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ABSTRACT: The last 30 years have been both exciting and frustrating for those in the field of traumatic brain injury (TBI). Much has been learned, but no new treatment has been shown to improve patient outcomes despite the execution of many clinical trials. The overall incidence of TBI has decreased, probably because of intensive efforts toward prevention and education. Rigorous assessment of available research has produced several evidence-based guidelines for the management of neurotrauma patients. The creation of organized emergency medical services systems in many regions has improved prehospital care. Computed tomographic scans have become the gold standard for obtaining immediate images of patients with TBI, and ongoing advances in visualizing cerebral metabolism continue to be remarkable. The major current question regarding surgical treatment for TBI involves the role of decompressive craniectomy, an operation that first fell out of favor and has since (in the last three decades) enjoyed a resurgence of interest. Growing interest in the intensive care management of TBI patients helped to establish the new field of neurocritical care. Prophylactic hyperventilation is no longer recommended, and earlier recommendations for aggressive elevation of blood pressure have been softened to endorsement of a cerebral perfusion pressure of 60 mmHg. Recombinant factor VIIa is increasingly used for minimizing complications related to coagulopathy. Intracranial pressure monitoring is now recommended for the majority of TBI patients. At present, available technologies allow measurement of other aspects of cerebral metabolism including cerebral blood flow, brain oxygen tension, biochemistry, and electrical activity. Therapeutic interventions that are growing in popularity or are presently under investigation include administration of hypertonic saline, hyperoxygenation, decompressive craniectomy, and hypothermia. Rehabilitation has become accepted as an important part of the TBI recovery process, and additional work is needed to identify optimal interventions in this area. Socioeconomic factors will play a growing role in our treatment of TBI patients. Although much progress has been made in the last 30 years, the challenge now is to find ways to translate that progress into improved care and outcomes for TBI patients.
Neurosurgery 08/2007; 61(1 Suppl):203-20; discussion 220-1. · 2.79 Impact Factor
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ABSTRACT: Acute traumatic subdural hematoma complicated by brain parenchymal injury is associated with a 60 to 90% mortality rate. Early surgical evacuation of the mass lesion is essential for a favorable outcome, but the severity of the underlying brain injury determines the outcome, even when surgery has been prompt. The purpose of this study was to analyze tissue biochemical patterns in the brain underlying an evacuated acute subdural hematoma to identify a characteristic pattern of changes that might indicate evolving brain injury.
Prospectively collected data from 33 patients after surgical evacuation of acute subdural hematoma were analyzed. Both a brain tissue oxygen tension probe and an intracerebral microdialysis probe were placed in brain tissue exposed at surgery. On the basis of the postoperative clinical course, the patients were divided into three groups: patients with early intractable intracranial hypertension, patients with evolution of delayed traumatic injury (DTI), and patients with an uncomplicated course (the no-DTI group).
The overall mortality rate was 46%, with 100% mortality in the intracranial hypertension group (five patients). Mortality in the DTI group was 53% compared with only 9% in the no-DTI group (P = 0.002). There were no significant differences in the initial computed tomographic scan characteristics, such as thickness of the subdural hematoma or amount of midline shift, among the three groups. Physiological variables, as well as the microdialysate measures of brain biochemistry, were markedly different in the intracranial hypertension group compared with the other groups. Differences between the other two groups were more subtle but were significant. Significantly lower values of brain tissue oxygen tension (14 +/- 8 mm Hg versus 27 +/- 14 mm Hg) and higher dialysate values of lactate and pyruvate were documented in patients who developed a delayed injury compared with patients with uncomplicated courses (4.1 +/- 2.3 mmol/L versus 1.7 +/- 0.7 mmol/L for lactate, and 104 +/- 47 micromol/L versus 73 +/- 54 micromol/L for pyruvate at 24 h after injury).
