    Title The Future of Emergency Medicine.
    Date November 2010
    Journal The Journal of Emergency Medicine
    Excerpt

    BACKGROUND: The specialty of emergency medicine (EM) continues to experience a significant workforce shortage in the face of increasing demand for emergency care. SUMMARY: In July 2009, representatives of the leading EM organizations met in Dallas for the Future of Emergency Medicine Summit. Attendees at the Future of Emergency Medicine Summit agreed on the following: 1) Emergency medical care is an essential community service that should be available to all; 2) An insufficient emergency physician workforce also represents a potential threat to patient safety; 3) Accreditation Council for Graduate Medical Education/American Osteopathic Association (AOA)-accredited EM residency training and American Board of Medical Specialties/AOA EM board certification is the recognized standard for physician providers currently entering a career in emergency care; 4) Physician supply shortages in all fields contribute to-and will continue to contribute to-a situation in which providers with other levels of training may be a necessary part of the workforce for the foreseeable future; 5) A maldistribution of EM residency-trained physicians persists, with few pursuing practice in small hospital or rural settings; 6) Assuring that the public receives high quality emergency care while continuing to produce highly skilled EM specialists through EM training programs is the challenge for EM's future; 7) It is important that all providers of emergency care receive continuing postgraduate education.

    Title The Future of Emergency Medicine.
    Date October 2010
    Journal Journal of Emergency Nursing: Jen : Official Publication of the Emergency Department Nurses Association
    Excerpt

    Physician shortages are being projected for most medical specialties. The specialty of emergency medicine continues to experience a significant workforce shortage in the face of increasing demand for emergency care. The limited supply of emergency physicians, emergency nurses, and other resources is creating an urgent, untenable patient care problem. In July 2009, representatives of the leading emergency medicine organizations met in Dallas, TX, for the Future of Emergency Medicine Summit. This consensus document, agreed to and cowritten by all participating organizations, describes the substantive issues discussed and provides a foundation for the future of the specialty.

    Title Adsorption of Chlorine Dioxide Gas on Activated Carbons.
    Date October 2010
    Journal Journal of the Air & Waste Management Association (1995)
    Excerpt

    Research and field experience with chlorine dioxide (ClO2) gas to decontaminate structures contaminated with Bacillus anthracis spores and other microorganisms have demonstrated the effectiveness of this sterilant technology. However, because of its hazardous properties, the unreacted ClO2, gas must be contained and captured during fumigation events. Although activated carbon has been used during some decontamination events to capture the ClO2 gas, no data are available to quantify the performance of the activated carbon in terms of adsorption capacity and other sorbent property operational features. Laboratory experiments were conducted to determine and compare the ClO2 adsorption capacities of five different types of activated carbon as a function of the challenge ClO2 concentration. Tests were also conducted to investigate other sorbent properties, including screening tests to determine gaseous species desorbed from the saturated sorbent upon warming (to provide an indication of how immobile the ClO2 gas and related compounds are once captured on the sorbent). In the adsorption tests, ClO2 gas was measured continuously using a photometric-based instrument, and these measurements were verified with a noncontinuous method utilizing wet chemistry analysis. The results show that the simple activated carbons (not impregnated or containing other activated sorbent materials) were the most effective, with maximum adsorption capacities of approximately 110 mg/g. In the desorption tests, there was minimal release of ClO(2) from all sorbents tested, but desorption levels of chlorine (Cl2) gas (detected as chloride) varied, with a maximum release of nearly 15% of the mass of ClO2 adsorbed.

    Title Can Labs Give Emr Software to Referring Physicians?
    Date August 2010
    Journal Mlo: Medical Laboratory Observer
    Title Rapid and Delayed Death of Cultured Trabecular Meshwork Cells After Selective Laser Trabeculoplasty.
    Date August 2010
    Journal Lasers in Surgery and Medicine
    Excerpt

    Selective laser trabeculoplasty (SLT) is becoming increasingly employed to reduce elevated intraocular pressure in glaucoma patients. SLT is known to target the ocular trabecular meshwork (TM), but the exact response mechanisms to this treatment have not been clearly delineated. The aim of the present study, therefore, was to investigate the modes of death of cultured bovine TM cells subjected to SLT in vitro.

    Title The Future of Emergency Medicine.
    Date August 2010
    Journal Annals of Emergency Medicine
    Title A Comparison of Differentiation Protocols for Rgc-5 Cells.
    Date August 2010
    Journal Investigative Ophthalmology & Visual Science
    Excerpt

    PURPOSE. Although the RGC-5 cell line is widely used in retinal ganglion cell (RGC) research, recent data have raised questions about the nature of these cells. The authors performed a systematic analysis of RGC-5 cells to determine which RGC or neuronal markers are expressed after treatment with known differentiating agents, thus providing further insight into the nature of these cells and assisting in defining their future use. METHODS. RGC-5 cells were treated for 5 days with staurosporine (STSN; 316 nM), trichostatin A (TSA; 500 nM), or succinyl-concanavalin A (sConA; 50 microg/mL), after which they were assayed for specific marker antigen/mRNA expression. Treated cells were also assayed for excitotoxic responsiveness. RESULTS. Neither treated nor untreated RGC-5 cells expressed any specific RGC marker mRNAs or proteins (Brn-3, neurofilaments, Thy-1) or calbindin, calretinin, synaptophysin, PKCalpha, or glial fibrillary acidic protein. However, control RGC-5 cells did express the neuronal markers tau, betaIII-tubulin, microtubule-associated protein (MAP)-1b, MAP2, and PGP9.5. Although treatment with sConA had no effect on the expression of these markers, STSN and (dose dependently) TSA increased their expression and induced excitotoxic responsiveness. All cells, treated or not, expressed high levels of nestin but no other progenitor cell markers. All cells also expressed cone-specific, but not rod-specific, opsin indicative of cone photoreceptor lineage. CONCLUSIONS. RGC-5 cells expressed neuronal, but not RGC-specific, markers that were dose dependently upregulated by TSA. Hence, TSA provided the best tested means to terminally differentiate the cells to a neuronal phenotype from a precursor-like lineage.

    Title Stark and Anti-kickback Laws Limit Lab-marketing Methods.
    Date July 2010
    Journal Mlo: Medical Laboratory Observer
    Title The Effect of Hyperglycemia on Hypoperfusion-induced Injury.
    Date April 2010
    Journal Investigative Ophthalmology & Visual Science
    Excerpt

    Purpose. Because of differences in energy metabolism between the brain and retina, the hypothesis for the study was that, in a model of ocular and cerebral hypoperfusion, the retina would be protected by short-term hyperglycemia, whereas brain injury would be exacerbated. Methods. Hyperglycemia was induced by intraperitoneal streptozotocin. An initial experiment determined the effect of hyperglycemia alone in sham-surgery rats. Simultaneous retinal and cerebral hypoperfusion was achieved by two-vessel occlusion (2VO; permanent ligation of both common carotid arteries). Hyperglycemia was induced 3 days before 2VO by streptozotocin injection. The rats were killed 7 days after 2VO or sham surgery. The retina of one eye was collected for histology/immunohistochemistry and the fellow retina was collected for real-time RT-PCR. The retinas were analyzed for neuronal and glial markers and heat shock protein-27. The brains were processed for histology and immunohistochemistry. Results. Short-term (approximately 10 days) hyperglycemia alone caused no discernible injury to the retina. The retinas of the normoglycemic 2VO animals showed a marked loss of retinal ganglion cells and horizontal cells, thinning of the inner retina, glial cell activation, and infiltration of macrophages. The hyperglycemic 2VO rats displayed remarkable protection of the retinal structure and reduced glial cell activation compared with the normoglycemic 2VO animals. There was a significantly greater number of heat shock protein-27-positive retinal ganglion cells in the normoglycemic animals than in the hyperglycemic ones. Brains of both the normoglycemic and hyperglycemic 2VO animals displayed scattered ischemic infarcts and mild white matter injury. Conclusions. Short-term hyperglycemia affords robust protection against retinal hypoperfusion injury, but in the same animals, brain injury is not ameliorated. The mechanism of this retinal hyperglycemia-induced neuroprotection requires further study.

    Title Spatiotemporal Characterization of Optic Nerve Degeneration After Chronic Hypoperfusion in the Rat.
    Date March 2010
    Journal Investigative Ophthalmology & Visual Science
    Excerpt

    Permanent, bilateral occlusion of the common carotid arteries (2VO) is an established model of chronic hypoperfusion. Previous studies have noted the vulnerability of the optic nerve (ON) to 2VO; however, little information is available regarding the spatiotemporal pattern of axonal degeneration and the accompanying glial cell responses. The present study was conducted to investigate these topics.

    Title Correlation of Sonographic Measurements of the Internal Jugular Vein with Central Venous Pressure.
    Date September 2009
    Journal The American Journal of Emergency Medicine
    Excerpt

    Determination of volume status is crucial in treating acutely ill patients. This study examined bedside ultrasonography of the internal jugular vein (IJV) to predict central venous pressure (CVP). Ultrasonography was performed on 34 nonventilated patients with monitored CVPs. The IJV was measured during the respiratory cycle and with the patient in different positions. Mean IJV diameter in patients with CVP less than 10 cm H2O was 7.0 mm (95% confidence interval [CI], 5.7-8.3) vs 12.5 mm (95% CI, 11.2-13.8) in patients with CVP of 10 cm H2O and greater. Measurement of end expiratory diameter with the patient supine had the highest correlation coefficient: 0.82 (95% CI). There was strong agreement among ultrasonographers: correlation coefficient, 0.92 (95% CI). This pilot study shows promise that ultrasonography of the IJV can be a noninvasive tool to predict CVP. Measurement of end expiratory diameter in supine patients exhibited a high correlation to CVP.

    Title Recharacterization of the Rgc-5 Retinal Ganglion Cell Line.
    Date September 2009
    Journal Investigative Ophthalmology & Visual Science
    Excerpt

    The transformed RGC-5 retinal ganglion cell line is used widely in glaucoma research. Increased resistance to glutamate was noted in published literature and led to the recharacterization of the RGC-5 cell line.

    Title Evaluation of Fluoro-jade C As a Marker of Degenerating Neurons in the Rat Retina and Optic Nerve.
    Date May 2009
    Journal Experimental Eye Research
    Excerpt

    Detection of neuronal death is an essential requirement for researchers investigating retinal degeneration. Fluoro-Jade C (FJC) is a novel, fluorescent dye that has been successfully used to label degenerating neurons in the brain, but its effectiveness in the eye has not been ascertained. In the current study, we determined the efficacy of FJC for detection of neuronal degeneration in the retina and optic nerve in various paradigms of injury. N-methyl-D-aspartate (NMDA) and kainic acid-induced excitotoxicity, optic nerve transection, and bilateral occlusion of the common carotid arteries (BCCAO) were performed using standard techniques. Rats were killed at various time points and the retinas with optic nerves attached were removed for tissue processing prior to labelling for FJC, for DNA fragmentation by TUNEL or for immunohistochemical analysis. Retinas from RCS rats of different ages were also analysed. After excitotoxicity-induced injury, cell bodies and dendrites within the ganglion cell and inner plexiform layers were specifically labelled by FJC within 6h, a time point comparable to the appearance of TUNEL-positive nuclei and to reductions in mRNA levels of retinal ganglion cell-specific proteins, but in advance of alterations in some immunohistochemical markers. The number of FJC-labelled cell bodies in the retina declined over time as cell loss proceeded, although dendritic staining remained prominent. Colocalisation of FJC with TUNEL and with immunohistochemical neuronal markers was achieved. FJC was successful at identifying somato-dendritic degeneration following ischemia induced by BCCAO, but surprisingly, not after optic nerve transection. FJC visualised photoreceptor degeneration in the RCS rat, albeit less effectively than with the TUNEL assay, and was also effective for imaging and quantifying degenerating axons in the optic nerve after multiple injuries. In addition to labelling degenerating neurons, however, FJC also bound non-specifically to astrocytes and to blood cells in unperfused rats. Since the ganglion cell layer is adjacent to astrocytes within the nerve fibre layer, caution is needed when using FJC as a quantitative tool for detecting ganglion cell death.

