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Search Results: 1 - 10 of 17892 matches for " Mark Coburn "
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Responses of Human Endothelial Cells to Pathogenic and Non-Pathogenic Leptospira Species
Denise G. Martinez-Lopez,Mark Fahey,Jenifer Coburn
PLOS Neglected Tropical Diseases , 2010, DOI: 10.1371/journal.pntd.0000918
Abstract: Leptospirosis is a widespread zoonotic infection that primarily affects residents of tropical regions, but causes infections in animals and humans in temperate regions as well. The agents of leptospirosis comprise several members of the genus Leptospira, which also includes non-pathogenic, saprophytic species. Leptospirosis can vary in severity from a mild, non-specific illness to severe disease that includes multi-organ failure and widespread endothelial damage and hemorrhage. To begin to investigate how pathogenic leptospires affect endothelial cells, we compared the responses of two endothelial cell lines to infection by pathogenic versus non-pathogenic leptospires. Microarray analyses suggested that pathogenic L. interrogans and non-pathogenic L. biflexa triggered changes in expression of genes whose products are involved in cellular architecture and interactions with the matrix, but that the changes were in opposite directions, with infection by L. biflexa primarily predicted to increase or maintain cell layer integrity, while L. interrogans lead primarily to changes predicted to disrupt cell layer integrity. Neither bacterial strain caused necrosis or apoptosis of the cells even after prolonged incubation. The pathogenic L. interrogans, however, did result in significant disruption of endothelial cell layers as assessed by microscopy and the ability of the bacteria to cross the cell layers. This disruption of endothelial layer integrity was abrogated by addition of the endothelial protective drug lisinopril at physiologically relevant concentrations. These results suggest that, through adhesion of L. interrogans to endothelial cells, the bacteria may disrupt endothelial barrier function, promoting dissemination of the bacteria and contributing to severe disease manifestations. In addition, supplementing antibiotic therapy with lisinopril or derivatives with endothelial protective activities may decrease the severity of leptospirosis.
The Hip Fracture Surgery in Elderly Patients (HIPELD) study: protocol for a randomized, multicenter controlled trial evaluating the effect of xenon on postoperative delirium in older patients undergoing hip fracture surgery
Coburn Mark,Sanders Robert D,Maze Mervyn,Rossaint Rolf
Trials , 2012, DOI: 10.1186/1745-6215-13-180
Abstract: Background Strategies to protect the brain from postoperative delirium (POD) after hip fracture are urgently needed. The development of delirium often is associated with the loss of independence, poor functional recovery, and increased morbidity, as well as increases in length of hospital stay, discharges to nursing facilities, and healthcare costs. We hypothesize that xenon may reduce the burden of POD, (i) by avoiding the need to provide anesthesia with a drug that targets the γ-amino-butyric acid (GABA)A receptor and (ii) through beneficial anesthetic and organ-protective effects. Methods and design An international, multicenter, phase 2, prospective, randomized, blinded, parallel group and controlled trial to evaluate the incidence of POD, diagnosed with the Confusion Assessment Method (CAM), in older patients undergoing hip fracture surgery under general anesthesia with xenon or sevoflurane, for a period of 4 days post surgery (primary outcome) is planned. Secondary objectives are to compare the incidence of POD between xenon and sevoflurane, to evaluate the incidence of POD from day 5 post surgery until discharge from hospital, to determine the time to first POD diagnosis, to evaluate the duration of POD, to evaluate the evolution of the physiological status of the patients in the postoperative period, to evaluate the recovery parameters, to collect preliminary data to evaluate the economical impact of POD in the postoperative period and to collect safety data. Patients are eligible if they are older aged (≥ 75 years) and assigned to a planned hip fracture surgery within 48 h after the hip fracture. Furthermore, patients need to be willing and able to complete the requirements of this study including the signature of the written informed consent. A total of 256 randomized patients in the 10 participating centers will be recruited, that is, 128 randomized patients in each of the 2 study groups (receiving either xenon or sevoflurane). Trial registration EudraCT Identifier: 2009-017153-35; ClinicalTrials.gov Identifier: NCT01199276
