Showing papers by "University of Louisville published in 1999"
TL;DR: An important implication of the phenomenon of myocardial stunning is that so-called chronic hibernation may in fact be the result of repetitive episodes of stunning, which have a cumulative effect and cause protracted postischemic dysfunction.
Abstract: The past two decades have witnessed an explosive growth of knowledge regarding postischemic myocardial dysfunction or myocardial “stunning.” The purpose of this review is to summarize current infor...
1,018 citations
TL;DR: The Sixth Conference on the "Standards of Laboratory Practice Series", sponsored by the National Academy of Clinical Biochemistry (NACB), was held on August 4-5, 1998, at the Annual Meeting of the American Association for Clinical Chemistry, in Chicago, IL, and an expert committee was assembled to write recommendations on the use of cardiac markers in coronary artery diseases.
Abstract: The Sixth Conference on the "Standards of Laboratory Practice Series", sponsored by the National Academy of Clinical Biochemistry (NACB), was held on August 4-5, 1998, at the Annual Meeting of the American Association for Clinical Chemistry, in Chicago, IL. An expert committee was assembled to write recommendations on the use of cardiac markers in coronary artery diseases. The NACB Committee prepared a preliminary draft of the guidelines, made them available on the World Wide Web (www.nacb.org), and distributed them before the presentations. The recommendations were divided into four areas: the use of markers in the triage of patients with chest pain, acute coronary syndromes, clinical applications other than acute myocardial infarction and research, and assay platforms and markers of acute myocardial infarction. The recommendations were revised and subsequently re-presented in part at the "Biomarkers in Acute Cardiac Syndromes Conference", sponsored by the Jewish Hospital Heart and Lung Institute, Louisville KY, on October 16-17, 1998. This report lists each recommendation, its scientific justification, and a summary of discussions from conference participants and reviewers. Approximately 100 individuals responded to various versions of these recommendations via direct correspondences, telephone calls to Committee members, electronic mail correspondence to the Committee Chairman, or oral questions and comments raised during one of the two conference presentations. Some of the recommendations were changed to reflect the consensus opinion. In cases in which there was no consensus, the Committee included pertinent discussion without necessarily changing the original recommendations. At times, the Committee members felt that although a particular recommendation might not be the current standard of care today, they anticipate that it likely will be adopted in the near future.
675 citations
TL;DR: The AMISTAD trial as discussed by the authors was designed to test the hypothesis that adenosine as an adjunct to thrombolysis would reduce myocardial infarct, and the results showed that the hypothesis was true.
546 citations
TL;DR: This article explored the linkages among these three constructs when services are classified on the basis of search, experience, and credence attributes, and found that perceived risk increases along a continuum from search to experience to credence service purchases.
Abstract: Though the marketing literature offers an abundance of research on the topics of perceived risk, information search, and purchase intentions, very few researchers have empirically examined these constructs in the context of services. This research explores the linkages among these three constructs when services are classified on the basis of search, experience, and credence attributes. Specific hypotheses are developed and tested. The results of this study indicate that perceived risk increases along a continuum from search to experience to credence service purchases. Other hypotheses relating to information search length, information sources, behavioral intentions, and service attributes, received moderate support. Finally, managerial implications of the study were provided, along with directions for future research.
509 citations
TL;DR: The current manner in which enteral tube feeding is delivered in the ICU results in grossly inadequate nutritional support and barely one half of patient caloric requirements are met because of underordering by physicians and reduced delivery through frequent and often inappropriate cessation of feedings.
Abstract: ObjectiveTo evaluate those factors that impact on the delivery of enteral tube feeding.DesignProspective study.SettingMedical intensive care units (ICU) and coronary care units at two university-based hospitals.PatientsForty-four medical ICU/coronary care unit patients (mean age, 57.8 yrs; 70% male)
490 citations
TL;DR: Rofecoxib, at doses 2-4 times the dose demonstrated to relieve symptoms of osteoarthritis, caused significantly less gastroduodenal ulceration than ibuprofen, with ulcer rates comparable to placebo.
447 citations
TL;DR: Although further analysis should investigate whether the mortality difference was solely due to a direct treatment effect or to other factors, DCLHb does not appear to be an effective resuscitation fluid.
Abstract: ContextSevere, uncompensated, traumatic hemorrhagic shock causes significant
morbidity and mortality, but resuscitation with an oxygen-carrying fluid might
improve patient outcomes.ObjectiveTo determine if the infusion of up to 1000 mL of diaspirin cross-linked
hemoglobin (DCLHb) during the initial hospital resuscitation could reduce
28-day mortality in traumatic hemorrhagic shock patients.Design and SettingMulticenter, randomized, controlled, single-blinded efficacy trial conducted
between February 1997 and January 1998 at 18 US trauma centers selected for
their high volume of critically injured trauma patients, but 1 did not enroll
patients.PatientsA total of 112 patients with traumatic hemorrhagic shock and unstable
vital signs or a critical base deficit, who had a mean (SD) patient age of
39 (20) years. Of the infused patients, 79% were male and 56% were white.