    Title Development and Field Testing of a Mobile Chlorine Dioxide Generation System for the Decontamination of Buildings Contaminated with Bacillus Anthracis.
    Date May 2009
    Journal Journal of Hazardous Materials
    Excerpt

    The numerous buildings that became contaminated with Bacillus anthracis (the bacterium causing the disease anthrax) in 2001, and more recent B. anthracis - related events, point to the need to have effective decontamination technologies for buildings contaminated with biological threat agents. The U.S. Government developed a portable chlorine dioxide (ClO(2)) generation system to decontaminate buildings contaminated with B. anthracis spores, and this so-called mobile decontamination trailer (MDT) prototype was tested through a series of three field trials. The first test of the MDT was conducted at Fort McClellan in Anniston, AL. during October 2004. Four test attempts occurred over two weekends; however, a number of system problems resulted in termination of the activity prior to any ClO(2) introduction into the test building. After making several design enhancements and equipment changes, the MDT was subjected to a second test. During this test, extensive leak checks were made using argon and nitrogen in lieu of chlorine gas; each subsystem was checked for functionality, and the MDT was operated for 24h. This second test demonstrated the MDT flow and control systems functioned satisfactorily, and thus it was decided to proceed to a third, more challenging field trial. In the last field test, ClO(2) was generated and routed directly to the scrubber in a 12-h continuous run. Measurement of ClO(2) levels at the generator outlet showed that the desired production rate was not achieved. Additionally, only one of the two scrubbers performed adequately with regard to maintaining ClO(2) emissions below the limit. Numerous lessons were learned in the field trials of this ClO(2) decontamination technology.

    Title "holding Me Back": Living with Arthritis While Recovering from Stroke.
    Date March 2009
    Journal Archives of Physical Medicine and Rehabilitation
    Excerpt

    To describe the experience of living with arthritis while recovering from stroke.

    Title A Paraneoplastic Manifestation of Metastatic Breast Cancer Responding to Endocrine Therapy: a Case Report.
    Date February 2009
    Journal World Journal of Surgical Oncology
    Excerpt

    Many cancers are known to be associated with paraneoplastic syndromes. These syndromes are usually treated by chemotherapy with or without immunosupression but they often respond poorly. There are no published reviews on response to endocrine treatment.

    Title Why Your Lease is an Important Asset.
    Date January 2009
    Journal Journal of the California Dental Association
    Excerpt

    The authors represent more than 3,500 dentists in California and have utilized their experience, knowledge and actual client examples to provide a thorough guide to protecting your future income and sale of your dental practice. This article is intended to provide an in-depth prospective of the value of the lease for your dental practice.

    Title Pilot-scale Experimental and Theoretical Investigations into the Thermal Destruction of a Bacillus Anthracis Surrogate Embedded in Building Decontamination Residue Bundles.
    Date December 2008
    Journal Environmental Science & Technology
    Excerpt

    Bacillus anthracis (B. anthracis) spores were released through the U.S. mail system in 2001, highlighting the need to develop efficacious methods of decontaminating and disposing of materials contaminated with biological agents. Incineration of building decontamination residue is a disposal option for such material, although the complete inactivation of bacterial spores via this technique is not a certainty. Tests revealed that under some circumstances, Geobacillus stearothermophilus (G. stearothermophilus; a surrogate for B. anthracis) spores embedded in building materials remained active after 35 min in a pilot-scale incinerator and survived with internal material bundle temperatures reaching over 500 degrees C. A model was also developed to predict survival of a bacterial spore population undergoing thermal treatment in an incinerator using the thermal destruction kinetic parameters obtained in a laboratory setting. The results of the pilot-scale incinerator experiments are compared to model predictions to assess the accuracy of the model.

    Title Bioenergetic-based Neuroprotection and Glaucoma.
    Date October 2008
    Journal Clinical & Experimental Ophthalmology
    Excerpt

    Primary open-angle glaucoma (POAG) is a pressure-sensitive optic neuropathy which results in the death of retinal ganglion cells and causes associated loss of vision. Presently, the only accepted treatment strategy is to lower the intraocular pressure; however, for some patients this is insufficient to prevent progressive disease. Although the pathogenesis of POAG remains unclear, there is considerable evidence that energy failure at the optic nerve head may be involved. Neuroprotection, a strategy which directly enhances the survival of neurons, is desirable, but remains clinically elusive. One particular form of neuroprotection involves the notion of enhancing the energy supply of neurons. These 'bioenergetic' methods of neuroprotection have proven successful in animal models of other neurodegenerative diseases and conditions, including Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and traumatic brain injury, but have been relatively unexplored in glaucoma models. This review focuses on some of the potential approaches for bioenergetic neuroprotection in the retina, including increasing the energy buffering capacity of damaged cells, decreasing the permeability of the mitochondrial membrane pore and free radical scavenging.

    Title In-vivo Evaluation of the Biophysio Valve Prosthesis in the Aortic Position.
    Date May 2008
    Journal The Journal of Heart Valve Disease
    Excerpt

    The new BioPhysio aortic prosthesis is a pericardial valve with a flexible stent that can be implanted with a single suture line. The study aim was to evaluate the in-vivo implantation characteristics, preservation of dynamic motion of the aortic root, and hemodynamic performance of this bioprosthesis.

    Title The Influence of Visible Light Exposure on Cultured Rgc-5 Cells.
    Date May 2008
    Journal Molecular Vision
    Excerpt

    To determine the effects of visible light on normal or metabolically compromised cultured rat RGC-5 cells.

    Title The Influence of Visible Light Exposure on Cultured Rgc-5 Cells.
    Date March 2008
    Journal Molecular Vision
    Excerpt

    To determine the effects of visible light on normal or metabolically compromised cultured rat RGC-5 cells.

    Title Expression of Osteopontin in the Rat Retina: Effects of Excitotoxic and Ischemic Injuries.
    Date March 2008
    Journal Investigative Ophthalmology & Visual Science
    Excerpt

    The cytokine osteopontin (OPN) has been localized to the retinal ganglion cell layer in the normal rodent retina, prompting the suggestion that it could serve as a useful marker for identifying and quantifying such neurons in models of retinal and optic nerve neurodegeneration. In the present study, we characterized the time course and cellular localization of OPN expression in the rat retina after excitotoxic and ischemic injuries.

    Title Pharmacological Neuroprotection for Glaucoma.
    Date July 2007
    Journal Drugs
    Excerpt

    Glaucoma represents a group of neurodegenerative diseases characterised by structural damage to the optic nerve and slow, progressive death of retinal ganglion cells (RGCs). Elevated intraocular pressure is traditionally considered to be the most important risk factor for glaucoma, and treatment options for the disease have hitherto been limited to its reduction. However, visual field loss and RGC death continue to occur in patients with well controlled intraocular pressures and, thus, a consensus has recently emerged that additional treatment strategies are needed. One such strategy is pharmacological neuroprotection, which in the context of glaucoma, refers to the situation in which a drug is deployed to interact with neuronal or glial elements within the retina/optic nerve head and thereby facilitate the survival of RGCs. The advent of animal models of chronic glaucoma has enhanced our understanding of many of the pathological processes occurring in glaucoma and, in doing so, described logical targets for pharmacological intervention. Such targets, which have been manipulated with varying degrees of success in relevant animal paradigms include glutamate receptors, autoimmune elements, neurotrophin deprivation, nitric oxide synthesis, oxidative stress products, sodium and calcium channels, heat shock proteins and apoptotic pathways. With exciting data now emerging from many research laboratories, it is obvious that pharmacological neuroprotection for glaucoma without doubt represents an exciting development in the search for a treatment modality for this debilitating disease.

    Title Visible Light Affects Mitochondrial Function and Induces Neuronal Death in Retinal Cell Cultures.
    Date June 2007
    Journal Vision Research
    Excerpt

    The aim of this study was to provide "proof of principle" for the hypothesis that light would have a detrimental influence on ganglion cells in certain situations, like in glaucoma, by directly impinging on the many mitochondria in their axons within the globe. In this study primary rat retinal cultures and freshly isolated liver mitochondria were exposed to light (400-760 nm; 500-4000 lux) as entering the eye. For culture assessment, 3,(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and 4-[3-(-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetzolio]-1,3-benzene disulfonate (WST-1) reduction assays were used to assess cell and mitochondrial viability, respectively. Furthermore, cultures were stained for reactive oxygen species (ROS), DNA breakdown, numbers of GABA-immunoreactive (IR) cells and caspase-3 content to provide information concerning the effect of light on neuronal survival. Uptake of (3)H-GABA by autoradiography was also used, to assess the effects of light on the energy status of neurons. Light, in an intensity-dependent and trolox-inhibitable manner, reduced cell viability, affected mitochondrial function, increased the number of TUNEL-positive cells, decreased the numbers of GABA-IR neurons and enhanced labelling for ROS. These effects were all exacerbated by the absence of serum. There was also an increased caspase-3 protein content and a reduction of (3)H-GABA uptake in light- compared with dark-treated cultures. These findings support the hypothesis that light can affect mitochondria which could lead to neuronal apoptosis if the energetic status of these neurons is already compromised.

    Title Assessment of Emergency Medical Technicians Serving the Phoenix Metropolitan Matrix of Primary Stroke Centers.
    Date June 2007
    Journal Stroke; a Journal of Cerebral Circulation
    Title Protein Kinase C-mediated Modulation of Glutamate Transporter Activity in Rat Retina.
    Date April 2007
    Journal Current Eye Research
    Excerpt

    It has previously been shown that inhibitors of protein kinase C (PKC) attenuate retinal glutamate uptake in situ. The aim of the current study was to determine whether PKCdelta-mediated inhibition differentially reduces the transport of glutamate into retinal Müller cells when compared with retinal neurons. The influence of two different types of PKC inhibitors on the uptake of [3H]D-aspartate was therefore compared in the intact retina, mixed retinal cultures, and Müller cell-enriched retinal cultures. It was found that 25 microM of the pan-isoform PKC inhibitor, chelerythrine, reduced [3H]D-aspartate uptake by 78%, 71%, and 68% in isolated retinas, mixed neuronal/glial cultures, and Müller cell-enriched cultures, respectively. Importantly, 20 microM of the PKCdelta-selective inhibitor rottlerin also reduced the uptake of D-aspartate to similar extents in all three systems, and the reductions were statistically similar to those found for the pan-specific PKC inhibitor. Neither pan-isoform nor PKCdelta-selective activators stimulated glutamate uptake in either culture system or the intact retina. The current results suggest that specific PKC inhibitors are quantitatively similar in reducing the uptake of glutamate into retinal neurons and Müller cells.

    Title Glutamate Excitotoxicity in Glaucoma: Truth or Fiction? By Aj Lotery.
    Date March 2007
    Journal Eye (london, England)
    Title Partial Mitochondrial Complex I Inhibition Induces Oxidative Damage and Perturbs Glutamate Transport in Primary Retinal Cultures. Relevance to Leber Hereditary Optic Neuropathy (lhon).
    Date January 2007
    Journal Neurobiology of Disease
    Excerpt

    Leber Hereditary Optic Neuropathy (LHON) is a maternally inherited form of visual loss, due to selective degeneration of retinal ganglion cells. Despite the established aetiological association between LHON and mitochondrial DNA mutations affecting complex I of the electron transport chain, the pathophysiology of this disorder remains obscure. Primary rat retinal cultures were exposed to increasing concentrations of rotenone to titrate complex I inhibition. Neural cells were more sensitive than Müller glial cells to rotenone toxicity. Rotenone induced an increase in mitochondrial-derived free radicals and lipid peroxidation. Sodium-dependent glutamate uptake, which is mostly mediated by the glutamate transporter GLAST expressed by Müller glial cells, was reduced dose-dependently by rotenone with no changes in GLAST expression. Our findings suggest that complex I-derived free radicals and disruption of glutamate transport might represent key elements for explaining the selective retinal ganglion cell death in LHON.

