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Sample records for acute neurological injury

  1. Neurological Effects of Blast Injury

    PubMed Central

    Hicks, Ramona R.; Fertig, Stephanie J.; Desrocher, Rebecca E.; Koroshetz, Walter J.; Pancrazio, Joseph J.

    2010-01-01

    Over the last few years, thousands of soldiers and an even greater number of civilians have suffered traumatic injuries due to blast exposure, largely attributed to improvised explosive devices in terrorist and insurgent activities. The use of body armor is allowing soldiers to survive blasts that would otherwise be fatal due to systemic damage. Emerging evidence suggests that exposure to a blast can produce neurological consequences in the brain, but much remains unknown. To elucidate the current scientific basis for understanding blast-induced traumatic brain injury (bTBI), the NIH convened a workshop in April, 2008. A multidisciplinary group of neuroscientists, engineers, and clinicians were invited to share insights on bTBI, specifically pertaining to: physics of blast explosions, acute clinical observations and treatments, preclinical and computational models, and lessons from the international community on civilian exposures. This report provides an overview of the state of scientific knowledge of bTBI, drawing from the published literature, as well as presentations, discussions, and recommendations from the workshop. One of the major recommendations from the workshop was the need to characterize the effects of blast exposure on clinical neuropathology. Clearer understanding of the human neuropathology would enable validation of preclinical and computational models, which are attempting to simulate blast wave interactions with the central nervous system. Furthermore, the civilian experience with bTBI suggests that polytrauma models incorporating both brain and lung injuries may be more relevant to the study of civilian countermeasures than considering models with a neurological focus alone. PMID:20453776

  2. [Acute vertigo of neurological origin].

    PubMed

    Bruun, Marie; Højgaard, Joan L Sunnleyg; Kondziella, Daniel

    2013-11-04

    Acute vertigo of neurological origin may be caused by haemorrhages and tumours in the posterior fossa and, most frequently, by ischaemic infarction in the vertebrobasilar circulation. Urgent diagnosis is necessary to avoid further ischaemic episodes, herniation due to cerebellar oedema and/or fatal brainstem infarction. The history should focus on accompanying neurological symptoms. However, vertigo with cerebellar lesions may be monosymptomatic and then bedside evaluation of oculomotor function is the key to correct diagnosis. This paper discusses the pathophysiology, symptomatology and clinical evaluation of acute vertigo of neurological origin.

  3. Neurological outcome after experimental lung injury.

    PubMed

    Bickenbach, Johannes; Biener, Ingeborg; Czaplik, Michael; Nolte, Kay; Dembinski, Rolf; Marx, Gernot; Rossaint, Rolf; Fries, Michael

    2011-12-15

    We examined the influences of acute lung injury and hypoxia on neurological outcome. Functional performance was assessed using a neurocognitive test and a neurologic deficit score (NDS) five days before. On experimental day, mechanically ventilated pigs were randomized to hypoxia only (HO group, n=5) or to acute lung injury (ALI group, n=5). Hemodynamics, respiratory mechanics, systemic cytokines and further physiologic variables were obtained at baseline, at the time of ALI, 2, 4 and 8h thereafter. Subsequently, injured lungs were recruited and animals weaned from the ventilator. Neurocognitive testing was re-examined for five days. Then, brains were harvested for neurohistopathology. After the experiment, neurocognitive performance was significantly worsened and the NDS increased in the ALI group. Histopathology revealed no significant differences. Oxygenation was comparable between groups although significantly higher inspiratory pressures occured after ALI. Cytokines showed a trend towards higher levels after ALI. Neurocognitive compromise after ALI seems due to a more pronounced inflammatory response and complex mechanical ventilation.

  4. Does surgical treatment within 4 hours after trauma have an influence on neurological remission in patients with acute spinal cord injury?

    PubMed Central

    Biglari, Bahram; Child, Christopher; Yildirim, Timur Mert; Swing, Tyler; Reitzel, Tim; Moghaddam, Arash

    2016-01-01

    Background The proper timing for surgery in patients with acute spinal cord injury is controversial. This study was conducted to detect if there is an advantage in early (within the first 4 hours after trauma) compared to late (between 4 and 24 hours after trauma) surgery on neurological outcome. Methods In this single institution prospective cohort study, data were analyzed from 51 spinal cord injured patients with an average age of 43.4 (±19.2) years. The influence of early (29 patients within the first 4 hours) as opposed to late (22 patients between 4 and 24 hours) decompression was evaluated by comparing data for neurological outcome. Patients of the study collectively suffered acute spinal fractures from C2 to L3 (cervical 39.2%, thoracic 29.4%, and lumbal 21.6%) or nonosseous lesions (9.8%). American Spinal Injury Association (ASIA) Impairment Scale (AIS) grades were assessed at time of admission and 6 months after trauma or longer depending on the time of release. Surgical treatment included early stabilization and decompression within 24 hours. Results No significant difference between improved neurological function, measured with the AIS, and an early or late surgery time can be seen (P=0.402). Furthermore, binary logistic regression shows no significant difference between sex or age, and AIS improvement as possible confounders. Conclusion In our study, all patients with spinal cord injury were treated with spine stabilization and decompression within the first 24 hours after trauma. Surgical decompression within the first 4 hours after trauma was not associated with improved neurological outcome compared to treatment between 4 and 24 hours. In a clinical context, this indicates that there is a time frame of at least 1 day in which optimal care is possible. PMID:27621643

  5. Prevention of Neurologic Injuries in Equestrian Sports.

    ERIC Educational Resources Information Center

    Brooks, William H.; Bixby-Hammett, Doris M.

    1988-01-01

    Risk of neurological injuries accompanies horseback riding, especially for children and adolescents. This article describes the mechanisms of craniospinal injuries and suggests measures to lessen risks. Measures include: identifying individuals who should not ride, developing criteria for resumption of riding after injury, developing protective…

  6. Acute kidney injury during pregnancy.

    PubMed

    Van Hook, James W

    2014-12-01

    Acute kidney injury complicates the care of a relatively small number of pregnant and postpartum women. Several pregnancy-related disorders such as preeclampsia and thrombotic microangiopathies may produce acute kidney injury. Prerenal azotemia is another common cause of acute kidney injury in pregnancy. This manuscript will review pregnancy-associated acute kidney injury from a renal functional perspective. Pathophysiology of acute kidney injury will be reviewed. Specific conditions causing acute kidney injury and treatments will be compared.

  7. [Acute radiation injury].

    PubMed

    Saito, Tsutomu

    2012-03-01

    Cell death due to DNA damage by ionizing radiation causes acute radiation injury of tissues and organs. Frequency and severity of the injuries increase according to dose increase, when the dose becomes more than threshold dose. The threshold dose of acute human radiation death is 1 Gy and LD50 of human is 4 Gy. Human dies due to the cerebrovascular syndrome, the gastrointestinal syndrome or the hematopoetic syndrome, when he received more than 20 Gy, 10-20 Gy or 3-8 Gy to his total body, respectively. Any tissue or organ, including embryo and fetus, does not show the acute injury, when it received less than 100 mSv. Acute injuries are usually reversible, and late injuries are sometimes irreversible.

  8. Neurological consequences of traumatic brain injuries in sports.

    PubMed

    Ling, Helen; Hardy, John; Zetterberg, Henrik

    2015-05-01

    Traumatic brain injury (TBI) is common in boxing and other contact sports. The long term irreversible and progressive aftermath of TBI in boxers depicted as punch drunk syndrome was described almost a century ago and is now widely referred as chronic traumatic encephalopathy (CTE). The short term sequelae of acute brain injury including subdural haematoma and catastrophic brain injury may lead to death, whereas mild TBI, or concussion, causes functional disturbance and axonal injury rather than gross structural brain damage. Following concussion, symptoms such as dizziness, nausea, reduced attention, amnesia and headache tend to develop acutely but usually resolve within a week or two. Severe concussion can also lead to loss of consciousness. Despite the transient nature of the clinical symptoms, functional neuroimaging, electrophysiological, neuropsychological and neurochemical assessments indicate that the disturbance of concussion takes over a month to return to baseline and neuropathological evaluation shows that concussion-induced axonopathy may persist for years. The developing brains in children and adolescents are more susceptible to concussion than adult brain. The mechanism by which acute TBI may lead to the neurodegenerative process of CTE associated with tau hyperphosphorylation and the development of neurofibrillary tangles (NFTs) remains speculative. Focal tau-positive NFTs and neurites in close proximity to focal axonal injury and foci of microhaemorrhage and the predilection of CTE-tau pathology for perivascular and subcortical regions suggest that acute TBI-related axonal injury, loss of microvascular integrity, breach of the blood brain barrier, resulting inflammatory cascade and microglia and astrocyte activation are likely to be the basis of the mechanistic link of TBI and CTE. This article provides an overview of the acute and long-term neurological consequences of TBI in sports. Clinical, neuropathological and the possible pathophysiological

  9. The neurologic manifestations of the acute porphyrias.

    PubMed

    Simon, Neil G; Herkes, Geoffrey K

    2011-09-01

    The porphyrias are diseases characterised by accumulation of porphyrins and porphyrin precursors owing to enzymatic deficiencies of the haem synthetic pathway. In the acute hepatic porphyrias accumulation of porphyrin precursors, in particular delta-aminolaevulinic acid (ALA), cause dysfunction of the central, peripheral and autonomic nervous systems. This leads to the characteristic clinical findings of abdominal pain, neuropsychiatric symptoms and neuropathy. The exact pathogenic mechanism is not clear but evidence to date suggests both direct toxic effects of ALA and intracellular metabolic derangement contribute to the neurologic disorders. This review explores the mechanisms of neural dysfunction in the acute porphyrias and the resultant clinical features of an acute attack.

  10. Early neurological stability predicts adverse outcome after acute ischemic stroke.

    PubMed

    Irvine, Hannah J; Battey, Thomas Wk; Ostwaldt, Ann-Christin; Campbell, Bruce Cv; Davis, Stephen M; Donnan, Geoffrey A; Sheth, Kevin N; Kimberly, W Taylor

    2016-10-01

    Background Deterioration in the National Institutes of Health Stroke Scale (NIHSS) in the early days after stroke is associated with progressive infarction, brain edema, and/or hemorrhage, leading to worse outcome. Aims We sought to determine whether a stable NIHSS score represents an adverse or favorable course. Methods Brain magnetic resonance images from a research cohort of acute ischemic stroke patients were analyzed. Using NIHSS scores at baseline and follow-up (day 3-5), patients were categorized into early neurological deterioration (ΔNIHSS ≥ 4), early neurological recovery (ΔNIHSS ≤ -4) or early neurological stability (ΔNIHSS between -3 and 3). The association between these categories and volume of infarct growth, volume of swelling, parenchymal hemorrhage, and 3-month modified Rankin Scale score were evaluated. Results Patients with early neurological deterioration or early neurological stability were less likely to be independent (modified Rankin Scale = 0-2) at 3 months compared to those with early neurological recovery ( P < 0.001). Patients with early neurological deterioration or early neurological stability were observed to have significantly greater infarct growth and swelling volumes than those with early neurological recovery ( P = 0.03; P < 0.001, respectively). Brain edema was more common than the other imaging markers investigated and was independently associated with a stable or worsening NIHSS score after adjustment for age, baseline stroke volume, infarct growth volume, presence of parenchymal hemorrhage, and reperfusion ( P < 0.0001). Conclusions Stable NIHSS score in the subacute period after ischemic stroke may not be benign and is associated with tissue injury, including infarct growth and brain edema. Early improvement is considerably more likely to occur in the absence of these factors.

  11. Improving hand hygiene after neurological injury.

    PubMed

    Duke, Lynsay; Gibbison, Lucy; McMahon, Victoria

    Caring for hands tightened by spasticity after stroke, brain injury or other neurological conditions can be challenging for care staff. Opening and cleaning the hand, managing pressure areas, cutting nails and reducing pain becomes more complex if muscles are tight and short. Hand hygiene is key for staff but literature on patients' hand and nail care is lacking, so specialist education and care planning may be needed to help staff ensure these activities are done well. This article outlines the importance of maintaining patients' hand hygiene, explores the barriers to providing effective care and discusses how they might be overcome.

  12. [Acute Kidney Injury].

    PubMed

    Brix, Silke; Stahl, Rolf

    2017-02-01

    Acute kidney injury (AKI) is an important part of renal diseases and a common clinical problem. AKI is an acute decline in renal function. Due to a lack of therapeutic options, prevention and optimal management of patients with AKI are the most important strategies. Although seldom the sole cause of patients' death, AKI is associated with a significant increase in mortality. Our objective is to draw the attention towards the prevention of AKI of non-renal causes.

  13. Acute injuries in orienteerers.

    PubMed

    Kujala, U M; Nylund, T; Taimela, S

    1995-02-01

    The aim of this study was to characterize the type and severeity of acute injuries occurring in Finnish orienteerers in 1987 to 1991. The study is based on the orienteering license insurance records accounting for 2189 orienteering injuries during 69268 person-years of exposure in active orienteerers. Of these orienteerers, 73.0% were male; 73.5% (N = 1608) of all injuries occurred in males, so the injury rate was similar in males and females. The rate was highest in orienteerers 20 to 24 years of age and lowest in children. Injuries occurred most commonly during May to September (78.9% or all injuries), the months which include the orienteering competition season, and were more common during competitions (59.8%) than during training. A high number of the injuries occurred during weekends (58.9% of injuries) including 68.1% of all competition injuries and 44.9% of all training injuries. The lower limbs were involved in 1611 (73.6%) of cases, the ankle (28.7%) and the knee (23.2%) being the two most common injury locations. Sprains, strains and contusions were the most common injuries. Wounds were proportionally more common in males than in females while ankle sprains were more common in females. Fractures, seven open and 94 closed, accounted for 4.6% of injuries; they were most common in the hand/wrist/forearm (N = 44) and ankle (N = 16), and were more frequent during competition (62.3%) than during training. The most important areas for preventive measures seem to be the ankle and the knee.

  14. The Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI): I. Construct validity.

    PubMed

    Wilde, Elisabeth A; McCauley, Stephen R; Kelly, Tara M; Weyand, Annie M; Pedroza, Claudia; Levin, Harvey S; Clifton, Guy L; Schnelle, Kathleen P; Shah, Monika V; Moretti, Paolo

    2010-06-01

    The Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI) is a measure adapted from the National Institutes of Health Stroke Scale (NIHSS), and is intended to capture essential neurological deficits impacting individuals with traumatic brain injury (TBI) (see Wilde et al., 2010 ). In the present study we evaluate the measure's construct validity via comparison with a quantified neurological examination performed by a neurologist. Spearman rank-order correlation between the NOS-TBI and the neurological examination was rho = 0.76, p < 0.0001, suggesting a high degree of correspondence (construct validity) between these two measures of neurological function. Additionally, items from the NOS-TBI compared favorably to the neurological examination items, with correlations ranging from 0.60 to 0.99 (all p < 0.0001). On formal neurological examination, some degree of neurological impairment was observed in every participant in this cohort of individuals undergoing rehabilitation for TBI, and on the NOS-TBI neurological impairment was evident in all but one participant. This study documents the presence of measurable neurological sequelae in a sample of patients with TBI in a post-acute rehabilitation setting, underscoring the need for formal measurement of the frequency and severity of neurological deficits in this population. The results suggest that the NOS-TBI is a valid measure of neurological functioning in patients with TBI.

  15. Boxing injuries: neurologic, radiologic, and neuropsychologic evaluation.

    PubMed

    Ross, R J; Casson, I R; Siegel, O; Cole, M

    1987-01-01

    Boxing is an endeavor that may have to be re-evaluated in the coming years as to whether it should be designated as a sport. It is the only "sport" in which victory is determined by the amount of physical damage done to the opponent. We have presented the largest number of professional and amateur boxers (58) evaluated by various modern diagnostic modalities and have unequivocally demonstrated the deleterious effects of boxing upon the brain. There have been few, if any, meaningful actions taken by the promoters of boxing to correct the conditions under which boxers are subjected to physical abuse. Recommendations regarding the creation of a National Board of Boxing to supervise this "sport" have not been heeded. Suggested safeguards for the boxer, including mandatory medical and boxing history records (passports), use of headgear and approved safe boxing gloves, avoiding blows to the head, improved boxing ring floors, mandatory neurologic examinations, and more competent physicians at ringsides making medical decisions, have essentially not been implemented. The suggestions that mandatory computed tomograms at various stages in a boxer's career be used to determine possible changes of atrophy have not been followed, even when the CT scans have been made available at no cost to the boxers. The effective use of neuropsychologic evaluation, even when offered at no cost, has also been denied. The established medical injuries due to boxing and the lack of any sustained and significant efforts on the part of organized boxing create an atmosphere that is conducive to following the call for the consideration of a ban of boxing.

  16. Acute Inhalation Injury

    PubMed Central

    Gorguner, Metin; Akgun, Metin

    2010-01-01

    Inhaled substances may cause injury in pulmonary epithelium at various levels of respiratory tract, leading from simple symptoms to severe disease. Acute inhalation injury (AII) is not uncommon condition. There are certain high risk groups but AII may occur at various places including home or workplace. Environmental exposure is also possible. In addition to individual susceptibility, the characteristics of inhaled substances such as water solubility, size of substances and chemical properties may affect disease severity as well as its location. Although AII cases may recover in a few days but AII may cause long-term complications, even death. We aimed to discuss the effects of short-term exposures (minutes to hours) to toxic substances on the lungs. PMID:25610115

  17. Neurological injuries and extracorporeal membrane oxygenation: the challenge of the new ECMO era.

    PubMed

    Martucci, Gennaro; Lo Re, Vincenzina; Arcadipane, Antonio

    2016-07-01

    Extracorporeal membrane oxygenation (ECMO) is a life-saving mechanical respiratory and/or circulatory support for potentially reversible severe heart or respiratory injury untreatable with conventional therapies. Thanks to the technical and management improvements the use of ECMO has increased dramatically in the last few years. Data in the literature show a progressive increase in the overall outcome. Considering the improving survival rate of patients on ECMO, and the catastrophic effect of neurological injuries in such patients, the topic of neurological damage during the ICU stay in ECMO is gaining importance. We present a case series of six neurological injuries that occurred in 1 year during the ECMO run or after the ECMO weaning. In each case the neurological complication had a dramatic effect: ranging from brain death to prolonged ICU stay and long term disability. This case series has an informative impact for the multidisciplinary teams treating ECMO patients because of its heterogeneity in pathogenesis and clinical manifestation: cerebral hemorrhage, ischemic stroke due to cerebral fat embolism, acute disseminated encephalomyelitis due to H1N1 Influenza. In our ECMO hub we started strict neurological monitoring involving intensivists, a neurologist and our radiology service, but neurological complications are still an insidious diagnosis and treatment. Considering several possible neurological injuries may help reduce delay in diagnosis and speed rehabilitation.

  18. Neurologic Disorders in Immunocompetent Patients with Autochthonous Acute Hepatitis E

    PubMed Central

    Perrin, H. Blasco; Cintas, P.; Abravanel, F.; Gérolami, R.; d'Alteroche, L.; Raynal, J.-N.; Alric, L.; Dupuis, E.; Prudhomme, L.; Vaucher, E.; Couzigou, P.; Liversain, J.-M.; Bureau, C.; Vinel, J.-P.; Kamar, N.; Izopet, J.

    2015-01-01

    Neurologic disorders, mainly Guillain-Barré syndrome and Parsonage–Turner syndrome (PTS), have been described in patients with hepatitis E virus (HEV) infection in industrialized and developing countries. We report a wider range of neurologic disorders in nonimmunocompromised patients with acute HEV infection. Data from 15 French immunocompetent patients with acute HEV infection and neurologic disorders were retrospectively recorded from January 2006 through June 2013. The disorders could be divided into 4 main entities: mononeuritis multiplex, PTS, meningoradiculitis, and acute demyelinating neuropathy. HEV infection was treated with ribavirin in 3 patients (for PTS or mononeuritis multiplex). One patient was treated with corticosteroids (for mononeuropathy multiplex), and 5 others received intravenous immunoglobulin (for PTS, meningoradiculitis, Guillain-Barré syndrome, or Miller Fisher syndrome). We conclude that pleiotropic neurologic disorders are seen in HEV-infected immunocompetent patients. Patients with acute neurologic manifestations and aminotransferase abnormalities should be screened for HEV infection. PMID:26490255

  19. Acute hand injuries in athletes.

    PubMed

    Rosenbaum, Yoseph A; Awan, Hisham M

    2017-03-22

    Hand and wrist injuries in athletes are common, representing between 3 and 25% of all sports injuries. As many as a quarter of all sports injuries involve the hand or wrist. We review the recent literature regarding acute hand injuries in athletes based on the structures involved - bone, muscle/tendon, ligament, and neurovascular - including diagnosis and pathophysiology of these injuries, focusing on athlete-specific facets of treatment, and when available, opinions on return to play.

  20. Acute Kidney Injury

    PubMed Central

    Zuk, Anna; Bonventre, Joseph V.

    2016-01-01

    Acute kidney injury (AKI) is a global public health concern associated with high morbidity, mortality, and healthcare costs. Other than dialysis, no therapeutic interventions reliably improve survival, limit injury, or speed recovery. Despite recognized shortcomings of in vivo animal models, the underlying pathophysiology of AKI and its consequence, chronic kidney disease (CKD), is rich with biological targets. We review recent findings relating to the renal vasculature and cellular stress responses, primarily the intersection of the unfolded protein response, mitochondrial dysfunction, autophagy, and the innate immune response. Maladaptive repair mechanisms that persist following the acute phase promote inflammation and fibrosis in the chronic phase. Here macrophages, growth-arrested tubular epithelial cells, the endothelium, and surrounding pericytes are key players in the progression to chronic disease. Better understanding of these complex interacting pathophysiological mechanisms, their relative importance in humans, and the utility of biomarkers will lead to therapeutic strategies to prevent and treat AKI or impede progression to CKD or end-stage renal disease (ESRD). PMID:26768243

  1. Hyperoxic Acute Lung Injury

    PubMed Central

    Kallet, Richard H; Matthay, Michael A

    2013-01-01

    Prolonged breathing of very high FIO2 (FIO2 ≥ 0.9) uniformly causes severe hyperoxic acute lung injury (HALI) and, without a reduction of FIO2, is usually fatal. The severity of HALI is directly proportional to PO2 (particularly above 450 mm Hg, or an FIO2 of 0.6) and exposure duration. Hyperoxia produces extraordinary amounts of reactive O2 species that overwhelms natural antioxidant defenses and destroys cellular structures through several pathways. Genetic predisposition has been shown to play an important role in HALI among animals, and some genetics-based epidemiologic research suggests that this may be true for humans as well. Clinically, the risk of HALI likely occurs when FIO2exceeds 0.7, and may become problematic when FIO2 exceeds 0.8 for an extended period of time. Both high-stretch mechanical ventilation and hyperoxia potentiate lung injury and may promote pulmonary infection. During the 1960s, confusion regarding the incidence and relevance of HALI largely reflected such issues as the primitive control of FIO2, the absence of PEEP, and the fact that at the time both ALI and ventilator-induced lung injury were unknown. The advent of PEEP and precise control over FIO2, as well as lung-protective ventilation, and other adjunctive therapies for severe hypoxemia, has greatly reduced the risk of HALI for the vast majority of patients requiring mechanical ventilation in the 21st century. However, a subset of patients with very severe ARDS requiring hyperoxic therapy is at substantial risk for developing HALI, therefore justifying the use of such adjunctive therapies. PMID:23271823

  2. Autophagy in Acute Kidney Injury

    PubMed Central

    Livingston, Man J.; Dong, Zheng

    2014-01-01

    Acute kidney injury is a major kidney disease associated with poor clinical outcomes. The pathogenesis of acute kidney injury is multifactorial and is characterized by tubular cell injury and death. Recent studies have demonstrated autophagy induction in proximal tubular cells during acute kidney injury. The regulatory mechanisms of tubular cell autophagy are poorly understood; however, some recent findings have set up a foundation for further investigation. Although autophagy may promote cell death under certain experimental conditions, pharmacological and autophagy-related gene knockout studies have established a renoprotective role for autophagy in acute kidney injury. The mechanisms by which autophagy protects cells from injury and how, possibly, its pro-survival role switches to pro-death under certain conditions are discussed. Further research is expected to help us understand the regulatory network of tubular cell autophagy, define its precise roles in specific context of acute kidney injury, and identify autophagy-targeting strategies for the prevention and treatment of acute kidney injury. PMID:24485026

  3. Neurologic Injuries in the Athlete's Shoulder

    PubMed Central

    Duralde, Xavier A.

    2000-01-01

    Objective: To review the presentation, evaluation, treatment, and prognosis of various nerve injuries about the shoulder in the athletic population. Included are injuries to the axillary, suprascapular, musculocutaneous, long thoracic, and spinal accessory nerves. Data Sources: This article represents a review of the literature regarding incidence, presentation, and results of treatment of these various nerve injuries. The clinically pertinent anatomy is also presented to better relate mechanism of injury to the occurrence of nerve injury. I searched MEDLINE from 1966 through 1999 and the Journal of Shoulder and Elbow Surgery from 1992 through 1999 for the key words “nerve” and “shoulder.” Data Synthesis: A historical review of treatment results is presented as well as a review of treatment options and the results of studies using modern techniques in the management of nerve injuries. Conclusions/Recommendations: Nerve injuries about the shoulder present as distinct clinical syndromes, although signs and symptoms can be subtle. The athletic trainer and team physician must be able to recognize the presentation of these injuries so that adequate evaluation and prompt treatment can be instituted to maximize the athlete's chance for early return to sport. ImagesFigure 1.Figure 2.Figure 4. PMID:16558645

  4. Fertility treatment in spinal cord injury and other neurologic disease

    PubMed Central

    Trofimenko, Vera

    2016-01-01

    Infertility in individuals with neurologic disorders is complex in etiology and manifestation. Its management therefore often requires a multimodal approach. This review addresses the implications of spinal cord injury (SCI) and other neurologic disease on fertility, including the high prevalence of sexual dysfunction, ejaculation disorders and compromised semen parameters. Available treatment approaches discussed include assisted ejaculation techniques and assisted reproductive technology including surgical sperm retrieval and intracytoplasmic sperm injection (ICSI). PMID:26904416

  5. Fertility treatment in spinal cord injury and other neurologic disease.

    PubMed

    Trofimenko, Vera; Hotaling, James M

    2016-02-01

    Infertility in individuals with neurologic disorders is complex in etiology and manifestation. Its management therefore often requires a multimodal approach. This review addresses the implications of spinal cord injury (SCI) and other neurologic disease on fertility, including the high prevalence of sexual dysfunction, ejaculation disorders and compromised semen parameters. Available treatment approaches discussed include assisted ejaculation techniques and assisted reproductive technology including surgical sperm retrieval and intracytoplasmic sperm injection (ICSI).

  6. Neurological complications of acute multifocal placoid pigment epitheliopathy.

    PubMed

    Brownlee, W J; Anderson, N E; Sims, J; Pereira, J A

    2016-09-01

    Acute multifocal placoid pigment epitheliopathy (AMPPE) is an autoimmune chorioretinal disease that can be complicated by neurological involvement. There is limited information on this potentially treatable condition in the neurological literature. The objective of this patient series is to describe the neurological complications of AMPPE. We retrospectively identified patients with neurological complications of AMPPE seen at Auckland Hospital between 2008 and 2013 and summarised cases in the literature between 1976 and 2013. We identified five patients with neurological complications of AMPPE at Auckland Hospital and 47 reported patients. These patients demonstrated a spectrum of neurological involvement including isolated headache, stroke or transient ischaemic attack, seizures, venous sinus thrombosis, optic neuritis, sensorineural hearing loss and peripheral vestibular disorder. We propose criteria to define AMPPE with neurological complications. A cerebrospinal fluid (CSF) lymphocytosis in a patient with isolated headache may predict the development of cerebrovascular complications of AMPPE. Patients with cerebrovascular complications of AMPPE have a poor prognosis with high rates of death and neurological disability among survivors. Predictors of poor outcome in those who develop neurological complications of AMPPE are a relapsing course, generalised seizures and multifocal infarction on MRI. All patients with neurological complications of AMPPE, including headache alone, should be investigated with an MRI brain and CSF examination. Patients with focal neurological symptoms should receive intravenous (IV) methylprednisolone followed by a tapering course of oral steroids for at least 3months. Patients with AMPPE and an isolated headache with a CSF pleocytosis should be treated with oral steroids.

  7. Biomarkers in acute lung injury.

    PubMed

    Mokra, Daniela; Kosutova, Petra

    2015-04-01

    Acute respiratory distress syndrome (ARDS) and its milder form acute lung injury (ALI) may result from various diseases and situations including sepsis, pneumonia, trauma, acute pancreatitis, aspiration of gastric contents, near-drowning etc. ALI/ARDS is characterized by diffuse alveolar injury, lung edema formation, neutrophil-derived inflammation, and surfactant dysfunction. Clinically, ALI/ARDS is manifested by decreased lung compliance, severe hypoxemia, and bilateral pulmonary infiltrates. Severity and further characteristics of ALI/ARDS may be detected by biomarkers in the plasma and bronchoalveolar lavage fluid (or tracheal aspirate) of patients. Changed concentrations of individual markers may suggest injury or activation of the specific types of lung cells-epithelial or endothelial cells, neutrophils, macrophages, etc.), and thereby help in diagnostics and in evaluation of the patient's clinical status and the treatment efficacy. This chapter reviews various biomarkers of acute lung injury and evaluates their usefulness in diagnostics and prognostication of ALI/ARDS.

  8. Neonatal Acute Kidney Injury.

    PubMed

    Selewski, David T; Charlton, Jennifer R; Jetton, Jennifer G; Guillet, Ronnie; Mhanna, Maroun J; Askenazi, David J; Kent, Alison L

    2015-08-01

    In recent years, there have been significant advancements in our understanding of acute kidney injury (AKI) and its impact on outcomes across medicine. Research based on single-center cohorts suggests that neonatal AKI is very common and associated with poor outcomes. In this state-of-the-art review on neonatal AKI, we highlight the unique aspects of neonatal renal physiology, definition, risk factors, epidemiology, outcomes, evaluation, and management of AKI in neonates. The changes in renal function with gestational and chronologic age are described. We put forth and describe the neonatal modified Kidney Diseases: Improving Global Outcomes AKI criteria and provide the rationale for its use as the standardized definition of neonatal AKI. We discuss risk factors for neonatal AKI and suggest which patient populations may warrant closer surveillance, including neonates <1500 g, infants who experience perinatal asphyxia, near term/ term infants with low Apgar scores, those treated with extracorporeal membrane oxygenation, and those requiring cardiac surgery. We provide recommendations for the evaluation and treatment of these patients, including medications and renal replacement therapies. We discuss the need for long-term follow-up of neonates with AKI to identify those children who will go on to develop chronic kidney disease. This review highlights the deficits in our understanding of neonatal AKI that require further investigation. In an effort to begin to address these needs, the Neonatal Kidney Collaborative was formed in 2014 with the goal of better understanding neonatal AKI, beginning to answer critical questions, and improving outcomes in these vulnerable populations.

  9. Acute neurological symptoms during hypobaric exposure: consider cerebral air embolism.

    PubMed

    Weenink, Robert P; Hollmann, Markus W; van Hulst, Robert A

    2012-11-01

    Cerebral arterial gas embolism (CAGE) is well known as a complication of invasive medical procedures and as a risk in diving and submarine escape. In the underwater environment, CAGE is caused by trapped air, which expands and leads to lung vessel rupture when ambient pressure decreases during ascent. Pressure decrease also occurs during hypobaric activities such as flying and, therefore, CAGE may theoretically be a risk in hypobaric exposure. We reviewed the available literature on this subject. Identified were 12 cases of CAGE due to hypobaric exposure. Based on these cases, we discuss pathophysiology, diagnosis, and treatment of CAGE due to hypobaric exposure. The low and slow pressure decrease during most hypobaric activities (as opposed to diving) account for the low incidence of CAGE during these exposures and suggest that severe air trapping must be present to cause barotrauma. This is also suggested by the large prevalence of air filled cysts in the case reports reviewed. We recommend considering CAGE in all patients presenting with acute central neurological injury during or shortly after pressure decrease such as flying. A CT scan of head and chest should be performed in these patients. Treatment with hyperbaric oxygen therapy should be initiated as soon as possible in cases of proven or probable CAGE.

  10. Acute injuries in Taekwondo.

    PubMed

    Schlüter-Brust, K; Leistenschneider, P; Dargel, J; Springorum, H P; Eysel, P; Michael, J W-P

    2011-08-01

    Although Taekwondo is becoming an increasingly popular sport, there is a lack of reliable epidemiologic data on Taekwondo injuries. To perform an epidemiologic study on the variety of types of injury in professional and amateur Taekwondo athletes and to find a relation between Taekwondo style, skill level, weight-class and warm-up routine and the occurrence of injuries, we analysed the injury data using a 7-page questionnaire from a total of 356 Taekwondo athletes who were randomly selected. Overall, we registered a total of 2,164 injuries in 356 athletes. Most traumas were contusions and sprains in the lower extremities. Professional Taekwondo athletes have an increased risk of injury in comparison to recreational athletes. Taekwondo style, weight class and tournament frequency have an influence on the athlete's injury profile. Warm-up routines were found to have a positive effect on injury rates. Overall, Taekwondo may be considered a rather benign activity, if injuries during Taekwondo tournaments can be avoided. If not, Taekwondo can result in serious musculoskeletal problems.

  11. Acute kidney injury after pediatric cardiac surgery

    PubMed Central

    Singh, Sarvesh Pal

    2016-01-01

    Acute kidney injury is a common complication after pediatric cardiac surgery. The definition, staging, risk factors, biomarkers and management of acute kidney injury in children is detailed in the following review article. PMID:27052074

  12. Update on traumatic acute spinal cord injury. Part 1.

    PubMed

    Galeiras Vázquez, R; Ferreiro Velasco, M E; Mourelo Fariña, M; Montoto Marqués, A; Salvador de la Barrera, S

    2017-02-01

    Traumatic spinal cord injury requires a multidisciplinary approach both for specialized treatment of the acute phase and for dealing with the secondary complications. A suspicion or diagnosis of spinal cord injury is the first step for a correct management. A review is made of the prehospital management and characteristics of the acute phase of spinal cord injury. Respiratory monitoring for early selective intubation, proper identification and treatment of neurogenic shock are essential for the prevention of secondary spinal cord injury. The use of corticosteroids is currently not a standard practice in neuroprotective treatment, and hemodynamic monitoring and early surgical decompression constitute the cornerstones of adequate management. Traumatic spinal cord injury usually occurs as part of multiple trauma, and this can make diagnosis difficult. Neurological examination and correct selection of radiological exams prevent delayed diagnosis of spinal cord injuries, and help to establish the prognosis.

  13. Neurological Manifestations of Acute Posterior Multifocal Placoid Pigment Epitheliopathy

    PubMed Central

    Alkhotani, Ashjan; Shirah, Bader

    2016-01-01

    Background and Purpose Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is an immune-mediated chorioretinal disease that causes acute visual symptoms with characteristic ophthalmoscopic findings. Neurological complications are rarely reported in the literature. Here we report two new cases of APMPPE that presented with neurological manifestations, one of which was associated with peripheral neuropathy, which has not been described before. Methods A retrospective database review of all patients with a diagnosis of APMPPE was performed. Clinical, ophthalmological, and neurological data were analyzed, and only cases of APMPPE with neurological complications were included. A literature review of several databases was also performed, and previous case reports were reviewed and analyzed in detail. Results In total, 56 cases of APMPPE-associated neurological complications were included in the analyses: 54 from the literature and 2 from our own practice. The most common complication was cerebral vasculitis, which affected 28 patients (50%), followed by headaches in 15 patients (26.8%). The other complications include sixth-cranial-nerve palsy, transient hearing loss, meningoencephalitis, cavernous sinus thrombosis, and viral meningitis. Conclusions This report adds to the literature of a novel association of APMPPE with peripheral neuropathy, and comprehensively reviews the neurological manifestations of this disease. A high level of suspicion should be applied when dealing with a case of APMPPE. We recommend applying detailed clinical neurological examinations and magnetic resonance imaging to APMPPE patients, and then early steroid treatment if the examination is positive or even suspicious. Early treatment with steroids and long-term treatment with immunosuppressive azathioprine with interval neurological evaluations will contribute positively to the outcomes and avoid fatal complications, namely strokes. PMID:27819416

  14. Management of acute traumatic spinal cord injuries.

    PubMed

    Shank, C D; Walters, B C; Hadley, M N

    2017-01-01

    Acute traumatic spinal cord injury (SCI) is a devastating disease process affecting tens of thousands of people across the USA each year. Despite the increase in primary prevention measures, such as educational programs, motor vehicle speed limits, automobile running lights, and safety technology that includes automobile passive restraint systems and airbags, SCIs continue to carry substantial permanent morbidity and mortality. Medical measures implemented following the initial injury are designed to limit secondary insult to the spinal cord and to stabilize the spinal column in an attempt to decrease devastating sequelae. This chapter is an overview of the contemporary management of an acute traumatic SCI patient from the time of injury through the stay in the intensive care unit. We discuss initial triage, immobilization, and transportation of the patient by emergency medical services personnel to a definitive treatment facility. Upon arrival at the emergency department, we review initial trauma protocols and the evidence-based recommendations for radiographic evaluation of the patient's vertebral column. Finally, we outline closed cervical spine reduction and various aggressive medical therapies aimed at improving neurologic outcome.

  15. Acute Neurological Issues in Pregnancy and the Peripartum

    PubMed Central

    Hosley, Catherine M.; McCullough, Louise D.

    2011-01-01

    Acute neurological diseases requiring hospitalization are relatively rare in women of childbearing age. However, during pregnancy and the postpartum period, several diseases increase in prevalence. Some are unique to the pregnant/postpartum state including preeclampsia and delivery-associated neuropathies. Others, although indirectly related to pregnancy, such as cerebral venous thrombosis, ischemic stroke, and intracerebral hemorrhage, increase in frequency and carry considerable risk of morbidity and mortality. In addition, treatment options are often limited. This review discusses the diseases more commonly seen during pregnancy and the postpartum period, with a focus on emergent neurological diseases and their management. Interventional therapies will also be discussed. PMID:23983844

  16. Acute Neurological Involvement in Diarrhea-Associated Hemolytic Uremic Syndrome

    PubMed Central

    Kwon, Thérésa; Elmaleh, Monique; Charbit, Marina; Launay, Emma Allain; Harambat, Jérôme; Brun, Muriel; Ranchin, Bruno; Bandin, Flavio; Cloarec, Sylvie; Bourdat-Michel, Guylhene; Piètrement, Christine; Champion, Gérard; Ulinski, Tim; Deschênes, Georges

    2010-01-01

    Background and objectives: Neurologic involvement is the most threatening complication of diarrhea-associated hemolytic uremic syndrome (D+HUS). Design, setting, participants, & measurements: We report a retrospective multicenter series of 52 patients with severe initial neurologic involvement that occurred in the course of D+HUS. Results: Verotoxigenic Escherichia coli infection was documented in 24. All except two patients had acute renal failure that required peritoneal dialysis, hemodialysis, or both techniques. A first group of eight patients remained with normal consciousness; five of them had protracted seizures. A second group of 23 patients had stuporous coma; five of these had protracted severe seizures, and 18 had a neurologic defect including pyramidal syndrome, hemiplegia or hemiparesia, and extrapyramidal syndrome. A third group of 21 patients had severe coma. Plasma exchanges were undertaken in 25 patients, 11 of whom were treated within 24 hours after the first neurologic sign; four died, two survived with severe sequelae, and five were alive without neurologic defect. Magnetic resonance imaging (MRI) for 29 patients showed that (1) every structure of the central nervous system was susceptible to involvement; (2) no correlation seemed to exist between special profile of localization on early MRI and the final prognosis; and (3) MRI did not exhibit any focal lesions in three patients. The overall prognosis of the series was marked by the death of nine patients and severe sequelae in 13. Conclusions: Neurologic involvement is associated with a severe renal disease but does not lead systematically to death or severe disability. PMID:20498239

  17. Update on traumatic acute spinal cord injury. Part 2.

    PubMed

    Mourelo Fariña, M; Salvador de la Barrera, S; Montoto Marqués, A; Ferreiro Velasco, M E; Galeiras Vázquez, R

    2017-02-01

    The aim of treatment in acute traumatic spinal cord injury is to preserve residual neurologic function, avoid secondary injury, and restore spinal alignment and stability. In this second part of the review, we describe the management of spinal cord injury focusing on issues related to short-term respiratory management, where the preservation of diaphragmatic function is a priority, with prediction of the duration of mechanical ventilation and the need for tracheostomy. Surgical assessment of spinal injuries based on updated criteria is discussed, taking into account that although the type of intervention depends on the surgical team, nowadays treatment should afford early spinal decompression and stabilization. Within a comprehensive strategy in spinal cord injury, it is essential to identify and properly treat patient anxiety and pain associated to spinal cord injury, as well as to prevent and ensure the early diagnosis of complications secondary to spinal cord injury (thromboembolic disease, gastrointestinal and urinary disorders, pressure ulcers).

  18. Endovascular treatment for acute pulmonary embolism in neurological patient

    PubMed Central

    Paul, Gunchan; Paul, Birinder S; Gautam, Parshotam L; Mohan, Bishav; Sharma, Shruti

    2015-01-01

    Among the spectrum of venous thrombo-embolic disease, acute pulmonary embolism accounts for the most life threatening manifestations with mortality exceeding 50%. It can affect many patient populations across various disciplines, hence immediate attention and aggressive treatment is crucial. With the advancement of technologies, various catheter-based devices are available to treat massive or submassive PE. In this paper we report two patients of acute pulmonary embolism with neurological issues where the life threatening emergency was successfully managed by utilizing endovascular directed thrombolytic reperfusion therapy. PMID:26609298

  19. Ritalin revisited: does it really help in neurological injury?

    PubMed

    Kajs-Wyllie, Marylyn

    2002-12-01

    Methylphenidate (Ritalin) is a commonly used central nervous stimulant. It has been used in various neurological conditions, including attention deficit disorder, depression, and narcolepsy. Methylphenidate has been advocated in patients with traumatic brain injury and stroke for a variety of cognitive, attention, and behavioral problems. It also has been shown to speed recovery from poststroke depression so that patients can participate more fully in rehabilitation programs. Research suggests that it also may have a role in augmenting activity of injured neuronal tissue in the comatose patient, thus facilitating a return to consciousness. The neuroscience nurse plays an important role in monitoring response to Ritalin, including identifying its side effects. A review of the limited studies on the use of Ritalin, its mechanisms of action, dosing, and weaning provide a current understanding of this adjunctive agent's role in treatment for the neurological population.

  20. Sepsis and Acute Kidney Injury.

    PubMed

    Bilgili, Beliz; Haliloğlu, Murat; Cinel, İsmail

    2014-12-01

    Acute kindney injury (AKI) is a clinical syndrome which is generally defined as an abrupt decline in glomerular filtration rate, causing accumulation of nitrogenous products and rapid development of fluid, electrolyte and acid base disorders. In intensive care unit sepsis and septic shock are leading causes of AKI. Sepsis-induced AKI literally acts as a biologic indicator of clinical deterioration. AKI triggers variety of immune, inflammatory, metabolic and humoral patways; ultimately leading distant organ dysfunction and increases morbidity and mortality. Serial mesurements of creatinine and urine volume do not make it possible to diagnose AKI at early stages. Serum creatinine influenced by age, weight, hydration status and become apparent only when the kidneys have lost 50% of their function. For that reason we need new markers, and many biomarkers in the diagnosis of early AKI activity is assessed. Historically "Risk-Injury-Failure-Loss-Endstage" (RIFLE), "Acute Kidney Injury Netwok" (AKIN) and "The Kidney Disease/ Improving Global Outcomes" (KDIGO) classification systems are used for diagnosing easily in clinical practice and research and grading disease. Classifications including diagnostic criteria are formed for the identification of AKI. Neutrophil gelatinase associated lipocalin (NGAL), cystatin-C (Cys-C), kidney injury molecule-1 (KIM-1) and also "cell cycle arrest" molecules has been concerned for clinical use. In this review the pathophysiology of AKI, with the relationship of sepsis and the importance of early diagnosis of AKI is evaluated.

  1. Sepsis and Acute Kidney Injury

    PubMed Central

    Bilgili, Beliz; Haliloğlu, Murat; Cinel, İsmail

    2014-01-01

    Acute kindney injury (AKI) is a clinical syndrome which is generally defined as an abrupt decline in glomerular filtration rate, causing accumulation of nitrogenous products and rapid development of fluid, electrolyte and acid base disorders. In intensive care unit sepsis and septic shock are leading causes of AKI. Sepsis-induced AKI literally acts as a biologic indicator of clinical deterioration. AKI triggers variety of immune, inflammatory, metabolic and humoral patways; ultimately leading distant organ dysfunction and increases morbidity and mortality. Serial mesurements of creatinine and urine volume do not make it possible to diagnose AKI at early stages. Serum creatinine influenced by age, weight, hydration status and become apparent only when the kidneys have lost 50% of their function. For that reason we need new markers, and many biomarkers in the diagnosis of early AKI activity is assessed. Historically “Risk-Injury-Failure-Loss-Endstage” (RIFLE), “Acute Kidney Injury Netwok” (AKIN) and “The Kidney Disease/ Improving Global Outcomes” (KDIGO) classification systems are used for diagnosing easily in clinical practice and research and grading disease. Classifications including diagnostic criteria are formed for the identification of AKI. Neutrophil gelatinase associated lipocalin (NGAL), cystatin-C (Cys-C), kidney injury molecule-1 (KIM-1) and also “cell cycle arrest” molecules has been concerned for clinical use. In this review the pathophysiology of AKI, with the relationship of sepsis and the importance of early diagnosis of AKI is evaluated. PMID:27366441

  2. Pathophysiology of Acute Kidney Injury

    PubMed Central

    Basile, David P.; Anderson, Melissa D.; Sutton, Timothy A.

    2014-01-01

    Acute kidney injury (AKI) is the leading cause of nephrology consultation and is associated with high mortality rates. The primary causes of AKI include ischemia, hypoxia or nephrotoxicity. An underlying feature is a rapid decline in GFR usually associated with decreases in renal blood flow. Inflammation represents an important additional component of AKI leading to the extension phase of injury, which may be associated with insensitivity to vasodilator therapy. It is suggested that targeting the extension phase represents an area potential of treatment with the greatest possible impact. The underlying basis of renal injury appears to be impaired energetics of the highly metabolically active nephron segments (i.e., proximal tubules and thick ascending limb) in the renal outer medulla, which can trigger conversion from transient hypoxia to intrinsic renal failure. Injury to kidney cells can be lethal or sublethal. Sublethal injury represents an important component in AKI, as it may profoundly influence GFR and renal blood flow. The nature of the recovery response is mediated by the degree to which sublethal cells can restore normal function and promote regeneration. The successful recovery from AKI depends on the degree to which these repair processes ensue and these may be compromised in elderly or CKD patients. Recent data suggest that AKI represents a potential link to CKD in surviving patients. Finally, earlier diagnosis of AKI represents an important area in treating patients with AKI that has spawned increased awareness of the potential that biomarkers of AKI may play in the future. PMID:23798302

  3. Central Venous Line and Acute Neurological Deficit: A Case Series

    PubMed Central

    Ahmadi, Seyed Hossein; Shirzad, Mahmood; Zeraatian, Sam; Salehiomran, Abbas; Abbasi, Seyed Hesameddin; Ghiasi, Atefeh

    2014-01-01

    Abstract Central venous catheter (CVC) insertion is a practical way to assess patients hemodynamic specially in cardiovascular surgery but this relatively simple junior level procedure is not risk free and its common reported complications include; pneumothorax, hydrothorax, hemothorax, local hematoma, cardiac tamponade, vascular injury, thrombosis, embolism, and catheter disruption. Here in this article we are going to present 6 patients with very unusual presentation of CVC complication which was neurological deficit presented by agitation, unconsciousness, disorientation to time and place and hemiparesis. All patients undergone neurologic consult and brain computed tomography. Final diagnosis was brain ischemic damage and finally we kept them on conservative management; fortunately we did not have any permanent damage. PMID:25870645

  4. Endovascular Treatment of Acute and Chronic Thoracic Aortic Injury

    SciTech Connect

    Raupach, Jan Ferko, Alexander; Lojik, Miroslav; Krajina, Antonin; Harrer, Jan; Dominik, Jan

    2007-11-15

    Our aim is to present midterm results after endovascular repair of acute and chronic blunt aortic injury. Between December 1999 and December 2005, 13 patients were endovascularly treated for blunt aortic injury. Ten patients, 8 men and 2 women, mean age 38.7 years, were treated for acute traumatic injury in the isthmus region of thoracic aorta. Stent-graftings were performed between the fifth hour and the sixth day after injury. Three patients (all males; mean age, 66 years; range, 59-71 years) were treated due to the presence of symptoms of chronic posttraumatic pseudoaneurysm of the thoracic aorta (mean time after injury, 29.4 years, range, 28-32). Fifteen stent-grafts were implanted in 13 patients. In the group with acute aortic injury one patient died due to failure of endovascular technique. Lower leg paraparesis appeared in one patient; the other eight patients were regularly followed up (1-72 months; mean, 35.6 months), without complications. In the group with posttraumatic pseudoaneurysms all three patients are alive. One patient suffered postoperatively from upper arm claudication, which was treated by carotidosubclavian bypass. We conclude that the endoluminal technique can be used successfully in the acute repair of aortic trauma and its consequences. Midterm results are satisfactory, with a low incidence of neurologic complications.

  5. Rock Climbing Injuries: Acute and Chronic Repetitive Trauma.

    PubMed

    Chang, Connie Y; Torriani, Martin; Huang, Ambrose J

    2016-01-01

    Rock climbing has increased in popularity as a sport, and specific injuries related to its practice are becoming more common. Chronic repetitive injuries are more common than acute injuries, although acute injuries tend to be more severe. We review both acute and chronic upper and lower extremity injuries. Understanding the injury pattern in rock climbers is important for accurate diagnosis.

  6. Infrared pupillometry, the Neurological Pupil index and unilateral pupillary dilation after traumatic brain injury: implications for treatment paradigms.

    PubMed

    Chen, Jefferson William; Vakil-Gilani, Kiana; Williamson, Kay Lyn; Cecil, Sandy

    2014-01-01

    Pupillary dysfunction, a concerning finding in the neurologic examination of the patient with an acute traumatic brain injury often dictates the subsequent treatment paradigm. Patients were monitored closely with an infrared pupillometer, with NPi technology, for acute changes in pupillary function. NPi technology applies a scalar value to pupillary function. A retrospective chart review was performed of traumatic brain injury patients with acute unilateral pupillary dilation, admitted to Legacy Emanuel Medical Center's NeuroTrauma Unit, Portland, OR, and followed as outpatients, between January 2012 and December 2013. Clinical exam findings of pupillary size, NPi scores, and brain Magnetic Resonance Imaging and Computed Tomography images were analyzed. Five traumatic brain injury patients were identified with unilateral pupillary dysfunction with long-term follow-up after the initial injury. Each patient was monitored closely in the trauma bay for neurological deterioration with a pupillometer and the clinical exam. Two patients underwent subsequent intracranial pressure monitoring based on a deteriorating clinical scenario, including consistent abnormal unilateral NPi scores. One patient with consistent abnormal NPi scores and an improved clinical exam did not undergo invasive interventions. Two patients showed early improvement in NPi scores correlating with the normalization of their pupillary reactivity. Anisocoria improved in all patients despite concurrent abnormal NPi scores. Magnetic Resonance Imaging and Computed Tomography imaging studies, with a focus on the third nerve, revealed focal abnormalities consistent with the clinical findings. A unilateral blown pupil and abnormal NPi score in a traumatic brain injury patient are not necessarily indicative of intracranial pressure issues, and must be correlated with the entire clinical scenario, to determine the etiology of the third nerve injury and direct potential therapeutic interventions. Early NPi score

  7. Secondary neurological deterioration in traumatic spinal injury: data from medicolegal cases.

    PubMed

    Todd, N V; Skinner, D; Wilson-MacDonald, J

    2015-04-01

    We assessed the frequency and causes of neurological deterioration in 59 patients with spinal cord injury on whom reports were prepared for clinical negligence litigation. In those who deteriorated neurologically we assessed the causes of the change in neurology and whether that neurological deterioration was potentially preventable. In all 27 patients (46%) changed neurologically, 20 patients (74% of those who deteriorated) had no primary neurological deficit. Of those who deteriorated, 13 (48%) became Frankel A. Neurological deterioration occurred in 23 of 38 patients (61%) with unstable fractures and/or dislocations; all 23 patients probably deteriorated either because of failures to immobilise the spine or because of inappropriate removal of spinal immobilisation. Of the 27 patients who altered neurologically, neurological deterioration was, probably, avoidable in 25 (excess movement in 23 patients with unstable injuries, failure to evacuate an epidural haematoma in one patient and over-distraction following manipulation of the cervical spine in one patient). If existing guidelines and standards for the management of actual or potential spinal cord injury had been followed, neurological deterioration would have been prevented in 25 of the 27 patients (93%) who experienced a deterioration in their neurological status.

  8. Pathophysiology of ischaemic acute kidney injury.

    PubMed

    Kanagasundaram, Nigel Suren

    2015-03-01

    Acute kidney injury is common, dangerous and costly, affecting around one in five patients emergency admissions to hospital. Although survival decreases as disease worsens, it is now apparent that even modest degrees of dysfunction are not only associated with higher mortality but are an independent risk factor for death. This review focuses on the pathophysiology of acute kidney injury secondary to ischaemia - its commonest aetiology. The haemodynamic disturbances, endothelial injury, epithelial cell injury and immunological mechanisms underpinning its initiation and extension will be discussed along with the considerable and complex interplay between these factors that lead to an intense, pro-inflammatory state. Mechanisms of tubular recovery will be discussed but also the pathophysiology of abnormal repair with its direct consequences for long-term renal function. Finally, the concept of 'organ cross-talk' will be introduced as a potential explanation for the higher mortality observed with acute kidney injury that might be deemed modest in conventional biochemical terms.

  9. Neurological outcome in a series of 58 patients operated for traumatic thoracolumbar spinal cord injuries

    PubMed Central

    Dobran, Mauro; Iacoangeli, Maurizio; Di Somma, Lucia Giovanna Maria; Di Rienzo, A.; Colasanti, Roberto; Nocchi, Niccolò; Alvaro, Lorenzo; Moriconi, Elisa; Nasi, Davide; Scerrati, Massimo

    2014-01-01

    Background: Traumatic thoracolumbar spinal fractures represent approximately 65% of all traumatic spinal fractures and are frequently associated to permanent disability with significant social and economic impact. These injuries create severe physical limitations depending on neurological status, level of fracture, severity of injury, patient age and comorbidities. Predicting neurological improvement in patients with traumatic spinal cord injuries (SCIs) is very difficult because it is related to different preoperative prognostic factors. We evaluated the neurological improvement related to the preoperative neurological conditions and the anatomic level of spinal cord injury. Methods: From January 2004 to June 2010, we operated 207 patients for unstable thoracolumbar spinal fractures. We carried out a retrospective analysis of 69 patients with traumatic SCIs operated on by a posterior fixation performed within 24 hours from the trauma. The preoperative neurological conditions (ASIA grade), the type of the fracture, the anatomic level of spinal cord injury and the postoperative neurological improvement were evaluated for each patient. Results: The ASIA grade at admission (P = 0,0005), the fracture type according to the AO spine classification (P = 0,0002), and the anatomic location of the injury (P = 0,0213) represented predictive factors of neurological improvement at univariate analysis. The preoperative neurological status (P = 0,0491) and the fracture type (P = 0,049) confirmed a positive predictive value also in the multivariate analysis. Conclusions: Our study confirms that the preoperative neurological status, the fracture type and the anatomic location of the fracture are predictive factors of the neurological outcome in patients with spinal cord injury. PMID:25289154

  10. Neurological Complication After Low-Voltage Electric Injury: A Case Report

    PubMed Central

    Kim, Ha Min; Ko, Yeong-A; Kim, Joon Sung; Lim, Seong Hoon

    2014-01-01

    Electrical shock can result in neurological complications, involving both peripheral and central nervous systems, which may present immediately or later on. However, delayed neurological complications caused by low-voltage electric shock are rarely reported. Here, a case of a man suffering from weakness and aphasia due to the delayed-onset of the peripheral nerve injury and ischemic stroke following an electrical shock is presented. Possible mechanisms underlying the neurological complications include thermal injury to perineural tissue, overactivity of the sympathetic nervous system, vascular injury, and histological or electrophysiological changes. Moreover, vasospasms caused by low-voltage alternating current may predispose individuals to ischemic stroke. Therefore, clinicians should consider the possibility of neurological complications, even if the onset of the symptoms is delayed, and should perform diagnostic tests, such as electrophysiology or imaging, when patients present with weakness following an electric injury. PMID:24855625

  11. Neurological Diseases, Disorders and Injuries in Canada: Highlights of a National Study.

    PubMed

    Bray, Garth M; Huggett, Deanna L

    2016-01-01

    The National Population Health Study of Neurological Conditions, a partnership between Neurological Health Charities Canada and the Government of Canada, was the largest study of neurological diseases, disorders, and injuries ever conducted in Canada. Undertaken between 2009 and 2013, the expansive program of research addressed the epidemiology, impacts, health services, and risk factors of 18 neurological conditions and estimated the health outcomes and costs of these conditions in Canada through 2031. This review summarizes highlights from the component projects of the study as presented in the synthesis report, Mapping Connections: An Understanding of Neurological Conditions in Canada. The key findings included new prevalence and incidence estimates, documentation of the diverse and often debilitating effects of neurological conditions, and identification of the utilization, economic costs, and current limitations of related health services. The study findings will support health charities, governments, and other stakeholders to reduce the impact of neurological conditions in Canada.

  12. Neurologic impairment following closed head injury predicts post-traumatic neurogenesis

    PubMed Central

    Villasana, L.E.; Westbrook, G.L.; Schnell, E.

    2014-01-01

    In the mammalian hippocampus, neurogenesis persists into adulthood, and increased generation of newborn neurons could be of clinical benefit following concussive head injuries. Post-traumatic neurogenesis has been well documented using “open” traumatic brain injury (TBI) models in rodents; however, human TBI most commonly involves closed head injury. Here we used a closed head injury (CHI) model to examine post-traumatic hippocampal neurogenesis in mice. All mice were subjected to the same CHI protocol, and a gross-motor based injury severity score was used to characterize neurologic impairment one hour after the injury. When analyzed 2 weeks later, post-traumatic neurogenesis was significantly increased only in mice with a high degree of transient neurologic impairment immediately after injury. This increase was associated with an early increase in c-fos activity, and subsequent reactive astrocytosis and microglial activation in the dentate gyrus. Our results demonstrate that the initial degree of neurologic impairment after closed head injury predicts the induction of secondary physiologic and pathophysiologic processes, and that animals with severe neurologic impairment early after injury manifest an increase in post-traumatic neurogenesis in the absence of gross anatomic pathology. PMID:24861442

  13. Acute epididymitis: a work-related injury?

    PubMed Central

    Sawyer, E. K.; Anderson, J. R.

    1996-01-01

    Occupational medicine physicians frequently are presented with requests by employers to determine the work-relatedness of medical illnesses or injuries. Occasionally, this involves a sudden onset of acute epididymitis in the male employee after strenuous activity in the workplace. Because the vast majority of acute epididymitis cases have an underlying sexually transmitted disease component, this poses a real dilemma for the consulting physician. This article discusses the etiology and pathogenesis of acute epididymitis along with its epidemiologic significance and reviews workers' compensation and its possible legal interpretation when acute epididymitis occurs at the worksite. PMID:8691501

  14. The 'ouR-HOPE' approach for ethics and communication about neonatal neurological injury.

    PubMed

    Racine, Eric; Bell, Emily; Farlow, Barbara; Miller, Steven; Payot, Antoine; Rasmussen, Lisa Anne; Shevell, Michael I; Thomson, Donna; Wintermark, Pia

    2017-02-01

    Predicting neurological outcomes of neonates with acute brain injury is an essential component of shared decision-making, in order to guide the development of treatment goals and appropriate care plans. It can aid parents in imagining the child's future, and guide timely and ongoing treatment decisions, including shifting treatment goals and focusing on comfort care. However, numerous challenges have been reported with respect to evidence-based practices for prognostication such as biases about prognosis among clinicians. Additionally, the evaluation or appreciation of living with disability can differ, including the well-known disability paradox where patients self-report a good quality of life in spite of severe disability. Herein, we put forward a set of five practice principles captured in the "ouR-HOPE" approach (Reflection, Humility, Open-mindedness, Partnership, and Engagement) and related questions to encourage clinicians to self-assess their practice and engage with others in responding to these challenges. We hope that this proposal paves the way to greater discussion and attention to ethical aspects of communicating prognosis in the context of neonatal brain injury.

  15. Acute injuries from mountain biking.

    PubMed Central

    Chow, T K; Bracker, M D; Patrick, K

    1993-01-01

    We questioned members of 2 southern California off-road bicycling organizations about injuries associated with the use of all-terrain bicycles. Cyclists were asked about riding and safety habits, the kind(s) of injury sustained with their most recent accident and whether they sought medical treatment, and the circumstances of the accident. Of 459 mailed surveys, 268 (58.4%) were returned. Respondents (82.8% of whom were male) ranged in age from 14 to 68 years. Of these, 225 (84%) had been injured while riding all-terrain bicycles, 51% in the past year. Although most injuries were characterized as minor, 26% required professional medical care, and 4.4% of those injured were admitted to hospital. Extremity injuries--abrasions, lacerations, contusions--occurred in 201 (90%) cyclists with 27 (12%) sustaining a fracture or dislocation. High levels of helmet use (88%) may explain the low occurrence of head and neck trauma (12%). Frequent riding and riding on paved terrain were associated with increased severity of injury, although most accidents--197 (87.6%)--occurred off paved roads. These results suggest that, compared with regular bicyclists, all-terrain cyclists have more, but not necessarily more severe, injuries. Clinicians and emergency medical personnel should be aware that the increasing popularity of off-road cycling may change the frequency and nature of bicycling injuries. PMID:8212679

  16. [The acute knee injury - practical considerations].

    PubMed

    Bouaicha, Samy

    2014-04-09

    The acute knee injury represents one of the most common reasons to visit a general practitioner or an emergency department in a hospital. The initial assessment of an acute knee injury usually is affected by severe swelling, pain and a significant lack of motion. Conventional radiographs in three planes may provide additional information to limit the differential diagnosis. A clinical re-evaluation after five to ten days usually allows proper functional testing and therefore correct diagnosis in the majority of cases can be made. With suspicious clinical findings, MRI may be helpful to evaluate ligamentous, meniscal and cartilaginous structures. Femoro-tibial knee dislocation represents the most harmful acute knee injury and needs to be further evaluated and treated in an adequate medical institution in every suspicious case. Rapid vascular diagnostic with (CT)-angiography is crucial. Behind a multi-ligament injury of the knee a spontaneously reduced dislocation may hide and proper neuro-vascular exam therefore is mandatory in every patient. When fracture, blocking and major instability can be excluded at initial assessment, there is usually no need for any acute surgical intervention and initial conservative treatment may be conducted on an out-patient basis for most of the patients. Priority of surgical treatment depends on the injury pattern and delayed intervention with a pre-habilitative phase may be beneficial for certain pathologies.

  17. [Pregnancy-related acute kidney injury].

    PubMed

    Filipowicz, Ewa; Staszków, Monika

    Acute kidney injury (AKI) in obstetrics may be caused by the same disorders that are observed in the general population or may be specific for a pregnancy such as: preeclampsia, HELLP syndrome or acute fatty liver of pregnancy. The renal changes may be only temporary, and resolve within a few weeks postpartum, or may become irreversible leading to a progression of chronic kidney disease (CKD). In the article the most important pregnancy related syndromes associated with AKI have been shortly reviewed.

  18. DNA repair in ischemic acute kidney injury.

    PubMed

    Pressly, Jeffrey D; Park, Frank

    2017-04-01

    Ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury leading to an induction of oxidative stress, cellular dysfunction, and loss of renal function. DNA damage, including oxidative base modifications and physical DNA strand breaks, is a consequence of renal IRI. Like many other organs in the body, a redundant and highly conserved set of endogenous repair pathways have evolved to selectively recognize the various types of cellular DNA damage and combat its negative effects on cell viability. Severe damage to the DNA, however, can trigger cell death and elimination of the injured tubular epithelial cells. In this minireview, we summarize the state of the current field of DNA damage and repair in the kidney and provide some expected and, in some cases, unexpected effects of IRI on DNA damage and repair in the kidney. These findings may be applicable to other forms of acute kidney injury and could provide new opportunities for renal research.

  19. Mechanical factors and bone health: effects of weightlessness and neurologic injury.

    PubMed

    Amin, Shreyasee

    2010-06-01

    Bone is a dynamic tissue with homeostasis governed by many factors. Among them, mechanical stimuli appear to be particularly critical for bone structure and strength. With removal of mechanical stimuli, a profound bone loss occurs, as best observed in the extreme examples following exposure to space flight or neurologic impairment. This review provides an overview of the changes in bone density and structure that occur during and after space flight as well as following neurologic injury from stroke and spinal cord injury. It also discusses the potential mechanisms through which mechanical stimuli are postulated to act on bone tissue.

  20. Protein methionine oxidation augments reperfusion injury in acute ischemic stroke

    PubMed Central

    Gu, Sean X.; Blokhin, Ilya O.; Wilson, Katina M.; Dhanesha, Nirav; Doddapattar, Prakash; Grumbach, Isabella M.; Chauhan, Anil K.; Lentz, Steven R.

    2016-01-01

    Reperfusion injury can exacerbate tissue damage in ischemic stroke, but little is known about the mechanisms linking ROS to stroke severity. Here, we tested the hypothesis that protein methionine oxidation potentiates NF-κB activation and contributes to cerebral ischemia/reperfusion injury. We found that overexpression of methionine sulfoxide reductase A (MsrA), an antioxidant enzyme that reverses protein methionine oxidation, attenuated ROS-augmented NF-κB activation in endothelial cells, in part, by protecting against the oxidation of methionine residues in the regulatory domain of calcium/calmodulin-dependent protein kinase II (CaMKII). In a murine model, MsrA deficiency resulted in increased NF-κB activation and neutrophil infiltration, larger infarct volumes, and more severe neurological impairment after transient cerebral ischemia/reperfusion injury. This phenotype was prevented by inhibition of NF-κB or CaMKII. MsrA-deficient mice also exhibited enhanced leukocyte rolling and upregulation of E-selectin, an endothelial NF-κB–dependent adhesion molecule known to contribute to neurovascular inflammation in ischemic stroke. Finally, bone marrow transplantation experiments demonstrated that the neuroprotective effect was mediated by MsrA expressed in nonhematopoietic cells. These findings suggest that protein methionine oxidation in nonmyeloid cells is a key mechanism of postischemic oxidative injury mediated by NF-κB activation, leading to neutrophil recruitment and neurovascular inflammation in acute ischemic stroke. PMID:27294204

  1. Visualizing the Propagation of Acute Lung Injury

    PubMed Central

    Cereda, Maurizio; Xin, Yi; Meeder, Natalie; Zeng, Johnathan; Jiang, YunQing; Hamedani, Hooman; Profka, Harrilla; Kadlecek, Stephen; Clapp, Justin; Deshpande, Charuhas G.; Wu, Jue; Gee, James C.; Kavanagh, Brian P.; Rizi, Rahim R.

    2015-01-01

    Background Mechanical ventilation worsens acute respiratory distress syndrome (ARDS), but this secondary ‘ventilator-associated’ injury is variable and difficult to predict. We aimed to visualize the propagation of such ventilator-induced injury, in the presence (and absence) of a primary underlying lung injury, and to determine the predictors of propagation. Methods Anesthetized rats (n=20) received acid aspiration (HCl) followed by ventilation with moderate tidal volume (VT). In animals surviving ventilation for at least two hours, propagation of injury was quantified using serial computed tomography (CT). Baseline lung status was assessed by oxygenation, lung weight, and lung strain (VT/expiratory lung volume). Separate groups of rats without HCl aspiration were ventilated with large (n=10) or moderate (n=6) VT. Results In 15 rats surviving longer than two hours, CT opacities spread outwards from the initial site of injury. Propagation was associated with higher baseline strain (propagation vs. no propagation, mean ± SD: 1.52 ± 0.13 vs. 1.16 ± 0.20, p<0.01), but similar oxygenation and lung weight. Propagation did not occur where baseline strain <1.29. In healthy animals, large VT caused injury that was propagated inwards from the lung periphery; in the absence of preexisting injury, propagation did not occur where strain was <2.0. Conclusions Compared with healthy lungs, underlying injury causes propagation to occur at a lower strain threshold and, it originates at the site of injury; this suggests that tissue around the primary lesion is more sensitive. Understanding how injury is propagated may ultimately facilitate a more individualized monitoring or management. PMID:26536308

  2. Matrix Metalloproteinases as a Therapeutic Target to Improve Neurologic Recovery After Spinal Cord Injury

    DTIC Science & Technology

    2015-12-01

    Award Number: W81XWH-11-1-0797 TITLE: Matrix metalloproteinases as a therapeutic target to improve neurologic recovery after spinal cord injury...after spinal cord injury 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-1-0797 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Linda J. Noble, Alpa...SUPPLEMENTARY NOTES 14. ABSTRACT Purpose: We are evaluating efficacy of GM6001, a matrix metalloproteinase (MMP) inhibitor in a murine model of spinal cord

  3. Predation as a cause of neurologic signs and acute mortality in a pheasant flock.

    PubMed

    Martin, M P; Anderson, C M; Johnson, B; Wakenell, P S

    2006-09-01

    A flock of approximately 15,000 ring-necked pheasants (Phasianus colchicus) was evaluated for a sudden increase in mortality and acute neurological signs after having been previously diagnosed 3 wk earlier with a chronic respiratory disease of undetermined etiology. Approximately 25 live birds were displaying neurological signs including circling, ataxia, and obtunded behavior and 50 birds were dead. Three birds with neurological signs were submitted for evaluation. Extensive subcutaneous hemorrhage over the head and penetrating puncture wounds through the skull and into the brain were found. Trauma from a wild predatory mammal, most likely the long-tailed weasel (Mustela frenata) that had invaded the pheasant house and expressed surplus killing behavior was determined to be the cause of the acute neurological signs and mortality. The relationship of the chronic respiratory disease to the predation episode was not determined but it is possible that pheasants with severe respiratory disease may have had increased susceptibility to predation.

  4. Sodium hypochlorite-induced acute kidney injury.

    PubMed

    Peck, Brandon W; Workeneh, Biruh; Kadikoy, Huseyin; Abdellatif, Abdul

    2014-03-01

    Sodium hypochlorite (bleach) is commonly used as an irrigant during dental procedures as well as a topical antiseptic agent. Although it is generally safe when applied topically, reports of accidental injection of sodium hypochlorite into tissue have been reported. Local necrosis, pain and nerve damage have been described as a result of exposure, but sodium hypo-chlorite has never been implicated as a cause of an acute kidney injury (AKI). In this report, we describe the first case of accidental sodium hypochlorite injection into the infraorbital tissue during a dental procedure that precipitated the AKI. We speculate that oxidative species induced by sodium hypochlorite caused AKI secondary to the renal tubular injury, causing mild acute tubular necrosis.

  5. Psychosocial outcomes among youth with spinal cord injury by neurological impairment

    PubMed Central

    Riordan, Anne; Kelly, Erin H.; Klaas, Sara J.; Vogel, Lawrence C.

    2015-01-01

    Objective Examine psychosocial outcomes of youth with spinal cord injury (SCI) as a function of neurological level (paraplegia/tetraplegia) and severity (American Spinal Injury Association (ASIA) Impairment Scale (AIS)). Design Survey research. Setting Three pediatric SCI specialty centers in the USA. Participants Youth with SCI ages 5–18 with neurological impairment classifications of: tetraplegia AIS ABC (tetraplegia ABC), paraplegia AIS ABC (paraplegia ABC), or AIS D. Outcome Measures Children's Assessment of Participation and Enjoyment, Pediatric Quality of Life Inventory, Revised Children's Manifest Anxiety Scale, and Children's Depression Inventory. Results Three hundred and forty youth participated; 57% were male; 60% were Caucasian, 21% Hispanic, 7% African-American, 2% Native American, and 3% reported “other”. Their mean age was 8.15 years (standard deviation (SD) = 5.84) at injury and 13.18 years (SD = 3.87) at interview. Ninety-six youth (28%) had tetraplegia ABC injuries, 191 (56%) paraplegia ABC injuries, and 53 (16%) AIS D injuries. Neurological impairment was significantly related to participation and quality of life (QOL). Specifically, youth with paraplegia ABC and AIS D injuries participated in more activities than youth with tetraplegia ABC (P = 0.002; P = 0.018, respectively) and youth with paraplegia ABC participated more often than youth with tetraplegia ABC (P = 0.006). Youth with paraplegia ABC reported higher social QOL than youth with tetraplegia ABC (P = 0.001) and AIS D injuries (P = 0.002). Groups did not differ regarding mental health. Conclusion Interventions should target youth with tetraplegia ABC, as they may need support in terms of participation, and both youth with tetraplegia ABC and AIS D injuries in terms of social integration. PMID:24621027

  6. Dengue-associated acute kidney injury

    PubMed Central

    Oliveira, João Fernando Picollo; Burdmann, Emmanuel A.

    2015-01-01

    Dengue is presently the most relevant viral infection transmitted by a mosquito bite that represents a major threat to public health worldwide. Acute kidney injury (AKI) is a serious and potentially lethal complication of this disease, and the actual incidence is unknown. In this review, we will assess the most relevant epidemiological and clinical data regarding dengue and the available evidence on the frequency, etiopathogenesis, outcomes and treatment of dengue-associated AKI. PMID:26613023

  7. Interleukin-1 and acute brain injury

    PubMed Central

    Murray, Katie N.; Parry-Jones, Adrian R.; Allan, Stuart M.

    2015-01-01

    Inflammation is the key host-defense response to infection and injury, yet also a major contributor to a diverse range of diseases, both peripheral and central in origin. Brain injury as a result of stroke or trauma is a leading cause of death and disability worldwide, yet there are no effective treatments, resulting in enormous social and economic costs. Increasing evidence, both preclinical and clinical, highlights inflammation as an important factor in stroke, both in determining outcome and as a contributor to risk. A number of inflammatory mediators have been proposed as key targets for intervention to reduce the burden of stroke, several reaching clinical trial, but as yet yielding no success. Many factors could explain these failures, including the lack of robust preclinical evidence and poorly designed clinical trials, in addition to the complex nature of the clinical condition. Lack of consideration in preclinical studies of associated co-morbidities prevalent in the clinical stroke population is now seen as an important omission in previous work. These co-morbidities (atherosclerosis, hypertension, diabetes, infection) have a strong inflammatory component, supporting the need for greater understanding of how inflammation contributes to acute brain injury. Interleukin (IL)-1 is the prototypical pro-inflammatory cytokine, first identified many years ago as the endogenous pyrogen. Research over the last 20 years or so reveals that IL-1 is an important mediator of neuronal injury and blocking the actions of IL-1 is beneficial in a number of experimental models of brain damage. Mechanisms underlying the actions of IL-1 in brain injury remain unclear, though increasing evidence indicates the cerebrovasculature as a key target. Recent literature supporting this and other aspects of how IL-1 and systemic inflammation in general contribute to acute brain injury are discussed in this review. PMID:25705177

  8. Latent Growth Modeling of nursing care dependency of acute neurological inpatients.

    PubMed

    Piredda, M; Ghezzi, V; De Marinis, M G; Palese, A

    2015-01-01

    Longitudinal three-time point study, addressing how neurological adult patient care dependency varies from the admission time to the 3rd day of acute hospitalization. Nursing care dependency was measured with the Care Dependency Scale (CDS) and a Latent Growth Modeling approach was used to analyse the CDS trend in 124 neurosurgical and stroke inpatients. Care dependence followed a decreasing linear trend. Results can help nurse-managers planning an appropriate amount of nursing care for acute neurological patients during their initial stage of hospitalization. Further studies are needed aimed at investigating the determinants of nursing care dependence during the entire in-hospital stay.

