Search PubMed⌕ Search

Biomedical subjects

Guy M McKhann

Publications and source records attributed to Guy M McKhann.

At least 19 recordsLinked to original sources
PubMed2006

Randomized study of paclitaxel and tamoxifen deposition into human brain tumors: implications for the treatment of metastatic brain tumors.

PURPOSE: Drug resistance in brain tumors is partially mediated by the blood-brain barrier of which a key component is P-glycoprotein, which is highly expressed in cerebral capillaries. Tamoxifen is a nontoxic inhibitor of P-glycoprotein. This trial assessed, in primary and metastatic brain tumors, the differential deposition of paclitaxel and whether tamoxifen could increase paclitaxel deposition. EXPERIMENTAL DESIGN: Patients for surgical resection of their primary or metastatic brain tumors were prospectively randomized to prior paclitaxel alone (175 mg/m(2)/i.v.) or tamoxifen for 5 days followed by paclitaxel. Central and peripheral tumor, surrounding normal brain and plasma, were analyzed for paclitaxel and tamoxifen. RESULTS: Twenty-seven patients completed the study. Based on a multivariate linear regression model, no significant differences in paclitaxel concentrations between the two study arms were found after adjusting for treatment group (tamoxifen versus control). However, in analysis for tumor type, metastatic brain tumors had higher paclitaxel concentrations in the tumor center (1.93-fold, P = 0.10) and in the tumor periphery (2.46-fold, P = 0.039) compared with primary brain tumors. Pharmacokinetic analyses showed comparable paclitaxel areas under the serum concentration between treatment arms. CONCLUSIONS: Paclitaxel deposition was not increased with this tamoxifen schedule as the low plasma concentrations were likely secondary to concurrent use of P-450-inducing medications. However, the statistically higher paclitaxel deposition in the periphery of metastatic brain tumors provides functional evidence corroborating reports of decreased P-glycoprotein expression in metastatic versus primary brain tumors. This suggests that metastatic brain tumors may respond to paclitaxel if it has proven clinical efficacy for the primary tumor's histopathology.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Watershed strokes after cardiac surgery: diagnosis, etiology, and outcome.

BACKGROUND AND PURPOSE: Watershed strokes are more prevalent after cardiac surgery than in other stroke populations, but their mechanism in this setting is not understood. We investigated the role of intraoperative blood pressure in the development of watershed strokes and used MRI to evaluate diagnosis and outcomes associated with this stroke subtype. METHODS: From 1998 to 2003 we studied 98 patients with clinical stroke after cardiac surgery who underwent MRI with diffusion-weighted imaging. We used logistic regression to explore the relationship between mean arterial pressure and watershed infarcts, between watershed infarcts and outcome, and chi(2) analyses to compare detection by MRI versus CT of watershed infarcts. RESULTS: Bilateral watershed infarcts were present on 48% of MRIs and 22% of CTs (P<0.0001). Perioperative stroke patients with bilateral watershed infarcts, compared with those with other infarct patterns, were 17.3 times more likely to die, 12.5 and 6.2 times more likely to be discharged to a skilled nursing facility and to acute rehabilitation, respectively, than to be discharged home (P=0.0004). Patients with a decrease in mean arterial pressure of at least 10 mm Hg (intraoperative compared with preoperative) were 4.1 times more likely to have bilateral watershed infarcts than other infarct patterns. CONCLUSIONS: Bilateral watershed infarcts after cardiac surgery are most reliably detected by diffusion-weighted imaging MRI and are associated with poor short-term outcome, compared with other infarct types. The mechanism may include an intraoperative drop in blood pressure from a patient's baseline. These findings have implications for future clinical practice and research.

Aged↗
PubMed2006

A technique for minimally altering anatomically based subthalamic electrode targeting by microelectrode recording.