    Title [endovascular Interventions of the Descending Thoracic Aorta].
    Date December 2006
    Journal Herz
    Excerpt

    Endovascular interventions of the descending thoracic aorta have been established as an alternative to conventional open surgery. Initially, they were limited to elective patients with a high risk profile for open surgery, but soon their use was extended to emergencies as well. In the elective setting, endovascular interventions significantly lowered short-term morbidity and mortality. These excellent perioperative results were reproducible in the emergency setting, thereby leading to superior outcomes for patients treated by endovascular stent grafts when compared to the conventional open surgical approach. However, some questions regarding long-term durability of these devices remain unanswered. Stent-graft failures at mid and long-term follow-up have been reported in the literature. The progressive nature of stent graft-related mid- and long-term complications stresses the need for continued surveillance of these patients.

    Title Why an Attorney Cannot Represent Both Sides of a Practice Sale.
    Date September 2006
    Journal Journal of the California Dental Association
    Excerpt

    This article is designed to point out select problems dentists may encounter when two or more dentists in a transaction seek to have the same attorney represent all of their interests.

    Title Pathogenesis of Retinal Ganglion Cell Death in Leber Hereditary Optic Neuropathy (lhon): Possible Involvement of Mitochondria, Light and Glutamate.
    Date August 2006
    Journal Mitochondrion
    Title Mr Cholangiopancreatography in the Detection of Symptomatic Ectopic Pancreatitis in the Small-bowel Mesentery.
    Date August 2006
    Journal Ajr. American Journal of Roentgenology
    Title Pericardial Patch Augmentation for Reconstruction of Incompetent Bicuspid Aortic Valves.
    Date August 2006
    Journal The Annals of Thoracic Surgery
    Excerpt

    Reoperation rates after repair of bicuspid aortic valves are higher than for mitral valve reconstruction. Secondary changes and small coaptation surface render repair unreliable. Satisfactory results have been reported for patch augmentation for tricuspid aortic valves. We have applied this technique for the repair of bicuspid aortic valves.

    Title The Beta-adrenergic Receptor Antagonist Metipranolol Blunts Zinc-induced Photoreceptor and Rpe Apoptosis.
    Date August 2006
    Journal Investigative Ophthalmology & Visual Science
    Excerpt

    To determine the effect of zinc on retinal cells at concentrations at which it is known to cause oxidative stress. Furthermore, the effects of metipranolol, known to prevent retinal damage, and of other antiglaucoma drugs were determined on zinc-injured retinal cells.

    Title Affinity of Molecular Interactions in the Bacteriophage Phi29 Dna Packaging Motor.
    Date May 2006
    Journal Nucleic Acids Research
    Excerpt

    DNA packaging in the bacteriophage phi29 involves a molecular motor with protein and RNA components, including interactions between the viral connector protein and molecules of pRNA, both of which form multimeric complexes. Data are presented to demonstrate the higher order assembly of pRNA together with the affinity of pRNA:pRNA and pRNA:connector interactions, which are used to propose a model for motor function. In solution, pRNA can form dimeric and trimeric multimers in a magnesium-dependent manner, with dissociation constants for multimerization in the micromolar range. pRNA:connector binding is also facilitated by the presence of magnesium ions, with a nanomolar apparent dissociation constant for the interaction. From studies with a mutant pRNA, it appears that multimerization of pRNA is not essential for connector binding and it is likely that connector protein is involved in the stabilization of higher order RNA multimers. It is proposed that magnesium ions may promote conformational change that facilitate pRNA:connector interactions, essential for motor function.

    Title Dentists Who Represent Themselves when Leasing Office Space Have Fools for Clients.
    Date May 2006
    Journal Journal of the California Dental Association
    Title Left Ventricular Remodeling Impacts the Function of the Quattro Stentless Mitral Valve Bioprosthesis (a 4-year Experience).
    Date April 2006
    Journal American Heart Journal
    Excerpt

    The St Jude Quattro stentless mitral valve prosthesis (QMV) is sutured to the mitral annulus and the papillary muscle heads, thereby preserving the subvalvular apparatus. After mitral valve replacement, remodeling of the left ventricle is often observed, causing a dilated ventricle to shrink in diameter. It was our objective to assess these changes in left ventricular (LV) geometry and evaluate its effects on the function of the QMV.

    Title Second Symposium on the Definition and Management of Anaphylaxis: Summary Report--second National Institute of Allergy and Infectious Disease/food Allergy and Anaphylaxis Network Symposium.
    Date March 2006
    Journal Annals of Emergency Medicine
    Excerpt

    There is no universal agreement on the definition of anaphylaxis or the criteria for diagnosis. In July 2005, the National Institute of Allergy and Infectious Disease and Food Allergy and Anaphylaxis Network convened a second meeting on anaphylaxis, which included representatives from 16 different organizations or government bodies, including representatives from North America, Europe, and Australia, to continue working toward a universally accepted definition of anaphylaxis, establish clinical criteria that would accurately identify cases of anaphylaxis with high precision, further review the evidence on the most appropriate management of anaphylaxis, and outline the research needs in this area.

    Title Second Symposium on the Definition and Management of Anaphylaxis: Summary Report--second National Institute of Allergy and Infectious Disease/food Allergy and Anaphylaxis Network Symposium.
    Date March 2006
    Journal The Journal of Allergy and Clinical Immunology
    Excerpt

    There is no universal agreement on the definition of anaphylaxis or the criteria for diagnosis. In July 2005, the National Institute of Allergy and Infectious Disease and Food Allergy and Anaphylaxis Network convened a second meeting on anaphylaxis, which included representatives from 16 different organizations or government bodies, including representatives from North America, Europe, and Australia, to continue working toward a universally accepted definition of anaphylaxis, establish clinical criteria that would accurately identify cases of anaphylaxis with high precision, further review the evidence on the most appropriate management of anaphylaxis, and outline the research needs in this area.

    Title A Hypothesis to Suggest That Light is a Risk Factor in Glaucoma and the Mitochondrial Optic Neuropathies.
    Date February 2006
    Journal The British Journal of Ophthalmology
    Excerpt

    The authors propose that light entering the eye interacts with retinal ganglion cell (RGC) axon mitochondria to generate reactive oxygen intermediates (ROI) and that when these neurons are in an energetically low state, their capacity to remove these damaging molecules is exceeded and their survival is compromised. They suggest that in the initial stages of glaucoma, RGCs exist at a low energy level because of a reduced blood flow at the optic nerve head and that in the mitochondrial optic neuropathies (MONs), this results from a primary, genetic defect in aerobic metabolism. In these states RGCs function at a reduced energy level and incident light on the retina becomes a risk factor. Preliminary laboratory studies support this proposition. Firstly, the authors have shown that light is detrimental to isolated mitochondria in an intensity dependent manner. Secondly, light triggers apoptosis of cultured, transformed RGCs and this effect is exacerbated when the cells are nutritionally deprived. Detailed studies are under way to strengthen the proposed theory. On the basis of this proposal, the authors suggest that patients with optic neuropathies such as glaucoma or at risk of developing a MON may benefit from the use of spectral filters and reducing the intensity of light entering the eye.

    Title Do Pulmonary Autografts Provide Better Outcomes Than Mechanical Valves? A Prospective Randomized Trial.
    Date December 2005
    Journal The Annals of Thoracic Surgery
    Excerpt

    The objective of this study was to compare the performance of pulmonary autografts with mechanical aortic valves, in the treatment of aortic valve stenosis.

    Title High-temperature Sorption of Cesium and Strontium on Dispersed Kaolinite Powders.
    Date October 2005
    Journal Environmental Science & Technology
    Excerpt

    Sorption of cesium and strontium on kaolinite powders was investigated as a means to minimize the emissions of these metals during certain high-temperature processes currently being developed to isolate and dispose of radiological and mixed wastes. In this work, nonradioactive aqueous cesium acetate or strontium acetate was atomized down the center of a natural gas flame supported on a variable-swirl burner in a refractory-lined laboratory-scale combustion facility. Kaolinite powder was injected at a postflame location in the combustor. Cesium readily vaporized in the high-temperature regions of the combustor, but was reactively scavenged onto dispersed kaolinite. Global sorption mechanisms of cesium vapor on kaolinite were quantified, and are related to those available in the literature for sodium and lead. Both metal adsorption and substrate deactivation steps are important, so there is an optimum temperature, between 1400 and 1500 K, at which maximum sorption occurs. The presence of chlorine inhibits cesium sorption. In contrast to cesium, and in the absence of chlorine, strontium was only partially vaporized and was, therefore, only partially scavengeable. The strontium data did not allow quantification of global kinetic mechanisms of interaction, although equilibrium arguments provided insight into the effects of chlorine on strontium sorption. These results have implications for the use of sorbents to control cesium and strontium emissions during high-temperature waste processing including incineration and vitrification.

    Title Aortic Leaflet Replacement with the New 3f Stentless Aortic Bioprosthesis.
    Date September 2005
    Journal The Annals of Thoracic Surgery
    Excerpt

    Clinical trials with the new 3F stentless aortic bioprosthesis began October 2001, and as one of the first centers to implant this prosthesis in humans, we would like to present our experiences with this new device.

    Title Monocarboxylate Transporter Expression Remains Unchanged During the Development of Diabetic Retinal Neuropathy in the Rat.
    Date September 2005
    Journal Investigative Ophthalmology & Visual Science
    Excerpt

    To determine the effect of diabetes on monocarboxylate transporter (MCT) expression in the rat retina.

    Title Invited Review: Neuroprotective Properties of Certain Beta-adrenoceptor Antagonists Used for the Treatment of Glaucoma.
    Date August 2005
    Journal Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics
    Excerpt

    Although it is known that ganglion cell death causes loss of vision in glaucoma, the pathogenesis of the disease is complex, probably involving an initial ischemic insult to the ganglion cell axons and glial cells with the ganglion cell bodies eventually being affected. It may therefore be necessary to blunt many stages in the pathogenesis of the disease to obtain a clinically effective neuroprotective strategy. In animal experiments, one cause of ganglion cell death in ischemia is an overactivation of glutamate receptors and a subsequent rise in intracellular levels of sodium and calcium ions as well as a generation of reactive oxygen species. In contrast, optic nerve death in ischemia is mainly caused by an influx of sodium and reversal of the sodium/calcium exchanger, which leads to a rise in intracellular calcium. Thus, a substance that reduces the influx of sodium will protect the ganglion cell axon, and if it also reduces calcium influx and/or acts as an antioxidant it will protect the ganglion cell body in addition. Of all antiglaucoma drugs, only beta-blockers have both calcium and sodium channel blocking activity, with betaxolol being the most efficacious of those analyzed. In addition, of the tested ophthalmic beta-blockers only metipranolol has powerful antioxidant properties. Moreover, laboratory studies on rats have shown that topically applied beta-blockers attenuate ischemic injury to ganglion cells by mechanisms that do not appear to involve an action on beta-receptors. Thus, of the substances used to lower intraocular pressure in glaucoma, beta-blockers have unique additional characteristics that also give them the capacity to act as neuroprotectants.

