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Biomedical subjects

John Pile-Spellman

Publications and source records attributed to John Pile-Spellman.

30 records · Page 2Linked to original sources

Histopathological evaluation of middle cerebral artery after percutaneous intracranial transluminal angioplasty.

BACKGROUND: Intracranial atherosclerosis accounts for 8% to 10% of all ischemic strokes, and intracranial angioplasty is increasingly performed to treat stenotic lesions. We report an autopsy case and discuss the effects of intracranial angioplasty for atherosclerotic arteries. CASE DESCRIPTION: A 77-year-old patient died 9 days after angioplasty of the left middle cerebral artery as a result of cardiorespiratory failure. The patient was anticoagulated before, during, and after the procedure with heparin, aspirin, and clopidogrel. At the site of angioplasty, the densely fibrotic eccentric plaque was displaced from the adjacent media into the lumen, distorting it and forming elongated projections. No local thrombosis, plaque compression, or inflammation was observed. Additionally, an intramural hemorrhage extended from the site of angioplasty into the stenotic proximal inferior division of the left middle cerebral artery. CONCLUSIONS: Histopathological findings after intracranial angioplasty parallel those in other arterial territories. The implications of these pathological findings on the medical and endovascular treatment of intracranial atherosclerosis are discussed.

Aged↗

Conducting stroke research with an exception from the requirement for informed consent.

BACKGROUND: Obtaining viable informed consent from stroke patients for participation in clinical trials of acute stroke therapies is often problematic because of patients' neurological deficits. Furthermore, obtaining permission from surrogates is often not possible or not legally permissible. SUMMARY OF REVIEW: In 1996 the Food and Drug Administration and Department of Health and Human Services published regulations that allow investigators to conduct emergency research without patient consent under a narrowly defined set of circumstances. We review requirements of these regulations, paying particular attention to how they may be applied in a clinical trial of an acute stroke therapy. CONCLUSIONS: Acute stroke researchers should consider conducting clinical trials with an exception from the informed consent requirement permitted by this law.

Clinical Trials Data Monitoring Committees↗

Despite in vitro increase in cyclic guanosine monophosphate concentrations, intracarotid nitroprusside fails to augment cerebral blood flow of healthy baboons.

BACKGROUND: During cerebral angiography, intracarotid infusion of sodium nitroprusside (SNP), an endothelium-independent nitric oxide donor, fails to increase cerebral blood flow (CBF) of human subjects. A confounding effect of intracranial pathology or that of radiocontrast could not be ruled out in these experiments. The authors hypothesized that, if nitric oxide was a significant regulator of CBF of primates, then intracarotid SNP will augment CBF of baboons. METHODS: In studies, CBF (intraarterial (133)Xe technique) was measured in healthy baboons during isoflurane anesthesia at (1) baseline and during (2) induced hypertension with intravenous phenylephrine, (3) concurrent infusions of intravenous phenylephrine and intracarotid SNP, and (4) intracarotid verapamil (positive control drug). In studies, the authors measured tissue cyclic guanosine monophosphate (cGMP) by radioimmunoassay after incubating vascular rings obtained from freshly killed baboons (1) with increasing concentrations of SNP and (2) after SNP exposure following preincubation with the radiocontrast agent, iohexhol. RESULTS: In the studies, coinfusion of intravenous phenylephrine and intracarotid SNP did not increase CBF. However, intracarotid verapamil significantly increased CBF (from 26 +/- 7 to 43 +/- 11 ml x 100 g(-1) x min(-1); P < 0.0001) without a change in mean arterial pressure. In the studies, incubation of intracranial arterial rings in SNP resulted in dose-dependent increases in cGMP concentrations. A similar increase in cGMP content was evident despite iohexhol preincubation. CONCLUSIONS: Collectively, these results suggest that, in healthy baboons, intracarotid SNP does not decrease arteriolar resistance, although SNP could affect proximal arterial tone, as demonstrated by the increase in cGMP content of these vessels.

Animals↗

Neurobehavioral differences in superselective Wada testing with amobarbital versus lidocaine.

Four patients with cerebral arteriovenous malformations (AVMs) underwent superselective Wada testing with intraarterial amobarbital and lidocaine before embolization. In all four patients, the use of lidocaine detected clinically significant neurologic deficits that amobarbital alone did not, likely because of the pharmacodynamic differences of the two agents. The use of lidocaine with amobarbital for superselective Wada testing in patients with cerebral AVMs may improve the sensitivity and predictive value of this test in the future.