Evolution of DTI in the area of brain underlying an evacuated subdural hematoma is associated with a significant increase in mortality. Postoperatively decreasing brain tissue oxygen tension and increasing dialysate concentrations of lactate and pyruvate in this area may warn of evolving brain injury and evoke further diagnostic and therapeutic activity.
Neurosurgery 08/2007; 61(1 Suppl):249-54; discussion 254-5. · 2.79 Impact Factor
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Jose A Pineda,
Stephen B Lewis,
Alex B Valadka,
Linda Papa,
H Julia Hannay,
Shelley C Heaton,
Jason A Demery,
Ming Cheng Liu,
Jada M Aikman,
Veronica Akle,
Gretchen M Brophy,
Joseph J Tepas,
Kevin K W Wang, Claudia S Robertson,
Ronald L Hayes
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ABSTRACT: Following traumatic brain injury (TBI), the cytoskeletal protein alpha-II-spectrin is proteolyzed by calpain and caspase-3 to signature breakdown products. To determine whether alpha -II-spectrin proteolysis is a potentially reliable biomarker for TBI in humans, the present study (1) examined levels of spectrin breakdown products (SBDPs) in cerebrospinal fluid (CSF) from adults with severe TBI and (2) examined the relationship between these levels, severity of injury, and clinical outcome. This prospective case control study enrolled 41 patients with severe TBI, defined by a Glasgow Coma Scale (GCS) score of < or =8, who underwent intraventricular intracranial pressure monitoring. Patients without TBI requiring CSF drainage for other medical reasons served as controls. Ventricular CSF was sampled from each patient at 6, 12, 24, 48, 72, 96, and 120 h following TBI and analyzed for SBDPs. Outcome was assessed using the Glasgow Outcome Score (GOS) 6 months after injury. Calpain and caspase-3 mediated SBDP levels in CSF were significantly increased in TBI patients at several time points after injury, compared to control subjects. The time course of calpain mediated SBDP150 and SBDP145 differed from that of caspase-3 mediated SBDP120 during the post-injury period examined. Mean SBDP densitometry values measured early after injury correlated with severity of injury, computed tomography (CT) scan findings, and outcome at 6 months post-injury. Taken together, these results support that alpha -II-spectrin breakdown products are potentially useful biomarker of severe TBI in humans. Our data further suggests that both necrotic/oncotic and apoptotic cell death mechanisms are activated in humans following severe TBI, but with a different time course after injury.
Journal of Neurotrauma 03/2007; 24(2):354-66. · 3.65 Impact Factor
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ABSTRACT: Innovative approaches are needed to allow for research in the emergency setting while not compromising either the rights or the interests of the subjects enrolled in such research. The emergency consent exception was developed to meet this need.
The goal was to describe the timing of initial contact with relatives and the timing of obtaining informed consent for a research study in patients with severe traumatic brain injury.
The study was designed as a prospective, observational study of 129 patients enrolled in an emergency study of traumatic brain injury conducted under the emergency consent exception. Detailed descriptive information was collected both about the availability of relatives of patients enrolled in a study of traumatic brain injury to give prospective consent within the time period required for entering the study and about the extent to which they did give prospective consent during that time period.
The number of patients with relatives who could be contacted by research staff increased with time after injury, with 3% (95% CI=0 to 6%), 25% (95% CI=18 to 32%), and 43% (95% CI=35 to 52%) having family at 1, 3, and 6 h, respectively postinjury. An additional 15% were available within the next 6 h. The median time after injury to the initial family contact by the research staff was 2.0 h for patients who had relatives already present at the hospital and 5.7 h for patients whose family had already been contacted by the hospital. The percentage of family members actually giving prospective research consent was much smaller; only 18% actually gave prospective consent within 6 h postinjury. The proportion of critically ill patients with family available to give prospective consent for enrollment in emergency research studies depends primarily on the time period allowed for enrollment in the individual study and the length of the transition from initial contact to completed prospective consent.
The study was performed in a specific patient population and may not be generalizable to other settings.
