Biomedical subjects

Paul M Shore

Publications and source records attributed to Paul M Shore.

5 recordsLinked to original sources

PubMed2006

Reliability and validity of the Pediatric Intensity Level of Therapy (PILOT) scale: a measure of the use of intracranial pressure-directed therapies.

OBJECTIVE: To test the reliability and validity of the Pediatric Intensity Level of Therapy (PILOT) scale, a novel measure of overall therapeutic effort directed at controlling intracranial pressure (ICP) in the setting of severe (Glasgow Coma Scale of <or= 8) pediatric traumatic brain injury (TBI). DESIGN: Case-control study via retrospective review of medical records. SETTING: Tertiary-care, university-based children's hospital intensive care unit. PATIENTS: Randomly selected patients <or=18 yrs old admitted to the intensive care unit in 2002-2003 with severe TBI (cases: group 1, n = 27), mild-moderate TBI (control: group 2, n = 30), extracranial trauma (control: group 3, n = 29), or nontraumatic illnesses (control: group 4, n = 27). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A 38-point scale was developed to quantify daily ICP-directed therapeutic effort. All currently recommended therapies are represented. Demographic and physiologic data were collected on all patients. A total of 24 of 27 patients with severe TBI received ICP-directed therapy; three did not because of judgments of futility. No control patients received ICP-directed therapy. The PILOT scale score was assessed for the first 7 days posttrauma or postadmission. Interrater reliability was 0.91 (intraclass correlation coefficient) and intrarater reliability was 0.94. The highest PILOT scale scores were in patients with severe TBI (11.7 +/- 5.6 vs. 1.3 +/- 1.7 vs. 2.0 +/- 2.1 vs. 1.9 +/- 1.8 for groups 1, 2, 3 and 4, respectively [mean +/- sd]; p < .001 by analysis of variance/Bonferroni). Patients with severe TBI who received ICP-directed therapy had higher PILOT scale scores (12.6 +/- 5.3 vs. 5.0 +/- 3.0, p = .001) than those who did not. Pearson's correlation coefficients of mean PILOT scale scores with measures of injury severity, outcome, and ICP were as follows: Glasgow Coma Scales score, -0.73 (p < .001); overall Injury Severity Score, 0.37 (p < .001); Injury Severity Score (head component only), 0.53 (p < .001); 6-month Glasgow Outcome Scale, -0.26 (p = .006); ICP burden (hours per day with ICP above treatment threshold), 0.59 (p = .002); and mean ICP, 0.41 (p = .044). CONCLUSIONS: The PILOT scale score can be obtained retrospectively and has good reliability. It can discriminate patients receiving ICP-directed therapy, even among patients with severe TBI, and correlates with measures of injury severity, outcome, and ICP in an expected way. Thus, it seems to be a valid measure of the use of ICP-directed therapy, although prospective, multiple-center validation is recommended.

Brain Injuries↗

PubMed2005

Characterization of the effects of adenosine receptor agonists on cerebral blood flow in uninjured and traumatically injured rat brain using continuous arterial spin-labeled magnetic resonance imaging.

Hypoperfusion after traumatic brain injury may exacerbate damage. Adenosine, a vasodilator, regulates cerebral blood flow (CBF). Treatment with adenosine receptor agonists has shown benefit in experimental CNS trauma; however, their effects on CBF after injury remain undefined. We used magnetic resonance imaging to assess CBF in uninjured rats both early and at 24 h after intrahippocampal administration of either the nonselective adenosine receptor agonist 2-chloroadenosine (2-CA, 12 nmol) or the A(2A)-receptor agonist 2-p-(2-carboxyethyl)-phenethylamino-5'-N-ethylcarbox-amidoadenosine (CGS 21680, 6 nmol). We also assessed the effects of these agents on cerebral metabolic rate for glucose (CMRglu). We then assessed the effect of 2-CA on CBF at 3.5 to 5 h after controlled cortical impact (CCI). Injection of 2-CA into uninjured rat brain produced marked increases in CBF in ipsilateral hippocampus and cortex versus vehicle (P<0.05); CBF increases persisted even at 24 h. Measurement of hippocampal levels of 2-CA showed persistent increases to 24 h. CGS 21680 produced even more marked global increases in CBF than seen with 2-CA (2-6-fold versus vehicle, P<0.05 in 10/12 regions of interest (ROIs)). Neither agonist altered CMRglu versus vehicle. After CCI, 2-CA increased CBF in ipsilateral hippocampal and hemispheric ROIs (P<0.05 versus vehicle), but the response was attenuated at severe injury levels. We report marked increases in CBF after injection of adenosine receptor agonists into uninjured rat brain despite unaltered CMRglu. 2-Chloroadenosine produced enduring increases in CBF in uninjured brain and attenuated posttraumatic hypoperfusion. Future studies of adenosine-related therapies in CNS injury should address the role of CBF.