An exception to informed consent was used when necessary.InterventionAll patients were to be infused with 500 mL of DCLHb or saline solution.
Critically ill patients who still met entry criteria could have received up
to an additional 500 mL during the 1-hour infusion period.Main Outcome MeasuresTwenty-eight day mortality, 28-day morbidity, 48-hour mortality, and
24-hour lactate levels.ResultsOf the 112 patients, 98 (88%) were infused with DCLHb or saline solution.
At 28 days, 24 (46%) of the 52 patients infused with DCLHb died, and 8 (17%)
of the 46 patients infused with the saline solution died (P = .003). At 48 hours, 20 (38%) of the 52 patients infused with DCLHb
died and 7 (15%) of the 46 patients infused with the saline solution died
(P = .01). The 28-day morbidity rate, as measured
by the multiple organ dysfunction score, was 72% higher in the DCLHb group
(P = .03). There was no difference in adverse event
rates or the 24-hour lactate levels.ConclusionsMortality was higher for patients treated with DCLHb. Although further
analysis should investigate whether the mortality difference was solely due
to a direct treatment effect or to other factors, DCLHb does not appear to
be an effective resuscitation fluid.
445 citations
TL;DR: In a multicenter, double-blind, placebo-controlled trial, a significantly greater proportion of patients in the 5-mg pilocarpine group showed improvement compared with the placebo group (P#.01) in global assess- ments of dry mouth, dry eyes, and other symptoms of dryness.
Abstract: Background: Patients with Sjogren syndrome (SS) ex- perience slowly progressive infiltration of lacrimal and salivary glands by mononuclear cells. This leads to di- minished secretions, with resultant symptoms of xero- stomia and xerophthalmia. Although pilocarpine hydro- chloride tablets are currently indicated for the treatment of radiation-induced xerostomia, their effects on dry mouth or dry eyes in patients with SS are unclear. Objective: To assess the safety and efficacy of pilocar- pine (Salagen) tablets as symptomatic treatment for dry mouth and dry eyes caused by SS in a multicenter, double- blind, placebo-controlled trial. Methods: After providing written informed consent, 373 patients with primary or secondary SS and clinically sig- nificant dry mouth and dry eyes were randomized to re- ceive 2.5-mg pilocarpine, 5-mg pilocarpine, or placebo tablets 4 times daily for 12 weeks. Symptoms were as- sessed by questionnaires with visual analog scales or cat- egorical checkboxes. Whole-mouth salivary flow rates were measured. Results: A significantly greater proportion of patients in the 5-mg pilocarpine group showed improvement com- pared with the placebo group (P#.01) in global assess- ments of dry mouth, dry eyes, and other symptoms of dryness (P#.05). Salivary flow was significantly in- creased 2- to 3-fold (P,.001) after administration of the first dose and was maintained throughout the 12-week study. The most common adverse effect was sweating, and no serious drug-related adverse experiences were re- ported.
370 citations
TL;DR: In kinetic competition experiments using free radical-trapping agents, the capacity of IPA to scavenge hydroxyl radicals exceeded that of melatonin, an indoleamine considered to be the most potent naturally occurring scavenger of free radicals.
330 citations
TL;DR: Compared signaling pathways activated by GDNF in two neuronal cell lines expressing different complements of GDNF receptors are compared to indicate the existence of novel signaling mechanisms directly or indirectly mediated by GFRα receptors acting in a cell-autonomous manner independently of Ret.
325 citations
TL;DR: Moore et al. as discussed by the authors proposed a method for the identification of the most important genes in the Biology Department of the University of Louisville, Kentucky, 40292, USA, USA.
Abstract: Editor: Randy Moore, Biology Department, University of Louisville, Louisville, KY 40292, Phone: (502) 852-6490, E-mail: randy.moore@louisville.edu Managing Editor: Christine Chantry Associate Editor: Kris Collum Publisher: Wayne W. Carley Editorial Staff: Kay Acevedo, Carmen Altamirano, Cheryl Merrill ABT Produiction Office: 11250 Roger Bacon Drive, #19, Reston, VA 20190-5202, Phone: (703) 471-1134, Fax: (703) 435-5582, E-mail: NABTer@aol.com, Web site: www.nabt.org
TL;DR: This is the first demonstration that NO can promote NF-kappaB activation in the heart, a finding that identifies a new biological function of NO and may have important implications for various pathophysiological conditions in which NO is involved and for nitrate therapy.
