Geofrey Ling - Academia.edu (original) (raw)
Papers by Geofrey Ling
Digitization of the Battlespace V and Battlefield Biomedical Technologies II, 2000
ABSTRACT
Visualization of Temporal and Spatial Data for Civilian and Defense Applications, 2001
ABSTRACT
Stroke, 2002
Background and Purpose-Fabry disease is an X-linked inherited disorder resulting from a deficienc... more Background and Purpose-Fabry disease is an X-linked inherited disorder resulting from a deficiency of ␣-galactosidase A. Cerebrovascular disease in Fabry disease includes small-vessel disease and larger-vessel ectasia in a predominantly posterior distribution. We assessed transcranial Doppler (TCD) blood flow velocities in naive and enzyme-treated Fabry patients. Methods-TCD was used to noninvasively examine patients with Fabry disease for abnormal cerebral blood flow velocities. TCD measurements were also made during CO 2 retention by breathholding to examine cerebrovascular vessel reactivity. Twenty-six patients were enrolled in a 6-month, double-blind, placebo-controlled trial of enzyme replacement therapy consisting of biweekly intravenous ␣-galactosidase A infusions, with a subsequent 18-month follow-up in an open-label trial. Statistical analysis consisted of applying a mixed-effects ANOVA model for correlated outcomes. Results-Peak velocity, mean velocity, pulsatility index, and resistance index were found to be significantly higher in patients compared with control subjects. When the individual vessels were considered, elevated flow velocities were found in the middle cerebral M1 branch and the posterior cerebral artery. Enzyme replacement therapy significantly decreased peak, mean, and end-diastolic velocities and flow acceleration at the 18-month follow-up time point.
Neurosurgery, 2006
Blast-related neurotrauma is associated with the severest casualties from Operation Iraqi Freedom... more Blast-related neurotrauma is associated with the severest casualties from Operation Iraqi Freedom (OIF). A consequence of this is cerebral vasospasm. This study evaluated all inpatient neurosurgical consults related to battle injury from OIF. Evaluation of all admissions from OIF from April 2003 to October 2005 was performed on patients with neurotrauma and a diagnostic cerebral angiogram. Differences between patients with and without vasospasm and predictors of vasospasm were analyzed. Fifty-seven out of 119 neurosurgical consults were evaluated. Of these, 47.4% had traumatic vasospasm; 86.7% of patients without vasospasm and 80.8% of patients with vasospasm sustained blast trauma. Average spasm duration was 14.3 days, with a range of up to 30 days. Vasospasm was associated with the presence of pseudoaneurysm (P = 0.05), hemorrhage (P = 0.03), the number of lobes injured (P = 0.012), and mortality (P = 0.029). Those with vasospasm fared worse than those without (P = 0.002). The number of lobes injured and the presence of pseudoaneurysm were significant predictors of vasospasm (P = 0.016 and 0.02, respectively). There was a significant quadratic trend towards neurological improvement for those receiving aggressive open surgical treatment (P = 0.002). In the vasospasm group, angioplasty with microballoon significantly lowered middle cerebral artery and basilar blood-flow velocities(P = 0.046 and 0.026, respectively). Traumatic vasospasm occurred in a substantial number of patients with severe neurotrauma, and clinical outcomes were worse for those with this condition. However, aggressive open surgical and endovascular treatment strategies may have improved outcome. This was the first study to analyze the effects of blast-related injury on the cerebral vasculature.
Neurosurgery, 2001
We sought to analyze the regional concentrations of proinflammatory cytokines in the acute period... more We sought to analyze the regional concentrations of proinflammatory cytokines in the acute period of intracerebral hemorrhage (ICH) and to test the hypothesis that ICH is associated with the expression of proinflammatory cytokines in the acute period. Although the expression of cytokines and their role in neuronal injury and inflammation is well characterized in cerebral ischemia and head injury, no information exists regarding expression of cytokines in ICH. We introduced ICH in eight anesthetized mongrel dogs by autologous blood injection (6 ml) under arterial pressure in the deep white matter adjacent to the left basal ganglia. Samples of arterial blood and cerebrospinal fluid were collected, and tissue extracts were prepared from different regions of the brain for immunoassay of tumor necrosis factor alpha, interleukin (IL)-1beta, and IL-6 concentrations in animals with and without ICH. The tumor necrosis factor a levels (+/- standard error) in the cerebrospinal fluid 1 hour after ICH did not differ significantly between the ICH group and the control group (7.1 +/- 1.3 pg/ml versus 10.8 +/- 2.3 pg/ml, P = 0.22). Levels in the perihematoma region in the ICH group (96.6 +/- 3.1 pg/ml) were not significantly different from those in the control group (93.4 +/- 6.7 pg/ml, P = 0.7). IL-6 levels (+/- standard error) in the perihematoma region in the ICH group (116.3 +/- 13.3 pg/ml) did not differ significantly from those in corresponding regions in the control group (122.3 +/- 12.8 pg/ml, P = 0.7). IL-1beta levels were below 5 pg/ml in serum, cerebrospinal fluid, and extracts of different brain regions. The early pathophysiology of ICH does not involve significant expression of tumor necrosis factor a either in the perihematoma region or other regions of the brain. The observation suggests that the pathophysiology of ICH in the acute period is different from both cerebral ischemia and traumatic brain injury.
