Biomedical subjects

R S Marshall

Publications and source records attributed to R S Marshall.

At least 19 recordsLinked to original sources

PubMed2006

Time course of cholinesterase inhibition in adult rats treated acutely with carbaryl, carbofuran, formetanate, methomyl, methiocarb, oxamyl or propoxur.

To compare the toxicity of seven N-methyl carbamates, time course profiles for brain and red blood cell (RBC) cholinesterase (ChE) inhibition were established for each. Adult, male, Long Evans rats (n=4-5 dose group) were dosed orally with either carbaryl (30 mg/kg in corn oil); carbofuran (0.5 mg/kg in corn oil); formetanate HCl (10 mg/kg in water); methomyl (3 mg/kg in water); methiocarb (25 mg/kg in corn oil); oxamyl (1 mg/kg in water); or propoxur (20 mg/kg in corn oil). This level of dosing produced at least 40% brain ChE inhibition. Brain and blood were taken from 0.5 to 24 h after dosing for analysis of ChE activity using two different methods: (1) a radiometric method which limits the amount of reactivation of ChE activity, and (2) a spectrophotometric method (Ellman method using traditional, unmodified conditions) which may encourage reactivation. The time of peak ChE inhibition was similar for all seven N-methyl carbamate pesticides: 0.5-1.0 h after dosing. By 24 h, brain and RBC ChE activity in all animals returned to normal. The spectrophotometric method underestimated ChE inhibition. Moreover, there was a strong, direct correlation between brain and RBC ChE activity (radiometric assay) for all seven compounds combined (r(2)=0.73, slope 1.1), while the spectrophotometric analysis of the same samples showed a poor correlation (r(2)=0.09). For formetanate, propoxur, methomyl, and methiocarb, brain and RBC ChE inhibitions were not different over time, but for carbaryl, carbofuran and oxamyl, the RBC ChE was slightly more inhibited than brain ChE. These data indicate (1) the radiometric method is superior for analyses of ChE activity in tissues from carbamate-treated animals (2) that animals treated with these N-methyl carbamate pesticides are affected rapidly, and recover rapidly, and (3) generally, assessment of RBC ChE is an accurate predictor of brain ChE inhibition for these seven pesticides.

Animals↗

PubMed2006

Cerebrovascular reactivity and vasospasm after subarachnoid hemorrhage: a pilot study.

The authors performed serial transcranial Doppler (TCD) and carbon dioxide reactivity (CO2R) testing in 20 aneurysmal subarachnoid hemorrhage patients to determine whether impaired cerebrovascular reactivity was associated with symptomatic vasospasm. Symptomatic vasospasm occurred in 9 of 14 patients with abnormal CO2R and in none of 6 patients with preserved reactivity (p = 0.011). Abnormal CO2R preceded the onset of vasospasm in 7 of 9 patients. Abnormal standard TCD testing was not associated with vasospasm.

Adult↗

PubMed2005

Neurobehavioral effects of chronic dietary and repeated high-level spike exposure to chlorpyrifos in rats.

This study aimed to model long-term subtoxic human exposure to an organophosphorus pesticide, chlorpyrifos, and to examine the influence of that exposure on the response to intermittent high-dose acute challenges. Adult Long-Evans male rats were maintained at 350 g body weight by limited access to a chlorpyrifos-containing diet to produce an intake of 0, 1, or 5 mg/kg/day chlorpyrifos. During the year-long exposure, half of the rats in each dose group received bi-monthly challenges (spikes) of chlorpyrifos, and the other half received vehicle. Rats were periodically tested using a neurological battery of evaluations and motor activity to evaluate the magnitude of the acute response (spike days) as well as recovery and ongoing chronic effects (non-spike days). Effects of the spikes differed as a function of dietary level for several endpoints (e.g., tremor, lacrimation), and in general, the high-dose feed groups showed greater effects of the spike doses. Animals receiving the spikes also showed some neurobehavioral differences among treatment groups (e.g., hypothermia, sensory and neuromotor differences) in the intervening months. During the eleventh month, rats were tested in a Morris water maze. There were some cognitive deficits observed, demonstrated by slightly longer latency during spatial training, and decreased preference for the correct quadrant on probe trials. A consistent finding in the water maze was one of altered swim patterning, or search strategy. The high-dose feed groups showed more tendency to swim in the outer annulus or to swim very close to the walls of the tank (thigmotaxic behavior). Overall, dietary exposure to chlorpyrifos produced long-lasting neurobehavioral changes and also altered the response to acute challenges.