OBJECT: Implantation of a subthalamic nucleus (STN) deep brain stimulation (DBS) electrode is increasingly recognized as an effective treatment for advanced Parkinson disease (PD). Despite widespread use of microelectrode recording (MER) to delineate the boundaries of the STN prior to stimulator implantation, it remains unclear to what extent MER improves the clinical efficacy of this procedure. In this report, the authors analyze a series of patients who were treated at one surgical center to determine to what degree final electrode placement was altered, based on readings obtained with MER, from the calculated anatomical target. METHODS: Subthalamic DBS devices were placed bilaterally in nine patients with advanced PD. Frame-based volumetric magnetic resonance images were acquired and then transferred to a stereotactic workstation to determine the anterior and posterior commissure coordinates and plane. The initial anatomical target was 4 mm anterior, 4 mm deep, and 12 mm lateral to the midcommissural point. The MERs defined the STN boundaries along one or more parallel tracks, refining the final electrode placement by comparison of results with illustrations in a stereotactic atlas. In eight of 18 electrodes, the MER results did not prompt an alteration in the anatomically derived target. In another eight placements, MER altered the target by less than 1 mm and two of 18 electrode positions differed by less than 2 mm. The anterior-posterior difference was 0.53 +/- 0.65 mm, whereas the medial-lateral direction differed by 0.25 +/- 0.43 mm. The ventral boundary of the STN defined by MER was 2 +/- 0.72 mm below the calculated target (all values are the means +/- standard deviation). All patients attained clinical improvement, similar to previous reports. CONCLUSIONS: In this series of patients, microelectrode mapping of the STN altered the anatomically based target only slightly. Because it is not clear whether such minor adjustments improve clinical efficacy, a prospective clinical comparison of MER-refined and anatomical targeting may be warranted.

Brain Mapping↗
PubMed2006

Spinal cord endoplasmic reticulum stress associated with a microsomal accumulation of mutant superoxide dismutase-1 in an ALS model.

Mutation in superoxide dismutase-1 (SOD1), which is a cause of ALS, alters the folding patterns of this protein. Accumulation of misfolded mutant SOD1 might activate endoplasmic reticulum (ER) stress pathways. Here we show that transgenic mice expressing ALS-linked SOD1 mutants exhibit molecular alterations indicative of a recruitment of ER's signaling machinery. We demonstrate by biochemical and morphological methods that mutant SOD1 accumulates inside the ER, where it forms insoluble high molecular weight species and interacts with the ER chaperone immunoglobulin-binding protein. These alterations are age- and region-specific, because they develop over the course of the disease and occur in the affected spinal cord but not in the nonaffected cerebellum in transgenic mutant SOD1 mice. Our results suggest a toxic mechanism for mutant SOD1 by which this ubiquitously expressed pathogenic protein could affect motor neuron survival and contribute to the selective motor neuronal degeneration in ALS.

Animals↗
PubMed2006

Tamoxifen paradoxically decreases paclitaxel deposition into cerebrospinal fluid of brain tumor patients.

BACKGROUND: P-glycoprotein (Pgp) mediates, in part, resistance to natural product chemotherapy drugs which constitute over half of the available drugs for cancer treatment. Tamoxifen (TAM) enhances intracellular deposition of natural product chemotherapy in human cell lines by inhibition of Pgp. Pgp is highly expressed in the choroid plexus and is thought to be a key component of the blood-cerebrospinal fluid barrier (BCSFB). We conducted a prospective, randomized study to assess if Pgp inhibition by TAM alters deposition of paclitaxel in cerebrospinal fluid (CSF). METHODS: Ten patients with either primary or metastatic brain tumors were randomized to: paclitaxel alone (175 mg/m2/IV) or a course of TAM (160 mg/m2 PO BID on Days 1-5) followed by paclitaxel (175 mg/m2/IV on Day 5). CSF and plasma samples were obtained following paclitaxel infusion; paclitaxel and TAM concentrations were measured by high-performance liquid chromatography assays. RESULTS: Paclitaxel was detected in the CSF of six of the 10 patients. Peak CSF paclitaxel concentrations of the paclitaxel and paclitaxel-TAM groups ranged between 3.5-57.4 and 2.3-24.6 nM, respectively. Though there was a 2.4-fold higher mean CSF paclitaxel concentration and a 3.7-fold higher median peak CSF:plasma paclitaxel ratio for those who received paclitaxel alone as compared to combined paclitaxel-TAM, it was not statistically significant (P = 0.22). In one patient enrolled to both arms, higher CSF concentrations of paclitaxel and higher paclitaxel CSF: plasma ratios were observed when given paclitaxel alone. CONCLUSIONS: The trend towards lower paclitaxel CSF concentrations when given with TAM is consistent with the published finding that Pgp's localization in the endothelial cells of the choroid plexus works in an opposite direction and keeps drugs in the CSF. Thus, agents which inhibit Pgp, such as TAM, may increase efflux of Pgp substrates out of the BCSFB and may paradoxically lower CSF concentrations of natural product chemotherapy drugs. Conceptually, this finding implies that the Pgp in the BBB and BCSFB keeps natural toxins such as paclitaxel, from entering the brain (BBB) and, if they do enter the brain, keeps them in the CSF (BCSFB) where they may be less harmful than if they re-entered the brain. Thus, our work supports this novel idea and adds to the understanding of the functions of the BCSFB.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Cognitive and neurobehavioral dysfunction after cardiac bypass procedures.