    Title Neuronal Death in Primary Retinal Cultures is Related to Nitric Oxide Production, and is Inhibited by Erythropoietin in a Glucose-sensitive Manner.
    Date June 2005
    Journal Journal of Neurochemistry
    Excerpt

    The aim of this work was to investigate the interrelated effects of glucose, nitric oxide (NO) and erythropoietin on neuronal survival in retinal cultures, thereby exploring the mechanism of neuronal death in the diabetic retina. Rat retinal cells were cultured in low (5 mM) or high (15 mM) glucose concentrations. After 9 days, cell viability was assessed by (3,4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and NO production was determined by the Griess reaction. Immunohistochemistry was used to quantify GABA-labelled neurones and cells staining for DNA breakdown. High or low glucose concentrations had no effect on basal NO production or the survival of neurones in culture, but treatment with N-nitro-L-arginine methyl ester reduced extracellular levels of NO and increased neuronal survival at both concentrations of glucose. Erythropoietin decreased cell death and NO levels, but only in cultures grown in low concentrations of glucose. It is concluded that erythropoietin's neurotrophic function in the retina is attenuated at glucose concentrations similar to those which occur in diabetes.

    Title Energy Substrate Requirements for Survival of Rat Retinal Cells in Culture: the Importance of Glucose and Monocarboxylates.
    Date June 2005
    Journal Journal of Neurochemistry
    Excerpt

    The process of metabolic coupling has been described as a means of providing additional fuel for neurons during periods of intense activity. This process has been suggested to occur in the mammalian retina, but whether retinal neurons can metabolise glial-derived monocarboxylates remains uncertain. The present study therefore sought to define the preferred energy substrates for maintenance of different retinal cells in culture, in order to clarify whether metabolic coupling can potentially occur in this tissue. All cells in rat retinal cultures were detrimentally affected by glucose deprivation. The effect on some neurons, however, could be partially reversed by 5 mm pyruvate or lactate. Furthermore, the glycolytic inhibitor, iodoacetic acid, caused a dose-dependent loss of all retinal cells in culture, whereas the mitochondrial inhibitor, 2,4-dinitrophenol, only led to a decrease in the number of neurons. Finally, inhibition of transporters for glucose or monocarboxylates caused the respective loss of glia or neurons from cultures. These data together demonstrate that, although cells do preferentially metabolise glucose, monocarboxylates such as lactate or pyruvate do play an important role in neuronal maintenance. These data therefore give partial support to the notion that metabolic coupling may occur in the retina.

    Title Optic Nerve and Neuroprotection Strategies.
    Date April 2005
    Journal Eye (london, England)
    Excerpt

    Experimental studies have yielded a wealth of information related to the mechanism of ganglion cell death following injury either to the myelinated ganglion cell axon or to the ganglion cell body. However, no suitable animal models exist where injury can be directed to the optic nerve head region, particularly the unmyelinated ganglion cell axons. The process of relating the data from the various animal models to many different types of optic neuropathies in man must, therefore, be cautious.

    Title Symposium on the Definition and Management of Anaphylaxis: Summary Report.
    Date April 2005
    Journal The Journal of Allergy and Clinical Immunology
    Title Emergency Endovascular Interventions for Acute Thoracic Aortic Rupture: Four-year Follow-up.
    Date April 2005
    Journal The Journal of Thoracic and Cardiovascular Surgery
    Excerpt

    High mortality and paraplegia rates associated with the surgical management of acute thoracic aortic ruptures limit its success. It was our objective to evaluate whether emergency endovascular interventions would improve the outcomes of these patients.

    Title Prevention of Glutathione Depletion-induced Apoptosis in Cultured Human Rpe Cells by Flupirtine.
    Date February 2005
    Journal Restorative Neurology and Neuroscience
    Excerpt

    We have recently reported that the non-opiate analgesic, flupirtine, counteracts apoptosis in cultures of human retinal pigmented epithelial (RPE) cells induced by deprivation of serum, oxygen and glucose (experimental ischaemia). In the present study, human RPE cells grown on coverslips were treated with buthionine sulphoxamine (BSO), a compound that inhibits glutathione biosynthesis. BSO caused a dose-dependent reduction in culture density and an increase in the number of cell nuclei that were positively labelled by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) procedure. These data show that reduction of glutathione levels causes apoptosis in the RPE cultures. When flupirtine gluconate was co-incubated with BSO, it dose-dependently prevented the induction of apoptosis. The most effective concentration of flupitine found to inhibit cell death caused by BSO (1 micro M - 1 mM) was 100 micro M. The presence of serum (2% or 10%) in the culture medium did not have any effect on the outcome of apoptosis and overall cell death caused by BSO. Futhermore, melatonin, also known to reduce experimental ischaemia-induced overall cell death and apoptosis of cultured RPE cells had only a mild protective effect at 1 mM. The combined data suggest that flupirtine prevents apoptosis by increasing the cellular levels of reduced glutathione and/or protects the cells against the damaging effects of reactive oxygen species (ROS) that are produced subsequent to inhibition of glutathione production.

    Title Expression of Monocarboxylate Transporters in Rat Ocular Tissues.
    Date February 2005
    Journal American Journal of Physiology. Cell Physiology
    Excerpt

    The aim of the present study was to determine the distribution of monocarboxylate transporter (MCT) subtypes 1-4 in the various structures of the rat eye by using a combination of conventional and real-time RT-PCR, immunoblotting, and immunohistochemistry. Retinal samples expressed mRNAs encoding all four MCTs. MCT1 immunoreactivity was observed in photoreceptor inner segments, Muller cells, retinal capillaries, and the two plexiform layers. MCT2 labeling was concentrated in the inner and outer plexiform layers. MCT4 immunolabeling was present only in the inner retina, particularly in putative Muller cells, and the plexiform layers. No MCT3 labeling could be observed. The retinal pigment epithelium (RPE)/choroid expressed high levels of MCT1 and MCT3 mRNAs but lower levels of MCT2 and MCT4 mRNAs. MCT1 was localized to the apical and MCT3 to the basal membrane of the RPE, whereas MCT2 staining was faint. Although MCT1-MCT4 mRNAs were all detectable in iris and ciliary body samples, only MCT1 and MCT2 proteins were expressed. These were present in the iris epithelium and the nonpigmented epithelium of the ciliary processes. MCT4 was localized to the smooth muscle lining of large vessels in the iris-ciliary body and choroid. In the cornea, MCT1 and MCT2 mRNAs and proteins were detectable in the epithelium and endothelium, whereas evidence was found for the presence of MCT4 and, to a lesser extent, MCT1 in the lens epithelium. The unique distribution of MCT subtypes in the eye is indicative of the pivotal role that these transporters play in the maintenance of ocular function.

    Title Methamphetamine Exacerbates the Toxic Effect of Kainic Acid in the Adult Rat Retina.
    Date December 2004
    Journal Neurochemistry International
    Excerpt

    The recreational use of the psychoactive drug, methamphetamine has increased markedly over the last three decades. It has long been known that this drug has detrimental effects upon the mammalian brain monoaminergic system, but the long- or short-term effects on the retina, a neurological extension of the central nervous system, have received little attention. The aim of this study was, therefore, to determine whether intraocular injection of methamphetamine (MA) is toxic to the healthy adult rat retina and to analyse its effects on the compromised retina after an injection of the ionotropic glutamate receptor agonist, kainate, which is known to cause retinal neuropathology. The equivalent of 1 mM (in the vitreous humour) MA and/or kainate (40 microM) were injected intravitreally. Flash electroretinograms (ERGs) were recorded before and 2 and 4 days after treatment. Five days after treatment, animals were killed and the retinas analysed either for the immunohistochemical localisation of various antigens or for electrophoresis/Western blotting. Some animals were kept for 19 days after treatment and the retinas analysed for tyrosine hydroxylase immunoreactivity. No differences could be found between vehicle- and MA-treated retinas with respect to the nature or localisation of either tyrosine hydroxylase immunoreactivity after 5 or 19 days or other antigens after 5 days. Moreover, the normal ERG and GFAP and calretinin protein antigens were unaffected by MA. Kainate treatment, however, caused a change in the ERGs after 2 and 4 days, an alteration in every antigen localised by immunohistochemistry and an increase in the retinal levels of calretinin and GFAP proteins. Significantly, the changes seen in the b-wave amplitude and implicit time of the ERG after 4 days and the increased level of GFAP protein after 5 days following kainate treatment were enhanced when MA was co-injected. Intravitreal injection of methamphetamine had no detectable detrimental effect on the normal adult rat retina but exacerbated the damaging effects of kainic acid. Such data suggest that a neurotoxic effect of MA may be more obviously illustrated when the tissue is already compromised as occurs in, for example, ischemia.

    Title Manifesto for the Creation of the Specialization of Emergency Medicine in Spain.
    Date December 2004
    Journal European Journal of Emergency Medicine : Official Journal of the European Society for Emergency Medicine
    Title Specialty Histology Labs Increase Risks.
    Date November 2004
    Journal Mlo: Medical Laboratory Observer
    Title Metipranolol Blunts Nitric Oxide-induced Lipid Peroxidation and Death of Retinal Photoreceptors: a Comparison with Other Anti-glaucoma Drugs.
    Date November 2004
    Journal Investigative Ophthalmology & Visual Science
    Excerpt

    To determine the effect of the nitric oxide donor sodium nitroprusside (SNP) on rat retinas and to see whether detrimental changes could be attenuated by known antiglaucoma drugs.

    Title Hypoglycaemia Exacerbates Ischaemic Retinal Injury in Rats.
    Date June 2004
    Journal The British Journal of Ophthalmology
    Excerpt

    To determine the effect of hypoglycaemia on ischaemic retinal injury.

    Title Effectiveness of Levobetaxolol and Timolol at Blunting Retinal Ischaemia is Related to Their Calcium and Sodium Blocking Activities: Relevance to Glaucoma.
    Date May 2004
    Journal Brain Research Bulletin
    Excerpt

    Glaucoma is a chronic optic neuropathy in which retinal ganglion cells die over a number of years. The initiation of the disease and its progression may involve an ischaemic-like insult to the ganglion cell axons caused by an alteration in the quality of blood flow. Thus, to effectively treat glaucoma it may be necessary to counteract the ischaemic-like insult to the region of the optic nerve head. Studies on the isolated optic nerve suggest that substances that reduce the influx of sodium would be particularly effective neuroprotectants. Significantly, of the presently used antiglaucoma substances, only beta-blockers can reduce sodium influx into cells. Moreover, they also reduce the influx of calcium and this would be expected to benefit the survival of insulted neurones. Betaxolol is the most effective antiglaucoma drug at reducing sodium/calcium influx. Our electroretinographic data indicated that topical application of levobetaxolol to rats attenuated the effects of ischaemia/reperfusion injury. Timolol was also effective but to a lesser extent. Based on these data we conclude that beta-blockers may be able to blunt ganglion cell death in glaucoma, and that levobetaxolol may be a more effective neuroprotectant than timolol because of its greater capacity to block sodium and calcium influx.

    Title Energy Substrate Requirements of Rat Retinal Pigmented Epithelial Cells in Culture: Relative Importance of Glucose, Amino Acids, and Monocarboxylates.
    Date April 2004
    Journal Investigative Ophthalmology & Visual Science
    Excerpt

    To determine the metabolic conditions that provide maintenance of viability for cultured rat RPE cells and to determine whether monocarboxylates such as lactate or pyruvate, which are known to exist at high concentrations in the subretinal space, can provide an alternative energy source to maintain cells when other nutritive supplies are limited.

    Title The Effect of Hyperglycemia on Experimental Retinal Ischemia.
    Date March 2004
    Journal Archives of Ophthalmology
    Excerpt

    To determine the effect of hyperglycemia and intraocular glucose delivery on ischemic retinal injury.

