bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electrical Injuries in Canadian Burn Care: Identification of Unsolved Problems
Authors: TREDGET EDWARD E. , SHANKOWSKY HEATHER A. , TILLEY WENDY A. 
Published: February 2006

ABSTRACT: Over the past decade, the Firefighters' Burn Treatment Unit of the University of Alberta Hospital in Edmonton, Alberta, Canada, has treated 1399 in‐patients suffering from thermal injury. Regional burn care is provided in a 10‐bed intensive care unit with 18 plastic surgery reconstructive beds for a large referral region of central and northern Alberta, portions of the Northwest Territories, and neighboring provinces of British Columbia and Saskatchewan.Of the total burn inpatients during this period, 74 electrical injuries were treated (5.3% of all admissions): 71 were males (95.9%) and 3 females (4.1%). The mean age of all patients was 33.9 ± 12.6 years (range 1‐67). Compared to our general population of thermally injured patients, those with electrical injuries had smaller injuries [9.9 ± 12.9% TBSA (range 1‐65) versus 15.1 ± 10.1], shorter length of hospitalization [18.6 ± 7.3 days (range 1‐80) versus 26.2 ± 0.8], and substantially lower mortality once reaching the hospital (0% versus 4%).Electrical injuries were classified as flash in 30 cases, contact in 42 cases, and lightning in 2 cases; 74.3% of injuries occurred during work‐related activities. A total of 118 operative procedures were performed during the acute admission (1.6 procedures per patient), including 19 amputations: 12 in the upper and 7 in the lower extremity. The mean time of amputation was 9.3 ± 5.3 days after admission.In contact injuries of the upper extremity, 14 patients suffered amputations or neurologic injury that required reconstruction with free tissue transfers and nerve grafts. Long‐term functional outcome of these patients using sensory testing, the Jebsen‐Taylor hand function test, and wound coverage has revealed that these patients have substantial persistent sensory impairment of their upper extremities postinjury despite reconstruction, although many remain active and functional with acceptable wound coverage.Based on our analysis of electrical injury as it presents to one typical Canadian burn unit, our patients suffer limb loss on a delayed basis, which leads to substantial morbidity. Reconstruction of the upper extremity with microsurgical techniques after profound electrical injury has provided acceptable coverage, but in many instances is associated with poor or marginal sensory recovery limiting reemployment options for patients with upper extremity electrical burns. Further understanding of the cellular biology of delayed tissue loss after electric injury would offer the potential for reduction in amputation rate and improvement in functional outcome and overall morbidity.
Changes in Electroporation Thresholds of Lipid Membranes by Surfactants and Peptides
Authors: TUNG LESLIE , TROIANO GREG C. , SHARMA VINOD , RAPHAEL ROBERT M. , STEBE KATHLEEN J. 
Published: February 2006

ABSTRACT: This article reviews recent work from our laboratory that explores how chemical additives may alter the threshold of electroporation of synthetic lipid bilayers. The addition of the nonionic block copolymeric surfactant, poloxamer 188 (P188), at a concentration of 1 mM increased the electroporation thresholds of planar lipid bilayer membranes made of azolectin. For a 10‐μs rectangular pulse, P188‐treated membranes were found to have a statistically higher threshold voltage, longer latency time to rupture, and lower postpulse conductance. Addition of the nonionic surfactant, octaethyleneglycol‐mono‐n‐dodecyl‐ether (C12E8), decreased the electroporation threshold of bilayer membranes made of 1‐palmitoyl‐2‐oleoyl‐phosphatidylcholine (POPC) by 10‐40% for 10‐μs‐ to 10‐s‐duration pulses, in a concentration‐dependent manner over concentrations ranging from 0.1 to 10 mM. Postpulse membrane conductance also increased. The opposite effects of the two surfactants on electroporation thresholds may result from their very different structures, which would encourage different modes of surfactant‐lipid interactions.To examine protein‐lipid interactions and their effects on the electroporation threshold, the effects of a channel‐forming polypeptide, gramicidin D (gD), was studied on membrane conductance and electroporation threshold. Electroporation thresholds for 15‐ms pulses were unaffected by addition of gramicidin to POPC at a peptide:lipid concentration estimated to be 1:10,000, but increased significantly at ratios of 1:500 and 1:15, while membrane conductance increased monotonically with peptide concentration. A micropipette aspiration technique was applied to giant unilamellar POPC vesicles to measure changes in the membrane physical properties. When gD was added to give an estimated peptide:lipid ratio of 1:15, the membrane area expansivity modulus increased, indicating that the increase in electroporation threshold is correlated with a change in membrane stiffness. Thus, these findings demonstrate that surfactants or peptides can mediate the electroporation threshold of lipid bilayers.
Strategies in Disability Management: Corporate Disability Management Programs Implemented at the Work Site
Authors: KALINA CHRISTINE M. 
Published: February 2006