From a cognitive standpoint, CABG as currently practiced appears to be safe for the great majority of patients, but transient changes involving memory, executive functions, and motor speed may still occur in a subset of patients during the first few days to weeks after CABG. The etiology most likely is multifactorial and includes a synergistic effect of microemboli, hypo-perfusion, and other variables associated with major surgery. Older age and degree of pre-existing cerebrovascular disease have been identified as important risk factors. The short-term cognitive changes appear to be reversible by 3 months after surgery for most patients. Late cognitive decline after CABG,occurring between 1 and 5 years after the surgery, has been well documented,but controlled studies demonstrating that this decline is specifically attributable to the use of cardiopulmonary bypass itself rather than to progression of underlying cerebrovascular disease or other age-related changes are pending.

Atrial Fibrillation↗
PubMed2006

Radiographic characteristics fail to predict clinical course after subdural electrode placement.

OBJECTIVE: Subdural arrays of grid and strip electrodes are frequently used in epilepsy patients to localize the seizure focus and determine the location of critical brain functions via stimulation mapping. Postoperatively, the majority of patients with implanted subdural electrodes develop subacute extra-axial collections (EACs). Although conservative management is appropriate in most of these cases, occasionally patients manifest neurological symptoms that may necessitate reoperation for collection evacuation. Currently, there is little information available regarding the range of EAC size and the potential correlation between EAC size and symptom development. To facilitate treatment decision-making in postoperative subdural electrode patients, we reviewed and compared the computed tomographic (CT) features of postelectrode placement EACs in asymptomatic and symptomatic patients. METHODS: We retrospectively reviewed the medical records and CT scans of 22 consecutive patients who underwent craniotomy for placement of subdural grid and strip electrodes at Columbia University Medical Center. Medical records were reviewed for neurological complications from the time of grid placement until its removal. Each EAC was measured on CT for volume (% of total cranial volume), maximal thickness, and midline shift. One patient was excluded secondary to the development of an intracerebral hemorrhage. RESULTS: Thirteen of 21 patients remained asymptomatic or minimally symptomatic during their hospitalization, with only mild to moderate, intermittent, postoperative headaches. The remaining eight developed symptoms such as persistent and severe headache, transient motor deficit, or speech impairment. Two of these patients underwent reoperation for hematoma evacuation. EACs in asymptomatic patients had a mean volume, maximal thickness, and midline shift of 5.7%, 1.25 cm, and 0.33 cm, respectively. EACs in symptomatic patients had a mean volume, maximal thickness, and midline shift of 7.7%, 1.46 cm, and 0.5 cm, respectively. Differences between maximal thickness and midline shift did not approach statistical significance. Despite this, the difference between the mean volume of symptomatic and asymptomatic EACs was statistically significant (P = 0.04). CONCLUSION: The conventional methods of midline shift and maximal thickness for assessing EAC size did not adequately differentiate symptomatic and asymptomatic subdural electrode patients with EACs. Although total volume calculation using digital planimetric analysis demonstrated a statistically significant difference, we found no clear threshold volume that correlated with clinical course. Therefore, the appearance of EACs on CT scans is of limited use in predicting the development of symptoms and possible postoperative complications after subdural grid placement. Clinical judgment must guide management and determine the potential need for reoperation.