  9. Silica nanoparticles as vehicles for therapy delivery in neurological injury

    NASA Astrophysics Data System (ADS)

    Schenk, Desiree

    Acrolein, a very reactive aldehyde, is a culprit in the biochemical cascade after primary, mechanical spinal cord injury (SCI), which leads to the destruction of tissue initially unharmed, referred to as "secondary injury". Additionally, in models of multiple sclerosis (MS) and some clinical research, acrolein levels are significantly increased. This aldehyde overwhelms the natural anti-oxidant system, reacts freely with proteins, and releases during lipid peroxidation (LPO), effectively regenerating its self. Due to its ability to make more copies of itself in the presence of tissue via lipid peroxidation, researchers believe that acrolein plays a role in the increased destruction of the central nervous system in both SCI and MS. Hydralazine, an FDA-approved hypertension drug, has been shown to scavenge acrolein, but its side effects and short half life at the appropriate dose for acrolein scavenging must be improved for beneficial clinical translation. Due to the inefficient delivery of therapeutic drugs, nanoparticles have become a major field of exploration for medical applications. Based on their material properties, they can help treat disease by delivering drugs to specific tissues, enhancing detection methods, or a mixture of both. Nanoparticles made from silica provide distinct advantages. They form porous networks that can carry therapeutic molecules throughout the body. Therefore, a nanomedical approach has been designed using silica nanoparticles as a porous delivery vehicle hydralazine. The silica nanoparticles are formed in a one-step method that incorporates poly(ethylene) glycol (PEG), a stealth molecule, directly onto the nanoparticles. As an additional avenue for study, a natural product in green tea, epigallocatechin gallate (EGCG), has been explored for its ability to react with acrolein, disabling its reactive capabilities. Upon demonstration of attenuating acrolein, EGCG's delivery may also be improved using the nanomedical approach. The

  10. Pertussis immunisation and serious acute neurological illness in children.

    PubMed Central

    Miller, D L; Ross, E M; Alderslade, R; Bellman, M H; Rawson, N S

    1981-01-01

    The first 1000 cases notified to the National Childhood Encephalopathy Study were analysed. The diagnoses included encephalitis/encephalopathy, prolonged convulsions, infantile spasms, and Reye's syndrome. Eighty-eight of the children had had a recent infectious disease, including 19 with pertussis. Only 35 of the notified children (3.5%) had received pertussis antigen within seven days before becoming ill. Of 1955 control children matched for age, sex, and area of residence, 34 (1.7%) had been immunised with pertussis vaccine within the seven days before the date on which they became of the same age as the corresponding notified child. The relative risk of a notified child having had pertussis immunisation within that time interval was 2.4 (p less than 0.001). Of the 35 notified children, 32 had no previous neurological abnormality. A year later two had died, nine had developmental retardation, and 21 were normal. A significance association was shown between serious neurological illness and pertussis vaccine, though cases were few and most children recovered completely. PMID:6786580

  11. Psychological Characteristics in Acute Mild Traumatic Brain Injury: An MMPI-2 Study.

    PubMed

    Gass, Carlton S; Rogers, David; Kinne, Erica

    2017-01-01

    The psychological characteristics of acute traumatic brain injury (TBI) have received limited research focus, despite empirical evidence of their relevance for subsequent psychological adjustment and early therapeutic intervention. This study addressed a wide range of psychological features in 47 individuals who were hospitalized as a result of acute mild TBI (mTBI). Participants were screened from amongst consecutive TBI admissions for moderate to severe brain injury, and for pre-injury neurological, psychiatric, or substance abuse histories. Clinical and content scale scores on the MMPI-2 were explored in relation to patient gender, age, level of education, and extent of cognitive complaints. The results revealed diverse psychosocial problem areas across the sample, the most common of which were somatic and cognitive complaints, compromised insight, and a naively optimistic self-perception. The mediating roles of injury severity and demographic variables are discussed. Clinical implications and specific recommendations are presented.

  12. Epidemiology of Overuse and Acute Injuries Among Competitive Collegiate Athletes

    PubMed Central

    Yang, Jingzhen; Tibbetts, Abigail S.; Covassin, Tracey; Cheng, Gang; Nayar, Saloni; Heiden, Erin

    2012-01-01

    Context: Although overuse injuries are gaining attention, epidemiologic studies on overuse injuries in male and female collegiate athletes are lacking. (70.7%) acute injuries were reported. The overall injury rate was Objective: To report the epidemiology of overuse injuries sustained by collegiate athletes and to compare the rates of overuse and acute injuries. Design: Descriptive epidemiology study. Setting: A National Collegiate Athletic Association Division I university. Patients or Other Participants: A total of 1317 reported injuries sustained by 573 male and female athletes in 16 collegiate sports teams during the 2005–2008 seasons. Main Outcome Measure(s): The injury and athlete-exposure (AE) data were obtained from the Sports Injury Monitoring System. An injury was coded as either overuse or acute based on the nature of injury. Injury rate was calculated as the total number of overuse (or acute) injuries during the study period divided by the total number of AEs during the same period. Results: A total of 386 (29.3%) overuse injuries and 931 63.1 per 10000 AEs. The rate ratio (RR) of acute versus overuse injuries was 2.34 (95% confidence interval [CI] = 2.05, 2.67). Football had the highest RR (RR = 8.35, 95% CI = 5.38, 12.97), and women's rowing had the lowest (RR = 0.75, 95% CI = 0.51, 1.10). Men had a higher acute injury rate than women (49.8 versus 38.6 per 10000 AEs). Female athletes had a higher rate of overuse injury than male athletes (24.6 versus 13.2 per 10000 AEs). More than half of the overuse injuries (50.8%) resulted in no time loss from sport. Conclusions: Additional studies are needed to examine why female athletes are at greater risk for overuse injuries and identify the best practices for prevention and rehabilitation of overuse injuries. PMID:22488286

  13. Combination of methylprednisolone and rosiglitazone promotes recovery of neurological function after spinal cord injury

    PubMed Central

    Li, Xi-gong; Lin, Xiang-jin; Du, Jun-hua; Xu, San-zhong; Lou, Xian-feng; Chen, Zhong

    2016-01-01

    Methylprednisolone exhibits anti-inflammatory antioxidant properties, and rosiglitazone acts as an anti-inflammatory and antioxidant by activating peroxisome proliferator-activated receptor-γ in the spinal cord. Methylprednisolone and rosiglitazone have been clinically used during the early stages of secondary spinal cord injury. Because of the complexity and diversity of the inflammatory process after spinal cord injury, a single drug cannot completely inhibit inflammation. Therefore, we assumed that a combination of methylprednisolone and rosiglitazone might promote recovery of neurological function after secondary spinal cord injury. In this study, rats were intraperitoneally injected with methylprednisolone (30 mg/kg) and rosiglitazone (2 mg/kg) at 1 hour after injury, and methylprednisolone (15 mg/kg) at 24 and 48 hours after injury. Rosiglitazone was then administered once every 12 hours for 7 consecutive days. Our results demonstrated that a combined treatment with methylprednisolone and rosiglitazone had a more pronounced effect on attenuation of inflammation and cell apoptosis, as well as increased functional recovery, compared with either single treatment alone, indicating that a combination better promoted recovery of neurological function after injury. PMID:27904502

  14. Acute Kidney Injury in Patients with Cirrhosis

    PubMed Central

    Russ, Kirk B.; Stevens, Todd M; Singal, Ashwani K.

    2015-01-01

    Acute kidney injury (AKI) occurs commonly in patients with advanced cirrhosis and negatively impacts pre- and post-transplant outcomes. Physiologic changes that occur in patients with decompensated cirrhosis with ascites, place these patients at high risk of AKI. The most common causes of AKI in cirrhosis include prerenal injury, acute tubular necrosis (ATN), and the hepatorenal syndrome (HRS), accounting for more than 80% of AKI in this population. Distinguishing between these causes is particularly important for prognostication and treatment. Treatment of Type 1 HRS with vasoconstrictors and albumin improves short term survival and renal function in some patients while awaiting liver transplantation. Patients with HRS who fail to respond to medical therapy or those with severe renal failure of other etiology may require renal replacement therapy. Simultaneous liver kidney transplant (SLK) is needed in many of these patients to improve their post-transplant outcomes. However, the criteria to select patients who would benefit from SLK transplantation are based on consensus and lack strong evidence to support them. In this regard, novel serum and/or urinary biomarkers such as neutrophil gelatinase-associated lipocalin, interleukins-6 and 18, kidney injury molecule-1, fatty acid binding protein, and endothelin-1 are emerging with a potential for accurately differentiating common causes of AKI. Prospective studies are needed on the use of these biomarkers to predict accurately renal function recovery after liver transplantation alone in order to optimize personalized use of SLK. PMID:26623266

  15. Uncommon acute neurologic presentation of canine distemper in 4 adult dogs

    PubMed Central

    Galán, Alba; Gamito, Araceli; Carletti, Beatrice E.; Guisado, Alicia; de las Mulas, Juana Martín; Pérez, José; Martín, Eva M.

    2014-01-01

    Four uncommon cases of canine distemper (CD) were diagnosed in vaccinated adult dogs. All dogs had acute onset of neurologic signs, including seizures, abnormal mentation, ataxia, and proprioceptive deficits. Polymerase chain reaction for CD virus was positive on cerebrospinal fluid in 2 cases. Due to rapid deterioration the dogs were euthanized and CD was confirmed by postmortem examination. PMID:24688139

  16. Uncommon acute neurologic presentation of canine distemper in 4 adult dogs.

    PubMed

    Galán, Alba; Gamito, Araceli; Carletti, Beatrice E; Guisado, Alicia; de las Mulas, Juana Martín; Pérez, José; Martín, Eva M

    2014-04-01

    Four uncommon cases of canine distemper (CD) were diagnosed in vaccinated adult dogs. All dogs had acute onset of neurologic signs, including seizures, abnormal mentation, ataxia, and proprioceptive deficits. Polymerase chain reaction for CD virus was positive on cerebrospinal fluid in 2 cases. Due to rapid deterioration the dogs were euthanized and CD was confirmed by postmortem examination.

  17. Rhabdomyolysis and acute kidney injury after acupuncture sessions.

    PubMed

    Papasotiriou, Marios; Betsi, Grigoria; Tsironi, Maria; Assimakopoulos, Georgios

    2014-05-01

    Rhabdomyolysis is usually caused by muscle injury, drugs or alcohol and presents with muscle weakness and pain. It is characterized by rise in serum creatine kinase, aminotransferases and electrolytes as well as myoglobinuria. Myoglobinuria may cause acute kidney injury by direct proximal tubule cytotoxicity, renal vasoconstriction, intraluminal cast formation and distal tubule obstruction. Muscle pain and weakness as well as vascular injury have been reported after acupuncture. We report a case of severe rhabdomyolysis and acute kidney injury after acupuncture sessions.

  18. Medical and Nonstroke Neurologic Causes of Acute, Continuous Vestibular Symptoms.

    PubMed

    Edlow, Jonathan A; Newman-Toker, David E

    2015-08-01

    Most patients with the acute vestibular syndrome (AVS) have vestibular neuritis or stroke or, in the setting of trauma, a posttraumatic vestibular cause. Some medical and nonstroke causes of the AVS must also be considered. Multiple sclerosis is the most common diagnosis in this group. Other less common causes include cerebellar masses, inflammation and infection, mal de debarquement, various toxins, Wernicke disease, celiac-related dizziness, and bilateral vestibulopathy. Finally, there may be unmasking of prior posterior circulation events by various physiologic alterations such as alterations of temperature, blood pressure, electrolytes, or various medications, especially sedating agents.

  19. International Standards for Neurological Classification of Spinal Cord Injury: Cases with classification challenges

    PubMed Central

    Kirshblum, S. C.; Biering-Sorensen, F.; Betz, R.; Burns, S.; Donovan, W.; Graves, D. E.; Johansen, M.; Jones, L.; Mulcahey, M. J.; Rodriguez, G. M.; Schmidt-Read, M.; Steeves, J. D.; Tansey, K.; Waring, W.

    2014-01-01

    The International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) is routinely used to determine the levels of injury and to classify the severity of the injury. Questions are often posed to the International Standards Committee of the American Spinal Injury Association regarding the classification. The committee felt that disseminating some of the challenging questions posed, as well as the responses, would be of benefit for professionals utilizing the ISNCSCI. Case scenarios that were submitted to the committee are presented with the responses as well as the thought processes considered by the committee members. The importance of this documentation is to clarify some points as well as update the SCI community regarding possible revisions that will be needed in the future based upon some rules that require clarification. PMID:24559416

  20. International Standards for Neurological Classification of Spinal Cord Injury: Cases With Classification Challenges

    PubMed Central

    Biering-Sørensen, F.; Betz, R.; Burns, S.; Donovan, W.; Graves, D.E.; Johansen, M.; Jones, L.; Mulcahey, M.J.; Rodriguez, G.M.; Schmidt-Read, M.; Steeves, J.D.; Tansey, K.; Waring, W.

    2014-01-01

    The International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) is routinely used to determine levels of injury and to classify the severity of the injury. Questions are often posed to the International Standards Committee of the American Spinal Injury Association (ASIA) regarding the classification. The committee felt that disseminating some of the challenging questions posed, as well as the responses, would be of benefit for professionals utilizing the ISNCSCI. Case scenarios that were submitted to the committee are presented with the responses as well as the thought processes considered by the committee members. The importance of this documentation is to clarify some points as well as update the SCI community regarding possible revisions that will be needed in the future based upon some rules that require clarification. PMID:25477729

  1. International Standards for Neurological Classification of Spinal Cord Injury: cases with classification challenges.

    PubMed

    Kirshblum, S C; Biering-Sorensen, F; Betz, R; Burns, S; Donovan, W; Graves, D E; Johansen, M; Jones, L; Mulcahey, M J; Rodriguez, G M; Schmidt-Read, M; Steeves, J D; Tansey, K; Waring, W

    2014-03-01

    The International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) is routinely used to determine the levels of injury and to classify the severity of the injury. Questions are often posed to the International Standards Committee of the American Spinal Injury Association regarding the classification. The committee felt that disseminating some of the challenging questions posed, as well as the responses, would be of benefit for professionals utilizing the ISNCSCI. Case scenarios that were submitted to the committee are presented with the responses as well as the thought processes considered by the committee members. The importance of this documentation is to clarify some points as well as update the SCI community regarding possible revisions that will be needed in the future based upon some rules that require clarification.

  2. Acute kidney injury in the cancer patient.

    PubMed

    Campbell, G Adam; Hu, Daniel; Okusa, Mark D

    2014-01-01

    Acute kidney injury (AKI) is a frequent and significant complication of cancer and cancer therapy. Cancer patients frequently encounter risk factors for AKI including older age, CKD, prerenal conditions, sepsis, exposure to nephrotoxins, and obstructive physiology. AKI can also be secondary to paraneoplastic conditions, including glomerulonephritis and microangiopathic processes. This complication can have significant consequences, including effects on patients' ability to continue to receive therapy for their malignancy. This review will serve to summarize potential etiologies of AKI that present in patients with cancer as well as to highlight specific patient populations, such as the critically ill cancer patient.

  3. Synthetic cannabinoids and acute kidney injury

    PubMed Central

    Jamal, Faisal; Prabhakar, Sharma

    2015-01-01

    Synthetic cannabinoids (SCB) are a family of chemicals that bind to cannabinoid receptors and cause psychoactive effects. Over the past few years, they have been increasingly used for recreational purposes, especially by young adults, and have been reported to have many adverse effects. Acute kidney injury (AKI) has been recently reported; the pathophysiology of SCB-induced AKI is unknown. We report three cases of AKI in the setting of SCB use. The peak serum creatinine levels ranged from 3.0 to 5.7 mg/dL; one patient required hemodialysis. SCB can induce AKI. PMID:26424946

  4. Acute kidney injury in the elderly.

    PubMed

    Rosner, Mitchell H

    2013-08-01

    Most patients who develop acute kidney injury (AKI) are older than 65 years. Specific structural and functional changes that occur in the aging kidney predispose the elderly patient to AKI. This risk is further compounded by comorbid conditions, polypharmacy, and the need for invasive procedures. When AKI does occur, it is associated with significant morbidity and mortality. Although morbidity and mortality increases with advancing age, many elderly patients can survive AKI and do well. Thus, decision making should be thoughtful and individualized, and not dependent on age. Whenever possible, preventive approaches should be pursued to lessen the burden of AKI.

  5. Acute Kidney Injury: Diagnostic Approaches and Controversies

    PubMed Central

    Makris, Konstantinos; Spanou, Loukia

    2016-01-01

    Acute kidney injury (AKI) is a significant independent risk factor for morbidity and mortality. In the last ten years a large number of publications have highlighted the limitations of traditional approaches and the inadequacies of conventional biomarkers to diagnose and monitor renal insufficiency in the acute setting. A great effort was directed not only to the discovery and validation of new biomarkers aimed to detect AKI more accurately but also to standardise the definition of AKI. Despite the advances in both areas, biomarkers have not yet entered into routine clinical practice and the definition of this syndrome has many areas of uncertainty. This review will discuss the controversies in diagnosis and the potential of novel biomarkers to improve the definition of the syndrome. PMID:28167845

  6. Updates for the International Standards for Neurological Classification of Spinal Cord Injury.

    PubMed

    Kirshblum, Steven; Waring, William

    2014-08-01

    The International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) is the most widely used classification in the field of spinal cord injury medicine. Since its first publication in 1982, multiple revisions refining the recommended examination, scaling, and classification have taken place to improve communication, consistency, and clarity. This article describes a brief historical perspective on the development and changes over the years leading to the current ISNCSCI, detailing the most recent updates of 2011 and the worksheet 2013 as well as issues facing the ISNCSCI for the future.

  7. The Impact of Acupuncture on Neurological Recovery in Spinal Cord Injury: A Systematic Review and Meta-Analysis.

    PubMed

    Ma, Ruijie; Liu, Xin; Clark, Justin; Williams, Gail M; Doi, Suhail A

    2015-12-15

    Spinal cord injury (SCI) has become a significant social and economic burden for patients and their families. The effect of acupuncture on neurological recovery in individuals with SCI remains inconclusive despite previous studies and meta-analyses. The aim of the current study was to perform a more rigorous systematic review and bias-adjusted meta-analysis of studies so that the overall impact of acupuncture on neurological recovery in SCI can be determined. Randomized controlled trials (RCTs) only were included and were searched for in seven databases through to August 2014. Four key outcomes were assessed: neurological recovery, motor function, sensory function, and functional recovery. Several statistical approaches were compared, models were tested for robustness using sensitivity analysis, and results are presented as weighted mean difference (WMD) or standardized mean difference (SMD) for continuous outcomes and relative risk (RR) for binary outcomes. The included studies' susceptibility to bias was also assessed. A total of 12 studies were included after exclusions were applied. Heterogeneity was evident among the studies included. Pooled analyses showed that acupuncture may have a beneficial effect on neurological recovery (RRs: 1.28, 95% confidence interval [CI]: 1.12-1.50), motor function (WMD: 6.86, 95% CI: 0.41-13.31), and functional recovery (SMD: 0.88, 95% CI: 0.56-1.21) and all statistical approaches concurred. Sensitivity analyses suggested that the smaller studies (sample size <30), those with acute disease, and studies that used varying acupuncture sessions demonstrated a larger magnitude of effect. However, studies were generally of poor quality and publication bias favoring positive studies was evident. Therefore, the benefit of acupuncture we report is by no means definitive and well-designed future studies are recommended to confirm this.

  8. Acute kidney injury in the pregnant patient.

    PubMed

    Nwoko, Rosemary; Plecas, Darko; Garovic, Vesna D

    2012-12-01

    Acute kidney injury (AKI) is costly and is associated with increased mortality and morbidity. An understanding of the renal physiologic changes that occur during pregnancy is essential for proper evaluation, diagnosis, and management of AKI. As in the general population, AKI can occur from prerenal, intrinsic, and post-renal causes. Major causes of pre-renal azotemia include hyperemesis gravidarum and uterine hemorrhage in the setting of placental abruption. Intrinsic etiologies include infections from acute pyelonephritis and septic abortion, bilateral cortical necrosis, and acute tubular necrosis. Particular attention should be paid to specific conditions that lead to AKI during the second and third trimesters, such as preeclampsia, HELLP syndrome, acute fatty liver of pregnancy, and TTP-HUS. For each of these disorders, delivery of the fetus is the recommended therapeutic option, with additional therapies indicated for each specific disease entity. An understanding of the various etiologies of AKI in the pregnant patient is key to the appropriate clinical management, prevention of adverse maternal outcomes, and safe delivery of the fetus. In pregnant women with pre-existing kidney disease, the degree of renal dysfunction is the major determining factor of pregnancy outcomes, which may further be complicated by a prior history of hypertension.

  9. Tree stand falls: A persistent cause of neurological injury in hunting

    PubMed Central

    Pierre, Clifford A; Plog, Benjamin A; Srinivasan, Vasisht; Srinivasan, Kaushik; Petraglia, Anthony L; Huang, Jason H

    2014-01-01

    AIM: To characterize and compare our current series of patients to prior reports in order to identify any changes in the incidence of neurological injury related to hunting accidents in Rochester, New York. METHODS: All tree stand-related injuries referred to our regional trauma center from September 2003 through November 2011 were reviewed. Information was obtained from the hospital’s trauma registry and medical records were retrospectively reviewed for data pertaining to the injuries. RESULTS: Fifty-four patients were identified. Ninety-six percent of patients were male with a mean age of 47.9 years (range 15-69). The mean Injury Severity Score was 12.53 ± 1.17 (range 2-34). The average height of fall was 18.2 feet (range 4-40 feet). All patients fell to the ground with the exception of one who landed on rocks, and many hit the tree or branches on the way down. A reason for the fall was documented in only 13 patients, and included tree stand construction (3), loss of balance (3), falling asleep (3), structural failure (2), safety harness breakage (3) or light-headedness (1). The most common injuries were spinal fractures (54%), most commonly in the cervical spine (69%), followed by the thoracic (38%) and lumbar (21%) spine. Eight patients required operative repair. Head injuries occurred in 22%. Other systemic injuries include rib/clavicular fractures (47%), pelvic fractures (11%), solid organ injury (23%), and pneumothorax or hemothorax (19%). No patient deaths were reported. The average hospital length of stay was 6.56 ± 1.07 d. Most patients were discharged home without (72%) or with (11%) services and 17% required rehabilitation. CONCLUSION: Falls from hunting tree stands are still common, with a high rate of neurological injury. Compared to a decade ago we have made no progress in preventing these neurological injuries, despite an increase in safety advances. Neurosurgeons must continue to advocate for increased safety awareness and participate in

  10. Getting soldiers with brain injury back to work: the defence medical rehabilitation centre neurological vocational pathway.

    PubMed

    Olivier, Elizabeth; Duncan-Anderson, J; Mitchell, J; Etherington, J; McGilloway, E

    2016-04-01

    The Neuro-Rehabilitation Group at the Defence Medical Rehabilitation Centre (DMRC) has developed an integrated vocational pathway to transition service personnel back into employment. This article describes how vocational rehabilitation at DMRC fits with the wider UK military, in comparison with civilian rehabilitation. It also describes the ongoing development of the vocational pathway, which contributes to improved outcomes from neurological disorders, including traumatic brain injury. We present two cases to highlight how the programme integrates with and influences patient care.

  11. Acute mild traumatic brain injury is not associated with white matter change on diffusion tensor imaging.

    PubMed

    Ilvesmäki, Tero; Luoto, Teemu M; Hakulinen, Ullamari; Brander, Antti; Ryymin, Pertti; Eskola, Hannu; Iverson, Grant L; Ohman, Juha

    2014-07-01

    This study was designed to (i) evaluate the influence of age on diffusion tensor imaging measures of white matter assessed using tract-based spatial statistics; (ii) determine if mild traumatic brain injury is associated with microstructural changes in white matter, in the acute phase following injury, in a large homogenous sample that was carefully screened for pre-injury medical, psychiatric, or neurological problems; and (iii) examine if injury severity is related to white matter changes. Participants were 75 patients with acute mild traumatic brain injury (age = 37.2 ± 12.0 years, 45 males and 30 females) and 40 controls (age = 40.6 ± 12.2 yrs, 20 males and 20 females). Age effects were analysed by comparing control subgroups aged 31-40, 41-50, and 51-60 years against a group of 18-30-year-old control subjects. Widespread statistically significant areas of abnormal diffusion tensor measures were observed in older groups. Patients and controls were compared using age and gender as covariates and in age- and gender-matched subgroups. Subgroups of patients with more severe injuries were compared to age-and gender-matched controls. No significant differences were detected in patient-control or severity analyses (all P-value > 0.01). In this large, carefully screened sample, acute mild traumatic brain injury was not associated with diffusion tensor imaging abnormalities detectable with tract-based spatial statistics.

  12. Adenosine and protection from acute kidney injury

    PubMed Central

    Yap, Steven C.; Lee, H. Thomas

    2012-01-01

    Purpose of Review Acute Kidney Injury (AKI) is a major clinical problem without effective therapy. Development of AKI among hospitalized patients drastically increases mortality, and morbidity. With increases in complex surgical procedures together with a growing elderly population, the incidence of AKI is rising. Renal adenosine receptor (AR) manipulation may have great therapeutic potential in mitigating AKI. In this review, we discuss renal AR biology and potential clinical therapies for AKI. Recent Findings The 4 AR subtypes (A1AR, A2AAR, A2BAR and A3AR) have diverse effects on the kidney. The pathophysiology of AKI may dictate the specific AR subtype activation needed to produce renal protection. The A1AR activation in renal tubules and endothelial cells produces beneficial effects against ischemia and reperfusion (IR) injury by modulating metabolic demand, decreasing necrosis, apoptosis and inflammation. The A2AAR protects against AKI by modulating leukocyte-mediated renal and systemic inflammation whereas the A2BAR activation protects by direct activation of renal parenchymal ARs. In contrast, the A1AR antagonism may play a protective role in nephrotoxic AKI and radiocontrast induced nephropathy by reversing vascular constriction and inducing naturesis and diuresis. Furthermore, as the A3AR-activation exacerbates apoptosis and tissue damage due to renal IR, selective A3AR antagonism may hold promise to attenuate renal IR injury. Finally, renal A1AR activation also protects against renal endothelial dysfunction caused by hepatic IR injury. Summary Despite the current lack of therapies for the treatment and prevention of AKI, recent research suggests that modulation of renal ARs holds promise in treating AKI and extrarenal injury. PMID:22080856

  13. Historical perspective: neurological advances from studies of war injuries and illnesses.

    PubMed

    Lanska, Douglas J

    2009-10-01

    Early in the 20th century during the Russo-Japanese War and World War I (WWI), some of the most important, lasting contributions to clinical neurology were descriptive clinical studies, especially those concerning war-related peripheral nerve disorders (eg, Hoffmann-Tinel sign, Guillain-Barré-Strohl syndrome [GBS]) and occipital bullet wounds (eg, the retinal projection on the cortex by Inouye and later by Holmes and Lister, and the functional partitioning of visual processes in the occipital cortex by Riddoch), but there were also other important descriptive studies concerning war-related aphasia, cerebellar injuries, and spinal cord injuries (eg, cerebellar injuries by Holmes, and autonomic dysreflexia by Head and Riddoch). Later progress, during and shortly after World War II (WWII), included major progress in understanding the pathophysiology of traumatic brain injuries by Denny-Brown, Russell, and Holbourn, pioneering accident injury studies by Cairns and Holbourn, promulgation of helmets to prevent motorcycle injuries by Cairns, development of comprehensive multidisciplinary neurorehabilitation by Rusk, and development of spinal cord injury care by Munro, Guttman, and Bors. These studies and developments were possible only because of the large number of cases that allowed individual physicians the opportunity to collect, collate, and synthesize observations of numerous cases in a short span of time. Such studies also required dedicated, disciplined, and knowledgeable investigators who made the most out of their opportunities to systematically assess large numbers of seriously ill and injured soldiers under stressful and often overtly dangerous situations.

  14. Torsade de pointes indicates early neurologic damage in acute ischemic stroke.

    PubMed

    Huang, Li-Yen; Lin, Wei-Shiang; Lin, Wen-Yu; Cheng, Cheng-Chung; Cheng, Shu-Meng; Tsai, Tsung-Neng

    2013-12-01

    Torsade de pointes (TdP) is a life-threatening polymorphic ventricular tachycardia that is related to QT prolongation. Although QT prolongation is commonly seen in acute stroke, TdP is rare. We report the case of a 78-year-old woman with ischemic stroke who presented with TdP as the initial manifestation of early neurologic deterioration. We hypothesized that an increase in intracranial pressure may result in neurohormonal activation, QT prolongation, and then myocardial damage, leading to TdP. We highlight that new onset of TdP in a patient with stroke may reflect neurologic deterioration, requiring further evaluation and specific intervention.

  15. Acute neurologic disease in Porcine rubulavirus experimentally infected piglets.

    PubMed

    Herrera, Jenifer; Gómez-Núñez, Luis; Lara-Romero, Rocío; Diosdado, Fernando; Martínez-Lara, Atalo; Jasso, Miguel; Ramírez-Mendoza, Humberto; Pérez-Torres, Armando; Rivera-Benítez, José Francisco

    2017-02-15

    The objective of this study was to evaluate the clinical disease, humoral response and viral distribution of recent Porcine rubulavirus (PorPV) isolates in experimentally infected pigs. Four, 6-piglet (5-days old) groups were employed (G1-84, G2-93, G3-147, and G4-T). Three viral strains were used for the experimental infection: the reference strain LPMV-1984 (Michoacán 1984) and two other strains isolated in 2013, one in Queretaro (Qro/93/2013) and the other in Michoacán (Mich/147/2013). Each strain was genetically characterized by amplification and sequencing of the gene encoding hemagglutinin-neuroamidase (HN). The inoculation was performed through the oronasal and ocular routes, at a dose of 1×10(6)TCID50/ml. Subsequently, the signs were evaluated daily and necropsies were performed on 3 different days post infection (dpi). We recorded all micro- and macroscopic lesions. Organs from the nervous, lymphatic, and respiratory system were analyzed by quantifying the viral RNA load and the presence of the infectious virus. The presence of the viral antigen in organs was evidenced through immunohistochemistry. Seroconversion was evaluated through the use of a hemagglutination inhibition test. In the characterization of gene HN, only three substitutions were identified in strain Mich/147/2013, two in strain LPMV/1984 (fourth passage) and one in strain Qro/93/2013, with respect to reference strain LPMV-84, these changes had not been identified as virulence factors in previously reported strains. Neurological alterations associated with the infection were found in all three experimental groups starting from 3dpi. Groups G1-84 and G3-147 presented the most exacerbated nervous signs. Group G2-93 only presented milder signs including slight motor incoordination, and an increased rectal temperature starting from day 5 post infection (PI). The main histopathological findings were the presence of a mononuclear inflammatory infiltrate (lymphocytic/monocytic) surrounding the

  16. Acute Kidney Injury Subsequent to Cardiac Surgery

    PubMed Central

    Kramer, Robert S.; Herron, Crystal R.; Groom, Robert C.; Brown, Jeremiah R.

    2015-01-01

    Abstract: Acute kidney injury (AKI) after cardiac surgery is a common and underappreciated syndrome that is associated with poor short- and long-term outcomes. AKI after cardiac surgery may be epiphenomenon, a signal for adverse outcomes by virtue of other affected organ systems, and a consequence of multiple factors. Subtle increases in serum creatinine (SCr) postoperatively, once considered inconsequential, have been shown to reflect a kidney injury that likely occurred in the operating room during cardiopulmonary bypass (CPB) and more often in susceptible individuals. The postoperative elevation in SCr is a delayed signal reflecting the intraoperative injury. Preoperative checklists and the conduct of CPB represent opportunities for prevention of AKI. Newer definitions of AKI provide us with an opportunity to scrutinize perioperative processes of care and determine strategies to decrease the incidence of AKI subsequent to cardiac surgery. Recognizing and mitigating risk factors preoperatively and optimizing intraoperative practices may, in the aggregate, decrease the incidence of AKI. This review explores the pathophysiology of AKI and addresses the features of patients who are the most vulnerable to AKI. Preoperative strategies are discussed with particular attention to a readiness for surgery checklist. Intraoperative strategies include minimizing hemodilution and maximizing oxygen delivery with specific suggestions regarding fluid management and plasma preservation. PMID:26390675

  17. The pharmacology of neurotrophic treatment with Cerebrolysin: brain protection and repair to counteract pathologies of acute and chronic neurological disorders.

    PubMed

    Masliah, E; Díez-Tejedor, E

    2012-04-01

    Neurotrophic factors are considered as part of the therapeutic strategy for neurological disorders like dementia, stroke and traumatic brain injury. Cerebrolysin is a neuropeptide preparation which mimics the action of endogenous neurotrophic factors on brain protection and repair. In dementia models, Cerebrolysin decreases β-amyloid deposition and microtubule-associated protein tau phosphorylation by regulating glycogen synthase kinase-3β and cyclin-dependent kinase 5 activity, increases synaptic density and restores neuronal cytoarchitecture. These effects protect integrity of the neuronal circuits and thus result in improved cognitive and behavioral performance. Furthermore, Cerebrolysin enhances neurogenesis in the dentate gyrus, the basis for neuronal replacement therapy in neurodegenerative diseases. Experimental studies in stroke animal models have shown that Cerebrolysin stabilizes the structural integrity of cells by inhibition of calpain and reduces the number of apoptotic cells after ischemic lesion. Cerebrolysin induces restorative processes, decreases infarct volume and edema formation and promotes functional recovery. Stroke-induced neurogenesis in the subventricular zone was also promoted by Cerebrolysin, thus supporting the brain's self-repair after stroke. Both, traumatic brain and spinal cord injury conditions stimulate the expression of natural neurotrophic factors to promote repair and regeneration processes -axonal regeneration, neuronal plasticity and neurogenesis- that is considered to be crucial for the future recovery. Neuroprotective effects of Cerebrolysin on experimentally induced traumatic spinal cord injury have shown that Cerebrolysin prevents apoptosis of lesioned motoneurons and promotes functional recovery. This section summarizes the most relevant data on the pharmacology of Cerebrolysin obtained from in vitro assays (biochemical and cell cultures) and in vivo animal models of acute and chronic neurological disorders.

  18. Parallel Metabolomic Profiling of Cerebrospinal Fluid and Serum for Identifying Biomarkers of Injury Severity after Acute Human Spinal Cord Injury

    PubMed Central

    Wu, Yiman; Streijger, Femke; Wang, Yining; Lin, Guohui; Christie, Sean; Mac-Thiong, Jean-Marc; Parent, Stefan; Bailey, Christopher S.; Paquette, Scott; Boyd, Michael C.; Ailon, Tamir; Street, John; Fisher, Charles G.; Dvorak, Marcel F.; Kwon, Brian K.; Li, Liang

    2016-01-01

    Suffering an acute spinal cord injury (SCI) can result in catastrophic physical and emotional loss. Efforts to translate novel therapies in acute clinical trials are impeded by the SCI community’s singular dependence upon functional outcome measures. Therefore, a compelling rationale exists to establish neurochemical biomarkers for the objective classification of injury severity. In this study, CSF and serum samples were obtained at 3 time points (~24, 48, and 72 hours post-injury) from 30 acute SCI patients (10 AIS A, 12 AIS B, and 8 AIS C). A differential chemical isotope labeling liquid chromatography mass spectrometry (CIL LC-MS) with a universal metabolome standard (UMS) was applied to the metabolomic profiling of these samples. This method provided enhanced detection of the amine- and phenol-containing submetabolome. Metabolic pathway analysis revealed dysregulations in arginine-proline metabolism following SCI. Six CSF metabolites were identified as potential biomarkers of baseline injury severity, and good classification performance (AUC > 0.869) was achieved by using combinations of these metabolites in pair-wise comparisons of AIS A, B and C patients. Using the UMS strategy, the current data set can be expanded to a larger cohort for biomarker validation, as well as discovering biomarkers for predicting neurologic outcome. PMID:27966539

  19. Brain Injuries and Neurological System Failure are the Most Common Proximate Cause of Death in Children Admitted to a Pediatric Intensive Care Unit

    PubMed Central

    Au, Alicia K.; Carcillo, Joseph A.; Clark, Robert S. B.; Bell, Michael J.

    2016-01-01

    Objective Mortality rates from critical illness in children have declined over the past several decades, now averaging between 2-5% in most Pediatric Intensive Care Units (PICUs). While these rates, and mortality rates from specific disorders, are widely understood, the impact of acute neurological injuries in such children who die and the role of these injuries in the cause of death are not well understood. We hypothesized that neurological injuries are an important cause of death in children. Design Retrospective review. Setting PICU at Children's Hospital of Pittsburgh, an academic tertiary care center Patients Seventy-eight children who died within the PICU from April 2006-February 2008. Measurements and Main Results Data regarding admission diagnosis, presence of chronic illness, diagnosis of brain injury, and cause of death were collected. Mortality was attributed to brain injury in 65.4% (51/78) of deaths. Ninety-six (28/29) percent of previously healthy children died with brain injuries, compared to 46.9% (23/49) of chronically-ill children (p<0.05). The diagnosed brain injury was the proximate cause of death in 89.3% of previously healthy children and 91.3% with chronic illnesses. PICU and hospital length of stay was longer in those with chronic illnesses (38.8d±7.0 vs. 8.9d±3.7 and 49.2d±8.3 vs. 9.0d±3.8, p<0.05 and p<0.001, respectively) Conclusion Brain injury was exceedingly common in children who died in our PICU and was the proximate cause of death in a large majority of cases. Neuroprotective measures for a wide variety of admission diagnoses, and initiatives directed to prevention or treatment of brain injury are likely to attain further improvements in mortality in previously healthy children in the modern PICU. PMID:21037501

  20. Activation of P2X7 promotes cerebral edema and neurological injury after traumatic brain injury in mice.

    PubMed

    Kimbler, Donald E; Shields, Jessica; Yanasak, Nathan; Vender, John R; Dhandapani, Krishnan M

    2012-01-01

    Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Cerebral edema, the abnormal accumulation of fluid within the brain parenchyma, contributes to elevated intracranial pressure (ICP) and is a common life-threatening neurological complication following TBI. Unfortunately, neurosurgical approaches to alleviate increased ICP remain controversial and medical therapies are lacking due in part to the absence of viable drug targets. In the present study, genetic inhibition (P2X7-/- mice) of the purinergic P2x7 receptor attenuated the expression of the pro-inflammatory cytokine, interleukin-1β (IL-1β) and reduced cerebral edema following controlled cortical impact, as compared to wild-type mice. Similarly, brilliant blue G (BBG), a clinically non-toxic P2X7 inhibitor, inhibited IL-1β expression, limited edemic development, and improved neurobehavioral outcomes after TBI. The beneficial effects of BBG followed either prophylactic administration via the drinking water for one week prior to injury or via an intravenous bolus administration up to four hours after TBI, suggesting a clinically-implementable therapeutic window. Notably, P2X7 localized within astrocytic end feet and administration of BBG decreased the expression of glial fibrillary acidic protein (GFAP), a reactive astrocyte marker, and attenuated the expression of aquaporin-4 (AQP4), an astrocytic water channel that promotes cellular edema. Together, these data implicate P2X7 as a novel therapeutic target to prevent secondary neurological injury after TBI, a finding that warrants further investigation.

  1. Optimizing sedation in patients with acute brain injury.

    PubMed

    Oddo, Mauro; Crippa, Ilaria Alice; Mehta, Sangeeta; Menon, David; Payen, Jean-Francois; Taccone, Fabio Silvio; Citerio, Giuseppe

    2016-05-05

    Daily interruption of sedative therapy and limitation of deep sedation have been shown in several randomized trials to reduce the duration of mechanical ventilation and hospital length of stay, and to improve the outcome of critically ill patients. However, patients with severe acute brain injury (ABI; including subjects with coma after traumatic brain injury, ischaemic/haemorrhagic stroke, cardiac arrest, status epilepticus) were excluded from these studies. Therefore, whether the new paradigm of minimal sedation can be translated to the neuro-ICU (NICU) is unclear. In patients with ABI, sedation has 'general' indications (control of anxiety, pain, discomfort, agitation, facilitation of mechanical ventilation) and 'neuro-specific' indications (reduction of cerebral metabolic demand, improved brain tolerance to ischaemia). Sedation also is an essential therapeutic component of intracranial pressure therapy, targeted temperature management and seizure control. Given the lack of large trials which have evaluated clinically relevant endpoints, sedative selection depends on the effect of each agent on cerebral and systemic haemodynamics. Titration and withdrawal of sedation in the NICU setting has to be balanced between the risk that interrupting sedation might exacerbate brain injury (e.g. intracranial pressure elevation) and the potential benefits of enhanced neurological function and reduced complications. In this review, we provide a concise summary of cerebral physiologic effects of sedatives and analgesics, the advantages/disadvantages of each agent, the comparative effects of standard sedatives (propofol and midazolam) and the emerging role of alternative drugs (ketamine). We suggest a pragmatic approach for the use of sedation-analgesia in the NICU, focusing on some practical aspects, including optimal titration and management of sedation withdrawal according to ABI severity.

  2. Erythropoietin (EPO) in acute kidney injury.

    PubMed

    Moore, Elizabeth; Bellomo, Rinaldo

    2011-03-21

    Erythropoietin (EPO) is a 30.4 kDa glycoprotein produced by the kidney, and is mostly well-known for its physiological function in regulating red blood cell production in the bone marrow. Accumulating evidence, however, suggests that EPO has additional organ protective effects, which may be useful in the prevention or treatment of acute kidney injury. These protective mechanisms are multifactorial in nature and include inhibition of apoptotic cell death, stimulation of cellular regeneration, inhibition of deleterious pathways, and promotion of recovery.In this article, we review the physiology of EPO, assess previous work that supports the role of EPO as a general tissue protective agent, and explain the mechanisms by which it may achieve this tissue protective effect. We then focus on experimental and clinical data that suggest that EPO has a kidney protective effect.

  3. Acute liver injury secondary to sertraline.

    PubMed

    Suen, Christopher F D Li Wai; Boyapati, Ray; Simpson, Ian; Dev, Anouk

    2013-09-26

    Sertraline is widely prescribed to treat depression and anxiety disorders. However, hepatitis secondary to its use is a rare entity. We report the case of a 26-year-old woman in her 20th week of pregnancy presented with nausea, vomiting, malaise and dark urine. This occurred 6 months after sertraline 50 mg daily was started for the treatment of depression. Three weeks prior to her presentation, the dose of sertraline was increased to 100 mg daily. The patient's liver biochemical profile demonstrated increased transaminases. The biopsy of the liver showed lobular hepatitis, with a mild prominence of eosinophils, suggestive of a drug-induced or toxin-induced aetiology. Extensive biochemical work-up failed to show any other pathology to account for her hepatitis. Liver function tests normalised after cessation of sertraline, indicating a probable association between sertraline use and acute hepatocellular injury in our patient.

  4. Nitric oxide and hyperoxic acute lung injury

    PubMed Central

    Liu, Wen-wu; Han, Cui-hong; Zhang, Pei-xi; Zheng, Juan; Liu, Kan; Sun, Xue-jun

    2016-01-01

    Hyperoxic acute lung injury (HALI) refers to the damage to the lungs secondary to exposure to elevated oxygen partial pressure. HALI has been a concern in clinical practice with the development of deep diving and the use of normobaric as well as hyperbaric oxygen in clinical practice. Although the pathogenesis of HALI has been extensively studied, the findings are still controversial. Nitric oxide (NO) is an intercellular messenger and has been considered as a signaling molecule involved in many physiological and pathological processes. Although the role of NO in the occurrence and development of pulmonary diseases including HALI has been extensively studied, the findings on the role of NO in HALI are conflicting. Moreover, inhalation of NO has been approved as a therapeutic strategy for several diseases. In this paper, we briefly summarize the role of NO in the pathogenesis of HALI and the therapeutic potential of inhaled NO in HALI. PMID:27867474

  5. Fluid management in acute kidney injury.

    PubMed

    Goldstein, Stuart L

    2014-01-01

    Fluid management in critical illness has undergone extensive reevaluation in the past decade. Since a significant percentage of critically ill patients develop acute kidney injury (AKI), optimal fluid management is even more paramount to prevent the ill effects of either underhydration or overhydration. The concepts of early goal-directed fluid therapy (EGDT) and conservative late fluid management permeate current clinical research, and the independent association between fluid accumulation and mortality has been repeatedly demonstrated. A number of prospective randomized trials are planned to provide an adequately powered assessment of the effect of EGDT or earlier renal replacement therapy initiation in patients with, or at risk for AKI. The aim of this analytical review is to use existing clinical and physiological studies to support a 3-phase model of fluid management in the critically ill patient with AKI.

  6. Transfusion-related acute lung injury (TRALI).

    PubMed

    Roberts, George H

    2004-01-01

    Transfusion is an inevitable event in the life of many individuals. Transfusion medicine personnel attempt to provide blood products that will result in a safe and harmless transfusion. However, this is not always possible since no laboratory test gives totally accurate and reliable results all the time and testing in routine transfusion services is devoted primarily to the identification of red blood cell problems. Thus, when patients are transfused, several possible adverse effects may occur in the transfused patient even though quality testing indicates no potential problem. These adverse events include infectious complications, hemolytic reactions, anaphylaxis, urticaria, circulatory overload, transfusion-associated graft-versus-host disease, chills and fever, immunomodulation, and transfusion-related acute lung injury (TRALI).

  7. Transfusion-related acute lung injury.

    PubMed

    Federico, Anne

    2009-02-01

    Approximately one person in 5,000 will experience an episode of transfusion-related acute lung injury (TRALI) in conjunction with the transfusion of whole blood or blood components. Its hallmarks include hypoxemia, dyspnea, fever, hypotension, and bilateral pulmonary edema (noncardiogenic). The mortality for reported cases is 16.3%. The incidence and mortality may be even higher than estimated because of under-recognition and under-reporting. Although TRALI was identified as a clinical entity in the 1980s, a lack of consensus regarding a definition was present until 2004. An exact cause has yet to be identified; however, there are two theories regarding the etiology: the "antibody" and the "two-hit" theories. These theories involve both donor and recipient factors. Further education and research are needed to assist in the development of strategies for the prevention and treatment of TRALI.

  8. Blood brain barrier dysfunction and delayed neurological deficits in mild traumatic brain injury induced by blast shock waves

    PubMed Central

    Shetty, Ashok K.; Mishra, Vikas; Kodali, Maheedhar; Hattiangady, Bharathi

    2014-01-01

    Mild traumatic brain injury (mTBI) resulting from exposure to blast shock waves (BSWs) is one of the most predominant causes of illnesses among veterans who served in the recent Iraq and Afghanistan wars. Such mTBI can also happen to civilians if exposed to shock waves of bomb attacks by terrorists. While cognitive problems, memory dysfunction, depression, anxiety and diffuse white matter injury have been observed at both early and/or delayed time-points, an initial brain pathology resulting from exposure to BSWs appears to be the dysfunction or disruption of the blood-brain barrier (BBB). Studies in animal models suggest that exposure to relatively milder BSWs (123 kPa) initially induces free radical generating enzymes in and around brain capillaries, which enhances oxidative stress resulting in loss of tight junction (TJ) proteins, edema formation, and leakiness of BBB with disruption or loss of its components pericytes and astrocyte end-feet. On the other hand, exposure to more intense BSWs (145–323 kPa) causes acute disruption of the BBB with vascular lesions in the brain. Both of these scenarios lead to apoptosis of endothelial and neural cells and neuroinflammation in and around capillaries, which may progress into chronic traumatic encephalopathy (CTE) and/or a variety of neurological impairments, depending on brain regions that are afflicted with such lesions. This review discusses studies that examined alterations in the brain milieu causing dysfunction or disruption of the BBB and neuroinflammation following exposure to different intensities of BSWs. Furthermore, potential of early intervention strategies capable of easing oxidative stress, repairing the BBB or blocking inflammation for minimizing delayed neurological deficits resulting from exposure to BSWs is conferred. PMID:25165433

  9. Pre-Adult MRI of Brain Cancer and Neurological Injury: Multivariate Analyses.

    PubMed

    Levman, Jacob; Takahashi, Emi

    2016-01-01

    Brain cancer and neurological injuries, such as stroke, are life-threatening conditions for which further research is needed to overcome the many challenges associated with providing optimal patient care. Multivariate analysis (MVA) is a class of pattern recognition technique involving the processing of data that contains multiple measurements per sample. MVA can be used to address a wide variety of neuroimaging challenges, including identifying variables associated with patient outcomes; understanding an injury's etiology, development, and progression; creating diagnostic tests; assisting in treatment monitoring; and more. Compared to adults, imaging of the developing brain has attracted less attention from MVA researchers, however, remarkable MVA growth has occurred in recent years. This paper presents the results of a systematic review of the literature focusing on MVA technologies applied to brain injury and cancer in neurological fetal, neonatal, and pediatric magnetic resonance imaging (MRI). With a wide variety of MRI modalities providing physiologically meaningful biomarkers and new biomarker measurements constantly under development, MVA techniques hold enormous potential toward combining available measurements toward improving basic research and the creation of technologies that contribute to improving patient care.

  10. Autophagy in acute kidney injury and repair.

    PubMed

    He, Liyu; Livingston, Man J; Dong, Zheng

    2014-01-01

    Acute kidney injury (AKI) is a major kidney disease associated with a poor clinical outcome both in the short and long term. Autophagy is a cellular stress response that plays important roles in the pathogenesis of various diseases. Autophagy is induced in proximal tubules during AKI. A renoprotective role of autophagy in AKI has been demonstrated by pharmacological and genetic inhibition studies. The role of autophagy in kidney recovery and repair from AKI, however, remains largely unknown. A dynamic change in autophagy during the recovery phase of AKI seems to be important for tubular proliferation and repair. In renal fibrosis, autophagy may either promote this via the induction of tubular atrophy and decomposition, or prevent it via effects on the intracellular degradation of excessive collagen. Further research is expected to improve the understanding of the regulation of autophagy in kidney injury and repair, elucidate the pathological roles of autophagy in renal fibrosis, and discover therapeutic targets for treating AKI and preventing its progression to chronic kidney disease.

  11. Traumatic brain injury is associated with subsequent neurologic and psychiatric disease: a meta-analysis

    PubMed Central

    Perry, David C.; Sturm, Virginia E.; Peterson, Matthew J.; Pieper, Carl F.; Bullock, Thomas; Boeve, Bradley F.; Miller, Bruce L.; Guskiewicz, Kevin M.; Berger, Mitchel S.; Kramer, Joel H.; Welsh-Bohmer, Kathleen A.

    2016-01-01

    Object Mild traumatic brain injury (TBI) has been proposed as a risk factor for development of Alzheimer’s disease, Parkinson’s disease, depression, and other illnesses. This study’s objective was to determine the association of prior mild TBI with subsequent diagnosis (i.e., at least one year post-injury) of neurologic or psychiatric disease. Methods All studies from 1995–2012 reporting TBI as a risk factor for diagnoses of interest were identified by searching PubMed, study references, and review articles. Reviewers abstracted the data and assessed study design and characteristics. Results 57 studies met inclusion criteria. A random effects meta-analysis revealed a significant association of prior TBI with subsequent neurologic and psychiatric diagnosis. The pooled odds ratio (OR) for TBI on development of any illness was 1.67 (95% CI 1.44–1.93, p<.001). Prior TBI was independently associated with both neurologic [OR 1.55 (95% CI 1.31–1.83, p<.001)] and psychiatric [OR 2.00 (95% CI 1.50–2.66, p<.001)] outcomes. Analyses of individual diagnoses found higher odds of Alzheimer’s disease, Parkinson’s disease, mild cognitive impairment, depression, mixed affective disorders, and bipolar disorder in individuals with previous TBI compared to those without TBI. This association was present when examining only studies of mild TBI and when considering the influence of study design and characteristics. Analysis of a subset of studies found no evidence that multiple TBIs were associated with higher odds of disease than a single TBI. Conclusions History of TBI, including mild TBI, is associated with the development of neurologic and psychiatric illness. This indicates that either TBI is a risk factor for heterogeneous pathologic processes or that TBI may contribute to a common pathologic mechanism. PMID:26315003

  12. Acute kidney injury: global health alert.

    PubMed

    Li, Philip Kam Tao; Burdmann, Emmanuel A; Mehta, Ravindra L

    2013-05-01

    Acute kidney injury (AKI) is increasingly prevalent in developing and developed countries and is associated with severe morbidity and mortality. Most etiologies of AKI can be prevented by interventions at the individual, community, regional and in-hospital levels. Effective measures must include community-wide efforts to increase an awareness of the devastating effects of AKI and provide guidance on preventive strategies, as well as early recognition and management. Efforts should be focused on minimizing causes of AKI, increasing awareness of the importance of serial measurements of serum creatinine in high-risk patients, and documenting urine volume in acutely ill people to achieve early diagnosis; there is as yet no definitive role for alternative biomarkers. Protocols need to be developed to systematically manage prerenal conditions and specific infections. More accurate data about the true incidence and clinical impact of AKI will help to raise the importance of the disease in the community, and increase awareness of AKI by governments, the public, general and family physicians and other healthcare professionals to help prevent the disease. Prevention is the key to avoid the heavy burden of mortality and morbidity associated with AKI.

  13. Acute renal injury after partial hepatectomy

    PubMed Central

    Peres, Luis Alberto Batista; Bredt, Luis Cesar; Cipriani, Raphael Flavio Fachini

    2016-01-01

    Currently, partial hepatectomy is the treatment of choice for a wide variety of liver and biliary conditions. Among the possible complications of partial hepatectomy, acute kidney injury (AKI) should be considered as an important cause of increased morbidity and postoperative mortality. Difficulties in the data analysis related to postoperative AKI after liver resections are mainly due to the multiplicity of factors to be considered in the surgical patients, moreover, there is no consensus of the exact definition of AKI after liver resection in the literature, which hampers comparison and analysis of the scarce data published on the subject. Despite this multiplicity of risk factors for postoperative AKI after partial hepatectomy, there are main factors that clearly contribute to its occurrence. First factor relates to large blood losses with renal hypoperfusion during the operation, second factor relates to the occurrence of post-hepatectomy liver failure with consequent distributive circulatory changes and hepatorenal syndrome. Eventually, patients can have more than one factor contributing to post-operative AKI, and frequently these combinations of acute insults can be aggravated by sepsis or exposure to nephrotoxic drugs. PMID:27478539

  14. Acute kidney injury in the tropics

    PubMed Central

    Mathew, Ashish Jacob; George, Jacob

    2011-01-01

    Acute kidney injury (AKI) is one of the most challenging problems faced by clinicians in the tropics owing to its fast-changing burden. AKI in the tropics is strikingly different from that in the developed world in terms of etiology and presentation. In addition, there is a stark contrast between well-developed and poor areas in the tropics. The true epidemiological picture of AKI in the tropics is not well understood due to the late presentation of patients to tertiary centers. Infections remain the major culprit in most cases of AKI, with high mortality rates in the tropics. Human immunodeficiency virus–related AKI, related to nephrotoxicity due to antiretroviral therapy, is on the rise. Acute tubular necrosis and thrombotic microangiopathy are the most common mechanisms of AKI. A notable problem in the tropics is the scarcity of resources in health centers to support patients who require critical care due to AKI. This article reviews the unique and contrasting nature of AKI in the tropics and describes its management in each situation. PMID:21911980

  15. Acute kidney injury in the tropics.

    PubMed

    Mathew, Ashish Jacob; George, Jacob

    2011-01-01

    Acute kidney injury (AKI) is one of the most challenging problems faced by clinicians in the tropics owing to its fast-changing burden. AKI in the tropics is strikingly different from that in the developed world in terms of etiology and presentation. In addition, there is a stark contrast between well-developed and poor areas in the tropics. The true epidemiological picture of AKI in the tropics is not well understood due to the late presentation of patients to tertiary centers. Infections remain the major culprit in most cases of AKI, with high mortality rates in the tropics. Human immunodeficiency virus-related AKI, related to nephrotoxicity due to antiretroviral therapy, is on the rise. Acute tubular necrosis and thrombotic microangiopathy are the most common mechanisms of AKI. A notable problem in the tropics is the scarcity of resources in health centers to support patients who require critical care due to AKI. This article reviews the unique and contrasting nature of AKI in the tropics and describes its management in each situation.

  16. [Transfusion-related acute lung injury (TRALI)].

    PubMed

    Schweisfurth, H; Sopivnik, I; Moog, R

    2014-09-01

    Transfusion-related acute lung injury (TRALI) is primarily caused by transfusion of fresh frozen plasma or platelet concentrates and occurs by definition within 6 hours after transfusion with acute shortness of breath, hypoxemia and radiographically detectable bilateral infiltrates of the lung. Mostly leucocyte antibodies in the plasma of the blood donor (immunogenic TRALI) are responsible. Apart from antibodies, other substances such as biologically active lipids, mainly arising from the storage of platelet and red blood cell concentrates, can activate neutrophilic granulocytes and trigger a non-immunogenic TRALI. Pathophysiologically, granulocytes in the capillaries of the lung vessels release oxygen radicals and enzymes which damage the endothelial cells and cause pulmonary edema. Therapeutically, nasal oxygen administration may be sufficient. In severe cases, mechanical ventilation, invasive hemodynamic monitoring and fluid intake are required. Diuretics should be avoided. The administration of glucocorticoids is controversial. Antibody-related TRALI reactions occurred mainly after transfusion of fresh frozen plasma, which had been obtained from womenimmunized during pregnancy against leukocyte antigens. Therefore, in Germany, since 2009 only plasma from female donors without a history of prior or current pregnancy or negative testing for antibodies against HLA I, II or HNA has been used with the result that since then no TRALI-related death has been registered.

  17. Alveolar edema fluid clearance and acute lung injury.

    PubMed

    Berthiaume, Yves; Matthay, Michael A

    2007-12-15

    Although lung-protective ventilation strategies have substantially reduced mortality of acute lung injury patients there is still a need for new therapies that can further decrease mortality in patients with acute lung injury. Studies of epithelial ion and fluid transport across the distal pulmonary epithelia have provided important new concepts regarding potential new therapies for acute lung injury. Overall, there is convincing evidence that the alveolar epithelium is not only a tight epithelial barrier that resists the movement of edema fluid into the alveoli, but it is also actively involved in the transport of ions and solutes, a process that is essential for edema fluid clearance and the resolution of acute lung injury. The objective of this article is to consider some areas of recent progress in the field of alveolar fluid transport under normal and pathologic conditions. Vectorial ion transport across the alveolar and distal airway epithelia is the primary determinant of alveolar fluid clearance. The general paradigm is that active Na(+) and Cl(-) transport drives net alveolar fluid clearance, as demonstrated in several different species, including the human lung. Although these transport processes can be impaired in severe lung injury, multiple experimental studies suggest that upregulation of Na(+) and Cl(-) transport might be an effective therapy in acute lung injury. We will review mechanisms involved in pharmacological modulation of ion transport in lung injury with a special focus on the use of beta-adrenergic agonists which has generated considerable interest and is a promising therapy for clinical acute lung injury.

  18. Acute Kidney Injury Predicts Mortality after Charcoal Burning Suicide

    PubMed Central

    Chen, Yu-Chin; Tseng, Yi-Chia; Huang, Wen-Hung; Hsu, Ching-Wei; Weng, Cheng-Hao; Liu, Shou-Hsuan; Yang, Huang-Yu; Chen, Kuan-Hsin; Chen, Hui-Ling; Fu, Jen-Fen; Lin, Wey-Ran; Wang, I-Kuan; Yen, Tzung-Hai

    2016-01-01

    A paucity of literature exists on risk factors for mortality in charcoal burning suicide. In this observational study, we analyzed the data of 126 patients with charcoal burning suicide that seen between 2002 and 2013. Patients were grouped according to status of renal damage as acute kidney injury (N = 49) or non-acute kidney injury (N = 77). It was found that patients with acute kidney injury suffered severer complications such as respiratory failure (P = 0.002), myocardial injury (P = 0.049), hepatic injury (P < 0.001), rhabdomyolysis (P = 0.045) and out-of-hospital cardiac arrest (P = 0.028) than patients without acute kidney injury. Moreover, patients with acute kidney injury suffered longer hospitalization duration (16.9 ± 18.3 versus 10.7 ± 10.9, P = 0.002) and had higher mortality rate (8.2% versus 0%, P = 0.011) than patients without injury. In a multivariate Cox regression model, it was demonstrated that serum creatinine level (P = 0.019) and heart rate (P = 0.022) were significant risk factors for mortality. Finally, Kaplan-Meier analysis revealed that patients with acute kidney injury suffered lower cumulative survival than without injury (P = 0.016). In summary, the overall mortality rate of charcoal burning suicide population was 3.2%, and acute kidney injury was a powerful predictor of mortality. Further studies are warranted. PMID:27430168

  19. Rehabilitative potential of Ayurveda for neurological deficits caused by traumatic spinal cord injury

    PubMed Central

    Rastogi, Sanjeev

    2014-01-01

    Spinal cord injury (SCI) is associated with worst outcomes and requires a prolonged rehabilitation. Ayurvedic indigenous methods of rehabilitation are often utilized to treat such conditions. A case of SCI was followed up for 3 months upon an Ayurvedic composite intervention and subsequently reported. The composite treatment plan involved Ayurvedic oral medications as well as a few selected external and internal pancha karma procedures. A substantial clinical and patient centered outcome improvement in existing neurological deficits and quality of life was observed after 3 months of the Ayurvedic treatment given to this case. PMID:24812477

  20. Acute liver injury induced by weight-loss herbal supplements

    PubMed Central

    Chen, Gary C; Ramanathan, Vivek S; Law, David; Funchain, Pauline; Chen, George C; French, Samuel; Shlopov, Boris; Eysselein, Viktor; Chung, David; Reicher, Sonya; Pham, Binh V

    2010-01-01

    We report three cases of patients with acute liver injury induced by weight-loss herbal supplements. One patient took Hydroxycut while the other two took Herbalife supplements. Liver biopsies for all patients demonstrated findings consistent with drug-induced acute liver injury. To our knowledge, we are the first institute to report acute liver injury from both of these two types of weight-loss herbal supplements together as a case series. The series emphasizes the importance of taking a cautious approach when consuming herbal supplements for the purpose of weight loss. PMID:21173910

  1. Acute liver injury induced by weight-loss herbal supplements.

    PubMed

    Chen, Gary C; Ramanathan, Vivek S; Law, David; Funchain, Pauline; Chen, George C; French, Samuel; Shlopov, Boris; Eysselein, Viktor; Chung, David; Reicher, Sonya; Pham, Binh V

    2010-11-27

    We report three cases of patients with acute liver injury induced by weight-loss herbal supplements. One patient took Hydroxycut while the other two took Herbalife supplements. Liver biopsies for all patients demonstrated findings consistent with drug-induced acute liver injury. To our knowledge, we are the first institute to report acute liver injury from both of these two types of weight-loss herbal supplements together as a case series. The series emphasizes the importance of taking a cautious approach when consuming herbal supplements for the purpose of weight loss.

  2. Nontraumatic spinal cord injury at the neurological intensive care unit: spectrum, causes of admission and predictors of mortality

    PubMed Central

    Grassner, Lukas; Marschallinger, Julia; Dünser, Martin W.; Novak, Helmut F.; Zerbs, Alexander; Aigner, Ludwig; Trinka, Eugen; Sellner, Johann

    2015-01-01

    Objective: Nontraumatic spinal cord injuries (NTSCIs) form a heterogeneous group of diseases, which may evolve into a life-threatening condition. We sought to characterize spectrum, causes of admission and predictors of death in patients with NTSCI treated at the neurological intensive care unit (NICU). Methods: We performed a retrospective observational analysis of NTSCI cases treated at a tertiary care center between 2001 and 2013. Among the 3937 NICU admissions were 93 patients with NTSCI (2.4%). Using multivariate logistic regression analysis, we examined predictors of mortality including demographics, etiology, reasons for admission and GCS/SAPS (Glasgow Coma Scale/Simplified Acute Physiology Score) scores. Results: Infectious and inflammatory/autoimmune causes made up 50% of the NTSCI cases. The most common reasons for NICU admission were rapidly progressing paresis (49.5%) and abundance of respiratory insufficiency (26.9%). The mortality rate was 22.6% and 2.5-fold higher than in the cohort of all other patients treated at the NICU. Respiratory insufficiency as the reason for NICU admission [odds ratio (OR) 4.97, 95% confidence interval (CI) 1.38–17.9; p < 0.01], high initial SAPS scores (OR 1.04; 95% CI 1.003–1.08; p = 0.04), and the development of acute kidney injury throughout the stay (OR 7.25, 1.9–27.5; p = 0.004) were independent risk factors for NICU death. Conclusions: Patients with NTSCI account for a subset of patients admitted to the NICU and are at risk for adverse outcome. A better understanding of predisposing conditions and further knowledge of management of critically ill patients with NTSCI is mandatory. PMID:27006696

  3. Bath salt intoxication causing acute kidney injury requiring hemodialysis.

    PubMed

    Regunath, Hariharan; Ariyamuthu, Venkatesh Kumar; Dalal, Pranavkumar; Misra, Madhukar

    2012-10-01

    Traditional bath salts contain a combination of inorganic salts like Epsom salts, table salt, baking soda, sodium metaphosphate, and borax that have cleansing properties. Since 2010, there have been rising concerns about a new type of substance abuse in the name of "bath salts." They are beta-ketone amphetamine analogs and are derivates of cathinone, a naturally occurring amphetamine analog found in the "khat" plant (Catha edulis). Effects reported with intake included increased energy, empathy, openness, and increased libido. Serious adverse effects reported with intoxication included cardiac, psychiatric, and neurological signs and symptoms. Not much is known about the toxicology and metabolism of these compounds. They inhibit monoamine reuptake (dopamine, nor epinephrine, etc.) and act as central nervous system stimulants with high additive and abuse potential because of their clinical and biochemical similarities to effects from use of cocaine, amphetamine, and 3,4-methylenedioxy-N-methylamphetamine. Deaths associated with use of these compounds have also been reported. We report a case of acute kidney injury associated with the use of "bath salt" pills that improved with hemodialysis.

  4. Worse Neurological State During Acute Ischemic Stroke is Associated with a Decrease in Serum Albumin Levels.

    PubMed

    Bielewicz, Joanna; Kurzepa, Jacek; Czekajska-Chehab, Elżbieta; Kamieniak, Piotr; Daniluk, Beata; Bartosik-Psujek, Halina; Rejdak, Konrad

    2016-04-01

    High serum albumin levels during ischemic stroke (IS) decrease the risk of a poor outcome. This study aimed to determine whether serum albumin levels within the first days after IS correlate with radiological and biochemical markers of brain tissue damage. Fifty-six IS patients were enrolled into the study. Neurological examinations were based on the National Institute of Health Stroke Scale. Serum albumin levels and S100BB were evaluated using commercially available ELISA kits. The albumin decrease index (ADI) was calculated as the difference between serum albumin levels measured on days 1 and 10 of IS. All parameters were estimated on the 1st, 3rd, 5th, and 10th days of IS, and the volume of ischemic focus was measured on the 10th day. Mean serum albumin levels were decreased during acute IS. There were correlations between the ADI and mean S100BB serum levels (r = 0.36, p < 0.05), the volume of ischemic focus (r = 0.39, p < 0.05), and the patients' neurological state when measured on day 10 of IS (r = 0.59, p < 0.001). A decrease in serum albumin levels during the acute phase of IS corresponds to a worse neurological state as a result of a large ischemic focus with intense catabolic processes.

  5. Acute Acquired Comitant Esotropia in Adults: Is It Neurologic or Not?

    PubMed Central

    Kansu, Tulay

    2016-01-01

    Objectives. Acute acquired comitant esotropia (AACE) can be a diagnostic challenge for ophthalmologists and neurologists because of its association with neurological pathologies. Our study describes a series of adult patients with AACE of undetermined etiology. Methods. Data on the clinical findings of patients presented with AACE of undetermined etiology with a minimum follow-up of 1 year were retrieved from the medical records and the results analyzed. Results. A series of 9 esotropia cases (age range: 20–43 years) was reviewed. All patients had full duction and versions, without an A-pattern or V-pattern. All patients had esotropia for distance and near. Neurological evaluation in all cases was normal. Among patients, 3 were treated with prisms, 4 were treated with strabismus surgery, and 1 was treated with botulinum toxin injections; 1 patient declined treatment. In treated patients posttreatment sensory testing indicated restoration of binocularity that remained stable throughout follow-up of 1–9 years. The patient that declined treatment had binocular function with base-out prisms. Conclusion. Acute onset esotropia may be seen without a neurological pathology in adults. Good motor and sensory outcomes can be achieved in these patients with AACE of undetermined etiology via surgical and nonsurgical methods. PMID:28018672

  6. Transfusion related acute lung injury presenting with acute dyspnoea: a case report

    PubMed Central

    Haji, Altaf Gauhar; Sharma, Shekhar; Vijaykumar, DK; Paul, Jerry

    2008-01-01

    Introduction Transfusion-related acute lung injury is emerging as a common cause of transfusion-related adverse events. However, awareness about this entity in the medical fraternity is low and it, consequently, remains a very under-reported and often an under-diagnosed complication of transfusion therapy. Case presentation We report a case of a 46-year old woman who developed acute respiratory and hemodynamic instability following a single unit blood transfusion in the postoperative period. Investigation results were non-specific and a diagnosis of transfusion-related acute lung injury was made after excluding other possible causes of acute lung injury. She responded to symptomatic management with ventilatory and vasopressor support and recovered completely over the next 72 hours. Conclusion The diagnosis of transfusion-related acute lung injury relies on excluding other causes of acute pulmonary edema following transfusion, such as sepsis, volume overload, and cardiogenic pulmonary edema. All plasma containing blood products have been implicated in transfusion-related acute lung injury, with the majority being linked to whole blood, packed red blood cells, platelets, and fresh-frozen plasma. The pathogenesis of transfusion-related acute lung injury may be explained by a "two-hit" hypothesis, involving priming of the inflammatory machinery and then activation of this primed mechanism. Treatment is supportive, with prognosis being substantially better than for most other causes of acute lung injury. PMID:18957111

  7. Acupuncture Improved Neurological Recovery after Traumatic Brain Injury by Activating BDNF/TrkB Pathway

    PubMed Central

    Li, Xiaohong; Chen, Chong; Yang, Xiping; Wang, Jingjing; Zhao, Ming-liang; Sun, Hongtao

    2017-01-01

    How to promote neural repair following traumatic brain injury (TBI) has long been an intractable problem. Although acupuncture has been demonstrated to facilitate the neurological recovery, the underlying mechanism is elusive. Brain-derived neurotrophic factor (BDNF) exerts substantial protective effects for neurological disorders. In this study, we found that the level of BDNF and tropomyosin receptor kinase B (TrkB) was elevated spontaneously after TBI and reached up to the peak at 12 h. Nevertheless, this enhancement is quickly declined to the normal at 48 h. After combined stimulation at the acupoints of Baihui, Renzhong, Hegu, and Zusanli, we found that BDNF and TrkB were still significantly elevated at 168 h. We also observed that the downstream molecular p-Akt and p-Erk1/2 were significantly increased, suggesting that acupuncture could persistently activate the BDNF/TrkB pathway. To further verify that acupuncture improved recovery through activating BDNF/TrkB pathway, K252a (specific inhibitor of TrkB) was treated by injection stereotaxically into lateral ventricle. We observed that K252a could significantly prevent the acupuncture-induced amelioration of motor, sensation, cognition, and synaptic plasticity. These data indicated that acupuncture promoted the recovery of neurological impairment after TBI by activating BDNF/TrkB signaling pathway, providing new molecular mechanism for understanding traditional therapy of acupuncture. PMID:28243312

  8. The throw: biomechanics and acute injury.

    PubMed

    Gainor, B J; Piotrowski, G; Puhl, J; Allen, W C; Hagen, R

    1980-01-01

    The throw and its modifications are integral components of many sports. This study correlates case histories of acute injuries in throwing with a biomechanical analysis of the throwing mechanism. Comparisons are made with a similar analysis of the kick analyzed by the same film technique and computer program. Just prior to ball release, the pitching arm extends through an arc of about 73 degress in 40 msec, beginning with the elbow flexed at 80 degrees. This produces an axial load on the humerus and coincides with a pulse of external torque at the shoulder. This acts as stress protection to the humerus which is developing an internal torque of 14,000 inch-lb prior to ball release. The change in angular velocity, or the angular acceleration, during the throw is acquired in a much shorter time than in the kick. Torque is directly proportional to angular acceleration. This necessitates the development of substantially higher torques in the humerus during the throw than about the knee during a kick. The kinetic energy in the arm is 27,000 inch-lb during the throw. This is much higher than the kinetic energy in the kicking leg because the kinetic energy varies proportionally with the square of the angular velocity of the extremity. The angular velocity of the arm is about twice that of the leg. Thus, the pitching arm contains about four times as much kinetic energy as the kicking leg. These severe overloading conditions predispose the upper extremity to injury in the throwing mechanism.

  9. Pre-Adult MRI of Brain Cancer and Neurological Injury: Multivariate Analyses

    PubMed Central

    Levman, Jacob; Takahashi, Emi

    2016-01-01

    Brain cancer and neurological injuries, such as stroke, are life-threatening conditions for which further research is needed to overcome the many challenges associated with providing optimal patient care. Multivariate analysis (MVA) is a class of pattern recognition technique involving the processing of data that contains multiple measurements per sample. MVA can be used to address a wide variety of neuroimaging challenges, including identifying variables associated with patient outcomes; understanding an injury’s etiology, development, and progression; creating diagnostic tests; assisting in treatment monitoring; and more. Compared to adults, imaging of the developing brain has attracted less attention from MVA researchers, however, remarkable MVA growth has occurred in recent years. This paper presents the results of a systematic review of the literature focusing on MVA technologies applied to brain injury and cancer in neurological fetal, neonatal, and pediatric magnetic resonance imaging (MRI). With a wide variety of MRI modalities providing physiologically meaningful biomarkers and new biomarker measurements constantly under development, MVA techniques hold enormous potential toward combining available measurements toward improving basic research and the creation of technologies that contribute to improving patient care. PMID:27446888

  10. [Positive end-expiratory pressure : adjustment in acute lung injury].

    PubMed

    Bruells, C S; Dembinski, R

    2012-04-01

    Treatment of patients suffering from acute lung injury is a challenge for the treating physician. In recent years ventilation of patients with acute hypoxic lung injury has changed fundamentally. Besides the use of low tidal volumes, the most beneficial setting of positive end-expiratory pressure (PEEP) has been in the focus of researchers. The findings allow adaption of treatment to milder forms of acute lung injury and severe forms. Additionally computed tomography techniques to assess the pulmonary situation and recruitment potential as well as bed-side techniques to adjust PEEP on the ward have been modified and improved. This review gives an outline of recent developments in PEEP adjustment for patients suffering from acute hypoxic and hypercapnic lung injury and explains the fundamental pathophysiology necessary as a basis for correct treatment.

  11. Alcohol Exposure after Mild Focal Traumatic Brain Injury Impairs Neurological Recovery and Exacerbates Localized Neuroinflammation

    PubMed Central

    Teng, Sophie X; Katz, Paige S; Maxi, John K; Mayeux, Jacques P; Gilpin, Nicholas W; Molina, Patricia E

    2014-01-01

    Traumatic brain injury (TBI) represents a leading cause of morbidity and mortality among young individuals. Alcohol abuse is a risk factor associated with increased TBI incidence. In addition, up to 26% of TBI patients engage in alcohol consumption after TBI. Limited preclinical studies have examined the impact of post-injury alcohol exposure on TBI recovery. The aim of this study was to determine the isolated and combined effects of TBI and alcohol on cognitive, behavioral, and physical recovery, as well as on associated neuroinflammatory changes. Male Sprague-Dawley rats (~300 g) were subjected to a mild focal TBI by lateral fluid percussion (~30 PSI, ~25 ms) under isoflurane anesthesia. On day 4 after TBI, animals were exposed to either sub-chronic intermittent alcohol vapor (95% ethanol 14h on /10h off; BAL~200 mg/dL) or room air for 10 days. TBI induced neurological dysfunction reflected by an increased neurological severity score (NSS) showed progressive improvement in injured animals exposed to room air (TBI/air). In contrast, TBI animals exposed to alcohol vapor (TBI/alcohol) showed impaired NSS recovery throughout the 10-day period of alcohol exposure. Open-field exploration test revealed an increased anxiety-like behavior in TBI/alcohol group compared to TBI/air group. Additionally, alcohol-exposed animals showed decreased locomotion and impaired novel object recognition. Immunofluorescence showed enhanced reactive astrocytes, microglial activation, and HMGB1 expression localized to the injured cortex of TBI/alcohol as compared to TBI/air animals. The expression of neuroinflammatory markers showed significant positive correlation with NSS. These findings indicated a close relationship between accentuated neuroinflammation and impaired neurological recovery from post-TBI alcohol exposure. The clinical implications of long-term consequences in TBI patients exposed to alcohol during recovery warrant further investigation. PMID:25489880

  12. Alcohol exposure after mild focal traumatic brain injury impairs neurological recovery and exacerbates localized neuroinflammation.

    PubMed

    Teng, Sophie X; Katz, Paige S; Maxi, John K; Mayeux, Jacques P; Gilpin, Nicholas W; Molina, Patricia E

    2015-03-01

    Traumatic brain injury (TBI) represents a leading cause of morbidity and mortality among young individuals. Alcohol abuse is a risk factor associated with increased TBI incidence. In addition, up to 26% of TBI patients engage in alcohol consumption after TBI. Limited preclinical studies have examined the impact of post-injury alcohol exposure on TBI recovery. The aim of this study was to determine the isolated and combined effects of TBI and alcohol on cognitive, behavioral, and physical recovery, as well as on associated neuroinflammatory changes. Male Sprague-Dawley rats (∼300g) were subjected to a mild focal TBI by lateral fluid percussion (∼30PSI, ∼25ms) under isoflurane anesthesia. On day 4 after TBI, animals were exposed to either sub-chronic intermittent alcohol vapor (95% ethanol 14h on/10h off; BAL∼200mg/dL) or room air for 10days. TBI induced neurological dysfunction reflected by an increased neurological severity score (NSS) showed progressive improvement in injured animals exposed to room air (TBI/air). In contrast, TBI animals exposed to alcohol vapor (TBI/alcohol) showed impaired NSS recovery throughout the 10-day period of alcohol exposure. Open-field exploration test revealed an increased anxiety-like behavior in TBI/alcohol group compared to TBI/air group. Additionally, alcohol-exposed animals showed decreased locomotion and impaired novel object recognition. Immunofluorescence showed enhanced reactive astrocytes, microglial activation, and HMGB1 expression localized to the injured cortex of TBI/alcohol as compared to TBI/air animals. The expression of neuroinflammatory markers showed significant positive correlation with NSS. These findings indicated a close relationship between accentuated neuroinflammation and impaired neurological recovery from post-TBI alcohol exposure. The clinical implications of long-term consequences in TBI patients exposed to alcohol during recovery warrant further investigation.