Animals↗

PubMed2003

Urgent endovascular revascularization for symptomatic intracranial atherosclerotic stenosis.

BACKGROUND: Endovascular revascularization for intracranial atherosclerotic stenoses is being increasingly performed at major medical centers and has been reported to be technically feasible and safe. The authors report their experience with patients who underwent such a procedure for impending stroke and neurologic instability. METHOD: All 18 patients (21 intracranial lesions) treated between 1997 and 2002 at the authors' institution with endovascular revascularization were retrospectively reviewed. Each patient had failed maximal medical therapy and was thought to be at high risk for an imminent stroke. RESULTS: Endovascular revascularization was performed on eight distal internal carotid artery lesions, six middle cerebral artery lesions, four intracranial vertebral artery lesions, and three basilar artery lesions. Recanalization was complete in 5 arteries (Thrombolysis in Myocardial Infarction [TIMI] Grade III), partial in 14 arteries (TIMI Grade II), and complete occlusion (TIMI 0) developed in 1 artery. In a patient with a tight basilar stenosis, no angioplasty could be performed because of the inability to cross the stenosis with the guidewire. Major periprocedural complications occurred in 9 (50%) patients: intracranial hemorrhage in 3 (17%), disabling ischemic stroke in 2 (11%), and major extracranial hemorrhage in 4 (22%). Three patients died: one from intracerebral hemorrhage and two from cardiorespiratory failure. CONCLUSIONS: Endovascular revascularization of intracranial vessels is technically feasible and may be performed successfully. However, periprocedural complication and fatality rates in neurologically unstable patients are high. The results suggest that patient selection, procedure timing, and periprocedural medical management are critical factors to reduce periprocedural morbidity and mortality.

Adult↗

PubMed2001

Recovery of brain function during induced cerebral hypoperfusion.

We used the setting of clinically indicated internal carotid artery balloon test occlusions in 44 patients with inoperable carotid cavernous aneurysms or head and neck tumours to examine real-time changes in higher cerebral function that correlate with specific levels of cerebral blood flow. By making detailed haemodynamic and neurobehavioural measurements during the 30 min the carotid artery was occluded, we were able to quantify higher cerebral function patterns in relation to absolute cerebral blood flow (CBF) levels. We found that once the carotid artery was occluded, patients whose CBF averaged 47 ml/100 g/min (no different from baseline) maintained consistent performance on a sustained attention task; those whose CBF dropped to an average 37 ml/100 g/min had a reversible deterioration of sustained attention, and those whose CBF fell to 27 ml/100 g/min had impaired sustained attention that persisted until the carotid occlusion was reversed. The relevance of these results to the pathological state of clinical stroke is discussed with respect to the haemodynamic and physiological mechanisms that may determine how brain function is lost and regained in the setting of acute cerebral hypoperfusion.

Attention↗

PubMed2001

Effect of intracarotid papaverine on human cerebral blood flow and vascular resistance during acute hemispheric arterial hypotension.

This study assessed the feasibility of augmenting cerebral blood flow (CBF) and decreasing hemispheric cerebrovascular resistance (CVR) by intracarotid papaverine during acute cerebral hypotension. Awake patients (n = 10) undergoing transfemoral balloon occlusion of an internal carotid artery (ICA) with nitroprusside (SNP)-induced systemic hypotension (10% reduction of mean arterial pressure) were studied. We measured mean femoral artery pressure (MAP), mean distal ICA pressure (P(ica)), and CBF (intracarotid 133Xe) at two time points: before and after intracarotid papaverine infusion (1 or 7 mg/min). Two patients became symptomatic immediately after ICA occlusion and were excluded. One patient developed a focal seizure during papaverine infusion. In another, the occlusion balloon deflated prematurely. Of the remaining six patients, two of the three patients who received high-dose papaverine (7 mg/min) developed transient obtundation. The remaining three patients, who received low-dose papaverine (1 mg/min), did not develop any neurologic symptoms. There was a trend for intracarotid papaverine to increase hemispheric CBF by 36% (33 +/- 10 versus 45 +/- 22 ml x 100 g(-1) x min(-1), P = .084, n = 6); papaverine decreased CVR from 1.3 +/- 0.4 to 1.0 +/- 0.3 mm Hg x ml(-1) x 100 g(-1) x min(-1) (P = .049). There was no significant change in heart rate, MAP, or P(ica) during experimental protocol. Manipulation of CVR by intracarotid papaverine during acute hemispheric arterial hypotension appears to be feasible. Further studies are needed to establish safety and efficacy.