ABSTRACT: Managers are challenged to demonstrate all programs as economically essential to the business, generating an appreciable return on investment. Further challenge exists to blend and integrate clinical and business objectives in program development. Disability management programs must be viewed as economically essential to the financial success of the business to assure management support for clinical interventions and return‐to‐work strategies essential for a successful program.This paper discusses a disability management program integrating clinical and business goals and objectives in return‐to‐work strategies to effect positive clinical, social‐cultural, and business results. Clinical, educational, social, and economic challenges in the development, implementation, and continued management of a disability program at a large corporation with multiple global work sites are defined. Continued discussion addresses the effective clinical interventions and educational strategies utilized successfully within the workplace environment in response to each defined challenge.A multiple disciplinary team approach, clinical and business outcome measures, and quality assurance indicators are discussed as major program components. This article discusses a successful program approach focusing on business process and methodology. These parameters are used to link resources to strategy, developing a product for implementing and managing a program demonstrating economic value added through effective clinical medical case management.
Neuroprotective “Agents” in Surgery: Secret “Agent” Man, or Common “Agent” Machine?
Authors: ANDREWS RUSSELL J. 
Published: February 2006

ABSTRACT: The search for clinically‐effective neuroprotective agents has received enormous support in recent years‐an estimated $200 million by pharmaceutical companies on clinical trials for traumatic brain injury alone. At the same time, the pathophysiology of brain injury has proved increasingly complex, rendering the likelihood of a single agent “magic bullet” even more remote.On the other hand, great progress continues with technology that makes surgery less invasive and less risky. One example is the application of endovascular techniques to treat coronary artery stenosis, where both the invasiveness of sternotomy and the significant neurological complication rate (due to microemboli showering the cerebral vasculature) can be eliminated.In this paper we review aspects of intraoperative neuroprotection both present and future. Explanations for the slow progress on pharmacologic neuroprotection during surgery are presented. Examples of technical advances that have had great impact on neuroprotection during surgery are given both from coronary artery stenosis surgery and from surgery for Parkinson's disease. To date, the progress in neuroprotection resulting from such technical advances is an order of magnitude greater than that resulting from pharmacologic agents used during surgery.The progress over the last 20 years in guidance during surgery (CT and MRI image‐guidance) and in surgical access (endoscopic and endovascular techniques) will soon be complemented by advances in our ability to evaluate biological tissue intraoperatively in real‐time. As an example of such technology, the NASA Smart Probe project is considered.In the long run (i.e., in 10 years or more), pharmacologic “agents” aimed at the complex pathophysiology of nervous system injury in man will be the key to true intraoperative neuroprotection. In the near term, however, it is more likely that mundane “agents” based on computers, microsensors, and microeffectors will be the major impetus to improved intraoperative neuroprotection.
Role of Glycemia in Acute Spinal Cord Injury: Data from a Rat Experimental Model and Clinical Experience
Authors: SALA FRANCESCO , MENNA GAETANO , BRICOLO ALBINO , YOUNG WISE 
Published: February 2006

ABSTRACT: While experimental and clinical evidence indicates that in brain injury blood glucose increases with injury severity and hyperglycemia worsens neurological outcome, the role of blood glucose in secondary mechanisms of neuronal damage after acute spinal cord injury has not yet been investigated. Data from spinal cord ischemia models suggests a deleterious effect of hyperglycemia, likely due to enhanced lactic acidosis, which is primarily dependent on the amount of glucose available to be metabolized. The purpose of this study is to summarize preliminary experimental and clinical observations on the role of blood glucose in acute spinal cord injury.Between 1995 and 1996 we used the New York University (NYU) rat spinal cord injury model to test the following hypotheses: 1) Blood glucose levels increase with injury severity. 2) Fasting protects from hyperglycemia and prevents secondary damage to the spinal cord. 3) Postinjury‐induced hyperglycemia (dextrose 5% 2 gm/Kg) enhances spinal lesion volume.From a clinical perspective, we reviewed blood glucose records of 47 patients admitted to the Department of Neurosrgery in Verona, between 1991 and 1995, within 24 hours of acute spinal cord injury in order to determine: a) the incidence of hyperglycemia (>140 mg/dl); b) the correlation between blood glucose and injury severity; and c) the role of methylprednisolone in affecting blood glucose.Results indicate that in a graded spinal cord injury model: 1) Early after injury, more severe contusions support significantly higher blood glucose levels. 2) Fasting overnight does not directly affect spinal cord lesion volume but influences blood gases, and we observed that a slightly systemic acidosis plays a minor neuroprotective role. Fasting also ensures more consistent normoglycemic baseline blood glucose values. 3) Postinjury‐induced moderate hyperglycemia (160–190 mg/dl) does not significantly affect spinal cord injury.In the clinical study, we observed that during the first 24 hours after spinal cord injury: a) Glycemia ranges between 90 and 243 mg/dl (mean value 143 mg/ dl), and close to 50% of the patients present blood glucose values higher than normal. b) Methylprednisolone administration is not associated to significantly higher blood glucose levels. c) There is a trend for larger glucose rises with more severe injury.
High Extracellular Glutamate and Neuronal Death in Neurological Disorders: Cause, Contribution or Consequence?
Authors: OBRENOVITCH TIHOMIR P. 
Published: February 2006