    Title Retinal Ischemia: Mechanisms of Damage and Potential Therapeutic Strategies.
    Date March 2004
    Journal Progress in Retinal and Eye Research
    Excerpt

    Retinal ischemia is a common cause of visual impairment and blindness. At the cellular level, ischemic retinal injury consists of a self-reinforcing destructive cascade involving neuronal depolarisation, calcium influx and oxidative stress initiated by energy failure and increased glutamatergic stimulation. There is a cell-specific sensitivity to ischemic injury which may reflect variability in the balance of excitatory and inhibitory neurotransmitter receptors on a given cell. A number of animal models and analytical techniques have been used to study retinal ischemia, and an increasing number of treatments have been shown to interrupt the "ischemic cascade" and attenuate the detrimental effects of retinal ischemia. Thus far, however, success in the laboratory has not been translated to the clinic. Difficulties with the route of administration, dosage, and adverse effects may render certain experimental treatments clinically unusable. Furthermore, neuroprotection-based treatment strategies for stroke have so far been disappointing. However, compared to the brain, the retina exhibits a remarkable natural resistance to ischemic injury, which may reflect its peculiar metabolism and unique environment. Given the increasing understanding of the events involved in ischemic neuronal injury it is hoped that clinically effective treatments for retinal ischemia will soon be available.

    Title The Effect of Retinal Ganglion Cell Injury on Light-induced Photoreceptor Degeneration.
    Date February 2004
    Journal Investigative Ophthalmology & Visual Science
    Excerpt

    To determine the effect of optic nerve transection (ONT) and excitotoxic retinal ganglion cell (RGC) injury on light-induced photoreceptor degeneration.

    Title Surgical Versus Endovascular Treatment of Acute Thoracic Aortic Rupture: a Single-center Experience.
    Date December 2003
    Journal The Annals of Thoracic Surgery
    Excerpt

    Surgical management of acute thoracic aortic ruptures is controversial, especially in patients with preexisting comorbidities; associated mortality and paraplegia rates remain high. It was our objective to evaluate whether treating these patients acutely with endovascular stent grafts would improve their outcome.

    Title Zinc and Energy Requirements in Induction of Oxidative Stress to Retinal Pigmented Epithelial Cells.
    Date November 2003
    Journal Neurochemical Research
    Excerpt

    In age-related macular degeneration (AMD), retinal pigmented epithelium (RPE) cells are believed to be detrimentally affected. It is thought that zinc may play a part in this process. In the past, therefore, zinc supplementation has been suggested as a treatment for AMD. Experimental data shown here confound this view by indicating that whereas low amounts of zinc do protect RPE cells in culture from stress-induced effects, greater amounts of zinc have the opposite influence. These effects are partly dependent upon the "health status" of the cells. Experimental data presented herein also show that zinc-induced death of RPE cells can, however, be attenuated by compounds such as antioxidants (alpha-tocopherol, trolox, and metipranolol), or cellular energy substrates (pyruvate and oxaloacetate). It is therefore concluded that a combination of zinc and antioxidants or energy substrates rather that zinc alone should provide a safer and more effective way to treat a disease such as AMD.

    Title The Clamshell Approach for the Treatment of Extensive Thoracic Aortic Disease.
    Date November 2003
    Journal The Journal of Thoracic and Cardiovascular Surgery
    Excerpt

    Management of extensive thoracic aortic disease may present an immense technical challenge. The choice of surgical access and subsequent exposure determines whether a single-stage or a 2-stage approach can be adopted.

    Title Beta-adrenergic Receptor Agonists and Antagonists Counteract Lps-induced Neuronal Death in Retinal Cultures by Different Mechanisms.
    Date November 2003
    Journal Brain Research
    Excerpt

    Treatment with lipopolysaccharide (LPS) for 72 h was shown to dose-dependently increase nitric oxide production from 6-day-old retinal cultures. Cell death, as determined by lactate dehydrogenase (LDH) release and an increase in neuronal labelling for TUNEL, was elevated concurrently. During treatment there was an increase of both inducible nitric oxide synthase and glial fibrillary acidic protein labelling in glial cells and a reduction in the number of gamma-aminobutyric acid-positive neurones. The NOS inhibitors, N-nitro-L-arginine methyl ester, dexamethasone and indomethacin potently inhibited both nitric oxide stimulation and cell death caused by LPS. In this study, the beta(2)- (ICI-18551), beta(1)- (betaxolol) and mixed beta(1)/beta(2)- (timolol, metipranolol) adrenergic receptor antagonists were all shown to attenuate LPS-induced LDH release from these cultures, but to have no effect on LPS-stimulated nitric oxide production. This effect was mimicked by the calcium channel blocker, nifedipine. Interestingly, the beta-adrenergic receptor agonists, salbutamol, arterenol and isoproterenol were also able to attenuate cell death caused by LPS. Moreover, these compounds also inhibited LPS-stimulated nitric oxide release. These studies suggest that LPS stimulates nitric oxide release from cultured retinal glial cells and that this process leads to neurone death. beta-adrenergic receptor agonists prevent the effects of LPS by inhibiting the stimulation of nitric oxide production. The data also suggest that beta-adrenergic receptor antagonists can attenuate LPS-induced death of neurones, but that these compounds act in a manner that is neurone-dependent, is mimicked by blockade of calcium channels and is independent of the stimulation of nitric oxide release.

    Title Emergent Endovascular Stent Grafting for Perforated Acute Type B Dissections and Ruptured Thoracic Aortic Aneurysms.
    Date September 2003
    Journal The Annals of Thoracic Surgery
    Excerpt

    The purpose of our study was to demonstrate the effectiveness of endovascular stent grafts in the treatment of acutely ruptured thoracic aortic aneurysms and type B dissections as an alternative to the conventional surgical approach in an emergency setting.

    Title Performance of Stentless Versus Stented Aortic Valve Bioprostheses in the Elderly Patient: a Prospective Randomized Trial.
    Date July 2003
    Journal European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery
    Excerpt

    Although stentless aortic bioprostheses are believed to offer improved outcomes, benefits remain unsubstantiated. The aim of our study was to compare stentless with stented bioprostheses, with regard to postoperative changes in left ventricular mass and hemodynamic performance, in the elderly patient.

    Title Alpha-lipoic Acid Protects the Retina Against Ischemia-reperfusion.
    Date June 2003
    Journal Neuropharmacology
    Excerpt

    The aim of this study was to examine whether the antioxidant alpha-lipoic acid protects retinal neurons from ischemia-reperfusion injury. Rats were injected intraperitoneally with either vehicle or alpha-lipoic acid (100 mg/kg) once daily for 11 days. On the third day, ischemia was delivered to the rat retina by raising the intraocular pressure above systolic blood pressure for 45 min. The electroretinogram was measured prior to ischemia and 5 days after reperfusion. Rats were killed 5 or 8 days after reperfusion and the retinas were processed for immunohistochemistry and for determination of mRNA levels by RT-PCR. Ischemia-reperfusion caused a significant reduction of the a- and b-wave amplitudes of the electroretinogram, a decrease in nitric oxide synthase and Thy-1 immunoreactivities, a decrease of retinal ganglion cell-specific mRNAs and an increase in bFGF and CNTF mRNA levels. All of these changes were clearly counteracted by alpha-lipoic acid. Moreover, in mixed rat retinal cultures, alpha-lipoic acid partially counteracted the loss of GABA-immunoreactive neurons induced by anoxia. The results of the study demonstrate that alpha-lipoic acid provides protection to the retina as a whole, and to ganglion cells in particular, from ischemia-reperfusion injuries. alpha-Lipoic acid also displayed negligible affinity for voltage-dependent sodium and calcium channels.

    Title The Beta-adrenoceptor Antagonists Metipranolol and Timolol Are Retinal Neuroprotectants: Comparison with Betaxolol.
    Date May 2003
    Journal Experimental Eye Research
    Excerpt

    beta-adrenoceptor antagonists are used clinically to reduce elevated intraocular pressure in glaucoma which is characterised by a loss of retinal ganglion cells. Previous studies have shown that the beta(1)-selective adrenoceptor antagonist, betaxolol, is additionally able to protect retinal neurones in vitro and ganglion cells in vivo from the detrimental effects of either ischemia-reperfusion or from excitotoxicity, after topical application. The neuroprotective effect of betaxolol is thought not to be elicited through an interaction with beta-adrenoceptors, but by its ability to reduce influx of sodium and calcium through voltage-sensitive calcium and sodium channels. In the present study it is shown that the non-selective beta-adrenoceptor antagonists, metipranolol and timolol behave like betaxolol. When topically applied they all attenuate the detrimental effect of ischemia-reperfusion. Protection of the retina was determined by evaluating changes in the electroretinogram and by assessing the loss of mRNA for Thy-1, which is expressed in retinal ganglion cells. In addition, studies conducted on neurones in mixed retinal cultures demonstrated that metipranolol, betaxolol and timolol were all able to partially counteract anoxia-induced cell loss and viability reduction. The influence of timolol was, however, not significant. Within the confines of these investigations, an order of neuroprotective efficacy was delineated for the three beta-adrenoceptor antagonists: betaxolol>metipranolol>timolol. The ability of the beta-adrenoceptor antagonists to attenuate ligand-induced stimulation of calcium and sodium entry into neuronal preparations showed a similar order of effectiveness. In conclusion, the ability to confer neuroprotection to retinal neurones is a common feature of three ophthalmic beta-adrenoceptor antagonists (betaxolol, metipranolol and timolol). A comparison of the effectiveness of the individual compounds in protecting retinal cells in vivo was not possible in these studies. However, in vitro studies show that the capacity of the individual beta-adrenoceptor antagonists to act as neuroprotectants appears to relate to their capacity to attenuate neuronal calcium and sodium influx.

    Title Vacuum-assisted Suction Drainage Versus Conventional Treatment in the Management of Poststernotomy Osteomyelitis.
    Date March 2003
    Journal European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery
    Excerpt

    The purpose of our study was to compare vacuum-assisted suction drainage (VASD) to conventional wound management, in the treatment of poststernotomy osteomyelitis (SOM).

    Title The Effect of Ischemic Preconditioning on Light-induced Photoreceptor Injury.
    Date March 2003
    Journal Investigative Ophthalmology & Visual Science
    Excerpt

    To determine whether ischemic preconditioning (IPC) upregulates certain retinal survival factors and to assess the protective effect of retinal IPC against light-induced photoreceptor degeneration.

    Title A Recently Described Polymorphism in the Cd28 Gene on Chromosome 2q33 is Not Associated with Susceptibility to Type 1 Diabetes.
    Date January 2003
    Journal European Journal of Immunogenetics : Official Journal of the British Society for Histocompatibility and Immunogenetics
    Excerpt

    Type 1 diabetes mellitus is an autoimmune disease with a strong genetic background. The CTLA4 gene region (IDDM12) has been implicated in genetic susceptibility to type 1 diabetes by genome scanning and both family- and population-based analyses. As the genes encoding the costimulatory molecules CTLA4 and CD28, which compete for the receptor B7, reside close together on chromosome 2q33 and have high sequence homology, we investigated a recently described polymorphism in intron 3 of the CD28 gene and the CLTA4 codon 17 polymorphism in 176 patients with type 1 diabetes and 220 healthy controls. Whereas CTLA4 was found to be associated with type 1 diabetes, the frequency of the CD28 polymorphism did not differ between patients and controls, either in the entire sample or after stratification for CTLA4 genotype. Thus, the CD28 intron 3 polymorphism does not appear to be associated with susceptibility to type 1 diabetes.