Aged↗

PubMed2000

The experience of Wernicke's aphasia.

The authors induced a transient Wernicke's aphasia in a patient with left frontal arteriovenous malformation by superselective Wada injection exclusively into the lower division of the left middle cerebral artery. The patient was then asked to recall his experience, which the authors matched against his language during anesthesia. The patient's account showed that there was a more systematic attempt to respond appropriately than the authors could infer from his overt behavior. His narrative suggests that a thought process not measured by aphasia examinations may exist independent of language.

Aphasia, Wernicke↗

PubMed2000

Late intra-arterial thrombolysis.

A 70-year-old woman with a progressive dominant hemisphere syndrome but only mild hemiparesis and a normal brain scan (>3 hours from stroke onset) showed angiographic occlusion of the left anterior cerebral artery and the middle cerebral artery at its trifurcation with preservation of the rolandic artery. Intra-arterial thrombolysis was started >6 hours from onset of symptoms. Recanalization occurred and the patient recovered with a transcortical motor aphasia and no motor deficit. A negative brain scan and an incomplete large hemispheric syndrome may indicate an extended time-window for intra-arterial thrombolysis.

Aged↗

PubMed2000

Interhemispheric transfer of language in patients with left frontal cerebral arteriovenous malformation.

Cerebral arteriovenous malformations (AVMs) are frequently evaluated before therapeutic embolization by superselective injection of anesthetics into individual arterial branches so as to determine whether permanent occlusion would affect eloquent function. In Experiment 1, we used this adaptation of the Wada procedure to study three right-handed adult patients with left frontal cerebral AVMs by injecting vessels in Wernicke's and Broca's areas, respectively, and assessing language functions. The results showed that superselective testing in the inferior division of the left MCA in all three patients produced a dense Wernicke's aphasia. Injections into the left frontal regions, however, resulted in right paresis in all patients, but no language deficits including no loss of fluency. In Experiment 2, Patient 2 underwent fMRI activation for spontaneous word-list generation using multi-slice echo planar BOLD techniques at 1.5 Tesla. A voxel-by-voxel comparison of rest vs activation for each task was performed with a Z-score threshold of 2.5 SD for activated voxels. There was activation in the right hemisphere in the insula, frontal operculum pars opercularis, and inferior frontal gyrus, an area homologous to Broca's area in the left hemisphere. There was also activation in the left hemisphere in the Rolandic region, but language function was unaffected during Wada testing in this area. These data suggested that features of expressive language were no longer controlled by the left frontal lobe where the AVM was located, and provided new evidence for interhemispheric re-organization under conditions of chronic neurovascular disease.

Adult↗

PubMed2000

Subcortical infarction resulting in acquired stuttering.

Stuttering is an uncommon presentation of acute stroke. Reported cases have often been associated with left sided cortical lesions, aphasia, and difficulties with other non-linguistic tests of rhythmic motor control. Three patients with subcortical lesions resulting in stuttering are discussed. In one patient the ability to perform time estimations with a computerised repetitive time estimation task was characterised. One patient had a pontine infarct with clinical evidence of cerebellar dysfunction. A second patient had a left basal ganglionic infarct and a disruption of timing estimation. A third patient had a left subcortical infarct and a mild aphasia. These findings expand the reported distribution of infarction that can result in acquired stuttering. Subcortical mechanisms of speech control and timing may contribute to the pathophysiology of acquired stuttering.

Brain↗

PubMed2000

Evolution of cortical activation during recovery from corticospinal tract infarction.