Careful attention should be paid by investigators and IRBs as to whether the emergency consent exception is really required for a particular study, or whether the study could proceed using only prospective consent with a longer recruitment period, more research sites, and a higher yield of available family members giving prospective consent. Measures that could shorten the time between initial contact and obtaining informed consent (for example, allowing consent over the phone rather than requiring written consent) might decrease the need for the emergency consent exception.
Clinical Trials 02/2007; 4(6):631-7. · 1.92 Impact Factor
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ABSTRACT: Effective treatment of intracranial hypertension involves meticulous avoidance of factors that precipitate or aggravate increased intracranial pressure. When intracranial pressure becomes elevated, it is important to rule out new mass lesions that should be surgically evacuated. medical management of increased intracranial pressure should include sedation and paralysis, drainage of cerebrospinal fluid, and osmotherapy with either mannitol or hypertonic saline. For intracranial hypertension refractory to initial medical management, barbiturate coma, hypothermia, or decompressive craniectomy should be considered. Steroids are not indicated and may be harmful in the treatment of intracranial hypertension resulting from traumatic brain injury.
Critical Care Clinics 11/2006; 22(4):713-32; abstract ix. · 2.05 Impact Factor
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ABSTRACT: Dynamic testing of cerebral pressure autoregulation is more practical than static testing for critically ill patients. The process of cuff deflation is innocuous in the normal subject, but the systemic and cerebral effects of cuff deflation in severely head-injured patients have not been studied. The purposes of this study were to examine the physiological effects of cuff deflation and to study their impact on the calculation of autoregulatory index (ARI).
In 24 severely head-injured patients, 388 thigh cuff deflations were analyzed. The physiological parameters were recorded before, during, and after a transient decrease in blood pressure. Autoregulation was graded by generating an ARI value from 0 to 9.
Mean arterial blood pressure (MAP) dropped rapidly during the first 2-3 seconds, but the nadir MAP was not reached until 8 +/- 7 seconds after the cuff deflation. MAP decreased by an average value of 19 +/- 5 mmHg. Initially the tracings for MAP and cerebral perfusion pressure (CPP) were nearly identical, but after 30 seconds, variable increases in intracranial pressure caused some differences between the MAP and CPP curves. The difference between the ARI values calculated twice using MAP as well as CPP was zero for 70% of left-sided studies and 73% for right-sided studies and less than or equal to 1 for 93% of left- and 95% of right-sided cuff deflations.
Transient and relatively minor perturbations were detected in systemic physiology induced by dynamic testing of cerebral pressure autoregulation. Furthermore, this study confirms that the early changes in MAP and CPP after cuff deflation are nearly identical. MAP can substitute for CPP in the calculation of ARI even in the severely brain-injured patient.
Neurocritical Care 02/2006; 4(2):127-32. · 2.47 Impact Factor
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ABSTRACT: Induced hypertension is commonly used to improve cerebral perfusion, but this treatment may have the deleterious side effect of raising intracranial pressure (ICP). We tested the hypothesis that dynamic pressure autoregulation testing could identify patients who might develop increased ICP during induced hypertension.
Twenty-two studies were performed in 21 patients. Baseline dynamic testing of autoregulation by cuff deflation and carotid compression techniques was performed. After phenylephrine was infused to increase mean arterial pressure by 20 to 30 mm Hg, cuff deflation tests were repeated.
The average increase in mean arterial pressure was 32.2 +/- 16.1 mm Hg. This increase was accompanied by increased flow velocity (P < 0.001), brain tissue PO2 (P = 0.011), and regional cerebral blood flow (P = 0.008). Also, dynamic pressure autoregulation consistently improved (P = 0.015). Induced hypertension caused increased ICP (iICP) in 12 patients and a decrease in ICP (dICP) in 9. Baseline jugular venous oxygen saturation in the iICP group was 82 +/- 10% compared with 70 +/- 10% in dICP patients (P = 0.02). Baseline dynamic autoregulatory index for the cuff deflation tests (1.8 +/- 1.4) and baseline transient hyperemic response ratio for the carotid compression tests (1.11 +/- 0.07) were significantly lower in iICP patients (dICP group: autoregulatory index 3.2 +/- 1.7, P = 0.06; transient hyperemic response ratio 1.26 +/- 0.11, P = 0.009). Flow velocity increased more with the increase in blood pressure in the iICP group than in the dICP group: 19.0 +/- 6.8 cm/s versus 10.2 +/- 6.3 cm/s (P = 0.007).