    Title The Variable Endogenous Retroviral Insertion in the Human Complement C4 Gene: a Transmission Study in Type I Diabetes Mellitus.
    Date December 2002
    Journal Human Immunology
    Excerpt

    A variable endogenous retroviral element has been identified in intron 9 of the complement C4 gene [HERV-K(C4)], which maps to the class III region of the major histocompatibility complex (MHC) on chromosome 6p21.3. Genetic susceptibility to type I diabetes is mainly conferred by the MHC locus and the complement C4 region has been implied to contribute to human leukocyte antigen DQ (HLA-DQ) mediated disease risk. As the HERV-K(C4) insertion has been suggested to modulate expression of homologous genes, we investigated its transmission in 220 families with an offspring affected by type I diabetes as a potential disease susceptibility marker. There was no preferential transmission of the HERV-K(C4) insertion to affected offspring (P(TDT) = 0.79). Although 77.7% of HLA-DQ8 carried the HERV-K(C4) insertion, only 52.9% of -DQ2 haplotypes did (P(chi(2)) < 0.01). However, its insertion or deletion did not modulate the risk conferred by HLA-DQ8 (DQA1*0301-DQB1*0302) (P(chi(2)) = 0.27) or -DQ2 (DQA1*0501-DQB1*0201) (P(chi(2)) = 0.46). Thus, the HERV-K(C4) insertion is not associated with type I diabetes in Germans.

    Title Cd45 Exon 4 Point Mutation Does Not Confer Susceptibility to Type 1 Diabetes Mellitus or Graves' Disease.
    Date December 2002
    Journal European Journal of Immunogenetics : Official Journal of the British Society for Histocompatibility and Immunogenetics
    Excerpt

    A point mutation in the leukocyte common antigen (CD45, C-->G77, exon 4) was investigated in patients with type 1 diabetes (IDDM), patients with Graves' disease and controls. The distribution did not differ significantly between patients and controls. This CD45 variant does not therefore confer susceptibility to either IDDM or Graves' disease.

    Title Topical Flunarizine Reduces Iop and Protects the Retina Against Ischemia-excitotoxicity.
    Date June 2002
    Journal Investigative Ophthalmology & Visual Science
    Excerpt

    To determine whether topical application of flunarizine reduces intraocular pressure (IOP) and acts as a retinal neuroprotectant and to compare the effectiveness of flunarizine with betaxolol and nifedipine at reducing the influx of calcium and sodium.

    Title A Hypothesis to Explain Ganglion Cell Death Caused by Vascular Insults at the Optic Nerve Head: Possible Implication for the Treatment of Glaucoma.
    Date October 2001
    Journal The British Journal of Ophthalmology
    Title Expectations in the Treatment of Retinal Diseases: Neuroprotection.
    Date October 2001
    Journal Current Eye Research
    Title Vasovagal Syncope and Anaesthetic Practice.
    Date October 2001
    Journal European Journal of Anaesthesiology
    Excerpt

    We surveyed anaesthetists working in North-West England and in North Wales concerning episodes of vasovagal syncope encountered in their practice. Eighty-eight anaesthetists described 109 such events occurring in either patients or their relatives and the estimated frequency of syncope was 1 in 5000 anaesthetic episodes. The patient syncopal episodes were triggered by venous cannulation in 16 instances and regional or local techniques in 20 instances. Thirty-three of the 53 patients were in the upright position when syncope occurred. Thirty-nine of the 56 relatives were male partners of female patients and four of these partners suffered some morbidity. The results of the survey are consistent with our current knowledge of the pathophysiology of vasovagal syncope, which is summarized, and also highlight the common anaesthetic scenarios where fainting is most likely to occur. Given this information anaesthetists will be in a better position to avoid such potentially harmful episodes in the future.

    Title Topically Applied Betaxolol Attenuates Ischaemia-induced Effects to the Rat Retina and Stimulates Bdnf Mrna.
    Date May 2001
    Journal Experimental Eye Research
    Excerpt

    It has previously been reported that the beta(1)-adrenoceptor antagonist, betaxolol, can protect retinal neurones from ischaemia when applied topically. It has further been shown that betaxolol can reduce influx of both sodium or calcium into neurones through interaction at neurotoxin site 2 of the sodium channel and the L-type calcium channel, respectively. The present study sought to further investigate the neuroprotective mode of action of betaxolol in the rat retina. Rats were treated topically with L-betaxolol for 10, 5 and 1 min before ischaemia, induced by raising the intraocular pressure above systolic blood pressure for 45 min. This was followed by reperfusion of 3 or 5 days where L-betaxolol was applied topically twice daily. Ischaemia plus reperfusion caused both a loss of immunoreactivity for choline acetyl transferase (ChAT) and a marked reduction of the b-wave of the electroretinogram (ERG). Treatment, as described, with topical L-betaxolol, completely blunted the effects upon ChAT immunoreactivity and caused a significant reversal of the ERG changes. Furthermore, other rats treated topically with commercially available racemic betaxolol (Betoptic Solution, 0.5%) for 6 hr had raised levels of mRNA for brain derived neurotrophic factor (BDNF) but not for basic fibroblast growth factor (bFGF) in their retinas. The combined data provide further evidence that betaxolol can blunt the effects of ischaemia to the rat retina when applied topically just before the insult. Furthermore, the finding that retinal levels of BDNF mRNA are raised following topical betaxolol treatment shows that not only can this drug reach the retina but that it can also induce changes in expression of factors which are known, themselves, to provide neuroprotection to retinal neurones.

    Title Catheter Fixation Problems--attention to Detail Required.
    Date March 2001
    Journal Anaesthesia
    Title The Influence of Zinc on Caspase-3 and Dna Breakdown in Cultured Human Retinal Pigment Epithelial Cells.
    Date January 2001
    Journal Archives of Ophthalmology
    Excerpt

    To investigate the role of extracellular zinc on the death process of cultured human retinal pigment epithelial (RPE) cells.

    Title A Guide to Your First Employment Contract.
    Date December 2000
    Journal Annals of Emergency Medicine
    Title An Investigation into the Potential Mechanisms Underlying the Neuroprotective Effect of Clonidine in the Retina.
    Date November 2000
    Journal Brain Research
    Excerpt

    alpha(2)-adrenoceptor agonists, such as clonidine, attenuate hypoxia-induced damage to brain and retinal neurones by a mechanism of action which likely involves stimulation of alpha(2)-adrenoceptors. In addition, the neuroprotective effect of alpha(2)-adrenoceptor agonists in the retina may involve stimulation of bFGF production. The purpose of this study was to examine more thoroughly the neuroprotective properties of clonidine. In particular, studies were designed to ascertain whether clonidine acts as a free radical scavenger. It is thought that betaxolol, a beta(1)-adrenoceptor antagonist, acts as a neuroprotective agent by interacting with sodium and L-type calcium channels to reduce the influx of these ions into stressed neurones. Studies were therefore undertaken to determine whether clonidine has similar properties. In addition, studies were undertaken to determine whether i.p. injections of clonidine or betaxolol affect retinal bFGF mRNA levels. In vitro data were generally in agreement that clonidine and bFGF counteracted the effect of NMDA as would occur in hypoxia. No evidence could be found that clonidine interacts with sodium or L-type calcium channels, reduces calcium influx into neurones or acts as a free radical scavenger at concentrations below 100 microM. Moreover, i.p. injection of clonidine, but not betaxolol, elevated bFGF mRNA levels in the retina. The conclusion from this study is that the neuroprotective properties of alpha(2)-adrenoceptor agonists, like clonidine, are very different from betaxolol. The fact that both betaxolol and clonidine blunt hypoxia-induced death to retinal ganglion cells suggests that combining the two drugs may be a way forward to producing more effective neuroprotection.

    Title 5-hydroxytryptamine1a Agonists: Potential Use in Glaucoma. Evidence from Animal Studies.
    Date October 2000
    Journal Eye (london, England)
    Excerpt

    Various classes of compounds exist to lower intraocular pressure (IOP) in the treatment of glaucoma. None of them is ideal since some patients respond better than others and the side effects vary between individuals. New classes of compounds need to be introduced to allow the clinician greater scope for effective treatment of all patients. It is now generally agreed that the cause of ganglion cell dysfunction in glaucoma is likely to be multifactorial and that concentrating solely on reducing IOP is inadequate. Irrespective of the reason for the dysfunction, the future goal must be to attenuate cell death. This may be achieved with drugs that interact with components of the retina, and is termed 'neuroprotection'. Thus, drugs that can both reduce IOP and act as neuroprotectants would be ideal for the treatment of glaucoma. In this article we summarise studies on animals which show serotonergic 5-HT1A agonists to both reduce IOP when topically applied to the rabbit eye and blunt the damaging effect to the rat retina and ganglion cells induced by glutamate toxicity or ischaemia. Reduction of IOP occurs via stimulation of 5-HT1A receptors associated with the ciliary processes. Neuroprotection of retinal neurones appears to involve the interaction of 5-HT1A agonists with membrane sodium channels and/or 5-HT1A or even possibly 5-HT7 receptors. Various 5-HT1A agonists are used in patients to treat depression, so classes of these drugs have a proven safety profile for use in patients. The animal studies summarised in this article suggest that 5-HT1A agonists need to be considered as a new class of drugs for the treatment of glaucoma.

    Title Flupirtine Ameliorates Ischaemic-like Death of Rat Retinal Ganglion Cells by Preventing Calcium Influx.
    Date May 2000
    Journal Brain Research
    Excerpt

    The effect of flupirtine on the loss of retinal ganglion cells following transient elevation of intraocular pressure (experimental ischaemia) or NMDA-induced excitotoxicity was studied. Ischaemia (60 min) or intravitreal injection of NMDA (20 nmol) caused a decrease in Thy-1 mRNA and Thy-1 immunoreactivity which are associated with ganglion cells. Administration of flupirtine counteracted these changes. Moreover, flupirtine dose-dependently inhibited NMDA-induced 45Ca(2+) influx into cultured cortical neurones and retinal pieces in vitro with maximal inhibition being observed at 200 microM. A similar concentration of flupirtine failed to inhibit kainate-stimulated calcium influx into cultured cortical neurones. In addition, flupirtine had no significant effect on [3H]nitrendipine or [3H]diltiazem binding to cortical membranes. The present studies are consistent with previous findings which suggested flupirtine to act as a NMDA antagonist by a mechanism that still remains to be clarified.

    Title Lower-extremity Doppler for Deep Venous Thrombosis--can Emergency Physicians Be Accurate and Fast?
    Date March 2000
    Journal Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine
    Excerpt

    Clinical diagnosis of lower-extremity (LE) deep venous thrombosis (DVT) requires confirmation by an imaging study before committing the patient to anticoagulation therapy. Studies have shown that demonstrating compressibility of leg veins under ultrasound is accurate for ruling out DVTs when performed by vascular specialists. Although LE Doppler has become the preferred test for diagnosing DVTs, it is not always available 24 hours per day. OBJECTIVES: To evaluate the accuracy and speed with which emergency physicians (EPs) could perform LE color duplex ultrasonography for the detection of DVT. METHODS: Patients presenting to an urban community emergency department (ED) between August 1, 1998, and March 3, 1999, were enrolled into this prospective study. The EPs, who underwent brief and standardized training, scanned patients at high risk for DVT with leg pain, swelling, or both. Physicians performed color duplex ultrasound examinations with compression at the common femoral and popliteal veins. The time until completion of the ED scan was recorded with a standardized method. The vascular laboratory performed a complete duplex ultrasound examination within eight hours. RESULTS: One hundred twelve patients were enrolled in the study, with 34 positive for DVT. The median examination time was 3 minutes 28 seconds (95% CI = 2 min 45 sec to 4 min 2 sec; IQR 3 min 9 sec). Times ranged from 1:02 to 18:20 minutes. The ED results had a high correlation with vascular laboratory studies, giving a kappa of 0.9 and a 98% agreement (95% CI = 95.4% to 100%). CONCLUSION: Emergency physicians can perform LE duplex ultrasound examinations accurately and quickly.