Effects of different fibrinogen concentrations on blood loss and coagulation parameters in a pig model of coagulopathy with blunt liver injury
Oliver Grottke, Till Braunschweig, Dietrich Henzler, Mark Coburn, Rene Tolba, Rolf Rossaint
Critical Care , 2010, DOI: 10.1186/cc8960
Abstract: Coagulopathy was induced in 18 anaesthetized pigs (32 ± 1.6 kg body weight) by replacing 80% of blood volume with hydroxyethylstarch 130/0.4 and Ringer's lactated solution, and re-transfusion of erythrocytes. Animals were randomly assigned to receive either 70 mg kg-1 (F-70) or 200 mg kg-1 (F-200) fibrinogen or placebo before inducing blunt liver injury using a force of 225 ± 26 Newton. Haemodynamics, coagulation parameters and blood loss were monitored for 2 hours. After death, histological examination of internal organs was performed to assess the presence of emboli and the equality of liver injury.Plasma dilution caused severe coagulopathy. Measured by thromboelastography fibrinogen restored coagulation dose-dependently. Total blood loss was significantly lower and survival better in both fibrinogen groups as compared to controls (P < 0.05). Between the F-70 (1317 ± 113 ml) and the F-200 group (1155 ± 232 ml) no significant difference in total blood loss could be observed, despite improved coagulation parameters in the F-200 group (P < 0.05). Microscopy revealed even injury pattern and no (micro) thrombi for either group.Restoring fibrinogen with 70 or 200 mg kg-1 after severe dilutional coagulopathy safely improved coagulation and attenuated blood loss after experimental blunt liver trauma. The higher dosage of fibrinogen was not associated with a further reduction in blood loss.Traumatised and surgical patients with massive haemorrhage are predisposed to develop coagulopathy, as a result of multiple mechanisms including acidosis, hypothermia, anaemia, hyperfibrinolysis and hypotension-induced inflammation, as well as consumption and dilution of coagulation factors [1]. Dilutional coagulopathy may occur after massive blood loss, as crystalloid and colloid solutions are infused for fluid resuscitation. The degree of coagulopathy depends on the type and volume of the fluids infused [2]. Resuscitation with colloid plasma expanders may lead to a functional fibrinoge
Propofol: neuroprotection in an in vitro model of traumatic brain injury
Jan Rossaint, Rolf Rossaint, Joachim Weis, Michael Fries, Steffen Rex, Mark Coburn
Critical Care , 2009, DOI: 10.1186/cc7795
Abstract: In this controlled laboratory study organotypic hippocampal brain-slice cultures were gained from six- to eight-day-old mice pups. After 14 days in culture, hippocampal brain slices were subjected to a focal mechanical trauma and subsequently treated with different molar concentrations of propofol under both normo- and hypothermic conditions. After 72 hours of incubation, tissue injury assessment was performed using propidium iodide (PI), a staining agent that becomes fluorescent only when it enters damaged cells via perforated cell membranes. Inside the cell, PI forms a fluorescent complex with nuclear DNA.A dose-dependent reduction of both total and secondary tissue injury could be observed in the presence of propofol under both normo- and hypothermic conditions. This effect was further amplified when the slices were incubated at 32°C after trauma.When used in combination, the dose-dependent neuroprotective effect of propofol is additive to the neuroprotective effect of hypothermia in an in vitro model of traumatic brain injury.Traumatic brain injury (TBI) is a common consequence of traffic-related accidents and incidents at work and at home. The annual incidence of TBI in the UK is estimated to be approximately 400 per 100,000 patients per year [1]. The treatment of patients with traumatic injury to the brain accounts for a considerable proportion of the budget spent annually on health care and the subsequent costs for rehabilitation, post-hospital long-term care and disability are a significant burden for the economy and society. It should be noted that all currently available therapy approaches for TBI are symptomatic in nature. To date, no clinically established therapy exists that specifically counteracts the actual pathological mechanisms leading to traumatic brain tissue injury.Propofol (2,6-diisopropylphenol) is a short-acting, intravenous hypnotic agent widely used for the induction and maintenance of general anaesthesia in the perioperative setting, for