ABSTRACT: In models of neurological disorders, increased extracellular glutamate and beneficial effects produced by glutamate‐receptor antagonists are consistently taken as supporting evidence of excitotoxicity. This systematic interpretation is over‐simplified and potentially misleading.High extracellular glutamate is not a reliable indicator of endogenous excitotoxixity, i.e., the intrinsic, potential neurotoxicity of endogenous glutamate whenever it accumulates extracellularly. Firstly, because the extracellular levels of glutamate necessary to produce depolarization and death in vivo, are far above those measured in models of neurological disorders. Secondly, because changes in the concentration of glutamate in the synaptic cleft (i.e., the relevant compartment for endogenous excitotoxicity) are not reflected extracellularly.Protection by glutamate‐receptor antagonists does not necessarily imply inhibition of excitotoxic abnormalities. Indeed, neuronal death initiated by insults such as ischemia results from multifactorial processes that may be interrelated. Therefore, beneficial effects resulting from an interaction with glutamate‐mediated transmission may actually render the cell more resistant to other deleterious mechanisms (e.g., mitochondrial injury, oxidative stress).
Neuroprotective Properties of Nitric Oxide
Authors: CHIUEH CHUANG C. 
Published: February 2006

ABSTRACT: The discoveries of physiological roles of nitric oxide (·NO) as the mediator of endothelium‐derived relaxing factor (EDRF) action and the activator of guanylyl cyclase to increase cyclic guanosine monophosphate (cGMP), which lead to vasorelaxation in the cardiovascular system, have been awarded with the 1998 Nobel Prize of Medicine. The present review discusses putative beneficial effects of ·NO in the central nervous system (CNS). In addition to its prominent roles of the regulation of cerebral blood flow and the modulation of cell to cell communication in the brain, recent in vitro and in vivo results indicated that ·NO is a potent antioxidative agent. ·NO terminates oxidant stress in the brain by (i) suppressing iron‐induced generation of hydroxyl radicals (·OH) via the Fenton reaction, (ii) interrupting the chain reaction of lipid peroxidation, (iii) augmenting the antioxidative potency of reduced glutathione (GSH) and (iv) inhibiting cysteine proteases.It is apparent that ·NO‐a relative long half‐life nitrogen‐centered weak radical‐scavenges those short‐lived, highly reactive free radicals such as superoxide anion (O2·−), ·OH, peroxyl lipid radicals (LOO·) and thiyl radicals (i.e., GS·), yielding reactive nitrogen species including nitrites, nitrates, S‐nitrosoglutathione (GSNO) and peroxynitrite (ONOO−). GSNO is 100‐fold more potent than GSH; it completely inhibits the weak peroxidative effect of ONOO−. Moreover, CO2 and ·NO neutralize prooxidative effects of ONOO−. CO2 prevents protein oxidation but not 3‐nitrotyrosine formation caused by ONOO−. Finally, neuroprotective effects of GSNO and ·NO have been demonstrated in brain preparations in vivo.These novel neuroprotective properties of ·NO and GSNO may have their physiological significance, since oxidative stress depletes GSH while increasing GS· and ·NO formation in astroglial and endothelial cells, resulting in the generation of a more potent antioxidant GSNO and providing additional neuroprotection at μM concentrations. This putative GSNO pathway (GSH → GS·→ GSNO →·NO + GSSG → GSH) may be an important part of endogenous antioxidative defense system, which could protect neurons and other brain cells against oxidative stress caused by oxidants, iron complexes, proteases and cytokines. In conclusion, ·NO is a potent antioxidant against oxidative damage caused by reactive oxygen species, which are generated by Fenton reaction or other mechanisms in the brain via redox cycling of iron complexes.
The Unique Histopathological Responses of the Injured Spinal Cord: Implications for Neuroprotective Therapy
Authors: GUTH LLOYD , ZHANG ZIYIN , STEWARD OSWALD 
Published: February 2006