  13. Tracking Spinal Cord Injury: Differences in Cytokine Expression of IGF-1, TGF- B1, and sCD95l Can Be Measured in Blood Samples and Correspond to Neurological Remission in a 12-Week Follow-Up.

    PubMed

    Ferbert, Thomas; Child, Christopher; Graeser, Viola; Swing, Tyler; Akbar, Michael; Heller, Raban; Biglari, Bahram; Moghaddam, Arash

    2017-02-01

    Neuroinflammation presumably has an important impact on the secondary phase of spinal cord injury and is regulated by pro- and anti-inflammatory cytokines. We analyzed serum levels of three different cytokines (insulin-like-growth-factor [IGF]-1, tumor growth factor [TGF]-β1, and soluble CD 95 ligand [sCD95L]), in blood samples of 23 patients admitted with acute traumatic spinal cord injury between November 2010 and July 2013 with a follow-up period of 12 weeks. Quantification was performed using Human Quantikine Immunoassays, classification of neurological impairment was performed using the American Spinal Cord Injury Impairment Scale at time of admission and after 12 weeks. After an initial drop of all three cytokine serum levels, IGF-1, TGF-β1, and sCD95L showed significantly increased serum levels during the acute and sub-acute phases. For IGF-1 and sCD95L, we could also observe significantly higher serum levels in patients without neurological improvement compared with patients who had improvement after 12 weeks. In this study, we were able to show differences in cytokine serum levels in patients with different neurological outcome. Measuring the serum level patterns of IGF-1, TGF-β1, and sCD95L might be a useful tool for prognosis in patients with neurological improvement and tracking the pathophysiology in further studies. Further, our observations might link promising therapeutic efforts in numerous animal studies and future studies in human patients.

  14. Acute kidney injury and dialysis in children: illustrative cases.

    PubMed

    Symons, Jordan M; Picca, Stefano

    2008-09-01

    Pediatric nephrologists and critical care physicians are faced with a heterogeneous patient population with varied epidemiology caring for children with acute kidney injury or other diseases that may require renal replacement therapy provision. We have composed 4 detailed case scenarios to highlight the challenges and interdisciplinary approach required for optimal care provision to children, and that serve to direct the different articles contained in this special issue of Seminars of Nephrology devoted to acute kidney injury in children.

  15. Prostatic surgery associated acute kidney injury

    PubMed Central

    Costalonga, Elerson Carlos; Costa e Silva, Verônica Torres; Caires, Renato; Hung, James; Yu, Luis; Burdmann, Emmanuel A

    2014-01-01

    Acute kidney injury (AKI) is associated with extended hospital stays, high risks of in-hospital and long-term mortality, and increased risk of incident and progressive chronic kidney disease. Patients with urological diseases are a high-risk group for AKI owing to the coexistence of obstructive uropathy, older age, and preexistent chronic kidney disease. Nonetheless, precise data on the incidence and outcomes of postoperative AKI in urological procedures are lacking. Benign prostatic hyperplasia and prostate cancer are common diagnoses in older men and are frequently treated with surgical procedures. Whereas severe AKI after prostate surgery in general appears to be unusual, AKI associated with transurethral resection of the prostate (TURP) syndrome and with rhabdomyolysis (RM) after radical prostatectomy have been frequently described. The purpose of this review is to discuss the current knowledge regarding the epidemiology, risk factors, outcomes, prevention, and treatment of AKI associated with prostatic surgery. The mechanisms of TURP syndrome and RM following prostatic surgeries will be emphasized. PMID:25374813

  16. Acute Kidney Injury in Diabetes Mellitus

    PubMed Central

    Müller, G. A.

    2016-01-01

    Diabetes mellitus (DM) significantly increases the overall morbidity and mortality, particularly by elevating the cardiovascular risk. The kidneys are severely affected as well, partly as a result of intrarenal athero- and arteriosclerosis but also due to noninflammatory glomerular damage (diabetic nephropathy). DM is the most frequent cause of end-stage renal disease in our society. Acute kidney injury (AKI) remains a clinical and prognostic problem of fundamental importance since incidences have been increased in recent years while mortality has not substantially been improved. As a matter of fact, not many studies particularly addressed the topic “AKI in diabetes mellitus.” Aim of this article is to summarize AKI epidemiology and outcomes in DM and current recommendations on blood glucose control in the intensive care unit with regard to the risk for acquiring AKI, and finally several aspects related to postischemic microvasculopathy in AKI of diabetic patients shall be discussed. We intend to deal with this relevant topic, last but not least with regard to increasing incidences and prevalences of both disorders, AKI and DM. PMID:27974972

  17. Cardiac surgery-associated acute kidney injury

    PubMed Central

    Ortega-Loubon, Christian; Fernández-Molina, Manuel; Carrascal-Hinojal, Yolanda; Fulquet-Carreras, Enrique

    2016-01-01

    Cardiac surgery-associated acute kidney injury (CSA-AKI) is a well-recognized complication resulting with the higher morbid-mortality after cardiac surgery. In its most severe form, it increases the odds ratio of operative mortality 3–8-fold, length of stay in the Intensive Care Unit and hospital, and costs of care. Early diagnosis is critical for an optimal treatment of this complication. Just as the identification and correction of preoperative risk factors, the use of prophylactic measures during and after surgery to optimize renal function is essential to improve postoperative morbidity and mortality of these patients. Cardiopulmonary bypass produces an increased in tubular damage markers. Their measurement may be the most sensitive means of early detection of AKI because serum creatinine changes occur 48 h to 7 days after the original insult. Tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 are most promising as an early diagnostic tool. However, the ideal noninvasive, specific, sensitive, reproducible biomarker for the detection of AKI within 24 h is still not found. This article provides a review of the different perspectives of the CSA-AKI, including pathogenesis, risk factors, diagnosis, biomarkers, classification, postoperative management, and treatment. We searched the electronic databases, MEDLINE, PubMed, EMBASE using search terms relevant including pathogenesis, risk factors, diagnosis, biomarkers, classification, postoperative management, and treatment, in order to provide an exhaustive review of the different perspectives of the CSA-AKI. PMID:27716701

  18. Post-partum acute kidney injury.

    PubMed

    Pahwa, Naresh; Bharani, Rajesh; Kumar, Ravindra

    2014-11-01

    To determine the risk factors, course of hospital stay and mortality rate among women with post-partum acute kidney injury (AKI), we studied (of 752 patients with AKI admitted to a tertiary care center during the study period between November 2009 and August 2012) 27 (3.59%) women with post-partum AKI. The data regarding age, parity, cause of renal failure, course of hospital stay and requirement of dialysis were recorded. Sepsis was the major cause (70.3%) of post-partum AKI. Other causes included disseminated intravascular coagulation (55.5%), pre-eclampsia/eclampsia (40.7%), ante- and post-partum hemorrhage (40.7% and 22.2%) and hemolytic anemia and elevated liver enzymes and low platelet count syndrome (29.6%); most patients had more than one cause of AKI. We found a very high prevalence (18.5%) of cortical necrosis in our study patients. A significant correlation was also found between the creatinine level on admission and the period of onset of disease after delivery. In conclusion, several factors are involved in causing post-partum AKI in our population, and sepsis was the most common of them.

  19. Urodynamic profile in acute transverse myelitis patients: Its correlation with neurological outcome

    PubMed Central

    Gupta, Anupam; Kumar, Sushruth Nagesh; Taly, Arun B.

    2017-01-01

    Objective: The objective of this study was to observe urodynamic profile of acute transverse myelitis (ATM) patients and its correlation with neurological outcome. Patients and Methods: This prospective study was conducted in the neurorehabilitation unit of a tertiary university research hospital from July 2012 to June 2014. Forty-three patients (19 men) with ATM with bladder dysfunction, admitted in the rehabilitation unit, were included in this study. Urodynamic study (UDS) was performed in all the patients. Their neurological status was assessed using ASIA impairment scale and functional status was assessed using spinal cord independence measure. Bladder management was based on UDS findings. Results: In total, 17 patients had tetraplegia and 26 had paraplegia. Thirty-six patients (83.7%) had complaints of increased frequency and urgency of urine with 26 patients reported at least one episode of urge incontinence. Seven patients reported obstructive urinary complaints in the form of straining to void with 13 patients reported both urgency and straining to void and 3 also had stress incontinence. Thirty-seven (86.1%) patients had neurogenic overactive detrusor with or without sphincter dyssynergia and five patients had acontractile detrusor on UDS. No definitive pattern was observed between neurological status and bladder characteristics. All patients showed significant neurological and functional recovery with inpatient rehabilitation (P < 0.05 and P < 0.001, respectively). Conclusions: The problem of neurogenic bladder dysfunction is integral to ATM. Bladder management in these patients should be based on UDS findings. Bladder characteristics have no definitive pattern consistent with the neurological status. PMID:28149080

  20. Subspace based adaptive denoising of surface EMG from neurological injury patients

    NASA Astrophysics Data System (ADS)

    Liu, Jie; Ying, Dongwen; Zev Rymer, William; Zhou, Ping

    2014-10-01

    Objective: After neurological injuries such as spinal cord injury, voluntary surface electromyogram (EMG) signals recorded from affected muscles are often corrupted by interferences, such as spurious involuntary spikes and background noises produced by physiological and extrinsic/accidental origins, imposing difficulties for signal processing. Conventional methods did not well address the problem caused by interferences. It is difficult to mitigate such interferences using conventional methods. The aim of this study was to develop a subspace-based denoising method to suppress involuntary background spikes contaminating voluntary surface EMG recordings. Approach: The Karhunen-Loeve transform was utilized to decompose a noisy signal into a signal subspace and a noise subspace. An optimal estimate of EMG signal is derived from the signal subspace and the noise power. Specifically, this estimator is capable of making a tradeoff between interference reduction and signal distortion. Since the estimator partially relies on the estimate of noise power, an adaptive method was presented to sequentially track the variation of interference power. The proposed method was evaluated using both semi-synthetic and real surface EMG signals. Main results: The experiments confirmed that the proposed method can effectively suppress interferences while keep the distortion of voluntary EMG signal in a low level. The proposed method can greatly facilitate further signal processing, such as onset detection of voluntary muscle activity. Significance: The proposed method can provide a powerful tool for suppressing background spikes and noise contaminating voluntary surface EMG signals of paretic muscles after neurological injuries, which is of great importance for their multi-purpose applications.

  1. Inductive and Deductive Approaches to Acute Cell Injury

    PubMed Central

    DeGracia, Donald J.; Tri Anggraini, Fika; Taha, Doaa Taha Metwally; Huang, Zhi-Feng

    2014-01-01

    Many clinically relevant forms of acute injury, such as stroke, traumatic brain injury, and myocardial infarction, have resisted treatments to prevent cell death following injury. The clinical failures can be linked to the currently used inductive models based on biological specifics of the injury system. Here we contrast the application of inductive and deductive models of acute cell injury. Using brain ischemia as a case study, we discuss limitations in inductive inferences, including the inability to unambiguously assign cell death causality and the lack of a systematic quantitative framework. These limitations follow from an overemphasis on qualitative molecular pathways specific to the injured system. Our recently developed nonlinear dynamical theory of cell injury provides a generic, systematic approach to cell injury in which attractor states and system parameters are used to quantitatively characterize acute injury systems. The theoretical, empirical, and therapeutic implications of shifting to a deductive framework are discussed. We illustrate how a deductive mathematical framework offers tangible advantages over qualitative inductive models for the development of therapeutics of acutely injured biological systems. PMID:27437490

  2. Transverse Myelitis in Acute Hepatitis A Infection: The Rare Co-Occurrence of Hepatology and Neurology

    PubMed Central

    Chonmaitree, Piyanant; Methawasin, Kulthida

    2016-01-01

    Transverse myelitis refers to the inflammatory process involving the spinal cord. Clinical features can be either acute or subacute onset that results in neurological deficits such as weakness and/or numbness of extremities as well as autonomic dysfunctions. While there are some etiologies related, a viral infection is common. However, the hepatitis A virus rarely causes myelitis. This report provides details of a hepatitis A infectious patient who developed myelitis as comorbidity. Although, the disability was initially severe, the patient successfully recovered with corticosteroid treatment. PMID:27403101

  3. The influence of time from injury to surgery on motor recovery and length of hospital stay in acute traumatic spinal cord injury: an observational Canadian cohort study.

    PubMed

    Dvorak, Marcel F; Noonan, Vanessa K; Fallah, Nader; Fisher, Charles G; Finkelstein, Joel; Kwon, Brian K; Rivers, Carly S; Ahn, Henry; Paquet, Jérôme; Tsai, Eve C; Townson, Andrea; Attabib, Najmedden; Bailey, Christopher S; Christie, Sean D; Drew, Brian; Fourney, Daryl R; Fox, Richard; Hurlbert, R John; Johnson, Michael G; Linassi, A G; Parent, Stefan; Fehlings, Michael G

    2015-05-01

    To determine the influence of time from injury to surgery on neurological recovery and length of stay (LOS) in an observational cohort of individuals with traumatic spinal cord injury (tSCI), we analyzed the baseline and follow-up motor scores of participants in the Rick Hansen Spinal Cord Injury Registry to specifically assess the effect of an early (less than 24 h from injury) surgical procedure on motor recovery and on LOS. One thousand four hundred and ten patients who sustained acute tSCIs with baseline American Spinal Injury Association Impairment Scale (AIS) grades A, B, C, or D and were treated surgically were analyzed to determine the effect of the timing of surgery (24, 48, or 72 h from injury) on motor recovery and LOS. Depending on the distribution of data, we used different types of generalized linear models, including multiple linear regression, gamma regression, and negative binomial regression. Persons with incomplete AIS B, C, and D injuries from C2 to L2 demonstrated motor recovery improvement of an additional 6.3 motor points (SE=2.8 p<0.03) when they underwent surgical treatment within 24 h from the time of injury, compared with those who had surgery later than 24 h post-injury. This beneficial effect of early surgery on motor recovery was not seen in the patients with AIS A complete SCI. AIS A and B patients who received early surgery experienced shorter hospital LOS. While the issues of when to perform surgery and what specific operation to perform remain controversial, this work provides evidence that for an incomplete acute tSCI in the cervical, thoracic, or thoracolumbar spine, surgery performed within 24 h from injury improves motor neurological recovery. Early surgery also reduces LOS.

  4. Glomerular haematuria, renal interstitial haemorrhage and acute kidney injury.

    PubMed

    Martín Cleary, Catalina; Moreno, Juan Antonio; Fernández, Beatriz; Ortiz, Alberto; Parra, Emilio G; Gracia, Carolina; Blanco-Colio, Luis M; Barat, Antonio; Egido, Jesús

    2010-12-01

    Macroscopic haematuria of glomerular origin has been associated with acute kidney injury. We report a patient with IgA nephropathy, macroscopic haematuria and acute kidney injury. Systemic anticoagulation may have aggravated haematuria. There was extensive interstitial and intratubular red blood cell extravasation, and interstitial haemosiderin deposits. The abundant presence of macrophages expressing the haemoglobin scavenger receptor CD163 and of cells stained for oxidative stress markers (NADPH-p22 phox and heme-oxigenase-1) in areas of interstitial haemorrhage and red blood cell cast-containing tubules provided evidence for a role for free haemoglobin in tubulointerstitial renal injury in human glomerular disease.

  5. Bath Salts: A Newly Recognized Cause of Acute Kidney Injury

    PubMed Central

    McNeely, Jonathan; Parikh, Samir; Valentine, Christopher; Haddad, Nabil; Shidham, Ganesh; Rovin, Brad; Hebert, Lee; Agarwal, Anil

    2012-01-01

    Bath salts are substance of abuse that are becoming more common and are difficult to recognize due to negative toxicology screening. Acute kidney injury due to bath salt use has not previously been described. We present the case of a previously healthy male who developed acute kidney injury and dialysis dependence after bath salt ingestion and insufflation. This was self-reported with negative toxicology screening. Clinical course was marked by severe hyperthermia, hyperkalemia, rhabdomyolysis, disseminated intravascular coagulation, oliguria, and sepsis. We discuss signs and symptoms, differential diagnoses, potential mechanisms of injury, management, and review of the literature related to bath salt toxicity. PMID:24555135

  6. Giant multinucleated macrophages occur in acute spinal cord injury.

    PubMed

    Leskovar, A; Turek, J; Borgens, R B

    2001-05-01

    Using a cell-isolation and -culture procedure specific for macrophages, we report the existence of giant (more than 50 microm diameter), multinucleated macrophages within an acute, 5-day-old adult rat spinal cord injury. The size and multinuclearity of these isolated giant cells was confirmed using transmission electron microscopy. Giant macrophages are markers for long-term infection, disease, and chronic injury in other soft tissues and are unexpected in the acute inflammatory stage of central nervous system injury. To our knowledge, this descriptive report is the first confirming the existence of giant macrophages in any injured nervous tissue, with additional data suggesting some of these cells to be multinucleated.

  7. Nonlinear Dynamic Theory of Acute Cell Injuries and Brain Ischemia

    NASA Astrophysics Data System (ADS)

    Taha, Doaa; Anggraini, Fika; Degracia, Donald; Huang, Zhi-Feng

    2015-03-01

    Cerebral ischemia in the form of stroke and cardiac arrest brain damage affect over 1 million people per year in the USA alone. In spite of close to 200 clinical trials and decades of research, there are no treatments to stop post-ischemic neuron death. We have argued that a major weakness of current brain ischemia research is lack of a deductive theoretical framework of acute cell injury to guide empirical studies. A previously published autonomous model based on the concept of nonlinear dynamic network was shown to capture important facets of cell injury, linking the concept of therapeutic to bistable dynamics. Here we present an improved, non-autonomous formulation of the nonlinear dynamic model of cell injury that allows multiple acute injuries over time, thereby allowing simulations of both therapeutic treatment and preconditioning. Our results are connected to the experimental data of gene expression and proteomics of neuron cells. Importantly, this new model may be construed as a novel approach to pharmacodynamics of acute cell injury. The model makes explicit that any pro-survival therapy is always a form of sub-lethal injury. This insight is expected to widely influence treatment of acute injury conditions that have defied successful treatment to date. This work is supported by NIH NINDS (NS081347) and Wayne State University President's Research Enhancement Award.

  8. Laboratory Test Surveillance following Acute Kidney Injury

    PubMed Central

    Matheny, Michael E.; Peterson, Josh F.; Eden, Svetlana K.; Hung, Adriana M.; Speroff, Theodore; Abdel-Kader, Khaled; Parr, Sharidan K.; Ikizler, T. Alp; Siew, Edward D.

    2014-01-01

    Background Patients with hospitalized acute kidney injury (AKI) are at increased risk for accelerated loss of kidney function, morbidity, and mortality. We sought to inform efforts at improving post-AKI outcomes by describing the receipt of renal-specific laboratory test surveillance among a large high-risk cohort. Methods We acquired clinical data from the Electronic health record (EHR) of 5 Veterans Affairs (VA) hospitals to identify patients hospitalized with AKI from January 1st, 2002 to December 31st, 2009, and followed these patients for 1 year or until death, enrollment in palliative care, or improvement in renal function to estimated GFR (eGFR) ≥60 L/min/1.73 m2. Using demographic data, administrative codes, and laboratory test data, we evaluated the receipt and timing of outpatient testing for serum concentrations of creatinine and any as well as quantitative proteinuria recommended for CKD risk stratification. Additionally, we reported the rate of phosphorus and parathyroid hormone (PTH) monitoring recommended for chronic kidney disease (CKD) patients. Results A total of 10,955 patients admitted with AKI were discharged with an eGFR<60 mL/min/1.73 m2. During outpatient follow-up at 90 and 365 days, respectively, creatinine was measured on 69% and 85% of patients, quantitative proteinuria was measured on 6% and 12% of patients, PTH or phosphorus was measured on 10% and 15% of patients. Conclusions Measurement of creatinine was common among all patients following AKI. However, patients with AKI were infrequently monitored with assessments of quantitative proteinuria or mineral metabolism disorder, even for patients with baseline kidney disease. PMID:25117447

  9. Acute kidney injury in pregnancy: a clinical challenge.

    PubMed

    Machado, Susana; Figueiredo, Nuno; Borges, Andreia; São José Pais, Maria; Freitas, Luís; Moura, Paulo; Campos, Mário

    2012-01-01

    The incidence of acute kidney injury in pregnancy declined significantly over the second half of the 20th century; however, it is still associated with major maternal and perinatal morbidity and mortality. A set of systemic and renal physiological adaptive mechanisms occur during a normal gestation that will constrain several changes in laboratory parameters of renal function, electrolytes, fluid and acid-base balances. The diagnosis of acute kidney injury in pregnancy is based on the serum creatinine increase. The usual formulas for estimating glomerular filtration rate are not validated in this population. During the first trimester of gestation, acute kidney injury develops most often due to hyperemesis gravidarum or septic abortion. In the third trimester, the differential diagnosis is more challenging for the obstetrician and the nephrologist and comprises some pathologies that are reviewed in this article: preeclampsia/HELLP syndrome, acute fatty liver of pregnancy and thrombotic microangiopathies.

  10. Acute hydrogen sulfide-induced neuropathology and neurological sequelae: challenges for translational neuroprotective research.

    PubMed

    Rumbeiha, Wilson; Whitley, Elizabeth; Anantharam, Poojya; Kim, Dong-Suk; Kanthasamy, Arthi

    2016-08-01

    Hydrogen sulfide (H2 S), the gas with the odor of rotten eggs, was formally discovered in 1777, over 239 years ago. For many years, it was considered an environmental pollutant and a health concern only in occupational settings. Recently, however, it was discovered that H2 S is produced endogenously and plays critical physiological roles as a gasotransmitter. Although at low physiological concentrations it is physiologically beneficial, exposure to high concentrations of H2 S is known to cause brain damage, leading to neurodegeneration and long-term neurological sequelae or death. Neurological sequelae include motor, behavioral, and cognitive deficits, which are incapacitating. Currently, there are concerns about accidental or malicious acute mass civilian exposure to H2 S. There is a major unmet need for an ideal neuroprotective treatment, for use in the field, in the event of mass civilian exposure to high H2 S concentrations. This review focuses on the neuropathology of high acute H2 S exposure, knowledge gaps, and the challenges associated with development of effective neuroprotective therapy to counteract H2 S-induced neurodegeneration.

  11. Acute hydrogen sulfide–induced neuropathology and neurological sequelae: challenges for translational neuroprotective research

    PubMed Central

    Whitley, Elizabeth; Anantharam, Poojya; Kim, Dong‐Suk; Kanthasamy, Arthi

    2016-01-01

    Hydrogen sulfide (H2S), the gas with the odor of rotten eggs, was formally discovered in 1777, over 239 years ago. For many years, it was considered an environmental pollutant and a health concern only in occupational settings. Recently, however, it was discovered that H2S is produced endogenously and plays critical physiological roles as a gasotransmitter. Although at low physiological concentrations it is physiologically beneficial, exposure to high concentrations of H2S is known to cause brain damage, leading to neurodegeneration and long‐term neurological sequelae or death. Neurological sequelae include motor, behavioral, and cognitive deficits, which are incapacitating. Currently, there are concerns about accidental or malicious acute mass civilian exposure to H2S. There is a major unmet need for an ideal neuroprotective treatment, for use in the field, in the event of mass civilian exposure to high H2S concentrations. This review focuses on the neuropathology of high acute H2S exposure, knowledge gaps, and the challenges associated with development of effective neuroprotective therapy to counteract H2S‐induced neurodegeneration. PMID:27442775

  12. The anatomy and biomechanics of acute and chronic whiplash injury.

    PubMed

    Siegmund, Gunter P; Winkelstein, Beth A; Ivancic, Paul C; Svensson, Mats Y; Vasavada, Anita

    2009-04-01

    Whiplash injury is the most common motor vehicle injury, yet it is also one of the most poorly understood. Here we examine the evidence supporting an organic basis for acute and chronic whiplash injuries and review the anatomical sites within the neck that are potentially injured during these collisions. For each proposed anatomical site--facet joints, spinal ligaments, intervertebral discs, vertebral arteries, dorsal root ganglia, and neck muscles--we present the clinical evidence supporting that injury site, its relevant anatomy, the mechanism of and tolerance to injury, and the future research needed to determine whether that site is responsible for some whiplash injuries. This article serves as a snapshot of the current state of whiplash biomechanics research and provides a roadmap for future research to better understand and ultimately prevent whiplash injuries.

  13. A new perspective in the understanding of hand dysfunction following neurological injury.

    PubMed

    Sangole, Archana P; Levin, Mindy F

    2007-01-01

    The human hand is inherently complex and versatile. Its use in everyday activities requires its careful positioning relative to the arm and fine adjustments of the fingers to secure the object in the hand to perform a desired task. Understanding the mechanics of prehension requires an appreciation of the anatomy, biomechanics, kinematics, and control of the hand. This article summarizes these complex mechanisms as well as the central nervous system control of hand movement. We propose a measure to characterize the biomechanics of palmar arch modulation during grasping. We also highlight questions to be investigated in future studies to stimulate further understanding of the motor control of hand function and of the recovery of hand functioning after neurological injury.

  14. Neurology and neuropathology of Soman-induced brain injury: an overview.

    PubMed Central

    Petras, J M

    1994-01-01

    Battlefield use of nerve agents poses serious medical threats to combat troops and to civilians in the immediate or adjacent environment. The experiments reported herein were carried out in the 1980s to help to define both the neurological and neuropathological consequences of exposure to the organophosphate nerve agent Soman. These data contributed to the scientific foundation for a program of drug development to find agents that would prevent or reduce the risk of injury to the central nervous system and specifically pointed to the importance of including an anticonvulsant in the treatment of agent exposure. Since these experiments were conducted, research efforts have continued to improve pretreatment and treatment, such as the inclusion of the anticonvulsant diazepam in the medical treatment of exposed personnel. Images Fig. 1. Fig. 2. Fig. 3. PMID:8169578

  15. 2009 Review and Revisions of the International Standards for the Neurological Classification of Spinal Cord Injury

    PubMed Central

    Waring, William P; Biering-Sorensen, Fin; Burns, Stephen; Donovan, William; Graves, Daniel; Jha, Amitabh; Jones, Linda; Kirshblum, Steven; Marino, Ralph; Mulcahey, M.J; Reeves, Ronald; Scelza, William M; Schmidt-Read, Mary; Stein, Adam

    2010-01-01

    Summary: The International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) were recently reviewed by the ASIA's Education and Standards Committees, in collaboration with the International Spinal Cord Society's Education Committee. Available educational materials for the ISNCSCI were also reviewed. The last citable reference for the ISNCSCI's methodology is the ISNCSCI Reference Manual, published in 2003 by ASIA. The Standards Committee recommended that the numerous items that were revised should be published and a precedent established for a routine published review of the ISNCSCI. The Standards Committee also noted that, although the 2008 reprint pocket booklet is current, the reference manual should be revised after proposals to modify/revise the ASIA Impairment Scale (AIS as modified from Frankel) are considered. In addition, the Standards Committee adopted a process for thorough and transparent review of requests to revise the ISNCSCI. PMID:21061894

  16. _ 2009 review and revisions of the international standards for the neurological classification of spinal cord injury.

    PubMed

    Waring, William P; Biering-Sorensen, Fin; Burns, Stephen; Donovan, William; Graves, Daniel; Jha, Amitabh; Jones, Linda; Kirshblum, Steven; Marino, Ralph; Mulcahey, M J; Reeves, Ronald; Scelza, William M; Schmidt-Read, Mary; Stein, Adam

    2010-01-01

    The International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) were recently reviewed by the ASIA's Education and Standards Committees, in collaboration with the International Spinal Cord Society's Education Committee. Available educational materials for the ISNCSCI were also reviewed. The last citable reference for the ISNCSCI's methodology is the ISNCSCI Reference Manual, published in 2003 by ASIA. The Standards Committee recommended that the numerous items that were revised should be published and a precedent established for a routine published review of the ISNCSCI. The Standards Committee also noted that, although the 2008 reprint pocket booklet is current, the reference manual should be revised after proposals to modify/revise the ASIA Impairment Scale (AIS as modified from Frankel) are considered. In addition, the Standards Committee adopted a process for thorough and transparent review of requests to revise the ISNCSCI.

  17. Cerebrolysin effects on neurological outcomes and cerebral blood flow in acute ischemic stroke

    PubMed Central

    Amiri-Nikpour, Mohammad Reza; Nazarbaghi, Surena; Ahmadi-Salmasi, Babak; Mokari, Tayebeh; Tahamtan, Urya; Rezaei, Yousef

    2014-01-01

    Background Cerebrolysin, a brain-derived neuropeptide, has been shown to improve the neurological outcomes of stroke, but no study has demonstrated its effect on cerebral blood flow. This study aimed to determine the cerebrolysin impact on the neurological outcomes and cerebral blood flow. Methods In a randomized, double-blinded, placebo-controlled trial, 46 patients who had acute focal ischemic stroke were randomly assigned into two groups to receive intravenously either 30 mL of cerebrolysin diluted in normal saline daily for 10 days (n=23) or normal saline alone (n=23) adjunct to 100 mg of aspirin daily. All patients were examined using the National Institutes of Health Stroke Scale and transcranial Doppler to measure the mean flow velocity and pulsatility index (PI) of their cerebral arteries at baseline as well as on days 30, 60, and 90. Results The patients’ mean age was 60±9.7 years, and 51.2% of patients were male. The National Institutes of Health Stroke Scale was significantly lower in the cerebrolysin group compared with the placebo group on day 60 (median 10, interquartile range 9–11, P=0.008) and day 90 (median 11, interquartile range 10–13.5, P=0.001). The median of PI in the right middle cerebral artery was significantly lower in the cerebrolysin group compared with the placebo group on days 30, 60, and 90 (P<0.05). One patient in the cerebrolysin group and two patients in the placebo group died before day 30 (4.3% versus 8.7%). Conclusion Cerebrolysin can be useful to improve the neurological outcomes and the PI of middle cerebral artery in patients with acute focal ischemic stroke. PMID:25516711

  18. Responsiveness to therapy for increased intracranial pressure in traumatic brain injury is associated with neurological outcome.

    PubMed

    Colton, K; Yang, S; Hu, P F; Chen, H H; Stansbury, L G; Scalea, T M; Stein, D M

    2014-12-01

    In patients with severe traumatic brain injury, increased intracranial pressure (ICP) is associated with poor functional outcome or death. Hypertonic saline (HTS) is a hyperosmolar therapy commonly used to treat increased ICP; this study aimed to measure initial patient response to HTS and look for association with patient outcome. Patients >17 years old, admitted and requiring ICP monitoring between 2008 and 2010 at a large urban tertiary care facility were retrospectively enrolled. The first dose of hypertonic saline administered after admission for ICP >19mmHg was recorded and correlated with vital signs recorded at the bedside. The absolute and relative change in ICP at 1 and 2h after HTS administration was calculated. Patients were stratified by mortality and long-term (≥6 months) functional neurological outcome. We identified 46 patients who received at least 1 dose of HTS for ICP>19, of whom 80% were male, mean age 34.4, with a median post-resuscitation GCS score of 6. All patients showed a significant decrease in ICP 1h after HTS administration. Two hours post-administration, survivors showed a further decrease in ICP (43% reduction from baseline), while ICP began to rebound in non-survivors (17% reduction from baseline). When patients were stratified for long-term neurological outcome, results were similar, with a significant difference in groups by 2h after HTS administration. In patients treated with HTS for intracranial hypertension, those who survived or had good neurological outcome, when compared to those who died or had poor outcomes, showed a significantly larger sustained decrease in ICP 2h after administration. This suggests that even early in a patient's treatment, treatment responsiveness is associated with mortality or poor functional outcome. While this work is preliminary, it suggests that early failure to obtain a sustainable response to hyperosmolar therapy may warrant greater treatment intensity or therapy escalation.

  19. Methylprednisolone for the Treatment of Patients with Acute Spinal Cord Injuries: A Propensity Score-Matched Cohort Study from a Canadian Multi-Center Spinal Cord Injury Registry

    PubMed Central

    Evaniew, Nathan; Noonan, Vanessa K.; Fallah, Nader; Kwon, Brian K.; Rivers, Carly S.; Ahn, Henry; Bailey, Christopher S.; Christie, Sean D.; Fourney, Daryl R.; Hurlbert, R. John; Linassi, A.G.; Fehlings, Michael G.

    2015-01-01

    Abstract In prior analyses of the effectiveness of methylprednisolone for the treatment of patients with acute traumatic spinal cord injuries (TSCIs), the prognostic importance of patients' neurological levels of injury and their baseline severity of impairment has not been considered. Our objective was to determine whether methylprednisolone improved motor recovery among participants in the Rick Hansen Spinal Cord Injury Registry (RHSCIR). We identified RHSCIR participants who received methylprednisolone according to the Second National Spinal Cord Injury Study (NASCIS-II) protocol and used propensity score matching to account for age, sex, time of neurological exam, varying neurological level of injury, and baseline severity of neurological impairment. We compared changes in total, upper extremity, and lower extremity motor scores using the Wilcoxon signed-rank test and performed sensitivity analyses using negative binomial regression. Forty-six patients received methylprednisolone and 1555 received no steroid treatment. There were no significant differences between matched participants for each of total (13.7 vs. 14.1, respectively; p=0.43), upper extremity (7.3 vs. 6.4; p=0.38), and lower extremity (6.5 vs. 7.7; p=0.40) motor recovery. This result was confirmed using a multivariate model and, as predicted, only cervical (C1–T1) rather than thoracolumbar (T2–L3) injury levels (p<0.01) and reduced baseline injury severity (American Spinal Injury Association [ASIA] Impairment Scale grades; p<0.01) were associated with greater motor score recovery. There was no in-hospital mortality in either group; however, the NASCIS-II methylprednisolone group had a significantly higher rate of total complications (61% vs. 36%; p=0.02) NASCIS-II methylprednisolone did not improve motor score recovery in RHSCIR patients with acute TSCIs in either the cervical or thoracic spine when the influence of anatomical level and severity of injury were included in the analysis. There

  20. Acute lung injury in fulminant hepatic failure following paracetamol poisoning.

    PubMed Central

    Baudouin, S. V.; Howdle, P.; O'Grady, J. G.; Webster, N. R.

    1995-01-01

    BACKGROUND--There is little information on the incidence of acute lung injury or changes in the pulmonary circulation in acute liver failure. The aim of this study was to record the incidence of acute lung injury in fulminant hepatic failure caused by paracetamol poisoning, to document the associated pulmonary circulatory changes, and to assess the impact of lung injury on patient outcome. METHODS--The degree of lung injury was retrospectively assessed by a standard scoring system (modified from Murray) in all patients with fulminant hepatic failure caused by paracetamol poisoning, admitted to the intensive care unit over a one year period. The severity of liver failure and illness, other organ system failure, and patient outcome were also analysed. RESULTS--Twenty four patients with paracetamol-induced liver failure were admitted and nine developed lung injury of whom eight (33%) had severe injury (Murray score > 2.5). In two patients hypoxaemia contributed to death. Patients with lung injury had higher median encephalopathy grades (4 v 2 in the non-injured group) and APACHE II scores (29 v 16). Circulatory failure, requiring vasoconstrictor support, occurred in all patients with lung injury but in only 40% of those without. Cerebral oedema, as detected by abnormal rises in intracranial pressure, also occurred in all patients with lung injury but in only 27% of the non-injured patients. The incidence of renal failure requiring renal replacement therapy was similar in both groups (67% and 47%). Pulmonary artery occlusion pressures were normal in the lung injury group. Cardiac output was high (median 11.2 1/min), systemic vascular resistance low (median 503 dynes/s/cm-5), and pulmonary vascular resistance low (median 70 dynes/s/cm-5), but not significantly different from the group without lung injury. Mortality was much higher in the lung injury group than in the non-injured group (89% v 13%). CONCLUSIONS--Acute lung injury was common in patients with paracetamol

  1. Correlation of brain levels of progesterone and dehydroepiandrosterone with neurological recovery after traumatic brain injury in female mice.

    PubMed

    Lopez-Rodriguez, Ana Belen; Acaz-Fonseca, Estefania; Giatti, Silvia; Caruso, Donatella; Viveros, Maria-Paz; Melcangi, Roberto C; Garcia-Segura, Luis M

    2015-06-01

    Traumatic brain injury (TBI) is an important cause of disability in humans. Neuroactive steroids, such as progesterone and dehydroepiandrosterone (DHEA), are neuroprotective in TBI models. However in order to design potential neuroprotective strategies based on neuroactive steroids it is important to determine whether its brain levels are altered by TBI. In this study we have used a weight-drop model of TBI in young adult female mice to determine the levels of neuroactive steroids in the brain and plasma at 24h, 72 h and 2 weeks after injury. We have also analyzed whether the levels of neuroactive steroids after TBI correlated with the neurological score of the animals. TBI caused neurological deficit detectable at 24 and 72 h, which recovered by 2 weeks after injury. Brain levels of progesterone, tetrahydroprogesterone (THP), isopregnanolone and 17β-estradiol were decreased 24h, 72 h and 2 weeks after TBI. DHEA and brain testosterone levels presented a transient decrease at 24h after lesion. Brain levels of progesterone and DHEA showed a positive correlation with neurological recovery. Plasma analyses showed that progesterone was decreased 72 h after lesion but, in contrast with brain progesterone, its levels did not correlate with neurological deficit. These findings indicate that TBI alters the levels of neuroactive steroids in the brain with independence of its plasma levels and suggest that the pharmacological increase in the brain of the levels of progesterone and DHEA may result in the improvement of neurological recovery after TBI.

  2. Urine specific gravity as a predictor of early neurological deterioration in acute ischemic stroke.

    PubMed

    Lin, L C; Fann, W C; Chou, M H; Chen, H W; Su, Y C; Chen, J C

    2011-07-01

    We previously found that a blood urea nitrogen/creatinine (BUN/Cr) ratio>15 is an independent predictor of early neurological deterioration after acute ischemic stroke, which suggests that dehydration may be a cause of early deterioration. The aim of this study was to determine whether urine specific gravity, which is another indicator of hydration status and one that is more easily obtained, is also an independent predictor of early deterioration or stroke-in-evolution (SIE). Demographic and clinical data were recorded at admission from patients with acute ischemic stroke who were prospectively enrolled from October 2007 to June 2010. We compared patients with and without stroke-in-evolution (based on an increase of 3 points or more points on the National Institutes of Health Stroke Scale within 3 days). Univariate and multivariate statistical analyses were carried out. A total of 317 patients (43 SIE and 274 non-SIE) were enrolled; the first 196 patients comprised the cohort of our previous study. The only two independent predictors of early deterioration or SIE were BUN/Cr>15 and urine specific gravity>1.010. After adjusting for age and gender, patients with a urine specific gravity>1.010 were 2.78 times more likely to develop SIE (95% CI=1.11-6.96; P=0.030). Urine specific gravity may be useful as an early predictor of early deterioration in patients with acute ischemic stroke. Patients with urine specific gravity ≤ 1.010 therefore may have a reduced likelihood of early neurological deterioration.

  3. Long-Term Consequences of Traumatic Brain Injury: Current Status of Potential Mechanisms of Injury and Neurological Outcomes

    PubMed Central

    Dietrich, W. Dalton

    2015-01-01

    Abstract Traumatic brain injury (TBI) is a significant clinical problem with few therapeutic interventions successfully translated to the clinic. Increased importance on the progressive, long-term consequences of TBI have been emphasized, both in the experimental and clinical literature. Thus, there is a need for a better understanding of the chronic consequences of TBI, with the ultimate goal of developing novel therapeutic interventions to treat the devastating consequences of brain injury. In models of mild, moderate, and severe TBI, histopathological and behavioral studies have emphasized the progressive nature of the initial traumatic insult and the involvement of multiple pathophysiological mechanisms, including sustained injury cascades leading to prolonged motor and cognitive deficits. Recently, the increased incidence in age-dependent neurodegenerative diseases in this patient population has also been emphasized. Pathomechanisms felt to be active in the acute and long-term consequences of TBI include excitotoxicity, apoptosis, inflammatory events, seizures, demyelination, white matter pathology, as well as decreased neurogenesis. The current article will review many of these pathophysiological mechanisms that may be important targets for limiting the chronic consequences of TBI. PMID:25158206

  4. Biomarkers in acute kidney injury: Evidence or paradigm?

    PubMed

    Lombi, Fernando; Muryan, Alexis; Canzonieri, Romina; Trimarchi, Hernán

    2016-01-01

    Acute kidney injury in the critically ill represents an independent risk factor of morbidity and mortality in the short and long terms, with significant economic impacts in terms of public health costs. Currently its diagnosis is still based on the presence of oliguria and/or a gradual increase in serum creatinine, which make the diagnosis a delayed event and to detriment of the so-called 'therapeutic window'. The appearance of new biomarkers of acute kidney injury could potentially improve this situation, contributing to the detection of 'subclinical acute kidney injury', which could allow the precocious employment of multiple treatment strategies in order to preserve kidney function. However these new biomarkers display sensitive features that may threaten their full capacity of action, which focus specifically on their additional contribution in the early approach of the situation, given the lack of specific validated treatments for acute kidney injury. This review aims to analyze the strengths and weaknesses of these new tools in the early management of acute kidney injury.

  5. Diffuse Brain Injury Induces Acute Post-Traumatic Sleep

    PubMed Central

    Rowe, Rachel K.; Striz, Martin; Bachstetter, Adam D.; Van Eldik, Linda J.; Donohue, Kevin D.; O'Hara, Bruce F.; Lifshitz, Jonathan

    2014-01-01

    Objective Clinical observations report excessive sleepiness immediately following traumatic brain injury (TBI); however, there is a lack of experimental evidence to support or refute the benefit of sleep following a brain injury. The aim of this study is to investigate acute post-traumatic sleep. Methods Sham, mild or moderate diffuse TBI was induced by midline fluid percussion injury (mFPI) in male C57BL/6J mice at 9:00 or 21:00 to evaluate injury-induced sleep behavior at sleep and wake onset, respectively. Sleep profiles were measured post-injury using a non-invasive, piezoelectric cage system. In separate cohorts of mice, inflammatory cytokines in the neocortex were quantified by immunoassay, and microglial activation was visualized by immunohistochemistry. Results Immediately after diffuse TBI, quantitative measures of sleep were characterized by a significant increase in sleep (>50%) for the first 6 hours post-injury, resulting from increases in sleep bout length, compared to sham. Acute post-traumatic sleep increased significantly independent of injury severity and time of injury (9:00 vs 21:00). The pro-inflammatory cytokine IL-1β increased in brain-injured mice compared to sham over the first 9 hours post-injury. Iba-1 positive microglia were evident in brain-injured cortex at 6 hours post-injury. Conclusion Post-traumatic sleep occurs for up to 6 hours after diffuse brain injury in the mouse regardless of injury severity or time of day. The temporal profile of secondary injury cascades may be driving the significant increase in post-traumatic sleep and contribute to the natural course of recovery through cellular repair. PMID:24416145

  6. Review of control strategies for robotic movement training after neurologic injury

    PubMed Central

    Marchal-Crespo, Laura; Reinkensmeyer, David J

    2009-01-01

    There is increasing interest in using robotic devices to assist in movement training following neurologic injuries such as stroke and spinal cord injury. This paper reviews control strategies for robotic therapy devices. Several categories of strategies have been proposed, including, assistive, challenge-based, haptic simulation, and coaching. The greatest amount of work has been done on developing assistive strategies, and thus the majority of this review summarizes techniques for implementing assistive strategies, including impedance-, counterbalance-, and EMG- based controllers, as well as adaptive controllers that modify control parameters based on ongoing participant performance. Clinical evidence regarding the relative effectiveness of different types of robotic therapy controllers is limited, but there is initial evidence that some control strategies are more effective than others. It is also now apparent there may be mechanisms by which some robotic control approaches might actually decrease the recovery possible with comparable, non-robotic forms of training. In future research, there is a need for head-to-head comparison of control algorithms in randomized, controlled clinical trials, and for improved models of human motor recovery to provide a more rational framework for designing robotic therapy control strategies. PMID:19531254

  7. Bile Acid Signaling Is Involved in the Neurological Decline in a Murine Model of Acute Liver Failure

    PubMed Central

    McMillin, Matthew; Frampton, Gabriel; Quinn, Matthew; Ashfaq, Samir; de los Santos, Mario; Grant, Stephanie; DeMorrow, Sharon

    2017-01-01

    Hepatic encephalopathy is a serious neurological complication of liver failure. Serum bile acids are elevated after liver damage and may disrupt the blood-brain barrier and enter the brain. Our aim was to assess the role of serum bile acids in the neurological complications after acute liver failure. C57Bl/6 or cytochrome p450 7A1 knockout (Cyp7A1−/−) mice were fed a control, cholestyramine-containing, or bile acid–containing diet before azoxymethane (AOM)-induced acute liver failure. In parallel, mice were given an intracerebroventricular infusion of farnesoid X receptor (FXR) Vivo-morpholino before AOM injection. Liver damage, neurological decline, and molecular analyses of bile acid signaling were performed. Total bile acid levels were increased in the cortex of AOM-treated mice. Reducing serum bile acids via cholestyramine feeding or using Cyp7A1−/− mice reduced bile acid levels and delayed AOM-induced neurological decline, whereas cholic acid or deoxycholic acid feeding worsened AOM-induced neurological decline. The expression of bile acid signaling machinery apical sodium-dependent bile acid transporter, FXR, and small heterodimer partner increased in the frontal cortex, and blocking FXR signaling delayed AOM-induced neurological decline. In conclusion, circulating bile acids may play a pathological role during hepatic encephalopathy, although precisely how they dysregulate normal brain function is unknown. Strategies to minimize serum bile acid concentrations may reduce the severity of neurological complications associated with liver failure. PMID:26683664

  8. Increased Blood Pressure Variability Is Associated with Worse Neurologic Outcome in Acute Anterior Circulation Ischemic Stroke

    PubMed Central

    Bennett, Alicia; Stoddard, Gregory J.; Smith, Gordon; Wang, Haimei; Wold, Jana; Chung, Lee; Tirschwell, David L.; Majersik, Jennifer J.

    2016-01-01

    Background. Although research suggests that blood pressure variability (BPV) is detrimental in the weeks to months after acute ischemic stroke, it has not been adequately studied in the acute setting. Methods. We reviewed acute ischemic stroke patients from 2007 to 2014 with anterior circulation stroke. Mean blood pressure and three BPV indices (standard deviation, coefficient of variation, and successive variation) for the intervals 0–24, 0–72, and 0–120 hours after admission were correlated with follow-up modified Rankin Scale (mRS) in ordinal logistic regression models. The correlation between BPV and mRS was further analyzed by terciles of clinically informative stratifications. Results. Two hundred and fifteen patients met inclusion criteria. At all time intervals, increased systolic BPV was associated with higher mRS, but the relationship was not significant for diastolic BPV or mean blood pressure. This association was strongest in patients with proximal stroke parent artery vessel occlusion and lower mean blood pressure. Conclusion. Increased early systolic BPV is associated with worse neurologic outcome after ischemic stroke. This association is strongest in patients with lower mean blood pressure and proximal vessel occlusion, often despite endovascular or thrombolytic therapy. This hypothesis-generating dataset suggests potential benefit for interventions aimed at reducing BPV in this patient population. PMID:27974991

  9. [Neurologic complications induced by the treatment of the acute renal allograft rejection with the monoclonal antibody OKT3].

    PubMed

    Fernández, O; Romero, F; Bravo, M; Burgos, D; Cabello, M; González-Molina, M

    1993-10-01

    The treatment of the acute renal allograft rejection with the monoclonal antibody orthoclone OKT3 produces both systemic and neurologic alterations. In a series of 21 patients with an acute renal allograft rejection treated with this monoclonal antibody, 20 with a renal allograft transplantation and one with a renal and pancreatic allograft transplantation, 29% referred headache associated with fever and vomiting, and 14.2% presented severe neurological alterations induced by the treatment. We stress the need to know these secondary effects to differentiate them from other central nervous system disorders, particularly those of infectious origin.

  10. Neurological complications of cardiac surgery.

    PubMed

    McDonagh, David L; Berger, Miles; Mathew, Joseph P; Graffagnino, Carmelo; Milano, Carmelo A; Newman, Mark F

    2014-05-01

    As increasing numbers of elderly people undergo cardiac surgery, neurologists are frequently called upon to assess patients with neurological complications from the procedure. Some complications mandate acute intervention, whereas others need longer term observation and management. A large amount of published literature exists about these complications and guidance on best practice is constantly changing. Similarly, despite technological advances in surgical intervention and modifications in surgical technique to make cardiac procedures safer, these advances often create new avenues for neurological injury. Accordingly, rapid and precise neurological assessment and therapeutic intervention rests on a solid understanding of the evidence base and procedural variables.

  11. Acute gastroduodenal injury after ingestion of diluted herbicide pendimethalin.

    PubMed

    Tsukada, K; Azuhata, H; Katoh, H; Kuwano, H

    2009-03-01

    The herbicide, pendimethalin, is used worldwide, but its acute toxicity is not yet widely known. There have been some reported acute pendimethalin poisoning cases in humans and most of them intentionally ingested the concentrated formulation. We describe a 73-year-old man who developed corrosive gastroduodenal injury after accidental ingestion of the diluted (300 times with water) pendimethalin formulation. He had a history of reflux oesophagitis and had been taking omeprazol (10 mg/day) for a year. He consumed alcohol two hours after the accidental ingestion and then had nausea and epigastric pain. Endoscopy performed three days post-exposure revealed gastroduodenal injury. As he had consumed alcohol every day for years and had no history of gastroduodenal ulcer, the accidental ingestion may be associated with this injury. He was successfully treated by increasing his dosage of omeprazol (20 mg/day) for two weeks. This case indicates that ingestion of a small quantity of pendimethalin can provoke gastroduodenal injury.

  12. [Acute and overuse injuries in elite paracycling - an epidemiological study].

    PubMed

    Kromer, P; Röcker, K; Sommer, A; Baur, H; Konstantinidis, L; Gollhofer, A; Südkamp, N P; Hirschmüller, A

    2011-09-01

    Although paracycling is a growing discipline in high level competitive sports as well as in posttraumatic rehabilitation, epidemiological data of resulting injuries is still missing. Therefore, 19 athletes of the German national paracycling team were asked about their injuries during the 2008 season using a standardized questionnaire. Overall, 18 (94.7 %) of 19 athletes reported overuse injuries; most commonly localized at the back (83.3 %), neck/shoulder (77.8 %), knee (50 %), groin/buttock (50 %) and hands/wrists (38.9 %). Altogether, 18 accidents were registered, corresponding to an injury rate of 0,95 acute injuries per athlete per year (0,07 / 1000 km). The most common acute injuries were abrasions (69.2 %) and contusions (61.5 %), whereas fractures were stated only twice (11.8 %). The anatomical distribution of overuse injuries in disabled cyclists confirms the results of studies in able-bodied cycling, although the incidences in low-back pain and neck/shoulder pain is clearly higher in disabled cycling, as well as the rate of traumatic injuries.

  13. Adrenomedullin ameliorates lipopolysaccharide-induced acute lung injury in rats.

    PubMed

    Itoh, Takefumi; Obata, Hiroaki; Murakami, Shinsuke; Hamada, Kaoru; Kangawa, Kenji; Kimura, Hiroshi; Nagaya, Noritoshi

    2007-08-01

    Adrenomedullin (AM), an endogenous peptide, has been shown to have a variety of protective effects on the cardiovascular system. However, the effect of AM on acute lung injury remains unknown. Accordingly, we investigated whether AM infusion ameliorates lipopolysaccharide (LPS)-induced acute lung injury in rats. Rats were randomized to receive continuous intravenous infusion of AM (0.1 microg x kg(-1) x min(-1)) or vehicle through a microosmotic pump. The animals were intratracheally injected with either LPS (1 mg/kg) or saline. At 6 and 18 h after intratracheal instillation, we performed histological examination and bronchoalveolar lavage and assessed the lung wet/dry weight ratio as an index of acute lung injury. Then we measured the numbers of total cells and neutrophils and the levels of tumor necrosis factor (TNF)-alpha and cytokine-induced neutrophil chemoattractant (CINC) in bronchoalveolar lavage fluid (BALF). In addition, we evaluated BALF total protein and albumin levels as indexes of lung permeability. LPS instillation caused severe acute lung injury, as indicated by the histological findings and the lung wet/dry weight ratio. However, AM infusion attenuated these LPS-induced abnormalities. AM decreased the numbers of total cells and neutrophils and the levels of TNF-alpha and CINC in BALF. AM also reduced BALF total protein and albumin levels. In addition, AM significantly suppressed apoptosis of alveolar wall cells as indicated by cleaved caspase-3 staining. In conclusion, continuous infusion of AM ameliorated LPS-induced acute lung injury in rats. This beneficial effect of AM on acute lung injury may be mediated by inhibition of inflammation, hyperpermeability, and alveolar wall cell apoptosis.

  14. Hippotherapy acute impact on heart rate variability non-linear dynamics in neurological disorders.

    PubMed

    Cabiddu, Ramona; Borghi-Silva, Audrey; Trimer, Renata; Trimer, Vitor; Ricci, Paula Angélica; Italiano Monteiro, Clara; Camargo Magalhães Maniglia, Marcela; Silva Pereira, Ana Maria; Rodrigues das Chagas, Gustavo; Carvalho, Eliane Maria

    2016-05-15

    Neurological disorders are associated with autonomic dysfunction. Hippotherapy (HT) is a therapy treatment strategy that utilizes a horse in an interdisciplinary approach for the physical and mental rehabilitation of people with physical, mental and/or psychological disabilities. However, no studies have been carried out which evaluated the effects of HT on the autonomic control in these patients. Therefore, the objective of the present study was to investigate the effects of a single HT session on cardiovascular autonomic control by time domain and non-linear analysis of heart rate variability (HRV). The HRV signal was recorded continuously in twelve children affected by neurological disorders during a HT session, consisting in a 10-minute sitting position rest (P1), a 15-minute preparatory phase sitting on the horse (P2), a 15-minute HT session (P3) and a final 10-minute sitting position recovery (P4). Time domain and non-linear HRV indices, including Sample Entropy (SampEn), Lempel-Ziv Complexity (LZC) and Detrended Fluctuation Analysis (DFA), were calculated for each treatment phase. We observed that SampEn increased during P3 (SampEn=0.56±0.10) with respect to P1 (SampEn=0.40±0.14, p<0.05), while DFA decreased during P3 (DFA=1.10±0.10) with respect to P1 (DFA=1.26±0.14, p<0.05). A significant SDRR increase (p<0.05) was observed during the recovery period P4 (SDRR=50±30ms) with respect to the HT session period P3 (SDRR=30±10ms). Our results suggest that HT might benefit children with disabilities attributable to neurological disorders by eliciting an acute autonomic response during the therapy and during the recovery period.

  15. Ammonium dichromate poisoning: A rare cause of acute kidney injury.

    PubMed

    Radhakrishnan, H; Gopi, M; Arumugam, A

    2014-11-01

    Ammonium dichromate is an inorganic compound frequently used in screen and color printing. Being a strong oxidizing agent, it causes oxygen free radical injury resulting in organ failure. We report a 25-year-old female who presented with acute kidney injury after consumption of ammonium dichromate. She was managed successfully with hemodialysis and supportive measures. This case is reported to highlight the toxicity of ammonium dichromate.

  16. Acute kidney injury caused by zonisamide-induced hypersensitivity syndrome.

    PubMed

    Fujita, Yoshiro; Hasegawa, Midori; Nabeshima, Kuihiro; Tomita, Makoto; Murakami, Kazutaka; Nakai, Shigeru; Yamakita, Takashi; Matsunaga, Kayoko

    2010-01-01

    Drug rash with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome (DIHS), is a severe adverse drug reaction affecting multiple organs caused by drug treatment. The current report describes a man who was prescribed zonisamide for epilepsy and subsequently developed widespread skin rash, acute kidney injury, high-grade fever, eosinophilia, liver dysfunction, lymphadenopathy and an increase in antihuman herpesvirus-6 immunoglobulin G titer. Hypersensitivity to zonisamide was confirmed by the skin patch test. Based on these findings, the patient was diagnosed with DRESS/DIHS caused by zonisamide. This is the first report of acute kidney injury due to zonisamide-induced DRESS/DIHS.

  17. Hepatic encephalopathy with reversible focal neurologic signs resembling acute stroke: case report.

    PubMed

    Yamamoto, Yoshiya; Nishiyama, Yasuhiro; Katsura, Ken-Ichiro; Yamazaki, Mineo; Katayama, Yasuo

    2011-01-01

    A 64-year-old female with a history of primary biliary cirrhosis and esophageal varices starting at age 39 was brought to our Stroke Care Unit by ambulance with right-side weakness and speech difficulty. Physical examination revealed right hemiparesis (including the face), sensory disturbances, pathological reflexes, and slightly decreased consciousness, with a Glasgow Coma Scale rating of E3V4M6. Flapping tremors and speech disturbance, as well as anarithmia, construction apraxia, and ideomotor apraxia, were noted, and her National Institutes of Health Stroke Scale score was 13. Initially, the patient was diagnosed with acute stroke and treated accordingly; however, subsequent findings from clinical images and electroencephalography led to a diagnosis of focal neurologic signs due to hepatic encephalopathy (HE). The patient had significantly reduced cerebral blood flow in the left side of the brain, probably due to microsurgical repair of an aneurysm done 2 years earlier. HE with exaggerated chronic liver damage might have made the previously silent ischemia clinically apparent. This interpretation is supported by the fact that the patient's neurologic deficits resolved once HE was adequately controlled. This case illustrates the need for careful assessment of background pathophysiology when diagnosing patients with stroke-like symptoms.

  18. Neuroprotective effects of bloodletting at Jing points combined with mild induced hypothermia in acute severe traumatic brain injury

    PubMed Central

    Tu, Yue; Miao, Xiao-mei; Yi, Tai-long; Chen, Xu-yi; Sun, Hong-tao; Cheng, Shi-xiang; Zhang, Sai

    2016-01-01

    Bloodletting at Jing points has been used to treat coma in traditional Chinese medicine. Mild induced hypothermia has also been shown to have neuroprotective effects. However, the therapeutic effects of bloodletting at Jing points and mild induced hypothermia alone are limited. Therefore, we investigated whether combined treatment might have clinical effectiveness for the treatment of acute severe traumatic brain injury. Using a rat model of traumatic brain injury, combined treatment substantially alleviated cerebral edema and blood-brain barrier dysfunction. Furthermore, neurological function was ameliorated, and cellular necrosis and the inflammatory response were lessened. These findings suggest that the combined effects of bloodletting at Jing points (20 μL, twice a day, for 2 days) and mild induced hypothermia (6 hours) are better than their individual effects alone. Their combined application may have marked neuroprotective effects in the clinical treatment of acute severe traumatic brain injury. PMID:27482221

  19. Acute stroke care in a neurologically underserved state: lessons learned from the Iowa Stroke Survey.

    PubMed

    Albright, Karen C; Schott, Todd C; Boland, Debbie F; George, Leslie; Boland, Kevin P; Wohlford-Wessels, Mary Pat; Finnerty, Edward P; Jacoby, Michael R K

    2009-01-01

    Prior studies have suggested that stroke care is more fragmented in rural or neurologically underserved areas. The purpose of this study was to determine the availability of diagnostic and treatment services for acute stroke care in Iowa and to identify factors influencing care. Each of the 118 facilities in Iowa with emergency departments was surveyed by telephone. This survey consisted of 10 questions, focusing on the existence of pre-hospital and emergency room acute stroke protocols and the availability of essential personnel and diagnostic and treatment modalities essential for acute stroke care. Of the 118 hospitals with emergency departments, 109 (92.4%) had CT available. Within the subset having CT capabilities, 89.9% (98/109) had intravenous tissue plasminogen activator (IV t-PA) available. Of those facilities with both CT and IV t-PA, 46% (45/98) had around-the-clock in-house physician coverage. Further, 31% (14/45) of sites with CT, t-PA, and an in-house physician had a radiology technician on site. Only 12% (14/118) of centers could offer all essential components. Despite 88% of Iowa hospitals not providing all of these components, only 31% of these hospitals reported protocols for stabilization and immediate transfer of acute stroke patients. These findings indicate that the development of a stroke system is still in its infancy in Iowa. Collaborative efforts are needed to address barriers in rural Iowa and to assist facilities in providing the best possible care. Creativity will be paramount in establishing a functional statewide system to ensure optimum care for all Iowans.

  20. Low Tidal Volume Ventilation in Patients Without Acute Lung Injury.

    PubMed

    Tang, Weibing; Wang, Zhi; Liu, Ye; Zhu, Jing

    2015-05-01

    Acute respiratory distress syndrome is a life threatening respiratory condition characterized by breakdown of the alveolar-capillary barrier, leading to flooding of the alveolar space producing the classical chest radiograph of bilateral pulmonary infiltrates. In this study, we employed lung protective ventilation strategies in patients without acute lung injury (ALI) to determine whether mechanical ventilation with lower tidal volume would provide more clinical benefits to patients without ALI.

  1. Oral penicillin-associated acute kidney injury in an infant with acute pyelonephritis.

    PubMed

    Zieg, Jakub; Hacek, Jaromir

    2015-04-01

    Beta-lactam-associated acute tubulointerstitial nephritis (ATIN) is a rare condition in childhood. We report the case of an infant with penicillin-associated ATIN and concomitant acute pyelonephritis resulting in the development of severe acute kidney injury (AKI). The treatment consisted of penicillin suspension and appropriate AKI management, which required a short period of dialysis. Finally, full recovery and normalization of laboratory parameters occurred. We present here the first case of oral penicillin-associated ATIN in childhood.

  2. Neurologic Injury Associated with Rewarming from Hypothermia: Is Mild Hypothermia on Bypass Better than Deep Hypothermic Circulatory Arrest?

    PubMed Central

    Bhalala, Utpal S.; Appachi, Elumalai; Mumtaz, Muhammad Ali

    2016-01-01

    Many known risk factors for adverse cardiovascular and neurological outcomes in children with congenital heart defects (CHD) are not modifiable; however, the temperature and blood flow during cardiopulmonary bypass (CPB), are two risk factors, which may be altered in an attempt to improve long-term neurological outcomes. Deep hypothermic circulatory arrest, traditionally used for aortic arch repair, has been associated with short-term and long-term neurologic sequelae. Therefore, there is a rising interest in using moderate hypothermia with selective antegrade cerebral blood flow on CPB during aortic arch repair. Rewarming from moderate-to-deep hypothermia has been shown to be associated with neuronal injury, neuroinflammation, and loss of cerebrovascular autoregulation. A significantly lesser degree of rewarming is required following mild (33–35°C) hypothermia as compared with moderate (28–32°C), deep (21–27°C), and profound (less than 20°C) hypothermia. Therefore, we believe that mild hypothermia is associated with a lower risk of rewarming-induced neurologic injury. We hypothesize that mild hypothermia with selective antegrade cerebral perfusion during CPB for neonatal aortic arch repair would be associated with improved neurologic outcome. PMID:27734011

  3. Resveratrol Pretreatment Decreases Ischemic Injury and Improves Neurological Function Via Sonic Hedgehog Signaling After Stroke in Rats.

    PubMed

    Yu, Pingping; Wang, Li; Tang, Fanren; Zeng, Li; Zhou, Luling; Song, Xiaosong; Jia, Wei; Chen, Jixiang; Yang, Qin

    2017-01-01

    Resveratrol has neuroprotective effects for ischemic cerebral stroke. However, its neuroprotective mechanism for stroke is less well understood. Beneficial actions of the activated Sonic hedgehog (Shh) signaling pathway in stroke, such as improving neurological function, promoting neurogenesis, anti-oxidative, anti-apoptotic, and pro-angiogenic effects, have been noted, but relatively little is known about the role of Shh signaling in resveratrol-reduced cerebral ischemic injury after stroke. The present study tests whether the Shh pathway mediates resveratrol to decrease cerebral ischemic injury and improve neurological function after stroke. We observed that resveratrol pretreatment significantly improved neurological function, decreased infarct volume, enhanced vitality, and reduced apoptosis of neurons in vivo and vitro after stroke. Meanwhile, expression levels of Shh, Ptc-1, Smo, and Gli-1 mRNAs were significantly upregulated and Gli-1 was relocated to the nucleus. Intriguingly, in vivo and in vitro inhibition of the Shh signaling pathway with cyclopamine, a Smo inhibitor, completely reversed the above effects of resveratrol. These results suggest that decreased cerebral ischemic injury and improved neurological function by resveratrol may be mediated by the Shh signaling pathway.

  4. Neonatal acute kidney injury - Severity and recovery prediction and the role of serum and urinary biomarkers.

    PubMed

    Sweetman, Deirdre U

    2017-02-01

    Neonatal acute kidney injury is common, in part due to incomplete renal maturation and also due to frequent exposure to risk factors for acute kidney injury such as perinatal asphyxia, extracorporeal-membrane-oxygenation, cardiac surgery, sepsis, prematurity and nephrotoxicity. However the current method by which acute kidney injury is diagnosed is sub-optimal and not universally accepted which impairs the accurate estimation of the true incidence of neonatal acute kidney injury. Serum Cystatin-C, urinary NGAL, KIM-1 and IL-18 are promising neonatal acute kidney injury biomarkers however the diagnosis of acute kidney injury remains serum creatinine/urine output-based in many studies. Emerging biomarkers which require further study in the neonatal population include netrin-1 and EGF. Increased awareness amongst clinicians of nephrotoxic medications being a modifiable risk factor for the development of neonatal acute kidney injury is imperative. The burden of chronic kidney failure following neonatal acute kidney injury is unclear and requires further study.

  5. Severe but reversible acute kidney injury resulting from Amanita punctata poisoning

    PubMed Central

    Kang, Eunjung; Cheong, Ka-Young; Lee, Min-Jeong; Kim, Seirhan; Shin, Gyu-Tae; Kim, Heungsoo; Park, In-Whee

    2015-01-01

    Mushroom-related poisoning can cause acute kidney injury. Here we report a case of acute kidney injury after ingestion of Amanita punctata, which is considered an edible mushroom. Gastrointestinal symptoms occurred within 24 hours from the mushroom intake and were followed by an asymptomatic period, acute kidney injury, and elevation of liver and pancreatic enzymes. Kidney function recovered with supportive care. Nephrotoxic mushroom poisoning should be considered as a cause of acute kidney injury. PMID:26779427

  6. Socially constructed ‘value’ and vocational experiences following neurological injury

    PubMed Central

    Fadyl, Joanna K.; Payne, Deborah

    2016-01-01

    Abstract Purpose: Paid work is seen as a key outcome in rehabilitation. However, research demonstrates that because of normative expectations in the job market and workplace, experiences of disability can be intensified in a work context. We sought to explore this issue in more depth by analysing the effects of societal constructions of worker ‘value’ within individual case studies of people with acquired neurological injury. Method: Instrumental case study of four heterogeneous participants, employing a discourse analysis approach. Results: Participants described a perpetuation of discourses in which a disabled body or mind itself is seen to qualify, disqualify or limit a person’s value in employment. Nevertheless, interviews also highlighted discourses that constructed other worker identities: based on pre-injury identities, life experiences and other aspects of self. The contrasts between individuals illustrated how worker identities, when situated within broader societal discourses of worker ‘value’, can either constrain or expand the vocational opportunities available to individuals who experience disability. However, current and historical interactions about worker ‘value’ shaped the identities genuinely available to each individual. Conclusion: Understanding how societal discourses enable and constrain worker identities may be vital to (a) facilitating valid opportunities and (b) navigating situations that could unintentionally hinder vocational possibilities. Implications for RehabilitationThis study shows how worker identities, situated within societal discourses of worker ‘value’, can constrain or broaden vocational opportunities available to individuals who experience disability.Barriers to gaining, maintaining and developing in employment could be re-envisaged in terms of what is limiting a person’s ability to embody an enabling identity.A knowledge of both societal discourses and individuals’ interactions with them may be vital to

  7. Intrathecal Transplantation of Autologous Adherent Bone Marrow Cells Induces Functional Neurological Recovery in a Canine Model of Spinal Cord Injury.

    PubMed

    Gabr, Hala; El-Kheir, Wael Abo; Farghali, Haithem A M A; Ismail, Zeinab M K; Zickri, Maha B; El Maadawi, Zeinab M; Kishk, Nirmeen A; Sabaawy, Hatem E

    2015-01-01

    Spinal cord injury (SCI) results in demyelination of surviving axons, loss of oligodendrocytes, and impairment of motor and sensory functions. We have developed a clinical strategy of cell therapy for SCI through the use of autologous bone marrow cells for transplantation to augment remyelination and enhance neurological repair. In a preclinical large mammalian model of SCI, experimental dogs were subjected to a clipping contusion of the spinal cord. Two weeks after the injury, GFP-labeled autologous minimally manipulated adherent bone marrow cells (ABMCs) were transplanted intrathecally to investigate the safety and efficacy of autologous ABMC therapy. The effects of ABMC transplantation in dogs with SCI were determined using functional neurological scoring, and the integration of ABMCs into the injured cords was determined using histopathological and immunohistochemical investigations and electron microscopic analyses of sections from control and transplanted spinal cords. Our data demonstrate the presence of GFP-labeled cells in the injured spinal cord for up to 16 weeks after transplantation in the subacute SCI stage. GFP-labeled cells homed to the site of injury and were detected around white matter tracts and surviving axons. ABMC therapy in the canine SCI model enhanced remyelination and augmented neural regeneration, resulting in improved neurological functions. Therefore, autologous ABMC therapy appears to be a safe and promising therapy for spinal cord injuries.

  8. Accelerated recovery from acute brain injuries: clinical efficacy of neurotrophic treatment in stroke and traumatic brain injuries.

    PubMed

    Bornstein, N; Poon, W S

    2012-04-01

    Stroke is one of the most devastating vascular diseases in the world as it is responsible for almost five million deaths per year. Almost 90% of all strokes are ischemic and mainly due to atherosclerosis, cardiac embolism and small-vessel disease. Intracerebral or subarachnoid hemorrhage can lead to hemorrhagic stroke, which usually has the poorest prognosis. Cerebrolysin is a peptide preparation which mimics the action of a neurotrophic factor, protecting stroke-injured neurons and promoting neuroplasticity and neurogenesis. Cerebrolysin has been widely studied as a therapeutic tool for both ischemic and hemorrhagic stroke, as well as traumatic brain injury. In ischemic stroke, Cerebrolysin given as an adjuvant therapy to antiplatelet and rheologically active medication resulted in accelerated improvement in global, neurological and motor functions, cognitive performance and activities of daily living. Cerebrolysin was also safe and well tolerated when administered in patients suffering from hemorrhagic stroke. Traumatic brain injury leads to transient or chronic impairments in physical, cognitive, emotional and behavioral functions. This is associated with deficits in the recognition of basic emotions, the capacity to interpret the mental states of others, and executive functioning. Pilot clinical studies with adjuvant Cerebrolysin in the acute and postacute phases of the injury have shown faster recovery, which translates into an earlier onset of rehabilitation and shortened hospitalization time.

  9. CD47 deficiency improves neurological outcomes of traumatic brain injury in mice.

    PubMed

    Zhao, Song; Yu, Zhanyang; Liu, Yu; Bai, Yang; Jiang, Yinghua; van Leyen, Klaus; Yang, Yong-Guang; Lok, Josephine M; Whalen, Michael J; Lo, Eng H; Wang, Xiaoying

    2017-03-16

    CD47 is a receptor for signal-regulatory protein alpha (SIRPα) in self-recognition by the innate immune system, and a receptor of thrombospondin-1 (TSP-1) contributing to vascular impairment in response to stress. However, the roles of CD47 in traumatic brain injury (TBI) have not been investigated. In this study we aimed to test our hypothesis that CD47 mediates early neutrophil brain infiltration and late brain vascular remodeling after TBI. Mice were subjected to TBI using a controlled cortical impact (CCI) device. We examined early phase neutrophil infiltration, and late phase brain vessel density, pro-angiogenic markers VEGF and Ang-1 protein expression, neurological function deficits and lesion volumes for up to three weeks after TBI. Our results show that mice deficient in CD47 (CD47 Knockout) had significantly less brain neutrophil infiltration at 24h, upregulated VEGF expression in peri-lesion cortex at 7 and 14days, and increased blood vessel density at 21days after TBI, compared to wild type (WT) mice. CD47 knockout also significantly decreased sensorimotor function deficits and reduced brain lesion volume at 21days after TBI. We conclude that CD47 may play pathological roles in brain neutrophil infiltration, progression of brain tissue damage, impairment of cerebrovascular remodeling and functional recovery after TBI.

  10. L-arginine attenuates acute lung injury after smoke inhalation and burn injury in sheep.

    PubMed

    Murakami, Kazunori; Enkhbaatar, Perenlei; Yu, Yong-Ming; Traber, Lillian D; Cox, Robert A; Hawkins, Hal K; Tompkins, Ronald G; Herndon, David; Traber, Daniel L

    2007-10-01

    Thermal injury results in reduced plasma levels of arginine (Arg). With reduced Arg availability, NOS produces superoxide instead of NO. We hypothesized that Arg supplementation after burn and smoke inhalation (B + S) injury would attenuate the acute insult to the lungs and, thus, protect pulmonary function. Seventeen Suffolk ewes (n = 17) were randomly divided into three groups: (1) sham injury group (n = 6), (2) B + S injury plus saline treatment (n = 6), and (3) B + S injury plus L-ARG infusion at 57 mg.kg(-1).h(-1) (n = 5). Burn and smoke inhalation injury was induced by standardized procedures, including a 40% area full thickness flame burn combined with 48 breaths of smoke from burning cottons. All animals were immediately resuscitated by Ringer solution and supported by mechanical ventilation for 48 h, during which various variables of pulmonary function were monitored. The results demonstrated that Arg treatment attenuated the decline of plasma Arg concentration after B + S injury. A higher plasma Arg concentration was associated with a less decline in Pao2/Fio2 ratio and a reduced extent of airway obstruction after B + S injury. Histopathological examinations also indicated a remarkably reduced histopathological scores associated with B + S injury. Nitrotyrosine stain in lung tissue was positive after B + S injury, but was significantly reduced in the group with Arg. Therefore, L-Arg supplementation improved gas exchange and pulmonary function in ovine after B + S injury via its, at least in part, effect on reduction of oxidative stress through the peroxynitrite pathway.

  11. Acute kidney injury secondary to exposure to insecticides used for bedbug (Cimex lectularis) control.

    PubMed

    Bashir, Babar; Sharma, Shree G; Stein, Harold D; Sirota, Robert A; D'Agati, Vivette D

    2013-11-01

    Bedbug (Cimex lectularis) infestation is becoming a worldwide epidemic due to the emergence of insecticide-resistant strains. Pyrethroids are approved by the US Environmental Protection Agency for use against bedbugs and are considered minimally toxic to humans, with known respiratory, neurologic, and gastrointestinal effects. We present the first reported case of pyrethroid-induced toxic acute tubular necrosis (ATN). A 66-year-old healthy woman receiving no prior nephrotoxic medications presented with extreme weakness, decreased urine output, and acute kidney injury. She had administered multiple applications of a bedbug spray (permethrin) and a fogger (pyrethrin), exceeding the manufacturer's recommended amounts. She was found to have severe nonoliguric acute kidney injury associated with profound hypokalemia. Kidney biopsy revealed toxic ATN with extensive tubular degenerative changes and cytoplasmic vacuolization. With conservative management, serum creatinine level decreased from 13.0 mg/dL (estimated glomerular filtration rate, 3 mL/min/1.73 m(2)) to 1.67 mg/dL (estimated glomerular filtration rate, 37 mL/min/1.73 m(2)) within 6 weeks. Literature review uncovered no prior report of pyrethroid insecticide-induced ATN in humans, although there are reports of ATN with similar tubular vacuolization in rats exposed to this agent. Bedbug insecticides containing pyrethroids should be used with caution due to the potential development of toxic ATN after prolonged exposure.

  12. Growth and development alter susceptibility to acute renal injury.

    PubMed

    Zager, Richard A; Johnson, Ali C M; Naito, Masayo; Lund, Steve R; Kim, Nayeon; Bomsztyk, Karol

    2008-09-01

    Many of the studies of acute renal injury have been conducted in young mice usually during their rapid growth phase; yet, the impact of age or growth stage on the degree of injury is unknown. To address this issue, we studied three forms of injury (endotoxemic-, glycerol-, and maleate-induced) in mice ranging in age from adolescence (3 weeks) to maturity (16 weeks). The severity of injury within each model significantly correlated with weight and age. We also noticed a progressive age-dependent reduction in renal cholesterol content, a potential injury modifier. As the animals grew and aged they also exhibited stepwise decrements in the mRNAs of HMG CoA reductase and the low density lipoprotein receptor, two key cholesterol homeostatic genes. This was paralleled by decreased amounts of RNA polymerase II and the transcription factor SREBP1/2 at the reductase and lipoprotein receptor gene loci as measured by chromatin immunoprecipitation. Our study shows that the early phase of mouse growth can profoundly alter renal susceptibility to diverse forms of experimental acute renal injury.