BACKGROUND AND PURPOSE: Recovery from hemiparesis due to corticospinal tract infarction is well documented, but the mechanism of recovery is unknown. Functional MRI (fMRI) provides a means of identifying focal brain activity related to movement of a paretic hand. Although prior studies have suggested that supplementary motor regions in the ipsilesional and contralesional hemisphere play a role in recovery, little is known about the time course of cortical activation in these regions as recovery proceeds. METHODS: Eight patients with first-ever corticospinal tract lacunes causing hemiparesis had serial fMRIs within the first few days after stroke and at 3 to 6 months. Six healthy subjects were used as controls. Statistically significant voxels during a finger-thumb opposition task were identified with an automated image processing program. An index of ipsilateral versus contralateral activity was used to compare relative contributions of the 2 hemispheres to motor function in the acute and chronic phases after stroke. RESULTS: Controls showed expected activation in the contralateral sensorimotor cortex (SMC), premotor, and supplementary motor areas. Stroke patients differed from control patients in showing greater activation in the ipsilateral SMC, ipsilateral posterior parietal, and bilateral prefrontal regions. Compared with the nonparetic hand, the ratio of contralateral to ipsilateral SMC activity during movement of the paretic hand increased significantly over time as the paretic hand regained function. CONCLUSIONS: The evolution of activation in the SMC from early contralesional activity to late ipsilesional activity suggests that a dynamic bihemispheric reorganization of motor networks occurs during recovery from hemiparesis.

Adult↗

PubMed1999

Developmental deficits in adult patients with arteriovenous malformations.

BACKGROUND: Cerebral arteriovenous malformations (AVMs) are congenital masses of arteries and veins that appear to undergo an unclear "maturation" for many years. Using structured interviews, we compared developmental history of adult patients with AVM with a comparison group of patients with cerebral tumor or aneurysm. OBJECTIVE: To determine whether a remote history of developmental abnormality in adult patients with AVM might be an early marker of cerebral status. DESIGN: Adult patients with AVM and a comparison group of patients with cerebral aneurysm or low-grade tumor participated in a survey. SETTING: Urban medical school-based tertiary care center. PATIENTS: Forty-four randomly selected patients with AVM from the Columbia-Presbyterian AVM Database. There were 32 comparison patients:15 randomly chosen patients from the institution's Cerebral Aneurysm Database and all 17 patients who underwent a biopsy from 1990 to 1995 with a diagnosis of low-grade tumor and who could be contacted. MAIN OUTCOME MEASURES: A brief, structured interview adapted from the Centers for Disease Control and Prevention for its 1994 study of the prevalence of learning disabilities in American children. We defined the positive occurrence of a condition as an affirmative answer to the question, " Did have (condition) during his/her school-age years?" Each patient was also asked if there had been any problems in the following skill areas: reading, writing, listening, speaking, attention, impulsivity, organization, mathematics, or drawing. The AVM size was calculated on the angiographic film by measuring its longest diameter in any dimension. RESULTS: Patients with AVM were significantly more likely to report a positive occurrence to any survey question (P<.05). Two thirds of all patients with AVM (66%) reported at least 1 skill difficulty during their school years, significantly more than the comparison group (P<.001). Neither the maximum AVM diameter nor the occurrence of hemorrhage as an adult differed between patients with AVM with and without early skill difficulty. CONCLUSIONS: Patients with AVM are more likely to report a developmental learning disorder than patients with tumor or aneurysm despite the absence of other neurologic symptoms of diseases not diagnosed for another 20 years. These data support the notion that disorders of behavioral and intellectual function are sensitive markers of early cerebral status.

Adult↗

PubMed1999

Higher cerebral function and hemispheric blood flow during awake carotid artery balloon test occlusions.

OBJECTIVES: Measures capable of detecting early alterations of brain function during acute cerebral ischaemia have not been adequately defined. Internal carotid artery (ICA) test occlusions provide a well controlled environment to investigate the effects of reversible acute hemispheric hypoperfusion on brain function. A continuous time estimation task was developed that reliably demonstrated alterations in higher cerebral function before development of any deficits in elementary neurological function during ICA balloon catheter test occlusions. In the present study, we hypothesised that alterations in our behavioural task would correlate significantly with absolute level of ipsilateral CBF. METHODS: Twenty five patients underwent awake ICA test occlusions during which sustained attention and ipsilateral CBF were measured simultaneously using our time estimation task and the intracarotid 133Xe washout method. Alteration in sustained attention was correlated with CBF after occlusion using Fisher's exact test. RESULTS: Deterioration in sustained attention was significantly associated with ipsilateral CBF below 30 ml/g/min (Fisher's exact test, p=0.047). Changes in individual patients' performance on the behavioural task correlated in real time with changes occurring either at the point of occlusion or at a specific threshold of induced hypotension. Sensitivity for our behavioural test in predicting CBF was 75%; specificity 70%. CONCLUSIONS: Monitoring sustained attention during carotid balloon test occlusions seems to be a sensitive means to detect decreases in CBF as measured by 133Xe washout. Correlation between higher cerebral function and CBF can allow more detailed investigations of physiological relations between cerebral haemodynamics and brain function in human conditions of cerebral ischaemia.