Adolescent↗
PubMed2006

Critical postcraniotomy cerebrospinal fluid hypovolemia: risk factors and outcome analysis.

OBJECTIVE: Critical cerebrospinal fluid (CSF) hypovolemia may cause acute postoperative clinical deterioration in aneurysmal subarachnoid hemorrhage patients after craniotomy for microsurgical aneurysm clipping. We sought to identify risk factors for critical CSF hypovolemia and determine this syndrome's effect on clinical outcome. METHODS: Between April 2001 and June 2004 at Columbia University Medical Center, 16 aneurysmal subarachnoid hemorrhage patients were diagnosed with postoperative critical CSF hypovolemia, whereas 151 patients who underwent craniotomy for clipping were not. The demographics, as well as the presenting radiographic and clinical characteristics, of these groups were evaluated. In addition, a 2:1 matched case-control comparison of patients with and without critical CSF hypovolemia was completed using clinical data, operative variables, and outcome data. Outcome analysis was performed with a battery of tests designed to assess global outcome, cognitive function, independence, and quality of life. RESULTS: There was no difference in clinical grade, Fisher score, age, and sex distribution between patients diagnosed with critical CSF hypovolemia and the general aneurysmal subarachnoid hemorrhage population at Columbia University Medical Center. Subsequent 2:1 matched case-control comparison demonstrated a higher incidence of global cerebral edema on admission computed tomographic scans (75 versus 31%; P < 0.01) and a significantly longer operative time for patients with critical CSF hypovolemia (5 h 18 min versus 4 h 22 min; P < 0.03). No significant differences were observed between groups in outcome assessments at the time of hospital discharge or the 3-month follow-up examination. CONCLUSION: Risk factors associated with an increased incidence of critical CSF hypovolemia after aneurysm surgery include the presence of global cerebral edema on admission head computed tomographic scans and prolonged operative time. In such patients, heightened suspicion of CSF hypovolemia is crucial because rapid and appropriate management obviates excess morbidity and mortality.

Adult↗
PubMed2006

Ventriculoperitoneal shunting of idiopathic normal pressure hydrocephalus increases midbrain size: a potential mechanism for gait improvement.

OBJECTIVE: Idiopathic normal pressure hydrocephalus (INPH) is characterized by a classic clinical triad of symptoms, including dementia, urinary incontinence, and gait disturbance. Recent work has demonstrated that the maximal midbrain anteroposterior (AP) diameter is significantly smaller in patients with INPH than in healthy, age-matched controls. The current study was undertaken to determine the effect of ventriculoperitoneal shunt placement on midbrain dimensions in INPH patients. METHODS: Twelve consecutive INPH patients undergoing ventriculoperitoneal shunt placement with pre- and postoperative computed tomographic scans at the Columbia University Medical Center were enrolled. Each patient's pre- and postoperative maximum AP and left-to-right diameters of the midbrain at the pontomesencephalic junction were independently measured in a blinded fashion by two of the authors. The average value of each dimension was computed by calculating the mean values of the measurements of the two observers. RESULTS: Both the mean AP diameter (preoperative mean, 2.06 +/- 0.04 cm; postoperative mean, 2.27 +/- 0.05; P = 0.0007) and left-to-right diameter (preoperative mean, 2.80 +/- 0.07; postoperative mean, 3.03 +/- 0.08; P = 0.0029) increased from pre- to postoperative imaging. The approximate cross-sectional area determined as the product of AP and left-to-right diameters also increased from pre- to postoperative images (preoperative mean, 5.79 +/- 0.22 cm; postoperative mean, 6.90 +/- 0.25 cm; P = 0.00049). CONCLUSION: This study provides supportive evidence that midbrain cytoarchitecture may play a role in the pathophysiology and post-ventriculoperitoneal shunt gait improvement of INPH patients.