ABSTRACT: Tissue destruction at the primary site of a spinal cord injury leads to persistent necrosis that progressively enlarges the lesion. Steroids attenuate this necrotizing process and promote tissue repair even though such anti‐inflammatory drugs interfere with wound healing in non‐CNS organs. To address this paradox, the spinal cord of rats and mice was crushed extradurally and the effects of the following anti‐inflammatory agents studied by light microscopical image analysis: allopurinol, aminoguanidine, indomethacin, a bacterial lipopolysaccharide, naproxen, and pregnenolone. The contribution of Wallerian degeneration to progressive necrosis was studied in a mutant mouse strain (WldS) that is characterized by delayed Wallerian degeneration.In rats, the anti‐inflammatory agents selectively attenuated progressive necrosis and encouraged wound healing. In mice, considerable tissue repair occurred without pharmacological intervention; this wound‐healing process was delayed in the mutant WldS strain. Since spinal cord injury results in concomitant tissue necrosis and wound healing, a goal of neuroprotective therapy is to regulate the dynamic balance between these destructive and reparative processes.
Intracellular Survival Pathways against Glutamate Receptor Agonist Excitotoxicity in Cultured Neurons: Intracellular Calcium Responsesa
Authors: MARINI ANN M. , UEDA YUJI , JUNE CARL H. 
Published: February 2006

ABSTRACT: Cultured rat cerebellar granule cells are resistant to the excitotoxic effects of N‐methyl‐d‐aspartate (NMDA) and non‐NMDA receptor agonists under three conditions: 1) prior to day seven in vitro when cultured in depolarizing concentrations of potassium [25 mM]; 2) at any time in vitro when cultured in non‐depolarizing concentrations of potassium [5 mM]; and 3) when neurons, cultured in depolarizing concentrations of potassium [25 mM] for eight days in vitro, are pretreated with a subtoxic concentration of NMDA. The focus of this paper is to determine: a) whether the resistance to excitotoxicity by NMDA and non‐NMDA receptor agonists is due to a decreased intracellular calcium [Ca++]i response to glutamate receptor agonists in cultured rat cerebellar granule cells; or b) whether [Ca++]i levels induced by the agonists are similar to those observed under excitotoxic conditions.Granule cells, matured in non‐depolarizing growth medium, treated with glutamate resulted in an increase in [Ca++]i followed by a plateau that remained above baseline in virtually all neurons that responded to glutamate. The response was rapid in onset (<10 sec) and the pattern of response heterogeneous in that cells responsive to glutamate increased their [Ca++]i to different extents; some cells did not respond to glutamate. Kainate also produced significant elevations in [Ca++]i.The [Ca++]i response to glutamate in neurons matured in depolarizing (25 mM K+) growth medium for three days was rapid, transient and heterogeneous, which reached a plateau that was elevated above baseline levels; removing the glutamate markedly reduced the [Ca++]i concentration. Activation of the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA)/kainate receptors by kainic acid produced similar changes in [Ca++]i responses. At a time when cultured cerebellar granule cells become susceptible to the excitotoxic effects of glutamate acting at NMDA receptors (day in vitro (DIV) 8) in depolarizing growth medium, glutamate elicited [Ca++]i responses similar to those observed at a culture time when the neurons are not susceptible to the excitotoxic effects of glutamate (DIV 3). Pretreatment of the cultured neurons with a subtoxic concentration of NMDA, which protects all neurons against the excitotoxic effects of glutamate, did not alter the maximal [Ca++]i elicited by an excitotoxic concentration of glutamate.
Neuroprotective Actions of Novel and Potent Ligands of Group I and Group II Metabotropic Glutamate Receptors
Authors: KINGSTON A. E. , O'NEILL M. J. , BOND A. , BRUNO V. , BATTAGLIA G. , NICOLETTI F. , HARRIS J. R. , CLARK B. P. , MONN J. A. , LODGE D. , SCHOEPP D. D. 
Published: February 2006