2-Chloroadenosine↗

PubMed2004

Continuous versus intermittent cerebrospinal fluid drainage after severe traumatic brain injury in children: effect on biochemical markers.

Drainage of cerebrospinal fluid (CSF) is routinely used in the treatment of severe traumatic brain injury (TBI), either continuously or intermittently in response to increases in intracranial pressure (ICP). There has been little study of the effect of CSF drainage method on the biochemistry, pathophysiology or outcome of TBI in adults or children. Having previously reported that a variety of markers of injury or repair increase in CSF after severe TBI, we chose to evaluate directly the effect of CSF drainage method on the biochemistry and volume of CSF drained as well as ICP. We hypothesized that concentrations of these markers would be similar in CSF drained continuously vs intermittently. We compared CSF levels of markers of neuronal injury (neuron specific enolase, [NSE]), glial injury (s100B), inflammation (interleukin-6 [IL-6]), and regeneration (vascular endothelial growth factor [VEGF]) (measured by ELISA) in 80 CSF samples from 19 severely injured children whose CSF was drained continuously (n = 13) versus intermittently (n = 6) as part of standard care in two institutions. Compared to continuous CSF drainage, intermittent drainage of CSF was associated with twofold greater CSF concentrations of NSE, s100B, IL-6 and VEGF (p < 0.05) and with about half the volume of CSF removal than continuous drainage (p = 0.002). The resulting elimination (concentration x volume) of these biochemicals, however, was not influenced by drainage method. Patients treated with continuous drainage had lower mean ICPs than those with intermittent drainage (13.6 +/- 0.69 vs. 21.8 +/- 0.95 mm Hg, p < 0.0001). We conclude that the method of CSF drainage greatly affects concentrations of CSF markers after TBI and may influence ICP. The influence of method on CSF marker concentration must be kept in mind when interpreting studies of CSF biomarkers. The striking difference in biomarker concentration, CSF volume drained, and ICP suggests the need for a randomized trial directly comparing these two approaches in infants and children with severe TBI.

Adolescent↗

PubMed2004

Vascular endothelial growth factor is increased in cerebrospinal fluid after traumatic brain injury in infants and children.

OBJECTIVE: Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis, the formation of which is triggered by hypoxia, cytokines, and growth factors and is also induced by activation of the adenosine 2B receptor. VEGF is neuroprotective in several models of experimental brain injury and is increased in brain after traumatic brain injury (TBI) in humans and experimental animals. Adenosine is a neuroprotective purine metabolite that increases in cerebrospinal fluid (CSF) after clinical TBI in children. We hypothesized that VEGF levels would 1). be increased in CSF after TBI in infants and children, and 2). be preceded by increases in CSF adenosine. To test this hypothesis, we designed a case-control study to compare the CSF of infants and children after severe TBI with that of uninjured children. METHODS: Using an Institutional Review Board-approved protocol, we compared CSF concentrations of VEGF (by enzyme-linked immunosorbent assay) and adenosine (by high-performance liquid chromatography) in 73 samples from 14 infants and children with severe TBI (Glasgow Coma Scale score <or=8) with those in CSF from 5 noninjured control subjects. Patients received standard neurointensive care. RESULTS: Mean VEGF levels were increased after TBI versus control (39.8 +/- 6.2 versus 14.9 +/- 1.5 ng/dl, mean +/- standard error of the mean, P = 0.0002) and peaked at 91.6 +/- 26.4 ng/dl, approximately 6 times control (P = 0.001). Peak VEGF occurred at 22.4 hours after injury. There was a trend toward increased adenosine concentration after TBI versus control (18.3 +/- 3.5 versus 11.5 +/- 2.3 nmol/L), but this did not reach statistical significance. A multivariate regression model showed an independent, significant association between the concentrations of VEGF and adenosine. CONCLUSION: VEGF is increased in CSF after pediatric TBI, and this increase is associated with an increase in CSF adenosine. These results may imply that a component of the vascular regenerative response of the brain is initiated rapidly after TBI and continues for several days after injury. Further investigation is warranted to determine 1). whether this association is causative, 2). the role of adenosine in triggering the increase in CSF VEGF concentration, and 3). the exact role VEGF that plays after injury.

Adenosine↗

PubMed2002

Adolescent asystolic syncope.

When the etiology of syncope is considered, age is a major parameter. Breath-holding spells are thought of as an entity of early childhood, whereas neurogenic syncope is limited to older children and adults. Both entities, however, involve a similar derangement of the autonomic nervous system. We report an adolescent with a history of breath-holding spells presenting to our institution with neurogenic syncope. Her response to vagal stimulation is consistent with that seen by other investigators in both entities. We propose that pallid breath-holding spells and neurogenic syncope are the same entity.

Adolescent↗