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Geoffrey S F Ling

Publications and source records attributed to Geoffrey S F Ling.

10 recordsLinked to original sources
PubMed2006

Severity level and injury track determine outcome following a penetrating ballistic-like brain injury in the rat.

Penetrating ballistic brain injury (PBBI) is a high-energy transfer wound causing direct damage to the cerebrum. Outcome is directly related to the ballistic's anatomical path and degree of energy transfer. In this study we evaluated differences in outcome induced by altering the 'projectile' paths and severity levels of a simulated bullet wound using a newly characterized rat model of PBBI. Severity levels (5, 10, and 15%) were compared across three distinct injury paths: (1) unilateral 'frontal', (2) 'bilateral' hemispheric, and (3) unilateral 'caudal' (including cerebellum/midbrain). Outcome was assessed by differences in mortality rate and motor dysfunction (e.g. neurological and balance beam deficits). Results indicated that outcome was dependent not only on the severity level of PBBI (P<0.001, r=0.535) but also brain regions injured (P<0.001, r=0.398). A unilateral caudal injury was associated with the highest degree of mortality (up to 100%) and motor dysfunction (64-100% disability). Bilateral hemispheric injuries were also potentially fatal, while the best outcomes were associated with a unilateral frontal injury (no mortality and 14-39% motor disability). These data closely resemble clinical reports of ballistic wounds to the head and further validate the rat PBBI model with the ultimate intent to investigate novel therapeutic approaches for diagnosis and treatment of the neuropathological damage associated with PBBI.

Animals↗
PubMed2006

Cullin 5 gene expression in the rat cerebral cortex and hippocampus following traumatic brain injury (TBI).

Cullin-5 (Cul-5), a member of the cullin gene family of scaffold proteins of E3 ubiquitin-ligase complexes, has a role in proteolysis and cell cycle regulation. We recently demonstrated that cul-5 mRNA is ubiquitously expressed in the central nervous system. The present study used quantitative real time polymerase chain reaction and western blotting to measure changes in cul-5 mRNA and Cul-5 protein expression, respectively, in the injured CNS in response to traumatic brain injury (TBI). cul-5 mRNA levels were significantly decreased in the ipsilateral rat cerebral cortex on Days 1 and 7, but not on Day 3 following TBI. In the ipsilateral hippocampus, cul-5 mRNA was significantly reduced on Day 1 after TBI. Cul-5 protein levels were significantly decreased in the ipsilateral rat cerebral cortex on Days 1-7 post-TBI while levels were significantly lower in the ipsilateral hippocampus on Days 3-7 post-TBI. Since Cul-5 is ubiquitously expressed in eukaryotic cells and is linked to proteasome-mediated protein degradation, it may have a role in CNS cell fate determination under conditions of traumatic stress.

Animals↗
PubMed2005

Physician knowledge of the Glasgow Coma Scale.

Appropriate triage is critical to optimizing outcome from battle related injuries. The Glasgow Coma Scale (GCS) is the primary means by which combat casualties, who have suffered head injury, are triaged. For the GCS to be reliable in this critical role, it must be applied accurately. To determine the level of knowledge of the GCS among military physicians with exposure and/or training in the scale we administered a prospective, voluntary, and anonymous survey to physicians of all levels of training at military medical centers with significant patient referral base. The main outcome measures were correct identification of title and categories of the GCS along with appropriate scoring of each category. Overall performance on the survey was marginal. Many were able to identify what "GCS" stands for, but far fewer were able to identify the titles of the specific categories, let alone identify the specific scoring of each category. When evaluated based on medical specialties, those in surgical specialties outperformed those in the medical specialties. When comparing the different levels of training, residents and fellows performed better than attending staff or interns. Finally, those with Advanced Trauma Life Support (ATLS) certification performed significantly better than those without the training. Physician knowledge of the GCS, as demonstrated in this study, is poor, even in a population of individuals with specific training in the use of the scale. It is concluded that, to optimize outcome from combat related head injury, methods for improving accurate quantitation of neurologic state need to be explored.

Certification↗
PubMed2005

Progesterone differentially regulates pro- and anti-apoptotic gene expression in cerebral cortex following traumatic brain injury in rats.