Aged↗
PubMed2006

Defective receptor expression and dendritic cell differentiation of monocytes in glioblastomas.

OBJECTIVE: Better characterization of the changes that occur in the circulating monocytes of patients with glioblastoma has become more important recently as monocyte-derived dendritic cells are used as adjuvants in the development of glioma vaccines. This study seeks to develop understanding of the phenotypic changes that occur in circulating monocytes of patients with intracranial cancer and to assess the ability of these cells to differentiate into mature dendritic cells. METHODS: Monocyte expression levels of HLA-ABC, HLA-DR, CD86, ICAM-1, TNFRII, and GMCSFR were compared between three cohorts: patients with intracranial glioblastoma (n = 15), patients with intracranial metastases (n = 9), and a group of healthy controls (n = 10). Monocytes were then tested for their ability to differentiate into mature dentritic cells based on morphology, CD83 expression and high levels of co-stimulatory molecules. RESULTS: Comprehensive analysis of monocyte receptor expression demonstrated significantly reduced HLA-ABC, HLA-DR, CD86, ICAM-1, and TNFRII in patients with glioblastoma but not in patients with intracranial metastases compared with a group of healthy controls. GMCSFR expression was significantly reduced in both patients with glioblastoma and intracranial metastases. Additionally, the monocytes of patients with glioblastoma showed a reduced capacity to differentiate into mature dendritic cells as identified by CD83 expression, receptor expression, and morphology. CONCLUSION: Peripheral monocytes are phenotypically altered in the setting of glioblastoma and display a reduced functional capacity to differentiate into mature dendritic cells.

Adult↗
PubMed2005

Stroke and encephalopathy after cardiac surgery: an update.

BACKGROUND AND PURPOSE: As a result of advances in surgical, anesthetic, and medical management, cardiac surgery can now be performed on older, sicker patients, some of whom have had prior cardiac interventions. As surgical mortality has declined in recent years, attention has focused on the complications of stroke and encephalopathy after cardiac surgery. SUMMARY OF REVIEW: Patients with preexisting cerebrovascular disease are at increased risk for these untoward neurological outcomes, which are associated with longer lengths of hospital stay, higher costs, and greater mortality. The mechanisms underlying these neurological events may include microemboli and hypoperfusion during surgery, and postoperative atrial fibrillation. Predictive models, based on information available before surgery, allow identification of these "high risk" patients. CONCLUSIONS: Establishing the degree of functionally significant vascular disease of the brain before surgery should be an essential part of the preoperative evaluation, particularly when modifications in surgical technique or novel neuroprotective agents are being evaluated.

Aged↗
PubMed2005

Subthalamic stimulation for Parkinson disease: determination of electrode location necessary for clinical efficacy.

OBJECT: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) performed using intraoperative microelectrode recording (MER) to adjust electrode placement has become a widely used treatment for patients with advanced Parkinson disease (PD). Few studies have been conducted to examine the location of implanted electrodes relative to the intended target, and even fewer have been undertaken to investigate the degree to which variations in the location of these electrodes impacts their clinical efficacy. This study was performed to examine these issues. METHODS: The authors located 52 bilaterally implanted DBS electrode tips on postoperative magnetic resonance (MR) images obtained in 26 consecutive patients. Postoperative and preoperative planning MR images were merged to determine the DBS electrode tip coordinates relative to the midcommissural point. Surgical records listed the intended target coordinates for each DBS electrode tip. Clinical outcome assessment included the Unified PD Rating Scale (UPDRS) motor score at 1 year, standardized questionnaires, and routine follow-up visits. The mean difference between electrode tip location and intended target for all 52 electrodes was less than 2 mm in all axes. Only one electrode was farther than 3 mm from the intended target, and this was the only electrode that had to be replaced due to lack of clinical efficacy (lack of tremor suppression); its reimplantation 4 mm more medially provided excellent tremor control. High correlation coefficients indicate that the MR imaging analysis accurately determined the anatomical location of the electrode tips. Blinded videotape reviews of UPDRS motor scores comparing effects of stimulation in patients who were "on" and "off" medication identified subgroups in whom there was minimal and maximal stimulation response. Patients in these subgroups had no differences between the MR imaging-determined actual electrode tip location and its intended location. Similarly, improvements of dyskinesias and severity of symptoms encountered during the wearing-off period for the drug did not correlate with variations of electrode tip location. CONCLUSIONS: The findings in this study lead the authors to suggest that a DBS electrode placed anywhere within a 6-mm-diameter cylinder centered at the presumed middle of the STN (based on stereotactic atlas coordinates) provides similar clinical efficacy. Future studies may be warranted to evaluate prospectively the degree to which MER modification of the anatomically and/or image-determined target improves clinical efficacy of DBS electrodes.