Adult↗

PubMed1998

SPECT imaging of odor identification in schizophrenia.

Deficits in olfactory identification, despite normal odor perception, are found in some neuropsychiatric disorders, including schizophrenia. We examined if regional cerebral blood flow (rCBF) differed between schizophrenia patients and controls during odor identification, hypothesizing that these brain regions could be relevant to odor identification impairments. Eight schizophrenia and eight comparison subjects provided a baseline (picture identity matching) and activation (odor identification) SPECT scan, obtained using 99mTc-HMPAO in a low dose/high dose design. Six patients and seven controls had analyzable data. MEDX data saved in ANALYZE format for SPM 95 generated paired t-test statistical data for display in Talairach space, with rCBF changes given as Z-scores. There was no schizophrenia vs. control group difference in rCBF for the baseline picture-matching test. For odor identification, schizophrenia patients had a hypometabolic right-sided cortical region that included the frontal lobe Broca's area, superior temporal lobe, and supramarginal and angular gyri. Post hoc within-group contrasts of picture-matching vs. odor identification showed that the controls significantly increased rCBF in the right-sided inferior temporal fusiform gyrus, and bilateral hippocampi and visual association areas for the odor test. The schizophrenia group showed no rCBF differences for picture-matching compared to odor identification. Patients showed significant hypometabolism in right-sided cortical areas for odor identification. They also failed to show increased rCBF in the hippocampus and visual association area, as seen in controls for odor identification compared to picture-matching. These regions may be unique to schizophrenia or have broader implications for olfactory memory retrieval.

Adult↗

PubMed1998

Stimulus context in hemineglect.

Rightward deviation on bisection of a horizontal line is well described in patients with right brain injury and left hemineglect. Because of the observation that hemineglect patients may bisect very short lines to the left of the true midpoint (the so-called crossover effect), additional models have been proposed to incorporate this finding into existing theories of hemineglect. We investigated a line-length effect in six patients with left hemineglect. When presented with any set of lines of uniform (reference) length, percentage rightward deviation on line bisection remained constant across different line lengths. When lines of a second length were mixed into any uniform set of lines, bisection performance on the reference lines changed. A rightward shift in the perceived midpoint of the reference line occurred if the added lines were shorter than the reference lines; a leftward shift occurred if the added lines were longer. Leftward shifts included shifts across the true midpoint, reproducing the crossover effect. Shifts in the perceived midpoint occurred both on a manual line bisection task and on a line bisection discrimination task in which no manual response was required. We propose that the crossover effect may be part of a more general stimulus-context effect in which the perceived midpoint of a line is related not to absolute length, but to the line's length relative to other lines with which it is presented. Such a context effect has not hitherto been described in the neglect syndrome. A possible mechanism for the effect is a generalization of length estimation produced by the combined influence of the focal stimulus and all stimuli that precede it.

Adult↗

PubMed1997

Changes in regional cerebral blood flow related to line bisection discrimination and visual attention using HMPAO-SPECT.

Behavioral tasks requiring visual-spatial discrimination such as line bisection are used clinically to assess right hemisphere function, yet the anatomical substrate of line bisection has yet to be elucidated by functional imaging. In the current study, nine right-handed, healthy adult subjects underwent split-dose technetium-99m-hexamethylpropylene amine oxime single photon emission tomography during performance of two visual tasks. Statistical parametric maps that represented significant changes in regional cerebral blood flow (rCBF) for each task were generated. Increases in rCBF were seen in the right dorsolateral prefrontal cortex, the insula, and the superior temporal lobe with a line-bisection discrimination task, whereas increases in the visual association areas, the posterior cingulate gyrus bilaterally, and the anterior cingulate gyrus on the right were seen with a similar control task which required sustained visual attention, but no visual spatial discrimination. We conclude that distinct areas in the nondominant hemisphere can be shown to be active during performance of line-bisection discrimination and sustained visual attention.