The patients who had an increase in ICP with induced hypertension had a greater degree of impairment of autoregulation and induced hypertension resulted in a greater increase in flow velocity.
Neurosurgery 11/2005; 57(5):917-23; discussion 917-23. · 2.79 Impact Factor
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ABSTRACT: The nitric oxide (NO)/cGMP pathway in the vascular smooth muscle cell (VSMC) is an important cellular signaling system for the regulation of VSMC relaxation. We present a mathematical model to investigate the underlying mechanisms of this pathway. The model describes the flow of NO-driven signal transduction: NO activation of soluble guanylate cyclase (sGC), sGC- and phosphodiesterase-catalyzed cGMP production and degradation, cGMP-mediated regulation of protein targets including the Ca2+-activated K+ (KCa) channel, and the myosin contractile system. Model simulations reproduce major NO/cGMP-induced VSMC relaxation effects, including intracellular Ca2+ concentration reduction and Ca2+ desensitization of myosin phosphorylation and force generation. Using the model, we examine several testable principles. 1) Rapid sGC desensitization is caused by end-product cGMP feedback inhibition; a large fraction of the steady-state sGC population is in an inactivated intermediate state, and cGMP production is limited well below maximum. 2) NO activates the K(Ca) channel with both cGMP-dependent and -independent mechanisms; moderate NO concentration affects the K(Ca) via the cGMP-dependent pathway, whereas higher NO concentration is accommodated by a cGMP-independent mechanism. 3) Chronic NO synthase inhibition may cause underexpressions of K+ channels including inward rectifier and K(Ca) channels. 4) Ca2+ desensitization of the contractile system is distinguished from Ca2+ sensitivity of myosin phosphorylation. The model integrates these interactions among the heterogeneous components of the NO signaling system and can serve as a general modeling framework for studying NO-mediated VSMC relaxation under various physiological and pathological conditions. New data can be readily incorporated into this framework for interpretation and possible modification and improvement of the model.
AJP Heart and Circulatory Physiology 09/2005; 289(2):H886-97. · 3.71 Impact Factor
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Rabih O Darouiche,
David H Berger,
Nancy Khardori, Claudia S Robertson,
Matthew J Wall,
Michael H Metzler,
Seema Shah,
Mohammad D Mansouri,
Colleen Cerra-Stewart,
James Versalovic,
Michael J Reardon,
Issam I Raad
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ABSTRACT: We sought to compare the impact of antimicrobial impregnation to that of tunneling of long-term central venous catheters on the rates of catheter colonization and catheter-related bloodstream infection.
Tunneling of catheters constitutes a standard of care for preventing infections associated with long-term vascular access. Although antimicrobial coating of short-term central venous catheters has been demonstrated to protect against catheter-related bloodstream infection, the applicability of this preventive approach to long-term vascular access has not been established.
A prospective, randomized clinical trial in 7 university-affiliated hospitals of adult patients who required a vascular access for > or = 2 weeks. Patients were randomized to receive a silicone central venous catheter that was either impregnated with minocycline and rifampin or tunneled. The occurrence of catheter colonization and catheter-related bloodstream infection was determined.