Adult↗
PubMed2005

Microelectrode recording-determined subthalamic nucleus length not predictive of stimulation-induced side effects.

OBJECT: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become a popular treatment for patients with medically refractory Parkinson disease. Many surgeons believe that microelectrode recording (MER) during DBS electrode implantation is needed to optimize placement, whereas stimulation-induced side effects such as paresthesias, dystonic contractions, dyskinesias, and ocular motor signs that become apparent postoperatively may be an indicator of the proximity of the electrode to various boundaries of the STN. This study was performed to evaluate the relationship between mapping of the STN by using MER and postoperative stimulation-induced side effects. METHODS: Eighty-two electrodes implanted in 75 patients between March 1999 and March 2003 were retrospectively examined to evaluate the length of the STN defined by MER, and the number of and threshold for postoperative stimulation-induced side effects. Electrodes were typically tested with increasing stimulation amplitudes (maximum 6 V) by using a monopolar array. The 82 electrodes were associated with 97 stimulation-induced side effects. The mean time between surgery and testing stimulation-induced side effects was 3.9 months. Statistical analysis (two-tailed t-test) revealed no significant difference in the number of stimulation-induced side effects (or the mean threshold for paresthesias, the most common side effect) for electrodes associated with an STN length less than 4.5 mm (13 electrodes) compared with those associated with an STN greater than or equal to 4.5 mm (69 electrodes, p = 0.616). For every electrode, the target adjustment based on MER results was within 2 mm of the image-planned target (usually 1 mm anterior). In the x axis (medial-lateral orientation), there was no systematic difference in adjustments made for the electrodes associated with the shorter compared with the longer STN lengths. In the y axis (anterior-posterior orientation), there was a very small statistically significant difference in the mean adjustment (0.4 mm) between the two groups. CONCLUSIONS: Analysis of these results suggests that a shorter MER-determined STN length alone does not reliably predict the incidence of stimulation-induced side effects.

Chi-Square Distribution↗
PubMed2005

Brain stimulation reveals critical auditory naming cortex.

One challenge in dominant temporal lobe epilepsy surgery is to remove sufficient epileptogenic tissue without compromising post-operative language functioning. Pre-resection electrical stimulation mapping enables identification of language areas that can be spared from resection, and also provides a unique opportunity to investigate brain-language relationships. Visual object naming is the gold standard for identifying 'essential' language cortex; however, sparing visual naming (VN) sites has not reliably prevented post-operative language decline. In addition to visual object naming, we included a more 'ecologically valid' auditory description naming task in our pre-resection cortical mapping protocol. Of the seven patients who had auditory naming (AN) sites removed, six declined post-operatively, whereas of the 12 patients who did not have AN sites removed, only 3 declined post-operatively (P = 0.02), suggesting an association between AN site removal and post-operative naming decline. Interestingly, although VN sites were preserved in all patients, AN site removal resulted in decline in both auditory and VN tasks. These findings not only have potentially critical clinical significance, but also argue for modality specificity, with considerable integration within the semantic system.

Adolescent↗
PubMed2005

Neurocognitive complications after coronary artery bypass surgery.