Adult↗

PubMed1997

Manipulation of cerebrovascular resistance during internal carotid artery occlusion by intraarterial verapamil.

UNLABELLED: Occlusion of the internal carotid artery (ICA) results in acute cerebral hypotension. We hypothesized that during acute cerebral hypotension, in addition to physiological autoregulation, further arteriolar relaxation is possible by pharmacological means. We tested the feasibility of using intracarotid verapamil, a calcium channel blocker, to decrease the cerebrovascular resistance (CVR) and augment cerebral blood flow (CBF) at low postocclusion distal ICA pressures (PICA). Eleven patients undergoing trial occlusion of ICA were enrolled. Distal ICA or stump pressure, hemispheric CBF, and CVR were determined before and after carotid occlusion. During ICA occlusion, CBF and other physiological variables were determined before and after intracarotid verapamil. Two patients were excluded from the study. Carotid occlusion (n = 9) significantly decreased PICA (mean +/- SD, from 82 +/- 22 to 46 +/- 11 mm Hg, P = 0.001) and CBF (from 42 +/- 11 to 33 +/- 11 mL.100 g-1.min-1, P < 0.05). During occlusion, after intracarotid verapamil (3.9 +/- 1.6 mg), hemispheric CBF tended to increase from 31 +/- 11 to 35 +/- 14 mL.100 g-1.min-1 (P = 0.067). However, the percent increase in CBF after verapamil was a linear function of PICA (y = 1.01 x -32, n = 9, r2 = 0.84, P = 0.006). The decrease in CBF during carotid occlusion suggests that near maximal cerebral autoregulatory vasodilation had occurred, although our results indicate that it may be feasible to further augment CBF by pharmacological means during acute cerebral hypotension. IMPLICATIONS: When the internal carotid artery is occluded during neurosurgical procedures, there may be a significant reduction in cerebral perfusion. The authors have demonstrated that the intraarterial administration of verapamil increases cerebral blood flow as a linear function of cerebral artery pressure. Intracarotid injection of vasodilators may augment cerebral blood flow during acute cerebral hypotension.

Adult↗

PubMed1997

Treatment of inoperable carotid aneurysms with endovascular carotid occlusion after extracranial-intracranial bypass surgery.

OBJECTIVE: Hunterian ligation of the internal carotid artery (ICA) is an accepted treatment for inoperable carotid aneurysms. Preliminary extracranial-intracranial (EC-IC) bypass surgery is required in some patients. The reported incidence of thromboembolic and ischemic complications remains significant for these patients, despite a variety of advocated management strategies. We present our treatment paradigm. METHODS: Between April 1992 and March 1997, nine patients with inoperable ICA aneurysms were treated using EC-IC bypass surgery and then permanent endovascular ICA occlusion. All of the patients except one had been selected for bypass surgery on the basis of failing results of the ICA test occlusion with hypotensive challenge. ICA occlusion was performed by endovascular means and was delayed after bypass surgery was performed by a mean of 6 days (range, 2-20 d). All patients were managed in the intensive care unit after ICA occlusion. RESULTS: Clinical improvement was noted in all patients (mean follow-up, 21 mo; range, 3-42 mo). There were no major complications. Aneurysmal thrombosis was confirmed in all patients. Although ICA occlusion was delayed after bypass surgery, only one bypass was noted to be occluded. The occluded bypass occurred in a patient who subsequently underwent successful ICA occlusion. This patient was thought to have been improperly selected for bypass surgery. CONCLUSION: Certain carotid aneurysms can be effectively managed with hunterian ICA ligation. After preliminary identification of patients with borderline cerebrovascular reserve as candidates for EC-IC bypass surgery, close attention to the following points may help enhance clinical outcome: 1) excellence in surgical technique for EC-IC bypass surgery, 2) occlusion of the parent vessel as close to the aneurysm neck as possible by endovascular means, and 3) judicious postoperative combination of anticoagulation, fluid, and pressure management.

Adult↗