The use of the Airtraq? optical laryngoscope for routine tracheal intubation in high-risk cardio-surgical patients
Gereon Sch?lte, Ulrike Scheid, Steffen Rex, Mark Coburn, Britta Fiedler, Rolf Rossaint, Norbert Zoremba
BMC Research Notes , 2011, DOI: 10.1186/1756-0500-4-425
Abstract: 123 consecutive ASA III patients undergoing elective coronary artery bypass grafting were routinely intubated with the Airtraq? laryngoscope. Induction of anesthesia was standardized according to our institutional protocol. All tracheal intubations were performed by six anesthetists trained in the use of the Airtraq? prior.Overall success rate was 100% (n = 123). All but five patients trachea could be intubated in the first attempt (95,9%). 5 patients were intubated in a 2nd (n = 4) or 3rd (n = 1) attempt. Mean intubation time was 24.3 s (range 16-128 s). Heart rate, arterial blood pressure and SpO2 were not significantly altered. Minor complications were observed in 6 patients (4,8%), i.e. two lesions of the lips and four minor superficial mucosal bleedings. Intubation duration (p = 0.62) and number of attempts (p = 0.26) were independent from BMI and Mallampati score.Tracheal intubation with the Airtraq? optical laryngoscope was feasible, save and easy to perform in high-risk patients undergoing cardiac surgery. In all patients, a sufficient view on the vocal cords could be obtained, independent from BMI and preoperative Mallampati score.DRKS 00003230Tracheal intubation is still the golden standard of securing the airway under clinical and preclinical conditions. In case of resuscitation, respiratory failure, unconsciousness and loss of a patent airway it is life saving. Since its introduction in 1941, the Macintosh laryngoscope has been the most popular device used for intubation worldwide.However, tracheal intubation using this laryngoscope has been demonstrated to fail in up to 35% of patients with an unpredicted difficult airway [1,2]. Problems in securing the airway are still the main contributors to anesthesia-related morbidity and mortality [3]. Therefore, a wide variety of alternatives to the Macintosh laryngoscope have been introduced into clinical routine, including the Miller-, McCoy-, and Bullard-laryngoscope. Since 1982 Archie Brain's supra glottic la
Neuroprotective properties of levosimendan in an in vitro model of traumatic brain injury
Anna B Roehl, Marc Hein, Philipp D Loetscher, Jan Rossaint, Joachim Weis, Rolf Rossaint, Mark Coburn
BMC Neurology , 2010, DOI: 10.1186/1471-2377-10-97
Abstract: Organotypic hippocampal brain slices from mouse pups were subjected to a focal mechanical trauma. Slices were treated after the injury with three different concentrations of levosimendan (0.001, 0.01 and 0.1 μM) and compared to vehicle-treated slices. After 72 hrs, the trauma was quantified using propidium iodide to mark the injured cells.A significant dose-dependent reduction of both total and secondary tissue injury was observed in cells treated with either 0.01 or 0.1 μM levosimendan compared to vehicle-treated slices.Levosimendan represents a promising new pharmacological tool for neuroprotection after brain injury and warrants further investigation in an in vivo model.Traumatic brain injury (TBI) is common, carries high rates of morbidity and mortality and lacks specific treatment. In our study of TBI, the initial lesion results from direct mechanical damage at the impact site. Subsequently, several cellular and molecular processes expand the local injury. This so-called secondary injury is due to several factors: excitotoxicity; mitochondrial dysfunction resulting in the up-regulation of cell-death genes and the formation of free radicals; and proapoptotic mediator pathway activation [1]. At present, medical intervention cannot rescue directly traumatised, dying cells. Therefore, current neuroprotective drugs target the surviving cells near the impact site [2]. Hypotension, hypoxia, hyper- and hypocapnia, and hyper- and hypoglycemia remain potentially avoidable insults, all of which aggravate the outcomes of TBI [3]. Levosimendan is a novel inodilator that enhances myocardial performance without leading to substantial changes in oxygen consumption. Levosimendan's positive inotropic and vasodilator effects are tied to its abilities to increase calcium sensitivity and open ATP-sensitive K+ channels (mitoKATPchannels) [4]. In a swine model of cardiac arrest, levosimendan significantly improved the initial resuscitation success, increased coronary perfusion pressu