  13. Body temperature control in sepsis-induced acute lung injury.

    PubMed

    Wang, Giueng-Chueng; Chi, Wei-Ming; Perng, Wan-Cherng; Huang, Kun-Lun

    2003-12-31

    Body temperature is precisely regulated to maintain homeostasis in homeothermic animals. Although it remains unproved whether change of body temperature constitutes a beneficial or a detrimental component of the septic response, temperature control should be an important entity in septic experiments. We investigated the effect of body temperature control on the lipopolysaccharide (LPS)-induced lung injury. Acute lung injury in rats was induced by intratracheal spray of LPS and body temperature was either clamped at 37 degrees C for 5 hours or not controlled. The severity of lung injury was evaluated at the end of the experiment. Intratracheal administration of aerosolized LPS caused a persistent decline in body temperature and a significant lung injury as indicated by an elevation of protein-concentration and LDH activity in the bronchoalveolar lavage (BAL) fluid and wet/dry weight (W/D) ratio of lungs. Administration of LPS also caused neutrophil sequestration and lipid peroxidation in the lung tissue as indicated by increase in myeloperoxidase (MPO) activity and malondialdehyde (MDA) production, respectively. Control of body temperature at 37 degrees C after LPS (LPS/BT37, n = 11) significantly reduced acute lung injury as evidenced by decreases in BAL fluid protein concentration (983 +/- 189 vs. 1403 +/- 155 mg/L) and LDH activity (56 +/- 10 vs. 123 +/- 17 deltamAbs/min) compared with the LPS group (n = 11). Although the W/D ratio of lung and MDA level were lower in the rats received temperature control compared with those received LPS only, the differences were not statistically significant. Our results demonstrated that intratracheal administration of aerosolized LPS induced a hypothermic response and acute lung injury in rats and controlling body temperature at a normal range may alleviate the LPS-induced lung injury.

  14. Progesterone alleviates acute brain injury via reducing apoptosis and oxidative stress in a rat experimental subarachnoid hemorrhage model.

    PubMed

    Cai, Jing; Cao, Shenglong; Chen, Jingyin; Yan, Feng; Chen, Gao; Dai, Yuying

    2015-07-23

    This study aimed to investigate the therapeutic effect of progesterone on acute brain injury after subarachnoid hemorrhage (SAH). Subarachnoid hemorrhage was induced in male Sprague-Dawley rats (n=72) by endovascular perforation. Progesterone (8 mg/kg or 16 mg/kg) was administered to rats at 1, 6, and 12h after SAH. Mortality, neurologic deficits, cell apoptosis, expression of apoptotic markers, the level of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were assayed at 24h after experimental SAH. Mortality, cell apoptosis and the expression of caspase-3 were decreased, and improved neurological function was observed in the progesterone-treated SAH rats. Further, exploration demonstrated that progesterone significantly reduced the ratio of Bax/Bcl-2 and attenuated the release of cytochrome c from mitochondria. Progesterone also induced anti-oxidative effects by elevating the activity of SOD and decreasing MDA content after SAH. Furthermore, dose-response relationships for progesterone treatment were observed, and high doses of progesterone enhanced the neuroprotective effects. Progesterone treatment could alleviate acute brain injury after SAH by inhibiting cell apoptosis and decreasing damage due to oxidative stress. The mechanism involved in the anti-apoptotic effect was related to the mitochondrial pathway. These results indicate that progesterone possesses the potential to be a novel therapeutic agent for the treatment of acute brain injury after SAH.

  15. Understanding acute ankle ligamentous sprain injury in sports.

    PubMed

    Fong, Daniel Tp; Chan, Yue-Yan; Mok, Kam-Ming; Yung, Patrick Sh; Chan, Kai-Ming

    2009-07-30

    This paper summarizes the current understanding on acute ankle sprain injury, which is the most common acute sport trauma, accounting for about 14% of all sport-related injuries. Among, 80% are ligamentous sprains caused by explosive inversion or supination. The injury motion often happens at the subtalar joint and tears the anterior talofibular ligament (ATFL) which possesses the lowest ultimate load among the lateral ligaments at the ankle. For extrinsic risk factors to ankle sprain injury, prescribing orthosis decreases the risk while increased exercise intensity in soccer raises the risk. For intrinsic factors, a foot size with increased width, an increased ankle eversion to inversion strength, plantarflexion strength and ratio between dorsiflexion and plantarflexion strength, and limb dominance could increase the ankle sprain injury risk. Players with a previous sprain history, players wearing shoes with air cells, players who do not stretch before exercising, players with inferior single leg balance, and overweight players are 4.9, 4.3, 2.6, 2.4 and 3.9 times more likely to sustain an ankle sprain injury. The aetiology of most ankle sprain injuries is incorrect foot positioning at landing - a medially-deviated vertical ground reaction force causes an explosive supination or inversion moment at the subtalar joint in a short time (about 50 ms). Another aetiology is the delayed reaction time of the peroneal muscles at the lateral aspect of the ankle (60-90 ms). The failure supination or inversion torque is about 41-45 Nm to cause ligamentous rupture in simulated spraining tests on cadaver. A previous case report revealed that the ankle joint reached 48 degrees inversion and 10 degrees internal rotation during an accidental grade I ankle ligamentous sprain injury during a dynamic cutting trial in laboratory. Diagnosis techniques and grading systems vary, but the management of ankle ligamentous sprain injury is mainly conservative. Immobilization should not be

  16. Understanding acute ankle ligamentous sprain injury in sports

    PubMed Central

    Fong, Daniel TP; Chan, Yue-Yan; Mok, Kam-Ming; Yung, Patrick SH; Chan, Kai-Ming

    2009-01-01

    This paper summarizes the current understanding on acute ankle sprain injury, which is the most common acute sport trauma, accounting for about 14% of all sport-related injuries. Among, 80% are ligamentous sprains caused by explosive inversion or supination. The injury motion often happens at the subtalar joint and tears the anterior talofibular ligament (ATFL) which possesses the lowest ultimate load among the lateral ligaments at the ankle. For extrinsic risk factors to ankle sprain injury, prescribing orthosis decreases the risk while increased exercise intensity in soccer raises the risk. For intrinsic factors, a foot size with increased width, an increased ankle eversion to inversion strength, plantarflexion strength and ratio between dorsiflexion and plantarflexion strength, and limb dominance could increase the ankle sprain injury risk. Players with a previous sprain history, players wearing shoes with air cells, players who do not stretch before exercising, players with inferior single leg balance, and overweight players are 4.9, 4.3, 2.6, 2.4 and 3.9 times more likely to sustain an ankle sprain injury. The aetiology of most ankle sprain injuries is incorrect foot positioning at landing – a medially-deviated vertical ground reaction force causes an explosive supination or inversion moment at the subtalar joint in a short time (about 50 ms). Another aetiology is the delayed reaction time of the peroneal muscles at the lateral aspect of the ankle (60–90 ms). The failure supination or inversion torque is about 41–45 Nm to cause ligamentous rupture in simulated spraining tests on cadaver. A previous case report revealed that the ankle joint reached 48 degrees inversion and 10 degrees internal rotation during an accidental grade I ankle ligamentous sprain injury during a dynamic cutting trial in laboratory. Diagnosis techniques and grading systems vary, but the management of ankle ligamentous sprain injury is mainly conservative. Immobilization should not

  17. [Evidence for treatment of acute syndesmosis injuries in sports].

    PubMed

    Best, R; Mauch, F; Bauer, G

    2013-06-01

    Injuries of the distal syndesmosis often accompany acute ankle sprains especially in professional team sports. While small partial syndesmosis lesions can often be missed as a consequence of impressive symptoms due to ventrolateral capsuloligamentous injuries, higher grade injuries of the syndesmosis can mostly be diagnosed without any problem. Furthermore, there is a consensus concerning the necessity of operative treatment in significantly unstable situations as well concerning conservative treatment of incomplete partial lesions. Consequently, the greatest challenge regarding diagnostic tools, quantification and optimal therapy arises in the most common form of sport-associated, complete or partial lesions of the distal syndesmosis. This review article summarizes sports-associated injuries of the distal tibiofibular syndesmosis considering the current literature and placing the emphasis on the anatomy, pathobiomechanics, diagnostics and therapy of syndesmosis lesions from an evidence-based viewpoint.

  18. Anti-oxidative aspect of inhaled anesthetic gases against acute brain injury

    PubMed Central

    Yang, Tuo; Sun, Yang; Zhang, Feng

    2016-01-01

    Acute brain injury is a critical and emergent condition in clinical settings, which needs to be addressed urgently. Commonly acute brain injuries include traumatic brain injury, ischemic and hemorrhagic strokes. Oxidative stress is a key contributor to the subsequent injuries and impedes the reparative process after acute brain injury; therefore, facilitating an anti-oxidative approach is important in the care of those diseases. Readiness to deliver and permeability to blood brain barrier are essential for the use of this purpose. Inhaled anesthetic gases are a group of such agents. In this article, we discuss the anti-oxidative roles of anesthetic gases against acute brain injury. PMID:28217295

  19. Acute ethanol intake attenuates inflammatory cytokines after brain injury in rats: a possible role for corticosterone.

    PubMed

    Gottesfeld, Zehava; Moore, Anthony N; Dash, Pramod K

    2002-03-01

    It has been reported that acute ethanol intoxication exerts dose-dependent effects, both beneficial and detrimental, on the outcome of traumatic brain injury (TBI), although the mechanism(s) has not been determined. Given that pro-inflammatory cytokines are either neuroprotective or neurotoxic, depending on their tissue levels, ethanol-induced alterations in brain cytokine production may be involved in determining the recovery after TBI. The present study was undertaken to examine the effect of acute ethanol pretreatments (producing blood alcohol concentrations of 100+/-16 mg/dL, and 220+/-10 mg/dL, considered low and intoxicating doses, respectively) on interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) levels in discrete brain regions. In addition, serum corticosterone levels were also examined because the hormone is a modulator of cytokine production, its secretion is stimulated by ethanol, and it has been associated with the severity of post-injury neurologic dysfunction. The data presented in this report demonstrate that moderate cortical impact brain injury elicits a marked increase in IL-1beta and TNF-alpha in the injured cortex as well as in the hippocampus ipsilateral to the injury. Ethanol pretreatment lowered cytokine levels in the cortex, hippocampus and hypothalamus in a dose-dependent manner after TBI compared to the untreated injured rats. Serum corticosterone levels were markedly increased in the injured rats, and were further augmented in the ethanol-pretreated injured animals in a dose-dependent manner. Our findings suggest that ethanol-induced decrease in pro-inflammatory cytokine production may be linked to increased circulating corticosterone, both of which may contribute to the outcome of brain injury.

  20. Acute Phase Proteins in Cerebrospinal Fluid from Dogs with Naturally-Occurring Spinal Cord Injury

    PubMed Central

    Anderson, Kimberly M.; Welsh, C. Jane; Young, Colin; Levine, Gwendolyn J.; Kerwin, Sharon C.; Boudreau, C. Elizabeth; Reyes, Ismael; Mondragon, Armando; Griffin, John F.; Cohen, Noah D.

    2015-01-01

    Abstract Spinal cord injury (SCI) affects thousands of people each year and there are no treatments that dramatically improve clinical outcome. Canine intervertebral disc herniation is a naturally-occurring SCI that has similarities to human injury and can be used as a translational model for evaluating therapeutic interventions. Here, we characterized cerebrospinal fluid (CSF) acute phase proteins (APPs) that have altered expression across a spectrum of neurological disorders, using this canine model system. The concentrations of C-reactive protein (CRP), haptoglobin (Hp), alpha-1-glycoprotein, and serum amyloid A were determined in the CSF of 42 acutely injured dogs, compared with 21 healthy control dogs. Concentrations of APPs also were examined with respect to initial injury severity and motor outcome 42 d post-injury. Hp concentration was significantly higher (p<0.0001) in the CSF of affected dogs, compared with healthy control dogs. Additionally, the concentrations of CRP and Hp were significantly (p=0.0001 and p=0.0079, respectively) and positively associated with CSF total protein concentration. The concentrations of CRP and Hp were significantly higher (p=0.0071 and p=0.0197, respectively) in dogs with severe injury, compared with those with mild-to-moderate SCI, but there was no significant correlation between assessed CSF APP concentrations and 42 d motor outcome. This study demonstrated that CSF APPs were dysregulated in dogs with naturally-occurring SCI and could be used as markers for SCI severity. As Hp was increased following severe SCI and is neuroprotective across a number of model systems, it may represent a viable therapeutic target. PMID:26186466

  1. A simple rat model of mild traumatic brain injury: a device to reproduce anatomical and neurological changes of mild traumatic brain injury

    PubMed Central

    Kim, Ho Jeong

    2017-01-01

    Mild traumatic brain injury typically involves temporary impairment of neurological function. Previous studies used water pressure or rotational injury for designing the device to make a rat a mild traumatic brain injury model. The objective of this study was to make a simple model of causing mild traumatic brain injury in rats. The device consisted of a free-fall impactor that was targeted onto the rat skull. The weight (175 g) was freely dropped 30 cm to rat’s skull bregma. We installed a safety device made of acrylic panel. To confirm a mild traumatic brain injury in 36 Sprague-Dawley rats, we performed magnetic resonance imaging (MRI) of the brain within 24 h after injury. We evaluated behavior and chemical changes in rats before and after mild traumatic brain injury. The brain MRI did not show high or low signal intensity in 34 rats. The mobility on grid floor was decreased after mild traumatic brain injury. The absolute number of foot-fault and foot-fault ratio were decreased after mild traumatic brain injury. However, the difference of the ratio was a less than absolute number of foot-fault. These results show that the device is capable of reproducing mild traumatic brain injury in rats. Our device can reduce the potential to cause brain hemorrhage and reflect the mechanism of real mild traumatic brain injury compared with existing methods and behaviors. This model can be useful in exploring physiology and management of mild traumatic brain injury. PMID:28070456

  2. Early Acute Kidney Injury in Military Casualties

    DTIC Science & Technology

    2015-05-01

    J. A.; Kwan, H. K.; Glass, K. R.; Morrow, B . D.; Latack, W.; Henderson, A. T.; Saenz, K. K.; Siew, E. D.; Ikizler, T. A.; Chung, K. K.; 5d. PROJECT...19a. NAME OF RESPONSIBLE PERSON a. REPORT unclassified b . ABSTRACT unclassified c. THIS PAGE unclassified Standard Form 298 (Rev. 8-98...among trauma patients. Ann Surg. 2010;252:158Y165. 12. Skinner DL, Hardcastle TC, Rodseth RN, Muckart DJ. The incidence and outcomes of acute kidney

  3. Hypothyroidism causing paralytic ileus and acute kidney injury - case report

    PubMed Central

    2011-01-01

    We present a patient with severe hypothyroidism complicated by paralytic ileus and acute kidney injury. A 65 year old male patient, diagnosed with hypothyroidism one year ago was transferred to our unit in a state of drowsiness and confusion. He was severely hypothyroid and had paralytic ileus and impaired renal function at the time of transfer. Hypokalaemia was present, and was likely to have contributed to the paralytic ileus and this together with dehydration was likely to have contributed to renal injury. Nonetheless, hypothyroidism is very likely to have been the principal precipitant of both these complications, and both paralytic ileus and acute kidney injury improved with thyroxine replacement. Unfortunately, the patient died unexpectedly eight days after admission to the unit. Hypothyroidism may induce de novo acute kidney injury or it may exacerbate ongoing chronic kidney disease. This rare complication is assumed to be due to the hypodynamic circulatory state created by thyroid hormone deficiency. Paralytic ileus is an even rarer fatal manifestation of hypothyroidism and is thought to be due to an autonomic neuropathy affecting the intestines that is reversible with thyroxine replacement. To our knowledge, both these complications have not been observed in a single patient so far. It is important that clinicians are aware of these rare manifestations of hypothyroidism as in most occasions, thyroxine deficiency may be missed, and treatment can reverse the complications. PMID:21303532

  4. Hypothyroidism causing paralytic ileus and acute kidney injury - case report.

    PubMed

    Rodrigo, Chaturaka; Gamakaranage, Champika Sssk; Epa, Dhanesha S; Gnanathasan, Ariaranee; Rajapakse, Senaka

    2011-02-08

    We present a patient with severe hypothyroidism complicated by paralytic ileus and acute kidney injury. A 65 year old male patient, diagnosed with hypothyroidism one year ago was transferred to our unit in a state of drowsiness and confusion. He was severely hypothyroid and had paralytic ileus and impaired renal function at the time of transfer. Hypokalaemia was present, and was likely to have contributed to the paralytic ileus and this together with dehydration was likely to have contributed to renal injury. Nonetheless, hypothyroidism is very likely to have been the principal precipitant of both these complications, and both paralytic ileus and acute kidney injury improved with thyroxine replacement. Unfortunately, the patient died unexpectedly eight days after admission to the unit.Hypothyroidism may induce de novo acute kidney injury or it may exacerbate ongoing chronic kidney disease. This rare complication is assumed to be due to the hypodynamic circulatory state created by thyroid hormone deficiency. Paralytic ileus is an even rarer fatal manifestation of hypothyroidism and is thought to be due to an autonomic neuropathy affecting the intestines that is reversible with thyroxine replacement. To our knowledge, both these complications have not been observed in a single patient so far.It is important that clinicians are aware of these rare manifestations of hypothyroidism as in most occasions, thyroxine deficiency may be missed, and treatment can reverse the complications.

  5. Severe neurologic manifestations in acute intermittent porphyria developed after spine surgery under general anesthesia: a case report

    PubMed Central

    Park, Eun Young; Kim, Yi Seul; Lim, Kyung-Jee; Lee, Hye Kyoung; Lee, Soo Kyung; Choi, Hyun

    2014-01-01

    Porphyrias are inherited metabolic disorders resulting from a specific enzyme defect in the heme biosynthetic pathway. Porphyrias are induced by various precipitants. Clinical features include abdominal pain, neurologic manifestations, autonomic neuropathy, and mental disturbance. Diagnosis may be delayed because of variable symptoms that mimic other diseases and because of the rarity of of porphyrias. Although most patients with known porphyria can complete anesthesia and surgery safely, undiagnosed porphyric patients are in danger of porphyric crisis due to inadvertent exposure to precipitating drugs and environment. We report a case of a patient who experienced delayed emergence with neurological disturbance after general anesthesia, ultimately diagnosed as acute intermittent porphyria. PMID:25302100

  6. Neurologic Evaluation of Acute Lacrimomimetic Effect of Cyclosporine in an Experimental Rabbit Dry Eye Model

    PubMed Central

    Toshida, Hiroshi; Nguyen, Doan H.; Beuerman, Roger W.; Murakami, Akira

    2010-01-01

    PURPOSE To evaluate neurologically acute lacrimation caused by cyclosporine (CsA) eyedrops in rabbit. METHODS Normal adult male New Zealand White rabbits and those that underwent parasympathectomy each received a single instillation of 0.1% CsA or vehicle eyedrops. Schirmer tear test (STT) results, flow rate of lacrimal gland (LG) fluid from the excretory lacrimal duct of the main LG, and blink rate (over a 3-minute period) were measured before and after instillation of CsA or vehicle. Light microscopy was performed to examine the main LG in vitro. Protein release from LG fragments was assessed after incubation with CsA for 30 minutes. RESULTS In normal rabbits, the STT value and the flow rate of LG fluid were significantly increased after treatment with CsA compared with vehicle (P < 0.05). In contrast, no changes were found in denervated eyes. The blink rate of CsA-treated eyes was significantly higher than that of vehicle- treated eyes in normal rabbits (P < 0.005), whereas that of denervated eyes decreased significantly after CsA instillation compared with before administration (P < 0.005). Light microscopy showed that the cytoplasm of acinar cells was packed with secretory granules in denervated LG tissue 7 days after parasympathectomy. The same finding was observed 3 hours after CsA instillation. CsA had no stimulatory effect on protein release by acinar cells in LG fragments at all concentrations tested. CONCLUSIONS These results suggest that CsA has no direct effect on tear fluid secretion from the LG in an acute model. Instead, CsA increases reflex tear flow. PMID:19218606

  7. Neurorestorative targets of dietary long-chain omega-3 fatty acids in neurological injury

    PubMed Central

    Figueroa, Johnny D.; De Leon, Marino

    2014-01-01

    Long-chain omega-3 polyunsaturated fatty acids (LC-O3PUFAs) exhibit therapeutic potential for the treatment and prevention of the neurological deficits associated with spinal cord injury (SCI). However, the mechanisms implicated in these protective responses remain unclear. The objective of the present functional metabolomics study was to identify and define the dominant metabolic pathways targeted by dietary LC-O3PUFAs. Sprague-Dawley rats were fed rodent purified chows containing menhaden fish oil-derived LC-O3PUFAs for 8 weeks before being subjected to sham or spinal cord contusion surgeries. We show, through untargeted metabolomics, that dietary LC-O3PUFAs regulate important biochemical signatures associated with amino acid metabolism and free radical scavenging in both the injured and sham-operated spinal cord. Of particular significance, the spinal cord metabolome of animals fed with LC-O3PUFAs exhibited reduced glucose levels (−48%) and polar uncharged/hydrophobic amino acids (<−20%) while showing significant increases in the levels of antioxidant/anti-inflammatory amino acids and peptides metabolites, including β-alanine (+24%), carnosine (+33%), homocarnosine (+27%), kynurenine (+88%), when compared to animals receiving control diets (p < 0.05). Further, we found that dietary LC-O3PUFAs impacted the levels of neurotransmitters and the mitochondrial metabolism, as evidenced by significant increases in the levels of N-acetylglutamate (+43%) and acetyl-CoA levels (+27%), respectively. Interestingly, this dietary intervention resulted in a global correction of the pro-oxidant metabolic profile that characterized the SCI-mediated sensorimotor dysfunction. In summary, the significant benefits of metabolic homeostasis and increased antioxidant defenses unlock important neurorestorative pathways of dietary LC-O3PUFAs against SCI. PMID:24740740

  8. Molluscan Memory of Injury: Evolutionary Insights into Chronic Pain and Neurological Disorders

    PubMed Central

    Walters, Edgar T.; Moroz, Leonid L.

    2009-01-01

    Molluscan preparations have yielded seminal discoveries in neuroscience, but the experimental advantages of this group have not, until now, been complemented by adequate molecular or genomic information for comparisons to genetically defined model organisms in other phyla. The recent sequencing of the transcriptome and genome of Aplysia californica, however, will enable extensive comparative studies at the molecular level. Among other benefits, this will bring the power of individually identifiable and manipulable neurons to bear upon questions of cellular function for evolutionarily conserved genes associated with clinically important neural dysfunction. Because of the slower rate of gene evolution in this molluscan lineage, more homologs of genes associated with human disease are present in Aplysia than in leading model organisms from Arthropoda (Drosophila) or Nematoda (Caenorhabditis elegans). Research has hardly begun in molluscs on the cellular functions of gene products that in humans are associated with neurological diseases. On the other hand, much is known about molecular and cellular mechanisms of long-term neuronal plasticity. Persistent nociceptive sensitization of nociceptors in Aplysia displays many functional similarities to alterations in mammalian nociceptors associated with the clinical problem of chronic pain. Moreover, in Aplysia and mammals the same cell signaling pathways trigger persistent enhancement of excitability and synaptic transmission following noxious stimulation, and these highly conserved pathways are also used to induce memory traces in neural circuits of diverse species. This functional and molecular overlap in distantly related lineages and neuronal types supports the proposal that fundamental plasticity mechanisms important for memory, chronic pain, and other lasting alterations evolved from adaptive responses to peripheral injury in the earliest neurons. Molluscan preparations should become increasingly useful for comparative

  9. NMDA Receptor Antagonist Attenuates Bleomycin-Induced Acute Lung Injury

    PubMed Central

    Li, Yang; Liu, Yong; Peng, XiangPing; Liu, Wei; Zhao, FeiYan; Feng, DanDan; Han, JianZhong; Huang, YanHong; Luo, SiWei; Li, Lian; Yue, Shao Jie; Cheng, QingMei; Huang, XiaoTing; Luo, ZiQiang

    2015-01-01

    Background Glutamate is a major neurotransmitter in the central nervous system (CNS). Large amount of glutamate can overstimulate N-methyl-D-aspartate receptor (NMDAR), causing neuronal injury and death. Recently, NMDAR has been reported to be found in the lungs. The aim of this study is to examine the effects of memantine, a NMDAR channel blocker, on bleomycin-induced lung injury mice. Methods C57BL/6 mice were intratracheally injected with bleomycin (BLM) to induce lung injury. Mice were randomized to receive saline, memantine (Me), BLM, BLM plus Me. Lungs and BALF were harvested on day 3 or 7 for further evaluation. Results BLM caused leukocyte infiltration, pulmonary edema and increase in cytokines, and imposed significant oxidative stress (MDA as a marker) in lungs. Memantine significantly mitigated the oxidative stress, lung inflammatory response and acute lung injury caused by BLM. Moreover, activation of NMDAR enhances CD11b expression on neutrophils. Conclusions Memantine mitigates oxidative stress, lung inflammatory response and acute lung injury in BLM challenged mice. PMID:25942563

  10. Paeoniflorin ameliorates acute necrotizing pancreatitis and pancreatitis‑induced acute renal injury.

    PubMed

    Wang, Peng; Wang, Weixing; Shi, Qiao; Zhao, Liang; Mei, Fangchao; Li, Chen; Zuo, Teng; He, Xiaobo

    2016-08-01

    Acute renal injury caused by acute necrotizing pancreatitis (ANP) is a common complication that is associated with a high rate of mortality. Paeoniflorin is the active ingredient of paeonia radix and exhibits a number of pharmacological effects, such as anti‑inflammatory, anticancer, analgesic and immunomodulatory effects. The present study detected the potential treatment effects of paeoniflorin on acute renal injury induced by ANP in a rat model. The optimal dose of paeoniflorin for preventing acute renal injury induced by ANP was determined. Then, the possible protective mechanism of paeoniflorin was investigated. The serum levels of tumor necrosis factor (TNF)‑α, interleukin (IL)‑1β and IL‑6 were measured with enzyme‑linked immunosorbent assay kits. Renal inflammation and apoptosis were measured by immunohistochemistry and terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling assay. The expression of nitric oxide in kidney tissues was also evaluated. The p38 mitogen‑activated protein kinases (MAPKs) were measured by western blotting. The results shown that paeoniflorin may ameliorate acute renal injury following ANP in rats by inhibiting inflammatory responses and renal cell apoptosis. These effects may be associated with the p38MAPK and nuclear factor‑κB signal pathway.

  11. Acute disseminated encephalomyelitis with severe neurological outcomes following virosomal seasonal influenza vaccine.

    PubMed

    Alicino, Cristiano; Infante, Maria Teresa; Gandoglia, Ilaria; Miolo, Nadia; Mancardi, Gian Luigi; Zappettini, Simona; Capello, Elisabetta; Orsi, Andrea; Tamburini, Tiziano; Grandis, Marina

    2014-01-01

    Acute disseminated encephalomyelitis (ADEM) is an inflammatory, usually monophasic, immune mediate, demyelinating disease of the central nervous system which involves the white matter. ADEM is more frequent in children and usually occurs after viral infections, but may follow vaccinations, bacterial infections, or may occur without previous events. Only 5% of cases of ADEM are preceded by vaccination within one month prior to symptoms onset. The diagnosis of ADEM requires both multifocal involvement and encephalopathy and specific demyelinating lesions of white matter. Overall prognosis of ADEM patients is often favorable, with full recovery reported in 23% to 100% of patients from pediatric cohorts, and more severe outcome in adult patients. We describe the first case of ADEM occurred few days after administration of virosomal seasonal influenza vaccine. The patient, a 59-year-old caucasic man with unremarkable past medical history presented at admission decreased alertness, 10 days after flu vaccination. During the 2 days following hospitalization, his clinical conditions deteriorated with drowsiness and fever until coma. The magnetic resonance imaging of the brain showed multiple and symmetrical white matter lesions in both cerebellar and cerebral hemispheres, suggesting demyelinating disease with inflammatory activity, compatible with ADEM. The patient was treated with high dose of steroids and intravenous immunoglobulin with relevant sequelae and severe neurological outcomes.

  12. Acute Pharmacological DVT Prophylaxis after Spinal Cord Injury

    PubMed Central

    Thibault-Halman, Ginette; Casha, Steven

    2011-01-01

    Abstract A systematic review of the literature was performed to address pertinent clinical questions regarding deep vein thrombosis (DVT) prophylaxis in the setting of acute spinal cord injury (SCI). Deep vein thromboses are a common occurrence following SCI. Administration of low-molecular-weight heparin (LMWH) within 72 h of injury is recommended to minimize the occurrence of DVT. Furthermore, when surgical intervention is required, LMWH should be held the morning of surgery, and resumed within 24 h post-operatively. PMID:20795870

  13. The role of pharmacotherapy in modifying the neurological status of patients with spinal and spinal cord injuries.

    PubMed

    do Vale Ramos, Renato Carlos; Alegrete, Nuno

    2015-01-01

    The aim here was to conduct a review of the literature on pharmacological therapies for modifying the neurological status of patients with spinal cord injuries. The PubMed database was searched for articles with the terms "spinal cord injury AND methylprednisolone/GM1/apoptosis inhibitor/calpain inhibitor/naloxone/tempol/tirilazad", in Portuguese or in English, published over the last five years. Older studies were included because of their historical importance. The pharmacological groups were divided according to their capacity to interfere with the physiopathological mechanisms of secondary injuries. Use of methylprednisolone needs to be carefully weighed up: other anti-inflammatory agents have shown benefits in humans or in animals. GM1 does not seem to have greater efficacy than methylprednisolone, but longer-term studies are needed. Many inhibitors of apoptosis have shown benefits in in vitro studies or in animals. Naloxone has not shown benefits. Tempol inhibits the main consequences of oxidation at the level of the spinal cord and other antioxidant drugs seem to have an effect superior to that of methylprednisolone. There is an urgent need to find new treatments that improve the neurological status of patients with spinal cord injuries. The benefits from treatment with methylprednisolone have been questioned, with concerns regarding its safety. Other drugs have been studied, and some of these may provide promising alternatives. Additional studies are needed in order to reach conclusions regarding the benefits of these agents in clinical practice.

  14. The effect of increased T2 signal intensity in the spinal cord on the injury severity and early neurological recovery in patients with central cord syndrome.

    PubMed

    Schroeder, Gregory D; Hjelm, Nik; Vaccaro, Alexander R; Weinstein, Michael S; Kepler, Christopher K

    2016-05-01

    OBJECTIVE The aim of this paper was to compare the severity of the initial neurological injury as well as the early changes in the American Spinal Injury Association (ASIA) motor score (AMS) between central cord syndrome (CCS) patients with and without an increased T2 signal intensity in their spinal cord. METHODS Patients with CCS were identified and stratified based on the presence of increased T2 signal intensity in their spinal cord. The severity of the initial neurological injury and the progression of the neurological injury over the 1st week were measured according to the patient's AMS. The effect of age, sex, congenital stenosis, surgery within 24 hours, and surgery in the initial hospitalization on the change in AMS was determined using an analysis of variance. RESULTS Patients with increased signal intensity had a more severe initial neurological injury (AMS 57.6 vs 75.3, respectively, p = 0.01). However, the change in AMS over the 1st week was less severe in patients with an increase in T2 signal intensity (-0.85 vs -4.3, p = 0.07). Analysis of variance did not find that age, sex, Injury Severity Score, congenital stenosis, surgery within 24 hours, or surgery during the initial hospitalization affected the change in AMS. CONCLUSIONS The neurological injury is different between patients with and without an increased T2 signal intensity. Patients with an increased T2 signal intensity are likely to have a more severe initial neurological deficit but will have relatively minimal early neurological deterioration. Comparatively, patients without an increase in the T2 signal intensity will likely have a less severe initial injury but can expect to have a slight decline in neurological function in the 1st week.

  15. Osteoporosis Self-Assessment Tool for Asians Can Predict Neurologic Prognosis in Patients with Isolated Moderate Traumatic Brain Injury

    PubMed Central

    Chan, Hon-Man; Huang, Shiuh-Lin; Lin, Chih-Lung; Kwan, Aij-Lie; Lou, Yun-Ting; Chen, Chao-Wen

    2015-01-01

    Objectives Osteoporosis Self-Assessment Tool for Asians (OSTA) has been proved to be a simple and effective tool for recognizing osteoporosis risk. Our previous study has demonstrated that the preoperative OSTA index was a good prognostic predictor for stage II and III colon cancer patients after surgery. We aim to evaluate the value of OSTA index in prognostication of isolated traumatic brain injury with moderate severity (GCS 9-13). Methods We retrospectively reviewed all patients visiting Kaohsiung Medical University Hospital emergency department due to isolated moderate traumatic brain injury from Jan. 2010 to Dec. 2012. Background data (including the OSTA index), clinical presentations, management and outcomes (ICU admission days, total admission days, complications, Glasgow outcome score (GOS) at discharge, mortality) of the patients were recorded for further analysis. Our major outcome was good neurologic recovery defined as GOS of 5. Pearson chi-square test and the Mann-Whitney U test were used to compare demographic features. Multiple logistic regression was used to identify independent risk factors. Results 107 isolated moderate TBI patients were studied. 40 patients (37.4%) showed good recovery and 10 (9.3%) died at discharge. The univariate analysis revealed that younger age, higher OSTA index, lower ISS, lower AIS-H, and avoidance to neurosurgery were associated with better neurologic outcome for all moderate TBI patients. Multivariate analysis revealed that lower ISS, higher OSTA, and the avoidance of neurosurgery were independent risk factors predicting good neurologic recovery. Conclusion Higher ISS, lower OSTA index and exposure to neurosurgery were the independent risk factors for poorer recovery from isolated moderate TBI. In addition to labeling the cohort harboring osteoporotic risk, OSTA index could predict neurologic prognosis in patients with isolated moderate traumatic brain injury. PMID:26186582

  16. Acute kidney injury and ESRD management in austere environments.

    PubMed

    Raman, Gaurav; Perkins, Robert M; Jaar, Bernard G

    2012-05-01

    Current knowledge about managing acute kidney injury in disaster situations stems mostly from lessons learned while taking care of crush syndrome patients during major earthquakes. More recently, there has been a greater focus on emergency preparedness for ESRD management. Natural or man-made disasters create an "austere environment," wherein resources to administer standard of care are limited. Advance planning and timely coordinated intervention during disasters are paramount to administer effective therapies and save lives. This article reviews the presentation and management of disaster victims with acute kidney injury and those requiring renal replacement therapies. Major contributions of some key national and international organizations in the field of disaster nephrology are highlighted. The article intends to increase awareness about nephrology care of disaster victims, among nephrology and non-nephrology providers alike.

  17. Experimental Models of Transfusion-Related Acute Lung Injury (TRALI)

    PubMed Central

    Gilliss, Brian M.; Looney, Mark R.

    2010-01-01

    Transfusion-related acute lung injury (TRALI) is defined clinically as acute lung injury occurring within six hours of the transfusion of any blood product. It is the leading cause of transfusion-related death in the United States, but under-recognition and diagnostic uncertainty have limited clinical research to smaller case control studies. In this review we will discuss the contribution of experimental models to the understanding of TRALI pathophysiology and potential therapeutic approaches. Experimental models suggest that TRALI occurs when a host, with a primed immune system, is exposed to an activating agent such as anti-leukocyte antibody or a biologic response modifier such as lysophosphatidylcholines. Recent work has suggested a critical role for platelets in antibody-based experimental models and identified potential therapeutic strategies for TRALI. PMID:21134622

  18. [Current concept of TRALI (transfusion-related acute lung injury)].

    PubMed

    Iijima, Takehiko; Okazai, Hitoshi

    2007-11-01

    It is only 20 years since TRALI was clinically recognized. As it is gradually recognized among Japanese medical community, the number of cases reported is increasing gradually. In the past nine years (1997-2005), Japanese Red Cross confirmed 118 TRALI cases and 38 possible TRALI cases in Japan. Twelve TRALI cases among them occurred during or after anesthesia on the day of operation. Since acute lung injury is caused by multiple pathological factors, it is difficult to identify its main cause as transfusion. Therefore, TRALI has been underdiagnosed and underreported. Several mechanisms have been proposed. Although anti-HLA antibody, anti-HNA antibody, or other immunoreactive substances appear to be involved in developing TRALI, underlying conditions like systemic inflammation may be required for igniting TRALI Although TRALI developed in the operating theater seems to be a small fraction of whole TRALI cases, anesthesiologists should be aware of TRALI, and remember it as one of the causes of acute lung injury.

  19. Diagnostic Criteria for Acute Kidney Injury: Present and Future

    PubMed Central

    Kellum, John A.

    2015-01-01

    Synopsis Acute kidney injury in a clinical diagnosis guided by standard criteria based on changes in serum creatinine, urine output or both. Severity of acute kidney injury is determined by the magnitude of increase in serum creatinine or decrease in urine output. Patients manifesting both oliguria and azotemia and those in which these impairments are persistent are more likely to have worse disease and worse outcomes. Both short- and long-term outcomes are worse when patients have some stage of AKI by both criteria. Duration of AKI was also a significant predictor of long-term outcomes irrespective of severity. New biomarkers for AKI may substantially aid in the risk assessment and evaluation of patients at risk for AKI. PMID:26410133

  20. Suramin protects from cisplatin-induced acute kidney injury.

    PubMed

    Dupre, Tess V; Doll, Mark A; Shah, Parag P; Sharp, Cierra N; Kiefer, Alex; Scherzer, Michael T; Saurabh, Kumar; Saforo, Doug; Siow, Deanna; Casson, Lavona; Arteel, Gavin E; Jenson, Alfred Bennett; Megyesi, Judit; Schnellmann, Rick G; Beverly, Levi J; Siskind, Leah J

    2016-02-01

    Cisplatin, a commonly used cancer chemotherapeutic, has a dose-limiting side effect of nephrotoxicity. Approximately 30% of patients administered cisplatin suffer from kidney injury, and there are limited treatment options for the treatment of cisplatin-induced kidney injury. Suramin, which is Federal Drug Administration-approved for the treatment of trypanosomiasis, improves kidney function after various forms of kidney injury in rodent models. We hypothesized that suramin would attenuate cisplatin-induced kidney injury. Suramin treatment before cisplatin administration reduced cisplatin-induced decreases in kidney function and injury. Furthermore, suramin attenuated cisplatin-induced expression of inflammatory cytokines and chemokines, endoplasmic reticulum stress, and apoptosis in the kidney cortex. Treatment of mice with suramin 24 h after cisplatin also improved kidney function, suggesting that the mechanism of protection is not by inhibition of tubular cisplatin uptake or its metabolism to nephrotoxic species. If suramin is to be used in the context of cancer, then it cannot prevent cisplatin-induced cytotoxicity of cancer cells. Suramin did not alter the dose-response curve of cisplatin in lung adenocarcinoma cells in vitro. In addition, suramin pretreatment of mice harboring lung adenocarcinomas did not alter the initial cytotoxic effects of cisplatin (DNA damage and apoptosis) on tumor cells. These results provide evidence that suramin has potential as a renoprotective agent for the treatment/prevention of cisplatin-induced acute kidney injury and justify future long-term preclinical studies using cotreatment of suramin and cisplatin in mouse models of cancer.

  1. Acute kidney injury requiring haemodialysis following ingestion of mephedrone

    PubMed Central

    Rhidian, Rhys; Babu, Adarsh

    2013-01-01

    A 25-year-old man was found to have acute kidney injury (AKI) following ingestion of mephedrone. He presented to this local emergency department with worsening bilateral loin pain. He became oligoanuric, serum creatine peaked at 1214 µmol/l and he required several sessions of haemodialysis before kidney function began to improve. The mechanism of AKI and legal aspects of the use of mephedrone are discussed. PMID:23456157

  2. Transfusion related acute lung injury (TRALI): a review.

    PubMed

    Menitove, Jay E

    2007-01-01

    Transfusion Related Acute Lung Injury, or TRALI, denotes the most frequently reported fatal complication of blood transfusion. TRALI accounted for 34% of transfusion associated mortalities reported to the Food and Drug Administration (FDA) in 2005. TRALI caused more deaths than those attributed to hemolytic reactions following incorrect blood administration or sepsis resulting from bacterial contamination of platelet and red cell components. (Holness, Leslie. Food and Drug Administration. Personal Communication, 2006) This paper reviews TRALI for the clinical physician.

  3. Presumptive acute lung injury following multiple surgeries in a cat.

    PubMed

    Katayama, Masaaki; Okamura, Yasuhiko; Katayama, Rieko; Sasaki, Jun; Shimamura, Shunsuke; Uzuka, Yuji; Kamishina, Hiroaki; Nezu, Yoshinori

    2013-04-01

    A 12-year-old, 3.5-kg spayed female domestic shorthair cat had a tracheal mass identified as malignant B-cell lymphoma. The cat had tracheal resection and subsequently developed laryngeal paralysis. Due to multiple episodes of respiratory distress the cat subsequently had tracheal surgeries. Finally, the cat had a sudden onset of severe respiratory distress and collapsed. Computed tomography imaging and arterial blood gas analysis supported a diagnosis of acute lung injury.

  4. Acetaminophen-induced acute liver injury in HCV transgenic mice

    SciTech Connect

    Uehara, Takeki; Kosyk, Oksana; Jeannot, Emmanuelle; Bradford, Blair U.; Tech, Katherine; Macdonald, Jeffrey M.; Boorman, Gary A.; Chatterjee, Saurabh; Mason, Ronald P.; Melnyk, Stepan B.; Tryndyak, Volodymyr P.; Pogribny, Igor P.; Rusyn, Ivan

    2013-01-15

    The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wild type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24 h after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility. -- Highlights: ► Acetaminophen-induced liver injury is a significant clinical challenge. ► HCV-infected subjects may be at higher risk for acetaminophen-induced liver injury. ► We used HCV transgenics to test if liver injury due to acetaminophen is exacerbated.

  5. Biomarkers of increased diffusion anisotropy in semi-acute mild traumatic brain injury: a longitudinal perspective.

    PubMed

    Ling, Josef M; Peña, Amanda; Yeo, Ronald A; Merideth, Flannery L; Klimaj, Stefan; Gasparovic, Charles; Mayer, Andrew R

    2012-04-01

    Mild traumatic brain injury is the most prevalent neurological insult and frequently results in neurobehavioural sequelae. However, little is known about the pathophysiology underlying the injury and how these injuries change as a function of time. Although diffusion tensor imaging holds promise for in vivo characterization of white matter pathology, both the direction and magnitude of anisotropic water diffusion abnormalities in axonal tracts are actively debated. The current study therefore represents both an independent replication effort (n = 28) of our previous findings (n = 22) of increased fractional anisotropy during semi-acute injury, as well as a prospective study (n = 26) on the putative recovery of diffusion abnormalities. Moreover, new analytical strategies were applied to capture spatially heterogeneous white matter injuries, which minimize implicit assumptions of uniform injury across diverse clinical presentations. Results indicate that whereas a general pattern of high anisotropic diffusion/low radial diffusivity was present in various white matter tracts in both the replication and original cohorts, this pattern was only consistently observed in the genu of the corpus callosum across both samples. Evidence for a greater number of localized clusters with increased anisotropic diffusion was identified across both cohorts at trend levels, confirming heterogeneity in white matter injury. Pooled analyses (50 patients; 50 controls) suggested that measures of diffusion within the genu were predictive of patient classification, albeit at very modest levels (71% accuracy). Finally, we observed evidence of recovery in lesion load in returning patients across a 4-month interval, which was correlated with a reduction in self-reported post-concussive symptomatology. In summary, the corpus callosum may serve as a common point of injury in mild traumatic brain injury secondary to anatomical (high frequency of long unmyelinated fibres) and biomechanics factors. A

  6. Limiting the use of routine radiography for acute ankle injuries.

    PubMed Central

    Cockshott, W. P.; Jenkin, J. K.; Pui, M.

    1983-01-01

    In the diagnosis of ankle injuries routine radiography is often productive. An international survey of the average number of radiographs made of injured ankles suggested that two projections are adequate to detect fractures. This was confirmed in a prospective study of 242 patients coming to a hospital emergency department with recent ankle injuries. All the fractures could be identified on an anteroposterior or a lateral projection, although some were more obvious on an oblique view. As well, all the fractures were associated with malleolar soft-tissue swelling. Thus, radiography for acute ankle injuries could safely be restricted to patients with soft-tissue swelling, and fractures could be diagnosed using only two routine projections, though for management purposes additional projections might be needed. With a policy of limiting the use of radiography substantial cost reductions are possible. Images FIG. 1 PMID:6407744

  7. Autophagy in Acute Brain Injury: Feast, Famine, or Folly?

    PubMed Central

    Smith, Craig M.; Chen, Yaming; Sullivan, Mara L.; Kochanek, Patrick M.; Clark, Robert S. B.

    2010-01-01

    In the central nervous system, increased autophagy has now been reported after traumatic brain and spinal cord injury, cerebral ischemia, intracerebral hemorrhage, and seizures. This increase in autophagy could be physiologic, converting damaged or dysfunctional proteins, lipids and/or organelles to their amino acid and fatty acid components for recycling. On the other hand, this increase in autophagy could be supraphysiologic, perhaps consuming and eliminating functional proteins, lipids and/or organelles as well. Whether an increase in autophagy is beneficial (feast) or detrimental (famine) in brain likely depends on both the burden of intracellular substrate targeted for autophagy and the capacity of the cell’s autophagic machinery. Of course, increased autophagy observed after brain injury could also simply be an epiphenomenon (folly). These divergent possibilities have clear ramifications for designing therapeutic strategies targeting autophagy after acute brain injury, and are the subject of this review. PMID:20883784

  8. Intrafacility transportation of patients with acute brain injury.

    PubMed

    Tu, Hsinfen

    2014-06-01

    Patients with acute brain injury (ABI) frequently require diagnostic and therapeutic procedures in the areas located outside of the intensive care unit. Transports can be risky for critically ill patients with ABI. Secondary brain injury can occur during the transport from causes such as ischemia, hypotension, hypoxia, hypercapnia, and cerebral edema. Preparation and implementation of preventive procedures including pretransport assessment, monitoring during transport, and posttransport examination and documentation for transports of patients with ABI deem to be necessary. The purpose of this article is to review the typical risks associated with the transports of the patients with ABI out of the intensive care unit and to propose the strategies that can be used to minimize the risks of secondary brain injury.

  9. Hyperhomocysteinemia Exacerbates Cisplatin-induced Acute Kidney Injury

    PubMed Central

    Long, Yanjun; Zhen, Xin; Zhu, Fengxin; Hu, Zheng; Lei, Wenjing; Li, Shuang; Zha, Yan; Nie, Jing

    2017-01-01

    Hyperhomocysteinemia (HHcy) has been linked to several clinical manifestations including chronic kidney disease. However, it is not known whether HHcy has a role in the development of acute kidney injury (AKI). In the present study, we reported that HHcy mice developed more severe renal injury after cisplatin injection and ischemia-reperfusion injury shown as more severe renal tubular damage and higher serum creatinine. In response to cisplatin, HHcy mice showed more prevalent tubular cell apoptosis and decreased tubular cell proliferation. Mechanistically, a heightened ER stress and a reduced Akt activity were observed in kidney tissues of HHcy mice after cisplatin injection. Stimulating cultured NRK-52E cells with Hcy significantly increased the fraction of cells in G2/M phase and cell apoptosis together with decreased Akt kinase activity. Akt agonist IGF-1 rescued HHcy-induced cell cycle arrest and cell apoptosis. In conclusion, the present study provides evidence that HHcy increases the sensitivity and severity of AKI. PMID:28255274

  10. Targeted Lipid Profiling Discovers Plasma Biomarkers of Acute Brain Injury

    PubMed Central

    Sheth, Sunil A.; Iavarone, Anthony T.; Liebeskind, David S.; Won, Seok Joon; Swanson, Raymond A.

    2015-01-01

    Prior efforts to identify a blood biomarker of brain injury have relied almost exclusively on proteins; however their low levels at early time points and poor correlation with injury severity have been limiting. Lipids, on the other hand, are the most abundant molecules in the brain and readily cross the blood-brain barrier. We previously showed that certain sphingolipid (SL) species are highly specific to the brain. Here we examined the feasibility of using SLs as biomarkers for acute brain injury. A rat model of traumatic brain injury (TBI) and a mouse model of stroke were used to identify candidate SL species though our mass-spectrometry based lipid profiling approach. Plasma samples collected after TBI in the rat showed large increases in many circulating SLs following injury, and larger lesions produced proportionately larger increases. Plasma samples collected 24 hours after stroke in mice similarly revealed a large increase in many SLs. We constructed an SL score (sum of the two SL species showing the largest relative increases in the mouse stroke model) and then evaluated the diagnostic value of this score on a small sample of patients (n = 14) who presented with acute stroke symptoms. Patients with true stroke had significantly higher SL scores than patients found to have non-stroke causes of their symptoms. The SL score correlated with the volume of ischemic brain tissue. These results demonstrate the feasibility of using lipid biomarkers to diagnose brain injury. Future studies will be needed to further characterize the diagnostic utility of this approach and to transition to an assay method applicable to clinical settings. PMID:26076478

  11. Free fat interpositional graft in acute physeal injuries: the anticipatory Langenskiöld procedure.

    PubMed

    Foster, B K; John, B; Hasler, C

    2000-01-01

    Free fat graft interposition has been used extensively in management of physeal injuries with established growth disturbances. The use of this technique as part of the management of acute physeal injuries has not been reported. Here we report on its application in acute physeal injuries, where it has prevented the formation of an anticipated physeal arrest.

  12. Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury: a randomized controlled trial

    PubMed Central

    Xiao, Guomin; Wei, Jing; Yan, Weiqi; Wang, Weimin; Lu, Zhenhui

    2008-01-01

    Background Severe traumatic brain injury (TBI) has been increasing with greater incidence of injuries from traffic or sporting accidents. Although there are a number of animal models of TBI using progesterone for head injury, the effects of progesterone on neurologic outcome of acute TBI patients remain unclear. The aim of the present clinical study was to assess the longer-term efficacy of progesterone on the improvement in neurologic outcome of patients with acute severe TBI. Methods A total of 159 patients who arrived within 8 hours of injury with a Glasgow Coma Score ≤ 8 were enrolled in the study. A prospective, randomized, placebo-controlled trial of progesterone was conducted in the Neurotrauma Center of our teaching hospital. The patients were randomized to receive either progesterone or placebo. The primary endpoint was the Glasgow Outcome Scale score 3 months after brain injury. Secondary efficacy endpoints included the modified Functional Independence Measure score and mortality. In a follow-up protocol at 6 months, the Glasgow Outcome Scale and the modified Functional Independence Measure scores were again determined. Results Of the 159 patients randomized, 82 received progesterone and 77 received placebo. The demographic characteristics, the mechanism of injury, and the time of treatment were compared for the two groups. After 3 months and 6 months of treatment, the dichotomized Glasgow Outcome Scale score analysis exhibited more favorable outcomes among the patients who were given progesterone compared with the control individuals (P = 0.034 and P = 0.048, respectively). The modified Functional Independence Measure scores in the progesterone group were higher than those in the placebo group at both 3-month and 6-month follow-up (P < 0.05 and P < 0.01). The mortality rate of the progesterone group was significantly lower than that of the placebo group at 6-month follow-up (P < 0.05). The mean intracranial pressure values 72 hours and 7 days after

  13. Wiener filtering of surface EMG with a priori SNR estimation toward myoelectric control for neurological injury patients.

    PubMed

    Liu, Jie; Ying, Dongwen; Zhou, Ping

    2014-12-01

    Voluntary surface electromyogram (EMG) signals from neurological injury patients are often corrupted by involuntary background interference or spikes, imposing difficulties for myoelectric control. We present a novel framework to suppress involuntary background spikes during voluntary surface EMG recordings. The framework applies a Wiener filter to restore voluntary surface EMG signals based on tracking a priori signal to noise ratio (SNR) by using the decision-directed method. Semi-synthetic surface EMG signals contaminated by different levels of involuntary background spikes were constructed from a database of surface EMG recordings in a group of spinal cord injury subjects. After the processing, the onset detection of voluntary muscle activity was significantly improved against involuntary background spikes. The magnitude of voluntary surface EMG signals can also be reliably estimated for myoelectric control purpose. Compared with the previous sample entropy analysis for suppressing involuntary background spikes, the proposed framework is characterized by quick and simple implementation, making it more suitable for application in a myoelectric control system toward neurological injury rehabilitation.

  14. Neurologic Emergencies in the Elderly.

    PubMed

    Nentwich, Lauren M; Grimmnitz, Benjamin

    2016-08-01

    Neurologic diseases are a major cause of death and disability in elderly patients. Due to the physiologic changes and increased comorbidities that occur as people age, neurologic diseases are more common in geriatric patients and a major cause of death and disability in this population. This article discusses the elderly patient presenting to the emergency department with acute ischemic stroke, transient ischemic attack, intracerebral hemorrhage, subarachnoid hemorrhage, chronic subdural hematoma, traumatic brain injury, seizures, and central nervous system infections. This article reviews the subtle presentations, difficult workups, and complicated treatment decisions as they pertain to our older patients."

  15. Effects of estrogen on functional and neurological recovery after spinal cord injury: An experimental study with rats

    PubMed Central

    Letaif, Olavo Biraghi; Cristante, Alexandre Fogaça; de Barros Filho, Tarcísio Eloy Pessoa; Ferreira, Ricardo; dos Santos, Gustavo Bispo; da Rocha, Ivan Dias; Marcon, Raphael Martus

    2015-01-01

    OBJECTIVES: To evaluate the functional and histological effects of estrogen as a neuroprotective agent after a standard experimentally induced spinal cord lesion. METHODS: In this experimental study, 20 male Wistar rats were divided into two groups: one group with rats undergoing spinal cord injury (SCI) at T10 and receiving estrogen therapy with 17-beta estradiol (4mg/kg) immediately following the injury and after the placement of skin sutures and a control group with rats only subjected to SCI. A moderate standard experimentally induced SCI was produced using a computerized device that dropped a weight on the rat's spine from a height of 12.5 mm. Functional recovery was verified with the Basso, Beattie and Bresnahan scale on the 2nd, 7th, 14th, 21st, 28th, 35th and 42nd days after injury and by quantifying the motor-evoked potential on the 42nd day after injury. Histopathological evaluation of the SCI area was performed after euthanasia on the 42nd day. RESULTS: The experimental group showed a significantly greater functional improvement from the 28th to the 42nd day of observation compared to the control group. The experimental group showed statistically significant improvements in the motor-evoked potential compared with the control group. The results of pathological histomorphometry evaluations showed a better neurological recovery in the experimental group, with respect to the proportion and diameter of the quantified nerve fibers. CONCLUSIONS: Estrogen administration provided benefits in neurological and functional motor recovery in rats with SCI beginning at the 28th day after injury. PMID:26598084

  16. Acute aseptic meningitis and diffuse myelitis as the presenting features of neurological Behcet disease.

    PubMed

    Mullins, G M; Elamin, M; Saidha, S; Ali, E; Jennings, L; Counihan, T J; Hennessy, M

    2009-12-01

    We report an explosive presentation of neurological Behcet disease, in an Irish male patient. We present the clinical and radiological findings in our patient and discuss a novel and effective therapeutic approach. We review other treatment modalities of patients with neurological involvement.

  17. Cell proliferation contributes to PNEC hyperplasia after acute airway injury.

    PubMed

    Stevens, T P; McBride, J T; Peake, J L; Pinkerton, K E; Stripp, B R

    1997-03-01

    Pulmonary neuroendocrine cells (PNECs) are airway epithelial cells that are capable of secreting a variety of neuropeptides. PNECs are scattered throughout the bronchial tree either as individual cells or clusters of cells termed neuroepithelial bodies (NEBs). PNECs and their secretory peptides have been considered to play a role in fetal lung development. Although the normal physiological function of PNECs and neuropeptides in normal adult lungs and in repair from lung injury is not known, PNEC hyperplasia has been associated with chronic lung diseases, such as bronchopulmonary dysplasia, and with chronic exposures, such as hypoxia, tobacco smoke, nitrosamines, and ozone. To evaluate changes in PNEC number and distribution after acute airway injury, FVB/n mice were treated with either naphthalene or vehicle. Naphthalene is an aromatic hydrocarbon that, at the dose used in this study, selectively destroys nonciliated bronchial epithelial cells (Clara cells) through cytochrome P-450-mediated metabolic activation into cytotoxic epoxides. PNECs were identified by immunohistochemical analysis of calcitonin gene-related peptide-like immunoreactivity (CGRP-IR). Proliferating cells were marked with [(3)H]thymidine incorporation. Acute naphthalene toxicity results in PNEC hyperplasia that is detectable after 5 days of recovery. PNEC hyperplasia is characterized by increased numbers of NEBs without significant changes in the number of isolated PNECs and by increased [(3)H]thymidine labeling of CGRP-IR cells. These data show that cell proliferation contributes to PNEC hyperplasia after acute airway injury and suggest that PNECs may be capable of more rapidly increasing their number in response to injury than previously recognized.

  18. Acute Neurological Illness in a Kidney Transplant Recipient Following Infection With Enterovirus-D68: An Emerging Infection?

    PubMed

    Wali, R K; Lee, A H; Kam, J C; Jonsson, J; Thatcher, A; Poretz, D; Ambardar, S; Piper, J; Lynch, C; Kulkarni, S; Cochran, J; Djurkovic, S

    2015-12-01

    We report the first case of enterovirus-D68 infection in an adult living-donor kidney transplant recipient who developed rapidly progressive bulbar weakness and acute flaccid limb paralysis following an upper respiratory infection. We present a 45-year-old gentleman who underwent pre-emptive living-donor kidney transplantation for IgA nephropathy. Eight weeks following transplantation, he developed an acute respiratory illness from enterovirus/rhinovirus that was detectable in nasopharyngeal (NP) swabs. Within 24 h of onset of respiratory symptoms, the patient developed binocular diplopia which rapidly progressed to multiple cranial nerve dysfunctions (acute bulbar syndrome) over the next 24 h. Within the next 48 h, asymmetric flaccid paralysis of the left arm and urinary retention developed. While his neurological symptoms were evolving, the Centers for Disease Control reported that the enterovirus strain from the NP swabs was, in fact, Enterovirus-D68 (EV-D68). Magnetic resonance imaging of the brain demonstrated unique gray matter and anterior horn cell changes in the midbrain and spinal cord, respectively. Constellation of these neurological symptoms and signs was suggestive for postinfectious encephalomyelitis (acute disseminated encephalomyelitis [ADEM]) from EV-D68. Treatment based on the principles of ADEM included intensive physical therapy and other supportive measures, which resulted in a steady albeit slow improvement in his left arm and bulbar weakness, while maintaining stable allograft function.

  19. Acute sports-related traumatic brain injury and repetitive concussion.

    PubMed

    Guskiewicz, Kevin M; Broglio, Steven P

    2015-01-01

    Concussions are described as functional, not structural injuries, and therefore cannot be easily detected through standard diagnostic imaging. The vast differences between individual athletes makes identifying and evaluating sport-related concussion one of the most complex and perplexing injuries faced by medical personnel. The literature, as well as most consensus statements, supports the use of a multifaceted approach to concussion evaluation on the sideline of the athletic field. Using a standardized clinical examination that is supported by objective measures of concussion-related symptoms, cognitive function, and balance provides clinicians with the ability to track recovery in an objective manner. When used in combination, these tests allow for more informed diagnosis and treatment plan, which should involve a graduated return to play progression. Establishing a comprehensive emergency action plan that can guide the on-field management of a more serious and potentially catastrophic brain injury is also essential. This review will address these management issues, as well as the recent concerns about the risk of long-term neurologic conditions believed to be associated with repetitive concussion.

  20. Biomarkers of acute kidney injury and associations with short- and long-term outcomes

    PubMed Central

    Schaub, Jennifer A.; Parikh, Chirag R.

    2016-01-01

    Acute kidney injury is strongly associated with increased mortality and other adverse outcomes. Medical researchers have intensively investigated novel biomarkers to predict short- and long-term outcomes of acute kidney injury in many patient care settings, such as cardiac surgery, intensive care units, heart failure, and transplant. Future research should focus on leveraging this relationship to improve enrollment for clinical trials of acute kidney injury. PMID:27239295

  1. Alpinetin inhibits lipopolysaccharide-induced acute kidney injury in mice.

    PubMed

    Huang, Yi; Zhou, Li-shan; Yan, Li; Ren, Juan; Zhou, Dai-xing; Li, Shu-Sheng

    2015-10-01

    Alpinetin, a novel plant flavonoid isolated from Alpinia katsumadai Hayata, has been demonstrated to have anti-inflammatory and antioxidant effects. However, the effects of alpinetin on lipopolysaccharide (LPS)-induced acute kidney injury have not been reported. In the present study, we investigated the protective effects and the underlying mechanism of alpinetin against LPS-induced acute kidney injury in mice. The results showed that alpinetin inhibited LPS-induced kidney histopathologic changes, blood urea nitrogen (BUN) and creatinine levels. Alpinetin also inhibited LPS-induced ROS, MDA, and inflammatory cytokines TNF-α, IL-6 and IL-1β production in kidney tissues. Meanwhile, Western blot analysis showed that alpinetin suppressed LPS-induced TLR4 expression and NF-κB activation in kidney tissues. In addition, alpinetin was found to up-regulate the expression of Nrf2 and HO-1 in a dose-dependent manner. In conclusion, alpinetin protected LPS-induced kidney injury through activating Nrf2 and inhibiting TLR4 expression.

  2. Suppression of microglia activation after hypoxia-ischemia results in age-dependent improvements in neurologic injury

    PubMed Central

    Cikla, Ulas; Chanana, Vishal; Kintner, Douglas B.; Covert, Lucia; Dewall, Taylor; Waldman, Alex; Rowley, Paul; Cengiz, Pelin; Ferrazzano, Peter

    2015-01-01

    We previously found increased microglial proliferation and pro-inflammatory cytokine release in infant mice compared to juvenile mice after hypoxia-ischemia (HI). The aim of the current study was to assess for differences in the effect of microglial suppression on HI-induced brain injury in infant and juvenile mice. HI was induced in neonatal (P9) and juvenile (P30) mice and minocycline or vehicle was administered at 2 hours and 24 hours post-HI. P9 minocycline-treated mice demonstrated early but transient improvements in neurologic injury, while P30 minocycline-treated mice demonstrated sustained improvements in cerebral atrophy and Morris Water Maze performance at 60 days post-HI. PMID:26857490

  3. Targeting L-Selectin to Improve Neurologic and Urologic Function After Spinal Cord Injury

    DTIC Science & Technology

    2015-10-01

    We have demonstrated no adverse effects of DFA on bladder function following spinal cord injury. However, the drug resulted in no improvement in...We demonstrated that 40 mg/kg DFA is the minimally effective dose to induce L-selectin shedding in a mouse model of spinal cord injury -We...using this paradigm for two injury severities, mild and severe, suggesting a robust therapeutic effect -We identified no adverse effects to animal

  4. Transplanting Kidneys from Deceased Donors With Severe Acute Kidney Injury.

    PubMed

    Heilman, R L; Smith, M L; Kurian, S M; Huskey, J; Batra, R K; Chakkera, H A; Katariya, N N; Khamash, H; Moss, A; Salomon, D R; Reddy, K S

    2015-08-01

    Our aim was to determine outcomes with transplanting kidneys from deceased donors with acute kidney injury, defined as a donor with terminal serum creatinine ≥2.0 mg/dL, or a donor requiring acute renal replacement therapy. We included all patients who received deceased donor kidney transplant from June 2004 to October 2013. There were 162 AKI donor transplant recipients (21% of deceased donor transplants): 139 in the standard criteria donor (SCD) and 23 in the expanded criteria donor (ECD) cohort. 71% of the AKI donors had stage 3 (severe AKI), based on acute kidney injury network (AKIN) staging. Protocol biopsies were done at 1, 4, and 12 months posttransplant. One and four month formalin-fixed paraffin embedded (FFPE) biopsies from 48 patients (24 AKI donors, 24 non-AKI) underwent global gene expression profiling using DNA microarrays (96 arrays). DGF was more common in the AKI group but eGFR, graft survival at 1 year and proportion with IF/TA>2 at 1 year were similar for the two groups. At 1 month, there were 898 differentially expressed genes in the AKI group (p-value <0.005; FDR <10%), but by 4 months there were no differences. Transplanting selected kidneys from deceased donors with AKI is safe and has excellent outcomes.

  5. [Acute lung injury as a consequence of blood transfusion].

    PubMed

    Rodríguez-Moyado, Héctor

    2011-01-01

    Acute lung injury (ALI) has been recognized as a consequence of blood transfusion (BT) since 1978; the Food and Drug Administration, has classified it as the third BT mortality issue, in 2004, and in first place related with ALI. It can be mainly detected as: Acute respiratory distress syndrome (ARDS), transfusion associated circulatory overload (TACO) and transfusion related acute lung injury (TRALI). The clinical onset is: severe dyspnea, bilateral lung infiltration and low oxygen saturation. In USA, ARDS has an incidence of three to 22.4 cases/100 000 inhabitants, with 58.3 % mortality. TACO and TRALI are less frequent; they have been reported according to the number of transfusions: one in 1275 to 6000 for TRALI and one in 356 transfusions for TACO. Mortality is reported from two to 20 % in TRALI and 20 % in TACO. Antileukocyte antibodies in blood donors plasma, caused TRALI in 89 % of cases; also it has been found antigen specificity against leukocyte blood receptor in 59 %. The UCI patients who received a BT have ALI as a complication in 40 % of cases. The capillary pulmonary endothelia is the target of leukocyte antibodies and also plasma biologic modifiers of the stored plasma, most probable like a Sanarelli-Shwar-tzman phenomenon.

  6. Variability in the treatment of acute spinal cord injury in the United Kingdom: results of a national survey.

    PubMed

    Werndle, Melissa C; Zoumprouli, Argyro; Sedgwick, Philip; Papadopoulos, Marios C

    2012-03-20

    The aim of this study was to examine how traumatic spinal cord injury is managed in the United Kingdom via a questionnaire survey of all neurosurgical units. We contacted consultant neurosurgeons and neuroanesthetists in all neurosurgical centers that manage patients with acute spinal cord injury. Two clinical scenarios-of complete and incomplete cervical spinal cord injuries-were given to determine local treatment policies. There were 175 responders from the 33 centers (36% response rate). We ascertained neurosurgical views on urgency of transfer, timing of surgery, nature and aim of surgery, as well as neuroanesthetic views on type of anesthetic, essential intraoperative monitoring, drug treatment, and intensive care management. Approximately 70% of neurosurgeons will admit patients with incomplete spinal cord injury immediately, but only 40% will admit patients with complete spinal cord injury immediately. There is no consensus on the timing or even the role of surgery for incomplete or complete injuries. Most (96%) neuroanesthetists avoid anesthetics known to elevate intracranial pressure. What was deemed essential intraoperative monitoring, however, varied widely. Many (22%) neuroanesthetists do not routinely measure arterial blood pressure invasively, central venous pressure (85%), or cardiac output (94%) during surgery. There is no consensus among neuroanesthetists on the optimal levels of arterial blood pressure, or oxygen and carbon dioxide partial arterial pressure. We report wide variability among U.K. neurosurgeons and neuroanesthetists in their treatment of acute traumatic spinal cord injury. Our findings reflect the lack of Class 1 evidence that early surgical decompression and intensive medical management of patients with spinal cord injury improves neurological outcome.

  7. A case of life-threatening acute kidney injury with toxic encephalopathy caused by Dioscorea quinqueloba.

    PubMed

    Kang, Kyung-Sik; Heo, Sang Taek

    2015-01-01

    Some herbal medications induce acute kidney injury. The acute kidney injuries caused by herbal medications are mild and commonly treated by palliative care. A 51-years-old man who drank the juice squeezed from the raw tubers of Dioscorea quinqueloba (D. quinqueloba) was admitted with nausea, vomiting and chilling. He developed a seizure with decreased level of consciousness. He was diagnosed with acute kidney injury, which was cured by continuous venovenous hemodialfiltration. Non-detoxified D. quinqueloba can cause severe acute kidney injury with toxic encephalopathy. It is critical to inform possible adverse effects of the medicinal herbs and to implement more strict regulation of these products.

  8. Predictors of Acute Kidney Injury in Neurocritical Care Patients Receiving Continuous Hypertonic Saline

    PubMed Central

    Riha, Heidi; Bode, Lauren; Chang, Jason J.; Jones, G. Morgan

    2016-01-01

    Background and Purpose: Continuous intravenous 3% hypertonic saline (HTS) infusions are commonly used for the management of cerebral edema following severe neurologic injuries. Despite widespread use, data regarding the incidence and predictors of nephrotoxicity are lacking. The purpose of this study was to describe the incidence and identify predictors of acute kidney injury (AKI) in neurocritical care patients administered continuous infusion HTS. Methods: This was an institutional review board–approved, multicenter, retrospective cohort study of patients receiving HTS infusions at 2 academic medical centers. A univariate analysis and multivariable logistic regression were used to identify predictors of AKI. Data regarding AKI were evaluated during treatment with HTS and up to 24 hours after discontinuation. Results: A total of 329 patients were included in our analysis, with 54 (16%) developing AKI. Those who developed AKI experienced significantly longer stays in the intensive care unit (14.8 vs 11.5 days; P = .006) and higher mortality (48.1% vs 21.9%; P < .001). We identified past medical history of chronic kidney disease (odds ratio [OR]: 9.7, 95% confidence interval [CI]: 1.9-50.6; P = .007), serum sodium greater than 155 mmol/L (OR: 4.1, 95% CI: 2.1-8.0; P < .001), concomitant administration of piperacillin/tazobactam (OR: 3.9, 95% CI: 1.7-9.3; P = .002), male gender (OR: 3.2, 95% CI: 1.5-6.6; P = .002), and African American race (OR: 2.6, 95% CI: 1.3-5.2; P = .007) as independent predictors of AKI. Conclusion: Acute kidney injury is relatively common in patients receiving continuous HTS and may significantly impact clinical outcomes. PMID:28042364

  9. Traumatic Brain Injury in Domestic Violence Victims: A Retrospective Study at the Barrow Neurological Institute.

    PubMed

    Zieman, Glynnis; Bridwell, Ashley; Cárdenas, Javier F

    2017-02-15

    Domestic violence is a national health crisis, which affects people of all ages, races, and socioeconomic classes. Traumatic brain injury is common in victims because of the high frequency of head and neck injuries inflicted through abuse. These recurrent injuries can lead to chronic symptoms with high morbidity. We conducted a retrospective chart review of 115 patients with a history of head trauma as a result of domestic violence. All patients were seen in a subspecialty traumatic brain injury clinic, at which time information regarding their histories and self-reported symptoms were recorded. In total, 109 females and 6 males were included in our study, with an age range of 4-68 years. Overall, 88% reported more than one injury and 81% reported a history of loss of consciousness associated with their injuries. Only 21% sought medical help at the time of injury. Whereas 85% had a history of abuse in adulthood, 22% had experienced abuse in both childhood and adulthood, and 60% of the patients abused as children went on to be abused as adults. Headache was the most common chief complaint, but on a self-reported symptom severity scale, behavioral symptoms were the most severe. Psychiatric disease was present in 84% of patients. Traumatic brain injury is a frequent sequela of domestic violence, from which many victims sustain multiple injuries without seeking medical care. Brain injuries are often sustained over many years and lead to lasting physical, behavioral, and cognitive consequences. Better understanding of these injuries will lead to improved care for this population.

  10. Neurological assessment.

    PubMed

    Maher, Ann Butler

    2016-08-01

    Neurological system assessment is an important skill for the orthopaedic nurse because the nervous system has such an overlap with the musculoskeletal system. Nurses whose scope of practice includes such advanced evaluation, e.g. nurse practitioners, may conduct the examination described here but the information will also be useful for nurses caring for patients who have abnormal neurological assessment findings. Within the context of orthopaedic physical assessment, possible neurological findings are evaluated as they complement the patient's history and the examiner's findings. Specific neurological assessment is integral to diagnosis of some orthopaedic conditions such as carpal tunnel syndrome. In other situations such as crushing injury to the extremities, there is high risk of associated neurological or neurovascular injury. These patients need anticipatory examination and monitoring to prevent complications. This article describes a basic neurological assessment; emphasis is on sensory and motor findings that may overlap with an orthopaedic presentation. The orthopaedic nurse may incorporate all the testing covered here or choose those parts that further elucidate specific diagnostic questions suggested by the patient's history, general evaluation and focused musculoskeletal examination. Abnormal findings help to suggest further testing, consultation with colleagues or referral to a specialist.

  11. Pathophysiology of acute kidney injury: a new perspective.

    PubMed

    Wen, Xiaoyan; Murugan, Raghavan; Peng, Zhiyong; Kellum, John A

    2010-01-01

    Acute kidney injury (AKI) in critically ill patients is a devastating illness associated with prolonged hospital stay and high mortality. Limited progress has been made in the field of AKI, and its treatment using renal replacement therapy, at best, only provides partial renal support. Ischemia-reperfusion rodent AKI models do not resemble human renal injury and the absence of renal biopsy data limits our understanding of the pathophysiology of human AKI. However, laboratory and clinical evidence suggests that the inflammatory milieu leads to dysfunction of renal cells and this may be the key factor leading to AKI. Cells in injured tissues release immunological danger signals or danger-associated molecular pattern molecules which communicate with remote organs including the kidney, where they activate dendritic cells and T cells and thus initiate inflammation. Once the initial insult has passed, tubular epithelial cells undergo dedifferentiation, reacquire progenitorial ability to proliferate, migrate, and redifferentiate into mature intrinsic cells. Dissonance of mediator secretion and cell responses may lead to persistent injury and de novo chronic kidney disease. A number of soluble mediators including transforming growth factor-beta (TGF-beta) initiate a variety of pathophysiological processes at the beginning of kidney injury. TGF-beta also plays a fundamental role in cell proliferation and interstitial fibrosis in later phases. The renin-angiotensin-aldosterone system, especially angiotensin II, contributes to kidney injury through the angiotensin II type 1 receptor, TGF-beta receptor Smad and epidermal growth factor receptor by affecting general angiostasis and vascular remodeling, indirectly modulating inflammation and cell reactions. We review the pathophysiology of AKI in light of new information regarding renal injury and repair.

  12. Traumatic Brain Injury Induces Genome-Wide Transcriptomic, Methylomic, and Network Perturbations in Brain and Blood Predicting Neurological Disorders.

    PubMed

    Meng, Qingying; Zhuang, Yumei; Ying, Zhe; Agrawal, Rahul; Yang, Xia; Gomez-Pinilla, Fernando

    2017-02-01

    The complexity of the traumatic brain injury (TBI) pathology, particularly concussive injury, is a serious obstacle for diagnosis, treatment, and long-term prognosis. Here we utilize modern systems biology in a rodent model of concussive injury to gain a thorough view of the impact of TBI on fundamental aspects of gene regulation, which have the potential to drive or alter the course of the TBI pathology. TBI perturbed epigenomic programming, transcriptional activities (expression level and alternative splicing), and the organization of genes in networks centered around genes such as Anax2, Ogn, and Fmod. Transcriptomic signatures in the hippocampus are involved in neuronal signaling, metabolism, inflammation, and blood function, and they overlap with those in leukocytes from peripheral blood. The homology between genomic signatures from blood and brain elicited by TBI provides proof of concept information for development of biomarkers of TBI based on composite genomic patterns. By intersecting with human genome-wide association studies, many TBI signature genes and network regulators identified in our rodent model were causally associated with brain disorders with relevant link to TBI. The overall results show that concussive brain injury reprograms genes which could lead to predisposition to neurological and psychiatric disorders, and that genomic information from peripheral leukocytes has the potential to predict TBI pathogenesis in the brain.

  13. Susceptibility of the MMPI-2-RF neurological complaints and cognitive complaints scales to over-reporting in simulated head injury.

    PubMed

    Bolinger, Elizabeth; Reese, Caitlin; Suhr, Julie; Larrabee, Glenn J

    2014-02-01

    We examined the effect of simulated head injury on scores on the Neurological Complaints (NUC) and Cognitive Complaints (COG) scales of the Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF). Young adults with a history of mild head injury were randomly assigned to simulate head injury or give their best effort on a battery of neuropsychological tests, including the MMPI-2-RF. Simulators who also showed poor effort on performance validity tests (PVTs) were compared with controls who showed valid performance on PVTs. Results showed that both scales, but especially NUC, are elevated in individuals simulating head injury, with medium to large effect sizes. Although both scales were highly correlated with all MMPI-2-RF over-reporting validity scales, the relationship of Response Bias Scale to both NUC and COG was much stronger in the simulators than controls. Even accounting for over-reporting on the MMPI-2-RF, NUC was related to general somatic complaints regardless of group membership, whereas COG was related to both psychological distress and somatic complaints in the control group only. Neither scale was related to actual neuropsychological performance, regardless of group membership. Overall, results provide further evidence that self-reported cognitive symptoms can be due to many causes, not necessarily cognitive impairment, and can be exaggerated in a non-credible manner.