Abstract: —Although it is recognized that late preconditioning (PC) results from upregulation of cardioprotective genes, the specific transcription factor(s) that govern this genetic adaptation remains unknown. The aim of this study was to test the hypothesis that the development of late PC is mediated by nuclear factor-κB (NF-κB) and to elucidate the mechanisms that control the activation of NF-κB after an ischemic stimulus in vivo. A total of 152 chronically instrumented, conscious rabbits were used. A sequence of six 4-minute coronary occlusion/4-minute reperfusion cycles, which elicits late PC, induced rapid activation of NF-κB, as evidenced by a marked increase in p65 content (+164%; Western immunoblotting) and NF-κB DNA binding activity (+306%; electrophoretic mobility shift assay) in nuclear extracts isolated 30 minutes after the last reperfusion. These changes were attenuated 2 hours after ischemic PC and resolved by 4 hours. Competition and supershift assays confirmed the specificity of the NF-κB D...
TL;DR: In this article, the authors measured communities of macrophyte aboveground biomass, macro-organic matter (MOM), benthic invertebrates, and ecosystem processes (soil development, organic C, N, and P accumulation) of two constructed and paired natural S. alterniflora (Loisel) marshes in North Carolina during the past 25 years.
Abstract: Wetland creation and restoration are frequently used to replace ecological functions and values lost when natural wetlands are degraded or destroyed. On many sites, restoration of ecological attributes such as secondary production, habitat/species diversity, and wetland soil characteristics do not occur within the first decade, and no long-term studies exist to document the length of time required to achieve complete restoration of wetland dependent functions and values. Characteristics of community structure (macrophyte aboveground biomass, macro-organic matter [MOM], benthic invertebrates) and ecosystem processes (soil development, organic C, N, and P accumulation) of two constructed Spartina alterniflora (Loisel) marshes (established 1971 and 1974) and paired natural S. alterniflora marshes in North Carolina were periodically measured during the past 25 yr. On constructed marshes, the macrophyte community developed quickly, and within 5 to 10 yr, aboveground biomass and MOM were equivalent to or exceed...
TL;DR: In this paper, a statistical method for defining housing sub-markets was developed using household survey data for Sydney and Melbourne, Australia, and applied using principal component analysis (PCA) to extract a set of factors from the original variables for both local government area (LGA) data and a combined set of LGA and individual dwelling data.
Journal Article•
TL;DR: Mouse leukocyte CR3 (Mac-1, alphaMbeta2 integrin) was shown to function as a receptor for beta-glucans in the same way as human CR3, and the similarity of mouse and humanCR3 in response to beta-Glucans highlights the utility of mouse tumor models for development of therapeutic beta- glucans.
Abstract: Mouse leukocyte CR3 (Mac-1, alphaMbeta2 integrin) was shown to function as a receptor for beta-glucans in the same way as human CR3. Soluble zymosan polysaccharide (SZP) or pure beta-glucans labeled with FITC or 125I bound in a saturable and reversible manner to neutrophils, macrophages, and NK cells. This lectin activity was blocked by anti-CD11b mAb M1/70 or 5C6 and did not occur with leukocytes from CR3-/- (CD11b-deficient) mice. SZP preparations containing primarily mannose or glucose bound to CR3, and the binding of 125I-labeled beta-glucan to CR3 was competitively inhibited by beta-glucans from barley or seaweed, but not by yeast alpha-mannan. Also, as with human CR3, the lectin site of mouse CR3 was inhibited by alpha- or beta-methylglucoside (but not D-glucose), alpha- or beta-methylmannoside, and N-acetyl-D-glucosamine. Phagocytosis of zymosan and serum-opsonized zymosan was partially inhibited by anti-CR3 and was reduced to <40% of normal with leukocytes from CR3-/- mice. As with neutrophils from patients with CD18 deficiency, neutrophils from CR3-/- mice exhibited no phagocytosis of particulate beta-glucan. SZP or beta-glucans primed CR3 of neutrophils, macrophages, and NK cells for cytotoxicity of iC3b-opsonized tumor cells that otherwise did not trigger killing. beta-Glucan priming for cytotoxicity was inhibited by anti-CR3 and did not occur with leukocytes from CR3-/- mice. The primed state of macrophage and NK cell CR3 remained detectable for 18 to 24 h after pulsing with beta-glucans. The similarity of mouse and human CR3 in response to beta-glucans highlights the utility of mouse tumor models for development of therapeutic beta-glucans.
TL;DR: Results basically support the concept of replacing damaged photoreceptors with subretinally implanted stimulation devices and show no significant side effect of subretinal implants on retinal function or the architecture of the inner retina.