Adult↗

Real-time magnetic resonance imaging for interventional neuroradiological procedures.

Over the last two decades, interventional neuroradiologists have developed powerful techniques for the treatment of cerebrovascular disorders and brain tumors. Current interventional neuroradiological procedures are performed under X-ray fluoroscopy, which has allowed for high temporal and spatial resolution. However, these imaging techniques do not provide the treating physician with vital anatomic and functional information regarding vessel walls and the surrounding brain tissue. Better visualization of vessel structures and real-time information about the state of perfusion and metabolism of the surrounding brain tissue (real-time magnetic resonance arteriography, diffusion and perfusion-weighted imaging, apparent diffusion coefficient maps) would enhance safety and efficacy of neuroendovascular procedures available currently. Recent advances in magnetic resonance hardware and software have permitted significant enhancements in temporal and spatial resolution, which have resulted in the capability of visualizing anatomic structures with real-time fluoroscopy and angiography. This review outlines how real-time magnetic resonance procedures may replace conventional X-ray fluoroscopy in diagnostic and interventional neuroradiology during the next decade.

Brain Neoplasms↗

In nonhuman primates intracarotid adenosine, but not sodium nitroprusside, increases cerebral blood flow.

UNLABELLED: Intracarotid infusion of short-acting vasodilators, such as adenosine and nitroprusside, in doses that lack significant systemic side effects, may permit controlled manipulation of cerebrovascular resistance. In this experiment we assessed changes in cerebral blood flow (CBF) after intracarotid infusion of nitroprusside and adenosine. The study was conducted on six adult baboons under isoflurane anesthesia and controlled ventilation. Intracarotid drug infusion protocol avoided hypotension during nitroprusside infusion and tested for autoregulatory vasoconstriction. CBF (intraarterial (133)Xe technique) was measured four times during infusions of 1) intracarotid saline, 2) IV phenylephrine (0.2 microg x kg(-1) x min(-1)) aimed to increase mean arterial pressure by 10-15 mm Hg, 3) IV phenylephrine and intracarotid nitroprusside (0.5 microg x kg(-1) x min(-1)), and 4) intracarotid adenosine (1 mg/min). IV phenylephrine increased mean arterial pressure (69 +/- 8 to 91 +/- 9 mm Hg, P < 0.0001, n = 6), and concurrent infusion of intracarotid nitroprusside reversed this effect. However, compared with baseline, CBF did not change with IV phenylephrine or with concurrent infusion of IV phenylephrine and intracarotid nitroprusside. Intracarotid adenosine profoundly increased CBF (from 29 +/- 8 to 75 +/- 32 mL x 100 g(-1) x min(-1); P < 0.0001). In nonhuman primates, intracarotid adenosine increases CBF in doses that lack significant systemic side effects, whereas intracarotid nitroprusside has no effect. Intracarotid adenosine may be useful for manipulating cerebrovascular resistance and augmenting CBF during cerebral ischemia. IMPLICATIONS: Intraarterial (133)Xe cerebral blood flow (CBF) measurements suggest that intracarotid adenosine, in a dose that lacks significant systemic side effects, profoundly increases CBF, whereas nitroprusside has no effect.(5-12)

Adenosine↗

Intracarotid nitroprusside does not augment cerebral blood flow in human subjects.

BACKGROUND: The recent resurgence of interest in the cerebrovascular effects of nitroprusside can be attributed to the possibility of using nitric oxide donors in treating cerebrovascular insufficiency. However, limited human data suggest that intracarotid nitroprusside does not directly affect cerebrovascular resistance. In previous studies, physiologic or pharmacologic reactivity of the preparation was not tested at the time of nitroprusside challenge. The authors hypothesized that if nitric oxide is a potent modulator of human cerebral blood flow (CBF), then intracarotid infusion of nitroprusside will augment CBF. METHODS: Cerebral blood flow was measured (intraarterial (133)Xe technique) in sedated human subjects undergoing cerebral angiography during sequential infusions of (1) intracarotid saline, (2) intravenous phenylephrine to induce systemic hypertension, (3) intravenous phenylephrine with intracarotid nitroprusside (0.5 microg x kg(-1) x min(-1)), and (4) intracarotid verapamil (0.013 mg x kg(-1) x min(-1)). Data (mean +/- SD) were analyzed by repeated-measures analysis of variance and post hoc Bonferroni-Dunn test. RESULTS: Intravenous phenylephrine increased systemic mean arterial pressure (from 83 +/- 12 to 98 +/- 6 mmHg; n = 8; P < 0.001), and concurrent infusion of intravenous phenylephrine and intracarotid nitroprusside reversed this effect. However, compared with baseline, CBF did not change with intravenous phenylephrine or with concurrent infusions of intravenous phenylephrine and intracarotid nitroprusside. Intracarotid verapamil increased CBF (43 +/- 9 to 65 +/- 11 ml x 100 g(-1) x min(-1); P < 0.05). CONCLUSIONS: The authors conclude that, in humans, intracarotid nitroprusside sufficient to decrease mean arterial pressure during recirculation, does not augment CBF. Failure of intracarotid nitroprusside to augment CBF despite demonstrable autoregulatory vasoconstriction and pharmacologic vasodilation questions the significance of nitric oxide-mediated vasodilation in human cerebral circulation.