Of a total of 351 inserted catheters, 346 (186 antimicrobial-impregnated and 160 tunneled) were analyzed for catheter-related bloodstream infection. Clinical characteristics were comparable in the 2 study groups, but the antimicrobial-impregnated catheters remained in place for a shorter period of time (mean, 30.2 versus 43.8 days). Antimicrobial-impregnated catheters were as likely to be colonized as tunneled catheters (7.9 versus 6.3 per 1000 catheter-days). Bloodstream infection was 4 times less likely to originate from antimicrobial-impregnated than from tunneled catheters (0.36 versus 1.43 per 1000 catheter-days).
Antimicrobial impregnation of long-term central venous catheters may help obviate the need for tunneling of catheters.
Annals of Surgery 08/2005; 242(2):193-200. · 7.49 Impact Factor
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ABSTRACT: The purpose of this study was to compare the effects of L-arginine and tetrahydrobiopterin administration on post-traumatic cerebral blood flow (CBF) and tissue levels of NO in injured brain tissue. Rats were anesthetized with isoflurane. Mean blood pressure, intracranial pressure, cerebral blood flow using laser Doppler flowmetry (LDF) and brain tissue nitric oxide (NO) concentrations were measured prior to, and for 2 h after a controlled cortical impact injury. L-arginine, 300 mg/kg, tetrahydrobiopterin, 10 mg/kg, or equal volume of saline was given at 5 min after injury. In the saline-treated animals, LDF decreased to 34 +/- 4% of baseline values after injury. NO concentration also decreased by approximately 20 pmol/ml from baseline values. L-arginine and tetrahydrobiopterin administration both resulted in a significant preservation of tissue NO concentrations and an improvement in LDF, compared to control animals given saline. These studies demonstrate that tetrahydrobiopterin administration has a beneficial effect on cerebral blood flow that is similar to L-arginine administration, and may suggest that depletion of tetrahydrobiopterin plays a role in the post-traumatic hypoperfusion of the brain.
Journal of Neurotrauma 10/2004; 21(9):1196-203. · 3.65 Impact Factor
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ABSTRACT: Traumatic brain injury (TBI) makes the brain susceptible to secondary insults such as ischemia. This study tested the hypothesis that L-arginine would increase regional CBF (rCBF) and brain tissue PO2 (PbtO2) at the injury site.
A secondary insult model was employed in rodents. rCBF was measured with laser doppler flowmetry (LDF) and PbtO2 with a PO2 catheter at the impact site. Animals were randomized to receive L-arginine, D-arginine or saline intravenously, 5 minutes after impact.
In animals who received L-arginine, the percentage rCBF from baseline (%CBF) was higher at the impact site after impact (p < 0.001), during bilateral carotid occulation (BCO) (p = 0.001) and during reperfusion (p = 0.032). In contrast, PbtO2 was not significantly increased throughout the experiment for the L-arginine group.
Administration of L-arginine increased rCBF in the injured brain tissue, and resulted in better preservation of CBF during BCO than D-arginine and saline.
The Journal of trauma 08/2004; 57(2):244-50. · 2.48 Impact Factor
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ABSTRACT: The purpose of this study was to examine the patterns of change in microdialysate concentrations of glucose, lactate, pyruvate, and glutamate in the brain during periods of hypoxia/ischemia identified by monitoring brain tissue pO2 (PbtO2). Of particular interest was a better understanding of what additional information could be obtained by the microdialysis parameters that was not available from the PbtO2. Fifty-seven patients admitted with severe traumatic brain injury who had placement of both a brain tissue pO2 (PbtO2) and microdialysis probe were studied. The microdialysis probe was perfused with Ringer's solution at 0.3 microL/min and dialysate was collected at 1-h intervals. The concentration of glucose, pyruvate, lactate, and glutamate were measured in each dialysate sample. Changes in the microdialysis parameters were examined during episodes where the PbtO2 decreased to below 10 mm Hg. Ten episodes of tissue hypoxia/ischemia identified by a decrease in PbtO2 below 10 mm Hg were observed during the period of monitoring. The concentration of the dialysate glucose closely followed the PbtO2. The dialysate pyruvate concentration was more variable and in some patients transiently increased as the PbtO2 dropped below 10 mm Hg. The dialysate concentration of lactate was significantly increased as the PbtO2 decreased to less than 10 mm Hg. Dialysate glutamate was significantly elevated only when PbtO2 decreased to very low levels. Although changes in the PbtO2 provided the earliest sign of hypoxia/ischemia, the microdialysis assays provided additional information about the consequences that the reduced tissue pO2 has on brain metabolism, which may be helpful in managing these critically ill patients.