TL;DR: The results provide direct evidence that NO donors induce late PC by activating PKC and that among the 10 isozymes of PKC expressed in the rabbit heart, the epsilon isotype is specifically involved in the development of this form of pharmacological PC.
Abstract: Although isoform-selective translocation of protein kinase C (PKC) epsilon appears to play an important role in the late phase of ischemic preconditioning (PC), the mechanism(s) responsible for such translocation remains unclear. Furthermore, the signaling pathway that leads to the development of late PC after exogenous administration of NO in the absence of ischemia (NO donor-induced late PC) is unknown. In the present study we tested the hypothesis that NO activates PKC and that this is the mechanism for the development of both ischemia-induced and NO donor-induced late PC. A total of 95 chronically instrumented, conscious rabbits were used. In rabbits subjected to ischemic PC (six 4-minute occlusion/4-minute reperfusion cycles), administration of the NO synthase inhibitor Nomega-nitro-L-arginine (group III), at doses previously shown to block the development of late PC, completely blocked the ischemic PC-induced translocation of PKCepsilon but not of PKCeta, indicating that increased formation of NO is an essential mechanism whereby brief ischemia activates the epsilon isoform of PKC. Conversely, a translocation of PKCepsilon and -eta quantitatively similar to that induced by ischemic PC could be reproduced pharmacologically with the administration of 2 structurally unrelated NO donors, diethylenetriamine/NO (DETA/NO) and S-nitroso-N-acetylpenicillamine (SNAP), at doses previously shown to elicit a late PC effect. The particulate fraction of PKCepsilon increased from 35+/-2% of total in the control group (group I) to 60+/-1% after ischemic PC (group II) (P<0.05), to 54+/-2% after SNAP (group IV) (P<0.05) and to 52+/-2% after DETA/NO (group V) (P<0.05). The particulate fraction of PKCeta rose from 66+/-5% in the control group to 86+/-3% after ischemic PC (P<0.05), to 88+/-2% after SNAP (P<0.05) and to 85+/-1% after DETA/NO (P<0.05). Neither ischemic PC nor NO donors had any appreciable effect on the subcellular distribution of PKCalpha, -beta1, -beta2, -gamma, -delta, - micro, or -iota/lambda; on total PKC activity; or on the subcellular distribution of total PKC activity. Thus, the effects of SNAP and DETA/NO on PKC closely resembled those of ischemic PC. The DETA/NO-induced translocation of PKCepsilon (but not that of PKCeta) was completely prevented by the administration of the PKC inhibitor chelerythrine at a dose of 5 mg/kg (group VI) (particulate fraction of PKCepsilon, 38+/-4% of total, P<0.05 versus group V; particulate fraction of PKCeta, 79+/-2% of total). The same dose of chelerythrine completely prevented the DETA/NO-induced late PC effect against both myocardial stunning (groups VII through X) and myocardial infarction (groups XI through XV), indicating that NO donors induce late PC by activating PKC and that among the 10 isozymes of PKC expressed in the rabbit heart, the epsilon isotype is specifically involved in the development of this form of pharmacological PC. In all groups examined (groups I through VI), the changes in the subcellular distribution of PKCepsilon protein were associated with parallel changes in PKCepsilon isoform-selective activity, whereas total PKC activity was not significantly altered. Taken together, the results provide direct evidence that isoform-selective activation of PKCepsilon is a critical step in the signaling pathway whereby NO initiates the development of a late PC effect both after an ischemic stimulus (endogenous NO) and after treatment with NO-releasing agents (exogenous NO). To our knowledge, this is also the first report that NO can activate PKC in the heart. The finding that NO can promote isoform-specific activation of PKC identifies a new biological function of this radical and a new mechanism in the signaling cascade of ischemic PC and may also have important implications for other pathophysiological conditions in which NO is involved and for nitrate therapy.
TL;DR: It is suggested that the heightened energy demands of activated neurons are met through increased glial glycolytic flux, which is a crucial aerobic energy substrate that enables neurons to endure activation.
Abstract: Aerobic energy metabolism uses glucose and oxygen to produce all the energy needs of the brain. Several studies published over the last 13 years challenged the assumption that the activated brain increases its oxidative glucose metabolism to meet the increased energy demands. Neuronal function in rat hippocampal slices supplied with 4 mm glucose could tolerate a 15 min activation by a 5 mm concentration of the excitatory neurotransmitter glutamate (Glu), whereas slices supplied with 10 mm glucose could tolerate a 15 min activation by 20 mm Glu. However, in slices in which neuronal lactate use was inhibited by the lactate transporter inhibitor a-cyano-4-hydroxycinnamate (4-CIN), activation by Glu elicited a permanent loss of neuronal function, with a twofold to threefold increase in tissue lactate content. Inhibition of glycolysis with the glucose analog 2-deoxy-d-glucose (2DG) during the period of exposure to Glu diminished normal neuronal function in the majority of slices and significantly reduced the number of slices that exhibited neuronal function after activation. However, when lactate was added with 2DG, the majority of the slices were neuronally functional after activation by Glu. NMDA, a nontransportable Glu analog by the glial glutamate transporter, could not induce a significant increase in slice lactate level when administered in the presence of 4-CIN. It is suggested that the heightened energy demands of activated neurons are met through increased glial glycolytic flux. The lactate thus formed is a crucial aerobic energy substrate that enables neurons to endure activation.