Early cognitive function, recovery and well-being after sevoflurane and xenon anaesthesia in the elderly: a double-blinded randomized controlled trial
Jan Cremer, Christian Stoppe, Astrid V Fahlenkamp, Gereon Sch?lte, Steffen Rex, Rolf Rossaint, Mark Coburn
Medical Gas Research , 2011, DOI: 10.1186/2045-9912-1-9
Abstract: The study was approved by the local ethics committee and written informed consent was obtained from each patient. Patients aged 65-75 years (ASA I-III) scheduled for elective surgery (duration 60-180 min) were enrolled. Investigators performing cognitive testing and patients were blinded towards allocation to either xenon or sevoflurane anaesthesia. Baseline assessment of cognitive function was carried out 12-24 h before the operation. The results were compared to follow-up tests 6-12 and 66-72 h after surgery. Primary outcome parameter was the subtest "Alertness" of the computerized Test of Attentional Performance (TAP). Secondary outcome parameters included further subtests of the TAP, several Paper-Pencil-Tests, emergence times from anaesthesia, modified Aldrete scores and patients' well-being.40 patients were randomized and equally allocated to both groups. No significant differences were found in the TAP or the Paper-Pencil-Tests at 6-12 and 66-72 h after the operation. All emergence times were faster after xenon anaesthesia. The modified Aldrete scores were significantly higher during the first hour in the xenon group. No difference in well-being could be detected between both groups.The results show no difference in the incidence of postoperative cognitive dysfunction (POCD) after xenon or sevoflurane anaesthesia. Emergence from general anaesthesia was faster in the xenon group.Age is a known risk factor for postoperative cognitive dysfunction (POCD) after cardiac and non-cardiac surgery [1-3]. Up to 41% of patients aged 60 years and older are affected by POCD and exposed to an increased risk of death within the first 12 months after major non-cardiac surgery [1].Although a growing number of researchers are concentrating on POCD [4], no significant progress can be seen in the prevention of POCD.The noble gas xenon offers good haemodynamic stability [5-10] and favours rapid recovery from anaesthesia [11,12], both of which have been hypothesized to be beneficia
The Emergence of Severe Pulmonary Hemorrhagic Leptospirosis: Questions to Consider
Jenifer Coburn
Frontiers in Cellular and Infection Microbiology , 2012, DOI: 10.3389/fcimb.2011.00024
Abstract: Since the 1980s, the incidence of severe pulmonary hemorrhage caused by Leptospira spp. infection has increased. The mild, non-specific symptoms or the more classical form of severe disease with hepatorenal manifestations, Weil’s syndrome, predominate world-wide. However, several regions of the world have seen increases in numbers of patients with pulmonary hemorrhage attributed to leptospirosis. The reasons behind the emergence of this syndrome, which carries a high mortality rate, are not known. Several avenues for future research may shed light on the mechanisms involved in development of pulmonary hemorrhage, and inform targeted therapeutics to improve outcomes. Possibilities to consider include: (1) emergence of new bacterial strains, (2) acquisition of virulence traits by strains in the endemic regions, (3) changes in underlying health of the affected human populations, and (4) increased recognition of the syndrome and better record keeping by the medical and veterinary communities. Determining the causes of emerging clinical manifestations presents challenges and opportunities for potentially life-saving research into the pathogenesis of a number of infectious diseases, including leptospirosis.