ABSTRACT: The role of group I metabotropic glutamate (mGlu) receptors in neurodegeneration is controversial because of the contradictory effects of mGlu1/5 agonists in in vitro models of neuronal cell death. In this study, novel and selective antagonists of mGlu1 and mGlu5: LY367385 and LY367366 were found to show consistent neuroprotective effects against N‐methyl‐d‐aspartate (NMDA)‐induced excitotoxicity in vitro and in vivo. Furthermore, intraventricular administration of LY367385 reduced hippocampal cell death in gerbils subjected to transient global ischemia.Previous studies have also shown that activation of group II mGlu receptors may contribute to neuroprotective mechanisms in vitro and in vivo. Three potent group II mGlu agonists‐LY354740, LY379268 and LY389795‐were found to attenuate both NMDA excitotoxicity and staurosporine‐induced neuronal cell death. LY354740 and LY379268 were protective against transient global ischemia in gerbils when dosed intraperitoneally.These results support the view that antagonists of mGlu1 and mGlu5 and agonists of group II mGlu receptors may be useful agents in the therapeutic treatment of neurodegenerative disease.
NPS 1506, A Novel NMDA Receptor Antagonist and Neuroprotectant: Review of Preclinical and Clinical Studies
Authors: MUELLER ALAN L. , ARTMAN LINDA D. , BALANDRIN MANUEL F. , BRADY ELLEN , CHIEN YONGWEI (ERIC) , DELMAR ERIC G. , GEORGE KAREN , KIERSTEAD ALLISON , MARRIOTT THOMAS B. , MOE SCOTT T. , NEWMAN MICHAEL K. , RASZKIEWICZ JOANNA L. , SANGUINETTI ELIZABETH L. , VAN WAGENEN BRADFORD C. , WELLS DAVID 
Published: February 2006

ABSTRACT: NPS 1506 is a moderate affinity, uncompetitive N‐methyl‐d‐aspartate (NMDA) receptor antagonist. NPS 1506 is neuroprotective in rodent models of ischemic stroke, hemorrhagic stroke, and head trauma, with a 2‐hr window of opportunity. Neuroprotectant doses of NPS 1506 ranged from approximately 0.1–1.0 mg/kg, with peak plasma concentrations ranging from 8–80 ng/mL. Even at doses producing behavioral toxicity, NPS 1506 did not elicit MK‐801‐like behaviors, did not generalize to phencyclidine (PCP), and did not elicit neuronal vacuolization.In a Phase I study, intravenous (i.v.) doses of NPS 1506 from 5–100 mg were well tolerated and provided plasma concentrations in excess of those required for neuroprotection in rodents. Adverse events at the 100‐mg dose included mild dizziness and lightheadedness, and mild to moderate ataxia. Neither PCP‐like psychotomimetic effects nor cardiovascular effects were noted. The long plasma half‐life of NPS 1506 (∼60 hr) suggests that a single i.v. dose will provide prolonged neuroprotection in humans.
Lymphohematopoietic Stem Cell Engraftmenta
Authors: QUESENBERRY PETER J. , STEWART F. MARC , ZHONG SUJU , HABIBIAN HOURI , MCAULIFFE CHRISTINA , REILLY JUDY , CARLSON JANE , DOONER MARK , NILSSON SUSIE , PETERS STEFAN , STEIN GARY , STEIN JANET , EMMONS ROB , BENOIT BRIAN , BERTONCELLO IVAN , BECKER PAMELA 
Published: February 2006

Abstract: Traditional dogma has stated that space needs to be opened by cytoxic myeloablative therapy in order for marrow stem cells to engraft. Recent work in murine transplant models, however, indicates that engraftment is determined by the ratio of donor to host stem cells, i.e., stem cell competition. One hundred centigray whole body irradiation is stem cell toxic and nonmyelotoxic, thus allowing for higher donor chimerism in a murine syngeneic transplant setting. This nontoxic stem cell transplantation can be applied to allogeneic transplant with the addition of a tolerizing step; in this case presensitization with donor spleen cells and administration of CD40 ligand antibody to block costimulation.The stem cells that engraft in the nonmyeloablated are in G0, but are rapidly induced (by 12 hours) to enter the S phase after in vivo engraftment. Exposure of murine marrow to cytokines (IL‐3, IL‐6, IL‐11 and steel factor) expands progenitor clones, induces stem cells into cell cycle, and causes a fluctuating engraftment phenotype tied to phase of cell cycle. These data indicate that the concepts of stem cell competition and fluctuation of stem cell phenotype with cell cycle transit should underlie any new stem cell engraftment strategy.