Although the administration of progesterone has been shown to be neuroprotective in experimental models of traumatic brain injury (TBI), the mechanisms for this beneficial effect are still poorly understood. The present study examined the effects of progesterone on mRNA and protein levels of the Bcl-2 apoptosis regulatory genes, bax, bad, bcl-2, and bcl-x(L), in cerebral cortex after TBI. Male Sprague-Dawley rats were subjected to either sham surgery or lateral fluid percussion brain injury of moderate severity (2.4-2.6 atm). Within 1 h post-surgery, progesterone (4 mg/kg) or vehicle (corn oil) administration was initiated for 1-7 days postoperatively. Our results indicate that bax and bad mRNA levels and Bax and Bad protein expression in the ipsilateral, injured cerebral cortex were significantly elevated post-TBI, while mRNA levels of bcl-2 and bcl-x(L) or Bcl-2 and Bcl-x(L) protein expression were not changed. Under the sham-treated condition, progesterone significantly increased mRNA levels of the anti-apoptotic gene, bcl-2, but down-regulated pro-apoptotic gene expression (bax and bad) in cerebral cortex. After TBI, progesterone treatment reduced bax and bad mRNA levels in the ipsilateral cerebral cortex of TBI rats, and decreased Bax and Bad protein levels. In addition, bcl-2 and bcl-x(L) mRNA levels, as well as Bcl-2 and Bcl-x(L) protein expression, were increased by progesterone in TBI injured cortex. These data indicate that one of the neuroprotective mechanisms of progesterone may be related to its differential regulation of apoptotic signals.

Animals↗
PubMed2005

Maintaining cerebral perfusion pressure is a worthy clinical goal.

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. The present recommended threshold CPP for intervention in the literature is 70 mmHg. However, this specific CPP level is being challenged. There is increasing evidence that this and higher CPP thresholds are not necessary and that a lower CPP may be as clinically effective. There are clinical prospective, but not randomized, human trials showing that CPP 60 to 70 mmHg may be reasonable. Recently, the Brain Trauma Foundation updated their Web-based recommendation of a lower CPP goal of 60 mmHg. However, the lack of definitive data, such as from a randomized prospective intention-to-treat clinical trials, leaves this goal open to controversy. Therefore, for a variety of reasons, the physician may be most prudent to use the published CPP guideline of 70 mmHg until a consensus statement is published advocating a different value.

Blood Pressure↗
PubMed2005

Preventing ischemic stroke in the older adult.

Stroke is a deadly and disabling disease that preferentially afflicts older adults. It shares common risk factors with myocardial infarction (MI), such as hypertension, diabetes, and hyperlipidemia. Blood pressure control, cholesterol reduction with statins, and glucose control reduce the risk for both stroke and MI. Additionally, management of atrial fibrillation with warfarin reduces stroke risk. Beyond risk factor reduction, antiplatelet therapy is an effective option for lowering the likelihood of stroke in at-risk patients. Among antiplatelet agents, aspirin has been shown effective for secondary stroke prevention as well as primary and secondary MI prevention; clopidogrel for secondary stroke and MI prevention; and both ticlodipine and dipyridamole for secondary stroke prevention. Combining antiplatelet agents is rational. Carotid endarterectomy should be considered for stroke prevention in patients with ischemic symptoms; for patients with asymptomatic stenosis, potential benefit must be balanced against surgical risk.

Aged↗
PubMed2004

Intracranial insertion of a nasopharyngeal airway in a patient with craniofacial trauma.

Intracranial insertion of a nasopharyngeal airway is an unusual and catastrophic complication of airway management in the patient with a severe closed head injury. We present an unfortunate 43-year-old patient with intracranial insertion of a nasopharyngeal airway during trauma resuscitation. The nasopharyngeal airway was removed. Attempts to resuscitate the patient were continued, but were eventually unsuccessful. Blind nasopharyngeal airway insertion may result in iatrogenic injury when used in the head-injured patient. Oropharyngeal airways may be used to assist with ventilation. However, it is preferable to definitively secure the airway through inline endotracheal intubation or with surgical techniques in this patient population. Should violation of the skull base occur, removal is accomplished in the controlled environment of the operating room.

Accidents, Traffic↗
PubMed2002

Elevated cerebral blood flow velocities in Fabry disease with reversal after enzyme replacement.

BACKGROUND AND PURPOSE: Fabry disease is an X-linked inherited disorder resulting from a deficiency of alpha-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 CO2 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 alpha-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. CONCLUSIONS: Patients with Fabry disease have elevated cerebral blood flow velocities. These velocities significantly improved with enzyme replacement therapy.

Adult↗
PubMed1988

Unidirectional analgesic cross-tolerance between morphine and levorphanol in the rat.

Clinically, patients often demonstrate incomplete cross-tolerance between opiate analgesics. Although dispositional and pharmacokinetic factors may be a factor, our results suggest that differences in selectivity of various opioids for those opioid receptor subtypes involved in analgesia, mu 1, kappa and delta, also play an important role. In binding studies, levorphanol potently labelled all 3 classes whereas morphine was relatively selective for mu sites. Levorphanol infusions yielded tolerance to both morphine and levorphanol while morphine infusions selectively produced tolerance to morphine. This unidirectional tolerance might be due to the selectivity of morphine for mu receptors compared to levorphanol's ability to interact more potently with other relevant receptor subtypes. These observations raise the possibility that the order in which different opioid analgesics are administered may be of clinical significance.

Analgesia↗