TL;DR: This review discusses a novel type of immunotherapy for cancer that uses soluble yeast β-glucan to override the normal resistance of iC3b-opsonized tumor cells to the cytotoxic activation of phagocyte and NK cell CR3, allowing this important effector mechanism of the C system to function against tumor cells in the same way that it normally functions against bacteria and yeast.
TL;DR: The ability of HIV-1 gp120 to bind directly and specifically to the chemokine receptor CXCR4 in a CD4-dependent manner is demonstrated, using a conformationally complex structure on CX CR4.
Abstract: The interaction of the chemokine stromal cell-derived factor 1 (SDF-1) with its receptor CXCR4 is vital for cell trafficking during development, is capable of inhibiting human immunodeficiency virus type 1 (HIV-1) utilization of CXCR4 as a coreceptor, and has been implicated in delaying disease progression to AIDS in vivo. Because of the importance of this chemokine-chemokine receptor pair to both development and disease, we investigated the molecular basis of the interaction between CXCR4 and its ligands SDF-1 and HIV-1 envelope. Using CXCR4 chimeras and mutants, we determined that SDF-1 requires the CXCR4 amino terminus for binding and activates downstream signaling pathways by interacting with the second extracellular loop of CXCR4. SDF-1-mediated activation of CXCR4 required the Asp-Arg-Tyr motif in the second intracellular loop of CXCR4, was pertussis toxin sensitive, and did not require the distal C-terminal tail of CXCR4. Several CXCR4 mutants that were not capable of binding SDF-1 or signaling still supported HIV-1 infection, indicating that the ability of CXCR4 to function as a coreceptor is independent of its ability to signal. Direct binding studies using the X4 gp120s HXB, BH8, and MN demonstrated the ability of HIV-1 gp120 to bind directly and specifically to the chemokine receptor CXCR4 in a CD4-dependent manner, using a conformationally complex structure on CXCR4. Several CXCR4 variants that did not support binding of soluble gp120 could still function as viral coreceptors, indicating that detectable binding of monomeric gp120 is not always predictive of coreceptor function.
TL;DR: Gaining control of Legionella in environmental waters, where they are protected from disinfection by growing within protozoa and biofilms, remains a challenge, and one that must be overcome in order to eliminate sporadic outbreaks of legionellosis.
Abstract: Studies on Legionella show a continuum from environment to human disease. Legionellosis is caused by Legionella species acquired from environmental sources, principally water sources such as cooling towers, where Legionella grows intracellularly in protozoa within biofilms. Aquatic biofilms, which are widespread not only in nature, but also in medical and dental devices, are ecological niches in which Legionella survives and proliferates and the ultimate sources to which outbreaks of legionellosis can be traced. Invasion and intracellular replication of L. pneumophila within protozoa in the environment play a major role in the transmission of Legionnaires' disease. Protozoa provide the habitats for the environmental survival and reproduction of Legionella species. L. pneumophila proliferates intracellularly in various species of protozoa within vacuoles studded with ribosomes, as it also does within macrophages. Growth within protozoa enhances the environmental survival capability and the pathogenicity (virulence) of Legionella. The growth requirements of Legionella, the ability of Legionella to enter a viable non-culturable state, the association of Legionella with protozoa and the occurrence of Legionella within biofilms complicates the detection of Legionella and epidemiological investigations of legionellosis. Polymerase chain reaction (PCR) methods have been developed for the molecular detection of Legionella and used in environmental and epidemiological studies. Various physical and chemical disinfection methods have been developed to eliminate Legionella from environmental sources, but gaining control of Legionella in environmental waters, where they are protected from disinfection by growing within protozoa and biofilms, remains a challenge, and one that must be overcome in order to eliminate sporadic outbreaks of legionellosis.
TL;DR: There is strong evidence that the prognosis for neurologic recovery is adversely affected by both a higher percentage of canal narrowing and a longer duration of Canal narrowing after a spinal cord injury.