Neurocritical Care, 2005
Cerebral perfusion pressure (CPP) is one aspect of an all-encompassing approach in the management... more Cerebral perfusion pressure (CPP) is one aspect of an all-encompassing approach in the management of traumatic brain injury (TBI). The clinical use of CPP is based on theoretical considerations that optimal cerebral blood flow is necessary to meet the metabolic needs of the injured brain. The goal is to preserve the ischemic penumbra and avoid secondary insults. Unfortunately, lack of objective measures of local tissue response and randomized controlled clinical trials prevents confirmation that these goals are being met when actively treating CPP.
Journal of Neurotrauma, 2007
Cerebral edema (CE) is a frequent and potentially lethal consequence of various neurotraumas, inc... more Cerebral edema (CE) is a frequent and potentially lethal consequence of various neurotraumas, including penetrating brain injury (PBI). Aquaporin-4 (AQP4) water channel is predominantly expressed by astrocytes and plays an important role in regulating water balance in the normal and injured brain. Using a rat model of PBI, we show that AQP4 immunoreactivity was substantially increased in the peri-injury area at both 24 and 72 h after PBI. The increase in AQP4 expression was paralleled by increased GFAP expression. The two proteins were co-expressed by peri-vascular astrocytes, whereas reactive astroglia identified by their stellar morphology did not express AQP4 at either time points after injury. Western analysis confirmed the increase in AQP4 immunoreactivity observed in the injured tissue. The apparent increase in AQP4 immunoreactivity was likely due to de novo AQP4 protein synthesis, as most of the increased AQP4 immunoreactivity was found in the soluble (cytosolic) fraction. Our results demonstrate dynamic spatial and temporal changes in AQP4 expression that contribute to the molecular pathophysiology of PBI.
Journal of Cerebral Blood Flow & Metabolism, 2005
In conclusion, rats sustaining a moderate fluid percussion injury have a significant decrease in ... more In conclusion, rats sustaining a moderate fluid percussion injury have a significant decrease in injury volume when treated with one-hour of post-traumatic hypercarbia in the setting of normal oxygenation compared to rats with normal pCO2 values. These findings warrant further ...
Journal of Neurotrauma, 2009
The public reporting burden for this collection of information is estimated to average 1 hour per... more The public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing the burden, to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports 10704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid 0MB control number.
Digitization of the Battlespace V and Battlefield Biomedical Technologies II, 2000
ABSTRACT
Visualization of Temporal and Spatial Data for Civilian and Defense Applications, 2001
ABSTRACT
Stroke, 2002
Background and Purpose-Fabry disease is an X-linked inherited disorder resulting from a deficienc... more Background and Purpose-Fabry disease is an X-linked inherited disorder resulting from a deficiency of ␣-galactosidase A. Cerebrovascular disease in Fabry disease includes small-vessel disease and larger-vessel ectasia in a predominantly posterior distribution. We assessed transcranial Doppler (TCD) blood flow velocities in naive and enzyme-treated Fabry patients. Methods-TCD was used to noninvasively examine patients with Fabry disease for abnormal cerebral blood flow velocities. TCD measurements were also made during CO 2 retention by breathholding to examine cerebrovascular vessel reactivity. Twenty-six patients were enrolled in a 6-month, double-blind, placebo-controlled trial of enzyme replacement therapy consisting of biweekly intravenous ␣-galactosidase A infusions, with a subsequent 18-month follow-up in an open-label trial. Statistical analysis consisted of applying a mixed-effects ANOVA model for correlated outcomes. Results-Peak velocity, mean velocity, pulsatility index, and resistance index were found to be significantly higher in patients compared with control subjects. When the individual vessels were considered, elevated flow velocities were found in the middle cerebral M1 branch and the posterior cerebral artery. Enzyme replacement therapy significantly decreased peak, mean, and end-diastolic velocities and flow acceleration at the 18-month follow-up time point.
Neurosurgery, 2006
Blast-related neurotrauma is associated with the severest casualties from Operation Iraqi Freedom... more Blast-related neurotrauma is associated with the severest casualties from Operation Iraqi Freedom (OIF). A consequence of this is cerebral vasospasm. This study evaluated all inpatient neurosurgical consults related to battle injury from OIF. Evaluation of all admissions from OIF from April 2003 to October 2005 was performed on patients with neurotrauma and a diagnostic cerebral angiogram. Differences between patients with and without vasospasm and predictors of vasospasm were analyzed. Fifty-seven out of 119 neurosurgical consults were evaluated. Of these, 47.4% had traumatic vasospasm; 86.7% of patients without vasospasm and 80.8% of patients with vasospasm sustained blast trauma. Average spasm duration was 14.3 days, with a range of up to 30 days. Vasospasm was associated with the presence of pseudoaneurysm (P = 0.05), hemorrhage (P = 0.03), the number of lobes injured (P = 0.012), and mortality (P = 0.029). Those with vasospasm fared worse than those without (P = 0.002). The number of lobes injured and the presence of pseudoaneurysm were significant predictors of vasospasm (P = 0.016 and 0.02, respectively). There was a significant quadratic trend towards neurological improvement for those receiving aggressive open surgical treatment (P = 0.002). In the vasospasm group, angioplasty with microballoon significantly lowered middle cerebral artery and basilar blood-flow velocities(P = 0.046 and 0.026, respectively). Traumatic vasospasm occurred in a substantial number of patients with severe neurotrauma, and clinical outcomes were worse for those with this condition. However, aggressive open surgical and endovascular treatment strategies may have improved outcome. This was the first study to analyze the effects of blast-related injury on the cerebral vasculature.