  14. Acute cervical cord injuries in patients with epilepsy.

    PubMed Central

    Allen, J W; Kendall, B E; Kocen, R S; Milligan, N M

    1982-01-01

    Seven cases with acute cervical cord lesions associated with a fit and fall, were found in approximately 500 patients with epilepsy over a period of 7 years. In all patients the epilepsy was refractory to drug therapy and six suffered tonic fits which resulted in falls and frequent head injuries. Notable radiological changes were found in the cervical spine; there was ankylosis in five, hyperostosis in four and the minimum sagittal diameter of the bony canal was less than 11mm in three cases. The findings indicate that repetitive trauma may be a factor in producing bony changes in the cervical spine which put the patient at risk of cervical cord injury, especially when the spinal canal is developmentally narrow. Images PMID:7143009

  15. Molecular mechanisms of neuroinflammation and injury during acute viral encephalitis.

    PubMed

    Shives, Katherine D; Tyler, Kenneth L; Beckham, J David

    2017-03-11

    Viral infections in the central nervous system are a major cause of encephalitis. West Nile virus (WNV) and Herpes simplex virus (HSV) are the most common causes of viral encephalitis in the United States. We review the role of neuroinflammation in the pathogenesis of WNV and HSV infections in the central nervous system (CNS). We discuss the role of the innate and cell-mediated immune responses in peripheral control of viral infection, viral invasion of the CNS, and in inflammatory-mediated neuronal injury. By understanding the role of specific inflammatory responses to viral infections in the CNS, targeted therapeutic approaches can be developed to maximize control of acute viral infection while minimizing neuronal injury in the CNS.

  16. Dapagliflozin-Induced Acute-on-Chronic Liver Injury

    PubMed Central

    Levine, Joshua A.; Ann Lo, Amy; Wallia, Amisha; Rogers, Melinda

    2016-01-01

    Sodium-glucose cotransporter 2 inhibitors are a new class of oral hypoglycemic agents, and thus safety data are limited. We present a 48-year-old woman with type 2 diabetes mellitus and Child’s Class A cirrhosis secondary to nonalcoholic steatohepatitis presenting with jaundice and acute cholestatic liver injury. Other than starting dapagliflozin, she reported no medication changes or supplement use. Before treatment, her total bilirubin was 1.2 mg/dL. On admission, her liver values were elevated and liver biopsy was consistent with drug-induced liver injury. This report raises awareness about the potential hepatotoxic effects of dapagliflozin, particularly in patients with chronic liver disease. PMID:28008402

  17. Acute kidney injury: changing lexicography, definitions, and epidemiology.

    PubMed

    Himmelfarb, J; Ikizler, T A

    2007-05-01

    In recent years, there have been numerous advances in understanding the molecular determinants of functional kidney injury after ischemic and/or toxic exposure. However, translation of successful novel therapies designed to attenuate kidney functional injury from animal models to the clinical sphere has had modest results. This lack of translatability is at least in part due to lack of sufficient standardization in definitions and classification of cases of acute kidney injury (AKI), an incomplete understanding of the natural history of human AKI, and a limited understanding of how kidney injury interacts with other organ system failure in the context of systemic metabolic abnormalities. A concerted effort is now being made by nephrologists and intensivists to arrive at standardized terminology and classification of AKI. There have also been dramatic advances in our understanding of the epidemiology and natural history of AKI, particularly in the hospital and intensive care unit setting. Promising strategies are now being developed which may ultimately lead to improved outcomes for patients at risk for or who have developed AKI, which should be readily testable in the coming decade.

  18. Defining the acute kidney injury and repair transcriptome.

    PubMed

    Kumar, Sanjeev; Liu, Jing; McMahon, Andrew P

    2014-07-01

    The mammalian kidney has an intrinsic ability to repair after significant injury. However, this process is inefficient: patients are at high risk for the loss of kidney function in later life. No therapy exists to treat established acute kidney injury (AKI) per se: strategies to promote endogenous repair processes and retard associated fibrosis are a high priority. Whole-organ gene expression profiling has been used to identify repair responses initiated with AKI, and factors that may promote the transition from AKI to chronic kidney disease. Transcriptional profiling has shown molecular markers and potential regulatory pathways of renal repair. Activation of a few key developmental pathways has been reported during repair. Whether these are comparable networks with similar target genes with those in earlier nephrogenesis remains unclear. Altered microRNA profiles, persistent tubular injury responses, and distinct late inflammatory responses highlight continuing kidney pathology. Additional insights into injury and repair processes will be gained by study of the repair transcriptome and cell-specific translatome using high-resolution technologies such as RNA sequencing and translational profiling tailored to specific cellular compartments within the kidney. An enhanced understanding holds promise for both the identification of novel therapeutic targets and biomarker-based evaluation of the damage-repair process.

  19. Brain-derived neurotrophic factor-modified umbilical cord mesenchymal stem cell transplantation improves neurological deficits in rats with traumatic brain injury.

    PubMed

    Yuan, Yuan; Pan, Shumao; Sun, Zhaoming; Dan, Qiqin; Liu, Jia

    2014-07-01

    This study explored the effect of brain-derived neurotrophic factor (BDNF) gene-modified umbilical cord mesenchymal stem cell (UCMSC) transplantation on neurological functional improvement in rats after brain trauma. A rat model of cerebral contusion in the motor-sensory cortex was established by the weight hammer-falling method. UCMSCs were cultured and transferred with BDNF gene. After determining BDNF expression and activity, the BDNF gene-modified UCMSCs were implanted into brains of rats receiving the brain injury. The neurological function was evaluated 1 and 2 weeks after brain injury. BDNF expression was then determined by immunohistochemistry. Severe neurological dysfunction was observed in animals subjected to contusion brain injury (10.50 ± 0.53). A significant improvement in neurological function was found in the UCMSC transplantation animals (7.75 ± 0.71) compared with the brain injury only group (p < 0.01). Rats with BDNF gene-modified UCMSCs showed the highest improvement in behavior (5.50 ± 0.76; p < 0.01). BDNF gene-modified UCMSCs can survive and migrate in rat cerebral tissues. The transplantation of these UCMSCs can improve the neurological functions of rats with traumatic brain injury.

  20. When to correct coagulopathy in acute kidney injury?

    PubMed Central

    Kaur, Manpreet; Gupta, Babita; D’souza, Nita; Shende, Seema

    2012-01-01

    Incidence of acute kidney injury (AKI) in adult trauma patients is 18% with 70% requiring renal replacement therapy. It is a challenge to treat AKI with coagulopathy since there are no defined transfusion triggers for these patients. We report a case wherein a polytrauma patient developed AKI for which he/she was dialysed and subsequently had an intracerebral bleed. There is a need to develop guidelines to transfusion triggers in AKI patients keeping vigilance on fluid overload, hyperkalemia and uraemia-induced platelet dysfunction. PMID:25885629

  1. Management of Acute Kidney Injury in Pregnancy for the Obstetrician.

    PubMed

    Acharya, Anjali

    2016-12-01

    Acute kidney injury (AKI) is a complex disorder that occurs in several clinical settings. During pregnancy, there are additional unique conditions that contribute to AKI. The clinical manifestations of AKI during pregnancy range from a minimal elevation in serum creatinine to renal failure requiring renal replacement therapy, similar to AKI in the general population. Recent epidemiologic studies in the general population show an increase in mortality associated with AKI, particularly when dialysis is required. The incidence of AKI in pregnancy remains a cause of significant morbidity and mortality.

  2. Acute spinal cord injury: tetraplegia and paraplegia in small animals.

    PubMed

    Granger, Nicolas; Carwardine, Darren

    2014-11-01

    Spinal cord injury (SCI) is a common problem in animals for which definitive treatment is lacking, and information gained from its study has benefit for both companion animals and humans in developing new therapeutic approaches. This review provides an overview of the main concepts that are useful for clinicians in assessing companion animals with severe acute SCI. Current available advanced ancillary tests and those in development are reviewed. In addition, the current standard of care for companion animals following SCI and recent advances in the development of new therapies are presented, and new predictors of recovery discussed.

  3. Acute cardiac injury after subarachnoid haemorrhage: two case reports.

    PubMed

    Marcì, Marcello; Savatteri, Paolino; Pizzuto, Antonino; Giammona, Giuseppe; Renda, Baldassare; Lojacono, Francesca; Sanfilippo, Nicola

    2009-12-09

    It is well known that cardiopulmonary complications are often associated to subarachnoid haemorrhage. For appropriate therapeutic managing it is very important to distinguish acute coronary syndrome from neurogenic myocardial injury, which is a reversible condition. Furthermore, because the hearts of brain dead patients may be utilized for therapeutic purpose, it has became of importance to rule out erroneous diagnosis of cardiac ischemia in order to avoid rejection of hearts potential suitable for transplantation.We present a report of two female patients affected by cardiac complications caused by aneurismal subarachnoid haemorrhage admitted to our neurosurgical intensive care department.

  4. Acute kidney injury in pregnancy: the thrombotic microangiopathies.

    PubMed

    Ganesan, Chitra; Maynard, Sharon E

    2011-01-01

    Acute kidney injury (AKI) is a rare but serious complication of pregnancy. Although prerenal and ischemic causes of AKI are most common, renal insufficiency can complicate several other pregnancy-specific conditions. In particular, severe preeclampsia/HELLP syndrome, acute fatty liver of pregnancy (AFLP) and thrombotic thrombocytopenic purpura (TTP) are all frequently complicated by AKI, and share several clinical features which pose diagnostic challenges to the clinician. In this article, we discuss the clinical and laboratory features, pathophysiology and treatment of these 3 conditions, with particular attention to renal manifestations. It is imperative to distinguish these conditions to make appropriate therapeutic decisions which can be lifesaving for the mother and fetus. Typically AFLP and HELLP improve after delivery of the fetus, whereas plasma exchange is the first-line treatment for TTP.

  5. Acute renal injury induced by valacyclovir hydrochloride: A case report

    PubMed Central

    Zhang, Yanning; Cong, Yuxi; Teng, Yan

    2016-01-01

    Acyclovir has been a frequently used antiviral agent in the clinical treatment of leukemia, acute encephalitis, malignant tumor and herpes simplex. The adverse effects of this drug have been widely described in clinical practice. In the present study, a case of a 35-year-old female patient diagnosed with herpes simplex, who developed acute renal injury following treatment with valacyclovir hydrochloride, is described. Kidney biopsy, light microscopy and laboratory examination were performed, and all findings revealed the signs of evident vacuolar degeneration of capillary endothelial and renal tubular epithelial cells, erythrocyte aggregation in partial renal tubule and microvilli exfoliation from epithelial cells. Renal interstitial edema was clearly identified. The clinical evidence observed from this female patient indicated that renal functions should be closely monitored during valacyclovir hydrochloride administration. A variety of effective measures, such as hydration, alkalizing urine, promoting the discharge of medication and the use of antagonists are recommended following the administration of antiviral agents. PMID:28101180

  6. Long-Term Kinetics of Immunologic Components and Neurological Deficits in Rats Following Repetitive Mild Traumatic Brain Injury.

    PubMed

    Bai, Ruojing; Gao, Huabin; Han, Zhaoli; Ge, Xintong; Huang, Shan; Chen, Fanglian; Lei, Ping

    2017-04-08

    BACKGROUND Despite growing awareness of repetitive mild traumatic brain injury (rmTBI), understanding of the involvement of long-term kinetics of immunologic components in the central and peripheral immune system took part remains incomplete. The present study aimed to provide a quantitative assay for certain immune system parameters in rmTBI rats. MATERIAL AND METHODS Neurological functions were assessed by modified Neurological Severity Score (mNSS) and Morris Water Maze (MWM), immunologic components from brain and peripheral blood were analyzed by flow cytometry (FCM), and concentrations of inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 were measure by enzyme-linked immunosorbent assay (ELISA). RESULTS Neurological functions of rmTBI rats were seriously impaired. In the brain, T cells were up-regulated and peaked at week 1. The percentage of CD4+ T cells decreased from week 1 to week 4, while CD8+ T cells notably decreased at week 1, then increased until week 4. The infiltration proportion of Treg cells was reduced at week 1 and peaked at week 2. CD86+/CD11b+ M1 peaked at week 4 and CD206+/CD11b+ M2 rose at week 1. IL-6/IL-10 showed a similar pattern, whose rise corresponded to the decrease in TNF-α at week 2 after rmTBI. FCM demonstrated peripheral immune dysfunction after rmTBI. CONCLUSIONS mNSS and MWM demonstrated neuronal deficits in rmTBI rats, and central and peripheral immune systems were implicated in the pathophysiological processes of rmTBI. Long-term immune response may play dual roles in injury and repair of rmTBI.

  7. Epidemiology of Acute Kidney Injury in Critically Ill Children and Young Adults.

    PubMed

    Kaddourah, Ahmad; Basu, Rajit K; Bagshaw, Sean M; Goldstein, Stuart L

    2017-01-05

    Background The epidemiologic characteristics of children and young adults with acute kidney injury have been described in single-center and retrospective studies. We conducted a multinational, prospective study involving patients admitted to pediatric intensive care units to define the incremental risk of death and complications associated with severe acute kidney injury. Methods We used the Kidney Disease: Improving Global Outcomes criteria to define acute kidney injury. Severe acute kidney injury was defined as stage 2 or 3 acute kidney injury (plasma creatinine level ≥2 times the baseline level or urine output <0.5 ml per kilogram of body weight per hour for ≥12 hours) and was assessed for the first 7 days of intensive care. All patients 3 months to 25 years of age who were admitted to 1 of 32 participating units were screened during 3 consecutive months. The primary outcome was 28-day mortality. Results A total of 4683 patients were evaluated; acute kidney injury developed in 1261 patients (26.9%; 95% confidence interval [CI], 25.6 to 28.2), and severe acute kidney injury developed in 543 patients (11.6%; 95% CI, 10.7 to 12.5). Severe acute kidney injury conferred an increased risk of death by day 28 after adjustment for 16 covariates (adjusted odds ratio, 1.77; 95% CI, 1.17 to 2.68); death occurred in 60 of the 543 patients (11.0%) with severe acute kidney injury versus 105 of the 4140 patients (2.5%) without severe acute kidney injury (P<0.001). Severe acute kidney injury was associated with increased use of mechanical ventilation and renal-replacement therapy. A stepwise increase in 28-day mortality was associated with worsening severity of acute kidney injury (P<0.001 by log-rank test). Assessment of acute kidney injury according to the plasma creatinine level alone failed to identify acute kidney injury in 67.2% of the patients with low urine output. Conclusions Acute kidney injury is common and is associated with poor outcomes, including increased

  8. Acute Alcohol Intoxication Prolongs Neuroinflammation without Exacerbating Neurobehavioral Dysfunction following Mild Traumatic Brain Injury

    PubMed Central

    Teng, Sophie X.

    2014-01-01

    Abstract Traumatic brain injury (TBI) represents a leading cause of death and disability among young persons with ∼1.7 million reported cases in the United States annually. Although acute alcohol intoxication (AAI) is frequently present at the time of TBI, conflicting animal and clinical reports have failed to establish whether AAI significantly impacts short-term outcomes after TBI. The objective of this study was to determine whether AAI at the time of TBI aggravates neurobehavioral outcomes and neuroinflammatory sequelae post-TBI. Adult male Sprague-Dawley rats were surgically instrumented with gastric and vascular catheters before a left lateral craniotomy. After recovery, rats received either a primed constant intragastric alcohol infusion (2.5 g/kg+0.3 g/kg/h for 15 h) or isocaloric/isovolumic dextrose infusion followed by a lateral fluid percussion TBI (∼1.4 J, ∼30 ms). TBI induced apnea and a delay in righting reflex. AAI at the time of injury increased the TBI induced delay in righting reflex without altering apnea duration. Neurological and behavioral dysfunction was observed at 6 h and 24 h post-TBI, and this was not exacerbated by AAI. TBI induced a transient upregulation of cortical interleukin (IL)-6 and monocyte chemotactic protein (MCP)-1 mRNA expression at 6 h, which was resolved at 24 h. AAI did not modulate the inflammatory response at 6 h but prevented resolution of inflammation (IL-1, IL-6, tumor necrosis factor-α, and MCP-1 expression) at 24 h post-TBI. AAI at the time of TBI did not delay the recovery of neurological and neurobehavioral function but prevented the resolution of neuroinflammation post-TBI. PMID:24050411

  9. Acute Cortical Transhemispheric Diaschisis after Unilateral Traumatic Brain Injury.

    PubMed

    Le Prieult, Florie; Thal, Serge C; Engelhard, Kristin; Imbrosci, Barbara; Mittmann, Thomas

    2017-03-01

    Focal neocortical brain injuries lead to functional alterations, which can spread beyond lesion-neighboring brain areas. The undamaged hemisphere and its associated disturbances after a unilateral lesion, so-called transhemispheric diaschisis, have been progressively disclosed over the last decades; they are strongly involved in the pathophysiology and, potentially, recovery of brain injuries. Understanding the temporal dynamics of these transhemispheric functional changes is crucial to decipher the role of the undamaged cortex in the processes of functional reorganization at different stages post-lesion. In this regard, little is known about the acute-subacute processes after 24-48 h in the brain hemisphere contralateral to injury. In the present study, we performed a controlled cortical impact to produce a unilateral traumatic brain injury (TBI) in the motor and somatosensory cortex of mice. In vitro extracellular multi-unit recordings from large neuronal populations, together with single-cell patch-clamp recordings in the cortical network contralateral to the lesion, revealed a strong, but transient, neuronal hyperactivity as early as 24-48 h post-TBI. This abnormal excitable state in the intact hemisphere was not accompanied by alterations in neuronal intrinsic properties, but it was associated with an impairment of the phasic gamma aminobutyric acid (GABA)ergic transmission and an increased expression of GABAA receptor subunits related to tonic inhibition exclusively in the contralateral hemisphere. These data unravel a series of early transhemispheric functional alterations after diffuse unilateral cortical injury, which may compensate and stabilize the disrupted brain functions. Therefore, our findings support the hypothesis that the undamaged hemisphere could play a significant role in early functional reorganization processes after a TBI.

  10. Clinical Predictors of Neurological Outcome within 72 h after Traumatic Cervical Spinal Cord Injury

    PubMed Central

    Qiu, Zhi; Wang, Fangyong; Hong, Yi; Zhang, Junwei; Tang, Hehu; Li, Xiang; Jiang, Shudong; Lv, Zhen; Liu, Shujia; Chen, Shizheng; Liu, Jiesheng

    2016-01-01

    To investigate the prognostic values of clinical factors 72 h within traumatic cervical spinal cord injury (TCSCI). Data were extracted from the medical materials of 57 TCSCI cases. AIS was used as the outcome measure and divided into dichotomous variables by two methods, i.e. “complete(AIS = A)/incomplete(AIS ≠ A) SCI” and “motor complete(AIS = A or B)/incomplete(AIS ≠ A and B) SCI”. Relationships between evaluated factors and outcomes were investigated by univariate and multivariate methods. MRI Cord transection (MCT) cases, most significantly related to complete SCIs by univariate analysis (P = 0.006), all showed complete SCIs when discharged, which makes it unsuitable for logistic regression. With MCT cases removed, univariate analysis was conducted again, then logistic regression. At last, only C5 spine injury (P = 0.024, OR = 0.241) was related to complete SCI. Cases with compression flexion injury mechanism (CFIM), most significantly related to motor complete SCIs by univariate analysis (P = 0.001), was also unsuitable for logistic regression for the same reason. At last, C3 spine injury (P = 0.033, OR = 0.068) and high energy injury (P = 0.033, OR = 14.763) were related to motor complete SCIs with CFIM cases removed. The results show that MCT and C5 spine injury are good predictors for complete/incomplete SCIs. CFIM, C3 spine injury and high energy injury are good predictors for motor complete/incomplete SCIs. PMID:27941855

  11. Sympathoadrenal Activation is Associated with Acute Traumatic Coagulopathy and Endotheliopathy in Isolated Brain Injury

    PubMed Central

    Di Battista, Alex P.; Rizoli, Sandro B.; Lejnieks, Brandon; Min, Arimie; Shiu, Maria Y.; Peng, Henry T.; Baker, Andrew J.; Hutchison, Michael G.; Churchill, Nathan; Inaba, Kenji; Nascimento, Bartolomeu B.; de Oliveira Manoel, Airton Leonardo; Beckett, Andrew; Rhind, Shawn G.

    2016-01-01

    ABSTRACT Background: Acute coagulopathy after traumatic brain injury (TBI) involves a complex multifactorial hemostatic response that is poorly characterized. Objectives: To examine early posttraumatic alterations in coagulofibrinolytic, endothelial, and inflammatory blood biomarkers in relation to sympathetic nervous system (SNS) activation and 6-month patient outcomes, using multivariate partial least-squares (PLS) analysis. Patients and Methods: A multicenter observational study of 159 adult isolated TBI patients admitted to the emergency department at an urban level I trauma center, was performed. Plasma concentrations of 6 coagulofibrinolytic, 10 vascular endothelial, 19 inflammatory, and 2 catecholamine biomarkers were measured by immunoassay on admission and 24 h postinjury. Neurological outcome at 6 months was assessed using the Extended Glasgow Outcome Scale. PLS-discriminant analysis was used to identify salient biomarker contributions to unfavorable outcome, whereas PLS regression analysis was used to evaluate the covariance between SNS correlates (catecholamines) and biomarkers of coagulopathy, endotheliopathy, and inflammation. Results: Biomarker profiles in patients with an unfavorable outcome displayed procoagulation, hyperfibrinolysis, glycocalyx and endothelial damage, vasculature activation, and inflammation. A strong covariant relationship was evident between catecholamines and biomarkers of coagulopathy, endotheliopathy, and inflammation at both admission and 24 h postinjury. Conclusions: Biomarkers of coagulopathy and endotheliopathy are associated with poor outcome after TBI. Catecholamine levels were highly correlated with endotheliopathy and coagulopathy markers within the first 24 h after injury. Further research is warranted to characterize the pathogenic role of SNS-mediated hemostatic alterations in isolated TBI. PMID:27206278

  12. Cerebral salt wasting syndrome in children with acute central nervous system injury.

    PubMed

    Jiménez, Raquel; Casado-Flores, Juan; Nieto, Monserrat; García-Teresa, María Angeles

    2006-10-01

    The purpose of this investigation was to describe the causes, clinical pattern, and treatment of cerebral salt wasting syndrome in children with acute central nervous system injury. This retrospective study focused on patients120 mEq/L), and volume depletion. Fourteen patients were identified with cerebral salt wasting syndrome, 12 after a neurosurgical procedure (8 brain tumor, 4 hydrocephalus) and 2 after severe brain trauma. In 11 patients the cerebral salt wasting syndrome was diagnosed during the first 48 hours of admission. Prevalence of cerebral salt wasting syndrome in neurosurgical children was 11.3/1000 surgical procedures. The minimum sodium was 122+/-7 mEq/L, the maximum urine osmolarity 644+/-59 mOsm/kgH2O. The maximum sodium supply was 1 mEq/kg/h (range, 0.1-2.4). The mean duration of cerebral salt wasting syndrome was 6+/-5 days (range 1-9). In conclusion, cerebral salt wasting syndrome can complicate the postoperative course of children with brain injury; it is frequently present after surgery for brain tumors and hydrocephalus and in patients with severe head trauma. Close monitoring of salt and fluid balance is essential to prevent severe neurologic and hemodynamic complications.

  13. Effects of normobaric versus hyperbaric oxygen on cell injury induced by oxygen and glucose deprivation in acute brain slices

    PubMed Central

    Chazalviel, Laurent; Blatteau, Jean-Eric; Vallée, Nicolas; Risso, Jean-Jacques; Besnard, Stéphane; Abraini, Jacques H.

    2016-01-01

    Normobaric oxygen (NBO) and hyperbaric oxygen (HBO) are emerging as a possible co-treatment of acute ischemic stroke. Both have been shown to reduce infarct volume, to improve neurologic outcome, to promote endogenous tissue plasminogen activator-induced thrombolysis and cerebral blood flow, and to improve tissue oxygenation through oxygen diffusion in the ischemic areas, thereby questioning the interest of HBO compared to NBO. In the present study, in order to investigate and compare the oxygen diffusion effects of NBO and HBO on acute ischemic stroke independently of their effects at the vascular level, we used acute brain slices exposed to oxygen and glucose deprivation, an ex vivo model of brain ischemia that allows investigating the acute effects of NBO (partial pressure of oxygen (pO2) = 1 atmospheres absolute (ATA) = 0.1 MPa) and HBO (pO2 = 2.5 ATA = 0.25 MPa) through tissue oxygenation on ischemia-induced cell injury as measured by the release of lactate dehydrogenase. We found that HBO, but not NBO, reduced oxygen and glucose deprivation-induced cell injury, indicating that passive tissue oxygenation (i.e. without vascular support) of the brain parenchyma requires oxygen partial pressure higher than 1 ATA. PMID:27867486

  14. Effects of normobaric versus hyperbaric oxygen on cell injury induced by oxygen and glucose deprivation in acute brain slices.

    PubMed

    Chazalviel, Laurent; Blatteau, Jean-Eric; Vallée, Nicolas; Risso, Jean-Jacques; Besnard, Stéphane; Abraini, Jacques H

    2016-01-01

    Normobaric oxygen (NBO) and hyperbaric oxygen (HBO) are emerging as a possible co-treatment of acute ischemic stroke. Both have been shown to reduce infarct volume, to improve neurologic outcome, to promote endogenous tissue plasminogen activator-induced thrombolysis and cerebral blood flow, and to improve tissue oxygenation through oxygen diffusion in the ischemic areas, thereby questioning the interest of HBO compared to NBO. In the present study, in order to investigate and compare the oxygen diffusion effects of NBO and HBO on acute ischemic stroke independently of their effects at the vascular level, we used acute brain slices exposed to oxygen and glucose deprivation, an ex vivo model of brain ischemia that allows investigating the acute effects of NBO (partial pressure of oxygen (pO2) = 1 atmospheres absolute (ATA) = 0.1 MPa) and HBO (pO2 = 2.5 ATA = 0.25 MPa) through tissue oxygenation on ischemia-induced cell injury as measured by the release of lactate dehydrogenase. We found that HBO, but not NBO, reduced oxygen and glucose deprivation-induced cell injury, indicating that passive tissue oxygenation (i.e. without vascular support) of the brain parenchyma requires oxygen partial pressure higher than 1 ATA.

  15. A mouse model of weight-drop closed head injury: emphasis on cognitive and neurological deficiency

    PubMed Central

    Khalin, Igor; Jamari, Nor Laili Azua; Razak, Nadiawati Bt Abdul; Hasain, Zubaidah Bt; Nor, Mohd Asri bin Mohd; Zainudin, Mohd Hakimi bin Ahmad; Omar, Ainsah Bt; Alyautdin, Renad

    2016-01-01

    Traumatic brain injury (TBI) is a leading cause of death and disability in individuals worldwide. Producing a clinically relevant TBI model in small-sized animals remains fairly challenging. For good screening of potential therapeutics, which are effective in the treatment of TBI, animal models of TBI should be established and standardized. In this study, we established mouse models of closed head injury using the Shohami weight-drop method with some modifications concerning cognitive deficiency assessment and provided a detailed description of the severe TBI animal model. We found that 250 g falling weight from 2 cm height produced severe closed head injury in C57BL/6 male mice. Cognitive disorders in mice with severe closed head injury could be detected using passive avoidance test on day 7 after injury. Findings from this study indicate that weight-drop injury animal models are suitable for further screening of brain neuroprotectants and potentially are similar to those seen in human TBI. PMID:27212925

  16. Readmission to Acute Care Hospital during Inpatient Rehabilitation for Traumatic Brain Injury

    PubMed Central

    Hammond, Flora M.; Horn, Susan D.; Smout, Randall J.; Beaulieu, Cynthia L.; Barrett, Ryan S.; Ryser, David K.; Sommerfeld, Teri

    2015-01-01

    Objective To investigate frequency, reasons, and factors associated with readmission to acute care (RTAC) during inpatient rehabilitation for traumatic brain injury (TBI). Design Prospective observational cohort. Setting Inpatient rehabilitation. Participants 2,130 consecutive admissions for TBI rehabilitation. Interventions Not applicable. Main Outcome Measure(s) RTAC incidence, RTAC causes, rehabilitation length of stay (RLOS), and rehabilitation discharge location. Results 183 participants (9%) experienced RTAC for a total 210 episodes. 161 patients experienced 1 RTAC episode, 17 had 2, and 5 had 3. Mean days from rehabilitation admission to first RTAC was 22 days (SD 22). Mean duration in acute care during RTAC was 7 days (SD 8). 84 participants (46%) had >1 RTAC episode for medical reasons, 102 (56%) had >1 RTAC for surgical reasons, and RTAC reason was unknown for 6 (3%) participants. Most common surgical RTAC reasons were: neurosurgical (65%), pulmonary (9%), infection (5%), and orthopedic (5%); most common medical reasons were infection (26%), neurologic (23%), and cardiac (12%). Older age, history of coronary artery disease, history of congestive heart failure, acute care diagnosis of depression, craniotomy or craniectomy during acute care, and presence of dysphagia at rehabilitation admission predicted patients with RTAC. RTAC was less likely for patients with higher admission Functional Independence Measure Motor scores and education less than high school diploma. RTAC occurrence during rehabilitation was significantly associated with longer RLOS and smaller likelihood of discharge home. Conclusion(s) Approximately 9% of patients with TBI experience RTAC during inpatient rehabilitation for various medical and surgical reasons. This information may help inform interventions aimed at reducing interruptions in rehabilitation due to RTAC. RTACs were associated with longer RLOS and discharge to an institutional setting. PMID:26212405

  17. Adrenal insufficiency presenting as hypercalcemia and acute kidney injury

    PubMed Central

    Ahn, Seung Won; Kim, Tong Yoon; Lee, Sangmin; Jeong, Jeong Yeon; Shim, Hojoon; Han, Yu min; Choi, Kyu Eun; Shin, Seok Joon; Yoon, Hye Eun

    2016-01-01

    Adrenal insufficiency is an uncommon cause of hypercalcemia and not easily considered as an etiology of adrenal insufficiency in clinical practice, as not all cases of adrenal insufficiency manifest as hypercalcemia. We report a case of secondary adrenal insufficiency presenting as hypercalcemia and acute kidney injury in a 66-year-old female. The patient was admitted to the emergency department with general weakness and poor oral intake. Hypercalcemia (11.5 mg/dL) and moderate renal dysfunction (serum creatinine 4.9 mg/dL) were shown in her initial laboratory findings. Studies for malignancy and hyperparathyroidism showed negative results. Basal cortisol and adrenocorticotropic hormone levels and adrenocorticotropic hormone stimulation test confirmed the diagnosis of adrenal insufficiency. With the administration of oral hydrocortisone, hypercalcemia was dramatically resolved within 3 days. This case shows that adrenal insufficiency may manifest as hypercalcemia and acute kidney injury, which implicates that adrenal insufficiency should be considered a cause of hypercalcemia in clinical practice. PMID:27536162

  18. Electrolyte disturbances and acute kidney injury in patients with cancer.

    PubMed

    Lameire, Norbert; Van Biesen, Wim; Vanholder, Raymond

    2010-11-01

    The interrelation between kidney disease and cancer is complex and reciprocal. Among the most frequent cancer-associated kidney diseases are the electrolyte and acid-base disturbances, which occur frequently and often are associated with an ominous prognosis, and acute kidney injury. Tumor lysis syndrome is a potentially life-threatening condition that frequently occurs in patients with a high tumor burden and high cellular turnover after cytotoxic therapy (including steroids in steroid-sensitive hematologic malignancies). Electrolyte and acid-base disturbances are the consequence of neoplastic spread, anticancer treatment, or, more rarely, paraneoplastic phenomena of all types of tumors. This article reviews hyponatremia and hypernatremia, hypokalemia and hyperkalemia, hypomagnesemia, hypercalcemia and hypocalcemia, hypophosphatemia, and the most important disturbances in acid-base balance in cancer patients. Acute kidney injury (AKI) is a frequent occurrence in cancer patients and has the potential to substantially alter the outcome of patients with cancer and jeopardize their chances of receiving optimal cancer treatment and a potential cure. As in many other circumstances, the etiology of AKI in cancer patients is multifactorial. Initiation and/or continuation of dialysis in the AKI cancer patient should be based on the general clinical condition and overall life expectancy and the personal patient expectations on quality of life after eventual recovery.

  19. Acute kidney injury by radiographic contrast media: pathogenesis and prevention.

    PubMed

    Andreucci, Michele; Faga, Teresa; Pisani, Antonio; Sabbatini, Massimo; Michael, Ashour

    2014-01-01

    It is well known that iodinated radiographic contrast media may cause kidney dysfunction, particularly in patients with preexisting renal impairment associated with diabetes. This dysfunction, when severe, will cause acute renal failure (ARF). We may define contrast-induced Acute Kidney Injury (AKI) as ARF occurring within 24-72 hrs after the intravascular injection of iodinated radiographic contrast media that cannot be attributed to other causes. The mechanisms underlying contrast media nephrotoxicity have not been fully elucidated and may be due to several factors, including renal ischaemia, particularly in the renal medulla, the formation of reactive oxygen species (ROS), reduction of nitric oxide (NO) production, and tubular epithelial and vascular endothelial injury. However, contrast-induced AKI can be prevented, but in order to do so, we need to know the risk factors. We have reviewed the risk factors for contrast-induced AKI and measures for its prevention, providing a long list of references enabling readers to deeply evaluate them both.

  20. Microbiota protects mice against acute alcohol-induced liver injury

    PubMed Central

    Chen, Peng; Miyamoto, Yukiko; Mazagova, Magdalena; Lee, Kuei-Chuan; Eckmann, Lars; Schnabl, Bernd

    2015-01-01

    Background Chronic alcohol abuse is associated with intestinal bacterial overgrowth, increased intestinal permeability, and translocation of microbial products from the intestine to the portal circulation and liver. Translocated microbial products contribute to experimental alcoholic liver disease. Aim To investigate the physiological relevance of the intestinal microbiota in alcohol-induced liver injury. Methods We subjected germ-free and conventional C57BL/6 mice to a model of acute alcohol exposure that mimics binge drinking. Results Germ-free mice showed significantly greater liver injury and inflammation after oral gavage of ethanol compared with conventional mice. In parallel, germ-free mice exhibited increased hepatic steatosis and upregulated expression of genes involved in fatty acid and triglyceride synthesis compared with conventional mice after acute ethanol administration. The absence of microbiota was also associated with increased hepatic expression of ethanol metabolizing enzymes, which led to faster ethanol elimination from the blood and lower plasma ethanol concentrations. Intestinal levels of ethanol metabolizing genes showed regional expression differences, and were overall higher in germ-free relative to conventional mice. Conclusion Our findings indicate that absence of the intestinal microbiota increases hepatic ethanol metabolism and the susceptibility to binge-like alcohol drinking. PMID:26556636

  1. Acute kidney injury in patients with chronic liver disease

    PubMed Central

    Rognant, Nicolas

    2015-01-01

    Acute kidney injury (AKI) is a frequent clinical event in patients with liver disease, compounding their prognosis. Furthermore, it is likely that the occurrence of AKI has a detrimental impact on the subsequent renal function and the long-term survival of these patients. Recently, some authors advocated the use of new diagnostic criteria for detecting acute kidney injury in patients with cirrhosis. These criteria are based on the rapidity and extent of the creatinine increase comparing to the basal creatinine and also on the kinetics of diuresis decrease. Although their validity in this population requires further studies to be clearly established, these new criteria could have two advantages: (1) to allow earlier diagnosis of AKI and, thus, hepatorenal syndrome for which earlier intervention could improve patients’ survival; and (2) to promote more intensive monitoring of renal function in these patients with high risk of AKI. Finally, recent practice guidelines about the prevention and treatment of general AKI have been published which should be useful in optimising the management of AKI in cirrhotic patients. PMID:25954481

  2. Collective epithelial migration drives kidney repair after acute injury.

    PubMed

    Palmyre, Aurélien; Lee, Jeongeun; Ryklin, Gennadiy; Camarata, Troy; Selig, Martin K; Duchemin, Anne-Laure; Nowak, Paul; Arnaout, M Amin; Drummond, Iain A; Vasilyev, Aleksandr

    2014-01-01

    Acute kidney injury (AKI) is a common and significant medical problem. Despite the kidney's remarkable regenerative capacity, the mortality rate for the AKI patients is high. Thus, there remains a need to better understand the cellular mechanisms of nephron repair in order to develop new strategies that would enhance the intrinsic ability of kidney tissue to regenerate. Here, using a novel, laser ablation-based, zebrafish model of AKI, we show that collective migration of kidney epithelial cells is a primary early response to acute injury. We also show that cell proliferation is a late response of regenerating kidney epithelia that follows cell migration during kidney repair. We propose a computational model that predicts this temporal relationship and suggests that cell stretch is a mechanical link between migration and proliferation, and present experimental evidence in support of this hypothesis. Overall, this study advances our understanding of kidney repair mechanisms by highlighting a primary role for collective cell migration, laying a foundation for new approaches to treatment of AKI.

  3. Transfusion-related acute lung injury: a review.

    PubMed

    Looney, Mark R; Gropper, Michael A; Matthay, Michael A

    2004-07-01

    Transfusion-related acute lung injury (TRALI) is an underreported complication of transfusion therapy, and it is the third most common cause of transfusion-associated death. TRALI is defined as noncardiogenic pulmonary edema temporally related to transfusion therapy. The diagnosis of TRALI relies on excluding other diagnoses such as sepsis, volume overload, and cardiogenic pulmonary edema. Supportive diagnostic evidence includes identifying neutrophil or human leukocyte antigen (HLA) antibodies in the donor or recipient plasma. All plasma-containing blood products have been implicated in TRALI, with the majority of cases linked to whole blood, packed RBCs, platelets, and fresh-frozen plasma. The pathogenesis of TRALI may be explained by a "two-hit" hypothesis, with the first "hit" being a predisposing inflammatory condition commonly present in the operating room or ICU. The second hit may involve the passive transfer of neutrophil or HLA antibodies from the donor or the transfusion of biologically active lipids from older, cellular blood products. Treatment is supportive, with a prognosis substantially better than most causes of clinical acute lung injury.

  4. Acute kidney injury in pregnancy-current status.

    PubMed

    Acharya, Anjali; Santos, Jolina; Linde, Brian; Anis, Kisra

    2013-05-01

    Pregnancy-related acute kidney injury (PR-AKI) causes significant maternal and fetal morbidity and mortality. Management of PR-AKI warrants a thorough understanding of the physiologic adaptations in the kidney and the urinary tract. Categorization of etiologies of PR-AKI is similar to that of acute kidney injury (AKI) in the nonpregnant population. The causes differ between developed and developing countries, with thrombotic microangiopathies (TMAs) being common in the former and septic abortion and puerperal sepsis in the latter. The incidence of PR-AKI is reported to be on a decline, but there is no consensus on the exact definition of the condition. The physiologic changes in pregnancy make diagnosis of PR-AKI difficult. Newer biomarkers are being studied extensively but are not yet available for clinical use. Early and accurate diagnosis is necessary to improve maternal and fetal outcomes. Timely identification of "at-risk" individuals and treatment of underlying conditions such as sepsis, preeclampsia, and TMAs remain the cornerstone of management. Questions regarding renal replacement therapy such as modality, optimal prescription, and timing of initiation in PR-AKI remain unclear. There is a need to systematically explore these variables to improve care of women with PR-AKI.

  5. Neurological findings in pediatric penetrating head injury at a university teaching hospital in Durban, South Africa: a 23-year retrospective study.

    PubMed

    Muballe, Kadhaya David; Hardcastle, Timothy; Kiratu, Erastus

    2016-11-01

    OBJECTIVES Penetrating traumatic brain injuries (TBIs) can be divided into gunshot wounds or stab wounds based on the mechanisms of injury. Pediatric penetrating TBIs are of major concern as many parental and social factors may be involved in the causation. The authors describe the penetrating cranial injuries in pediatric patient subgroups at risk and presenting to the Department of Neurosurgery at the University of KwaZulu-Natal, by assessment of the Glasgow Coma Scale (GCS) score and review of the common neurological manifestations including cranial nerve abnormalities. METHODS The authors performed a retrospective chart review of children who presented with penetrating TBIs between 1985 and 2007 at a university teaching hospital. Descriptive statistical analysis with univariate and multivariate logistic regression was used to assess the variables. RESULTS Out of 223 children aged 16 years and younger with penetrating TBIs seen during the study period, stab wounds were causal in 127 (57%) of the patients, while gunshot injuries were causal in 96 (43%). Eighty-four percent of the patients were male. Apart from abnormal GCS scores, other neurological abnormalities were noted in 109 (48.9%) of the patients, the most common being cranial nerve deficits (22.4%) and hemiparesis. There was a strong correlation between left-sided stab wounds and development of seizures. The mean age of patients with neurological abnormalities was 11.72 years whereas that of patients with no neurological abnormalities was 8.96 years. CONCLUSIONS Penetrating head injuries in children are not as uncommon as previously thought. There was no correlation between the age group of the patients and the mechanism of injury, which implies that stab or gunshot injuries could occur in any of our pediatric population with the same frequency. While gunshot injuries accounted for 56% of the patient population, stab injuries still accounted for 44%. Following penetrating head injuries, neurological

  6. Adenosine 2A receptors in acute kidney injury.

    PubMed

    Vincent, I S; Okusa, M D

    2015-07-01

    Acute kidney injury (AKI) is an important clinical problem that may lead to death and for those who survive, the sequelae of AKI include loss of quality of life, chronic kidney disease and end-stage renal disease. The incidence of AKI continues to rise without clear successes in humans for the pharmacological prevention of AKI or treatment of established AKI. Dendritic cells and macrophages are critical early initiators of innate immunity in the kidney and orchestrate inflammation subsequent to ischaemia-reperfusion injury. These innate cells are the most abundant leucocytes present in the kidney, and they represent a heterogeneous population of cells that are capable of responding to cues from the microenvironment derived from pathogens or endogenous inflammatory mediators such as cytokines or anti-inflammatory mediators such as adenosine. Lymphocyte subsets such as natural killer T cells and Tregs also play roles in regulating ischaemic injury by promoting and suppressing inflammation respectively. Adenosine, produced in response to IR, is generally considered as a protective signalling molecule and elicits its physiological responses through four distinct adenosine receptors. However, its short half-life, lack of specificity and rapid metabolism limit the use of adenosine as a therapeutic agent. These adenosine receptors play various roles in regulating the activity of the aforementioned hematopoietic cells in elevated levels of adenosine such as during hypoxia. This review focuses on the importance of one receptor, the adenosine 2A subtype, in blocking inflammation associated with AKI.

  7. Vitamin D deficiency aggravates ischemic acute kidney injury in rats

    PubMed Central

    de Bragança, Ana Carolina; Volpini, Rildo A; Canale, Daniele; Gonçalves, Janaína G; Shimizu, Maria Heloisa M; Sanches, Talita R; Seguro, Antonio C; Andrade, Lúcia

    2015-01-01

    Vitamin D deficiency (VDD) increases the risk of death in hospitalized patients. Renal ischemia/reperfusion injury (IRI) induces acute kidney injury (AKI), which activates cell cycle inhibitors, including p21, a cyclin-dependent kinase inhibitor and genomic target of 25-hydroxyvitamin D, which is in turn a potent immunomodulator with antiproliferative effects. In this study, we assess the impact of VDD in renal IRI. Wistar rats were divided into groups, each evaluated for 30 days: control (receiving a standard diet); VDD (receiving a vitamin D-free diet); IRI (receiving a standard diet and subjected to 45-min bilateral renal ischemia on day 28); and VDD + IRI (receiving a vitamin D-free diet and subjected to 45-min bilateral renal ischemia on day 28). At 48 h after IRI, animals were euthanized; blood, urine, and kidney tissue samples were collected. Compared with IRI rats, VDD + IRI rats showed a more severe decrease in glomerular filtration rate, greater urinary protein excretion, a higher kidney/body weight ratio and lower renal aquaporin 2 expression, as well as greater morphological damage, characterized by increased interstitial area and tubular necrosis. Our results suggest that the severity of tubular damage in IRI may be associated with downregulation of vitamin D receptors and p21. VDD increases renal inflammation, cell proliferation and cell injury in ischemic AKI. PMID:25780095

  8. Biomarkers in acute kidney injury - pathophysiological basis and clinical performance.

    PubMed

    Schrezenmeier, E V; Barasch, J; Budde, K; Westhoff, T; Schmidt-Ott, K M

    2017-03-01

    Various biomarkers of acute kidney injury (AKI) have been discovered and characterized in the recent past. These molecules can be detected in urine or blood and signify structural damage to the kidney. Clinically, they are proposed as adjunct diagnostics to serum creatinine and urinary output to improve the early detection, differential diagnosis and prognostic assessment of AKI. The most obvious requirements for a biomarker include its reflection of the underlying pathophysiology of the disease. Hence, a biomarker of AKI should derive from the injured kidney and reflect a molecular process intimately connected with tissue injury. Here, we provide an overview of the basic pathophysiology, the cellular sources and the clinical performance of the most important currently proposed biomarkers of AKI: neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), interleukin-18 (IL-18), insulin-like growth factor-binding protein 7 (IGFBP7), tissue inhibitor of metalloproteinase 2 (TIMP-2) and calprotectin (S100A8/9). We also acknowledge each biomarker's advantages and disadvantages as well as important knowledge gaps and perspectives for future studies.

  9. Traumatic forequarter amputation associated acute lung injury (ALI): report of one case.

    PubMed

    Liang, K; Gan, X; Deng, Z

    2012-07-01

    One case of traumatic forequarter amputation associated acute lung injury (ALI) was presented. A discussion reviewing the treatment guidelines for this devastating injury, and pointing out the importance of supporting the lung and preventing the development of acute respiratory distress syndrome (ARDS) was included.

  10. Acute kidney injury requiring hemodialysis in the tropics.

    PubMed

    Okunola, Oluyomi O; Ayodele, Olugbenga E; Adekanle, Adebode D

    2012-11-01

    The morbidity and mortality from acute kidney injury (AKI) have remained relatively high over the last six decades. The triad of infections, nephrotoxins and obstetric complications are still major causes of acute kidney injury in the tropics. This retrospective study is a five-year audit of acute renal failure (ARF) (or stage 3 AKI) in patients requiring hemodialysis at the renal unit of the Department of Medicine of the Ladoke Akintola University of Technology (LAUTECH) Teaching Hospital, Osogbo, Nigeria. A total of 80 patients with AKI were treated over a five-year period at our center, of which 45 (56.2%) were in ARF, i.e. stage 3 AKI requiring hemodialysis. There were 24 males and 21 females. The most common cause of ARF among the patients was sepsis syndrome 16 (35.5%), while pregnancy-related cases accounted for 15 (33.3%) and nephrotoxins for 6 (13.3%). Five (33%) of the 15 pregnancy-related patients survived, and all were cases of septic abortion. Of the other 10 patients that did not survive, three (30%) had post-partum hemorrhage and seven (70%) post-partum eclampsia. In all, the mortality rate among our AKI presenting for hemodialysis at our center over a given year period was 28.8%. Majority of these were eclampsia related. The causes of ARF still remain the same in the tropics, eclampsia portends poor prognosis. Concerted efforts should be made at limiting this trend by active preventive services and early recognition of high-risk obstetrics cases.

  11. The intensive care medicine agenda on acute kidney injury.

    PubMed

    Pickkers, Peter; Ostermann, Marlies; Joannidis, Michael; Zarbock, Alexander; Hoste, Eric; Bellomo, Rinaldo; Prowle, John; Darmon, Michael; Bonventre, Joseph V; Forni, Lui; Bagshaw, Sean M; Schetz, Miet

    2017-01-30

    Acute kidney injury (AKI) is a common complication in the critically ill. Current standard of care mainly relies on identification of patients at risk, haemodynamic optimization, avoidance of nephrotoxicity and the use of renal replacement therapy (RRT) in established AKI. The detection of early biomarkers of renal tissue damage is a recent development that allows amending the late and insensitive diagnosis with current AKI criteria. Increasing evidence suggests that the consequences of an episode of AKI extend long beyond the acute hospitalization. Citrate has been established as the anticoagulant of choice for continuous RRT. Conflicting results have been published on the optimal timing of RRT and on the renoprotective effect of remote ischaemic preconditioning. Recent research has contradicted that acute tubular necrosis is the common pathology in AKI, that septic AKI is due to global kidney hypoperfusion, that aggressive fluid therapy benefits the kidney, that vasopressor therapy harms the kidney and that high doses of RRT improve outcome. Remaining uncertainties include the impact of aetiology and clinical context on pathophysiology, therapy and prognosis, the clinical benefit of biomarker-driven interventions, the optimal mode of RRT to improve short- and long-term patient and kidney outcomes, the contribution of AKI to failure of other organs and the optimal approach for assessing and promoting renal recovery. Based on the established gaps in current knowledge the trials that must have priority in the coming 10 years are proposed together with the definition of appropriate clinical endpoints.

  12. A case of acute paraneoplastic neurological syndrome in BRAF mutant metastatic melanoma.

    PubMed

    Lee, Shu F; Atkinson, Victoria

    2016-08-01

    A 58-year-old man with indolent metastatic BRAF mutant melanoma presented with several days' history of progressive ataxia and dysdiadochokinesia. His PET/computed tomography restaging scan indicated two new fluorine-18-fluorodeoxyglucose-avid mesenteric lymph nodes. Meanwhile, his MRI brain and whole spine were within normal limits. A lumbar puncture indicated an elevated protein level with a normal cell count and negative paraneoplastic antibodies. Because of the lack of an alternative differential, the diagnosis of paraneoplastic syndrome was made. He was started on high-dose corticosteroids as well as dabrafenib and trametinib. Despite this, his neurological symptoms continued to progress. Consequently, he was trialed on a course of intravenous immunoglobulin, which stabilized his symptoms. He continued to improve over several weeks, with near-complete resolution of all his neurological symptoms, and showed a complete radiological response of his disease. To our knowledge, this is the first reported case of paraneoplastic neurological syndrome with mixed neurology associated with BRAF mutant cutaneous melanoma that responded to BRAF targeted therapy.

  13. An unusual cause of acute kidney injury due to oxalate nephropathy in systemic scleroderma.

    PubMed

    Mascio, Heather M; Joya, Christie A; Plasse, Richard A; Baker, Thomas P; Flessner, Michael F; Nee, Robert

    2015-08-01

    Oxalate nephropathy is an uncommon cause of acute kidney injury. Far rarer is its association with scleroderma, with only one other published case report in the literature. We report a case of a 75-year-old African-American female with a history of systemic scleroderma manifested by chronic pseudo-obstruction and small intestinal bacterial overgrowth (SIBO) treated with rifaximin, who presented with acute kidney injury with normal blood pressure. A renal biopsy demonstrated extensive acute tubular injury with numerous intratubular birefringent crystals, consistent with oxalate nephropathy. We hypothesize that her recent treatment with rifaximin for SIBO and decreased intestinal transit time in pseudo-obstruction may have significantly increased intestinal oxalate absorption, leading to acute kidney injury. Oxalate nephropathy should be considered in the differential diagnosis of acute kidney injury in scleroderma with normotension, and subsequent evaluation should be focused on bowel function to include alterations in gut flora due to antibiotic administration.

  14. [Community-based rehabilitation and outpatient care for patients with acquired brain injury and chronic neurological disability in Germany: continuing support for social participation and re-integration in the neurological care system?].

    PubMed

    Reuther, P; Hendrich, A; Kringler, W; Vespo, E

    2012-12-01

    In Germany a number of patients who are suffering from acquired brain injury and chronic neurological disability are either undersupplied or exposed to inappropriate care in their social environment. The number of these patients is increasing due to the changes in the procedures of care and due to demographic factors. While acute medical care and early rehabilitative treatment is accessible throughout the German health care system the necessary multimodal and competent care is rare or absent in the social participative sites such as life and occupational environments of the patients. The complex impairment of the brain, the central organ for sensorial, executive and other cognitive functions of human beings, renders the affected patient an exception in the system of medical and social care - this has only inadequately been considered in the past. The authors explain the necessity to disclose the status of a "human-with acquired-brain damage (Mensch-mit-erworbener-Hirnschädigung, MeH)" explicitly as severely disabled. The paper recommends a number of structural and procedural elements that have proven to overcome the insufficient or inappropriate support in integrating the patients suffering from acquired brain injury and chronic neurological disability in their social environment as well as for a demand-focused support with sustainable rehabilitative and ambulant follow-up procedures. Comparisons with other developed health care systems and international guidelines show that with organizing of early-supported-discharge, community-ambulation, shared-care and community-based-rehabilitation these problems have long since been identified elsewhere. Community-based and resident-oriented concepts have already been systematically implemented. In order to achieve the necessary support for the individual patient, a nation-wide development is necessary in Germany to perform the principles of the German social code and the principles of the Convention on the Rights of

  15. Metallothionein-induced zinc partitioning exacerbates hyperoxic acute lung injury

    PubMed Central

    Lee, Sang-Min; McLaughlin, Joseph N.; Frederick, Daniel R.; Zhu, Lin; Thambiayya, Kalidasan; Wasserloos, Karla J.; Kaminski, Iris; Pearce, Linda L.; Peterson, Jim; Li, Jin; Latoche, Joseph D.; Peck Palmer, Octavia M.; Stolz, Donna Beer; Fattman, Cheryl L.; Alcorn, John F.; Oury, Tim D.; Angus, Derek C.; Pitt, Bruce R.

    2013-01-01

    Hypozincemia, with hepatic zinc accumulation at the expense of other organs, occurs in infection, inflammation, and aseptic lung injury. Mechanisms underlying zinc partitioning or its impact on extrahepatic organs are unclear. Here we show that the major zinc-binding protein, metallothionein (MT), is critical for zinc transmigration from lung to liver during hyperoxia and preservation of intrapulmonary zinc during hyperoxia is associated with an injury-resistant phenotype in MT-null mice. Particularly, lung-to-liver zinc ratios decreased in wild-type (WT) and increased significantly in MT-null mice breathing 95% oxygen for 72 h. Compared with female adult WT mice, MT-null mice were significantly protected against hyperoxic lung injury indicated by reduced inflammation and interstitial edema, fewer necrotic changes to distal airway epithelium, and sustained lung function at 72 h hyperoxia. Lungs of MT-null mice showed decreased levels of immunoreactive LC3, an autophagy marker, compared with WT mice. Analysis of superoxide dismutase (SOD) activity in the lungs revealed similar levels of manganese-SOD activity between strains under normoxia and hyperoxia. Lung extracellular SOD activity decreased significantly in both strains at 72 h of hyperoxia, although there was no difference between strains. Copper-zinc-SOD activity was ∼4× higher under normoxic conditions in MT-null compared with WT mice but was not affected in either group by hyperoxia. Collectively the data suggest that genetic deletion of MT-I/II in mice is associated with compensatory increase in copper-zinc-SOD activity, prevention of hyperoxia-induced zinc transmigration from lung to liver, and hyperoxia-resistant phenotype strongly associated with differences in zinc homeostasis during hyperoxic acute lung injury. PMID:23275622

  16. Histone lysine crotonylation during acute kidney injury in mice

    PubMed Central

    Ruiz-Andres, Olga; Sanchez-Niño, Maria Dolores; Cannata-Ortiz, Pablo; Ruiz-Ortega, Marta; Egido, Jesus; Ortiz, Alberto; Sanz, Ana Belen

    2016-01-01

    ABSTRACT Acute kidney injury (AKI) is a potentially lethal condition for which no therapy is available beyond replacement of renal function. Post-translational histone modifications modulate gene expression and kidney injury. Histone crotonylation is a recently described post-translational modification. We hypothesized that histone crotonylation might modulate kidney injury. Histone crotonylation was studied in cultured murine proximal tubular cells and in kidneys from mice with AKI induced by folic acid or cisplatin. Histone lysine crotonylation was observed in tubular cells from healthy murine and human kidney tissue. Kidney tissue histone crotonylation increased during AKI. This was reproduced by exposure to the protein TWEAK in cultured tubular cells. Specifically, ChIP-seq revealed enrichment of histone crotonylation at the genes encoding the mitochondrial biogenesis regulator PGC-1α and the sirtuin-3 decrotonylase in both TWEAK-stimulated tubular cells and in AKI kidney tissue. To assess the role of crotonylation in kidney injury, crotonate was used to increase histone crotonylation in cultured tubular cells or in the kidneys in vivo. Crotonate increased the expression of PGC-1α and sirtuin-3, and decreased CCL2 expression in cultured tubular cells and healthy kidneys. Systemic crotonate administration protected from experimental AKI, preventing the decrease in renal function and in kidney PGC-1α and sirtuin-3 levels as well as the increase in CCL2 expression. For the first time, we have identified factors such as cell stress and crotonate availability that increase histone crotonylation in vivo. Overall, increasing histone crotonylation might have a beneficial effect on AKI. This is the first observation of the in vivo potential of the therapeutic manipulation of histone crotonylation in a disease state. PMID:27125278

  17. Hepatic cryoablation-induced acute lung injury: histopathologic findings.

    PubMed

    Washington, K; Debelak, J P; Gobbell, C; Sztipanovits, D R; Shyr, Y; Olson, S; Chapman, W C

    2001-01-01

    We have previously shown that hepatic cryoablation (cryo), but not partial hepatectomy, induces a systemic inflammatory response, with distant organ injury and overproduction of NF-kappaB-dependent cytokines. Serum tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-2 (MIP-2) levels are markedly increased 1 h and beyond after cryo compared with partial hepatectomy where no elevation occurs. NF-kappaB activation (by electrophoretic mobility shift assay) is strikingly increased in the noncryo liver (but not in the lung) at 30 min and in both the liver and lung tissue 1 h after cryo, returning to the baseline by 2 h and beyond. The current study investigated the histopathologic changes associated with cryoablation-induced acute lung injury. Animals underwent 35% hepatic resection or a similar volume hepatic cryo and were sacrificed at 1, 2, 6, and 24 h. Pulmonary histologic features were assessed using hematoxylin and eosin and immunoperoxidase staining with a macrophage-specific antibody (anti-lysozyme, 1:200 dilution, Dako, Carpinteria, CA). The following features were graded semiquantitatively (0-3): perivascular lymphoid cuffs, airspace edema and hemorrhage, margination of neutrophils within pulmonary vasculature, and the presence of macrophages with foamy cytoplasm in the pulmonary interstitium. Hepatic resection (n = 21) resulted in slight perivascular edema at 1, 2, 6, and 24 h post-resection, but there were no other significant changes. Pulmonary findings after hepatic cryo (n = 22) included prominent perivascular lymphoid cuffs 1 and 2 h following hepatic injury that were not present at any other time point (P 0.01). Marginating PMNs and foamy macrophages were more common after cryo at all time points (P<0.05, cryo vs resection). Severe lung injury, as evidenced by airspace edema and parenchymal hemorrhage, was present in four of six (67%) animals at 24 h (P 0.03). In follow-up studies immediate resection (n = 15) of the cryo

  18. Development of an Animal Model of Thoracolumbar Burst Fracture Induced Acute Spinal Cord Injury

    DTIC Science & Technology

    2015-05-01

    AWARD NUMBER: W81XWH-14-2-0013 TITLE: DEVELOPMENT OF AN ANIMAL MODEL OF THORACOLUMBAR BURST FRACTURE - INDUCED ACUTE SPINAL CORD INJURY...2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER DEVELOPMENT OF AN ANIMAL MODEL OF THORACOLUMBAR BURST FRACTURE -INDUCED ACUTE SPINAL CORD INJURY 5b...leads to permanent disability following traumatic spine injury. A dramatic increase in blast related spinal burst fracture has been observed in

  19. Neurologic morbidity and quality of life in survivors of childhood acute lymphoblastic leukemia: a prospective cross-sectional study

    PubMed Central

    Khan, Raja B.; Hudson, Melissa M.; Ledet, Davonna S.; Morris, E. Brannon; Pui, Ching-Hon; Howard, Scott C.; Krull, Kevin R.; Hinds, Pamela S.; Crom, Debbie; Browne, Emily; Zhu, Liang; Rai, Shesh; Srivastava, Deokumar; Ness, Kirsten K.

    2014-01-01

    Purpose Childhood acute lymphoblastic leukemia (ALL) is treated with potentially neurotoxic drugs and neurologic complications in long-term survivors are inadequately studied. This study investigated neurologic morbidity and its effect on quality of life in long-term survivors of childhood ALL. Methods Prospective, single institution, cross-sectional, institutional review board-approved study of long-term ALL survivors. Participants were recruited from institutional clinics. Participants answered an investigator-administered questionnaire followed by evaluation by a neurologist. Quality of life (QOL) was also assessed. Results Of the 162 participants recruited over a 3-year period, 83.3 % reported at least one neurologic symptom of interest, 16.7 % had single symptom, 11.1 % had two symptoms, and 55.6 % had three or more symptoms. Symptoms were mild and disability was low in the majority of participants with neurologic symptoms. Median age at ALL diagnosis was 3.9 years (0.4–18.6), median age at study enrollment was 15.7 years (6.9–28.9), and median time from completion of ALL therapy was 7.4 years (1.9–20.3). On multivariable analyses, female sex correlated with presence of dizziness, urinary incontinence, constipation, and neuropathy; use of≥10 doses of triple intrathecal chemotherapy correlated with uri-nary incontinence, back pain, and neuropathy; cranial radiation with ataxia; history of ALL relapse with fatigue; and CNS leukemia at diagnosis with seizures. Decline in mental QOL was associated with migraine and tension type headaches, while physical QOL was impaired by presence of dizziness and falls. Overall, good QOL and physical function was maintained by a majority of participants. Conclusions Neurologic symptoms were present in 83 % long-term ALL survivors. Symptoms related morbidity and QOL impairment is low in majority of survivors. Female sex, ≥10 doses of intrathecal chemotherapy, and history of ALL relapse predispose to impaired QOL

  20. Taurine attenuates hippocampal and corpus callosum damage, and enhances neurological recovery after closed head injury in rats.

    PubMed

    Gu, Y; Zhao, Y; Qian, K; Sun, M

    2015-04-16

    The protective effects of taurine against closed head injury (CHI) have been reported. This study was designed to investigate whether taurine reduced white matter damage and hippocampal neuronal death through suppressing calpain activation after CHI in rats. Taurine (50 mg/kg) was administered intravenously 30 min and 4 h again after CHI. It was found that taurine lessened the corpus callosum damage, attenuated the neuronal cell death in hippocampal CA1 and CA3 subfields and improved the neurological functions 7 days after CHI. Moreover, it suppressed the over-activation of calpain, enhanced the levels of calpastatin, and reduced the degradation of neurofilament heavy protein, myelin basic protein and αII-spectrin in traumatic tissue 24 h after CHI. These data confirm the protective effects of taurine against gray and white matter damage due to CHI, and suggest that down-regulating calpain activation could be one of the protective mechanisms of taurine against CHI.

  1. Matrix Metalloproteinases as a Therapeutic Target to Improve Neurologic Recovery After Spinal Cord Injury

    DTIC Science & Technology

    2014-10-01

    journal.pone.0096408 Editor: Hatem E. Sabaawy, Rutgers- Robert wood Johnson Medical School, United States of America Received January 23, 2014; Accepted April 7...functional recovery after spinal cord injury. Journal of neurochemistry 121: 818–829. 8. Stirling DP, Yong VW (2008) Dynamics of the inflammatory response

  2. An unusual case of reversible acute kidney injury due to chlorine dioxide poisoning.

    PubMed

    Bathina, Gangadhar; Yadla, Manjusha; Burri, Srikanth; Enganti, Rama; Prasad Ch, Rajendra; Deshpande, Pradeep; Ch, Ramesh; Prayaga, Aruna; Uppin, Megha

    2013-09-01

    Chlorine dioxide is a commonly used water disinfectant. Toxicity of chlorine dioxide and its metabolites is rare. In experimental studies, it was shown that acute and chronic toxicity were associated with insignificant hematological changes. Acute kidney injury due to chlorine dioxide was not reported. Two cases of renal toxicity due to its metabolites, chlorate and chlorite were reported. Herein, we report a case of chlorine dioxide poisoning presenting with acute kidney injury.

  3. Injury to skeletal muscle of mice following acute and sub-acute pregabalin exposure

    PubMed Central

    Moshiri, Mohammad; Moallem, Seyed Adel; Attaranzadeh, Armin; Saberi, Zahra; Etemad, Leila

    2017-01-01

    Objective(s): Pregabalin (PGB) is a new antiepileptic drug that has received FDA approval for patient who suffers from central neuropathic pain, partial seizures, generalized anxiety disorder, fibromyalgia and sleep disorders. This study was undertaken to evaluate the possible adverse effects of PGB on the muscular system of mice. Materials and Methods: To evaluate the effect of PGB on skeletal muscle, the animals were exposed to a single dose of 1, 2 or 5 g /kg or daily doses of 20, 40 or 80 mg/kg for 21 days, intraperitoneally (IP). Twaenty-four hr after the last drug administration, all animals were sacrificed. The level of fast-twitch skeletal muscle troponin I and CK-MM activity were evaluated in blood as an indicator of muscle injury. Skeletal muscle pathological findings were also reported as scores ranging from 1 to 3 based on the observed lesion. Results: In the acute and sub-acute toxicity assay IP injection of PGB significantly increased the activity and levels of CK-MM and fsTnI compared to the control group. Sub-acute exposure to PGB caused damages that include muscle atrophy, infiltration of inflammatory cells and cell degeneration. Conclusion: PGB administration especially in long term care causes muscle atrophy with infiltration of inflammatory cells and cell degeneration. The fsTnI and CK-MM are reliable markers in PGB-related muscle injury. The exact mechanisms behind the muscular damage are unclear and necessitate further investigations. PMID:28392896

  4. Acute Kidney Injury Associated With Vancomycin When Laxity Leads to Injury and Findings on Kidney Biopsy.

    PubMed

    Katikaneni, Madhavi; Lwin, Lin; Villanueva, Hugo; Yoo, Jinil

    2016-01-01

    The issue of vancomycin-induced acute kidney injury (AKI) has resurged with the use of intravenous vancomycin as a first-line antibiotic, often for prolonged periods of time for the management of serious methicillin-resistant Staphylococcus aureus infections, and with a higher recommended trough level (15-20 μg/mL). We have observed 3 patients on intravenous vancomycin who developed very high trough levels (>40 μg/mL) and severe (stage 3) AKI. Those 3 patients underwent kidney biopsy for unresolving AKI, which revealed findings compatible with acute tubular necrosis. The first patient initially developed asymptomatic acute interstitial nephritis because of a concomitant antibiotic that caused worsening of kidney function, and the dose of vancomycin was not properly adjusted while staying at the nursing home. The second was an emaciated patient (BMI, 14) whose serum creatinine level was a deceptive marker of kidney function for the proper dosing of vancomycin, resulting in a toxic level. The third patient developed vancomycin-related AKI on an initially high therapeutic level, which then contributed to further rising in vancomycin level and subsequently causing severe AKI. One patient required hemodialysis, but all 3 patients ultimately recovered their kidney function significantly. A regular monitoring (preferably twice weekly) of serum creatinine and vancomycin trough level is advisable to minimize vancomycin-associated AKI, primarily acute tubular necrosis, for patients requiring prolonged administration of vancomycin (>2 weeks) on the currently recommended higher therapeutic trough levels (>15 μg/mL).

  5. Necroptosis in acute kidney injury: a shedding light

    PubMed Central

    Wang, S; Zhang, C; Hu, L; Yang, C

    2016-01-01

    Acute kidney injury (AKI) is a common and severe clinical condition with a heavy healthy burden around the world. In spite of supportive therapies, the mortality associated with AKI remains high. Our limited understanding of the complex cell death mechanism in the process of AKI impedes the development of desirable therapeutics. Necroptosis is a recently identified novel form of cell death contributing to numerable diseases and tissue damages. Increasing evidence has suggested that necroptosis has an important role in the pathogenesis of various types of AKI. Therefore, we present here the signaling pathways and main regulators of necroptosis that are potential candidate for therapeutic strategies. Moreover, we emphasize on the potential role and corresponding mechanisms of necroptosis in AKI based on recent advances, and also discuss the possible therapeutic regimens based on manipulating necroptosis. Taken together, the progress in this field sheds new light into the prevention and management of AKI in clinical practice. PMID:26938298

  6. Hypothermia-induced acute kidney injury in an elderly patient.

    PubMed

    Yoon, Hyun Ju; Kim, Mun Chul; Park, Jae Woo; Yang, Min A; Lee, Cheon Beom; Sun, In O; Lee, Kwang Young

    2014-01-01

    Hypothermia, defined as an unintentional decline in the core body temperature to below 35℃, is a life-threatening condition. Patients with malnutrition and diabetes mellitus as well as those of advanced age are at high risk for accidental hypothermia. Due to the high mortality rates of accidental hypothermia, proper management is critical for the wellbeing of patients. Accidental hypothermia was reported to be associated with acute kidney injury (AKI) in over 40% of cases. Although the pathogenesis remains to be elucidated, vasoconstriction and ischemia in the kidney were considered to be the main mechanisms involved. Cases of AKI associated with hypothermia have been reported worldwide, but there have been few reports of hypothermia-induced AKI in Korea. Here, we present a case of hypothermia-induced AKI that was treated successfully with rewarming and supportive care.

  7. Acute kidney injury after massive attack of Africanised bees

    PubMed Central

    Bridi, Ramaiane A; Balbi, Andre Luis; Neves, Precil M; Ponce, Daniela

    2014-01-01

    Acute kidney injury (AKI) is a well-documented complication of massive attack by Africanised bees and can be observed 48–72 h after the accident. We report a case of Africanised bees attack followed by severe and lethal AKI. A 56-year-old man was admitted to emergency department after a massive attack of Africanised bees (>1000 bee stings). He was unconscious, presenting with hypotension and tachycardia. Mechanical ventilation, volume expansion and care for anaphylaxis were instituted. The patient was transferred to the intensive care unit (ICU) and after 48 h he developed rhabdomyolysis, oliguria, increased creatinine levels, hyperkalaemia and refractory acidosis. A diagnosis of AKI secondary to rhabdomyolysis and shock was made. The patient was treated with a prolonged course of haemodialysis. However, he progressed to refractory shock and died 5 days after admission. PMID:24618864

  8. [Star fruit as a cause of acute kidney injury].

    PubMed

    Scaranello, Karilla Lany; Alvares, Valeria Regina de Cristo; Carneiro, Daniely Maria Queiroz; Barros, Flávio Henrique Soares; Gentil, Thais Marques Sanches; Thomaz, Myriam José; Pereira, Benedito Jorge; Pereira, Mariana Batista; Leme, Graziella Malzoni; Diz, Mary Carla Esteves; Laranja, Sandra Maria Rodrigues

    2014-01-01

    The star fruit belongs to the family Oxalidacea, species Averrhoa carambola. It is rich in minerals, vitamin A, C, B complex vitamins and oxalic acid. Recent studies show that the toxicity of the fruit differs between the patients and may be explained by single biological responses, age, and the intake quantity of the neurotoxin in each fruit in addition to glomerular filtration rate given by each patient. Additionally, the nephrotoxicity caused by the fruit is dose-dependent and may lead to the deposition of crystals of calcium oxalate intratubular, as well as by direct injury to the renal tubular epithelium, leading to apoptosis of the same. We report the case of a patient who after ingestion of the juice and fresh fruit, developed acute renal failure requiring dialysis, evolving with favourable outcome and recovery of renal function.

  9. Acute kidney injury in the fetus and neonate.

    PubMed

    Nada, Arwa; Bonachea, Elizabeth M; Askenazi, David J

    2017-04-01

    Acute kidney injury (AKI) is an under-recognized morbidity of neonates; the incidence remains unclear due to the absence of a unified definition of AKI in this population and because previous studies have varied greatly in screening for AKI with serum creatinine and urine output assessments. Premature infants may be born with less than half of the nephrons compared with term neonates, predisposing them to chronic kidney disease (CKD) early on in life and as they age. AKI can also lead to CKD, and premature infants with AKI may be at very high risk for long-term kidney problems. AKI in neonates is often multifactorial and may result from prenatal, perinatal, or postnatal insults as well as any combination thereof. This review focuses on the causes of AKI, the importance of early detection, the management of AKI in neonates, and long-term sequela of AKI in neonates.

  10. Galangin dampens mice lipopolysaccharide-induced acute lung injury.

    PubMed

    Shu, Yu-Sheng; Tao, Wei; Miao, Qian-Bing; Lu, Shi-Chun; Zhu, Ya-Bing

    2014-10-01

    Galangin, an active ingredient of Alpinia galangal, has been shown to possess anti-inflammatory and antioxidant activities. Inflammation and oxidative stress are known to play vital effect in the pathogenesis of acute lung injury (ALI). In this study, we determined whether galangin exerts lung protection in lipopolysaccharide (LPS)-induced ALI. Male BALB/c mice were randomized to receive galangin or vehicle intraperitoneal injection 3 h after LPS challenge. Samples were harvested 24 h post LPS administration. Galangin administration decreased biochemical parameters of oxidative stress and inflammation, and improved oxygenation and lung edema in a dose-dependent manner. These protective effects of galangin were associated with inhibition of nuclear factor (NF)-κB and upregulation of heme oxygenase (HO)-1. Galangin reduces LPS-induced ALI by inhibition of inflammation and oxidative stress.

  11. Warfarin related acute kidney injury: A case report

    PubMed Central

    Mendonca, S.; Gupta, D.; Valsan, A.; Tewari, R.

    2017-01-01

    Warfarin is an oral anticoagulant used extensively in clinical practice; However, its side-effect of causing renal damage has been recently detected. The mechanism leading to renal damage is glomerular hemorrhage and red blood cell tubular casts prothrombin time. Recently, it was found that warfarin causes renal damage in patients with chronic kidney disease and is also associated with progression of renal disease. Warfarin causing acute kidney injury in patients with normal renal function is a rare manifestation. It is important to be aware of this condition as its innocuous presence can lead to chronic kidney disease if not corrected in time. Further studies have also found that novel oral anticoagulants such as dabigatran also cause a similar syndrome and hence a new term called anticoagulant-related nephropathy is now in vogue. PMID:28182051

  12. Multiphoton imaging for assessing renal disposition in acute kidney injury

    NASA Astrophysics Data System (ADS)

    Liu, Xin; Liang, Xiaowen; Wang, Haolu; Roberts, Darren M.; Roberts, Michael S.

    2016-11-01

    Estimation of renal function and drug renal disposition in acute kidney injury (AKI), is important for appropriate dosing of drugs and adjustment of therapeutic strategies, but is challenging due to fluctuations in kidney function. Multiphoton microscopy has been shown to be a useful tool in studying drug disposition in liver and can reflect dynamic changes of liver function. We extend this imaging technique to investigate glomerular filtration rate (GFR) and tubular transporter functional change in various animal models of AKI, which mimic a broad range of causes of AKI such as hypoxia (renal ischemia- reperfusion), therapeutic drugs (e.g. cisplatin), rhabdomyolysis (e.g. glycerol-induced) and sepsis (e.g. LPSinduced). The MPM images revealed acute injury of tubular cells as indicated by reduced autofluorescence and cellular vacuolation in AKI groups compared to control group. In control animal, systemically injected FITC-labelled inulin was rapidly cleared from glomerulus, while the clearance of FITC-inulin was significantly delayed in most of animals in AKI group, which may reflect the reduced GFR in AKI. Following intravenous injection, rhodamine 123, a fluorescent substrate of p-glycoprotein (one of tubular transporter), was excreted into urine in proximal tubule via p-glycoprotein; in response to AKI, rhodamine 123 was retained in tubular cells as revealed by slower decay of fluorescence intensity, indicating P-gp transporter dysfunction in AKI. Thus, real-time changes in GFR and transporter function can be imaged in rodent kidney with AKI using multiphoton excitation of exogenously injected fluorescent markers.

  13. Voluntary Exercise Preconditioning Activates Multiple Antiapoptotic Mechanisms and Improves Neurological Recovery after Experimental Traumatic Brain Injury

    PubMed Central

    Zhao, Zaorui; Sabirzhanov, Boris; Wu, Junfang; Faden, Alan I.

    2015-01-01

    Abstract Physical activity can attenuate neuronal loss, reduce neuroinflammation, and facilitate recovery after brain injury. However, little is known about the mechanisms of exercise-induced neuroprotection after traumatic brain injury (TBI) or its modulation of post-traumatic neuronal cell death. Voluntary exercise, using a running wheel, was conducted for 4 weeks immediately preceding (preconditioning) moderate-level controlled cortical impact (CCI), a well-established experimental TBI model in mice. Compared to nonexercised controls, exercise preconditioning (pre-exercise) improved recovery of sensorimotor performance in the beam walk task, as well as cognitive/affective functions in the Morris water maze, novel object recognition, and tail-suspension tests. Further, pre-exercise reduced lesion size, attenuated neuronal loss in the hippocampus, cortex, and thalamus, and decreased microglial activation in the cortex. In addition, exercise preconditioning activated the brain-derived neurotrophic factor pathway before trauma and amplified the injury-dependent increase in heat shock protein 70 expression, thus attenuating key apoptotic pathways. The latter include reduction in CCI-induced up-regulation of proapoptotic B-cell lymphoma 2 (Bcl-2)-homology 3–only Bcl-2 family molecules (Bid, Puma), decreased mitochondria permeabilization with attenuated release of cytochrome c and apoptosis-inducing factor (AIF), reduced AIF translocation to the nucleus, and attenuated caspase activation. Given these neuroprotective actions, voluntary physical exercise may serve to limit the consequences of TBI. PMID:25419789

  14. Voluntary Exercise Preconditioning Activates Multiple Antiapoptotic Mechanisms and Improves Neurological Recovery after Experimental Traumatic Brain Injury.