    Title Ganglion Cell Death in Glaucoma: What Do We Really Know?
    Date January 2000
    Journal The British Journal of Ophthalmology
    Title The Significance of a New Right Bundle Branch Block in a Patient with Acute Chest Pain.
    Date December 1999
    Journal Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine
    Title Betaxolol, a Beta1-adrenoceptor Antagonist, Has an Affinity for L-type Ca2+ Channels.
    Date November 1999
    Journal European Journal of Pharmacology
    Excerpt

    The effect of betaxolol on the specific binding of [3H]diltiazem and [3H]nitrendipine to rat cortical membranes was examined. Betaxolol inhibited specific [3H]diltiazem and [3H]nitrendipine binding with IC50 values of 19.7 and 46.3 microM, respectively. The effect of betaxolol on L-type Ca2+ channels showed little stereospecificity, since similar inhibitions of radioligand binding were observed with both racemic betaxolol and L-betaxolol. The dissociation kinetics of [3H]diltiazem were unaffected by 30 microM betaxolol, whereas it increased the [3H]nitrendipine dissociation rate, thus suggesting that betaxolol directly interacts with the benzothiazepine binding site and allosterically modulates the dihydropyridine binding site. Carteolol, propranolol and timolol were also found to inhibit both specific [3H]diltiazem and [3H]nitrendipine binding to rat cortical membranes, but with less potency than betaxolol. The ability of betaxolol to interact with L-type Ca2+ channels may have a role in its therapeutic effects in the management of systemic hypertension and in reducing neuronal death as occurring in glaucoma.

    Title Topically Applied Betaxolol Attenuates Nmda-induced Toxicity to Ganglion Cells and the Effects of Ischaemia to the Retina.
    Date October 1999
    Journal Experimental Eye Research
    Excerpt

    The present results show that topically applied Betoptic(R)(0.5% betaxolol) to the rabbit or rat eye reaches the retina and can counteract the detrimental effects caused by ischaemia/reperfusion or N -methyl- d -aspartate (NMDA)-induced insults to the retina. Betaxolol is a beta(1)-adrenergic blocker but its neuroprotective action is generally thought to be due to its calcium channel blocking properties. Support for this view comes from studies on cultures of cortical neurones where it was found that betaxolol attenuated the NMDA-induced influx of(45)Ca(2+)while beta-adrenoreceptor agonists were ineffective. Topically applied Betoptic(R)to the rabbit eye was observed to reach the retina in maximal amounts within 60 min. Some of the substance was also found in the contralateral retina of the untreated eye suggesting that the agent reaches the retina by local systemic and retinal circulation. Concurrent treatment with Latanoprost(R)did not result in a greater amount of betaxolol reaching the retina. An ophthalmodynamometric procedure, which raises the intraocular pressure, was used to apply an ischaemic insult to the rabbit retina. After three days of reperfusion the b-wave of the electroretinogram was reduced by an average of 59% and the choline acetyltransferase immunoreactivity in the retina was almost obliterated. However, when experiments were carried out on animals which had been treated with one drop of Betoptic(R) twice daily for 4 weeks before ischaemia and also during the reperfusion phase, the reductions in both the b-wave of the electroretinogram and retinal choline acetyltransferase immunoreactivity due to ischaemia/reperfusion were greatly attenuated. Intravitreal injection of NMDA into the rat eye caused a decrease in the immunostaining for Thy-1 antigen which is associated with ganglion cells. The Thy-1 mRNA level was also reduced as was the mRNA for the common subunit of the NMDA receptor, the NR1 subunit. However, in animals subjected to a topical Betoptic(R)regime, before and after intravitreal injection of NMDA, the decreases in the mRNA levels of Thy-1 and NR1 were significantly attenuated.

    Title Neuroprotection in Relation to Retinal Ischemia and Relevance to Glaucoma.
    Date September 1999
    Journal Survey of Ophthalmology
    Excerpt

    Management of glaucoma is directed at the control of intraocular pressure (IOP), yet it is recognized now that increased IOP isjust an important risk factor in glaucoma. Therapy that prevents the death of ganglion cells is the main goal of treatment, but an understanding of the causes of ganglion cell death and precisely how it occurs remains speculative. Present information supports the working hypothesis that ganglion cell death may result from a particular form of ischemia. Support for this view comes from the fact that not all types of retinal ischemia lead to the pathologic findings seen in glaucomatous retinas or to cupping in the optic disk area. Moreover, in animal experiments in which ischemia is caused by elevated IOP, a retinal abnormality similar to that seen in true glaucoma is produced, whereas after occlusion of the carotid arteries a different pattern of damage is found. In ischemia, glutamate is released, and this initiates the death of neurons that contain ionotropic glutamate (NMDA) receptors. Elevated glutamate levels exist in the vitreous humor of patients with glaucoma, and NMDA receptors exist on ganglion cells and a subset of amacrine cells. Experimental studies have shown that a variety of agents can be used to prevent the death of retinal neurons (particularly ganglion cells) induced by ischemia. These agents are generally those that block NMDA receptors to prevent the action of the released glutamate or substances that interfere with the subsequent cycle of events that lead to cell death. The major causes of cell death after activation of NMDA receptors are the influx of calcium into cells and the generation of free radicals. Substances that prevent this cascade of events are, therefore, often found to act as neuroprotective agents. For a substance to have a role as a neuroprotective agent in glaucoma, it would ideally be delivered topically to the eye and used repeatedly. It is, therefore, of interest that betaxolol, a beta-blocker presently used to reduce IOP in humans, also has calcium channel-blocking functions. Moreover, experimental studies show that betaxolol is an efficient neuro protective agent against retinal ischemia in animals, when injected directly into the eye or intraperitoneally.

    Title The Potential of Neuroprotection in Glaucoma Treatment.
    Date July 1999
    Journal Current Opinion in Ophthalmology
    Excerpt

    Visual field loss in glaucoma is due to death of retinal ganglion cells. Reducing or slowing down the loss of ganglion cells in glaucoma, a concept known as neuroprotection, would appear to be the only way forward. This does not imply that treatment of risk factors, such as elevated intraocular pressure, must not be continuously implemented. In this paper we point out that very little is known about the mechanisms of ganglion cell death in glaucoma and that data derived from studies on the "ideal animal model for glaucoma" must not be overemphasized. We also propose that the death processes of neurones in various diseases are fundamentally the same but vary in cause. Experimental data show that the death rate of neuronal populations is dependent on the impact of the insult and that neuroprotectants are more likely to benefit a patient in diseases in which the neurones die slowly, as in glaucoma, than in a disease in which the death of a set of neurones is rapid. We conclude that if a putative neuroprotectant can be administered in such a way that it reaches the retina in appropriate amounts and has insignificant side effects, it is likely to attenuate ganglion cell death and thus benefit the glaucoma patient.

    Title Changes in Alveolar Septal Border Lengths with Postnatal Lung Growth.
    Date February 1999
    Journal The American Journal of Physiology
    Excerpt

    Evaluation of alveolar development beyond the postnatal period of rapid septation has generally involved alveolar counting. We used an alternate approach to assess postseptation parenchymal development: measurement of the lengths of various types of alveolar septal borders. This technique directly addresses changes in the elastin fiber network that determines parenchymal complexity. Lungs from weanling and adult ferrets, inflated to 15 cmH2O, were perfusion fixed and dehydrated, and 2-micrometer sections were stained with Miller's elastin stain for light microscopy. We used standard morphometric methods to measure the lengths of the various types of alveolar septal borders. Three types comprised >90% of all septal borders: 1) free septal ends ("ends") containing an elastin cable; 2) angled meetings of two alveolar septa ("bends"), also with a cable; and 3) the near-symmetrical intersections of three septa ("junctions") devoid of elastin. When scaled for lung volume, ends and bends were 23 and 37% greater in adults (P < 0.001), reflecting the increase in parenchymal complexity with growth. The 17% difference in scaled junction lengths was not significant (P = 0.10). Bends increased out of proportion to the increase in ends, and both bends and ends increased to a greater degree than any possible increase in junctions (P < 0.001 for all comparisons). Although the interpretation of changes in the distribution of alveolar border lengths is not straightforward, an increase in bends resulting in an increase in the complexity of individual alveoli may contribute to the increase in alveolar gas-exchanging surface area with growth. Septation, the process responsible for the rapid early postnatal increase in parenchymal complexity in many species, should tend to increase the lengths of ends and junctions and decrease the lengths of bends. Therefore, these data suggest that septation is not the predominant mechanism of later postnatal parenchymal development in the ferret.

    Title Melatonin Counteracts Ischemia-induced Apoptosis in Human Retinal Pigment Epithelial Cells.
    Date November 1998
    Journal Investigative Ophthalmology & Visual Science
    Excerpt

    To investigate whether the neurohormone melatonin can prevent apoptosis caused by deprivation of oxygen, glucose, and serum (experimental ischemia) in cultured human retinal pigment (RPE) cells.

    Title Expression of Protein Kinase C Isoenzymes in Cultured Hooded Rat Retinal Pigmented Epithelial Cells: Comparison with Dystrophic Royal College of Surgeons Rat.
    Date September 1998
    Journal Current Eye Research
    Excerpt

    To determine the isoenzymes of Protein Kinase C (PKC) that are present in cultured retinal pigmented epithelial (RPE) cells from both the Lister hooded rat and the Royal College of Surgeons (RCS) rat.

    Title Flupirtine, a Nonopioid Centrally Acting Analgesic, Acts As an Nmda Antagonist.
    Date May 1998
    Journal General Pharmacology
    Excerpt

    1. Flupirtine (Katadolon) is a member of a class of triaminopyridines and is used as a nonopioid analgesic agent with muscle relaxant properties. 2. In situ experiments have revealed that flupirtine protects against ischemic-induced insults to the retina and brain. 3. Data derived from in vitro and in vivo studies suggest that flupirtine functions as a weak N-methyl-D-aspartate (NMDA) antagonist with little evidence that it acts on AMPA-kainate type glutamate receptors. 4. No evidence could be found from binding studies to suggest that flupirtine has an affinity for any of the characterized binding sites associated with the NMDA receptor. 5. Studies on cultured cortical neurons show that the NMDA-induced influx of 45Ca2+ is more readily decreased by flupirtine when a reducing agent (dithiothreitol) is present. However, when N'-ethylmaleimide, which is thought to alkylate the NMDA receptor redox site, is present, no obvious effect on the NMDA-induced influx of 45Ca2+ is produced by flupirtine. 6. Flupirtine is also known to counteract the production of reactive oxygen species caused by ascorbate/iron as well as to prevent apoptosis in cells lacking NMDA receptors induced by oxidative stress. 7. To explain all the experimental data, it is suggested that flupirtine affects the redox state/pH/electrons in the cell. The specific way by which flupirtine antagonizes the NMDA receptor might be by an action on the known redox site of the receptor.

    Title Diagnosis of Hip Fracture by the Auscultatory Percussion Technique.
    Date April 1998
    Journal The American Journal of Emergency Medicine
    Excerpt

    Traumatic hip pain is a commonly encountered complaint in the emergency department. Occasionally, initial radiographs fail to show a fracture. A delayed diagnosis can result in significant patient morbidity. Diagnostic algorithms have been formulated to evaluate the patient with hip pain and negative initial radiographs. The auscultatory percussion technique can alert the physician of the presence or absence of an occult hip fracture. Consequently, the physician may order a more sophisticated imaging technique.