Neurosurgery, 2001
We sought to analyze the regional concentrations of proinflammatory cytokines in the acute period... more We sought to analyze the regional concentrations of proinflammatory cytokines in the acute period of intracerebral hemorrhage (ICH) and to test the hypothesis that ICH is associated with the expression of proinflammatory cytokines in the acute period. Although the expression of cytokines and their role in neuronal injury and inflammation is well characterized in cerebral ischemia and head injury, no information exists regarding expression of cytokines in ICH. We introduced ICH in eight anesthetized mongrel dogs by autologous blood injection (6 ml) under arterial pressure in the deep white matter adjacent to the left basal ganglia. Samples of arterial blood and cerebrospinal fluid were collected, and tissue extracts were prepared from different regions of the brain for immunoassay of tumor necrosis factor alpha, interleukin (IL)-1beta, and IL-6 concentrations in animals with and without ICH. The tumor necrosis factor a levels (+/- standard error) in the cerebrospinal fluid 1 hour after ICH did not differ significantly between the ICH group and the control group (7.1 +/- 1.3 pg/ml versus 10.8 +/- 2.3 pg/ml, P = 0.22). Levels in the perihematoma region in the ICH group (96.6 +/- 3.1 pg/ml) were not significantly different from those in the control group (93.4 +/- 6.7 pg/ml, P = 0.7). IL-6 levels (+/- standard error) in the perihematoma region in the ICH group (116.3 +/- 13.3 pg/ml) did not differ significantly from those in corresponding regions in the control group (122.3 +/- 12.8 pg/ml, P = 0.7). IL-1beta levels were below 5 pg/ml in serum, cerebrospinal fluid, and extracts of different brain regions. The early pathophysiology of ICH does not involve significant expression of tumor necrosis factor a either in the perihematoma region or other regions of the brain. The observation suggests that the pathophysiology of ICH in the acute period is different from both cerebral ischemia and traumatic brain injury.
Neurocritical Care, 2005
Cerebral perfusion pressure (CPP) is one aspect of an all-encompassing approach in the management... more Cerebral perfusion pressure (CPP) is one aspect of an all-encompassing approach in the management of traumatic brain injury (TBI). The clinical use of CPP is based on theoretical considerations that optimal cerebral blood flow is necessary to meet the metabolic needs of the injured brain. The goal is to preserve the ischemic penumbra and avoid secondary insults. Unfortunately, lack of objective measures of local tissue response and randomized controlled clinical trials prevents confirmation that these goals are being met when actively treating CPP.
Journal of Neurotrauma, 2007
Cerebral edema (CE) is a frequent and potentially lethal consequence of various neurotraumas, inc... more Cerebral edema (CE) is a frequent and potentially lethal consequence of various neurotraumas, including penetrating brain injury (PBI). Aquaporin-4 (AQP4) water channel is predominantly expressed by astrocytes and plays an important role in regulating water balance in the normal and injured brain. Using a rat model of PBI, we show that AQP4 immunoreactivity was substantially increased in the peri-injury area at both 24 and 72 h after PBI. The increase in AQP4 expression was paralleled by increased GFAP expression. The two proteins were co-expressed by peri-vascular astrocytes, whereas reactive astroglia identified by their stellar morphology did not express AQP4 at either time points after injury. Western analysis confirmed the increase in AQP4 immunoreactivity observed in the injured tissue. The apparent increase in AQP4 immunoreactivity was likely due to de novo AQP4 protein synthesis, as most of the increased AQP4 immunoreactivity was found in the soluble (cytosolic) fraction. Our results demonstrate dynamic spatial and temporal changes in AQP4 expression that contribute to the molecular pathophysiology of PBI.
Journal of Cerebral Blood Flow & Metabolism, 2005
In conclusion, rats sustaining a moderate fluid percussion injury have a significant decrease in ... more In conclusion, rats sustaining a moderate fluid percussion injury have a significant decrease in injury volume when treated with one-hour of post-traumatic hypercarbia in the setting of normal oxygenation compared to rats with normal pCO2 values. These findings warrant further ...
Journal of Neurotrauma, 2009
The public reporting burden for this collection of information is estimated to average 1 hour per... more The public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing the burden, to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports 10704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid 0MB control number.