Adult↗

Clinical utility of quantitative cerebral blood flow measurements during internal carotid artery test occlusions.

OBJECTIVE: Internal carotid artery (ICA) balloon test occlusions (BTOs) are performed in the angiography suite to predict whether the patient has adequate collateral circulation to prevent stroke when permanent ICA occlusion (PCO) is required for treatment. Although many criteria have been proposed to facilitate predictions of stroke risk after PCO, no BTO techniques have been subjected to predictive validity testing in outcome studies. We describe a prospective case series study that tests the predictive validity of quantitative cerebral blood flow (CBF) measurements during ICA BTO. METHODS: Thirty-three patients with clinical indications for PCO underwent ICA BTO and then PCO. During BTO, standard neurological examinations, sustained-attention testing, and quantitative CBF measurements were performed. Two scalp scintillation detectors recorded washout data after ipsilateral intracarotid injection of xenon-133 through a port at the tip of the ICA-occluding balloon. Patients were monitored for the outcome measure of ipsilateral stroke for a mean of 34 months. The variables of quantitative CBF values, neurological examination results, sustained-attention test results, age, sex, and side of occlusion were examined with Kaplan-Meier log-rank tests, predictive validity analyses, and logistic regression analyses. RESULTS: CBF of less than 30 ml/100 g/min during BTO was the only variable that predicted stroke after PCO (log rank = 5.87, P = 0.015). The negative and positive predictive values for CBF findings were superior to those for standard neurological examination findings and sustained-attention test results. Age, sex, and side of occlusion did not predict stroke. CONCLUSION: Quantitative CBF testing, via the intracarotid injection technique, during BTO seems to be an important predictor of stroke after PCO.

Adult↗

Characterization of the cerebral blood flow response to balloon deflation after temporary internal carotid artery test occlusion.

The authors tested the hypothesis that cerebral blood flow (CBF) would increase after acute and relatively brief internal carotid artery (ICA) test occlusion, and examined the relationship of the postdeflation CBF to the development of neurologic symptoms. In 16 patients undergoing ICA test occlusion with deliberate hypotension, the authors measured intracarotid 133Xe CBF at baseline, occlusion, and deflation. Four patients developed neurologic symptoms during occlusion. As positive controls, 11 other patients received intracarotid verapamil or papaverine before deflation as part of another protocol. Balloon occlusion was 23.1 +/- 10.5 minutes (mean +/- standard deviation) in duration. At 1.3 +/- 1.6 minutes after balloon deflation, there was a trend (12 +/- 31%) for CBF to increase (48 +/- 9 mL/100 g/min versus 53 +/- 17 mL/100 g/min, P =.15), and a 16 +/- 27% decrease in cerebrovascular resistance (CVR; 2.1 +/- 0.6 mm Hg/100 g/min/mL versus 1.7 +/- 0.6 mm Hg/100 g/min/mL, P =.03) compared with baseline values. By comparison, patients who received a intracarotid dilator demonstrated a 53 +/- 55% increase in CBF (48 +/- 10 mL/100/min versus 70 +/- 23 mL/100 g/min, P = .007) and a 33 +/- 31% decrease in CVR (2.2 +/- 0.6 mm Hg/100 g/min/mL versus 1.4 +/- 0.6 mm Hg/100 g/min/mL, P = .0007) compared with baseline. Analysis of variance and regression analysis showed no other relationships between postocclusion CBF and balloon occlusion duration, distal internal carotid occlusion ("stump") pressure, or the development of neurologic symptoms. Acute, temporary interruption of ICA blood flow resulted in minimal postocclusive changes in cerebrovascular hemodynamics, even in those patients who developed neurologic symptoms during the period of test occlusion.