Journal of Neurotrauma 08/2004; 21(7):894-906. · 3.65 Impact Factor
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ABSTRACT: Oxidative DNA lesions have not been well studied in traumatic brain injury (TBI).
TBI was induced with a controlled cortical impact injury in rats. Brain tissue was examined for 8-hydroxy-2'-deoxyguanosine (oh8dG) using mono-clonal antibodies at different time frames; 15 minutes (n = 4), 30 minutes (n = 7), 60 minutes (n = 6), and 240 minutes (n = 5). The control group consisted of sham-operated animals undergoing the same surgery without the controlled cortical impact injury (n = 5).
An elevation of oh8dG was detected in the nuclear and perinuclear (mitochondrial) regions of the ipsilateral cortex, but seldom in those of the contralateral cortex. The amount of oh8dG in those animals with TBI was significant in all time frames when compared with sham-operated controls (p < 0.001). The oh8dG levels were more prominent at 15 minutes (p < 0.0001) when compared with controls.
Oxidative DNA lesions occurred in this model of TBI maximally early after TBI. This suggests that oh8dGs may affect genetic material of the brain and that oh8dGs may adversely affect gene expression that occurs early after head injury.
The Journal of trauma 06/2004; 56(6):1235-40. · 2.48 Impact Factor
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ABSTRACT: Nitric oxide (NO) is a gaseous chemical messenger which has functions in the brain in a variety of broad physiological processes, including control of cerebral blood flow, interneuronal communications, synaptic plasticity, memory formation, receptor functions, intracellular signal transmission, and release of neurotransmitters. As might be expected from the numerous and complex roles that NO normally has, it can have both beneficial and detrimental effects in disease states, including traumatic brain injury. There are two periods of time after injury when NO accumulates in the brain, immediately after injury and then again several hours-days later. The initial immediate peak in NO after injury is probably due to the activity of endothelial NOS and neuronal NOS. Pre-injury treatment with 7-nitroindazole, which probably inhibits this immediate increase in NO by neuronal NOS, is effective in improving neurological outcome in some models of traumatic brain injury (TBI). After the initial peak in NO, there can be a period of relative deficiency in NO. This period of low NO levels is associated with a low cerebral blood flow (CBF). Administration of L-arginine at this early time improves CBF, and outcome in many models. The late peak in NO after traumatic injury is probably due primarily to the activity of inducible NOS. Inhibition of inducible NOS has neuroprotective effects in most models.
Brain Pathology 05/2004; 14(2):195-201. · 3.99 Impact Factor
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ABSTRACT: It is controversial whether a low cerebral blood flow (CBF) simply reflects the severity of injury or whether ischemia contributes to the brain's injury. It is also not clear whether posttraumatic cerebral hypoperfusion results from intracranial hypertension or from pathologic changes of the cerebral vasculature. The answers to these questions have important implications for whether and how to treat a low CBF.
We performed a retrospective analysis of 77 patients with severe traumatic brain injury who had measurement of CBF within 12 hours of injury. CBF was measured using xenon-enhanced computed tomography (XeCT). Global CBF, physiological parameters at the time of XeCT, and outcome measures were analyzed.
Average global CBF for the 77 patients was 36+/-16 mL/100 g/minutes. Nine patients had an average global CBF<18 (average 12+/-5). The remaining 68 patients had a global CBF of 39+/-15. The initial ICP was >20 mmHg in 90% and >30 mmHg in 80% of patients in the group with CBF<18, compared to 33% and 16%, respectively, in the patients with CBF>or=18. Mortality was 90% at 6 months postinjury in patients with CBF<18. Mortality in the patients with CBF>18 was 19% at 6 months after injury.