Abstract: STUDY DESIGN The effect of spinal canal narrowing and the timing of decompression after a spinal cord injury were evaluated using a rat model. OBJECTIVE To evaluate whether progressive spinal canal narrowing after a spinal cord injury results in a less favorable neurologic recovery. Additionally, to evaluate the effect of the timing of decompression after spinal cord injury on neurologic recovery. SUMMARY OF BACKGROUND DATA Results in previous studies are contradictory about whether the amount of canal narrowing or the timing of decompression after a spinal cord injury affects the degree of neurologic recovery. METHODS Forty adult male Sprague-Dawley rats were equally divided into a control group, in which spacers of 20%, 35%, and 50% were placed into the spinal canal after laminectomy, and an injury group in which the spacers were placed after a standardized incomplete spinal cord injury. After spacer removal, neurologic recovery in both was monitored by Basso, Beattie, Bresnahan (BBB) Locomotor Rating Scale (Ohio State University, Columbus, OH) motor scores and transcranial magnetic motor evoked potentials for 6 weeks followed by histologic examination of the spinal cords. Subsequently, 42 rats were divided into five groups in which, after spacer placement, the time until decompression was lengthened 0, 2, 6, 24, and 72 hours. Again, serial BBB motor scores and transcranial magnetic motor evoked potentials were used to assess neurologic recovery for 6 weeks until the animals were killed for histologic evaluation. RESULTS Spacer placement alone in the control animals resulted in no neurologic injury until canal narrowing reached 50%. All of the control groups (spacer only) exhibited significantly better (P < 0.05) motor scores compared with the injury groups (injury followed by spacer insertion). Within the injury groups the motor scores were progressively lower as spacer sizes increased from the no-spacer group to the 35% group. The results in the 35% and 50% groups were not statistically different. The results of the time until decompression demonstrated that the motor scores were consistently better the shorter the duration of spacer placement (P < 0.05) for each of the time groups (0, 2, 6, 24, and 72 hours) over the 6-week recovery period. Histologic analysis showed more severe spinal cord damage as both spinal canal narrowing and the time until decompression increased. CONCLUSION The results in this study present strong evidence that the prognosis for neurologic recovery is adversely affected by both a higher percentage of canal narrowing and a longer duration of canal narrowing after a spinal cord injury. The tolerance for spinal canal narrowing with a contused cord appears diminished, indicating that an injured spinal cord may benefit from early decompression. Additionally, it appears that the longer the spinal cord compression exists after an incomplete spinal cord injury, the worse the prognosis for neurologic recovery.
TL;DR: EH causes a progressive increase in BP, mediated in part through renal sympathetic nerve activity that acts to increase renin-angiotensin system activity through angiotens in II type 1 receptors.
Abstract: Previous studies in several strains of rats have demonstrated that 35 days of recurrent episodic hypoxia (EH) (7 hours per day), with a fractional concentration of inspired oxygen that produces desaturation equivalent to the recurrent hypoxemia of sleep apnea, results in an 8 to 13 mm Hg persistent increase in diurnal systemic blood pressure (BP). Carotid chemoreceptors and the sympathetic nervous system have been shown to be necessary for development of this BP increase. Both renal artery denervation and adrenal demedullation block the BP response to chronic EH. The present study was undertaken to define further the role of the kidneys and the renin-angiotensin system in this BP increase. Separate groups of male Sprague-Dawley rats had either (1) bilateral renal artery denervation with EH, (2) sham surgery with EH, (3) sham surgery with sham EH (compressed air), (4) EH with losartan, (5) unhandled with losartan, or (6) unhandled. The experimental period lasted 35 days. Both renal-artery denervated and losartan-treated animals showed no BP change or a lowering of BP in response to EH, whereas the sham-operated EH animals showed a progressive, sustained increase in resting room air BP. BP remained at basal levels or fell in unhandled and unhandled losartan-treated animals. Plasma renin activity was elevated 4-fold versus basal levels in EH animals with renal nerves intact but remained at baseline levels in denervated animals. At the end of the experiment, renal tissue catecholamines confirmed renal denervation in those animals. In conclusion, EH causes a progressive increase in BP, mediated in part through renal sympathetic nerve activity that acts to increase renin-angiotensin system activity through angiotensin II type 1 receptors.
TL;DR: Using simple clinical and laboratory criteria, a significant proportion of hospitalized patients with community-acquired pneumonia can be treated with early switch and early discharge, and this model did not affect patient outcome, decreased the length of hospitalization, and was associated with a high level of patient satisfaction.