Adult↗

Dexmedetomidine may impair cognitive testing during endovascular embolization of cerebral arteriovenous malformations: a retrospective case report series.

After the reported successful use of dexmedetomidine to sedate patients in the intensive care unit without respiratory depression, we began to use dexmedetomidine for interventional neuroradiologic procedures. We report on five patients who had dexmedetomidine administered for sedation during embolization of cerebral arteriovenous malformations. All patients were comfortably sedated and breathing spontaneously. However, although patients were awake and following simple commands 10 minutes after the discontinuation of the infusion of dexmedetomidine, they were nevertheless unable to undergo cognitive testing. They were still unable to undergo cognitive testing 45 minutes after the infusion was stopped. In contrast, 10 minutes after the discontinuation of the infusion of propofol, all patients were awake, alert, cooperative, and able to undergo cognitive testing without difficulty. In conclusion, on examination of five non-randomly selected case records, we found that dexmedetomidine significantly prevented neurologic and cognitive testing.

Adjuvants, Anesthesia↗

Intraarterially administered verapamil as adjunct therapy for cerebral vasospasm: safety and 2-year experience.

BACKGROUND AND PURPOSE: Despite the widespread use of angioplasty, adjunct chemical therapy is often needed to treat patients with cerebral vasospasm. In this study, we examined the safety of intraarterial administration of verapamil to patients with cerebral vasospasm. We herein summarize our 2-year experience with this treatment. METHODS: We retrospectively reviewed the procedure reports, anesthesia records, clinical charts, and brain images of 29 patients who received intraarterially administered verapamil in 34 procedures for the treatment of vasospasm after subarachnoid hemorrhage from July 1998 to June 2000. The average changes in mean arterial pressure and heart rate were used to measure cardiovascular side effects. The neurologic effects were assessed by angiographic findings, the results of neurologic examinations performed before and after the procedure, and findings of CT of the head. RESULTS: The average dose of verapamil per patient was 3 +/- 0 mg or 44 +/- 5 mcg/kg. The average changes in mean arterial pressure at 10 and 20 minutes were -5 +/- 1 mm Hg and -2 +/- 1 mm Hg or -3.8 +/- 1.0% and -1.7 +/- 1.1%, respectively. No significant change of heart rate was observed at 10 minutes. The patients showed no sign of increased intracranial pressure by hemodynamic parameters, neurologic examination, or CT of the head. On 10 occasions, when the effect of verapamil infusion was assessed angiographically, there was 44 +/- 9% increase of vessel diameter in the spastic segment. Neurologic improvement was noted after five of 17 procedures when verapamil was used as the sole treatment. CONCLUSION: Low dose verapamil is safe when administered intraarterially to patients with cerebral vasospasm. Beneficial effects are achieved in some patients, prompting further study of its efficacy.

Calcium Channel Blockers↗

Feasibility of using hyperosmolar mannitol as a liquid tumor embolization agent.

BACKGROUND AND PURPOSE: This study assesses the cytotoxicity of hyperosmolar mannitol on human endothelial and meningioma cells in vitro and summarizes the initial clinical experience of using mannitol as a liquid tumor embolization agent. METHODS: Human umbilical vein endothelial cells and primary meningioma cells from surgical specimens were treated with 300, 600, 900, and 1200 mOsm of mannitol, mannitol and iohexol mixture, saline, and iohexol alone. Cell death was evaluated with a Live/Dead kit and quantified with thymidine incorporation. From 1998 to 2004, 23 patients with meningioma were treated with mannitol and 31 patients were treated with polyvinyl alcohol (PVA) particles alone. Angiographic results, procedural complications, intraoperative observation, and estimated blood loss during surgical resection were retrospectively evaluated. RESULTS: Minimal endothelial cell death was seen after incubation with 300 mOsm of mannitol for 15 minutes, but 43 +/- 2% of endothelial cells were damaged by 1200 mOsm of mannitol after 30 minutes. Five meningioma cell lines exhibited significant cell death (22 +/- 2%; P < .05) after incubation with mannitol. Satisfactory angiographic results were obtained in all 23 patients. Tumor necrosis was observed intraoperatively and confirmed pathologically. There was no significant difference in estimated blood loss between mannitol- and PVA-embolized patients (407 +/- 64 mL vs 381 +/- 50 mL; P > .75). CONCLUSION: High concentration of mannitol can injure endothelial cells and meningioma cells in a short period of time. It is feasible to use mannitol as a liquid embolic agent to treat meningioma.

Chemoembolization, Therapeutic↗