In patients with CBF<18 mL/100 g/minutes, intracranial hypertension plays a major causative role in the reduction in CBF. Treatment would most likely be directed at controlling intracranial pressure, but the early, severe intracranial hypertension also probably indicates a severe brain injury. For levels of CBF between 18 and 40 mL/100 g/minutes, the presence of regional hypoperfusion was a more important factor in reducing the average CBF.
Neurocritical Care 01/2004; 1(1):69-83. · 2.47 Impact Factor
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ABSTRACT: Traumatic brain injury causes a reduction in cerebral blood flow, which may cause additional damage to the brain. The purpose of this study was to examine the role of nitric oxide produced by endothelial nitric oxide synthase (eNOS) in these vascular effects of trauma. To accomplish this, cerebral hemodynamics were monitored in mice deficient in eNOS and wild-type control mice that underwent lateral controlled cortical impact injury followed by administration of either L-arginine, 300 mg/kg, or saline at 5 min after the impact injury. The eNOS deficient mice had a greater reduction in laser Doppler flow (LDF) in the contused brain tissue at the impact site after injury, despite maintaining a higher blood pressure. L-Arginine administration increased LDF post-injury only in the wild-type mice. L-Arginine administration also resulted in a reduction in contusion volume, from 2.4 +/- 1.5 to 1.1 +/- 1.2 mm(3) in wild-type mice. Contusion volume in the eNOS deficient mice was not significantly altered by L-arginine administration. These differences in cerebral hemodynamics between the eNOS-deficient and the wild-type mice suggest an important role for nitric oxide produced by eNOS in the preservation of cerebral blood flow in contused brain following traumatic injury, and in the improvement in cerebral blood flow with L-arginine administration.
Journal of Neurotrauma 11/2003; 20(10):995-1006. · 3.65 Impact Factor
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ABSTRACT: We develop an integrated model of isolated rat arterial resistance vessel (RV), which can simulate its major property of myogenic response. The vascular smooth muscle cell is an important component of the wall of this vessel, and serves as a vasomotor organ providing the active tension generation that underlies the myogenic response of the wall to stretch. In the previous study, we focused on the development of a smooth muscle cell model that can mimic the strain-sensing and force-generating features of the myogenic mechanism. In the current model, we embed this cell model in a larger vessel wall configuration, and couple the time course of cellular contractile activation to macroscopic changes in vessel diameter. The integrated model is used to mimic published pressure-vessel diameter data obtained from isolated RVs that are mounted in a hydraulic test apparatus. The model provides biophysically based insights into the myogenic mechanism as it responds to changes in transmural pressure, in the presence and absence of Ca2+ blockers applied to the bathing fluid.It mimics measured data very well and provides a model that is able to link events at subcellular level to macroscopic changes in vessel diameter. The model initiates a mechanistic approach to investigate myogenic response, which has not been taken previously by any other models.
Medical Engineering & Physics 11/2003; 25(8):711-7. · 1.62 Impact Factor
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ABSTRACT: To determine differences between dalteparin and enoxaparin in patients with spinal cord injury.
This prospective, randomized, open-label study was performed as a multiple hospital trial in a large urban setting. A total of 100 patients with acute (<3 mo) spinal cord injury were recruited. A total of 95 patients met all inclusion criteria. Fifty received enoxaparin, and 45 received dalteparin. Main outcome measures included deep venous thrombosis, bleeding, compliance, Short Form-12 Health Status Survey, satisfaction, and medication/labor costs. Patients were randomized to receive 30 mg of enoxaparin subcutaneously every 12 hr or 5000 IU of dalteparin subcutaneously once daily. Prophylaxis was continued for 3 mo for motor-complete and 2 mo for motor-incomplete patients.