    PubMed

    Zhao, Zaorui; Sabirzhanov, Boris; Wu, Junfang; Faden, Alan I; Stoica, Bogdan A

    2015-09-01

    Physical activity can attenuate neuronal loss, reduce neuroinflammation, and facilitate recovery after brain injury. However, little is known about the mechanisms of exercise-induced neuroprotection after traumatic brain injury (TBI) or its modulation of post-traumatic neuronal cell death. Voluntary exercise, using a running wheel, was conducted for 4 weeks immediately preceding (preconditioning) moderate-level controlled cortical impact (CCI), a well-established experimental TBI model in mice. Compared to nonexercised controls, exercise preconditioning (pre-exercise) improved recovery of sensorimotor performance in the beam walk task, as well as cognitive/affective functions in the Morris water maze, novel object recognition, and tail-suspension tests. Further, pre-exercise reduced lesion size, attenuated neuronal loss in the hippocampus, cortex, and thalamus, and decreased microglial activation in the cortex. In addition, exercise preconditioning activated the brain-derived neurotrophic factor pathway before trauma and amplified the injury-dependent increase in heat shock protein 70 expression, thus attenuating key apoptotic pathways. The latter include reduction in CCI-induced up-regulation of proapoptotic B-cell lymphoma 2 (Bcl-2)-homology 3-only Bcl-2 family molecules (Bid, Puma), decreased mitochondria permeabilization with attenuated release of cytochrome c and apoptosis-inducing factor (AIF), reduced AIF translocation to the nucleus, and attenuated caspase activation. Given these neuroprotective actions, voluntary physical exercise may serve to limit the consequences of TBI.

  15. Principles of Motor Recovery After Neurological Injury Based on a Motor Control Theory.

    PubMed

    Levin, Mindy F

    2016-01-01

    Problems of neurological rehabilitation are considered based on two levels of the International Classification of Functioning (ICF)-Body Structures and Function level and Activity level-and modulating factors related to the individual and the environment. Specifically, at the Body Structures and Function level, problems addressed include spasticity, muscle weakness, disordered muscle activation patterns and disruptions in coordinated movement. At the Activity level, deficits in multi-joint and multi-segment upper limb reaching movements are reviewed. We address how physiologically well established principles in the control of actions, Threshold Control and Referent Control as outlined in the Equilibrium-Point theory can help advance the understanding of underlying deficits that may limit recovery at each level.

  16. Acute kidney injury associated with ingestion of star fruit: Acute oxalate nephropathy.

    PubMed

    Barman, A K; Goel, R; Sharma, M; Mahanta, P J

    2016-01-01

    Starfruit (Averrhoa carambola) and its juice are popular in the Indian subcontinent as an indigenous medicine. Oxalate concentration in this fruit and it's freshly prepared juice is very high. We present a report of patients presenting with acute kidney injury due to oxalate nephropathy admitted in a single center. All patients had history of ingesting star fruit. Patients became symptomatic after 10-12 h of eating and main symptoms were pain abdomen and decrease in urine output. Three patients needed hemodialysis. All improved with complete renal recovery. Taking star fruit in large amount on an empty stomach and in a dehydrated state is a risk factor for nephrotoxicity.

  17. Acute kidney injury associated with ingestion of star fruit: Acute oxalate nephropathy

    PubMed Central

    Barman, A. K.; Goel, R.; Sharma, M.; Mahanta, P. J.

    2016-01-01

    Starfruit (Averrhoa carambola) and its juice are popular in the Indian subcontinent as an indigenous medicine. Oxalate concentration in this fruit and it's freshly prepared juice is very high. We present a report of patients presenting with acute kidney injury due to oxalate nephropathy admitted in a single center. All patients had history of ingesting star fruit. Patients became symptomatic after 10–12 h of eating and main symptoms were pain abdomen and decrease in urine output. Three patients needed hemodialysis. All improved with complete renal recovery. Taking star fruit in large amount on an empty stomach and in a dehydrated state is a risk factor for nephrotoxicity. PMID:27942177

  18. Reversible anuric acute kidney injury secondary to acute renal autoregulatory dysfunction.

    PubMed

    Imbriano, Louis J; Maesaka, John K; Drakakis, James; Mattana, Joseph

    2014-02-01

    Autoregulation of glomerular capillary pressure via regulation of the resistances at the afferent and efferent arterioles plays a critical role in maintaining the glomerular filtration rate over a wide range of mean arterial pressure. Angiotensin II and prostaglandins are among the agents which contribute to autoregulation and drugs which interfere with these agents may have a substantial impact on afferent and efferent arteriolar resistance. We describe a patient who suffered an episode of anuric acute kidney injury following exposure to a nonsteroidal anti-inflammatory agent while on two diuretics, an angiotensin-converting enzyme inhibitor, and an angiotensin receptor blocker. The episode completely resolved and we review some of the mechanisms by which these events may have taken place and suggest the term "acute renal autoregulatory dysfunction" to describe this syndrome.

  19. Potential Application of Viral Empty Capsids for the Treatment of Acute Lung Injury/Acute Respiratory Distress Syndrome

    DTIC Science & Technology

    2016-07-01

    Acute Respiratory Distress Syndrome PRINCIPAL INVESTIGATOR: Prof. Ariella Oppenheim CONTRACTING ORGANIZATION: Hebrew University of Jerusalem...Lung / 5a. CONTRACT NUMBER Injury/Acute Respiratory Distress Syndrome 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Prof. Ariella...mechanism elicited by VLPs that attenuate 2CLP-induced sepsis, to be performed as the project continues. 15. SUBJECT TERMS Acute Respiratory Distress

  20. Acute Lung Injury Following Smoke Inhalation: Predictive Value of Sputum Biomarkers and Time Course of Lung Inflammation

    DTIC Science & Technology

    2007-05-01

    acute lung injury (ALI) and acute respiratory distress syndrome ( ARDS ). Criteria for diagnosing ALI and predicting...Rationale: Smoke inhalation victims are at high risk of developing acute respiratory distress syndrome ( ARDS ). Given the delay of 12 or more hours...Background: Although smoke inhalation injury victims frequently develop acute respiratory distress syndrome ( ARDS ), no early prognostic

  1. Acute Lung Injury Following Smoke Inhalation: Predictive Value of Sputum Biomarkers and Time Course of Lung Inflammation

    DTIC Science & Technology

    2006-04-01

    acute respiratory distress syndrome ( ARDS ). Given the delay of 12 or...Keywords: Inhalation Burns, Acute Respiratory Distress Syndrome , Interleukin-8, Interleukin- 1 beta. 4/14/2006 Markers of Smoke Inhalation Injury 2...Zimmerman 2005; Park et al., 2001), all hallmarks of acute lung injury (ALI) and acute respiratory distress syndrome ( ARDS ). The general

  2. Obesity, Acute Kidney Injury, and Mortality in Critical Illness

    PubMed Central

    Danziger, John; Chen, Ken; Lee, Joon; Feng, Mengling; Mark, Roger G.; Celi, Leo Anthony; Mukamal, Kenneth J.

    2015-01-01

    Background Although obesity is associated with risk for chronic kidney disease (CKD) and improved survival, less is known about the associations of obesity with risk of acute kidney injury (AKI) and post-AKI mortality. Methods In a single-center inception cohort of almost 15,000 critically ill patients, we evaluated the association of obesity with AKI and AKI severity, as well as in-hospital and one-year survival. AKI was defined using the Kidney Disease Outcome Quality Initiative criteria. Results The AKI incidence rates for normal, overweight, Class I, II, and III Obesity were 18.6, 20.6, 22.5, 24.3 and 24.0 percent respectively, and the adjusted odds ratios of AKI were 1.18 [95% CI 1.06–1.31], 1.35 [1.19–1.53], 1.47 [1.25–1.73], 1.59 [1.31–1.87], compared to normal weight, respectively. Each 5 kg/m2 increase in body mass index (BMI) was associated with a 10% risk [95% CI 1.06–1.24; p<0.001] of more severe AKI. Within-hospital and one-year survival rates associated with the AKI episodes were similar across BMI categories. In conclusion, obesity is a risk factor for AKI injury, which is associated with increased short- and long-term mortality. PMID:26496453

  3. [Transfusion related acute lung injury (TRALI): an unrecognised pathology].

    PubMed

    Moalic, V; Vaillant, C; Ferec, C

    2005-03-01

    Transfusion related acute lung injury (TRALI) is a rare but potentially severe complication of blood transfusion, manifested by pulmonary oedema, fever and hypotension. The signs and symptoms are often attributed to other clinical aspects of a patient's condition, and therefore, TRALI may go unrecognised. It has been estimated to be the third cause of transfusion related mortality, so it should be better diagnosed. Cases are related to multiple blood units, such as white blood cells, red blood cells, fresh frozen plasma, platelets or intravenous immunoglobulins. Physiopathology of TRALI is poorly understood, and still controversial. It is often due to an immunological conflict between transfused plasma antibodies and recipients' blood cells. These antibodies are either HLA (class I or II) or granulocyte-specific. They appear to act as mediators, which result in granulocytes aggregation, activation and micro vascular pulmonary injury. Lipids or cytokines in blood units are also involved as TRALI priming agents. Diagnosis is based on antibody screening in blood components and on specific-antigen detection in the recipient. The screening of anti-HLA or anti-granulocytes is recommended as part of prevention for female donors who had been pregnant. Preventative measures should also include leucoreduction and measures to decrease the amount of priming agents in blood components. In this article, we summarise what is known about TRALI, and we focus attention on unanswered questions and controversial issues related to TRALI.

  4. Acute kidney injury: Renal disease in the ICU.

    PubMed

    Seller-Pérez, G; Más-Font, S; Pérez-Calvo, C; Villa-Díaz, P; Celaya-López, M; Herrera-Gutiérrez, M E

    2016-01-01

    Acute kidney injury (AKI) in the ICU frequently requires costly supportive therapies, has high morbidity, and its long-term prognosis is not as good as it has been presumed so far. Consequently, AKI generates a significant burden for the healthcare system. The problem is that AKI lacks an effective treatment and the best approach relies on early secondary prevention. Therefore, to facilitate early diagnosis, a broader definition of AKI should be established, and a marker with more sensitivity and early-detection capacity than serum creatinine - the most common marker of AKI - should be identified. Fortunately, new classification systems (RIFLE, AKIN or KDIGO) have been developed to solve these problems, and the discovery of new biomarkers for kidney injury will hopefully change the way we approach renal patients. As a first step, the concept of renal failure has changed from being a "static" disease to being a "dynamic process" that requires continuous evaluation of kidney function adapted to the reality of the ICU patient.

  5. Postpartum acute kidney injury: a review of 99 cases.

    PubMed

    Eswarappa, Mahesh; Madhyastha, P Rakesh; Puri, Sonika; Varma, Vijay; Bhandari, Aneesh; Chennabassappa, Gurudev

    2016-07-01

    Postpartum acute kidney injury (PPAKI) constitutes an important cause of obstetric AKI. It is associated with high maternal and fetal mortality in developing nations. The aim of this study is to survey the etiology and outcomes of PPAKI in a tertiary care Indian hospital. Ninety-nine patients, without prior comorbidities, treated for PPAKI, between 2005-2014 at M.S. Ramaiah Medical College, were included for analysis in this retrospective, observational study. AKI was analyzed in terms of maximal stage of renal injury attained as per RIFLE criteria. Outcomes included requirement for renal replacement therapy (RRT), maternal and fetal outcomes. PPAKI constituted 60% of all obstetric AKI cases. Median maternal age was 23 years and 52% of patients were primigravidas. Mean serum creatinine was 4.1 mg/dL. Failure (33%) and injury (31%) were the major categories as per RIFLE criteria. Thirty-nine percent of cases required RRT. Sepsis, particularly puerperal sepsis, was the leading causes of PPAKI (75% of cases) and maternal mortality (94% of deaths). Maternal and fetal mortality were 19% and 22% respectively. The incidence of cortical necrosis was 10.3%. Three patients required long-term RRT. In conclusion, consistent with other Indian literature, we report a high incidence of PPAKI. We found incremental mortality on moving from "Risk" to "Failure" category of RIFLE. PPAKI was associated with high maternal and fetal mortality with sepsis being the leading cause. Our study highlights the need for provision of better quality of maternal care and fetal monitoring to decrease mortality associated with PPAKI in developing countries.

  6. A crucial role of nitric oxide in acute lung injury secondary to the acute necrotizing pancreatitis.

    PubMed

    Cheng, Shi; Yan, Wen-Mao; Yang, Bin; Shi, Jing-dong; Song, Mao-min; Zhao, Yuqian

    2010-04-01

    To investigate the role of nitric oxide (NO) in acute lung inflammation and injury secondary to acute necrotizing pancreatitis (ANP), 5% sodium taurocholate was retrogradely injected into the biliopancreatic duct of rats to ANP model. These ANP rats were given L-Arginine (L-Arg, 100 mg/kg), L-NAME (10 mg/kg), or their combination by intraperitoneal injection 30 min prior to ANP induction. At 1, 3, 6, and 12 hours after ANP induction, lung NO production, and inducible NO synthase (iNOS) expression were measured. Lung histopathological changes, bronchoalveolar lavage (BAL) protein concentration, proinflammatory mediators tumor necrotic factor alpha (TNF-alpha), and lung tissue myeloperoxidase (MPO) activity were examined. Results showed that NO production and iNOS mRNA expression in alveolar macrophages (AMs) were significantly increased along with significant increases in lung histological abnormalities and BAL proteins in the ANP group, all of which were further enhanced by pretreatment with L-Arg and attenuated by pretreatment with L-NAME, respectively. These markers were slightly attenuated by pretreatment with combination of L-Arg + L-NAME, suggesting that NO is required for initiating the acute lung damage in ANP rats, and also that L-Arg-enhanced lung injury is mediated by its NO generation rather than its direct effect. MPO activity and TNF-alpha expression in lung were upregulated in the ANP rats and further enhanced by pretreatment with L-Arg and attenuated by pretreatment with L-NAME, respectively. These results suggest that overproduction of NO mediated by iNOS in the lung is required for the acute lung inflammation and damage secondary to ANP.

  7. Can Surgery Improve Neurological Function in Penetrating Spinal Injury? A Review of the Military and Civilian Literature and Treatment Recommendations for Military Neurosurgeons

    DTIC Science & Technology

    2010-05-01

    was hit in the left shoulder, experienced immediate paraplegia , and died of his injury shortly thereafter. Other notable fatalities from spinal GSWs...acute spinal cord inju- ries in a war zone. J Neurosurg 34:164–167, 1971 19. Jacobson SA, Bors E: Spinal cord injury in Vietnamese com- bat. Paraplegia 7

  8. The TRIF-dependent signaling pathway is not required for acute cerebral ischemia/reperfusion injury in mice

    SciTech Connect

    Hua, Fang; Wang, Jun; Sayeed, Iqbal; Ishrat, Tauheed; Atif, Fahim; Stein, Donald G.

    2009-12-18

    TIR domain-containing adaptor protein (TRIF) is an adaptor protein in Toll-like receptor (TLR) signaling pathways. Activation of TRIF leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-{kappa}B). While studies have shown that TLRs are implicated in cerebral ischemia/reperfusion (I/R) injury and in neuroprotection against ischemia afforded by preconditioning, little is known about TRIF's role in the pathological process following cerebral I/R. The present study investigated the role that TRIF may play in acute cerebral I/R injury. In a mouse model of cerebral I/R induced by transient middle cerebral artery occlusion, we examined the activation of NF-{kappa}B and IRF3 signaling in ischemic cerebral tissue using ELISA and Western blots. Neurological function and cerebral infarct size were also evaluated 24 h after cerebral I/R. NF-{kappa}B activity and phosphorylation of the inhibitor of kappa B (I{kappa}B{alpha}) increased in ischemic brains, but IRF3, inhibitor of {kappa}B kinase complex-{epsilon} (IKK{epsilon}), and TANK-binding kinase1 (TBK1) were not activated after cerebral I/R in wild-type (WT) mice. Interestingly, TRIF deficit did not inhibit NF-{kappa}B activity or p-I{kappa}B{alpha} induced by cerebral I/R. Moreover, although cerebral I/R induced neurological and functional impairments and brain infarction in WT mice, the deficits were not improved and brain infarct size was not reduced in TRIF knockout mice compared to WT mice. Our results demonstrate that the TRIF-dependent signaling pathway is not required for the activation of NF-{kappa}B signaling and brain injury after acute cerebral I/R.

  9. Acute kidney injury in liver cirrhosis: new definition and application

    PubMed Central

    Wong, Florence

    2016-01-01

    The traditional diagnostic criteria of renal dysfunction in cirrhosis are a 50% increase in serum creatinine (SCr) with a final value above 1.5 mg/dL. This means that patients with milder degrees of renal dysfunction are not being diagnosed, and therefore not offered timely treatment. The International Ascites Club in 2015 adapted the term acute kidney injury (AKI) to represent acute renal dysfunction in cirrhosis, and defined it by an increase in SCr of 0.3 mg/dL (26.4 µmoL/L) in <48 hours, or a 50% increase in SCr from a baseline within ≤3 months. The severity of AKI is described by stages, with stage 1 represented by these minimal changes, while stages 2 and 3 AKI by 2-fold and 3-fold increases in SCr respectively. Hepatorenal syndrome (HRS), renamed AKI-HRS, is defined by stage 2 or 3 AKI that fulfils all other diagnostic criteria of HRS. Various studies in the past few years have indicated that these new diagnostic criteria are valid in the prediction of prognosis for patients with cirrhosis and AKI. The future in AKI diagnosis may include further refinements such as inclusion of biomarkers that can identify susceptibility for AKI, differentiating the various prototypes of AKI, or track its progression. PMID:27987536

  10. Effect of Thoracentesis on Intubated Patients with Acute Lung Injury.

    PubMed

    Bloom, Matthew B; Serna-Gallegos, Derek; Ault, Mark; Khan, Ahsan; Chung, Rex; Ley, Eric J; Melo, Nicolas; Margulies, Daniel R

    2016-03-01

    Pleural effusions occur frequently in mechanically ventilated patients, but no consensus exists regarding the clinical benefit of effusion drainage. We sought to determine the impact of thoracentesis on gas exchange in patients with differing severities of acute lung injury (ALI). A retrospective analysis was conducted on therapeutic thoracenteses performed on intubated patients in an adult surgical intensive care unit of a tertiary center. Effusions judged by ultrasound to be 400 mL or larger were drained. Subjects were divided into groups based on their initial P:F ratios: normal >300, ALI 200 to 300, and acute respiratory distress syndrome (ARDS) <200. Baseline characteristics, physiologic variables, arterial blood gases, and ventilator settings before and after the intervention were analyzed. The primary end point was the change in measures of oxygenation. Significant improvements in P:F ratios (mean ± SD) were seen only in patients with ARDS (50.4 ± 38.5, P = 0.001) and ALI (90.6 ± 161.7, P = 0.022). Statistically significant improvement was observed in the pO2 (31.1, P = 0.005) and O2 saturation (4.1, P < 0.001) of the ARDS group. The volume of effusion removed did not correlate with changes in individual patient's oxygenation. These data support the role of therapeutic thoracentesis for intubated patients with abnormal P:F ratios.

  11. Renal oxygenation in acute renal ischemia-reperfusion injury.

    PubMed

    Abdelkader, Amany; Ho, Julie; Ow, Connie P C; Eppel, Gabriela A; Rajapakse, Niwanthi W; Schlaich, Markus P; Evans, Roger G

    2014-05-01

    Tissue hypoxia has been demonstrated, in both the renal cortex and medulla, during the acute phase of reperfusion after ischemia induced by occlusion of the aorta upstream from the kidney. However, there are also recent clinical observations indicating relatively well preserved oxygenation in the nonfunctional transplanted kidney. To test whether severe acute kidney injury can occur in the absence of widespread renal tissue hypoxia, we measured cortical and inner medullary tissue Po2 as well as total renal O2 delivery (Do2) and O2 consumption (Vo2) during the first 2 h of reperfusion after 60 min of occlusion of the renal artery in anesthetized rats. To perform this experiment, we used a new method for measuring kidney Do2 and Vo2 that relies on implantation of fluorescence optodes in the femoral artery and renal vein. We were unable to detect reductions in renal cortical or inner medullary tissue Po2 during reperfusion after ischemia localized to the kidney. This is likely explained by the observation that Vo2 (-57%) was reduced by at least as much as Do2 (-45%), due to a large reduction in glomerular filtration (-94%). However, localized tissue hypoxia, as evidence by pimonidazole adduct immunohistochemistry, was detected in kidneys subjected to ischemia and reperfusion, particularly in, but not exclusive to, the outer medulla. Thus, cellular hypoxia, particularly in the outer medulla, may still be present during reperfusion even when reductions in tissue Po2 are not detected in the cortex or inner medulla.

  12. Special nutrition challenges: current approach to acute kidney injury.

    PubMed

    McCarthy, Mary S; Phipps, Shauna C

    2014-02-01

    Acute kidney injury (AKI), previously known as acute renal failure, is defined as a sudden decline in glomerular filtration rate with accumulation of metabolic waste products, toxins, and drugs, as well as alteration in the intrinsic functions of the kidney. Reports of mortality are as high as 80%, with numerous contributing causes including infection, cardiorespiratory complications, and cardiovascular disease. Concurrent with the high prevalence of critical illness in this population is the protein energy wasting (PEW), seen in up to 42% of patients upon intensive care unit admission. The pathophysiologic derangements of critical illness, the low energy and protein stores, and uremic complications require early nutrition intervention to attenuate the inflammatory response and oxidative stress, improve endothelial function, stabilize blood sugar, and preserve lean body mass. This article addresses the unique challenges of nutrition support for the patient with AKI in the setting of critical illness and renal replacement therapy. Evidence-based recommendations are provided to meet the macronutrient and micronutrient requirements of this heterogeneous and complex patient population.

  13. Acute kidney injury in liver cirrhosis: new definition and application.

    PubMed

    Wong, Florence

    2016-12-01

    The traditional diagnostic criteria of renal dysfunction in cirrhosis are a 50% increase in serum creatinine (SCr) with a final value above 1.5 mg/dL. This means that patients with milder degrees of renal dysfunction are not being diagnosed, and therefore not offered timely treatment. The International Ascites Club in 2015 adapted the term acute kidney injury (AKI) to represent acute renal dysfunction in cirrhosis, and defined it by an increase in SCr of 0.3 mg/dL (26.4 µmoL/L) in <48 hours, or a 50% increase in SCr from a baseline within ≤3 months. The severity of AKI is described by stages, with stage 1 represented by these minimal changes, while stages 2 and 3 AKI by 2-fold and 3-fold increases in SCr respectively. Hepatorenal syndrome (HRS), renamed AKI-HRS, is defined by stage 2 or 3 AKI that fulfils all other diagnostic criteria of HRS. Various studies in the past few years have indicated that these new diagnostic criteria are valid in the prediction of prognosis for patients with cirrhosis and AKI. The future in AKI diagnosis may include further refinements such as inclusion of biomarkers that can identify susceptibility for AKI, differentiating the various prototypes of AKI, or track its progression.

  14. Malarial acute kidney injury in a paediatric intensive care unit.

    PubMed

    Kapoor, Kapil; Gupta, Shalu

    2012-10-01

    Acute kidney injury (AKI) is a serious complication of malaria which has a very high mortality rate. A retrospective analysis of medical record data of children treated for malarial AKI in a paediatric intensive care unit (PICU) was performed in order to evaluate the incidence, poor prognostic factors and outcome of AKI with malaria. Eighteen (48.6%) malarial patients had AKI (11 Plasmodium vivax positive, six P. falciparum positive and one mixed infection) with a male-to-female ratio of 1:2. The mean age was 75 ± 32 months (range, 1 month to 10 years). Oliguria was present in 61.1% and 55.5% required renal replacement therapy. Mortality was noted in 33.3% of patients and full recovery was achieved in 50% of patients. Oliguria, shock, central nervous system involvement, jaundice, disseminated intravascular coagulopathy and acute respiratory distress syndrome emerged as bad prognostic factors in simple univariate analysis. Malaria patients with and without AKI differ significantly in terms of shock, ventilator requirement, mortality and length of PICU stay.

  15. Peptide nanomedicines for treatment of acute lung injury.

    PubMed

    Sadikot, Ruxana T

    2012-01-01

    Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent a heterogenous group of lung disease in critically ill patients. Despite the increased understanding of the molecular pathogenesis of ARDS, the mortality remains unacceptably high, ranging from 34% to 64%. Hence, ARDS represents an unmet medical need with an urgency to develop effective pharmacotherapies. Several promising targets that have been identified as potential therapies for ARDS have been limited because of difficulty with delivery. In particular, delivery of peptides and proteins to the lung is an ongoing challenge. Nanobiotechnology and nanoscience are the basis of innovative techniques to deliver drugs targeted to the site of inflamed organs, such as the lungs. Nanoscale drug delivery systems have the ability to improve the pharmacokinetics and pharmakodynamics of agents allowing an increase in the biodistribution of therapeutic agents to target organs, resulting in improved efficacy with reduction in drug toxicity. These systems are exploited for therapeutic purpose to carry the drug in the body in a controlled manner from the site of administration to the therapeutic target. Hence, it is an attractive strategy to test potential targets for ALI/ARDS using nanotechnology. To this end, we have identified several potential targets and proposed the delivery of these agents using nanomicelles to improve the drug delivery.

  16. VEGF Promotes Malaria-Associated Acute Lung Injury in Mice

    PubMed Central

    Carapau, Daniel; Pena, Ana C.; Ataíde, Ricardo; Monteiro, Carla A. A.; Félix, Nuno; Costa-Silva, Artur; Marinho, Claudio R. F.; Dias, Sérgio; Mota, Maria M.

    2010-01-01

    The spectrum of the clinical presentation and severity of malaria infections is broad, ranging from uncomplicated febrile illness to severe forms of disease such as cerebral malaria (CM), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pregnancy-associated malaria (PAM) or severe anemia (SA). Rodent models that mimic human CM, PAM and SA syndromes have been established. Here, we show that DBA/2 mice infected with P. berghei ANKA constitute a new model for malaria-associated ALI. Up to 60% of the mice showed dyspnea, airway obstruction and hypoxemia and died between days 7 and 12 post-infection. The most common pathological findings were pleural effusion, pulmonary hemorrhage and edema, consistent with increased lung vessel permeability, while the blood-brain barrier was intact. Malaria-associated ALI correlated with high levels of circulating VEGF, produced de novo in the spleen, and its blockage led to protection of mice from this syndrome. In addition, either splenectomization or administration of the anti-inflammatory molecule carbon monoxide led to a significant reduction in the levels of sera VEGF and to protection from ALI. The similarities between the physiopathological lesions described here and the ones occurring in humans, as well as the demonstration that VEGF is a critical host factor in the onset of malaria-associated ALI in mice, not only offers important mechanistic insights into the processes underlying the pathology related with malaria but may also pave the way for interventional studies. PMID:20502682

  17. Acute Kidney Injury in Hematopoietic Stem Cell Transplantation: A Review

    PubMed Central

    Gupta, Mohit; Manu, Gurusidda; Kwatra, Shivani; Owusu, Osei-Tutu

    2016-01-01

    Hematopoietic stem cell transplantation (HSCT) is a highly effective treatment strategy for lymphoproliferative disorders and bone marrow failure states including aplastic anemia and thalassemia. However, its use has been limited by the increased treatment related complications, including acute kidney injury (AKI) with an incidence ranging from 20% to 73%. AKI after HSCT has been associated with an increased risk of mortality. The incidence of AKI reported in recipients of myeloablative allogeneic transplant is considerably higher in comparison to other subclasses mainly due to use of cyclosporine and development of graft-versus-host disease (GVHD) in allogeneic groups. Acute GVHD is by itself a major independent risk factor for the development of AKI in HSCT recipients. The other major risk factors are sepsis, nephrotoxic medications (amphotericin B, acyclovir, aminoglycosides, and cyclosporine), hepatic sinusoidal obstruction syndrome (SOS), thrombotic microangiopathy (TMA), marrow infusion toxicity, and tumor lysis syndrome. The mainstay of management of AKI in these patients is avoidance of risk factors contributing to AKI, including use of reduced intensity-conditioning regimen, close monitoring of nephrotoxic medications, and use of alternative antifungals for prophylaxis against infection. Also, early identification and effective management of sepsis, tumor lysis syndrome, marrow infusion toxicity, and hepatic SOS help in reducing the incidence of AKI in HSCT recipients. PMID:27885340

  18. [Acute kidney injury and septic shock: experiences in treatment].

    PubMed

    Pozzato, Marco; Ferrari, Fiorenza; Livigni, Sergio; Quarello, Francesco

    2012-01-01

    Acute kidney injury (AKI) occurs in 5-45% of critically ill patients, and renal replacement therapy (RRT) is required in 4-10% of patients with AKI. AKI has long been considered to be hemodynamic damage from low blood flow resulting in shock, and efforts have been made to prevent and cure it by increasing the renal blood flow and improving the cardiac output and perfusion pressure. In recent years, new experimental studies on patients with septic AKI have shown that the renal blood flow remains unaltered or even increases in septic shock. An important mechanism in the pathophysiology of sepsis and septic shock appears to be apoptosis rather than ischemic necrosis. The type of treatment as well as the dose and timing of initiation of RRT seem to have strategic importance in the recovery of AKI in patients admitted to the ICU. In critically ill (often postsurgical and septic) patients with acute renal failure the use of new anticoagulation strategies has permitted to perform treatments for a sufficient number of hours to achieve the correct level of purification by minimizing the downtime and the bleeding risk. In our center the use of protocols for different methods and different types of anticoagulants has simplified the treatment of all patients with AKI and septic shock admitted to the ICU.

  19. The pathogenesis of transfusion-related acute lung injury (TRALI).

    PubMed

    Bux, Jürgen; Sachs, Ulrich J H

    2007-03-01

    In recent years, transfusion-related acute lung injury (TRALI) has developed from an almost unknown transfusion reaction to the most common cause of transfusion-related major morbidities and fatalities. A clinical definition of TRALI was established in 2004, based on acute respiratory distress, non-cardiogenic lung oedema temporal association with transfusion and hypoxaemia. Histological findings reveal lung oedema, capillary leucostasis and neutrophil extravasation. However, the pathogenesis of TRALI remains controversial. Leucocyte antibodies, present in fresh frozen plasma and platelet concentrates from multiparous donors, and neutrophil priming agents released in stored cellular blood components have been considered to be causative. As neutrophils and endothelial cells are pivotal in the pathogenesis of TRALI, a threshold model was established to try to unify the various reported findings on pathogenesis. This model comprises the priming of neutrophils and/or endothelium by the patient's co-morbidity, neutrophil and/or endothelial cell activation by the transfused blood component, and the severity of the TRALI reaction.

  20. Age and Diet Affect Genetically Separable Secondary Injuries that Cause Acute Mortality Following Traumatic Brain Injury in Drosophila

    PubMed Central

    Katzenberger, Rebeccah J.; Ganetzky, Barry; Wassarman, David A.

    2016-01-01

    Outcomes of traumatic brain injury (TBI) vary because of differences in primary and secondary injuries. Primary injuries occur at the time of a traumatic event, whereas secondary injuries occur later as a result of cellular and molecular events activated in the brain and other tissues by primary injuries. We used a Drosophila melanogaster TBI model to investigate secondary injuries that cause acute mortality. By analyzing mortality percentage within 24 hr of primary injuries, we previously found that age at the time of primary injuries and diet afterward affect the severity of secondary injuries. Here, we show that secondary injuries peaked in activity 1–8 hr after primary injuries. Additionally, we demonstrate that age and diet activated distinct secondary injuries in a genotype-specific manner, and that concurrent activation of age- and diet-regulated secondary injuries synergistically increased mortality. To identify genes involved in secondary injuries that cause mortality, we compared genome-wide mRNA expression profiles of uninjured and injured flies under age and diet conditions that had different mortalities. During the peak period of secondary injuries, innate immune response genes were the predominant class of genes that changed expression. Furthermore, age and diet affected the magnitude of the change in expression of some innate immune response genes, suggesting roles for these genes in inhibiting secondary injuries that cause mortality. Our results indicate that the complexity of TBI outcomes is due in part to distinct, genetically controlled, age- and diet-regulated mechanisms that promote secondary injuries and that involve a subset of innate immune response genes. PMID:27754853

  1. Precision and improving outcomes in acute kidney injury: Personalizing the approach.

    PubMed

    Forni, Lui G; Chawla, Lakhmir; Ronco, Claudio

    2017-02-01

    It is now well over a decade since attempts at harmonization of acute renal failure into a definable entity termed acute kidney injury. This has led to several landmark studies outlining the epidemiology of acute kidney injury, particularly in the critically ill, as well as providing insights into the long-term effects of the syndrome. Despite the introduction of consensus definitions and improvement in recognition, this has not been translated into outcome benefits as yet. The introduction of novel biomarkers associated with renal damage was primarily aimed at aiding early recognition of acute kidney injury. We argue that, in the future, using biomarkers may not only alert to acute kidney injury but may direct therapy in a personalized fashion rather than a one-size-fits-all approach.

  2. Remote effects of acute kidney injury in a porcine model.

    PubMed

    Gardner, David S; De Brot, Simone; Dunford, Louise J; Grau-Roma, Llorenc; Welham, Simon J M; Fallman, Rebecca; O'Sullivan, Saoirse E; Oh, Weng; Devonald, Mark A J

    2016-02-15

    Acute kidney injury (AKI) is a common and serious condition with no specific treatment. An episode of AKI may affect organs distant from the kidney, further increasing the morbidity associated with AKI. The mechanism of organ cross talk after AKI is unclear. The renal and immune systems of pigs and humans are alike. Using a preclinical animal (porcine) model, we tested the hypothesis that early effects of AKI on distant organs is by immune cell infiltration, leading to inflammatory cytokine production, extravasation, and edema. In 29 pigs exposed to either sham surgery or renal ischemia-reperfusion (control, n = 12; AKI, n = 17), we assessed remote organ (liver, lung, brain) effects in the short (from 2- to 48-h reperfusion) and longer term (5 wk later) using immunofluorescence (for leukocyte infiltration, apoptosis), a cytokine array, tissue elemental analysis (e.g., electrolytes), blood hematology and chemistry (e.g., liver enzymes), and PCR (for inflammatory markers). AKI elicited significant, short-term (∼24 h) increments in enzymes indicative of acute liver damage (e.g. , AST: ALT ratio; P = 0.02) and influenced tissue biochemistry in some remote organs (e.g., lung tissue [Ca(2+)] increased; P = 0.04). These effects largely resolved after 48 h, and no further histopathology, edema, apoptosis, or immune cell infiltration was noted in the liver, lung, or hippocampus in the short and longer term. AKI has subtle biochemical effects on remote organs in the short term, including a transient increment in markers of acute liver damage. These effects resolved by 48 h, and no further remote organ histopathology, apoptosis, edema, or immune cell infiltration was noted.

  3. A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries

    PubMed Central

    Mann, Aman P.; Scodeller, Pablo; Hussain, Sazid; Joo, Jinmyoung; Kwon, Ester; Braun, Gary B.; Mölder, Tarmo; She, Zhi-Gang; Kotamraju, Venkata Ramana; Ranscht, Barbara; Krajewski, Stan; Teesalu, Tambet; Bhatia, Sangeeta; Sailor, Michael J.; Ruoslahti, Erkki

    2016-01-01

    Traumatic brain injury (TBI) is a major health and socio-economic problem, but no pharmacological agent is currently approved for the treatment of acute TBI. Thus, there is a great need for advances in this field. Here, we describe a short peptide (sequence CAQK) identified by in vivo phage display screening in mice with acute brain injury. The CAQK peptide selectively binds to injured mouse and human brain, and systemically injected CAQK specifically homes to sites of brain injury in mouse models. The CAQK target is a proteoglycan complex upregulated in brain injuries. Coupling to CAQK increased injury site accumulation of systemically administered molecules ranging from a drug-sized molecule to nanoparticles. CAQK-coated nanoparticles containing silencing oligonucleotides provided the first evidence of gene silencing in injured brain parenchyma by systemically administered siRNA. These findings present an effective targeting strategy for the delivery of therapeutics in clinical management of acute brain injuries. PMID:27351915

  4. Acute Gastric Injury Caused by Undissolved Sodium Picosulfate/Magnesium Citrate Powder

    PubMed Central

    Ze, Eun Young; Choi, Chang Hwan; Kim, Jeong Wook

    2017-01-01

    Sodium picosulfate/magnesium citrate (SPMC) is a widely used oral bowel cleansing agent considered to be relatively safe. However, partially dissolved or undissolved SPMC powder may cause severe injuries of the esophagus and stomach. We report a very rare case of acute gastric injury without esophageal damage caused by the ingestion of undissolved SPMC powder. A 69-year-old man experienced epigastric pain after swallowing SPMC powder without dissolving it in water in preparation for a screening colonoscopy. He realized his mistake immediately and subsequently drank 2 L of water. The esophagogastroduodenoscopy conducted after 12 hours indicated an acute gastric ulceration without injury of the esophagus or duodenum. The endoscopy conducted after 6 weeks of oral proton pump inhibitor treatment showed healing of the gastric injury. This suggested that drinking large amounts of water after ingesting partially dissolved or undissolved SPMC powder can prevent serious esophageal injury, but offers no preventive benefit for acute gastric injury. PMID:27732774

  5. A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries

    NASA Astrophysics Data System (ADS)

    Mann, Aman P.; Scodeller, Pablo; Hussain, Sazid; Joo, Jinmyoung; Kwon, Ester; Braun, Gary B.; Mölder, Tarmo; She, Zhi-Gang; Kotamraju, Venkata Ramana; Ranscht, Barbara; Krajewski, Stan; Teesalu, Tambet; Bhatia, Sangeeta; Sailor, Michael J.; Ruoslahti, Erkki

    2016-06-01

    Traumatic brain injury (TBI) is a major health and socio-economic problem, but no pharmacological agent is currently approved for the treatment of acute TBI. Thus, there is a great need for advances in this field. Here, we describe a short peptide (sequence CAQK) identified by in vivo phage display screening in mice with acute brain injury. The CAQK peptide selectively binds to injured mouse and human brain, and systemically injected CAQK specifically homes to sites of brain injury in mouse models. The CAQK target is a proteoglycan complex upregulated in brain injuries. Coupling to CAQK increased injury site accumulation of systemically administered molecules ranging from a drug-sized molecule to nanoparticles. CAQK-coated nanoparticles containing silencing oligonucleotides provided the first evidence of gene silencing in injured brain parenchyma by systemically administered siRNA. These findings present an effective targeting strategy for the delivery of therapeutics in clinical management of acute brain injuries.

  6. Acute Respiratory Distress Syndrome: Role of Oleic Acid-Triggered Lung Injury and Inflammation

    PubMed Central

    Gonçalves-de-Albuquerque, Cassiano Felippe; Silva, Adriana Ribeiro; Burth, Patrícia; Castro-Faria, Mauro Velho; Castro-Faria-Neto, Hugo Caire

    2015-01-01

    Lung injury especially acute respiratory distress syndrome (ARDS) can be triggered by diverse stimuli, including fatty acids and microbes. ARDS affects thousands of people worldwide each year, presenting high mortality rate and having an economic impact. One of the hallmarks of lung injury is edema formation with alveoli flooding. Animal models are used to study lung injury. Oleic acid-induced lung injury is a widely used model resembling the human disease. The oleic acid has been linked to metabolic and inflammatory diseases; here we focus on lung injury. Firstly, we briefly discuss ARDS and secondly we address the mechanisms by which oleic acid triggers lung injury and inflammation. PMID:26640323

  7. Utility of serum concentration of protein S100 at admission to the medical intensive care unit in prediction of permanent neurological injury

    PubMed Central

    Knapik, Małgorzata; Partyka, Robert; Broll, Iwona; Cieśla, Daniel; Wawrzyńczyk, Maciej; Kokocińska, Danuta; Jałowiecki, Przemysław

    2016-01-01

    Introduction Admission to the intensive care unit (ICU) may be preceded by dramatic events leading to permanent neurological injury. Plasma S100 protein levels are proved to be clinically useful in predicting neurological outcome following cardiac arrest. It is unclear, however, whether this may be extrapolated to a broader population of ICU patients. Aim To assess the utility of plasma S100 protein in predicting death, permanent neurological damage, or unfavourable outcome at admission to the intensive care unit. Material and methods The concentration of plasma S100 protein was established in 102 patients on admission to the ICU, regardless of their neurological status and the reason for admission. The majority of patients were admitted with various cardiac diseases, excluding trauma patients. The patients were classified into three groups with the following binary outcomes: permanent neurological deficit or restoration of consciousness; unfavourable outcome (death or survival with permanent neurological deficit) or favourable outcome; and death or survival. Results Plasma S100 protein levels at admission facilitated the identification of patients who later developed a permanent neurological deficit or regained consciousness (p < 0.0001). All patients with plasma S100 protein over 0.532 μg/l at ICU admission either developed a permanent neurological deficit or had an unfavourable outcome (death or survival with permanent neurological deficit). However, sensitivity for this cut-off value was only 48% and 40%, respectively. Conclusions Plasma S100 protein levels over 0.532 μg/l are specific but not sensitive for both permanent neurological deficit and unfavourable outcome when assessed in a heterogeneous population at admission to the ICU. PMID:28096833

  8. Targeting L-Selectin to Improve Neurologic and Urologic Function After Spinal Cord Injury

    DTIC Science & Technology

    2013-10-01

    Terminal assessments of coordination and gait analysis were performed 6 weeks post-injury utilizing gridwalking (Figure 9) and CatWalk kinematic gait ...Finally, kinematic gait analysis was performed on a small cohort of mice at 6 weeks with CatWalk software. Mice were run across a glass walkway...distance in SCI mice receiving DFA. Vehicle N=10, 40mg/kg & 60mg/kg DFA N=12. One-way ANOVA. Figure 10. CatWalk kinematic gait analysis of SCI

  9. Peripheral Inflammatory Markers and Antioxidant Response during the Post-Acute and Chronic Phase after Severe Traumatic Brain Injury

    PubMed Central

    Licastro, Federico; Hrelia, Silvana; Porcellini, Elisa; Malaguti, Marco; Di Stefano, Cristina; Angeloni, Cristina; Carbone, Ilaria; Simoncini, Laura; Piperno, Roberto

    2016-01-01

    Traumatic brain injury (TBI) is a mechanical insult to the brain caused by external forces and associated with inflammation and oxidative stress. The patients may show different profiles of neurological recovery and a combination of oxidative damage and inflammatory processes can affect their courses. It is known that an overexpression of cytokines can be seen in peripheral blood in the early hours/days after the injury, but little is known about the weeks and months encompassing the post-acute and chronic phases. In addition, no information is available about the antioxidant responses mediated by the major enzymes that regulate reactive oxygen species levels: superoxide dismutase, catalase, peroxidases, and GSH-related enzymes. This study investigates the 6-month trends of inflammatory markers and antioxidant responses in 22 severe TBI patients with prolonged disorders of consciousness, consecutively recruited in a dedicated neurorehabilitation facility. Patients with a high degree of neurological impairment often show an uncertain outcome. In addition, the profiles of plasma activities were related to the neurological recovery after 12 months. Venous peripheral blood samples were taken blindly as soon as clinical signs and laboratory markers confirmed the absence of infections, 3 and 6 months later. The clinical and neuropsychological assessment continued up to 12 months. Nineteen patients completed the follow-up. In the chronic phase, persistent high plasma levels of cytokines can interfere with cognitive functioning and higher post-acute levels of cytokines [interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL1b, IL6] are associated with poorer cognitive recoveries 12 months later. Moreover, higher IFN-γ, higher TNF-α, and lower glutathione peroxidase activity are associated with greater disability. The results add evidence of persistent inflammatory response, provide information about long-term imbalance of antioxidant activity, and suggest that

  10. Peripheral Inflammatory Markers and Antioxidant Response during the Post-Acute and Chronic Phase after Severe Traumatic Brain Injury.

    PubMed

    Licastro, Federico; Hrelia, Silvana; Porcellini, Elisa; Malaguti, Marco; Di Stefano, Cristina; Angeloni, Cristina; Carbone, Ilaria; Simoncini, Laura; Piperno, Roberto

    2016-01-01

    Traumatic brain injury (TBI) is a mechanical insult to the brain caused by external forces and associated with inflammation and oxidative stress. The patients may show different profiles of neurological recovery and a combination of oxidative damage and inflammatory processes can affect their courses. It is known that an overexpression of cytokines can be seen in peripheral blood in the early hours/days after the injury, but little is known about the weeks and months encompassing the post-acute and chronic phases. In addition, no information is available about the antioxidant responses mediated by the major enzymes that regulate reactive oxygen species levels: superoxide dismutase, catalase, peroxidases, and GSH-related enzymes. This study investigates the 6-month trends of inflammatory markers and antioxidant responses in 22 severe TBI patients with prolonged disorders of consciousness, consecutively recruited in a dedicated neurorehabilitation facility. Patients with a high degree of neurological impairment often show an uncertain outcome. In addition, the profiles of plasma activities were related to the neurological recovery after 12 months. Venous peripheral blood samples were taken blindly as soon as clinical signs and laboratory markers confirmed the absence of infections, 3 and 6 months later. The clinical and neuropsychological assessment continued up to 12 months. Nineteen patients completed the follow-up. In the chronic phase, persistent high plasma levels of cytokines can interfere with cognitive functioning and higher post-acute levels of cytokines [interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL1b, IL6] are associated with poorer cognitive recoveries 12 months later. Moreover, higher IFN-γ, higher TNF-α, and lower glutathione peroxidase activity are associated with greater disability. The results add evidence of persistent inflammatory response, provide information about long-term imbalance of antioxidant activity, and suggest that

  11. Emergency Neurological Life Support: Intracranial Hypertension and Herniation

    PubMed Central

    Shoykhet, Michael; Cadena, Rhonda

    2016-01-01

    Sustained intracranial hypertension and acute brain herniation are “brain codes,” signifying catastrophic neurological events that require immediate recognition and treatment to prevent irreversible injury and death. As in cardiac arrest, a brain code mandates the organized implementation of a stepwise management algorithm. The goal of this emergency neurological life support protocol is to implement an evidence-based, standardized approach to the evaluation and management of patients with intracranial hypertension and/or herniation. PMID:26438459

  12. Preventing and Treating Acute Kidney Injury Among Hospitalized Patients with Cirrhosis and Ascites: A Narrative Review.

    PubMed

    Tapper, Elliot B; Bonder, Alan; Cardenas, Andres

    2016-05-01

    Acute kidney injury in the setting of ascites and cirrhosis is a medical emergency characterized by significant morbidity and mortality. Clinicians other than gastroenterologists are often the front line against acute kidney injury for patients with ascites. Owing to the specifics of cirrhotic physiology, the treatment and prevention of acute kidney injury in the setting of ascites has unique features, widespread knowledge of which will benefit our patients with cirrhosis. Early detection and treatment of infection, maximization of cardiac output, and avoidance of medications that limit cardiorenal adaptations to arterial underfilling are part of a multipronged strategy to protect the renal function of our patients with cirrhosis and ascites.

  13. Novel biomarkers for early diagnosis of acute kidney injury after cardiac surgery in adults

    PubMed Central

    Kališnik, Jurij Matija

    2016-01-01

    Acute kidney injury after cardiac surgery with cardiopulmonary bypass is a common and serious complication and it is associated with increased morbidity and mortality. Diagnosis of acute kidney injury is based on the serum creatinine levels which rise several hours to days after the initial injury. Thus, novel biomarkers that will enable faster diagnosis are needed in clinical practice. There are numerous urine and serum proteins that indicate kidney injury and are under extensive research. Despite promising basic research results and assembled data, which indicate superiority of some biomarkers to creatinine, we are still awaiting clinical application. PMID:27212976

  14. Effects of acute versus post-acute systemic delivery of neural progenitor cells on neurological recovery and brain remodeling after focal cerebral ischemia in mice.

    PubMed

    Doeppner, T R; Kaltwasser, B; Teli, M K; Bretschneider, E; Bähr, M; Hermann, D M

    2014-08-21

    Intravenous transplantation of neural progenitor cells (NPCs) induces functional recovery after stroke, albeit grafted cells are not integrated into residing neural networks. However, a systematic analysis of intravenous NPC delivery at acute and post-acute time points and their long-term consequences does not exist. Male C57BL6 mice were exposed to cerebral ischemia, and NPCs were intravenously grafted on day 0, on day 1 or on day 28. Animals were allowed to survive for up to 84 days. Mice and tissues were used for immunohistochemical analysis, flow cytometry, ELISA and behavioral tests. Density of grafted NPCs within the ischemic hemisphere was increased when cells were transplanted on day 28 as compared with transplantation on days 0 or 1. Likewise, transplantation on day 28 yielded enhanced neuronal differentiation rates of grafted cells. Post-ischemic brain injury, however, was only reduced when NPCs were grafted at acute time points. On the contrary, reduced post-ischemic functional deficits due to NPC delivery were independent of transplantation paradigms. NPC-induced neuroprotection after acute cell delivery was due to stabilization of the blood-brain barrier (BBB), reduction in microglial activation and modulation of both peripheral and central immune responses. On the other hand, post-acute NPC transplantation stimulated post-ischemic regeneration via enhanced angioneurogenesis and increased axonal plasticity. Acute NPC delivery yields long-term neuroprotection via enhanced BBB integrity and modulation of post-ischemic immune responses, whereas post-acute NPC delivery increases post-ischemic angioneurogenesis and axonal plasticity. Post-ischemic functional recovery, however, is independent of NPC delivery timing, which offers a broad therapeutic time window for stroke treatment.

  15. Inhibition of hepatic cells pyroptosis attenuates CLP-induced acute liver injury

    PubMed Central

    Chen, Yuan-Li; Xu, Guo; Liang, Xiao; Wei, Juan; Luo, Jing; Chen, Guan-Nan; Yan, Xiao-Di; Wen, Xue-Ping; Zhong, Ming; Lv, Xin

    2016-01-01

    Pyroptosis is a programmed cell death associated with caspase-1 and accompanied by the secretion of a large number of pro-inflammatory cytokines. In the acute stage of sepsis, the release of several pro-inflammatory cytokines aggravates hepatic cell death, and acute liver injury is aggravated with the progress of the disease, resulting in acute liver failure with a very high mortality rate. The present study investigated the effect of inhibiting hepatic cell pyroptosis on the septic acute liver injury. Septic acute liver injury mice model was established by cecal ligation and puncture (CLP model). The liver tissues were assessed for inflammatory infiltration by HE, serum concentrations of ALT, AST, IL-1β, and IL-18 were examined by ELISA, hepatic cell pyroptosis was determined by flow cytometry, and expressions of caspase-1 and NLRP3 were assessed by Western blot. CLP-induced acute liver injury was distinct at 24 h post-operation, with the highest hepatic cell pyroptosis rate. The pyroptosis rate and liver injury indexes were positively correlated. Western blot showed that the expressions of pyroptosis-related proteins, caspase-1, and NLRP3, were increased. Normal mouse hepatic cells were cultured in vitro and LPS+ATP introduced to establish the cell model of septic acute liver injury. The expressions of caspase-1, NLRP3, IL-1β, and IL-18 in LPS+ATP group were significantly higher than the control group by Western blot and ELISA. The inhibitors of NLRP3 (Glyburide) and caspase-1 (AC-YVAD-CMK) alone or in combination were used to pre-treat the hepatic cells, which revealed that the pyroptosis rate was decreased and the cell damage alleviated. The in vivo assay in rats showed that post inhibitor treatment, the 10-days survival was significantly improved and the liver damage reduced. Therefore, inhibiting the hepatic cell pyroptosis could alleviate CLP-induced acute liver injury, providing a novel treatment target for septic acute liver injury. PMID:28078039

  16. CT findings of a thoracic vertebral hemangioma presenting with acute neurological symptoms.

    PubMed

    Tan, Sinan; Kurt, Aydın; Okutan, Ozerk; Keskin, Suat

    2011-01-01

    Vertebral body hemangiomas are benign lesions and account for 4% of all spinal tumors. The most common histological type is cavernous hemangioma. These tumors generally locate in the vertebral body as a solitary lesion. Multiple lesions are seen in approximately 25-30% of vertebral hemangiomas. Mostly they are asymptomatic and incidentally found with radiological studies. Symptomatic vertebral hemangiomas are rare and represent < 1% of all hemangiomas; however, if untreated, they may cause local or radicular pain and neurological deficits ranging from myeloradiculopathy to paralysis. In this case we aim to present preoperative and postoperative Computed Tomography findings of a cavernous hemangioma that caused sudden motor deficit and was localised to the thoracic vertebra corpus and posterior elements.

  17. A Clinical Study of Acute Kidney Injury in Tropical Acute Febrile Illness

    PubMed Central

    Bhat, Ajay; Prabhu, Mangalore Venkatraya

    2016-01-01

    Introduction Tropical Acute Febrile Illness (TAFI) is one of the most common causes of morbidity within the community. Acute Kidney Injury (AKI) due to infective and non infective causes is a major complication. Presence of AKI is a major cause of mortality among patients with TAFI. Aim To study the spectrum of tropical acute febrile illness; the proportion, spectrum and staging of acute kidney injury; Renal Replacement Therapy (RRT) initiation and in-hospital mortality. Materials and Methods A total of 600 TAFI patients were prospectively studied at a tertiary care centre in coastal Karnataka between September 2012 and September 2014 for the aetiology of TAFI; the development and staging of AKI based on Kidney disease: Improving global outcomes (KDIGO) guidelines; the initiation of RRT and in-hospital mortality. Statistical Analysis: Data analysis was done using SPSS version 17.0 with statistical significance calculated using chi-square and Fisher’s exact t-test for which p-value <0.05 was considered significant. Results The spectrum of TAFI, in decreasing order, was vivax malaria, leptospirosis, dengue fever, falciparum malaria, mixed malaria, enteric fever, scrub typhus and the most common aetiology was malaria. The proportion of AKI was 54%. The most common cause of AKI, its stages 2 and 3, RRT initiation and in-hospital mortality was leptospirosis; and AKI stage 1 was dengue fever. KDIGO AKI stage 1, 2 and 3 was seen in 46.9%, 31.2% and 21.9% of AKI patients, respectively. RRT initiation was required in 10.2% of AKI patients and in-hospital mortality was 3% among all patients. AKI, RRT initiationand in-hospital mortality were significantly associated with older age, fever duration and other presenting complaints, examination findings, renal function and other parameters, leptospirosis, dengue fever, falciparum malaria. Conclusion The aetiology in about half of TAFI patients in coastal Karnataka was malaria. More than 50% develop AKI with greater than one

  18. A Type-II Positive Allosteric Modulator of α7 nAChRs Reduces Brain Injury and Improves Neurological Function after Focal Cerebral Ischemia in Rats

    PubMed Central

    Sun, Fen; Jin, Kunlin; Uteshev, Victor V.

    2013-01-01

    In the absence of clinically-efficacious therapies for ischemic stroke there is a critical need for development of new therapeutic concepts and approaches for prevention of brain injury secondary to cerebral ischemia. This study tests the hypothesis that administration of PNU-120596, a type-II positive allosteric modulator (PAM-II) of α7 nicotinic acetylcholine receptors (nAChRs), as long as 6 hours after the onset of focal cerebral ischemia significantly reduces brain injury and neurological deficits in an animal model of ischemic stroke. Focal cerebral ischemia was induced by a transient (90 min) middle cerebral artery occlusion (MCAO). Animals were then subdivided into two groups and injected intravenously (i.v.) 6 hours post-MCAO with either 1 mg/kg PNU-120596 (treated group) or vehicle only (untreated group). Measurements of cerebral infarct volumes and neurological behavioral tests were performed 24 hrs post-MCAO. PNU-120596 significantly reduced cerebral infarct volume and improved neurological function as evidenced by the results of Bederson, rolling cylinder and ladder rung walking tests. These results forecast a high therapeutic potential for PAMs-II as effective recruiters and activators of endogenous α7 nAChR-dependent cholinergic pathways to reduce brain injury and improve neurological function after cerebral ischemic stroke. PMID:23951360

  19. Targeted fibrillar nanocarbon RNAi treatment of acute kidney injury

    PubMed Central

    Alidori, Simone; Akhavein, Nima; Thorek, Daniel L. J.; Behling, Katja; Romin, Yevgeniy; Queen, Dawn; Beattie, Bradley J.; Manova-Todorova, Katia; Bergkvist, Magnus; Scheinberg, David A.; McDevitt, Michael R.

    2016-01-01

    RNA interference has tremendous yet unrealized potential to treat a wide range of illnesses. Innovative solutions are needed to protect and selectively deliver small interfering RNA (siRNA) cargo to and within a target cell to fully exploit siRNA as a therapeutic tool in vivo. Herein, we describe ammonium-functionalized carbon nanotube (fCNT)–mediated transport of siRNA selectively and with high efficiency to renal proximal tubule cells in animal models of acute kidney injury (AKI). fCNT enhanced siRNA delivery to tubule cells compared to siRNA alone and effectively knocked down the expression of several target genes, including Trp53, Mep1b, Ctr1, and EGFP. A clinically relevant cisplatin-induced murine model of AKI was used to evaluate the therapeutic potential of fCNT-targeted siRNA to effectively halt the pathogenesis of renal injury. Prophylactic treatment with a combination of fCNT/siMep1b and fCNT/siTrp53 significantly improved progression-free survival compared to controls via a mechanism that required concurrent reduction of meprin-1β and p53 expression. The fCNT/siRNA was well tolerated, and no toxicological consequences were observed in murine models. Toward clinical application of this platform, fCNTs were evaluated for the first time in nonhuman primates. The rapid and kidney-specific pharmacokinetic profile of fCNT in primates was comparable to what was observed in mice and suggests that this approach is amenable for use in humans. The nanocarbon-mediated delivery of siRNA provides a therapeutic means for the prevention of AKI to safely overcome the persistent barrier of nephrotoxicity during medical intervention. PMID:27009268

  20. Acute kidney injury following spinal instrumentation surgery in children

    PubMed Central

    Jöbsis, Jasper J; Alabbas, Abdullah; Milner, Ruth; Reilly, Christopher; Mulpuri, Kishore; Mammen, Cherry

    2017-01-01

    AIM To determine acute kidney in jury (AKI) incidence and potential risk factors of AKI in children undergoing spinal instrumentation surgery. METHODS AKI incidence in children undergoing spinal instrumentation surgery at British Columbia Children’s Hospital between January 2006 and December 2008 was determined by the Acute Kidney Injury Networ classification using serum creatinine and urine output criteria. During this specific time period, all patients following spinal surgery were monitored in the pediatric intensive care unit and had an indwelling Foley catheter permitting hourly urine output recording. Cases of AKI were identified from our database. From the remaining cohort, we selected group-matched controls that did not satisfy criteria for AKI. The controls were matched for sex, age and underlying diagnosis (idiopathic vs non-idiopathic scoliosis). RESULTS Thirty five of 208 patients met criteria for AKI with an incidence of 17% (95%CI: 12%-23%). Of all children who developed AKI, 17 (49%) developed mild AKI (AKI Stage 1), 17 (49%) developed moderate AKI (Stage 2) and 1 patient (3%) met criteria for severe AKI (Stage 3). An inverse relationship was observed with AKI incidence and the amount of fluids received intra-operatively. An inverse relationship was observed with AKI incidence and the amount of fluids received intra-operatively classified by fluid tertiles: 70% incidence in those that received the least amount of fluids vs 29% that received the most fluids (> 7.9, P = 0.02). Patients who developed AKI were more frequently exposed to nephrotoxins (non steroidal anti inflammatory drugs or aminoglycosides) than control patients during their peri-operative course (60% vs 22%, P < 0.001). CONCLUSION We observed a high incidence of AKI following spinal instrumentation surgery in children that is potentially related to the frequent use of nephrotoxins and the amount of fluid administered peri-operatively. PMID:28316941

  1. Oral Administration of Escin Inhibits Acute Inflammation and Reduces Intestinal Mucosal Injury in Animal Models

    PubMed Central

    Li, Minmin; Lu, Chengwen; Zhang, Leiming; Zhang, Jianqiao; Du, Yuan; Duan, Sijin; Wang, Tian; Fu, Fenghua

    2015-01-01

    The present study aimed to investigate the effects of oral administration of escin on acute inflammation and intestinal mucosal injury in animal models. The effects of escin on carrageenan-induced paw edema in a rat model of acute inflammation, cecal ligation and puncture (CLP) induced intestinal mucosal injury in a mouse model, were observed. It was shown that oral administration of escin inhibits carrageenan-induced paw edema and decreases the production of prostaglandin E2 (PGE2) and cyclooxygenase- (COX-) 2. In CLP model, low dose of escin ameliorates endotoxin induced liver injury and intestinal mucosal injury and increases the expression of tight junction protein claudin-5 in mice. These findings suggest that escin effectively inhibits acute inflammation and reduces intestinal mucosal injury in animal models. PMID:26199634

  2. A Multibiomarker-Based Model for Estimating the Risk of Septic Acute Kidney Injury

    PubMed Central

    Wong, Hector R.; Cvijanovich, Natalie Z.; Anas, Nick; Allen, Geoffrey L.; Thomas, Neal J.; Bigham, Michael T.; Weiss, Scott L.; Fitzgerald, Julie; Checchia, Paul A.; Meyer, Keith; Shanley, Thomas P.; Quasney, Michael; Hall, Mark; Gedeit, Rainer; Freishtat, Robert J.; Nowak, Jeffrey; Raj, Shekhar S.; Gertz, Shira; Dawson, Emily; Howard, Kelli; Harmon, Kelli; Lahni, Patrick; Frank, Erin; Hart, Kimberly W.; Lindsell, Christopher J.

    2015-01-01

    Objective The development of acute kidney injury in patients with sepsis is associated with worse outcomes. Identifying those at risk for septic acute kidney injury could help to inform clinical decision making. We derived and tested a multibiomarker-based model to estimate the risk of septic acute kidney injury in children with septic shock. Design Candidate serum protein septic acute kidney injury biomarkers were identified from previous transcriptomic studies. Model derivation involved measuring these biomarkers in serum samples from 241 subjects with septic shock obtained during the first 24 hours of admission and then using a Classification and Regression Tree approach to estimate the probability of septic acute kidney injury 3 days after the onset of septic shock, defined as at least two-fold increase from baseline serum creatinine. The model was then tested in a separate cohort of 200 subjects. Setting Multiple PICUs in the United States. Interventions None other than standard care. Measurements and Main Results The decision tree included a first-level decision node based on day 1 septic acute kidney injury status and five subsequent biomarker-based decision nodes. The area under the curve for the tree was 0.95 (CI95, 0.91–0.99), with a sensitivity of 93% and a specificity of 88%. The tree was superior to day 1 septic acute kidney injury status alone for estimating day 3 septic acute kidney injury risk. In the test cohort, the tree had an area under the curve of 0.83 (0.72–0.95), with a sensitivity of 85% and a specificity of 77% and was also superior to day 1 septic acute kidney injury status alone for estimating day 3 septic acute kidney injury risk. Conclusions We have derived and tested a model to estimate the risk of septic acute kidney injury on day 3 of septic shock using a novel panel of biomarkers. The model had very good performance in a test cohort and has test characteristics supporting clinical utility and further prospective evaluation

  3. Acute myocardial injury caused by Sydney funnel-web spider (Atrax robustus) envenoming.

    PubMed

    Isbister, G K; Warner, G

    2003-12-01

    A 67-year-old female suffered envenoming by a Sydney funnel-web spider (Atrax robustus), complicated by ST elevation and elevated troponin levels consistent with an acute myocardial injury. She was treated primarily with funnel-web spider antivenom, admission to intensive care and initial respiratory support for acute pulmonary oedema. The mechanism by which funnel-web spider envenomation caused myocardial injury is unclear but follow-up nuclear studies in the patient demonstrated that she had minimal atherosclerotic disease.

  4. Estrogen Effects after a Crush Muscle Injury and Acute Exposure to Hypobaric Hypoxia

    DTIC Science & Technology

    2015-03-01

    AFRL-SA-WP-TR-2015-0007 Estrogen Effects after a Crush Muscle Injury and Acute Exposure to Hypobaric Hypoxia Dr. Barbara St...after a Crush Muscle Injury and Acute Exposure to Hypobaric Hypoxia 5a. CONTRACT NUMBER FA7014-10-2-0001 5b. GRANT NUMBER 5c. PROGRAM...pressure equivalent to an altitude of 8,000 feet , which is considered high altitude, and lacks abundant supplemental oxygen systems, en route care

  5. Neuroinflammation and Neuroimmune Dysregulation after Acute Hypoxic-Ischemic Injury of Developing Brain

    PubMed Central

    Bhalala, Utpal S.; Koehler, Raymond C.; Kannan, Sujatha

    2015-01-01

    Hypoxic-ischemic (HI) injury to developing brain results from birth asphyxia in neonates and from cardiac arrest in infants and children. It is associated with varying degrees of neurologic sequelae, depending upon the severity and length of HI. Global HI triggers a series of cellular and biochemical pathways that lead to neuronal injury. One of the key cellular pathways of neuronal injury is inflammation. The inflammatory cascade comprises activation and migration of microglia – the so-called “brain macrophages,” infiltration of peripheral macrophages into the brain, and release of cytotoxic and proinflammatory cytokines. In this article, we review the inflammatory and immune mechanisms of secondary neuronal injury after global HI injury to developing brain. Specifically, we highlight the current literature on microglial activation in relation to neuronal injury, proinflammatory and anti-inflammatory/restorative pathways, the role of peripheral immune cells, and the potential use of immunomodulators as neuroprotective compounds. PMID:25642419

  6. ["Typical" and "less typical" sports injuries in the field of neurology].

    PubMed

    Kröss, R; Barolin, G S

    1983-07-31

    In times of increasing "sparetime pathology" sequels of sports are getting a new meaning in medicine. Surgeons are mainly involved in this issue but it also contacts neurologists. We differentiate between direct sequels of sports and concomitant incidents of sports. Besides the typical head injuries we saw a number of atypical traumatic damages such as a hit by a golf ball, fall on the buttocks and the header in football. Discprotrusions are mainly understood as concomitant incidents at sports because in most cases one has to consider preexisting disc lesions. Though there are typical motions in sports which rather lead to discprotrusions such as strong torsions of the body in football, serving in tennis, heavy lifting in wrestling or an unexpected fall into a hollow in skiing. In cerebrovascular events, sports is usually only one additive etiological component. Nevertheless the lack of adequate acclimatisation and the brisk beginning of stressing sports in high mountain areas (which is enabled through modern technic) can contribute a great deal to decompensation of cerebrovascular disorders. In this respect doping can have a serious influence since protecting physiological mechanisms are eliminated. Diving accidents are able to give rise to spinal, cerebral and cerebellar gasembolisation. Warning early symptoms of great value are TIA, vertigo and fits. Sport practice can figure as an unspecific test situation in order to provoke these events. Diagnostic investigation of the cardiovascular system and the CNS has to be performed in those cases. Particular regard should be paid to expert situations which tend to distort the clinical pictures.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Neurological benefits of omega-3 fatty acids.

    PubMed

    Dyall, S C; Michael-Titus, A T

    2008-01-01

    The central nervous system is highly enriched in long-chain polyunsaturated fatty acid (PUFA) of the omega-6 and omega-3 series. The presence of these fatty acids as structural components of neuronal membranes influences cellular function both directly, through effects on membrane properties, and also by acting as a precursor pool for lipid-derived messengers. An adequate intake of omega-3 PUFA is essential for optimal visual function and neural development. Furthermore, there is increasing evidence that increased intake of the long-chain omega-3 PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may confer benefits in a variety of psychiatric and neurological disorders, and in particular neurodegenerative conditions. However, the mechanisms underlying these beneficial effects are still poorly understood. Recent evidence also indicates that in addition to the positive effects seen in chronic neurodegenerative conditions, omega-3 PUFA may also have significant neuroprotective potential in acute neurological injury. Thus, these compounds offer an intriguing prospect as potentially new therapeutic approaches in both chronic and acute conditions. The purpose of this article is to review the current evidence of the neurological benefits of omega-3 PUFA, looking specifically at neurodegenerative conditions and acute neurological injury.

  8. A Novel Rat Model of Blast-Induced Traumatic Brain Injury Simulating Different Damage Degree: Implications for Morphological, Neurological, and Biomarker Changes

    PubMed Central

    Liu, Mengdong; Zhang, Chi; Liu, Wenbo; Luo, Peng; Zhang, Lei; Wang, Yuan; Wang, Zhanjiang; Fei, Zhou

    2015-01-01

    In current military conflicts and civilian terrorism, blast-induced traumatic brain injury (bTBI) is the primary cause of neurotrauma. However, the effects and mechanisms of bTBI are poorly understood. Although previous researchers have made significant contributions to establishing animal models for the simulation of bTBI, the precision and controllability of blast-induced injury in animal models must be improved. Therefore, we established a novel rat model to simulate blast-wave injury to the brain. To simulate different extents of bTBI injury, the animals were divided into moderate and severe injury groups. The miniature spherical explosives (pentaerythritol tetranitrate) used in each group were of different sizes (2.5 mm diameter in the moderate injury group and 3.0 mm diameter in the severe injury group). A specially designed apparatus was able to precisely adjust the positions of the miniature explosives and create eight rats with bTBI simultaneously, using a single electric detonator. Neurological functions, gross pathologies, histopathological changes and the expression levels of various biomarkers were examined after the explosion. Compared with the moderate injury group, there were significantly more neurological dysfunctions, cortical contusions, intraparenchymal hemorrhages, cortical expression of S-100β, myelin basic protein, neuron-specific enolase, IL-8, IL-10, inducible nitric oxide synthase, and HIF-1α in the severe injury group. These results demonstrate that we have created a reliable and reproducible bTBI model in rats. This model will be helpful for studying the mechanisms of bTBI and developing strategies for clinical bTBI treatment. PMID:25983677

  9. Nomogram for Predicting Time to Death After Withdrawal of Life-Sustaining Treatment in Patients With Devastating Neurological Injury.

    PubMed

    He, X; Xu, G; Liang, W; Liu, B; Xu, Y; Luan, Z; Lu, Y; Ko, D S C; Manyalich, M; Schroder, P M; Guo, Z

    2015-08-01

    Reliable prediction of time of death after withdrawal of life-sustaining treatment in patients with devastating neurological injury is crucial to successful donation after cardiac death. Herein, we conducted a study of 419 neurocritical patients who underwent life support withdrawal at four neurosurgical centers in China. Based on a retrospective cohort, we used multivariate Cox regression analysis to identify prognostic factors for patient death, which were then integrated into a nomogram. The model was calibrated and validated using data from an external retrospective cohort and a prospective cohort. We identified 10 variables that were incorporated into a nomogram. The C-indexes for predicting the 60-min death probability in the training, external validation and prospective validation cohorts were 0.96 (0.93-0.98), 0.94 (0.91-0.97), and 0.99 (0.97-1.00), respectively. The calibration plots after WLST showed an optimal agreement between the prediction of time to death by the nomogram and the actual observation for all cohorts. Then we identified 22, 26 and 37 as cut-points for risk stratification into four groups. Kaplan-Meier curves indicated distinct prognoses between patients in the different risk groups (p < 0.001). In conclusion, we have developed and validated a nomogram to accurately identify potential cardiac death donors in neurocritical patients in a Chinese population.

  10. Approaches to Predicting Outcomes in Patients with Acute Kidney Injury

    PubMed Central

    Saly, Danielle; Yang, Alina; Triebwasser, Corey; Oh, Janice; Sun, Qisi; Testani, Jeffrey; Parikh, Chirag R.; Bia, Joshua; Biswas, Aditya; Stetson, Chess; Chaisanguanthum, Kris

    2017-01-01

    Despite recognition that Acute Kidney Injury (AKI) leads to substantial increases in morbidity, mortality, and length of stay, accurate prognostication of these clinical events remains difficult. It remains unclear which approaches to variable selection and model building are most robust. We used data from a randomized trial of AKI alerting to develop time-updated prognostic models using stepwise regression compared to more advanced variable selection techniques. We randomly split data into training and validation cohorts. Outcomes of interest were death within 7 days, dialysis within 7 days, and length of stay. Data elements eligible for model-building included lab values, medications and dosages, procedures, and demographics. We assessed model discrimination using the area under the receiver operator characteristic curve and r-squared values. 2241 individuals were available for analysis. Both modeling techniques created viable models with very good discrimination ability, with AUCs exceeding 0.85 for dialysis and 0.8 for death prediction. Model performance was similar across model building strategies, though the strategy employing more advanced variable selection was more parsimonious. Very good to excellent prediction of outcome events is feasible in patients with AKI. More advanced techniques may lead to more parsimonious models, which may facilitate adoption in other settings. PMID:28122032

  11. Arctigenin attenuates lipopolysaccharide-induced acute lung injury in rats.

    PubMed

    Shi, Xianbao; Sun, Hongzhi; Zhou, Dun; Xi, Huanjiu; Shan, Lina

    2015-04-01

    Arctigenin (ATG) has been reported to possess anti-inflammatory properties. However, the effects of ATG on lipopolysaccharide (LPS)-induced acute lung injury (ALI) remains not well understood. In the present study, our investigation was designed to reveal the effect of ATG on LPS-induced ALI in rats. We found that ATG pretreatment attenuated the LPS-induced ALI, as evidenced by the reduced histological scores, myeloperoxidase activity, and wet-to-dry weight ratio in the lung tissues. This was accompanied by the decreased levels of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-1 (IL-6) in the bronchoalveolar lavage fluid. Furthermore, ATG downregulated the expression of nuclear factor kappa B (NF-κB) p65, promoted the phosphorylation of inhibitor of nuclear factor-κB-α (IκBα) and activated the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPKα) in the lung tissues. Our results suggested that ATG attenuates the LPS-induced ALI via activation of AMPK and suppression of NF-κB signaling pathway.

  12. [Metformin-associated lactic acidosis and acute kidney injury].

    PubMed

    Greco, Paolo; Regolisti, Giuseppe; Antoniotti, Riccardo; Maccari, Caterina; Parenti, Elisabetta; Corrado, Silvia; Fiaccadori, Enrico

    2016-01-01

    Metformin is recommended as the treatment of choice in patients with type 2 diabetes mellitus because of its efficacy, general tolerability and low cost. Recent guidelines have extended the use of metformin to patients with Chronic Kidney Disease (CKD) up to stage III. However, in the recent literature, cases of MALA (metformin-associated lactic acidosis) are increasingly reported. MALA is the most dangerous side effect of the drug, with an incidence rate of 2-9 cases per 100000 person-years of exposure. We report on two patients with accidental metformin overdose, severe lactic acidosis and acute kidney injury. In both cases, the usual dose of metformin was inappropriate with respect to the level of kidney dysfunction (CKD stage III). As both patients met the criteria for renal replacement therapy in metformin poisoning, they were treated effectively with sustained low-efficiency dialysis until normalization of serum lactate and bicarbonate values. Clinical status and kidney function improved and both patients could be discharged from the hospital.

  13. CXCL16 regulates cisplatin-induced acute kidney injury.

    PubMed

    Liang, Hua; Zhang, Zhengmao; He, Liqun; Wang, Yanlin

    2016-05-31

    The pathogenesis of cisplatin-induced acute kidney injury (AKI) is characterized by tubular cell apoptosis and inflammation. However, the molecular mechanisms are not fully understood. We found that CXCL16 was induced in renal tubular epithelial cells in response to cisplatin-induced AKI. Therefore, we investigated whether CXCL16 played a role in cisplatin-induced tubular cell apoptosis and inflammation. Wild-type and CXCL16 knockout mice were administrated with vehicle or cisplatin at 20 mg/kg by intraperitoneal injection. CXCL16 knockout mice had lower blood urea nitrogen and less tubular damage following cisplatin-induced AKI as compared with wild-type mice. Genetic disruption of CXCL16 reduced tubular epithelial cell apoptosis and decreased caspase-3 activation. Furthermore, CXCL16 deficiency inhibited infiltration of macrophages and T cells into the kidneys following cisplatin treatment, which was associated with reduced expression of the proinflammatory cytokines in the kidneys. Taken together, our results indicate that CXCL16 plays a crucial role in the pathogenesis of cisplatin-induced AKI through regulation of apoptosis and inflammation and maybe a novel therapeutic target for cisplatin-induced AKI.

  14. Community-acquired acute kidney injury in tropical countries.

    PubMed

    Jha, Vivekanand; Parameswaran, Sreejith

    2013-05-01

    Community-acquired acute kidney injury (AKI) in developing tropical countries is markedly different from AKI in developed countries with a temperate climate, which exemplifies the influence that environment can have on the epidemiology of human diseases. The aetiology and presentation of AKI reflect the ethnicity, socioeconomic factors, climatic and ecological characteristics in tropical countries. Tropical zones are characterized by high year-round temperatures and the absence of frost, which supports the propagation of infections that can cause AKI, including malaria, leptospirosis, HIV and diarrhoeal diseases. Other major causes of AKI in tropical countries are envenomation; ingestion of toxic herbs or chemicals; poisoning; and obstetric complications. These factors are associated with low levels of income, poor access to treatment, and social or cultural practices (such as the use of traditional herbal medicines and treatments) that contribute to poor outcomes of patients with AKI. Most causes of AKI in developing tropical countries are preventable, but strategies to improve the outcomes and reduce the burden of tropical AKI require both improvements in basic public health, achieved through effective interventions, and increased access to effective medical care (especially for patients with established AKI).