Both short- and long-term cognitive changes continue to occur after coronary artery bypass grafting (CABG), but the pathophysiology of these neurobehavioral changes remains incompletely understood. The persistence of mild postoperative neurocognitive changes despite multiple improvements in the cardiopulmonary bypass procedure may be partially because of surgical populations being older and having more prevalent comorbid disease. The cause of the early postoperative changes is most likely multifactorial and may include ischemic injury from microemboli, hypoperfusion, and other factors resulting from major surgery. Several lines of evidence suggest that the late cognitive decline between 1 and 5 years after surgery may be secondary to high rates of cerebrovascular disease among candidates for CABG. A history of hypertension and other risk factors for vascular disease is known to be associated with increased risk for long-term cognitive decline in community-dwelling elderly individuals. Cerebrovascular risk factors are also associated with silent magnetic resonance imaging abnormalities in patients undergoing CABG. Thus, whereas both short- and long-term postoperative cognitive changes have been associated with CABG, only the short-term, transient changes appear to be directly related to the use of cardiopulmonary bypass.

Anesthesia↗
PubMed2005

Electrophysiological and morphological characterization of dentate astrocytes in the hippocampus.

We studied electrophysiological and morphological properties of astrocytes in the dentate gyrus of the rat hippocampus in slices. Intracellular application of Lucifer yellow revealed two types of morphology: one with a long process extruding from the cell body, and the other with numerous short processes surrounding the cell body. Their electrophysiological properties were either passive, that is, no detectable voltage-dependent conductance, or complex, with Na+/K+ currents similar to those reported in the Ammon's horn astrocytes. We did not find any morphological correlate to the types of electrophysiological profile or dye coupling. Chelation of cytoplasmic calcium ([Ca2+]i) by BAPTA increased the incidence of detecting a low Na+) conductance and transient outward K+ currents. However, an inwardly rectifying K+ current (Kir), a hallmark of differentiated CA1/3 astrocytes, was not a representative K+-current in the complex dentate astrocytes, suggesting that these astrocytes could retain an immature form of K-currents. Dentate astrocytes may possess a distinct current profile that is different from those in CA1/3 Ammon's horn.

Animals↗
PubMed2005

Cognitive outcomes three years after coronary artery bypass surgery: a comparison of on-pump coronary artery bypass graft surgery and nonsurgical controls.

BACKGROUND: Coronary artery bypass grafting has been associated with both early and late postoperative cognitive decline, but interpretation of previous studies has been limited by lack of appropriate control groups. We compared changes in cognitive performance from baseline to 3 years in patients undergoing coronary artery bypass grafting with those of a control group of patients with known risk factors for coronary artery disease but without surgery. METHODS: Patients undergoing coronary artery bypass grafting (n = 140) and a demographically similar nonsurgical control group with coronary artery disease (n = 92) completed baseline neuropsychological assessment and were followed up prospectively at 3, 12, and 36 months. Cognitive performance was assessed with a battery of neuropsychological tests, measuring the cognitive domains of attention, language, verbal and visual memory, visuospatial, executive function, and psychomotor and motor speed. The statistical analyses were performed in two ways: using data from all tested individuals, and using a model imputing missing observations for individuals lost to follow-up. RESULTS: Both the coronary artery bypass grafting and nonsurgical control groups improved from baseline to 1 year, with additional improvement between 1 and 3 years for some cognitive tests. The coronary artery bypass grafting group had statistically significantly greater improvement than the nonsurgical controls for some subtests, and had a comparable longitudinal course for the remainder of the subtests. Both study groups had a trend toward nonsignificant decline at 3 years on some measures, but the overall differences between groups over time were not statistically significant. CONCLUSIONS: Prospective longitudinal neuropsychological performance of patients with coronary artery bypass grafting did not differ from that of a comparable nonsurgical control group of patients with coronary artery disease at 1 or 3 years after baseline examination. This finding suggests that previously reported late cognitive decline after coronary artery bypass grafting may not be specific to the use of cardiopulmonary bypass, but may also occur in patients with similar risk factors for cardiovascular and cerebrovascular disease.

Cognition↗