Six percent of the patients developed deep venous thrombosis while receiving enoxaparin and 4% while receiving dalteparin (chi2 = 0.44, df = 1, P = 0.51). Four percent developed bleeding while receiving dalteparin and 2% while receiving enoxaparin (chi2 = 0.13, df = 1, P = 0.72). No differences were noted in compliance, health status, or most of the satisfaction measures. It was, however, noted that after being discharged home, the patients receiving enoxaparin rated the shots significantly more inconvenient (two injections per day) compared with taking three pills per day, than those receiving dalteparin (one injection per day, P < 0.05). The cost of the medication was 1101 US dollars/mo for enoxaparin (two injections per day) and 750 US dollars/mo for dalteparin (one injection per day).
Similar compliance, health status, deep venous thrombosis, and bleeding rates were found between dalteparin and enoxaparin.
American Journal of Physical Medicine & Rehabilitation 10/2003; 82(9):678-85. · 1.58 Impact Factor
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ABSTRACT: Chiou-Tan FY, Garza H, Chan KT, Parsons KC, Donovan WH, Robertson CS, Holmes SA, Graves DE, Rintala DH: Comparison of dalteparin and enoxaparin for deep venous thrombosis prophylaxis in patients with spinal cord injury. Am J Phys Med Rehabil 2003;82:678-685.
Objective: To determine differences between dalteparin and enoxaparin in patients with spinal cord injury.
Design: This prospective, randomized, open-label study was performed as a multiple hospital trial in a large urban setting. A total of 100 patients with acute (<3 mo) spinal cord injury were recruited. A total of 95 patients met all inclusion criteria. Fifty received enoxaparin, and 45 received dalteparin. Main outcome measures included deep venous thrombosis, bleeding, compliance, Short Form-12 Health Status Survey, satisfaction, and medication/labor costs. Patients were randomized to receive 30 mg of enoxaparin subcutaneously every 12 hr or 5000 IU of dalteparin subcutaneously once daily. Prophylaxis was continued for 3 mo for motor-complete and 2 mo for motor-incomplete patients.
Results: Six percent of the patients developed deep venous thrombosis while receiving enoxaparin and 4% while receiving dalteparin (χ2 = 0.44, df = 1, P = 0.51). Four percent developed bleeding while receiving dalteparin and 2% while receiving enoxaparin (χ2 = 0.13, df = 1, P = 0.72). No differences were noted in compliance, health status, or most of the satisfaction measures. It was, however, noted that after being discharged home, the patients receiving enoxaparin rated the shots significantly more inconvenient (two injections per day) compared with taking three pills per day, than those receiving dalteparin (one injection per day, P < 0.05). The cost of the medication was $1101/mo for enoxaparin (two injections per day) and $750/mo for dalteparin (one injection per day).
Conclusion: Similar compliance, health status, deep venous thrombosis, and bleeding rates were found between dalteparin and enoxaparin.
American Journal of Physical Medicine & Rehabilitation 08/2003; 82(9):678-685. · 1.58 Impact Factor
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ABSTRACT: Arterial hypotension and intracranial hypertension are detrimental to the injured brain. Although artificial elevation of cerebral perfusion pressure (CPP) has been advocated as a means to maintain an adequate cerebral blood flow (CBF), the optimal CPP for the treatment of severe traumatic brain injury (TBI) remains unclear. In addition, CBF evolves significantly over time after TBI, and CBF may vary considerably in patient to patient. For these reasons, a more useful approach may be to consider the optimal CPP in an individual patient at any given time, rather than having an arbitrary goal applied uniformly to all patients. Important information for optimizing CBF is provided by monitoring intracranial pressure in combination with assessment of the adequacy of CBF by using global indicators (for example, jugular oximetry), supplemented when appropriate by local data, such as brain tissue oxygen tension.
Neurosurgical FOCUS 05/2003; 14(4):e2. · 2.87 Impact Factor