Abstract: Objectives: To determine the proportion of patients who can be treated with early switch to oral antibiotics and early discharge, to evaluate clinical outcome and patient satisfaction for patients treated with early switch and early discharge, and to define the factors that interfere with early discharge for some of the patients who underwent early switch to oral antibiotic therapy. Design: Prospective study. Participants: Two hundred consecutive hospitalized patients with community-acquired pneumonia. Main Outcome Measures: Number of days needed to switch to oral therapy and length of hospital stay. Clinical outcome and satisfaction with care were evaluated for those patients treated with early switch and early discharge. Results: Early switch to oral antibiotics (within the first 3 days of hospitalization) was performed in 133 patients (67%). Clinical failure was documented in 1 patient. Early switch and early discharge was performed in 88 patients (44%). The mean length of hospital stay for this group was 3.4 days. The most common reason for prolonged hospitalization after the switch to oral antibiotics was the need for diagnostic workup. More than 95% of patients were satisfied with the care they had received. Conclusions: Using simple clinical and laboratory criteria, a significant proportion of hospitalized patients with community-acquired pneumonia (44%) can be treated with early switch and early discharge. This model did not affect patient outcome, decreased the length of hospitalization, and was associated with a high level of patient satisfaction. Arch Intern Med. 1999;159:2449-2454
TL;DR: Using routine activity theory, the model highlights lifestyle behaviors and interactions as predictors of stalking victimization and emphasizes the role of women's social interactions and substance use in victimization risk.
Abstract: Drawing on surveys administered to 861 university women in nine institutions, this article presents a routine activity theory model for predicting stalking victimization likelihood for women. Using routine activity theory, the model highlights lifestyle behaviors and interactions as predictors of stalking victimization. Whereas routine activity theory often highlights the role of demographics and statuses as predictors, this analysis emphasizes the role of women's social interactions and substance use in victimization risk. Significant predictors of victimization likelihood include substance use variables, activities in public settings, and residence off campus.
TL;DR: The results suggest that neutrophils and adhesion molecules play an important role in mediating tissue injury with subsequent renal failure, and that chronic renal failure reduces neutrophil function and thereby can increase susceptibility to infection and sepsis.
TL;DR: The data suggest that IL‐10 protects against hepatic ischemia/reperfusion injury by suppressing NFκB activation and subsequent expression of proinflammatory mediators.
TL;DR: There was no difference in the rate of recurrent and de novo disease according to the transplant type (living related donor vs. cadaver, P=NS), and demographic findings were not significantly different.
Abstract: INTRODUCTION Short-term and long-term results of renal transplantation have improved over the past 15 years. However, there has been no change in the prevalence of recurrent and de novo diseases. A retrospective study was initiated through the Renal Allograft Disease Registry, to evaluate the prevalence and impact of recurrent and de novo diseases after transplantation. MATERIALS AND METHODS From October 1987 to December 1996, a total of 4913 renal transplants were performed on adults at the Medical College of Wisconsin, University of Cincinnati, University of California at San Francisco, University of Louisville, University of Washington, Seattle, and Washington University School of Medicine. The patients were followed for a minimum of 1 year. A total of 167 (3.4%) cases of recurrent and de novo disease were diagnosed by renal biopsy. These patients were compared with other patients who did not have recurrent and de novo disease (n=4746). There were more men (67.7% vs. 59.8%, P<0.035) and a higher number of re-transplants (17% vs. 11.5%, P<0.005) in the recurrent and de novo disease group. There was no difference in the rate of recurrent and de novo disease according to the transplant type (living related donor vs. cadaver, P=NS). Other demographic findings were not significantly different. Common forms of glomerulonephritis seen were focal segmental glomerulosclerosis (FSGS), 57; immunoglobulin A nephritis, 22; membranoproliferative glomerulonephritis (GN), 18; and membranous nephropathy, 16. Other diagnoses include: diabetic nephropathy, 19; immune complex GN, 12; crescentic GN (vasculitis), 6; hemolytic uremic syndrome-thrombotic thrombocytopenic purpura (HUS/TTP), 8; systemic lupus erythematosus, 3; Anti-glomerular basement membrane disease, 2; oxalosis, 2; and miscellaneous, 2. The diagnosis of recurrent and de novo disease was made after a mean period of 678 days after the transplant. During the follow-up period, there were significantly more graft failures in the recurrent disease group, 55% vs. 25%, P<0.001. The actuarial 1-, 2-, 3-, 4, and 5-year kidney survival rates for patients with recurrent and de novo disease was 86.5%, 78.5%, 65%, 47.7%, and 39.8%. The corresponding survival rates for patients without recurrent and de novo disease were 85.2%, 81.2%, 76.5%, 72%, and 67.6%, respectively (Log-rank test, P<0.0001). The median kidney survival rate for patients with and without recurrent and de novo disease was 1360 vs. 3382 days (P<0.0001). Multivariate analysis using the Cox proportional hazard model for graft failure was performed to identify various risk factors. Cadaveric transplants, prolonged cold ischemia time, elevated panel reactive antibody, and recurrent disease were identified as risk factors for allograft failure. The relative risk (95% confidence interval) for graft failure because of recurrent and de novo disease was 1.9 (1.57-2.40), P<0.0001. The relative risk for graft failure because of posttransplant FSGS was 2.25 (1.6-3.1), P<0.0001, for membranoprolifera. tive glomerulonephritis was 2.37 (1.3-4.2), P<0.003, and for HUS/TTP was 5.36 (2.2-12.9), P<0.0002. There was higher graft failure (64.9%) and shorter half-life (1244 days) in patients with recurrent FSGS. CONCLUSION In conclusion, recurrent and de novo disease are associated with poorer long-term survival, and the relative risk of allograft loss is double. Significant impact on graft survival was seen with recurrent and de novo FSGS, membranoproliferative glomerulonephritis, and HUS/TTP.