  15. Methylprednisolone for acute spinal cord injury: an increasingly philosophical debate.

    PubMed

    Bowers, Christian A; Kundu, Bornali; Hawryluk, Gregory W J

    2016-06-01

    Following publication of NASCIS II, methylprednisolone sodium succinate (MPSS) was hailed as a breakthrough for patients with acute spinal cord injury (SCI). MPSS use for SCI has since become very controversial and it is our opinion that additional evidence is unlikely to break the stalemate amongst clinicians. Patient opinion has the potential to break this stalemate and we review our recent findings which reported that spinal cord injured patients informed of the risks and benefits of MPSS reported a preference for MPSS administration. We discuss the implications of the current MPSS debate on translational research and seek to address some misconceptions which have evolved. As science has failed to resolve the MPSS debate we argue that the debate is an increasingly philosophical one. We question whether SCI might be viewed as a serious condition like cancer where serious side effects of therapeutics are tolerated even when benefits may be small. We also draw attention to the similarity between the side effects of MPSS and isotretinoin which is prescribed for the cosmetic disorder acne vulgaris. Ultimately we question how patient autonomy should be weighed in the context of current SCI guidelines and MPSS's status as a historical standard of care.

  16. IL-6 ameliorates acute lung injury in influenza virus infection

    PubMed Central

    Yang, Mei-Lin; Wang, Chung-Teng; Yang, Shiu-Ju; Leu, Chia-Hsing; Chen, Shun-Hua; Wu, Chao-Liang; Shiau, Ai-Li

    2017-01-01

    Interleukin 6 (IL-6) is involved in innate and adaptive immune responses to defend against pathogens. It also participates in the process of influenza infection by affecting viral clearance and immune cell responses. However, whether IL-6 impacts lung repair in influenza pathogenesis remains unclear. Here, we studied the role of IL-6 in acute influenza infection in mice. IL-6-deficient mice infected with influenza virus exhibited higher lethality, lost more body weight and had higher fibroblast accumulation and lower extracellular matrix (ECM) turnover in the lung than their wild-type counterparts. Deficiency in IL-6 enhanced proliferation, migration and survival of lung fibroblasts, as well as increased virus-induced apoptosis of lung epithelial cells. IL-6-deficient lung fibroblasts produced elevated levels of TGF-β, which may contribute to their survival. Furthermore, macrophage recruitment to the lung and phagocytic activities of macrophages during influenza infection were reduced in IL-6-deficient mice. Collectively, our results indicate that IL-6 is crucial for lung repair after influenza-induced lung injury through reducing fibroblast accumulation, promoting epithelial cell survival, increasing macrophage recruitment to the lung and enhancing phagocytosis of viruses by macrophages. This study suggests that IL-6 may be exploited for lung repair during influenza infection. PMID:28262742

  17. Acute kidney injury associated with Plasmodium malariae infection.

    PubMed

    Badiane, Aida S; Diongue, Khadim; Diallo, Seydou; Ndongo, Aliou A; Diedhiou, Cyrille K; Deme, Awa B; Ma, Diallo; Ndiaye, Mouhamadou; Seck, Mame C; Dieng, Therese; Ndir, Omar; Mboup, Souleymane; Ndiaye, Daouda

    2014-06-07

    According to current estimates, Plasmodium malariae is not very common in Senegal, as more than 98% of malaria cases are suspected to be due to Plasmodium falciparum. However, it is possible that other malarial species are being under-reported or misdiagnosed. This is a report of a case of P. malariae in a 30-year-old man previously hospitalized with acute kidney injury after treatment with quinine and re-hospitalized three months later. He was diagnosed with renal cortical necrosis post malaria treatment. Plasmodium malariae was identified with light microscope and confirmed using species-specific small-subunit rRNA (ssrRNA) amplification.The patient was treated for malaria with intravenous quinine for seven days, followed by three days of oral treatment; the bacterial infection was treated using ceftriaxone during the first hospitalization and ciprofloxacin associated with ceftriaxone the second time. He also had four rounds of dialysis after which he partially recovered the renal function. Given the complications that can be caused by P. malariae infection, it should be systematically looked for, even if the predominant species is P. falciparum in Senegal.

  18. Betulin protects mice from bacterial pneumonia and acute lung injury.

    PubMed

    Wu, Qianchao; Li, Hongyu; Qiu, Jiaming; Feng, Haihua

    2014-10-01

    Betulin, a naturally occurring triterpene, has shown anti-HIV activity, but details on the anti-inflammatory activity are scanty. In this study, we sought to investigate the effect of Betulin on LPS-induced activation of cell lines with relevance for lung inflammation in vitro and on lung inflammation elicited by either LPS or viable Escherichia coli (E. coli) in vivo. In vitro, Betulin inhibited LPS-induced tumor necrosis factor α (TNF-α) and (interleukin) IL-6 levels and up-regulated the level of IL-10. Also Betulin suppressed the phosphorylation of nuclear factor-κB (NF-κB) p65 protein in LPS-stimulated RAW 264.7 cells. In vivo, Betulin alleviated LPS-induced acute lung injury. Treatment with Betulin diminished pro-inflammatory cytokines, myeloperoxidase activity and bacterial loads in lung tissue during gram-negative pneumonia. Our findings demonstrated that Betulin inhibits pro-inflammatory responses induced by the gram-negative stimuli LPS and E. coli, suggesting that Betulin may represent a novel strategy for the treatment of lung inflammation.

  19. Early detection of acute kidney injury after pediatric cardiac surgery

    PubMed Central

    Jefferies, John Lynn; Devarajan, Prasad

    2016-01-01

    Acute kidney injury (AKI) is increasingly recognized as a common problem in children undergoing cardiac surgery, with well documented increases in morbidity and mortality in both the short and the long term. Traditional approaches to the identification of AKI such as changes in serum creatinine have revealed a large incidence in this population with significant negative impact on clinical outcomes. However, the traditional diagnostic approaches to AKI diagnosis have inherent limitations that may lead to under-diagnosis of this pathologic process. There is a dearth of randomized controlled trials for the prevention and treatment of AKI associated with cardiac surgery, at least in part due to the paucity of early predictive biomarkers. Novel non-invasive biomarkers have ushered in a new era that allows for earlier detection of AKI. With these new diagnostic tools, a more consistent approach can be employed across centers that may facilitate a more accurate representation of the actual prevalence of AKI and more importantly, clinical investigation that may minimize the occurrence of AKI following pediatric cardiac surgery. A thoughtful management approach is necessary to mitigate the effects of AKI after cardiac surgery, which is best accomplished in close collaboration with pediatric nephrologists. Long-term surveillance for improvement in kidney function and potential development of chronic kidney disease should also be a part of the comprehensive management strategy. PMID:27429538

  20. Protective effect of vitamin E against acute kidney injury.

    PubMed

    Liu, Pengfei; Feng, Yetong; Wang, Yi; Zhou, Yulai; Zhao, Lei

    2015-01-01

    It has been well-known for many years now that vitamin E is an essential nutrient; however, some of the physiological functions of this vitamin are still far from being understood. In recent years, a series of preclinical and clinical studies proposed a protective role of vitamin E on acute kidney injury (AKI), which has a high morbidity rate and mortality rate in clinical investigations. Based on the benefits associated with vitamin E, such as strong antioxidant function, low toxicity, rare side-effects, and low cost, this therapy strategy has garnered an extensive amount of interest in the scientific community for the development of new therapy modes against AKI. In this review, a concise overview of the application of vitamin E in the treatment of AKI is provided as well as a summary of a series of published data regarding the combination therapy modes and detailed therapy mechanisms of vitamin E-based therapy against AKI. At present, there are critical points of this therapy mode that are still in need of further clarification, meaning the current understanding of the role of vitamin E in the treatment of AKI remains incomplete. However, the development of more reliable pharmacological or biotechnical strategies with vitamin E for the eventual treatment of patients with AKI may guide the next chapter of vitamin E research.

  1. Treatment of acute kidney injury with cast nephropathy.

    PubMed

    Walther, Carl; Podoll, Amber S; Finkel, Kevin W

    2014-07-01

    Nearly 50% of patients with multiple myeloma develop renal disease; acute kidney injury (AKI) from cast nephropathy, or "myeloma kidney" is the most common type. Development of AKI is associated with worse 1-year survival and reduces the therapeutic options available to patients. Therefore, there is a great need to develop more effective therapies. Cast nephropathy is due to the interaction and aggregation of filtered free light chains (FLCs) and Tamm- Horsfall protein (THP) causing intratubular obstruction and damage. The key to treating cast nephropathy is rapid lowering of FLCs as this correlates with renal recovery. Newer chemotherapy agents lower FLCs and have been referred to as "renoprotective". However there remains great interest in using various extracorporeal therapies to remove serum FLCs. Initially, therapeutic plasma exchange (TPE) was thought to improve renal outcomes in cast nephropathy based on small trials. The largest randomized trial of TPE, however, failed to show any benefit. A newer technique is extended high cut-off hemodialysis (HCO-HD). This modality uses a high molecular weight cut-off filter to remove FLCs. To date, trials with HCO-HD in patients with cast nephropathy have been encouraging. However, there are no randomized trials demonstrating the benefit of HCOHD when used in addition to newer chemotherapeutic regimens. Until these studies are available, HCO-HD cannot be recommended as standard of care.

  2. Pathology consultation on transfusion-related acute lung injury (TRALI).

    PubMed

    Schmidt, Amy E; Adamski, Jill

    2012-10-01

    Transfusion-related acute lung injury (TRALI) is a serious condition characterized by respiratory distress, hypoxia, and bilateral pulmonary infiltrates, which occur within 6 hours of transfusion. Several theories have been proposed to explain the underlying pathologic mechanisms of TRALI. Immune-mediated TRALI accounts for over 80% of reported cases and is mediated by donor antibodies to HLAs and/or human neutrophil antigens (HNA). Immune-mediated TRALI is most commonly associated with donor plasma transfusion or other blood products from multiparous women, which has led many countries to reduce or exclude women from donating high-volume plasma products. This policy change has resulted in a decrease in the incidence of TRALI and highlighted the importance of nonimmune-mediated TRALI, which is thought to be caused by bioreactive lipids and other biologic response modifiers that accumulate during storage of blood products. When TRALI is suspected, clinical consultation with a transfusion medicine specialist helps differentiate it from other transfusion reactions with similar characteristics.

  3. Acute kidney injury in patients with pulmonary embolism

    PubMed Central

    Chang, Chih-Hsiang; Fu, Chung-Ming; Fan, Pei-Chun; Chen, Shao-Wei; Chang, Su-Wei; Mao, Chun-Tai; Tian, Ya-Chung; Chen, Yung-Chang; Chu, Pao-Hsien; Chen, Tien-Hsing

    2017-01-01

    Abstract Acute kidney injury (AKI) is overlooked in patients with pulmonary embolism (PE). Risk factors for and long-term outcomes of this complication remain unknown. This study evaluated the predictors and prognosis of AKI in patients with PE. This retrospective cohort study used Taiwan's National Health Insurance Research Database. We enrolled a total of 7588 patients who were admitted to a hospital for PE from January1997 to December 2011 and administered anticoagulation or thrombolytic agents. All demographic data, risk factors, and outcomes were analyzed. AKI was diagnosed in 372 (4.9%) patients. Multivariate logistic regression analysis revealed pre-existing chronic kidney disease, hypertension, diabetes mellitus, massive PE, anemia, and sepsis as independent risk factors for AKI. In the long-term follow-up, the survival rate was similar in the AKI and non-AKI groups. Careful risk factor screening and intensive intervention in patients with AKI might yield outcomes similar to those in patients without AKI. PMID:28248851

  4. Acute Kidney Injury: Definition, Pathophysiology and Clinical Phenotypes

    PubMed Central

    Makris, Konstantinos; Spanou, Loukia

    2016-01-01

    Acute kidney injury (AKI) is a clinical syndrome that complicates the course and worsens the outcome in a significant number of hospitalised patients. Recent advances in clinical and basic research will help with a more accurate definition of this syndrome and in the elucidation of its pathogenesis. With this knowledge we will be able to conduct more accurate epidemiologic studies in an effort to gain a better understanding of the impact of this syndrome. AKI is a syndrome that rarely has a sole and distinct pathophysiology. Recent evidence, in both basic science and clinical research, is beginning to change our view for AKI from a single organ failure syndrome to a syndrome where the kidney plays an active role in the progress of multi-organ dysfunction. Accurate and prompt recognition of AKI and better understanding of the pathophysiologic mechanisms underlying the various clinical phenotypes are of great importance to research for effective therapeutic interventions. In this review we provide the most recent updates in the definition, epidemiology and pathophysiology of AKI. PMID:28303073

  5. Continuous Venovenous Hemofiltration in Severely Burned Patients with Acute Kidney Injury: A Cohort Study

    DTIC Science & Technology

    2009-05-01

    FiO2: fraction of inspired oxygen; IHD: intermittent hemodialysis ; IQR: interquartile range; ISS: injury severity score; MODS: multiple organ...were compared. Definitions During the period after November 2005 our staff intensivists utilized the RIFLE (Risk, Injury, Failure, Loss, End-stage...for acute renal fail- ure which included: fluid resuscitation, minimization of nephro- toxic agents, and utilization of hemodialysis if classic

  6. Investigating Metacognition, Cognition, and Behavioral Deficits of College Students with Acute Traumatic Brain Injuries

    ERIC Educational Resources Information Center

    Martinez, Sarah; Davalos, Deana

    2016-01-01

    Objective: Executive dysfunction in college students who have had an acute traumatic brain injury (TBI) was investigated. The cognitive, behavioral, and metacognitive effects on college students who endorsed experiencing a brain injury were specifically explored. Participants: Participants were 121 college students who endorsed a mild TBI, and 121…

  7. Comparison of admission random glucose, fasting glucose, and glycated hemoglobin in predicting the neurological outcome of acute ischemic stroke: a retrospective study

    PubMed Central

    Sung, Jia-Ying; Chen, Chin-I; Hsieh, Yi-Chen; Chen, Yih-Ru; Wu, Hsin-Chiao; Chan, Lung; Hu, Chaur-Jong; Hu, Han-Hwa; Chiou, Hung-Yi

    2017-01-01

    Background Hyperglycemia is a known predictor of negative outcomes in stroke. Several glycemic measures, including admission random glucose, fasting glucose, and glycated hemoglobin (HbA1c), have been associated with bad neurological outcomes in acute ischemic stroke, particularly in nondiabetic patients. However, the predictive power of these glycemic measures is yet to be investigated. Methods This retrospective study enrolled 484 patients with acute ischemic stroke from January 2009 to March 2013, and complete records of initial stroke severity, neurological outcomes at three months, and glycemic measures were evaluated. We examined the predictive power of admission random glucose, fasting glucose, and HbA1c for neurological outcomes in acute ischemic stroke. Furthermore, subgroup analyses of nondiabetic patients and patients with diabetes were performed separately. Results Receiver operating characteristic (ROC) analysis revealed that admission random glucose and fasting glucose were significant predictors of poor neurological outcomes, whereas HbA1c was not (areas under the ROC curve (AUCs): admission random glucose = 0.564, p = 0.026; fasting glucose = 0.598, p = 0.001; HbA1c = 0.510, p = 0.742). Subgroup analyses of nondiabetic patients and those with diabetes revealed that only fasting glucose predicts neurological outcomes in patients with diabetes, and the AUCs of these three glycemic measures did not differ between the two groups. A multivariate logistic regression analysis of the study patients indicated that only age, initial stroke severity, and fasting glucose were independent predictors of poor neurological outcomes, whereas admission random glucose and HbA1c were not (adjusted odds ratio: admission random glucose = 1.002, p = 0.228; fasting glucose = 1.005, p = 0.039; HbA1c = 1.160, p = 0.076). Furthermore, subgroup multivariate logistic regression analyses of nondiabetic patients and those with diabetes indicated that none of the three glycemic

  8. Incidence and severity of reported acute sports injuries in 35 sports using insurance registry data.

    PubMed

    Åman, M; Forssblad, M; Henriksson-Larsén, K

    2016-04-01

    Acute injuries in sport are still a problem where limited knowledge of incidence and severity in different sports at national level exists. In Sweden, 80% of the sports federations have their mandatory injury insurance for all athletes in the same insurance company and injury data are systematically kept in a national database. The aim of the study was to identify high-risk sports with respect to incidence of acute and severe injuries in 35 sports reported to the database. The number and incidences of injuries as well as injuries leading to permanent medical impairment (PMI) were calculated during 2008-2011. Each year approximately 12,000 injuries and 1,162,660 licensed athletes were eligible for analysis. Eighty-five percent of the injuries were reported in football, ice hockey, floorball, and handball. The highest injury incidence as well as PMI was in motorcycle, handball, skating, and ice hockey. Females had higher risk of a PMI compared with males in automobile sport, handball, floorball, and football. High-risk sports with numerous injuries and high incidence of PMI injuries were motorcycle, handball, ice hockey, football, floorball, and automobile sports. Thus, these sports ought to be the target of preventive actions at national level.

  9. [Prognostication of acute-pancreatitis-associated pulmonary injury based on determination of cytokines levels].

    PubMed

    Fedorkiv, M B; Hudz, I M; Shevchuk, I M

    2013-07-01

    The results of examination of 68 patients, admitted to hospital for an acute pancreatitis during 48 h from its occurrence, were analyzed. In all the patients the cytokines (IL-8, IL-10, TNF-alpha) content was determined in the blood, using immunoenzymal analysis. Algorithm of prognostication of an acute pancreatitis-associated pulmonary injury, basing on determination of the cytokines contents, was elaborated.

  10. Aging potentiates the acute and chronic neurological symptoms of pyrithiamine-induced thiamine deficiency in the rodent.

    PubMed

    Pitkin, S R; Savage, L M

    2001-03-15

    The present study aimed to assess the role of advanced age in the development and manifestation of thiamine deficiency using an animal model of Wernicke-Korsakoff syndrome (WKS). Interactions between pyrithiamine-induced thiamine deficiency (PTD) and age were examined relative to working memory impairment and neuropathology in Fischer 344 rats. Young (2-3 months) and aged (22-23 months) F344 rats were assigned to one of two treatment conditions: PTD or pair-fed control (PF). Rats in the former group were further divided into three groups according to duration of PTD treatment. Working memory was assessed with an operant matching-to-position (MTP) task; after testing, animals were sacrificed and both gross and immunocytochemical measures of brain pathology were obtained. Aged rats exhibited acute neurological disturbances during the PTD treatment regime earlier than did young rats, and also developed more extensive neuropathology with a shorter duration of PTD. Aged rats displayed increased brain shrinkage (smaller frontal cortical and callosal thickness) as well as enhanced astrocytic activity in the thalamus and a decrease in ChAT-positive cell numbers in the medial septum; the latter two measures of neuropathology were potentiated by PTD. In both young and aged rats, and to a greater degree in the latter group, PTD reduced thalamic volume. Behaviorally, aged rats displayed impaired choice accuracy on the delayed MTP task. Regardless of age, rats with lesions centered on the internal medullary lamina of the thalamus also displayed impaired choice accuracy. Moreover, increased PTD treatment duration led to increased response times on the delayed MTP task. These results suggest that aging does indeed potentiate the neuropathology associated with experimental thiamine deficiency, supporting an age coupling hypothesis of alcohol-related neurological disorders.

  11. Plasma copeptin as a predictor of intoxication severity and delayed neurological sequelae in acute carbon monoxide poisoning.

    PubMed

    Pang, Li; Wang, He-Lei; Wang, Zhi-Hao; Wu, Yang; Dong, Ning; Xu, Da-Hai; Wang, Da-Wei; Xu, Hong; Zhang, Nan

    2014-09-01

    The present study was designed to assess the usefulness of measuring plasma levels of copeptin (a peptide co-released with the hypothalamic stress hormone vasopressin) as a biomarker for the severity of carbon monoxide (CO) poisoning and for predicting delayed neurological sequelae (DNS). Seventy-two patients with CO poisoning and 72 sex and age matched healthy individuals were recruited. Plasma copeptin levels were measured on admission from CO poisoning patients and for healthy individuals at study entry by using a sandwich immunoassay. The CO poisoning patients were divided into two groups according to severity (unconscious and conscious) and occurrence of DNS. The mean plasma copeptin levels (52.5±18.5 pmol/L) in the unconscious group were significantly higher than in the conscious group (26.3±12.7 pmol/L) (P<0.001). Plasma copeptin levels of more than 39.0 pmol/L detected CO poisoning with severe neurological symptoms e.g. unconsciousness (sensitivity 84.6% and specificity 81.4%). The plasma copeptin levels were higher in patients with DNS compared to patients without DNS (52.2±20.6 pmol/L vs. 27.9±14.8 pmol/L, P<0.001). Plasma copeptin levels higher than 40.5 pmol/L predicted the development of DNS (sensitivity 77.8%, specificity 82.1%). Plasma copeptin levels were identified as an independent predictor for intoxication severity [odds ratio (OR) 1.261, 95% confidence interval (CI) 1.112-1.638, P=0.002] and DNS (OR 1.313, 95% CI 1.106-1.859, P=0.001). Thus, plasma copeptin levels independently related to intoxication severity and were identified as a novel biomarker for predicting DNS after acute CO poisoning.

  12. Imbalance between nitric oxide and dopamine may underly aggression in acute neurological patients.

    PubMed

    Ramírez-Bermudez, J; Perez-Neri, I; Montes, S; Ramirez-Abascal, M; Nente, F; Abundes-Corona, A; Soto-Hernandez, J L; Rios, C

    2010-10-01

    The neurochemical basis of aggressive behavior in humans is not fully understood. In this study we explored the relationship between aggressiveness (as measured by the Overt Aggression Scale), cognitive performance (as measured by the Mini Mental State Examination), and biochemical markers of dopamine neurotransmission (homovanillic acid, HVA) and nitric oxide synthesis (nitrite plus nitrate, NO(x)) in cerebrospinal fluid from 70 patients with acute brain disorders, mainly brain infections. Aggressive behavior and cognitive performance showed an inverse correlation. NO(x)/HVA ratio was inversely correlated to aggressive behavior, and positively correlated to cognitive performance. A subanalysis with antipsychotic-naïve patients confirmed those results. The balance between nitric oxide and dopamine could be related to the cognitive control of aggressive impulse.

  13. Critical care in the ED: potentially fatal asthma and acute lung injury syndrome

    PubMed Central

    Hodder, Rick

    2012-01-01

    Emergency department clinicians are frequently called upon to assess, diagnose, and stabilize patients who present with acute respiratory failure. This review describes a rapid initial approach to acute respiratory failure in adults, illustrated by two common examples: (1) an airway disease – acute potentially fatal asthma, and (2) a pulmonary parenchymal disease – acute lung injury/acute respiratory distress syndrome. As such patients are usually admitted to hospital, discussion will be focused on those initial management aspects most relevant to the emergency department clinician. PMID:27147862

  14. Pretreatment with wortmannin alleviates lipopolysaccharide/d-galactosamine-induced acute liver injury.

    PubMed

    Li, Yan; Wang, Xiaoyan; Wei, Zengtao; Mao, Hongju; Gao, Meng; Liu, Yanping; Ma, Yanyan; Liu, Xingli; Guo, Chun; Zhang, Lining; Wang, Xiaoyan

    2014-12-12

    Intestinal endotoxemia-induced liver injury is a common clinical disease which leads to liver failure and death. Wortmannin, an inhibitor of phosphatidylinositol 3-kinase, could be used for suppressing autophagy in vitro and in vivo. Autophagy is an evolutionarily conserved and lysosome dependent protein degradation pathway, which participates in various physiological and pathological processes. The present study aims to explore the effect of pretreatment with wortmannin on acute liver injury and the autophagy in acute liver injury. We demonstrated that wortmannin could downregulate the expression of phosphorylated extracellular regulated protein kinase and p65, decrease the production and release of hepatic inflammatory cytokines, and then reduce hepatocytes apoptosis and necrosis. More importantly, we found that autophagy was induced to increase in LPS/D-GalN-induced acute liver injury, and pretreatment with wortmannin could effectively inhibit increased autophagy in acute liver injury. In conclusion, these results indicate that wortmannin plays a protective role in LPS/D-GalN induced hepatocytotoxity maybe by inhibiting autophagy and could be acted as a target for the treatment of acute liver injury.

  15. Protective role of fructokinase blockade in the pathogenesis of acute kidney injury in mice

    PubMed Central

    Andres-Hernando, Ana; Li, Nanxing; Cicerchi, Christina; Inaba, Shinichiro; Chen, Wei; Roncal-Jimenez, Carlos; Le, Myphuong T.; Wempe, Michael F.; Milagres, Tamara; Ishimoto, Takuji; Fini, Mehdi; Nakagawa, Takahiko; Johnson, Richard J.; Lanaspa, Miguel A.

    2017-01-01

    Acute kidney injury is associated with high mortality, especially in intensive care unit patients. The polyol pathway is a metabolic route able to convert glucose into fructose. Here we show the detrimental role of endogenous fructose production by the polyol pathway and its metabolism through fructokinase in the pathogenesis of ischaemic acute kidney injury (iAKI). Consistent with elevated urinary fructose in AKI patients, mice undergoing iAKI show significant polyol pathway activation in the kidney cortex characterized by high levels of aldose reductase, sorbitol and endogenous fructose. Wild type but not fructokinase knockout animals demonstrate severe kidney injury associated with ATP depletion, elevated uric acid, oxidative stress and inflammation. Interestingly, both the renal injury and dysfunction in wild-type mice undergoing iAKI is significantly ameliorated when exposed to luteolin, a recently discovered fructokinase inhibitor. This study demonstrates a role for fructokinase and endogenous fructose as mediators of acute renal disease. PMID:28194018

  16. Protective effects of imipramine in murine endotoxin-induced acute lung injury.

    PubMed

    Yang, Jin; Qu, Jie-ming; Summah, Hanssa; Zhang, Jin; Zhu, Ying-gang; Jiang, Hong-ni

    2010-07-25

    The tricyclic antidepressant imipramine has recently emerged as a cytoprotective agent, exerting beneficial effects in inflammatory tissue injury. The present study aimed to investigate therapeutic effects of imipramine in murine model of endotoxin-induced acute lung injury. Mice were administrated intraperitoneally with LPS (lipopolysaccharide) from Escherichia coli or vehicle. Imipramine was administrated intraperitoneally 30 min before LPS challenge. Pretreatment of mice with imipramine reduced lethality. Impramine also significantly attenuated lung inflammation, lung edema, MPO (myeloperoxidase) activity, lung tissue pathological changes and nuclear factor-kappaB DNA binding activity. The results of this study suggest that imipramine can exert protective effects in endotoxin-induced acute lung injury by suppressing nuclear factor-kappaB-mediated expression of inflammatory genes. Thus, imipramine could be a potential novel therapeutic agent for the treatment for acute lung injury.

  17. Depressive Symptoms and Impaired Physical Function after Acute Lung Injury

    PubMed Central

    Colantuoni, Elizabeth; Mendez-Tellez, Pedro A.; Dinglas, Victor D.; Shanholtz, Carl; Husain, Nadia; Dennison, Cheryl R.; Herridge, Margaret S.; Pronovost, Peter J.; Needham, Dale M.

    2012-01-01

    Rationale: Survivors of acute lung injury (ALI) frequently have substantial depressive symptoms and physical impairment, but the longitudinal epidemiology of these conditions remains unclear. Objectives: To evaluate the 2-year incidence and duration of depressive symptoms and physical impairment after ALI, as well as risk factors for these conditions. Methods: This prospective, longitudinal cohort study recruited patients from 13 intensive care units (ICUs) in four hospitals, with follow-up 3, 6, 12, and 24 months after ALI. The outcomes were Hospital Anxiety and Depression Scale depression score greater than or equal to 8 (“depressive symptoms”) in patients without a history of depression before ALI, and two or more dependencies in instrumental activities of daily living (“impaired physical function”) in patients without baseline impairment. Measurements and Main Results: During 2-year follow-up of 186 ALI survivors, the cumulative incidences of depressive symptoms and impaired physical function were 40 and 66%, respectively, with greatest incidence by 3-month follow-up; modal durations were greater than 21 months for each outcome. Risk factors for incident depressive symptoms were education 12 years or less, baseline disability or unemployment, higher baseline medical comorbidity, and lower blood glucose in the ICU. Risk factors for incident impaired physical function were longer ICU stay and prior depressive symptoms. Conclusions: Incident depressive symptoms and impaired physical function are common and long-lasting during the first 2 years after ALI. Interventions targeting potentially modifiable risk factors (e.g., substantial depressive symptoms in early recovery) should be evaluated to improve ALI survivors’ long-term outcomes. PMID:22161158

  18. Nonapnea Sleep Disorders and the Risk of Acute Kidney Injury

    PubMed Central

    Lin, Hugo You-Hsien; Chang, Kai-Ting; Chang, Yu-Han; Lu, Tzongshi; Liang, Chan-Jung; Wang, Dean-Chuan; Tsai, Jui-Hsiu; Hsu, Chung-Yao; Hung, Chi-Chih; Kuo, Mei-Chuan; Lin, Chang-Shen; Hwang, Shang-Jyh

    2016-01-01

    Abstract Nonapnea sleep disorders (NASDs) and associated problems, which are highly prevalent in patients with kidney diseases, are associated with unfavorable medical sequelae. Nonetheless, whether NASDs are associated with acute kidney injury (AKI) development has not been thoroughly analyzed. We examined the association between NASD and AKI. We conducted a population-based study by using 1,000,000 representative data from the Taiwan National Health Insurance Research Database for the period from January 1, 2000, to December 31, 2010. We studied the incidence and risk of AKI in 9178 newly diagnosed NASD patients compared with 27,534 people without NASD matched according to age, sex, index year, urbanization level, region of residence, and monthly income at a 1:3 ratio. The NASD cohort had an adjusted hazard ratio (hazard ratio [HR]; 95% confidence interval [CI] = 1.15–2.63) of subsequent AKI 1.74-fold higher than that of the control cohort. Older age and type 2 diabetes mellitus were significantly associated with an increased risk of AKI (P < 0.05). Among different types of NASDs, patients with insomnia had a 120% increased risk of developing AKI (95% CI = 1.38–3.51; P = 0.001), whereas patients with other sleep disorders had a 127% increased risk of subsequent AKI (95% CI = 1.07–4.80; P = 0.033). Men with NASDs were at a high risk of AKI (P < 0.05). This nationwide population-based cohort study provides evidence that patients with NASDs are at higher risk of developing AKI than people without NASDs. PMID:26986132

  19. Fluoroquinolone therapy and idiosyncratic acute liver injury: a population-based study

    PubMed Central

    Paterson, J. Michael; Mamdani, Muhammad M.; Manno, Michael; Juurlink, David N.

    2012-01-01

    Background: Although fluoroquinolones are sometimes associated with mild, transient elevations in aminotransferase levels, serious acute liver injury is uncommon. Regulatory warnings have identified moxifloxacin as presenting a particular risk of hepatotoxicity. Thus, we examined the risk of idiosyncratic acute liver injury associated with the use of moxifloxacin relative to other selected antibiotic agents. Methods: We conducted a population-based, nested, case–control study using health care data from Ontario for the period April 2002 to March 2011. We identified cases as outpatients aged 66 years or older with no history of liver disease, and who were admitted to hospital for acute liver injury within 30 days of receiving a prescription for 1 of 5 broad-spectrum antibiotic agents: moxifloxacin, levofloxacin, ciprofloxacin, cefuroxime axetil or clarithromycin. For each case, we selected up to 10 age- and sex-matched controls from among patients who had received a study antibiotic, but who were not admitted to hospital for acute liver injury. We calculated odds ratios (ORs) to determine the association between admission to hospital and previous exposure to an antibiotic agent, using clarithromycin as the reference. Results: A total of 144 patients were admitted to hospital for acute liver injury within 30 days of receiving a prescription for one of the identified drugs. Of these patients, 88 (61.1%) died while in hospital. After multivariable adjustment, use of either moxifloxacin (adjusted OR 2.20, 95% confidence interval [CI] 1.21–3.98) or levofloxacin (adjusted OR 1.85, 95% CI 1.01–3.39) was associated with an increase in risk of acute liver injury relative to the use of clarithromycin. We saw no such risk associated with the use of either ciprofloxacin or cefuroxime axetil. Interpretation: Among older outpatients with no evidence of liver disease, moxifloxacin and levofloxacin were associated with an increased risk of acute liver injury relative to

  20. Inhibition of caspase-9 aggravates acute liver injury through suppression of cytoprotective autophagy

    PubMed Central

    Guo, Rui; Lin, Bin; Pan, Jing Fei; Liong, Emily C.; Xu, Ai Min; Youdim, Moussa; Fung, Man Lung; So, Kwok Fai; Tipoe, George L.

    2016-01-01

    Acute liver disease is characterized by inflammation, oxidative stress and necrosis, which can greatly influence the long term clinical outcome and lead to liver failure or cancer. Here, we initially demonstrated the beneficial role of caspase-9-dependent autophagy in acute liver injury. Treatment with caspase-9 inhibitor z-LEHD-FMK in HepG2 cells, AML12 cells and C57BL/b6N mice exacerbated CCl4-induced acute hepatocellular damage, and also down-regulated autophagy markers expression levels, indicating that caspase-9 inhibition may aggravate acute liver damage by suppressing cytoprotective autophagy. CCl4 was used as an acute liver injury inducer which caused oxidative stress and apoptosis through up-regulation of HIF-1α, as well as triggered hepatic inflammation and necroptosis via TLR4/NF-κB pathway. Caspase-9 Thr125 site was firstly phosphorylated by ERK1/2 which subsequently activated the cytoprotective autophagy process to attenuate acute CCl4 injury. Caspase-9 inhibition further aggravated hepatic necroptosis through NF-κB expression, leading to increased pro-inflammatory mediators levels, suggesting a protective role of caspase-9-dependent autophagy in the inflammatory process as well as its possibility being a new therapeutic target for the treatment of acute liver injury. PMID:27580936

  1. Inhibition of caspase-9 aggravates acute liver injury through suppression of cytoprotective autophagy.

    PubMed

    Guo, Rui; Lin, Bin; Pan, Jing Fei; Liong, Emily C; Xu, Ai Min; Youdim, Moussa; Fung, Man Lung; So, Kwok Fai; Tipoe, George L

    2016-09-01

    Acute liver disease is characterized by inflammation, oxidative stress and necrosis, which can greatly influence the long term clinical outcome and lead to liver failure or cancer. Here, we initially demonstrated the beneficial role of caspase-9-dependent autophagy in acute liver injury. Treatment with caspase-9 inhibitor z-LEHD-FMK in HepG2 cells, AML12 cells and C57BL/b6N mice exacerbated CCl4-induced acute hepatocellular damage, and also down-regulated autophagy markers expression levels, indicating that caspase-9 inhibition may aggravate acute liver damage by suppressing cytoprotective autophagy. CCl4 was used as an acute liver injury inducer which caused oxidative stress and apoptosis through up-regulation of HIF-1α, as well as triggered hepatic inflammation and necroptosis via TLR4/NF-κB pathway. Caspase-9 Thr125 site was firstly phosphorylated by ERK1/2 which subsequently activated the cytoprotective autophagy process to attenuate acute CCl4 injury. Caspase-9 inhibition further aggravated hepatic necroptosis through NF-κB expression, leading to increased pro-inflammatory mediators levels, suggesting a protective role of caspase-9-dependent autophagy in the inflammatory process as well as its possibility being a new therapeutic target for the treatment of acute liver injury.

  2. A novel acute lethal liver injury mouse model with visualization of NF-κB activity for treatment of severe acute liver injury

    PubMed Central

    Liao, Huanjin; Cai, Jun; Zhang, Lifang; Peng, Yanxia; Wu, Ping; Xie, Tong; Pan, Qingjun

    2017-01-01

    Acute lethal inflammation, especially that related to liver injury, is an important clinical issue. To date, however, there is no model that can be used to assess this serious condition. This study was designed to establish a novel lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute lethal liver injury model in nuclear factor-κB (NF-κB) transgenic mice. The results show that a high dose of LPS (500 μg/kg) plus D-GalN (800 mg/kg) successfully established a novel mouse model of acute lethal liver injury with a lifespan of 8-10 h. Significantly increased NF-κB activity, detected with an in vivo imaging system (IVIS), peaked at approximately 4 h post-LPS/D-GalN challenge in NF-κB transgenic mice. Moreover, the serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1 were significantly increased and peaked at approximately 4 h post-i.p. injection of LPS/D-GalN. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) also sharply increased. Correlation analyses showed that NF-κB activity was significantly correlated with serum levels of ALT and AST. The mouse model livers showed marked congestion and hemorrhage, and hematoxylin and eosin (H&E) staining confirmed the destruction of the lobular structure and severe hepatocyte necrosis and hemorrhage. None of these changes were observed in the control mice. In summary, a novel LPS/D-GalN-induced acute lethal liver injury model with visualization of NF-κB activity was established in NF-κB transgenic mice. This model will provide the technology for developing new therapeutic strategies for treatment of severe acute liver injury complicated by endotoxemia or septicemia. PMID:28386325

  3. Astaxanthin as a Potential Neuroprotective Agent for Neurological Diseases

    PubMed Central

    Wu, Haijian; Niu, Huanjiang; Shao, Anwen; Wu, Cheng; Dixon, Brandon J.; Zhang, Jianmin; Yang, Shuxu; Wang, Yirong

    2015-01-01

    Neurological diseases, which consist of acute injuries and chronic neurodegeneration, are the leading causes of human death and disability. However, the pathophysiology of these diseases have not been fully elucidated, and effective treatments are still lacking. Astaxanthin, a member of the xanthophyll group, is a red-orange carotenoid with unique cell membrane actions and diverse biological activities. More importantly, there is evidence demonstrating that astaxanthin confers neuroprotective effects in experimental models of acute injuries, chronic neurodegenerative disorders, and neurological diseases. The beneficial effects of astaxanthin are linked to its oxidative, anti-inflammatory, and anti-apoptotic characteristics. In this review, we will focus on the neuroprotective properties of astaxanthin and explore the underlying mechanisms in the setting of neurological diseases. PMID:26378548

  4. Acute Gastrocnemius-Soleus Complex Injuries in National Football League Athletes

    PubMed Central

    Werner, Brian C.; Belkin, Nicole S.; Kennelly, Steve; Weiss, Leigh; Barnes, Ronnie P.; Potter, Hollis G.; Warren, Russell F.; Rodeo, Scott A.

    2017-01-01

    Background: Lower extremity muscle injuries are common in professional football. Although less common than hamstring or quadriceps injuries in National Football League (NFL) athletes, calf injuries occur with relative frequency and have not previously been studied. Purpose: To evaluate gastrocnemius-soleus complex muscle injuries over the past 13 years from a single NFL team to determine the incidence of such injuries, their imaging characteristics, and return to play after such injuries and any correlation between imaging findings and prolonged return to play. Study Design: Case series; Level of evidence, 4. Methods: A retrospective review of all acute calf muscle injuries on a single NFL team from 2003 to 2015 was performed. Player demographics and return-to-play data were obtained from the medical records. All available magnetic resonance images (MRIs) were reviewed by a musculoskeletal radiologist for specific imaging findings that correlated with return to play. Results: A total of 27 calf injuries in 24 NFL players were reviewed, yielding an incidence of 2.3 acute calf injuries per year on a single NFL team. Of these 27 injuries, 20 (74%) were isolated injuries to the gastrocnemius muscle, 4 (15%) were isolated injuries to the soleus muscle, and the remaining 3 injuries (11%) involved both. Defensive players were more likely to sustain injuries (P = .043). The mean time to return to play for all 27 players was 17.4 ± 14.6 days (range, 3-62 days). MRIs were available in 14 of the 27 injuries. The average size of the fascial defect (P = .032) and the presence of a fluid collection (P = .031) both correlated with return to play of longer than 2 weeks. Conclusion: Although less common than hamstring or quadriceps muscle injuries, calf muscle injuries occur with relative frequency in the NFL, and more so in defensive players. The majority of these injuries occur in the gastrocnemius and result in significant disability, with at least 2 weeks of missed playing

  5. Urinary Macrophage Migration Inhibitory Factor Serves as a Potential Biomarker for Acute Kidney Injury in Patients with Acute Pyelonephritis

    PubMed Central

    Hong, Ming-Yuan; Tseng, Chin-Chung; Chuang, Chia-Chang; Chen, Chia-Ling; Lin, Sheng-Hsiang; Lin, Chiou-Feng

    2012-01-01

    Conventional markers of kidney function that are familiar to clinicians, including the serum creatinine and blood urea nitrogen levels, are unable to reveal genuine injury to the kidney, and their use may delay treatment. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine, and the predictive role and pathogenic mechanism of MIF deregulation during kidney infections involving acute kidney injury (AKI) are not currently known. In this study, we showed that elevated urinary MIF levels accompanied the development of AKI during kidney infection in patients with acute pyelonephritis (APN). In addition to the MIF level, the urinary levels of interleukin (IL)-1β and kidney injury molecule (KIM)-1 were also upregulated and were positively correlated with the levels of urinary MIF. An elevated urinary MIF level, along with elevated IL-1β and KIM-1 levels, is speculated to be a potential biomarker for the presence of AKI in APN patients. PMID:23319831

  6. The QT dispersion and QTc dispersion in patients presenting with acute neurological events and its impact on early prognosis

    PubMed Central

    Rahar, Kailash Kumar; Pahadiya, Hans Raj; Barupal, Kishan Gopal; Mathur, C. P.; Lakhotia, Manoj

    2016-01-01

    TIA (P < 0.001). The mean QT dispersion and QTc dispersion was found significantly high in nonsurvivors (n = 16) as compared to survivors group (n = 36) (P < 0.05). The mean QT dispersion was directly correlated with the NIHSS and functional outcome score MRS. Patients with greater QT and QTc dispersion having high NIHSS had poor prognosis. Conclusion: We concluded that patients presenting with acute neurological events having increased QT dispersion and QTc dispersion is related to high mortality and poor functional outcomes on hospital discharge and if the values of dispersion score are very high we can predict for hemorrhagic stroke. PMID:26933346

  7. Airway pressure release ventilation in morbidly obese surgical patients with acute lung injury and acute respiratory distress syndrome.

    PubMed

    Testerman, George M; Breitman, Igal; Hensley, Sarah

    2013-03-01

    Morbidly obese patients with body mass index greater than 40 kg/m(2) and respiratory failure requiring critical care services are increasingly seen in trauma and acute care surgical centers. Baseline respiratory pathophysiology including decreased pulmonary compliance with dependent atelectasis and abnormal ventilation-perfusion relationships predisposes these patients to acute lung injury (ALI) and adult respiratory distress syndrome (ARDS) as well as prolonged stays in the intensive care unit. Airway pressure release ventilation (APRV) is an increasingly used alternative mode for salvage therapy in patients with hypoxemic respiratory failure that also provides lung protection from ventilator-induced lung injury. APRV provides the conceptual advantage of an "open lung" approach to ventilation that may be extended to the morbidly obese patient population with ALI and ARDS. We discuss the theoretical benefits and a recent clinical experience of APRV ventilation in the morbidly obese patient with respiratory failure at a Level I trauma, surgical critical care, and acute care surgery center.

  8. Pattern of Brain Injury in the Acute Setting of Human Septic Shock

    PubMed Central

    2013-01-01

    Background Sepsis-associated brain dysfunction has been linked to white matter lesions (leukoencephalopathy) and ischemic stroke. Our objective was to assess the prevalence of brain lesions in septic shock patients requiring magnetic resonance imaging (MRI) for an acute neurologic change. Method Seventy-one septic shock patients were included in a prospective observational study. Patients underwent daily neurological examination. Brain MRI was obtained in patients who developed focal neurological deficit, seizure, coma, or delirium. Electroencephalogy was performed in case of coma, delirium, or seizure. Leukoencephalopathy was graded and considered present when white matter lesions were either confluent or diffuse. Patient outcome was evaluated at 6 months with the Glasgow Outcome Scale (GOS). Results We included 71 patients with median age of 65 years (56 to 76) and SAPS II at admission of 49 (38 to 60). MRI was indicated on focal neurological sign in 13 (18%), seizure in 7 (10%), coma in 33 (46%), and delirium in 35 (49%). MRI was normal in 37 patients (52%) and showed cerebral infarcts in 21 (29%), leukoencephalopathy in 15 (21%), and mixed lesions in 6 (8%). EEG malignant pattern was more frequent in patients with ischemic stroke or leukoencephalopathy. Ischemic stroke was independently associated with disseminated intravascular coagulation (DIC), focal neurologic signs, increased mortality, and worse GOS at 6 months. Conclusions Brain MRI in septic shock patients who developed acute brain dysfunction can reveal leukoencephalopathy and ischemic stroke, which is associated with DIC and increased mortality. PMID:24047502

  9. The Acute Kidney Injury Network (AKIN) Criteria Applied in Burns

    DTIC Science & Technology

    2012-08-01

    and reported the RIFLE (risk, injury, failure, loss of function, end-stage renal disease ) criteria in 2004.4 Since this report, the RIFLE criteria...end-stage renal disease , or did not have burn injury and/or inhala- tion injury. If a patient was re-admitted, only the first hospitalization was...and creatinine continued to trend upward, then we backcalculated using the modification of diet in renal disease (MDRD) equation assuming a baseline

  10. Acute kidney injury burden in different clinical units: Data from nationwide survey in China

    PubMed Central

    Yu, Shengqiang; Yang, Li; Mei, Changlin

    2017-01-01

    Background The inpatient morbidity and mortality of acute kidney injury (AKI) vary considerably in different clinical units, yet studies to compare the difference remain limited. Methods We compared the clinical characteristics of AKI in Intensive Care Unit (ICU), medical and surgical departments by using the data derived from the 2013 nationwide cross-sectional survey of AKI in China to capture variations among different clinical departments in recognition, management, and outcomes of AKI. Suspected AKI patients were identified based on changes in serum creatinine during hospitalization, and confirmed by reviewing medical records. Results The detection rate of AKI was the highest in ICU (22.46%), followed by the rates in medical (1.96%) and surgical departments (0.96%). However, the absolute number of cases was the largest in medical departments, which contributed to 50% of the cases. In medical departments, 78% of AKI cases were extensively distributed in cardiac, nephrology, oncology, gastroenterology, pneumology and neurology departments. In contrast, 87% of AKI cases in surgical departments were mainly from urology, general surgery and cardiothoracic departments. The in-time recognition rates were extremely low in all departments except nephrology. Only 10.5~15.0% AKI patients from non-nephrology departments received renal referral. Among all the death cases, 50% and 39% came from ICU and medical departments while only 11% from surgical departments. Older age, higher AKI stage and renal replacement therapy indication were identified as risk factors for high mortality in all departments. Delayed recognition and no renal referral were significantly associated with increased mortality in medical and ICU patients. Conclusions These findings suggest that ICU and medical departments are major affected departments in China with a large number of AKI cases and subsequent high mortality. The reality is more alarming considering the low awareness of AKI and the paucity

  11. Strategies for prevention of acute kidney injury in cardiac surgery: an integrative review

    PubMed Central

    Santana-Santos, Eduesley; Marcusso, Marila Eduara Fátima; Rodrigues, Amanda Oliveira; de Queiroz, Fernanda Gomes; de Oliveira, Larissa Bertacchini; Rodrigues, Adriano Rogério Baldacin; Palomo, Jurema da Silva Herbas

    2014-01-01

    Acute kidney injury is a common complication after cardiac surgery and is associated with increased morbidity and mortality and increased length of stay in the intensive care unit. Considering the high prevalence of acute kidney injury and its association with worsened prognosis, the development of strategies for renal protection in hospitals is essential to reduce the associated high morbidity and mortality, especially for patients at high risk of developing acute kidney injury, such as patients who undergo cardiac surgery. This integrative review sought to assess the evidence available in the literature regarding the most effective interventions for the prevention of acute kidney injury in patients undergoing cardiac surgery. To select the articles, we used the CINAHL and MedLine databases. The sample of this review consisted of 16 articles. After analyzing the articles included in the review, the results of the studies showed that only hydration with saline has noteworthy results in the prevention of acute kidney injury. The other strategies are controversial and require further research to prove their effectiveness. PMID:25028954

  12. Asialoerythropoietin ameliorates bleomycin-induced acute lung injury in rabbits by reducing inflammation

    PubMed Central

    SONODA, AKINAGA; NITTA, NORIHISA; TSUCHIYA, KEIKO; OTANI, HIDEJI; WATANABE, SHOBU; MUKAISHO, KENICHI; TOMOZAWA, YUKI; NAGATANI, YUKIHIRO; OHTA, SHINICHI; TAKAHASHI, MASASHI; MURATA, KIYOSHI

    2014-01-01

    Acute lung injury, a critical illness characterized by acute respiratory failure with bilateral pulmonary infiltrates, remains unresponsive to current treatments. The condition involves injury to the alveolar capillary barrier, neutrophil accumulation and the induction of proinflammatory cytokines followed by lung fibrosis. In the present study, a rabbit model of bleomycin-induced acute lung injury was established to examine the effects of asialoerythropoietin (AEP), an agent with tissue-protective activities, on pulmonary inflammation. Six Japanese white rabbits were randomly divided into two equal groups. Acute lung injury was induced in all rabbits by intratracheally injecting bleomycin. The control group was injected with bleomycin only; the experimental (AEP) group was injected intravenously with AEP (80 μg/kg) prior to the bleomycin injection. Computed tomography (CT) studies were performed seven days later. The CT inflammatory scores of areas exhibiting abnormal density and the pathological inflammatory scores were recorded as a ratio on a 7×7 mm grid. The CT and pathological inflammatory scores were significantly different between the control and AEP groups [122±10 and 16.3±1.5 (controls) vs. 71±8.5 and 9.7±1.4 (AEP), respectively; P<0.01]. Thus, the present study revealed that AEP prevents bleomycin-induced acute lung injury in rabbits. PMID:25289037

  13. Preventive mechanisms of agmatine against ischemic acute kidney injury in rats.

    PubMed

    Sugiura, Takahiro; Kobuchi, Shuhei; Tsutsui, Hidenobu; Takaoka, Masanori; Fujii, Toshihide; Hayashi, Kentaro; Matsumura, Yasuo

    2009-01-28

    The excitation of renal sympathetic nervous system plays an important role in the development of ischemic acute kidney injury in rats. Recently, we found that agmatine, an adrenaline alpha(2)/imidazoline I(1)-receptor agonist, has preventive effects on ischemic acute kidney injury by suppressing the enhanced renal sympathetic nerve activity during renal ischemia and by decreasing the renal venous norepinephrine overflow after reperfusion. In the present study, we investigated preventive mechanisms of agmatine against ischemic acute kidney injury in rats. Ischemic acute kidney injury was induced by clamping the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after the contralateral nephrectomy. Pretreatment with efaroxan (30 mumol/kg, i.v.), an alpha(2)/I(1)-receptor antagonist, abolished the suppressive effects of agmatine on the enhanced renal sympathetic nerve activity during renal ischemia and on the elevated norepinephrine overflow after reperfusion, and eliminated the preventing effects of agmatine on the ischemia/reperfusion-induced renal dysfunction and histological damage. On the other hand, pretreatment with yohimbine (6 mumol/kg, i.v.), an alpha(2)-receptor antagonist, eliminated the preventing effects of agmatine on the ischemia/reperfusion-induced renal injury and norepinephrine overflow, without affecting the lowering effect of agmatine on renal sympathetic nerve activity. These results indicate that agmatine prevents the ischemic renal injury by sympathoinhibitory effect probably via I(1) receptors in central nervous system and by suppressing the norepinephrine overflow through alpha(2) or I(1) receptors on sympathetic nerve endings.

  14. Apoptosis of the Thick Ascending Limb Results in Acute Kidney Injury

    PubMed Central

    Srichai, Manakan B.; Hao, Chuanming; Davis, Linda; Golovin, Anastasia; Zhao, Min; Moeckel, Gilbert; Dunn, Steve; Bulus, Nada; Harris, Raymond C.; Zent, Roy; Breyer, Matthew D.

    2008-01-01

    Ischemia- or toxin-induced acute kidney injury is generally thought to affect the cells of the proximal tubule, but it has been difficult to define the involvement of other tubular segments because of the widespread damage caused by ischemia/reperfusion or toxin-induced injury in experimental models. For evaluation of whether thick ascending limb (TAL)-specific epithelial injury results in acute kidney injury, a novel transgenic mouse model that expresses the herpes simplex virus 1 thymidine kinase gene under the direction of the TAL-specific Tamm-Horsfall protein promoter was generated. After administration of gancyclovir, these mice demonstrated apoptosis only in TAL cells, with little evidence of neutrophil infiltration. Compared with control mice, blood urea nitrogen and creatinine levels were at least five-fold higher in the transgenic mice, which also developed oliguria and impaired urinary concentrating ability. These findings suggest that acute injury targeted only to the TAL is sufficient to cause severe acute kidney injury in mice with features similar to those observed in humans. PMID:18495962

  15. Apoptosis of the thick ascending limb results in acute kidney injury.

    PubMed

    Srichai, Manakan B; Hao, Chuanming; Davis, Linda; Golovin, Anastasia; Zhao, Min; Moeckel, Gilbert; Dunn, Steve; Bulus, Nada; Harris, Raymond C; Zent, Roy; Breyer, Matthew D

    2008-08-01

    Ischemia- or toxin-induced acute kidney injury is generally thought to affect the cells of the proximal tubule, but it has been difficult to define the involvement of other tubular segments because of the widespread damage caused by ischemia/reperfusion or toxin-induced injury in experimental models. For evaluation of whether thick ascending limb (TAL)-specific epithelial injury results in acute kidney injury, a novel transgenic mouse model that expresses the herpes simplex virus 1 thymidine kinase gene under the direction of the TAL-specific Tamm-Horsfall protein promoter was generated. After administration of gancyclovir, these mice demonstrated apoptosis only in TAL cells, with little evidence of neutrophil infiltration. Compared with control mice, blood urea nitrogen and creatinine levels were at least five-fold higher in the transgenic mice, which also developed oliguria and impaired urinary concentrating ability. These findings suggest that acute injury targeted only to the TAL is sufficient to cause severe acute kidney injury in mice with features similar to those observed in humans.

  16. Oxidation-Reduction Potential as a Biomarker for Severity and Acute Outcome in Traumatic Brain Injury

    PubMed Central

    Levy, Stewart; Carrick, Matthew; Mains, Charles W.; Slone, Denetta S.

    2016-01-01

    There are few reliable markers for assessing traumatic brain injury (TBI). Elevated levels of oxidative stress have been observed in TBI patients. We hypothesized that oxidation-reduction potential (ORP) could be a potent biomarker in TBI. Two types of ORP were measured in patient plasma samples: the static state of oxidative stress (sORP) and capacity for induced oxidative stress (icORP). Differences in ORP values as a function of time after injury, severity, and hospital discharge were compared using ANOVAs with significance at p ≤ 0.05. Logit regression analyses were used to predict acute outcome comparing ORP, Injury Severity Score (ISS), Abbreviated Injury Scale (AIS), and Glasgow Coma Scale (GCS). Antioxidant capacity (icORP) on day 4 was prognostic for acute outcomes (p < 0.05). An odds ratio of 4.08 was associated with poor acute outcome when icORP > 7.25 μC. IcORP was a better predictor than ISS, AIS, or GCS scores. sORP increased in those with the highest ISS values (p < 0.05). Based on these findings ORP is useful biomarker for severity and acute outcome in TBI patients. Changes in ORP values on day 4 after injury were the most prognostic, suggesting that patients' response to brain injury over time is a factor that determines outcome. PMID:27642494

  17. Systems biomarkers as acute diagnostics and chronic monitoring tools for traumatic brain injury

    NASA Astrophysics Data System (ADS)

    Wang, Kevin K. W.; Moghieb, Ahmed; Yang, Zhihui; Zhang, Zhiqun

    2013-05-01

    Traumatic brain injury (TBI) is a significant biomedical problem among military personnel and civilians. There exists an urgent need to develop and refine biological measures of acute brain injury and chronic recovery after brain injury. Such measures "biomarkers" can assist clinicians in helping to define and refine the recovery process and developing treatment paradigms for the acutely injured to reduce secondary injury processes. Recent biomarker studies in the acute phase of TBI have highlighted the importance and feasibilities of identifying clinically useful biomarkers. However, much less is known about the subacute and chronic phases of TBI. We propose here that for a complex biological problem such as TBI, multiple biomarker types might be needed to harness the wide range of pathological and systemic perturbations following injuries, including acute neuronal death, neuroinflammation, neurodegeneration and neuroregeneration to systemic responses. In terms of biomarker types, they range from brain-specific proteins, microRNA, genetic polymorphism, inflammatory cytokines and autoimmune markers and neuro-endocrine hormones. Furthermore, systems biology-driven biomarkers integration can help present a holistic approach to understanding scenarios and complexity pathways involved in brain injury.

  18. RNA-Seq Characterization of Spinal Cord Injury Transcriptome in Acute/Subacute Phases: A Resource for Understanding the Pathology at the Systems Level

    PubMed Central

    Chen, Kenian; Deng, Shuyun; Lu, Hezuo; Zheng, Yiyan; Yang, Guodong; Kim, Dong; Cao, Qilin; Wu, Jia Qian

    2013-01-01

    Spinal cord injury (SCI) is a devastating neurological disease without effective treatment. To generate a comprehensive view of the mechanisms involved in SCI pathology, we applied RNA-Sequencing (RNA-Seq) technology to characterize the temporal changes in global gene expression after contusive SCI in mice. We sequenced tissue samples from acute and subacute phases (2 days and 7 days after injury) and systematically characterized the transcriptomes with the goal of identifying pathways and genes critical in SCI pathology. The top enriched functional categories include “inflammation response,” “neurological disease,” “cell death and survival” and “nervous system development.” The top enriched pathways include LXR/RXR Activation and Atherosclerosis Signaling, etc. Furthermore, we developed a systems-based analysis framework in order to identify key determinants in the global gene networks of the acute and sub-acute phases. Some candidate genes that we identified have been shown to play important roles in SCI, which demonstrates the validity of our approach. There are also many genes whose functions in SCI have not been well studied and can be further investigated by future experiments. We have also incorporated pharmacogenomic information into our analyses. Among the genes identified, the ones with existing drug information can be readily tested in SCI animal models. Therefore, in this study we have described an example of how global gene profiling can be translated to identifying genes of interest for functional tests in the future and generating new hypotheses. Additionally, the RNA-Seq enables splicing isoform identification and the estimation of expression levels, thus providing useful information for increasing the specificity of drug design and reducing potential side effect. In summary, these results provide a valuable reference data resource for a better understanding of the SCI process in the acute and sub-acute phases. PMID:23951329

  19. Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms.

    PubMed

    Tator, C H; Fehlings, M G

    1991-07-01

    In patients with spinal cord injury, the primary or mechanical trauma seldom causes total transection, even though the functional loss may be complete. In addition, biochemical and pathological changes in the cord may worsen after injury. To explain these phenomena, the concept of the secondary injury has evolved for which numerous pathophysiological mechanisms have been postulated. This paper reviews the concept of secondary injury with special emphasis on vascular mechanisms. Evidence is presented to support the theory of secondary injury and the hypothesis that a key mechanism is posttraumatic ischemia with resultant infarction of the spinal cord. Evidence for the role of vascular mechanisms has been obtained from a variety of models of acute spinal cord injury in several species. Many different angiographic methods have been used for assessing microcirculation of the cord and for measuring spinal cord blood flow after trauma. With these techniques, the major systemic and local vascular effects of acute spinal cord injury have been identified and implicated in the etiology of secondary injury. The systemic effects of acute spinal cord injury include hypotension and reduced cardiac output. The local effects include loss of autoregulation in the injured segment of the spinal cord and a marked reduction of the microcirculation in both gray and white matter, especially in hemorrhagic regions and in adjacent zones. The microcirculatory loss extends for a considerable distance proximal and distal to the site of injury. Many studies have shown a dose-dependent reduction of spinal cord blood flow varying with the severity of injury, and a reduction of spinal cord blood flow which worsens with time after injury. The functional deficits due to acute spinal cord injury have been measured electrophysiologically with techniques such as motor and somatosensory evoked potentials and have been found proportional to the degree of posttraumatic ischemia. The histological effects

  20. A case-crossover study of transient risk factors for occupational acute hand injury

    PubMed Central

    Sorock, G; Lombardi, D; Hauser, R; Eisen, E; Herrick, R; Mittleman, M

    2004-01-01

    Background: Workers with acute hand injuries account for over 1 000 000 emergency department visits annually in the United States. Aims: To determine potential transient risk factors for occupational acute hand injury. Methods: Subjects were recruited from 23 occupational health clinics in five northeastern states in the USA. In a telephone interview, subjects were asked to report the occurrence of seven potential risk factors within a 90-minute time period before an acute hand injury. Each case also provided control information on exposures during the month before the injury. The self-matched feature of the study design controlled for stable between-person confounders. Results: A total of 1166 subjects were interviewed (891 men, 275 women), with a mean age (SD) of 37.2 years (11.4). The median time interval between injury and interview was 1.3 days. Sixty three per cent of subjects had a laceration. The relative risk of a hand injury was increased when working with equipment, tools, or work pieces not performing as expected (11.0, 95% CI 9.4 to 12.8), or when using a different work method to do a task (10.5, 95% CI 8.7 to 12.7). Other transient factors in decreasing order of relative risk were doing an unusual task, being distracted, and being rushed. Wearing gloves reduced the relative risk by 60% (0.4, 95% CI 0.3 to 0.5). Occupational category, job experience, and safety training were found to alter several of these effects. Conclusion: The results suggest the importance of these transient, potentially modifiable factors in the aetiology of acute hand injury at work. Attempts to modify these exposures by various strategies may reduce the incidence of acute hand injury at work. PMID:15031387

  1. Leptin treatment ameliorates acute lung injury in rats with cerulein-induced acute pancreatitis

    PubMed Central

    Gultekin, Fatma Ayca; Kerem, Mustafa; Tatlicioglu, Ertan; Aricioglu, Aysel; Unsal, Cigdem; Bukan, Neslihan

    2007-01-01

    AIM: To determine the effect of exogenous leptin on acute lung injury (ALI) in cerulein-induced acute pancreatitis (AP). METHODS: Forty-eight rats were randomly divided into 3 groups. AP was induced by intraperitoneal (i.p.) injection of cerulein (50 μg/kg) four times, at 1 h intervals. The rats received a single i.p. injection of 10 μg/kg leptin (leptin group) or 2 mL saline (AP group) after cerulein injections. In the sham group, animals were given a single i.p. injection of 2 mL saline. Experimental samples were collected for biochemical and histological evaluations at 24 h and 48 h after the induction of AP or saline administration. Blood samples were obtained for the determination of amylase, lipase, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, macrophage inflammatory peptide (MIP)-2 and soluble intercellular adhesion molecule (sICAM)-1 levels, while pancreatic and lung tissues were removed for myeloperoxidase (MPO) activity, nitric oxide (NOx) level, CD40 expression and histological evaluation. RESULTS: Cerulein injection caused severe AP, confirmed by an increase in serum amylase and lipase levels, histopathological findings of severe AP, and pancreatic MPO activity, compared to the values obtained in the sham group. In the leptin group, serum levels of MIP-2, sICMA-1, TNF-α, and IL-1β, pancreatic MPO activity, CD40 expression in pancreas and lung tissues, and NOx level in the lung tissue were lower compared to those in the AP group. Histologically, pancreatic and lung damage was less severe following leptin administration. CONCLUSION: Exogenous leptin attenuates inflamma-tory changes, and reduces pro-inflammatory cytokines, nitric oxide levels, and CD40 expression in cerulein-induced AP and may be protective in AP associated ALI. PMID:17589942

  2. The impact of acute hyponatraemia on severe traumatic brain injury in rats.

    PubMed

    Ke, C; Poon, W S; Ng, H K; Tang, N L; Chan, Y; Wang, J Y; Hsiang, J N

    2000-01-01

    The effect of experimental acute hyponatraemia on severe traumatic brain injury (TBI) was studied in a modified impact-acceleration model. The cortical contusional volume was quantified by image analysis on serial sections, injured axons were visualized and quantified by beta-Amyloid Precursor Protein (beta-APP) immunohistochemical staining. Regional brain water content was estimated by the wet-dry weight method. The experiment was conducted in Group I (injury only) and Group II (injury followed by acute hyponatraemia). Comparison between the two groups showed that acute hyponatraemia significantly increased contusional volume (3.24 +/- 0.70 mm3 vs. 1.80 +/- 0.65 mm3, P = 0.009) and the number of injured axons (128.7 +/- 44.3 vs. 41.7 +/- 50.1, P = 0.04) in the right thalamus & basal ganglia region. Water content of the brain stem region was also significantly increased by acute hyponatraemia (73.71 +/- 0.14% vs. 72.28 +/- 0.93%, P = 0.004). These results suggest that acute hyponatraemia potentiates secondary brain damage in severe TBI by augmentation of both focal contusion and diffuse axonal injury. The injured brain stem region is more susceptible to edema formation induced by experimental acute hyponatraemia.

  3. Acute foot drop syndrome mimicking peroneal nerve injury: an atypical presentation of ischemic stroke.

    PubMed

    Ricarte, Irapuá Ferreira; Figueiredo, Marcelo Marinho de; Fukuda, Thiago Gonçalves; Pedroso, José Luiz; Silva, Gisele Sampaio

    2014-01-01

    Foot drop syndrome is a frequent neurologic condition usually caused by peroneal nerve damage. On rare occasions, foot drop may present as the single neurologic manifestation of intracranial lesions. We presented a 43-year-old man admitted to our hospital with acute weakness in the dorsiflexion of his right foot that appeared 3 days before admission. Brain magnetic resonance imaging diffusion-weighted sequence revealed a small area of restricted diffusion in the left frontal cortex. Three months later, his motor deficit had completely improved (modified Rankin scale score = 0). To our knowledge, this is the second report of sudden isolated foot drop caused by a cortical infarction.

  4. Nilotinib ameliorates lipopolysaccharide-induced acute lung injury in rats

    SciTech Connect

    El-Agamy, Dina S.

    2011-06-01

    The present study aimed to investigate the effect of the new tyrosine kinase inhibitor, nilotinib on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats and explore its possible mechanisms. Male Sprague-Dawley rats were given nilotinib (10 mg/kg) by oral gavage twice daily for 1 week prior to exposure to aerosolized LPS. At 24 h after LPS exposure, bronchoalveolar lavage fluid (BALF) samples and lung tissue were collected. The lung wet/dry weight (W/D) ratio, protein level and the number of inflammatory cells in the BALF were determined. Optical microscopy was performed to examine the pathological changes in lungs. Malondialdehyde (MDA) content, superoxidase dismutase (SOD) and reduced glutathione (GSH) activities as well as nitrite/nitrate (NO{sub 2}{sup -}/NO{sub 3}{sup -}) levels were measured in lung tissues. The expression of inflammatory cytokines, tumor necrosis factor-{alpha} (TNF-{alpha}), transforming growth factor-{beta}{sub 1} (TGF-{beta}{sub 1}) and inducible nitric oxide synthase (iNOS) were determined in lung tissues. Treatment with nilotinib prior to LPS exposure significantly attenuated the LPS-induced pulmonary edema, as it significantly decreased lung W/D ratio, protein concentration and the accumulation of the inflammatory cells in the BALF. This was supported by the histopathological examination which revealed marked attenuation of LPS-induced ALI in nilotinib treated rats. In addition, nilotinib significantly increased SOD and GSH activities with significant decrease in MDA content in the lung. Nilotinib also reduced LPS mediated overproduction of pulmonary NO{sub 2}{sup -}/NO{sub 3}{sup -} levels. Importantly, nilotinib caused down-regulation of the inflammatory cytokines TNF-{alpha}, TGF-{beta}{sub 1} and iNOS levels in the lung. Taken together, these results demonstrate the protective effects of nilotinib against the LPS-induced ALI. This effect can be attributed to nilotinib ability to counteract the inflammatory cells

  5. Brain-derived neurotrophic factor delivered to the brain using poly (lactide-co-glycolide) nanoparticles improves neurological and cognitive outcome in mice with traumatic brain injury.

    PubMed

    Khalin, Igor; Alyautdin, Renad; Wong, Tin Wui; Gnanou, Justin; Kocherga, Ganna; Kreuter, Jörg

    2016-11-01

    Currently, traumatic brain injury (TBI) is the leading cause of death or disabilities in young individuals worldwide. The multi-complexity of its pathogenesis as well as impermeability of the blood-brain barrier (BBB) makes the drug choice and delivery very challenging. The brain-derived neurotrophic factor (BDNF) regulates neuronal plasticity, neuronal cell growth, proliferation, cell survival and long-term memory. However, its short half-life and low BBB permeability are the main hurdles to be an effective therapeutic for TBI. Poly (lactic-co-glycolic acid) (PLGA) nanoparticles coated by surfactant can enable the delivery of a variety of molecules across the BBB by receptor-mediated transcytosis. This study examines the ability of PLGA nanoparticles coated with poloxamer 188 (PX) to deliver BDNF into the brain and neuroprotective effects of BNDF in mice with TBI. C57bl/6 mice were subjected to weight-drop closed head injuries under anesthesia. Using enzyme-linked immunosorbent assay, we demonstrated that the intravenous (IV) injection of nanoparticle-bound BDNF coated by PX (NP-BDNF-PX) significantly increased BDNF levels in the brain of sham-operated mice (p < 0.001) and in both ipsi- (p < 0.001) and contralateral (p < 0.001) parts of brain in TBI mice compared to controls. This study also showed using the passive avoidance (PA) test, that IV injection of NP-BDNF-PX 3 h post-injury prolonged the latent time in mice with TBI thereby reversing cognitive deficits caused by brain trauma. Finally, neurological severity score test demonstrated that our compound efficiently reduced the scores at day 7 after the injury indicating the improvement of neurological deficit in animals with TBI. This study shows that PLGA nanoparticles coated with PX effectively delivered BDNF into the brain, and improved neurological and cognitive deficits in TBI mice, thereby providing a neuroprotective effect.

  6. Dihydro-Resveratrol Ameliorates Lung Injury in Rats with Cerulein-Induced Acute Pancreatitis.

    PubMed

    Lin, Ze-Si; Ku, Chuen Fai; Guan, Yi-Fu; Xiao, Hai-Tao; Shi, Xiao-Ke; Wang, Hong-Qi; Bian, Zhao-Xiang; Tsang, Siu Wai; Zhang, Hong-Jie

    2016-04-01

    Acute pancreatitis is an inflammatory process originated in the pancreas; however, it often leads to systemic complications that affect distant organs. Acute respiratory distress syndrome is indeed the predominant cause of death in patients with severe acute pancreatitis. In this study, we aimed to delineate the ameliorative effect of dihydro-resveratrol, a prominent analog of trans-resveratrol, against acute pancreatitis-associated lung injury and the underlying molecular actions. Acute pancreatitis was induced in rats with repetitive injections of cerulein (50 µg/kg/h) and a shot of lipopolysaccharide (7.5 mg/kg). By means of histological examination and biochemical assays, the severity of lung injury was assessed in the aspects of tissue damages, myeloperoxidase activity, and levels of pro-inflammatory cytokines. When treated with dihydro-resveratrol, pulmonary architectural distortion, hemorrhage, interstitial edema, and alveolar thickening were significantly reduced in rats with acute pancreatitis. In addition, the production of pro-inflammatory cytokines and the activity of myeloperoxidase in pulmonary tissues were notably repressed. Importantly, nuclear factor-kappaB (NF-κB) activation was attenuated. This study is the first to report the oral administration of dihydro-resveratrol ameliorated acute pancreatitis-associated lung injury via an inhibitory modulation of pro-inflammatory response, which was associated with a suppression of the NF-κB signaling pathway.

  7. Understanding the Acute Skin Injury Mechanism Caused by Player-Surface Contact During Soccer

    PubMed Central

    van den Eijnde, Wilbert A.J.; Peppelman, Malou; Lamers, Edwin A.D.; van de Kerkhof, Peter C.M.; van Erp, Piet E.J.

    2014-01-01

    Background: Superficial skin injuries are considered minor, and their incidence is probably underestimated. Insight into the incidence and mechanism of acute skin injury can be helpful in developing suitable preventive measures and safer playing surfaces for soccer and other field sports. Purpose: To gain insight into the incidence and severity of skin injuries related to soccer and to describe the skin injury mechanism due to player-surface contact. Study Design: Systematic review; Level of evidence, 4. Methods: The prevention model by van Mechelen et al (1992) combined with the injury causation model of Bahr and Krosshaug (2005) were used as a framework for the survey to describe the skin injury incidence and mechanism caused by player-surface contact. Results: The reviewed literature showed that common injury reporting methods are mainly based on time lost from participation or the need for medical attention. Because skin abrasions seldom lead to absence or medical attention, they are often not reported. When reported, the incidence of abrasion/laceration injuries varies from 0.8 to 6.1 injuries per 1000 player-hours. Wound assessment techniques such as the Skin Damage Area and Severity Index can be a valuable tool to obtain a more accurate estimation of the incidence and severity of acute skin injuries. Conclusion: The use of protective equipment, a skin lubricant, or wet surface conditions has a positive effect on preventing abrasion-type injuries from artificial turf surfaces. The literature also shows that essential biomechanical information of the sliding event is lacking, such as how energy is transferred to the area of contact. From a clinical and histological perspective, there are strong indications that a sliding-induced skin lesion is caused by mechanical rather than thermal injury to the skin. PMID:26535330

  8. Analyses of acute kidney injury biomarkers by ultra-high performance liquid chromatography with mass spectrometry.

    PubMed

    Al Za'abi, Mohammed; Ali, Badreldin H; ALOthman, Zeid A; Ali, Imran

    2016-01-01

    The newly developed acute kidney injury biomarkers are very important for the early and timely detection of kidney diseases. This review contains details of the analyses of several acute kidney injury biomarkers using ultra-high performance liquid chromatography-mass spectrometry in urine and plasma samples. In this review we attempt to discuss some aspects of the types of the biomarkers, patents, sample preparation, and the analyses. Besides, efforts were also made to discuss the possible uses of superficially porous (core-shell) columns in traditional and inexpensive high-performance liquid chromatography instruments. Additionally, the challenges and the future prospects are also highlighted. The present review will be useful for the academicians, scientists, and clinicians for the early detection of acute kidney injury biomarkers.

  9. Transient IgA nephropathy with acute kidney injury in a patient with dengue fever.

    PubMed

    Upadhaya, Bala Krishna; Sharma, Alok; Khaira, Ambar; Dinda, Amit K; Agarwal, Sanjay K; Tiwari, Suresh C

    2010-05-01

    Dengue virus infection can clinically manifest as dengue fever, dengue shock syndrome and dengue hemorrhagic fever. Acute kidney injury as a result of dengue virus infection can occur due to various reasons including hypotension, rhabdomyolysis, sepsis and rarely immune complex mediated glomerular injury. However, glomerulonephritis associated with IgA Nephropathy in dengue virus infection has not been reported previously. We report a case of 15-year-old boy who was admitted with dengue fever and dialysis dependant acute kidney injury. Urine examination showed microscopic glomerular hematuria and proteinuria. Kidney biopsy showed mesangial proliferation with mesangial IgA dominant immune complex deposits and acute tubular necrosis. A repeated kidney biopsy 6 weeks after clinical recovery showed reversal of glomerular changes as well as resolution of mesangial IgA deposits.

  10. Acute Stress Decreases but Chronic Stress Increases Myocardial Sensitivity to Ischemic Injury in Rodents

    PubMed Central

    Eisenmann, Eric D.; Rorabaugh, Boyd R.; Zoladz, Phillip R.

    2016-01-01

    Cardiovascular disease (CVD) is the largest cause of mortality worldwide, and stress is a significant contributor to the development of CVD. The relationship between acute and chronic stress and CVD is well evidenced. Acute stress can lead to arrhythmias and ischemic injury. However, recent evidence in rodent models suggests that acute stress can decrease sensitivity to myocardial ischemia–reperfusion injury (IRI). Conversely, chronic stress is arrhythmogenic and increases sensitivity to myocardial IRI. Few studies have examined the impact of validated animal models of stress-related psychological disorders on the ischemic heart. This review examines the work that has been completed using rat models to study the effects of stress on myocardial sensitivity to ischemic injury. Utilization of animal models of stress-related psychological disorders is critical in the prevention and treatment of cardiovascular disorders in patients experiencing stress-related psychiatric conditions. PMID:27199778

  11. Cocktail of chemical compounds robustly promoting cell reprogramming protects liver against acute injury.

    PubMed

    Tang, Yuewen; Cheng, Lin

    2017-02-11

    Tissue damage induces cells into reprogramming-like cellular state, which contributes to tissue regeneration. However, whether factors promoting the cell reprogramming favor tissue regeneration remains elusive. Here we identified combination of small chemical compounds including drug cocktails robustly promoting in vitro cell reprogramming. We then administrated the drug cocktails to mice with acute liver injuries induced by partial hepatectomy or toxic treatment. Our results demonstrated that the drug cocktails which promoted cell reprogramming in vitro improved liver regeneration and hepatic function in vivo after acute injuries. The underlying mechanism could be that expression of pluripotent genes activated after injury is further upregulated by drug cocktails. Thus our study offers proof-of-concept evidence that cocktail of clinical compounds improving cell reprogramming favors tissue recovery after acute damages, which is an attractive strategy for regenerative purpose.

  12. Attenuation of Acute Phase Injury in Rat Intracranial Hemorrhage by Cerebrolysin that Inhibits Brain Edema and Inflammatory Response.