    Title Induction of Apoptosis in Cultured Human Retinal Pigmented Epithelial Cells: the Effect of Protein Kinase C Activation and Inhibition.
    Date September 1997
    Journal Neurochemistry International
    Excerpt

    The presence of the non-selective protein kinase C (PKC) inhibitors, staurosporine (100 nM) and polymyxin B (100 microM) in cultured human RPE cells for more than 24 h triggers apoptotic death. Apoptosis is characterized by a diminishing number of cells, a labelling of nuclei by the TUNEL method and by observable morphological changes. An inhibitor of PKC and cyclic nucleotide-dependent protein kinases, 1-(5-isoquinolinesulphonyl)-2-methyl piperazine (H-7; 100 microM), was without effect, as was the specific PKC inhibitor, calphostin C (100 nM). The PKC-activating phorbol esters, phorbol-12-myristate-13-acetate (PMA; 1 microM) and phorbol-12,13-dibutyrate (PDB; 1 microM) and the non-tumour-promoting phorbol ester, 4 alpha-PMA (1 microM) were without effect, as was the diacyl glycerol analogue, 1,2-dioctanoyl-snglycerol (DOG; 10 microM). The PKC activators did not attenuate the apoptosis induced by staurosporine or polymyxin B. Furthermore, deprivation of glucose and oxygen (simulated ischemia) for 72 h induced apoptosis: this could be prevented by inclusion of 10% (v/v) foetal bovine serum (FBS) but not by a variety of PKC activators. Six PKC isoenzymes were shown to be present in RPE cells (alpha, beta 1, beta 2, delta, epsilon, E) and only the calcium-dependent cPKC levels changed after treatment with staurosporine or simulated ischaemia. Since only the less selective inhibitors of PKC induced apoptosis, it is suggested that PKC is not involved directly in the induction process of apoptosis in RPE cells. It is possible that the staurosporine and polymyxin B-induced effects of apoptosis in RPE cells are triggered by an unknown kinase-dependent pathway, but whether the 'ischaemia'-induced death is related to this same process remains to be elucidated.

    Title Induction of Apoptosis in Cultured Human Retinal Pigment Epithelial Cells is Counteracted by Flupirtine.
    Date June 1997
    Journal Investigative Ophthalmology & Visual Science
    Excerpt

    The aim of the study was to determine whether flupirtine can counteract the induction of apoptosis in cultured retinal pigment epithelium (RPE) cells.

    Title Protein Kinase C Activation by Serotonin Potentiates Agonist-induced Stimulation of Camp Production in Cultured Rat Retinal Pigment Epithelial Cells.
    Date June 1997
    Journal Experimental Eye Research
    Excerpt

    Serotonin stimulates inositol phosphate production and intracellular calcium mobilization in cultured rat retinal pigment epithelial (RPE) cells through interaction with 5-HT2A receptors, but decreases cAMP production in cultured human RPE cells via 5-HT1A receptors. Studies were therefore undertaken to investigate the effect of serotonin on the cAMP system in rat RPE cells. Exposure of cultured rat RPE cells to serotonin (100 microM) for 10 minutes had no effect on the basal levels of cAMP. However, a 5 minute preincubation with serotonin potentiated the production of cAMP induced by a 5 minute exposure to forskolin (5 microM), isoproterenol (1 microM) and 5'-[N-ethylcarboxamido]-adenosine (10 microM) by 133.0%, 296.8% and 651.9%, respectively. This effect of serotonin was dose-dependent on forskolin and 5'-[N-ethylcarboxamido]-adenosine with half-maximal effects close to those reported for its action on inositol phosphates production. The antagonists ketanserin, methysergide and spiperone attenuated the action of serotonin, while yohimbine and spiroxatrine were ineffectual, thus indicating that the potentiating effect was through the 5-HT1A receptor. Incubation of cultured rat RPE cells with bradykinin stimulates inositol phosphates production with half-maximal effect observed at 1 nM. Bradykinin also potentiates the action of forskolin, isoproterenol and 5'-[N-ethylcarboxamido]-adenosine on cAMP production in a dose-dependent manner with little effect on basal levels. RPE cells exposed to serotonin (500 microM) or phorbol 12-13 dibutyrate (1 microM) for 30 minutes showed translocation of protein kinase C to the membrane from the cytosol, with 53.3% and 29.4% increases in membrane activity, respectively. Forskolin- and 5'-[N-ethylcarboxamido]-adenosine-induced cAMP production was potentiated by phorbol 12-13 dibutyrate (1 microM) treatment. The effect of both serotonin and phorbol 12-13 dibutyrate on forskolin-induced cAMP production was attenuated by pretreatment of cell cultures with the protein kinase C antagonists staurosporin and calphostin C at 1 microM. Thus, the production of cAMP in cultured rat RPE cells is potentiated by 5-HT2A receptors through activation of protein kinase C. This effect is, however, not specific since bradykinin, which stimulates inositol phosphates turnover, also potentiates stimulated cAMP production.

    Title Retinal Protein Kinase C.
    Date April 1997
    Journal Neurochemistry International
    Excerpt

    The protein kinase C (PKC) family of serine/threonine kinase isoenzymes are universally expressed in vertebrate tissues where they control vital cellular functioning. PKC comprises twelve currently identified mammalian isoenzymes, described in three distinct groups according to their need for different effector stimulation. Immunological localisation studies in various vertebrate retinas have indicated the presence, so far, of eight of the PKC subspecies, each with a unique cellular distribution in this tissue. Use of these immunological probing techniques with antibodies raised to the individual PKC family members by immunohistochemistry and western blotting, along with biochemical tools such as the potent activators, the tumour-promoting phorbol esters can hopefully lead to elucidation of the roles of these enzymes in the neural retina. Research work to date has pinpointed a number of roles for PKC in this tissue including control of dopamine release, modulation of glutamate receptor function (probably by a process of direct receptor phosphorylation), phosphorylatory modulation of GABAC-receptor function, an involvement in the retinal ischaemic cascade process (the relevance of which is unknown as yet), involvement in control of cytoskeletal interactions by cytoskeletal element-kinase action and feedback control of enzymes involved in the process of inositol phosphate signalling. PKC has been shown to have an important regulatory role in the process of phototransduction: many of the enzymes and proteins making up the phototransduction cascade act as in vitro and in vivo substrates for PKC-dependent phosphorylation and can have their normal function modified in this way. Also, PKC has been implicated in the control of spinule formation in the retina, a process involved in retinal synaptic plasticity and functioning. All of this work has been described, herein. Collation and utilisation of knowledge of all of the work described here may help us to determine the exact roles for individual isoenzymes in the retina. This in turn may help us to understand and further to prevent pathological conditions leading to inappropriate retinal functioning and possible blindness. Furthermore, understanding the roles of PKC in the neural retina may lead us to vital clues in the understanding of the functioning of this important group of enzymes in the nervous system as a whole and eventually to the prevention of many major neuropathological disorders.

    Title Immunological Localization of Gabaa-receptor Subunits in Cultured Human and Rat Retinal Pigment Epithelium.
    Date January 1997
    Journal Experimental Eye Research
    Title Emergency Physicians' Obligations to Managed Care Patients Under Cobra.
    Date December 1996
    Journal Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine
    Excerpt

    In 1986 the federal government enacted a statute, the Consolidated Omnibus Budget Reconciliation Act (COBRA), intended to address the perceived problem of patients being denied essential emergency medical care, or being transferred in an unstable condition, because of the patient's lack of an adequate payer source. Compliance with COBRA has been a concern among hospitals and emergency physicians (EPs). Indeed, by the end of 1993, the federal government investigated > 1,500 allegations of COBRA violations. Since COBRA was enacted to address the problem of "economically motivated" transfers of indigent patients, many EPs are unaware of the potential for COBRA violations inherent in the accommodations currently being sought by some managed care organizations. This paper reviews hospitals' and physicians' obligations to managed care patients under COBRA.

    Title Identification and Triage of Nonemergency Patients from the Ed.
    Date August 1995
    Journal Annals of Emergency Medicine
    Title Phorbol Esters, Kainate and Ischaemia Influence Protein Kinase C Alpha, Delta and Zeta in the Rabbit Retina, in Vitro.
    Date February 1995
    Journal Biochemical Society Transactions
    Title How the Doctor Got Gagged.
    Date July 1992
    Journal Jama : the Journal of the American Medical Association
    Title Preferential Distribution of Streptomycin in Pig Kidney Cortex.
    Date February 1991
    Journal The Analyst
    Excerpt

    In 14 pig kidneys containing streptomycin, an average distribution ratio of 2.5:1 was found for the streptomycin between the cortex and medulla. It is suggested here that cortex alone be used, instead of mixed kidney tissue, in regulatory meat monitoring schemes.

    Title Tetanus.
    Date March 1984
    Journal Annals of Emergency Medicine
    Title Inability to Predict Relapse in Acute Asthma.
    Date March 1984
    Journal The New England Journal of Medicine
    Title Isoniazid Overdose Treated with High-dose Pyridoxine.
    Date November 1983
    Journal Annals of Emergency Medicine
    Excerpt

    Large doses of pyridoxine recently have been shown to prevent the seizures and acidosis caused by ingestion of more than two to three grams of isoniazid. We present three cases of massive isoniazid ingestion, producing seizures and acidosis, that were treated successfully by administration of one gram of pyridoxine intravenously for each gram of isoniazid ingested.

    Title Hereford Hospital Prescribing Study: Description and Usefulness.
    Date December 1981
    Journal Journal of the Royal Society of Medicine
    Title Laminectomy: is It Worth It?
    Date August 1979
    Journal The Journal of the American Osteopathic Association
    Title Lumbar Disk Surgery: Complications.
    Date January 1975
    Journal The Journal of the American Osteopathic Association
    Title Arkansas Medical Society. Address of the President.
    Date July 1974
    Journal The Journal of the Arkansas Medical Society
    Title Ruminating on 31 Years of Lumbar Disk Surgery: a Reminiscent Review.
    Date March 1974
    Journal The Journal of the American Osteopathic Association
    Title The Traumatized Knee Joint: a Statistical Review.
    Date June 1971
    Journal The Journal of the American Osteopathic Association
    Title Congenital Foot Problems, with Emphasis on Casting Technique.
    Date December 1966
    Journal The Journal of the American Osteopathic Association
    Title The Surgeon's Role in the Management of the Dyskinesias.
    Date December 1965
    Journal The Journal of the American Osteopathic Association
    Title Informed Consent to the Medical Treatment of Minors: Law and Practice.
    Date
    Journal Health Matrix (cleveland, Ohio : 1991)
    Title Dry Thermal Resistance of Bacillus Anthracis (sterne) Spores and Spores of Other Bacillus Species: Implications for Biological Agent Destruction Via Waste Incineration.
    Date
    Journal Journal of Applied Microbiology
    Excerpt

    To obtain needed data on the dry thermal resistance of Bacillus anthracis spores and other Bacillus species for waste incinerator applications.

    Title Prothrombin Activation on the Activated Platelet Surface Optimizes Expression of Procoagulant Activity.
    Date
    Journal Blood
    Excerpt

    Effective hemostasis relies on the timely formation of α-thrombin via prothrombinase, a Ca(2+)-dependent complex of factors Va and Xa assembled on the activated platelet surface, which cleaves prothrombin at Arg271 and Arg320. Whereas initial cleavage at Arg271 generates the inactive intermediate prethrombin-2, initial cleavage at Arg320 generates the enzymatically active intermediate meizothrombin. To determine which of these intermediates is formed when prothrombin is processed on the activated platelet surface, the cleavage of prothrombin, and prothrombin mutants lacking either one of the cleavage sites, was monitored on the surface of either thrombin- or collagen-activated platelets. Regardless of the agonist used, prothrombin was initially cleaved at Arg271 generating prethrombin-2, with α-thrombin formation quickly after via cleavage at Arg320. The pathway used was independent of the source of factor Va (plasma- or platelet-derived) and was unaffected by soluble components of the platelet releasate. When both cleavage sites are presented within the same substrate molecule, Arg271 effectively competes against Arg320 (with an apparent IC(50) = 0.3μM), such that more than 90% to 95% of the initial cleavage occurs at Arg271. We hypothesize that use of the prethrombin-2 pathway serves to optimize the procoagulant activity expressed by activated platelets, by limiting the anticoagulant functions of the alternate intermediate, meizothrombin.

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