Boston Children's Hospital1, University of Kansas2, Ohio State University3, Indiana University4, Cincinnati Children's Hospital Medical Center5, National Institutes of Health6, University of Kentucky7, Children's Memorial Hospital8, Baylor College of Medicine9, University of North Carolina at Chapel Hill10, University of Louisville11
TL;DR: The Childhood Myositis Assessment Scale is validated to quantitatively assess muscle function in the areas of strength and endurance in children with idiopathic inflammatory myopathies and can be used in routine clinical care as well as therapeutic trials.
Abstract: Objective
To develop, validate, and determine the measurement characteristics of a quantitative tool for assessing the severity of muscle involvement in children with idiopathic inflammatory myopathies
Methods
The Childhood Myositis Assessment Scale (CMAS) was developed from 2 existing observational functional assessment tools to assess muscle function in the areas of strength and endurance across a wide range of ability and ages The 14 ordinal items included were chosen to assess primarily axial and proximal muscle groups and are ranked with standard performance and scoring methods Following the development of the CMAS, a training video and written instructions were developed and reviewed by the physicians participating in this study Subsequently, utilizing a randomized block design, 12 physicians independently scored 10 children (9 with dermatomyositis, 1 with polymyositis; ages 4–15 years) twice in one day (morning and afternoon) on the CMAS A pediatric physical therapist performed quantitative manual muscle strength testing (MMT) twice on each child (morning and afternoon), including the neck, trunk, and proximal and distal extremity muscle groups
Results
The CMAS has a potential range of 0–51, with higher scores indicating greater muscle strength and endurance The observed mean for the 10 patients was 364 (median 44, SD 141, observed range 5–51) The total score for the CMAS correlated with the physician's global assessment (by visual analog scale) of disease activity, the MMT score, serum creatine kinase level, and the Juvenile Arthritis Functional Assessment Report score The score on the CMAS was not correlated with patient age Interrater reliability (Kendall's coefficient of concordance) ranged from 077 to 10 for individual items (all P < 0001), and overall, it was 095 (P < 0001) Intrarater reliability for the individual physicians was measured by correlation of the CMAS scores for each patient on 2 separate evaluations and ranged from 097 to 099, with an overall correlation for all physicians of 098 (all P < 0001)
Conclusion
The CMAS demonstrated an acceptable range of observed scores, excellent convergent validity, and excellent inter- and intrarater reliability The CMAS is validated to quantitatively assess muscle function in the areas of strength and endurance in children with idiopathic inflammatory myopathies It can be used in routine clinical care as well as therapeutic trials
TL;DR: In hemodynamically stable patients with blunt liver trauma, nonoperative management is the current treatment of choice, and most untoward outcomes can be successfully managed nonoperatively using alternative therapeutic options.
Abstract: Background: Nonoperative management has become the standard of care for hemodynamically stable patients with complex liver trauma. The benefits of such treatment may be obviated, though, by complications such as arteriovenous fistulas, bile leaks, intrahepatic or perihepatic abscesses, and abnormal communications between the vascular system and the biliary tree (hemobilia and bilhemia). Methods: We reviewed the hospital charts of 135 patients with blunt liver trauma who were treated nonoperatively between July 1995 and December 1997. Results: Thirty-two patients (24%) developed complications that required additional interventional treatment. Procedures less invasive than celiotomy were often performed, including arteriography and selective embolization in 12 patients (37%), computed tomography-guided drainage of infected collections in 10 patients (31%), endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy and biliary endostenting in 8 patients (25%), and laparoscopy in 2 patients (7%). Overall, nonoperative interventional procedures were used successfully to treat these complications in 27 patients (85%). Conclusion: In hemodynamically stable patients with blunt liver trauma, nonoperative management is the current treatment of choice. In patients with severe liver injuries, however, complications are common. Most untoward outcomes can be successfully managed nonoperatively using alternative therapeutic options. Early use of these interventional procedures is advocated in the initial management of the complications of severe blunt liver trauma.