    PubMed

    Yang, Yang; Zhang, Yan; Wang, Zhaotao; Wang, Shanshan; Gao, Mou; Xu, Ruxiang; Liang, Chunyang; Zhang, Hongtian

    2016-04-01

    The outcome of intracerebral hemorrhage (ICH) is mainly determined by the volume of the hemorrhage core and the secondary brain damage to penumbral tissues due to brain swelling, microcirculation disturbance and inflammation. The present study aims to investigate the protective effects of cerebrolysin on brain edema and inhibition of the inflammation response surrounding the hematoma core in the acute stage after ICH. The ICH model was induced by administration of type VII bacterial collagenase into the stratum of adult rats, which were then randomly divided into three groups: ICH + saline; ICH + Cerebrolysin (5 ml/kg) and sham. Cerebrolysin or saline was administered intraperitoneally 1 h post surgery. Neurological scores, extent of brain edema content and Evans blue dye extravasation were recorded. The levels of pro-inflammatory factors (IL-1β, TNF-α and IL-6) were assayed by Real-time PCR and Elisa kits. Aquaporin-4 (AQP4) and tight junction proteins (TJPs; claudin-5, occludin and zonula occluden-1) expression were measured at multiple time points. The morphological and intercellular changes were characterized by Electron microscopy. It is found that cerebrolysin (5 ml/kg) improved the neurological behavior and reduced the ipsilateral brain water content and Evans blue dye extravasation. After cerebrolysin treated, the levels of pro-inflammatory factors and AQP4 in the peri-hematomal areas were markedly reduced and were accompanied with higher expression of TJPs. Electron microscopy showed the astrocytic swelling and concentrated chromatin in the ICH group and confirmed the cell junction changes. Thus, early cerebrolysin treatment ameliorates secondary injury after ICH and promotes behavioral performance during the acute phase by reducing brain edema, inflammatory response, and blood-brain barrier permeability.

  13. Assessment of brainstem damage by the auditory brainstem response in acute severe head injury.

    PubMed Central

    Tsubokawa, T; Nishimoto, H; Yamamoto, T; Kitamura, M; Katayama, Y; Moriyasu, N

    1980-01-01

    In 64 cases suffering from severe head injury (Glasgow coma scale: less than seven- the auditory brainstem responses (FARs) recorded at the vertex, which are thought to be volumet conducted far-field potentials reflecting the sequential electrical activities of the auditory afferen) system in the brainstem, were recorded in the neurosurgical intensive care room immediately after admission. The alterations in the responses were compared with the types of primary injury, neurological signs., CT findings and outcome following treatment. Based on the results obtained, it is concluded that the FAR is a useful indicator for predicting the effects of treatment on brainstem damage in patients with severe head injury, and that it provides more reliable information about the function of the brainstem than the neurological signs or CT findings. Moreover, it also offers a diagnostic method for primary brainstem injury. Three cases or primary brainstem injury without lesions in the supratentorial region were diagnosed by means of combined CT and FAR recording. Images PMID:7441277

  14. Association of Blood Lead Level with Neurological Features in 972 Children Affected by an Acute Severe Lead Poisoning Outbreak in Zamfara State, Northern Nigeria

    PubMed Central

    Greig, Jane; Thurtle, Natalie; Cooney, Lauren; Ariti, Cono; Ahmed, Abdulkadir Ola; Ashagre, Teshome; Ayela, Anthony; Chukwumalu, Kingsley; Criado-Perez, Alison; Gómez-Restrepo, Camilo; Meredith, Caitlin; Neri, Antonio; Stellmach, Darryl; Sani-Gwarzo, Nasir; Nasidi, Abdulsalami; Shanks, Leslie; Dargan, Paul I.

    2014-01-01

    Background In 2010, Médecins Sans Frontières (MSF) investigated reports of high mortality in young children in Zamfara State, Nigeria, leading to confirmation of villages with widespread acute severe lead poisoning. In a retrospective analysis, we aimed to determine venous blood lead level (VBLL) thresholds and risk factors for encephalopathy using MSF programmatic data from the first year of the outbreak response. Methods and Findings We included children aged ≤5 years with VBLL ≥45 µg/dL before any chelation and recorded neurological status. Odds ratios (OR) for neurological features were estimated; the final model was adjusted for age and baseline VBLL, using random effects for village of residence. 972 children met inclusion criteria: 885 (91%) had no neurological features; 34 (4%) had severe features; 47 (5%) had reported recent seizures; and six (1%) had other neurological abnormalities. The geometric mean VBLLs for all groups with neurological features were >100 µg/dL vs 65.9 µg/dL for those without neurological features. The adjusted OR for neurological features increased with increasing VBLL: from 2.75, 95%CI 1.27–5.98 (80–99.9 µg/dL) to 22.95, 95%CI 10.54–49.96 (≥120 µg/dL). Neurological features were associated with younger age (OR 4.77 [95% CI 2.50–9.11] for 1–<2 years and 2.69 [95%CI 1.15–6.26] for 2–<3 years, both vs 3–5 years). Severe neurological features were seen at VBLL <105 µg/dL only in those with malaria. Interpretation Increasing VBLL (from ≥80 µg/dL) and age 1–<3 years were strongly associated with neurological features; in those tested for malaria, a positive test was also strongly associated. These factors will help clinicians managing children with lead poisoning in prioritising therapy and developing chelation protocols. PMID:24740291

  15. Aerosolized alpha-tocopherol ameliorates acute lung injury following combined burn and smoke inhalation injury in sheep.

    PubMed

    Morita, Naoki; Traber, Maret G; Enkhbaatar, Perenlei; Westphal, Martin; Murakami, Kazunori; Leonard, Scott W; Cox, Robert A; Hawkins, Hal K; Herndon, David; Traber, Lillian D; Traber, Daniel L

    2006-03-01

    Victims of fire accidents who sustain both thermal injury to the skin and smoke inhalation have gross evidence of oxidant injury. Therefore, we hypothesized that delivery of vitamin E, an oxygen superoxide scavenger, directly into the airway would attenuate acute lung injury postburn and smoke inhalation. Sheep (N = 17 female, 35 +/- 5 kg) were divided into 3 groups: (1) injured, then nebulized with vitamin E (B&S, Vitamin E, n = 6); (2) injured, nebulized with saline (B&S, Saline, n = 6); and (3) not injured, not treated (Sham, n = 5). While under deep anesthesia with isoflurane, the sheep were subjected to a flame burn (40% total body surface area, 3rd degree) and inhalation injury (48 breaths of cotton smoke, <40 degrees C). All groups were resuscitated with Ringer lactate solution (4 mL/kg/%burn/24 h) and placed on a ventilator [positive end-expiratory pressure (PEEP) = 5 cm H2O, tidal volume = 15 mL/kg] for 48 h. B&S injury halved the lung alpha-tocopherol concentrations (0.9 +/- 0.1 nmol/g) compared with sham-injured animals (1.5 +/- 0.3), whereas vitamin E treatment elevated the lung alpha-tocopherol concentrations (7.40 +/- 2.61) in the injured animals. B&S injury decreased pulmonary gas exchange (PaO2/FiO2 ratios) from 517 +/- 15 at baseline to 329 +/- 49 at 24 h and to 149 +/- 32 at 48 h compared with sham ratios of 477 +/- 14, 536 +/- 48, and 609 +/- 49, respectively. Vitamin E treatment resulted in a significant improvement of pulmonary gas exchange; ratios were 415 +/- 34 and 283 +/- 42 at 24 and 48 h, respectively. Vitamin E nebulization therapy improved the clinical responses to burn and smoke inhalation-induced acute lung injury.

  16. Targeted activation of CREB in reactive astrocytes is neuroprotective in focal acute cortical injury.

    PubMed

    Pardo, Luis; Schlüter, Agatha; Valor, Luis M; Barco, Angel; Giralt, Mercedes; Golbano, Arantxa; Hidalgo, Juan; Jia, Peilin; Zhao, Zhongming; Jové, Mariona; Portero-Otin, Manuel; Ruiz, Montserrat; Giménez-Llort, Lydia; Masgrau, Roser; Pujol, Aurora; Galea, Elena

    2016-05-01

    The clinical challenge in acute injury as in traumatic brain injury (TBI) is to halt the delayed neuronal loss that occurs hours and days after the insult. Here we report that the activation of CREB-dependent transcription in reactive astrocytes prevents secondary injury in cerebral cortex after experimental TBI. The study was performed in a novel bitransgenic mouse in which a constitutively active CREB, VP16-CREB, was targeted to astrocytes with the Tet-Off system. Using histochemistry, qPCR, and gene profiling we found less neuronal death and damage, reduced macrophage infiltration, preserved mitochondria, and rescued expression of genes related to mitochondrial metabolism in bitransgenic mice as compared to wild type littermates. Finally, with meta-analyses using publicly available databases we identified a core set of VP16-CREB candidate target genes that may account for the neuroprotective effect. Enhancing CREB activity in astrocytes thus emerges as a novel avenue in acute brain post-injury therapeutics.

  17. Early Decompression of Acute Subdural Hematoma for Postoperative Neurological Improvement: A Single Center Retrospective Review of 10 Years

    PubMed Central

    Oh, Chang Hyun; Shim, Yu Shik; Hyun, Dongkeun; Park, Hyeonseon; Kim, Eunyoung

    2016-01-01

    Objective This study was conducted to investigate survival related factors, as well as to evaluate the effects of early decompression on acute subdural hematoma (ASDH). Methods We retrospectively reviewed cases of decompressive craniectomy (DC) for decade. In total, 198 cases of DC involved ASDH were available for review, and 65 cases were excluded due to missing data on onset time and a delayed operation after closed observation with medical care. Finally, 133 cases of DC with ASDH were included in this study, and various factors including the time interval between trauma onset and operation were evaluated. Results In the present study, survival rate after DC in patients with ASDH was shown to be related to patient age (50 years old, p=0.012), brain compression ratio (p=0.042) and brain stem compression (p=0.020). Sex, preoperative mental status, and time interval between trauma onset and operation were not related with survival rate. Among those that survived (n=78), improvements in Glasgow Coma Scale (GCS) score of more than three points, compared to preoperative measurement, were more frequently observed among the early (less than 3 hours between trauma onset and operation) decompressed cases (p=0.013). However, improvements of more than 4 or 5 points on the GCS were not affected by early decompression. Conclusion Early decompression of ASDH was not correlated with survival rate, but was related with neurological improvement (more than three points on the GCS). Accordingly, early decompression in ASDH, if indicated, may be of particular benefit. PMID:27182496

  18. Value of MRI and DTI as Biomarkers for Classifying Acute Spinal Cord Injury

    DTIC Science & Technology

    2014-10-29

    trajectories. Results: Spinal cord hemorrhage and edema on anatomic MRI, and FA, ADC, RD and AD indices derived from DTI data correlate significantly to...features is reproducible among observers. MRI provides excellent definition of intramedullary hemorrhage and edema in animal models. The combination of...prognosis. Cord edema alone (Type II pattern of injury) was found in patients with mild to moderate initial neurologic deficits who subsequently showed

  19. Resolvin D1 protects against inflammation in experimental acute pancreatitis and associated lung injury.

    PubMed

    Liu, Yong; Zhou, Dan; Long, Fei-Wu; Chen, Ke-Ling; Yang, Hong-Wei; Lv, Zhao-Yin; Zhou, Bin; Peng, Zhi-Hai; Sun, Xiao-Feng; Li, Yuan; Zhou, Zong-Guang

    2016-03-01

    Acute pancreatitis is an inflammatory condition that may lead to multisystemic organ failure with considerable mortality. Recently, resolvin D1 (RvD1) as an endogenous anti-inflammatory lipid mediator has been confirmed to protect against many inflammatory diseases. This study was designed to investigate the effects of RvD1 in acute pancreatitis and associated lung injury. Acute pancreatitis varying from mild to severe was induced by cerulein or cerulein combined with LPS, respectively. Mice were pretreated with RvD1 at a dose of 300 ng/mouse 30 min before the first injection of cerulein. Severity of AP was assessed by biochemical markers and histology. Serum cytokines and myeloperoxidase (MPO) levels in pancreas and lung were determined for assessing the extent of inflammatory response. NF-κB activation was determined by Western blotting. The injection of cerulein or cerulein combined with LPS resulted in local injury in the pancreas and corresponding systemic inflammatory changes with pronounced severity in the cerulein and LPS group. Pretreated RvD1 significantly reduced the degree of amylase, lipase, TNF-α, and IL-6 serum levels; the MPO activities in the pancreas and the lungs; the pancreatic NF-κB activation; and the severity of pancreatic injury and associated lung injury, especially in the severe acute pancreatitis model. These results suggest that RvD1 is capable of improving injury of pancreas and lung and exerting anti-inflammatory effects through the inhibition of NF-κB activation in experimental acute pancreatitis, with more notable protective effect in severe acute pancreatitis. These findings indicate that RvD1 may constitute a novel therapeutic strategy in the management of severe acute pancreatitis.

  20. Sponge-mediated Lentivirus Delivery to Acute and Chronic Spinal Cord Injuries

    PubMed Central

    Thomas, Aline M.; Palma, Jaime L.; Shea, Lonnie D.

    2015-01-01

    The environment within the spinal cord after injury, which changes in the progression from the acute to chronic stages, limits the extent of regeneration. The delivery of inductive factors to promote regeneration following spinal cord injury has been promising, yet, few strategies are have are versatile to allow delivery during acute or chronic injury that would facilitate screening of candidate therapies. This report investigates the intrathecal delivery of lentiviruses for long-term expression of regenerative factors. Lentivirus-filled sponges were inserted into the intrathecal space surrounding the spinal cord, with transgene expression observed within multiple cell types that persists for 12 weeks for both intact and injured spinal cord, without any apparent damage to the spinal cord tissue. Sponges loaded with lentivirus encoding for Sonic hedgehog (Shh) were investigated for acute (delivered at 0 weeks) and chronic (at 4 weeks) injuries, and for multiple locations relative to the injury. In an acute model, sponges placed directly above the injury increased oligodendrocyte and decreased astrocyte presence. Sponges placed caudal to the injury had reduced impact on oligodendrocytes and astrocytes in the injury. In a chronic model, sponges increased oligodendrocyte and decreased astrocyte presence. Furthermore, the effect of Shh was shown to be mediated in part by reduction of Bmp signaling, monitored with an Msx2-sensitive reporter vector. The implantation of lentivirus-loaded biomaterials intrathecally provides the opportunity to induce the expression of a factor at a specified time without entering the spinal cord, and has the potential to promote gene delivery within the spinal cord, which can influence the extent of regeneration. PMID:25724274

  1. Assessment, management and treatment of acute fingertip injuries.

    PubMed

    Kearney, Anthony; Canty, Louise

    2016-06-01

    Fingertip injuries with nail bed trauma can require specialist hand surgery, depending on severity. However, most of these injuries can be managed in well-equipped emergency departments by emergency nurses with an in-depth knowledge and understanding of the anatomy and physiology of the fingernail and surrounding structures, assessment and examination, pain management and treatment. This article describes the surface and underlying anatomy and physiology of the nail, the most common mechanisms of injury, relevant diagnostic investigations, and initial assessment and management. It also discusses treatment options, referral pathways, and patient discharge advice.

  2. Eupafolin nanoparticle improves acute renal injury induced by LPS through inhibiting ROS and inflammation.

    PubMed

    Zhang, Hao; Chen, Ming-Kun; Li, Ke; Hu, Cheng; Lu, Min-Hua; Situ, Jie

    2017-01-01

    Acute renal injury is a common severe clinical syndrome, occurring in many clinical situations. It is necessary to explore effective drugs to treat it. Eupafolin is a flavonoid compound, derived from Phyla nodiflora, which has been previously reported to possess a variety of pharmacological activities, including anti-inflammatory and antioxidant effects. However, it is known little about how it works in acute renal injury. Also, eupafolin is characterized by skin penetration and poor water solubility, limiting its clinical applications. Thus, we synthesized an eupafolin nanoparticle delivery system. We found that eupafolin nanoparticle could address the physicochemical defects of raw eupafolin and increase water solubility without any toxicity to normal renal cells via reducing particle size. Eupafolin nanoparticle attenuated LPS-induced acute renal injury in mice through inhibiting oxidative stress and inflammation accompanied with up-regulated SOD activity and down-regulated pro-inflammatory cytokines. Additionally, inactivation of NF-κB and MAPKs of p38, ERK1/2 and JNK signaling pathways was a main molecular mechanism by which eupafolin nanoparticle improved renal injury. Together, eupafolin nanoparticle exhibits effective anti-oxidant and anti-inflammatory activities, which could be used as a potential drug to ameliorate acute renal injury clinically.

  3. Neurogenic Fever after Acute Traumatic Spinal Cord Injury: A Qualitative Systematic Review

    PubMed Central

    Savage, Katherine E.; Oleson, Christina V.; Schroeder, Gregory D.; Sidhu, Gursukhman S.; Vaccaro, Alexander R.

    2016-01-01

    Study Design  Systematic review. Objective  To determine the incidence, pathogenesis, and clinical outcomes related to neurogenic fevers following traumatic spinal cord injury (SCI). Methods  A systematic review of the literature was performed on thermodysregulation secondary to acute traumatic SCI in adult patients. A literature search was performed using PubMed (MEDLINE), Cochrane Central Register of Controlled Trials, and Scopus. Using strict inclusion and exclusion criteria, seven relevant articles were obtained. Results  The incidence of fever of all origins (both known and unknown) after SCI ranged from 22.5 to 71.7% with a mean incidence of 50.6% and a median incidence of 50.0%. The incidence of fever of unknown origin (neurogenic fever) ranged from 2.6 to 27.8% with a mean incidence of 8.0% and a median incidence of 4.7%. Cervical and thoracic spinal injuries were more commonly associated with fever than lumbar injuries. In addition, complete injuries had a higher incidence of fever than incomplete injuries. The pathogenesis of neurogenic fever after acute SCI is not thoroughly understood. Conclusion  Neurogenic fevers are relatively common following an acute SCI; however, there is little in the scientific literature to help physicians prevent or treat this condition. The paucity of research underscored by this review demonstrates the need for further studies with larger sample sizes, focusing on incidence rate, clinical outcomes, and pathogenesis of neurogenic fever following acute traumatic SCI. PMID:27556002

  4. Polymer-surfactant treatment of meconium-induced acute lung injury.

    PubMed

    Lu, K W; William Taeusch, H; Robertson, B; Goerke, J; Clements, J A

    2000-08-01

    Substances (for example, serum proteins or meconium) that interfere with the activity of pulmonary surfactant in vitro may also be important in the pathogenesis or progression of acute lung injury. Addition of polymers such as dextran or polyethylene glycol (PEG) to surfactants prevents and reverses surfactant inactivation. The purpose of this study was to find out whether surfactant/polymer mixtures are more effective for treating one form of acute lung injury than is surfactant alone. Acute lung injury in adult rats was created by tracheal instillation of human meconium. Injured animals, which were anesthetized, paralyzed, and ventilated with 100% oxygen and not treated with surfactant mixtures, remained hypoxic and required high ventilator pressures to maintain Pa(CO(2)) in the normal range over the 3 h of the experiment. Uninjured animals maintained normal values for oxygen and compliance of the respiratory system. The greatest improvement in both oxygenation (178%) and compliance (42%) occurred in animals with lung injury that were treated with Survanta and PEG (versus untreated control animals; p < 0.01), whereas little improvement was found after treatment with Survanta alone. Similar results were found when postmortem pulmonary pressure-volume curves and histology were examined. We conclude that adding PEG to Survanta improves gas exchange, pulmonary mechanics, and histologic appearance of the lungs in a rat model of acute lung injury caused by meconium.

  5. Acute Lung Injury Accompanying Alveolar Hemorrhage Associated with Flu Vaccination in the Elderly.

    PubMed

    Satoh, Etsuko; Nei, Takahito; Kuzu, Shinichi; Chubachi, Kumi; Nojima, Daisuke; Taniuchi, Namiko; Yamano, Yoshimitsu; Gemma, Akihiko

    2015-01-01

    Flu vaccinations are administered worldwide every winter for prevention. We herein describe a case of acute lung injury resulting from a pathologically confirmed alveolar hemorrhage, which may have been closely related to a preceding vaccination for pandemic influenza A of 2009/10. The present patient had been hospitalized with an acute lung injury after flu vaccination one year prior to the present hospitalization, however, he received another flu vaccination. We should consider a vaccine-related adverse reaction as a potential cause of pulmonary disease if patients present with this illness during the winter season.

  6. The serpentine path to a novel mechanism-based inhibitor of acute inflammatory lung injury

    PubMed Central

    2014-01-01

    The Comroe lecture on which this review is based described my research path during the past 45 years, beginning with studies of oxidant stress (hyperoxia) and eventuating in the discovery of a synthetic inhibitor of phospholipase A2 activity (called MJ33) that prevents acute lung injury in mice exposed to lipopolysaccharide. In between were studies of lung ischemia, lung surfactant metabolism, the protein peroxiredoxin 6 and its phospholipase A2 activity, and mechanisms for NADPH oxidase activation. These seemingly unrelated research activities provided the nexus for identification of a novel target and a potentially novel therapeutic agent for prevention or treatment of acute lung injury. PMID:24744383

  7. Recovery of Neurological Function Despite Immediate Sleep Disruption Following Diffuse Brain Injury in the Mouse: Clinical Relevance to Medically Untreated Concussion

    PubMed Central

    Rowe, Rachel K.; Harrison, Jordan L.; O'Hara, Bruce F.; Lifshitz, Jonathan

    2014-01-01

    Study Objective: We investigated the relationship between immediate disruption of posttraumatic sleep and functional outcome in the diffuse brain-injured mouse. Design: Adult male C57BL/6 mice were subjected to moderate midline fluid percussion injury (n = 65; 1.4 atm; 6-10 min righting reflex time) or sham injury (n = 44). Cohorts received either intentional sleep disruption (minimally stressful gentle handling) or no sleep disruption for 6 h following injury. Following disruption, serum corticosterone levels (enzyme-linked immunosorbent assay) and posttraumatic sleep (noninvasive piezoelectric sleep cages) were measured. For 1-7 days postinjury, sensorimotor outcome was assessed by Rotarod and a modified Neurological Severity Score (NSS). Cognitive function was measured using Novel Object Recognition (NOR) and Morris water maze (MWM) in the first week postinjury. Setting: Neurotrauma research laboratory. Measurements and Results: Disrupting posttraumatic sleep for 6 h did not affect serum corticosterone levels or functional outcome. In the hour following the first dark onset, sleep-disrupted mice exhibited a significant increase in sleep; however, this increase was not sustained and there was no rebound of lost sleep. Regardless of sleep disruption, mice showed a time-dependent improvement in Rotarod performance, with brain-injured mice having significantly shorter latencies on day 7 compared to sham. Further, brain-injured mice, regardless of sleep disruption, had significantly higher NSS scores postinjury compared with sham. Cognitive behavioral testing showed no group differences among any treatment group measured by MWM and NOR. Conclusion: Short-duration disruption of posttraumatic sleep did not affect functional outcome, measured by motor and cognitive performance. These data raise uncertainty about posttraumatic sleep as a mechanism of recovery from diffuse brain injury. Citation: Rowe RK; Harrison JL; O'Hara BF; Lifshitz J. Recovery of neurological

  8. The role of excessive versus acute administration of erythropoietin in attenuating hepatic ischemia-reperfusion injury.

    PubMed

    Pappo, Orit; Ben-Ari, Ziv; Shevtsov, Evgeni; Avlas, Orna; Gassmann, Max; Ravid, Amiram; Cheporko, Yelena; Hochhauser, Edith

    2010-12-01

    Ischemia-reperfusion injury (I/R) is the main cause of primary graft nonfunction. Our aim was to evaluate the effect of excessive versus acute administration of erythropoietin (EPO) in attenuating the hepatic injury induced by I/R in mice. The effect of segmental (70%) hepatic ischemia was evaluated in a transgenic mouse line with constitutive overexpression of human EPO cDNA and in wild-type (WT) mice. Mice were randomly allocated to 5 main experimental groups: (i) WT-sham, (ii) WT ischemia, (iii) WT ischemia + recombinant human erythropoietin (rhEPO), (iv) transgenic-sham, and (v) transgenic ischemia. The EPO-pretreated mice showed a significant reduction in liver enzyme levels and intrahepatic caspase-3 activity and fewer apoptotic hepatocytes (p < 0.05 for all) compared with the WT untreated I/R group. EPO decreased c-Jun N-terminal kinase (JNK) phosphorylation and nuclear factor-κB (NF-κB) expression during I/R. In transgenic I/R livers, baseline histology showed diffused hepatic injury, and no significant beneficial effect was noted between the WT untreated and the transgenic I/R mice. In conclusion, acute pretreatment with EPO in WT mice attenuated in vivo I/R liver injury. However, in excessive EPO overexpression, the initial liver injury abolished the beneficial effect of EPO. These findings have important implications for the potential use of acute EPO in I/R injury during liver transplantation.

  9. Divergent effects of RIP1 or RIP3 blockade in murine models of acute liver injury.

    PubMed

    Deutsch, M; Graffeo, C S; Rokosh, R; Pansari, M; Ochi, A; Levie, E M; Van Heerden, E; Tippens, D M; Greco, S; Barilla, R; Tomkötter, L; Zambirinis, C P; Avanzi, N; Gulati, R; Pachter, H L; Torres-Hernandez, A; Eisenthal, A; Daley, D; Miller, G

    2015-05-07

    Necroptosis is a recently described Caspase 8-independent method of cell death that denotes organized cellular necrosis. The roles of RIP1 and RIP3 in mediating hepatocyte death from acute liver injury are incompletely defined. Effects of necroptosis blockade were studied by separately targeting RIP1 and RIP3 in diverse murine models of acute liver injury. Blockade of necroptosis had disparate effects on disease outcome depending on the precise etiology of liver injury and component of the necrosome targeted. In ConA-induced autoimmune hepatitis, RIP3 deletion was protective, whereas RIP1 inhibition exacerbated disease, accelerated animal death, and was associated with increased hepatocyte apoptosis. Conversely, in acetaminophen-mediated liver injury, blockade of either RIP1 or RIP3 was protective and was associated with lower NLRP3 inflammasome activation. Our work highlights the fact that diverse modes of acute liver injury have differing requirements for RIP1 and RIP3; moreover, within a single injury model, RIP1 and RIP3 blockade can have diametrically opposite effects on tissue damage, suggesting that interference with distinct components of the necrosome must be considered separately.

  10. Divergent effects of RIP1 or RIP3 blockade in murine models of acute liver injury

    PubMed Central

    Deutsch, M; Graffeo, C S; Rokosh, R; Pansari, M; Ochi, A; Levie, E M; Van Heerden, E; Tippens, D M; Greco, S; Barilla, R; Tomkötter, L; Zambirinis, C P; Avanzi, N; Gulati, R; Pachter, H L; Torres-Hernandez, A; Eisenthal, A; Daley, D; Miller, G

    2015-01-01

    Necroptosis is a recently described Caspase 8-independent method of cell death that denotes organized cellular necrosis. The roles of RIP1 and RIP3 in mediating hepatocyte death from acute liver injury are incompletely defined. Effects of necroptosis blockade were studied by separately targeting RIP1 and RIP3 in diverse murine models of acute liver injury. Blockade of necroptosis had disparate effects on disease outcome depending on the precise etiology of liver injury and component of the necrosome targeted. In ConA-induced autoimmune hepatitis, RIP3 deletion was protective, whereas RIP1 inhibition exacerbated disease, accelerated animal death, and was associated with increased hepatocyte apoptosis. Conversely, in acetaminophen-mediated liver injury, blockade of either RIP1 or RIP3 was protective and was associated with lower NLRP3 inflammasome activation. Our work highlights the fact that diverse modes of acute liver injury have differing requirements for RIP1 and RIP3; moreover, within a single injury model, RIP1 and RIP3 blockade can have diametrically opposite effects on tissue damage, suggesting that interference with distinct components of the necrosome must be considered separately. PMID:25950489

  11. Biomarkers for oxidative stress in acute lung injury induced in rabbits submitted to different strategies of mechanical ventilation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oxidative damage has been said to play an important role in pulmonary injury, which is associated with the development and progression of acute respiratory distress syndrome (ARDS). We aimed to identify biomarkers to determine the oxidative stress in an animal model of acute lung injury (ALI) using ...

  12. The Impact of Surgical Timing in Acute Traumatic Spinal Cord Injury

    DTIC Science & Technology

    2014-10-01

    1 AWARD NUMBER: W81XWH-13-1-0396 TITLE: The impact of surgical timing in acute traumatic spinal ...TYPE Annual 3. DATES COVERED 30 Sep 2013 – 29 Sep 2014 4. TITLE AND SUBTITLE The impact of surgical timing in acute traumatic spinal cord...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The optimal surgical timing following a traumatic spinal cord injury (SCI) remains controversial

  13. Thyroid hormones regulate skeletal muscle regeneration after acute injury.

    PubMed

    Leal, Anna Lúcia R C; Albuquerque, João Paulo C; Matos, Marina S; Fortunato, Rodrigo S; Carvalho, Denise P; Rosenthal, Doris; da Costa, Vânia Maria Corrêa

    2015-02-01

    We evaluated the effects of hypo- and hyperthyroid statuses during the initial phase of skeletal muscle regeneration in rats. To induce hypo- or hyperthyroidism, adult male Wistar rats were treated with methimazole (0.03%) or T4 (10 μg/100 g), respectively, for 10 days. Three days before sacrifice, a crush injury was produced in the solear muscles of one half of the animals, while the other half remained intact. T3, T4, TSH, and leptin serum levels were not affected by the injury. Serum T3 and T4 levels were significantly increased in hyperthyroid and hyper-injury animals. Hypothyroidism was confirmed by the significant increase in serum TSH levels in hypothyroid and hypo-injury animals. Injury increased cell infiltration and macrophage accumulation especially in hyperthyroid animals. Both type 2 and type 3 deiodinases were induced by lesion, and the opposite occurred with the type 1 isoform, at least in the control and hyperthyroid groups. Injury increased both MyoD and myogenin expression in all the studied groups, but only MyoD expression was increased by thyroidal status only at the protein level. We conclude that thyroid hormones modulate skeletal muscle regeneration possibly by regulating the inflammatory process, as well as MyoD and myogenin expression in the injured tissue.

  14. Selective increases of extracellular brain concentrations of aromatic and branched-chain amino acids in relation to deterioration of neurological status in acute (ischemic) liver failure.

    PubMed

    Michalak, A; Butterworth, R F

    1997-12-01

    Previous reports based on studies in brain tissue from humans and experimental animals suggest that aromatic amino acids (AAAs) and branched-chain amino acids (BCAA's) accumulate in brain in acute liver failure. In order to assess these changes in relation to the severity of neurological impairment and to the degree of hyperammonemia, AAAs and BCAAs were measured in vivo by cerebral microdialysis in frontal cortex of rats at various stages during the development of hepatic encephalopathy due to acute liver failure resulting from portacaval anastomosis followed by hepatic artery ligation. Extracellular brain concentrations of AAAs and of valine and leucine were elevated 2 to 4-fold following hepatic devascularization and these increases were significantly correlated to arterial ammonia concentration (r= 0.71-0.84, p<0.05). Extracellular concentrations of tyrosine paralleled the deterioration of neurological status in acute liver failure rats. In view of their role as precursors of monoamine neurotransmitters, ammonia-induced alterations of intracellular/extracellular brain concentration ratios for AAAs could account for altered neuronal excitability and contribute to the encephalopathy characteristic of acute liver failure.

  15. Early-Stage Hyperoxia Is Associated with Favorable Neurological Outcomes and Survival after Severe Traumatic Brain Injury: A Post-Hoc Analysis of the Brain Hypothermia Study.

    PubMed

    Fujita, Motoki; Oda, Yasutaka; Yamashita, Susumu; Kaneda, Kotaro; Kaneko, Tadashi; Suehiro, Eiichi; Dohi, Kenji; Kuroda, Yasuhiro; Kobata, Hitoshi; Tsuruta, Ryosuke; Maekawa, Tsuyoshi

    2017-01-19

    The effects of hyperoxia on the neurological outcomes of patients with severe traumatic brain injury (TBI) are still controversial. We examined whether the partial pressure of arterial oxygen (PaO2) and hyperoxia were associated with neurological outcomes and survival by conducting post-hoc analyses of the Brain Hypothermia (B-HYPO) study, a multi-center randomized controlled trial of mild therapeutic hypothermia for severe TBI. The differences in PaO2 and PaO2/fraction of inspiratory oxygen (P/F) ratio on the 1st day of admission were compared between patients with favorable (n = 64) and unfavorable (n = 65) neurological outcomes and between survivors (n = 90) and deceased patients (n = 39). PaO2 and the P/F ratio were significantly greater in patients with favorable outcomes than in patients with unfavorable neurological outcomes (PaO2: 252 ± 122 vs. 202 ± 87 mm Hg, respectively, p = 0.008; P/F ratio: 455 ± 171 vs. 389 ± 155, respectively, p = 0.022) and in survivors than in deceased patients (PaO2: 242 ± 117 vs. 193 ± 75 mm Hg, respectively, p = 0.005; P/F ratio: 445 ± 171 vs. 370 ± 141, respectively, p = 0.018). Similar tendencies were observed in subgroup analyses in patients with fever control and therapeutic hypothermia, and in patients with an evacuated mass or other lesions (unevacuated lesions). PaO2 was independently associated with survival (odds ratio 1.008, p = 0.037). These results suggested that early-stage hyperoxia might be associated with favorable neurological outcomes and survival following severe TBI.

  16. Pulmonary function test findings in patients with acute inhalation injury caused by smoke bombs

    PubMed Central

    Cao, Lu; Zhang, Xin-Gang; Wang, Jian-Guo; Wang, Han-Bin; Chen, Yi-Bing; Zhao, Da-Hui; Shi, Wen-Fang

    2016-01-01

    Background This study aimed to determine the effects of smoke bomb-induced acute inhalation injury on pulmonary function at different stages of lung injury. Methods We performed pulmonary function tests (PFTs) in 15 patients with acute inhalation injury from days 3 to 180 after smoke inhalation. We measured the trace element zinc in whole blood on days 4 and 17, and correlations of zinc levels with PFTs were performed. Results In the acute stage of lung injury (day 3), 3 of 11 patients with mild symptoms had normal pulmonary function and 8 patients with restrictive ventilatory dysfunction and reduced diffusing capacity. Some patients also had mild obstructive ventilatory dysfunction (5 patients) and a decline in small airway function (6 patients). For patients with severe symptoms, PFT results showed moderate to severe restrictive ventilatory dysfunction and reduced diffusing capacity. PaCO2 was significantly higher (P=0.047) in patients with reduced small airway function compared with those with normal small airway function. Whole blood zinc levels in the convalescence stage (day 17) were significantly lower than those in the acute stage (day 4). Zinc in the acute stage was negatively correlated with DLCO/VA on days 3, 10, and 46 (r=−0.633, −0.676, and −0.675 respectively, P<0.05). Conclusions Smoke inhalation injury mainly causes restrictive ventilatory dysfunction and reduced diffusing capacity, and causes mild obstructive ventilatory dysfunction and small airway function decline in some patients. Zinc is negatively correlated with DLCO/VA. Zinc levels may be able to predict prognosis and indicate the degree of lung injury. PMID:28066595

  17. Acute pain in an emergency clinic: latency of onset and descriptor patterns related to different injuries.

    PubMed

    Melzack, R; Wall, P D; Ty, T C

    1982-09-01

    Features of acute pain were examined in patients at an emergency clinic. Patients who had severe, life-threatening injuries or who were agitated, drunk, or 'in shock' were excluded from the study. Of 138 patients who were alert, rational and coherent, 51 (37%) stated that they did not feel pain at the time of injury. The majority of these patients reported onset of pain within an hour of injury, although the delays were as long as 9 h or more in some patients. The predominant emotions of the patients were embarrassment at appearing careless or worry about loss of wages. None expressed any pleasure or indicated any prospect of gain as a result of the injury. The occurrence of delays in pain onset was related to the nature of the injury. Of 46 patients whose injuries were limited to skin (lacerations, cuts, abrasions, burns), 53% had a pain-free period. Of 86 patients with deep-tissue injuries (fractures, sprains, bruises, amputation of a finger, stabs and crushes), only 28% had a pain-free period. The McGill Pain Questionnaire was administered to patients who felt pain immediately after injury or after a delay, and revealed a normal distribution of sensory scores but very low affective scores compared to patients with chronic pain. The results indicate that the relationship between injury and pain is highly variable and complex.

  18. Acute sports-related spinal cord injury: contemporary management principles.

    PubMed

    Kim, David H; Vaccaro, Alexander R; Berta, Scott C

    2003-07-01

    Improvements in helmet and equipment design have led to significant decreases in overall injury incidence, but no available helmet can prevent catastrophic injury to the neck and cervical spine. The most effective strategy for preventing this type of injury appears to be careful instruction, training, and regulations designed to eliminate head-first contact. The incidence of football-related quadriplegia has decreased from a peak of 13 cases per one million players between 1976 and 1980 to 3 per million from 1991 to 1993, mostly as a result of systematic research and an organized effort to eliminate high-risk behavior. An episode of transient quadriparesis does not appear to be a risk factor for catastrophic spinal cord injury. Torg reported that 0 of 117 quadriplegics in the National Football Head and Neck Injuries Registry recalled a prior episode of transient quadriparesis, and 0 of the 45 patients originally studied in his transient quadriparesis cohort have subsequently suffered quadriplegia. The significance of developmental spinal stenosis is unclear. Plain radiographic identification of a narrow spinal canal in a player sustaining cervical cord neurapraxia warrants further evaluation by MRI to rule out functional stenosis. The presence of actual cord deformation or compression on MRI should preclude participation in high-risk contact or collision sports.

  19. [Nutritional and metabolic aspects of neurological diseases].

    PubMed

    Planas Vilà, Mercè

    2014-01-01

    The central nervous system regulates food intake, homoeostasis of glucose and electrolytes, and starts the sensations of hunger and satiety. Different nutritional factors are involved in the pathogenesis of several neurological diseases. Patients with acute neurological diseases (traumatic brain injury, cerebral vascular accident hemorrhagic or ischemic, spinal cord injuries, and cancer) and chronic neurological diseases (Alzheimer's Disease and other dementias, amyotrophic lateral sclerosis, Parkinson's Disease) increase the risk of malnutrition by multiple factors related to nutrient ingestion, abnormalities in the energy expenditure, changes in eating behavior, gastrointestinal changes, and by side effects of drugs administered. Patients with acute neurological diseases have in common the presence of hyper metabolism and hyper catabolism both associated to a period of prolonged fasting mainly for the frequent gastrointestinal complications, many times as a side effect of drugs administered. During the acute phase, spinal cord injuries presented a reduction in the energy expenditure but an increase in the nitrogen elimination. In order to correct the negative nitrogen balance increase intakes is performed with the result of a hyper alimentation that should be avoided due to the complications resulting. In patients with chronic neurological diseases and in the acute phase of cerebrovascular accident, dysphagia could be present which also affects intakes. Several chronic neurological diseases have also dementia, which lead to alterations in the eating behavior. The presence of malnutrition complicates the clinical evolution, increases muscular atrophy with higher incidence of respiratory failure and less capacity to disphagia recuperation, alters the immune response with higher rate of infections, increases the likelihood of fractures and of pressure ulcers, increases the incapacity degree and is an independent factor to increase mortality. The periodic nutritional

  20. Acute cervical spinal subdural hematoma not related to head injury.

    PubMed

    Kim, Hee Yul; Ju, Chang Il; Kim, Seok Won

    2010-06-01

    We report an extremely rare case of traumatic cervical spinal subdural hematoma not related to intracranial injury. There has been no report on traumatic cervical spinal subdrual hematoma not related to intracranial injury. A 27-year-old female patient was admitted to our emergency room due to severe neck pain and right arm motor weakness after car collision. On admission, she presented with complete monoplegia and hypoesthesia of right arm. Magnetic resonance imaging (MRI) revealed subdural hematoma compressing spinal cord. Lumbar cerebrospinal fluid (CSF) analysis revealed 210,000 red blood cells/mm(3). She was managed conservatively by administrations of steroid pulse therapy and CSF drainage. Her muscle power of right arm improved to a Grade III 16 days after admission. Follow-up MRI taken 16th days after admission revealed almost complete resolution of the hematoma. Here, the authors report a traumatic cervical spinal SDH not associated with intracranial injury.

  1. Changes in free and esterified cholesterol: hallmarks of acute renal tubular injury and acquired cytoresistance.

    PubMed

    Zager, R A; Kalhorn, T F

    2000-09-01

    Acute tubular cell injury is accompanied by plasma membrane phospholipid breakdown. Although cholesterol is a dominant membrane lipid which interdigitates with, and impacts, phospholipid homeostasis, its fate during the induction and recovery phases of acute renal failure (ARF) has remained ill defined. The present study was performed to ascertain whether altered cholesterol expression is a hallmark of evolving tubular damage. Using gas chromatographic analysis, free cholesterol (FC) and esterified cholesterol (CE) were quantified in: 1) isolated mouse proximal tubule segments (PTS) after 30 minutes of hypoxic or oxidant (ferrous ammonium sulfate) injury; 2) cultured proximal tubule (HK-2) cells after 4 or 18 hours of either ATP depletion/Ca(2+) ionophore- or ferrous ammonium sulfate-mediated injury; and 3) in renal cortex 18 hours after induction of glycerol-induced myoglobinuric ARF, a time corresponding to the so-called "acquired cytoresistance" state (ie, resistance to further renal damage). Hypoxic and oxidant injury each induced approximately 33% decrements in CE (but not FC) levels in PTS, corresponding with lethal cell injury ( approximately 50 to 60% LDH release). When comparable CE declines were induced in normal PTS by exogenous cholesterol esterase treatment, proportionate lethal cell injury resulted. During models of slowly evolving HK-2 cell injury, progressive CE increments occurred: these were first noted at 4 hours, and reached approximately 600% by 18 hours. In vivo myoglobinuric ARF produced comparable renal cortical CE (and to a lesser extent FC) increments. Renal CE accumulation strikingly correlated with the severity of ARF (eg, blood urea nitrogen versus CE; r, 0.84). Mevastatin blocked cholesterol accumulation in injured HK-2 cells, indicating de novo synthesis was responsible. Acute tubule injury first lowers, then raises, tubule cholesterol content. Based on previous observations that cholesterol has cytoprotectant properties, the present

  2. Work-Time Exposure and Acute Injuries in Inshore Lobstermen of the Northeast United States.

    PubMed

    Fulmer, Scott; Buchholz, Bryan; Jenkins, Paul; Scribani, Melissa

    2016-01-01

    The objective of this study was to inform efforts to reduce risk for musculoskeletal disorders among commercial lobstermen by characterizing and quantifying injuries that occur to people while harvesting lobsters commercially in the Northeast United States. This study aimed to estimate a denominator of exposure to lobstering in full-time equivalents (FTE), to estimate a fatality rate, and to calculate incidence rates for acute injuries within the sample population. Captains were randomly selected from those licensed to fish in Maine and Massachusetts. Data on work exposure and injuries with rapid onset that occurred on the boat ("acute injuries") were collected using a survey, which was administered quarterly via phone or face-to-face interview with the captain. The quarterly survey assessed the number of weeks worked during the quarter, average crew size, number of trips per week, and average trip length in hours. In addition, this survey captured relevant information (body segment affected, type of injury, and whether treatment was received) on all acute injuries occurring during the quarter. FTE were estimated using fishermen days and fishermen hours. The annual FTE estimated using days was 2,557 and using hours was 2,855. As expected, the summer months (3rd quarter) had the highest FTE and the winter (1st quarter) the lowest FTE. Fall (4th quarter) and spring (2nd quarter) ranked second and third, respectively. The incidence rates for all injuries (49.7/100 FTE) and injuries requiring treatment (15.0/100 FTE) were much higher than those reported in other studies of fishing that used Coast Guard data.

  3. The use of spinal manipulation to treat an acute on field athletic injury: a case report.

    PubMed

    Duquette, Sean A; Kazemi, Mohsen

    2016-06-01

    This case describes the utilization of spinal manipulative therapy for an acute athletic injury during a Taekwondo competition. During the tournament, an athlete had a sudden, non-traumatic, ballistic movement of the cervical spine. This resulted in the patient having a locked cervical spine with limited active motion in all directions. The attending chiropractor assessed the athlete, and deemed manipulation was appropriate. After the manipulation, the athlete's range of motion was returned and was able to finish the match. Spinal manipulation has multiple positive outcomes for an athlete with an acute injury including the increase of range of motion, decrease in pain and the relaxation of hypertonic muscles. However, there should be some caution when utilizing manipulation during an event. In the article the authors propose four criteria that should be met before utilizing manipulation for an acute, in competition, athletic injury. These include the lack of red flags, limited time for the intervention, preexisting doctor-patient relationship and the athlete has experience receiving spinal manipulation. Clinicians should be aware that manipulation may be an effective tool to treat an acute in competition athletic injury. The criteria set out in the article may help a practitioner decide if manipulation is a good option for them.

  4. The use of spinal manipulation to treat an acute on field athletic injury: a case report

    PubMed Central

    Duquette, Sean A.; Kazemi, Mohsen

    2016-01-01

    This case describes the utilization of spinal manipulative therapy for an acute athletic injury during a Taekwondo competition. During the tournament, an athlete had a sudden, non-traumatic, ballistic movement of the cervical spine. This resulted in the patient having a locked cervical spine with limited active motion in all directions. The attending chiropractor assessed the athlete, and deemed manipulation was appropriate. After the manipulation, the athlete’s range of motion was returned and was able to finish the match. Spinal manipulation has multiple positive outcomes for an athlete with an acute injury including the increase of range of motion, decrease in pain and the relaxation of hypertonic muscles. However, there should be some caution when utilizing manipulation during an event. In the article the authors propose four criteria that should be met before utilizing manipulation for an acute, in competition, athletic injury. These include the lack of red flags, limited time for the intervention, preexisting doctor-patient relationship and the athlete has experience receiving spinal manipulation. Clinicians should be aware that manipulation may be an effective tool to treat an acute in competition athletic injury. The criteria set out in the article may help a practitioner decide if manipulation is a good option for them. PMID:27385835

  5. MATRILYSIN PARTICIPATES IN THE ACUTE LUNG INJURY INDUCED BY OIL COMBUSTION PRODUCTS

    EPA Science Inventory

    ROLE OF MATRILYSIN IN THE ACUTE LUNG INJURY INDUCED BY OIL COMBUSTION PARTICLES.

    K L Dreher1, WY Su2 and C L Wilson3. 1US Environmental Protection Agency, Research Triangle Park, NC; 2Duke University, Durham, NC;3Washington University, St. Louis, MO.

    Mechanisms by ...

  6. Bioinforrnatics of Gene Expression Profiling Data Provide Mechanistic Understanding of Acute Ozone-Induced Lung injury

    EPA Science Inventory

    Acute ozone-induced pulmonary injury and inflammation are well characterized. A few studies have used gene expression profiling to determine the types of changes induced by ozone; however the mechanisms or the pathways involved are less well understood. We presumed that robust bi...

  7. CARDIOVASCULAR INJURY FROM ACUTE AND REPEATED EXPOSURE TO PARTICULATE MATTER (PM): POTENTIAL ROLE OF ZINC

    EPA Science Inventory

    CARDIOVASCULAR INJURY FROM ACUTE AND REPEATED EXPOSURE TO PARTICULATE MATTER (PM): POTENTIAL ROLE OF ZINC. UP Kodavanti, MC Schladweiler, AD Ledbetter, RH Jaskot, PS Gilmour, DC Christiani, WP Watkinson, DL Costa, JK McGee, A Nyska. NHEERL, USEPA, RTP, NC; CEMALB, UNC, Chapel Hil...

  8. Acute kidney injury in 2013: Breaking barriers for biomarkers in AKI--progress at last.

    PubMed

    Cruz, Dinna N; Mehta, Ravindra L

    2014-02-01

    In 2013, four important papers were published that provide new insights on biomarkers in acute kidney injury (AKI). These studies demonstrate the potential for biomarkers to aid clinicians in improving the therapeutic management of patients with AKI and potentially improve patient outcomes.

  9. Mechanism of Tissue Remodeling in Sepsis-Induced Acute Lung Injury

    DTIC Science & Technology

    2005-04-01

    acute lung injury have been identified (e.g., infection, trauma ), little is known about the factors that control the tissue remodeling response. This...in fibroblasts. This suggests that the main player in this process is acetaldehyde . To test this, we exposed cells to acetaldehyde and found that this

  10. Toxic Epidermal Necrolysis and Acute Kidney Injury due to Glyphosate Ingestion

    PubMed Central

    Indirakshi, J.; Sunnesh, A.; Aruna, M.; Reddy, M. Hari Krishna; Kumar, Anil C. V.; Chandra, V. Sarat; Sangeetha, B.; Katyarmal, D. T.; Ram, R.; Kumar, V. Siva

    2017-01-01

    The literature, particularly from India, is scarce on the renal effects of glyphosate poisoning. Glyphosate causes toxicity not only after its ingestion but also after dermal exposure by inhalation route and on eye exposure. We present a patient report of glyphosate consumption which resulted in toxic epidermal necrolysis – the first report after glyphosate consumption and acute kidney injury.

  11. Immature mice are more susceptible than adult mice to acetaminophen-induced acute liver injury

    PubMed Central

    Lu, Yan; Zhang, Cheng; Chen, Yuan-Hua; Wang, Hua; Zhang, Zhi-Hui; Chen, Xi; Xu, De-Xiang

    2017-01-01

    Acetaminophen (APAP) overdose induces acute liver injury. The aim of the present study was to analyze the difference of susceptibility between immature and adult mice to APAP-induced acute liver injury. Weanling immature and adult mice were injected with APAP (300 mg/kg). As expected, immature mice were more susceptible than adult mice to APAP-induced acute liver injury. APAP-evoked hepatic c-Jun N-terminal kinase phosphorylation was stronger in immature mice than in adult mice. Hepatic receptor-interacting protein (RIP)1 was obviously activated at APAP-exposed immature and adult mice. Interestingly, hepatic RIP3 activation was more obvious in APAP-treated immature mice than adult mice. Although there was no difference on hepatic GSH metabolic enzymes between immature and adult mice, immature mice were more susceptible than adult mice to APAP-induced hepatic GSH depletion. Of interest, immature mice expressed a much higher level of hepatic Cyp2e1 and Cyp3a11 mRNAs than adult mice. Correspondingly, immature mice expressed a higher level of hepatic CYP2E1, the key drug metabolic enzyme that metabolized APAP into the reactive metabolite NAPQI. These results suggest that a higher level of hepatic drug metabolic enzymes in immature mice than adult mice might contribute to the difference of susceptibility to APAP-induced acute liver injury. PMID:28205631

  12. ROLE OF CELL SIGNALING IN PROTECTION FROM DIESEL AND LPS INDUCED ACUTE LUNG INJURY

    EPA Science Inventory

    We have previously demonstrated in CD-1 mice that pre-administration of N-acetyl cysteine (NAC) or the p38 MAP kinase inhibitor (SB203580) reduces acute lung injury and inflammation following pulmonary exposures to diesel exhaust particles (DEP) or lipopolysaccharide (LPS). Here ...

  13. Retroperitoneal abscess and acute acalculous cholecystitis after iatrogenic colon injury: report of a case

    PubMed Central

    Dong, Chengwei; Wang, Yuxu; Hu, Sanyuan; Du, Futian; Ding, Wei

    2015-01-01

    Acute acalculous cholecystitis has a high mortality rate due to the difficulties in early diagnosis and high rate of complications like empyema, gangrene and perforation. We report a case of 20-year-old male with acute severe pancreatitis, acute renal failure and acute peripancreatic fluid collection who was transferred to our department after blood filtration treatment in ICU. After percutaneous catheter drainage for 20 hours, the patient got a high fever. Computed tomography revealed retroperitoneal colon injury. In this case, percutaneous catheter drainage was performed again and the pus cavity was flushed regularly, after which the patient’s state gradually improved. Unpredictably, septic shock appeared on the 51st day. Repeated computed tomography revealed acute acalculous cholecystitis and abscess formation. After percutaneous transhepatic gallbladder catheterization and drainage, the patient got better gradually. Three months later the retroperitoneal catheter was removed. Four months later, ultrasound examination showed normal gallbladder and the catheter was removed. PMID:26131252

  14. Molecular Ultrasound Imaging of Tissue Inflammation Using an Animal Model of Acute Kidney Injury

    PubMed Central

    Hoyt, Kenneth; Warram, Jason M.; Wang, Dezhi; Ratnayaka, Sithira; Traylor, Amie; Agarwal, Anupam

    2016-01-01

    Purpose The objective of this study was to evaluate the use of molecular ultrasound (US) imaging for monitoring the early inflammatory effects following acute kidney injury. Procedures A population of rats underwent 30 min of renal ischemia (acute kidney injury, N=6) or sham injury (N=4) using established surgical methods. Animals were divided and molecular US imaging was performed during the bolus injection of a targeted microbubble (MB) contrast agent to either P-selectin or vascular cell adhesion molecule 1 (VCAM-1). Imaging was performed before surgery and 4 and 24 h thereafter. After manual segmentation of renal tissue space, the molecular US signal was calculated as the difference between time-intensity curve data before MB injection and after reaching steady-state US image enhancement. All animals were terminated after the 24 h imaging time point and kidneys excised for immunohistochemical (IHC) analysis. Results Renal inflammation was analyzed using molecular US imaging. While results using the P-selectin and VCAM-1 targeted MBs were comparable, it appears that the former was more sensitive to biomarker expression. All molecular US imaging measures had a positive correlation with IHC findings. Conclusions Acute kidney injury is a serious disease in need of improved noninvasive methods to help diagnose the extent of injury and monitor the tissue throughout disease progression. Molecular US imaging appears well suited to address this challenge and more research is warranted. PMID:25905474

  15. Augmenting Effect of DA-9601 on Ghrelin in an Acute Gastric Injury Model

    PubMed Central

    Baek, Yoo Hum; Lee, Kang Nyeong; Jun, Dae Won; Yoon, Byung Chul; Kim, Ju Mi; Oh, Tae Young

    2011-01-01

    Background/Aims Acute gastric injury by alcohol or indomethacin has been reported to be prevented by DA-9601, an extract of the herb Artemisia asiatica. Ghrelin, an endogenously produced gastrointestinal peptide hormone, has also been demonstrated to play a role in gastric mucosal defense. The aim of this study was to investigate the effects of DA-9601 on ghrelin in an acute gastric injury model induced by alcohol or indomethacin. Methods A total of 140 Sprague-Dawley rats were divided into two groups, a placebo group and a DA-9601-pretreated group. Thirty minutes later, half of the rats in each group received ethanol injury and the other half received indomethacin injury. Levels of serum ghrelin and gastric mucosal ghrelin mRNA were measured by ELISA and RT-PCR, respectively. Results Immediately after ethanol administration, ghrelin increased in both groups pretreated with DA-9601 and placebo. However, the increase occurred more rapidly and was higher in the DA-9601-pretreated rats than in the controls that did not receive DA-9601-pretreatment. Similarly, from 30 minutes to 2 hours after indomethacin administration, the DA-9601-pretreated rats showed a significant increase in serum and gastric mucosal ghrelin concentrations, whereas placebo-pretreated rats showed only a mild increase. Conclusions DA-9601 potentiates the endogenous production and secretion of ghrelin in acute gastric injury models induced by ethanol or indomethacin. PMID:21461072

  16. Relationship of Acute Lung Inflammatory Injury to Fas/FasL System

    PubMed Central

    Neff, Thomas A.; Guo, Ren-Feng; Neff, Simona B.; Sarma, J. Vidya; Speyer, Cecilia L.; Gao, Hongwei; Bernacki, Kurt D.; Huber-Lang, Markus; McGuire, Stephanie; Hoesel, L. Marco; Riedemann, Niels C.; Beck-Schimmer, Beatrice; Zetoune, Firas S.; Ward, Peter A.

    2005-01-01

    There is mounting evidence that apoptosis plays a significant role in tissue damage during acute lung injury. To evaluate the role of the apoptosis mediators Fas and FasL in acute lung injury, Fas (lpr)- or FasL (gld)-deficient and wild-type mice were challenged with intrapulmonary deposition of IgG immune complexes. Lung injury parameters (125I-albumin leak, accumulation of myeloperoxidase, and wet lung weights) were measured and found to be consistently reduced in both lpr and gld mice. In wild-type mice, lung injury was associated with a marked increase in Fas protein in lung. Inflamed lungs of wild-type mice showed striking evidence of activated caspase-3, which was much diminished in inflamed lungs from lpr mice. Intratracheal administration of a monoclonal Fas-activating antibody (Jo2) in wild-type mice induced MIP-2 and KC production in bronchoalveolar lavage fluids, and a murine alveolar macrophage cell line (MH-S) showed significantly increased MIP-2 production after incubation with this antibody. Bronchoalveolar lavage fluid content of MIP-2 and KC was substantially reduced in lpr mice after lung injury when compared to levels in wild-type mice. These data suggest that the Fas/FasL system regulates the acute lung inflammatory response by positively affecting CXC-chemokine production, ultimately leading to enhanced neutrophil influx and tissue damage. PMID:15743781

  17. Preoperative Endogenous Ouabain Predicts Acute Kidney Injury in Cardiac Surgery Patients

    PubMed Central

    Bignami, Elena; Casamassima, Nunzia; Frati, Elena; Lanzani, Chiara; Corno, Laura; Alferi, Ottavio; Gottlieb, Stephen; Simonini, Marco; Shah, Keyur B.; Mizzi, Anna; Messaggio, Elisabetta; Zangrillo, Alberto; Ferrandi, Mara; Ferrari, Patrizia; Bianchi, Giuseppe; Hamlyn, John M.; Manunta, Paolo

    2013-01-01

    Objectives Acute kidney injury is a frequent complication of cardiac surgery and increases morbidity and mortality. As preoperative biomarkers predicting the development of acute kidney injury are not available, we have tested the hypothesis that preoperative plasma levels of endogenous ouabain may function as this type of biomarker. Rationale and Design Endogenous ouabain is an adrenal stress hormone associated with adverse cardiovascular outcomes. Its involvement in acute kidney injury is unknown. With studies in patients and animal settings, including isolated podocytes, we tested the above mentioned hypothesis. Patients Preoperative endogenous ouabain was measured in 407 patients admitted for elective cardiac surgery and in a validation population of 219 other patients. We also studied the effect of prolonged elevations of circulating exogenous ouabain on renal parameters in rats and the influence of ouabain on podocyte proteins both “in vivo” and “in vitro.” Main Results In the first group of patients, acute kidney injury (2.8%, 8.3%, 20.3%, p < 0.001) and ICU stay (1.4 ± 0.38, 1.7 ± 0.41, 2.4 ± 0.59 days, p = 0.014) increased with each incremental preoperative endogenous ouabain tertile. In a linear regression analysis, the circulating endogenous ouabain value before surgery was the strongest predictor of acute kidney injury. In the validation cohort, acute kidney injury (0%, 5.9%, 8.2%, p < 0.0001) and ICU stay (1.2 ± 0.09, 1.4 ± 0.23, 2.2 ± 0.77 days, p = 0.003) increased with the preoperative endogenous ouabain tertile. Values for preoperative endogenous ouabain significantly improved (area under curve: 0.85) risk prediction over the clinical score alone as measured by integrate discrimination improvement and net reclassification improvement. Finally, in the rat model, elevated circulating ouabain reduced creatinine clearance (–18%, p < 0.05), increased urinary protein excretion (+ 54%, p < 0.05), and reduced expression of podocyte nephrin

  18. Development and Evaluation of New Products for the Far-Forward Care of Combat Casualties With Acute Lung Injury

    DTIC Science & Technology

    2005-02-01

    acute respiratory distress syndrome ( ARDS ) caused by chlorine gas (C12). Background: Toxic industrial chemicals (TICs) have recently been identified as...Batchinsky A, Cancio L. An ovine model of acute respiratory distress syndrome ( ARDS ) secondary to inhalation of chlorine gas. Veterinary Pathology, 2004;41...TERMS 15. NUMBER OF PAGES 27 Chlorine, acute respiratory distress syndrome , inhalation injury 16. PRICECODE 17. SECURITY

  19. Acute Lung Injury Following Smoke Inhalation: Predictive Value of Sputum Biomarkers and Time Course of Lung Inflammation

    DTIC Science & Technology

    2005-05-01

    acute respiratory distress syndrome ( ARDS ). Laboratory assays on the bronchial lavage samples...at high risk of developing acute respiratory distress syndrome ( ARDS ). Given the delay of 12 or more hours from exposure to development of ARDS , a...AD Award Number: DAMD17-02-1-0673 TITLE : Acute Lung Injury Following Smoke Inhalation: Predictive Value of Sputum Biomarkers and Time Course of

  20. Septic versus non-septic acute kidney injury in critically ill patients: characteristics and clinical outcomes

    PubMed Central

    Cruz, Marília Galvão; Dantas, João Gabriel Athayde de Oliveira; Levi, Talita Machado; Rocha, Mário de Seixas; de Souza, Sérgio Pinto; Boa-Sorte, Ney; de Moura, Carlos Geraldo Guerreiro; Cruz, Constança Margarida Sampaio

    2014-01-01

    Objective This study aimed to describe and compare the characteristics and clinical outcomes of patients with septic and non-septic acute kidney injury. Methods This study evaluated an open cohort of 117 critically ill patients with acute kidney injury who were consecutively admitted to an intensive care unit, excluding patients with a history of advanced-stage chronic kidney disease, kidney transplantation, hospitalization or death in a period shorter than 24 hours. The presence of sepsis and in-hospital death were the exposure and primary variables in this study, respectively. A confounding analysis was performed using logistic regression. Results No significant differences were found between the mean ages of the groups with septic and non-septic acute kidney injury [65.30±21.27 years versus 66.35±12.82 years, respectively; p=0.75]. In the septic and non-septic acute kidney injury groups, a predominance of females (57.4% versus 52.4%, respectively; p=0.49) and Afro-descendants (81.5% versus 76.2%, respectively; p=0.49) was observed. Compared with the non-septic patients, the patients with sepsis had a higher mean Acute Physiology and Chronic Health Evaluation II score [21.73±7.26 versus 15.75±5.98; p<0.001)] and a higher mean water balance (p=0.001). Arterial hypertension (p=0.01) and heart failure (p<0.001) were more common in the non-septic patients. Septic acute kidney injury was associated with a greater number of patients who required dialysis (p=0.001) and a greater number of deaths (p<0.001); however, renal function recovery was more common in this group (p=0.01). Sepsis (OR: 3.88; 95%CI: 1.51-10.00) and an Acute Physiology and Chronic Health Evaluation II score >18.5 (OR: 9.77; 95%CI: 3.73-25.58) were associated with death in the multivariate analysis. Conclusion Sepsis was an independent predictor of death. Significant differences were found between the characteristics and clinical outcomes of patients with septic versus non-septic acute kidney

  1. beta2 adrenergic agonists in acute lung injury? The heart of the matter.

    PubMed

    Lee, Jae W

    2009-01-01

    Despite extensive research into its pathophysiology, acute lung injury/acute respiratory distress syndrome (ALI/ARDS) remains a devastating syndrome with mortality approaching 40%. Pharmacologic therapies that reduce the severity of lung injury in vivo and in vitro have not yet been translated to effective clinical treatment options, and innovative therapies are needed. Recently, the use of beta2 adrenergic agonists as potential therapy has gained considerable interest due to their ability to increase the resolution of pulmonary edema. However, the results of clinical trials of beta agonist therapy for ALI/ARDS have been conflicting in terms of benefit. In the previous issue of Critical Care, Briot and colleagues present evidence that may help clarify the inconsistent results. The authors demonstrate that, in oleic acid lung injury in dogs, the inotropic effect of beta agonists may recruit damaged pulmonary capillaries, leading to increased lung endothelial permeability.

  2. Repeated exposure to modern volatile anaesthetics may cause chronic hepatitis as well as acute liver injury.

    PubMed

    Nicoll, Amanda; Moore, David; Njoku, Dolores; Hockey, Brad

    2012-11-06

    Volatile anaesthetic agents are known to cause acute hepatitis and fulminant hepatic failure in susceptible individuals. Four patients were identified with prolonged liver injury due to volatile anaesthetic-induced hepatitis. Three had liver biopsy confirmation and all gave blood for specific diagnostic tests (TFA and CYP 2E1 IgG4 antibodies). The Roussel Uclaf Causality Assessment Method (RUCAM) drug causality scale was used to determine the likelihood of volatile anaesthetics causing the chronic liver injury. We describe four cases of volatile anaesthetic hepatitis in which three evolved into chronic hepatitis. The fourth followed a more typical pattern of acute hepatitis; however, resolution took a few months. These cases all occurred with modern volatile anaesthetics, predominantly sevoflurane, and all cases were proven with specific antibody tests, liver histology and a drug causality scale. This is the first report of chronic liver injury due to volatile anaesthetic exposure.

  3. Protective effects of Flos lonicera extract on acute liver injury by dimethylnitrosamine-induced in rats.

    PubMed

    Teng, Yang; Sun, Chang Hai; Li, Guangzhi; Sun, Guangchen; Nomachi, Yui; Yokota, Junko; Yoshioka, Saburo; Gang, Jinbo; Jiao, Shuqing; Zhang, Yu; Miyamura, Mitsuhiko

    2010-07-01

    The aim of this study is to investigate effects of Flos lonicera extract (FLE) on acute liver injury model rats which induced by 35 mg/kg dimethylnitrosamine (DMN). Model rats were divided into hepatic injury control group (administrated with water), FLE group (administrated with FLE) and silymarin group (administrated with silymarin which is hepatotherapeutic drug) as positive control. They were examined including ALT, AST, ALP, gamma-GT, ALB and TP levels in serum, and MDA, GPx levels in liver tissue. In addition, pathologic changes, particularly fibrosis, were examined by Azan staining. The results revealed that the ALT, AST, ALP, gamma-GT, MDA GPx and liver fibrosis degree in the LJE group were lower than the silymarin group and control group, ALB and TP were higher than the silymarin group and control group. These results suggested that LJE may help in inhibiting of acute liver injury greater than silymarin.

  4. Carfilzomib-related acute kidney injury may be prevented by N-acetyl-L-cysteine.

    PubMed

    Wanchoo, Rimda; Khan, Seyyar; Kolitz, Jonathan E; Jhaveri, Kenar D

    2015-08-01

    Carfilzomib is a second-generation epoxyketone proteasome inhibitor that is approved for treatment of relapsed and refractory multiple myeloma. Phase 2 trials have reported that 25% of treated patients have renal adverse effects. Pre-renal/vasoconstriction-related insult from this chemotherapy agent has been documented. We describe a case of a 78-year-old man with refractory multiple myeloma with acute kidney injury associated with carfilzomib treatment. We show that use of N-acetyl-l-cysteine in our patient partially mitigated the renal injury upon re-challenge. This case report hypothesizes that acute renal injury from carfilzomib is caused by vasoconstriction of the renal vessels, which may be prevented by N-acetyl-l-cysteine.

  5. Repeated exposure to modern volatile anaesthetics may cause chronic hepatitis as well as acute liver injury

    PubMed Central

    Nicoll, Amanda; Moore, David; Njoku, Dolores; Hockey, Brad

    2012-01-01

    Volatile anaesthetic agents are known to cause acute hepatitis and fulminant hepatic failure in susceptible individuals. Four patients were identified with prolonged liver injury due to volatile anaesthetic-induced hepatitis. Three had liver biopsy confirmation and all gave blood for specific diagnostic tests (TFA and CYP 2E1 IgG4 antibodies). The Roussel Uclaf Causality Assessment Method (RUCAM) drug causality scale was used to determine the likelihood of volatile anaesthetics causing the chronic liver injury. We describe four cases of volatile anaesthetic hepatitis in which three evolved into chronic hepatitis. The fourth followed a more typical pattern of acute hepatitis; however, resolution took a few months. These cases all occurred with modern volatile anaesthetics, predominantly sevoflurane, and all cases were proven with specific antibody tests, liver histology and a drug causality scale. This is the first report of chronic liver injury due to volatile anaesthetic exposure. PMID:23131606

  6. Neuroprotective and antiapoptotic activity of lineage-negative bone marrow cells after intravitreal injection in a mouse model of acute retinal injury.

    PubMed

    Machalińska, Anna; Rogińska, Dorota; Pius-Sadowska, Ewa; Kawa, Miłosz P; Paczkowska, Edyta; Rudnicki, Michał; Lejkowska, Renata; Baumert, Bartłomiej; Wiszniewska, Barbara; Machaliński, Bogusław

    2015-01-01

    We investigated effects of bone marrow-derived, lineage-negative cell (Lin(-)BMC) transplantation in acute retinal injury. Lin(-)BMCs were intravitreally injected into murine eyes at 24 h after NaIO3-induced injury. Morphology, function, and expression of apoptosis-related genes, including brain-derived neurotrophic factor (BDNF) and its receptor, were assessed in retinas at 7 days, 28 days, and 3 months after transplantation. Moreover, global gene expression at day 7 was analyzed by RNA arrays. We observed that Lin(-)BMCs integrated into outer retinal layers improving morphological retinal structure and induced molecular changes such as downregulation of proapoptotic caspase-3 gene, a decrease in BAX/BCL-2 gene ratio, and significant elevation of BDNF expression. Furthermore, transplanted Lin(-)BMCs differentiated locally into cells with a macrophage-like phenotype. Finally, Lin(-)BMCs treatment was associated with generation of two distinct transcriptomic patterns. The first relates to downregulated genes associated with regulation of neuron cell death and apoptosis, response to oxidative stress/hypoxia and external stimuli, and negative regulation of cell proliferation. The second relates to upregulated genes associated with neurological system processes and sensory perception. Collectively, our data demonstrate that transplanted Lin(-)BMCs exert neuroprotective function against acute retinal injury and this effect may be associated with their antiapoptotic properties and ability to express neurotrophic factors.

  7. Neuroprotective and Antiapoptotic Activity of Lineage-Negative Bone Marrow Cells after Intravitreal Injection in a Mouse Model of Acute Retinal Injury

    PubMed Central

    Machalińska, Anna; Pius-Sadowska, Ewa; Kawa, Miłosz P.; Paczkowska, Edyta; Rudnicki, Michał; Lejkowska, Renata; Baumert, Bartłomiej; Wiszniewska, Barbara; Machaliński, Bogusław

    2015-01-01

    We investigated effects of bone marrow-derived, lineage-negative cell (Lin−BMC) transplantation in acute retinal injury. Lin−BMCs were intravitreally injected into murine eyes at 24 h after NaIO3-induced injury. Morphology, function, and expression of apoptosis-related genes, including brain-derived neurotrophic factor (BDNF) and its receptor, were assessed in retinas at 7 days, 28 days, and 3 months after transplantation. Moreover, global gene expression at day 7 was analyzed by RNA arrays. We observed that Lin−BMCs integrated into outer retinal layers improving morphological retinal structure and induced molecular changes such as downregulation of proapoptotic caspase-3 gene, a decrease in BAX/BCL-2 gene ratio, and significant elevation of BDNF expression. Furthermore, transplanted Lin−BMCs differentiated locally into cells with a macrophage-like phenotype. Finally, Lin−BMCs treatment was associated with generation of two distinct transcriptomic patterns. The first relates to downregulated genes associated with regulation of neuron cell death and apoptosis, response to oxidative stress/hypoxia and external stimuli, and negative regulation of cell proliferation. The second relates to upregulated genes associated with neurological system processes and sensory perception. Collectively, our data demonstrate that transplanted Lin−BMCs exert neuroprotective function against acute retinal injury and this effect may be associated with their antiapoptotic properties and ability to express neurotrophic factors. PMID:25810725

  8. Practical Advice for Teachers and Coaches: Handling Acute Athletic Injuries

    ERIC Educational Resources Information Center

    Hunt, Kevin; Ormond, Tom; Griffin, Lisa; Maina, Michael; Jones, Christopher; Goldman, Alexander Steven; McMichael, Callaway

    2016-01-01

    Safety concerns are among the first considerations in the design and implementation of any curriculum. However, in the dynamic worlds of physical education and coaching, athletic injuries will inevitably arise, regardless of the proactive strategies in place. These situations will vary in nature, and the student's or athlete's risk of further…

  9. Partially anaortic clampless off-pump coronary artery bypass prevents neurologic injury compared to on-pump coronary surgery: a propensity score-matched study on 286 patients.

    PubMed

    Bassano, Carlo; Bovio, Emanuele; Uva, Floriano; Iacobelli, Simona; Iasevoli, Nicola; Farinaccio, Andrea; Ruvolo, Giovanni

    2016-09-01

    Anaortic coronary artery bypass proved to prevent early neurologic injury compared to on-pump CABG. The Cardica PAS-Port(®) is a fully automated device that might be able to perform proximal aorto-venous anastomoses without an increased embolic risk. We evaluated early post-operative neurologic outcome in a matched population following clampless OPCAB (CCAB: either "all-arterial" or with automatically anastomosed venous grafts) or on-pump CABG. 366 consecutive patients were submitted to isolated coronary bypass by a single surgeon experienced in both off and on-pump procedures between January 2009 and December 2013. Of these patients, 223 underwent a clampless off-pump revascularization. After propensity score matching, 143 pairs were selected, who received either off-pump or on-pump surgery. In the off-pump group, CCAB was performed with an all-arterial approach (n = 33) or with automated proximal anastomosis of the venous graft(s) by means of the Cardica PAS-Port(®) connector (n = 110). Neurologic injury was defined as non-reversible (NRNI: lethal coma or stroke) or reversible (RNI: TIA or delirium). Operative mortality was 2.4 % (CCAB 1.4 %; CABG 3.5 %; p = 0.14). The global rate of early neurologic injury was 5.6 % (CCAB 2.1 vs. CABG 9.1 %; p = 0.006). Incidence was 1.4 % for NRNI (CCAB 0 vs. CABG 2.8 %; p = 0.04) and 4.2 % for RNI (CCAB 2.1 vs. CABG 6.3 %; p = 0.06). No differences were found among other major perioperative outcomes. CCAB prevents both early post-operative RNI and NRNI. This result can be achieved with a totally anaortic strategy and also with the aid of a fully automated device for proximal aorto-venous anastomoses.

  10. Pyruvate dehydrogenase kinase 4 deficiency attenuates cisplatin-induced acute kidney injury.

    PubMed

    Oh, Chang Joo; Ha, Chae-Myeong; Choi, Young-Keun; Park, Sungmi; Choe, Mi Sun; Jeoung, Nam Ho; Huh, Yang Hoon; Kim, Hyo-Jeong; Kweon, Hee-Seok; Lee, Ji-Min; Lee, Sun Joo; Jeon, Jae-Han; Harris, Robert A; Park, Keun-Gyu; Lee, In-Kyu

    2017-04-01

    Clinical prescription of cisplatin, one of the most widely used chemotherapeutic agents, is limited by its side effects, particularly tubular injury-associated nephrotoxicity. Since details of the underlying mechanisms are not fully understood, we investigated the role of pyruvate dehydrogenase kinase (PDK) in cisplatin-induced acute kidney injury. Among the PDK isoforms, PDK4 mRNA and protein levels were markedly increased in the kidneys of mice treated with cisplatin, and c-Jun N-terminal kinase activation was involved in cisplatin-induced renal PDK4 expression. Treatment with the PDK inhibitor sodium dichloroacetate (DCA) or genetic knockout of PDK4 attenuated the signs of cisplatin-induced acute kidney injury, including apoptotic morphology of the kidney tubules along with numbers of TUNEL-positive cells, cleaved caspase-3, and renal tubular injury markers. Cisplatin-induced suppression of the mitochondrial membrane potential, oxygen consumption rate, expression of electron transport chain components, cytochrome c oxidase activity, and disruption of mitochondrial morphology were noticeably improved in the kidneys of DCA-treated or PDK4 knockout mice. Additionally, levels of the oxidative stress marker 4-hydroxynonenal and mitochondrial reactive oxygen species were attenuated, whereas superoxide dismutase 2 and catalase expression and glutathione synthetase and glutathione levels were recovered in DCA-treated or PDK4 knockout mice. Interestingly, lipid accumulation was considerably attenuated in DCA-treated or PDK4 knockout mice via recovered expression of peroxisome proliferator-activated receptor-α and coactivator PGC-1α, which was accompanied by recovery of mitochondrial biogenesis. Thus, PDK4 mediates cisplatin-induced acute kidney injury, suggesting that PDK4 might be a therapeutic target for attenuating cisplatin-induced acute kidney injury.

  11. MANAGEMENT OF ACUTE SPORTS INJURIES AND MEDICAL CONDITIONS BY PHYSICAL THERAPISTS: ASSESSMENT VIA CASE SCENARIOS

    PubMed Central

    Karges, Joy Renae; Salsbery, Mitchell A.; Smith, Danna; Stanley, Erica J.

    2011-01-01

    Purpose/Background: Some physical therapists (PTs) provide services at sporting events, but there are limited studies investigating whether PTs are properly prepared to provide such services. The purpose of this study was to assess acute sports injury and medical condition management decision-making skills of PTs. Methods: A Web-based survey presented 17 case scenarios related to acute medical conditions and sport injuries. PTs from the Sports Physical Therapy Section of The American Physical Therapy Association were e-mailed a cover letter/Web link to the survey and invited to participate over a 30-day period. Data were analyzed using SPSS 18.0. Results: A total of 411 of 5158 PTs who were members of the Sports Physical Therapy Association in 2009 and had valid e-mail addresses completed the survey, of which 389 (7.5%) were appropriate for analysis. Over 75.0% of respondents felt “prepared” or “somewhat prepared” to provide immediate care for 13 out of 16 medical conditions, with seizures, spinal cord injuries, and internal organ injuries having the lowest percentages. Over 75.0% of the respondents made “appropriate” or “overly cautious” decisions for 11 of the 17 acute injury or medical condition cases. Conclusions: Results of the current study indicate that PTs felt more “prepared” and tended to make “appropriate” return to play decisions on the