Dexmedetomidine is neuroprotective in an in vitro model for traumatic brain injury
Marc Schoeler, Philip D Loetscher, Rolf Rossaint, Astrid V Fahlenkamp, Georg Eberhardt, Steffen Rex, Joachim Weis, Mark Coburn
BMC Neurology , 2012, DOI: 10.1186/1471-2377-12-20
Abstract: Organotypic hippocampal slice cultures were subjected to a focal mechanical trauma and then exposed to varying concentrations of dexmedetomidine. After 72 h cell injury was assessed using propidium iodide. In addition, the effects of delayed dexmedetomidine application, of hypothermia and canonical signalling pathway inhibitors were examined.Dexmedetomidine showed a protective effect on traumatically injured hippocampal cells with a maximum effect at a dosage of 1 μM. This effect was partially reversed by the simultaneous administration of the ERK inhibitor PD98059.In this TBI model dexmedetomidine had a significant neuroprotective effect. Our results indicate that activation of ERK might be involved in mediating this effect.In the United States an estimated 1.1 million patients are treated for traumatic brain injury (TBI) annually [1]. Of these, 124.000 patients suffer from long-term disabilities and 50.000 die, which makes TBI a major cause of premature death [1,2]. In addition, long term medical care and loss of income create a considerable social and economical burden, which remains an unsolved public health problem [3]. Regrettably, to date there exists no clinically established therapy targeting the mechanisms involved in TBI and treatment remains limited to symptomatic approaches.Dexmedetomidine is a highly selective α2-adrenoreceptor agonist with sedative, analgesic and sympatholytic properties. It was developed and investigated during the 1980s and 1990s and was initially used to achieve sedation and analgesia in veterinary medicine. In 1999 it was approved for use in humans by the US Food and Drug Administration for short-term sedation (< 24 h) of patients in intensive care units and non-intubated patients prior to and during surgical procedures. Recently, dexmedetomidine was approved in Europe for sedation of adult intensive care unit patients requiring a sedation level not deeper than arousal in response to verbal stimulation.Besides dexmedetomidine's we
Does a 4 diagram manual enable laypersons to operate the laryngeal mask supreme?? A pilot study in the manikin
Gereon Sch?lte, Christian Stoppe, Rolf Rossaint, Laura Gilles, Maike Heuser, Steffen Rex, Mark Coburn, Norbert Zoremba, Annette Rieg
Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine , 2012, DOI: 10.1186/1757-7241-20-21
Abstract: An instruction manual of four illustrations with speech bubbles displaying the correct use of the LMAS was designed. Laypersons were handed a bag containing a LMAS, a bag mask valve device (BMV), a syringe prefilled with air and the instruction sheet, and were asked to perform and ventilate the manikin as displayed. Time to ventilation was recorded and degree of success evaluated.A total of 150 laypersons took part. Overall 145 participants (96.7%) inserted the LMAS in the manikin in the right direction. The device was inserted inverted or twisted in 13 (8.7%) attempts. Eight (5.3%) individuals recognized this and corrected the position. Within the first 2 minutes 119 (79.3%) applicants were able to insert the LMAS and provide tidal volumes greater than 150 ml (estimated dead space). Time to insertion and first ventilation was 83.2 ± 29 s. No significant difference related to previous BLS training (P = 0.85), technical education (P = 0.07) or gender could be demonstrated (P = 0.25).In manikin laypersons could insert LMAS in the correct direction after onsite instruction by a simple manual with a high success rate. This indicates some basic procedural understanding and intellectual transfer in principle. Operating errors (n = 91) were frequently not recognized and corrected (n = 77). Improvements in labeling and the quality of instructional photographs may reduce individual error and may optimize understanding.Layperson resuscitation plays an important role in providing lifesaving cardiopulmonary resuscitation (CPR) and bridging the interval to the arrival of healthcare professionals. However, only 50% of laypersons actually administer "first aid" in such situations [1,2]. Reasons given are various and include a lacking sense of personal responsibility when there are many other people "on site", an aversion to strangers' bodily fluids and the percieved risk of infection during "mouth to mouth" ventilation. Individuals may be discouraged from administering CPR by a la
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