Biomedical subjects
B G Thompson
Publications and source records attributed to B G Thompson.
Role of topical steroids in reducing dysfunction after nerve injury.
OBJECTIVE: To determine the efficacy of topical dexamethasone in reducing nerve dysfunction after axonotmesis injury. STUDY DESIGN: A three-armed, blinded study including sham, control, and test groups was designed using the rat sciatic nerve crush injury model. METHODS: Twenty-two rats were randomly assigned to a control group or a topical steroid group. A standardized sciatic nerve crush injury was performed under sterile conditions on each animal. A separate group of five rats underwent a sham operation to isolate the crush injury as the source of postoperative dysfunction in the control and steroid groups. All animals underwent walking track analysis with calculation of the sciatic functional index (SFI) before surgery and through the postoperative recovery period. Dexamethasone saturated Gelfoam was placed at the site of injury in the topical steroid group. The functional performance of each group was compared throughout the recovery period. RESULTS: No morbidity associated with topical application of steroids at the injury site was noted. The topical steroid group had improved recovery at postoperative days 14, 18, and 22. This difference was statistically significant at day 14. At the termination of the study, there was a clear trend toward superior recovery for the steroid group compared with controls (90% vs. 73%), but this difference did not reach statistical significance. CONCLUSIONS: Clinical use of topical steroids to reduce postoperative nerve dysfunction warrants further study.
Increased cerebral blood flow but no reversal or prevention of vasospasm in response to L-arginine infusion after subarachnoid hemorrhage.
OBJECT: The reduction in the level of nitric oxide (NO) is a purported mechanism of delayed vasospasm after subarachnoid hemorrhage (SAH). Evidence in support of a causative role for NO includes the disappearance of nitric oxide synthase (NOS) from the adventitia of vessels in spasm, the destruction of NO by hemoglobin released from the clot into the subarachnoid space, and reversal of vasospasm by intracarotid NO. The authors sought to establish whether administration of L-arginine, the substrate of the NO-producing enzyme NOS, would reverse and/or prevent vasospasm in a primate model of SAH. METHODS: The study was composed of two sets of experiments: one in which L-arginine was infused over a brief period into the carotid artery of monkeys with vasospasm, and the other in which L-arginine was intravenously infused into monkeys over a longer period of time starting at onset of SAH. In the short-term infusion experiment, the effect of a 3-minute intracarotid infusion of L-arginine (intracarotid concentration 10(-6) M) on the degree of vasospasm of the right middle cerebral artery (MCA) and on regional cerebral blood flow (rCBF) was examined in five cynomolgus monkeys. In the long-term infusion experiment, the effect of a 14-day intravenous infusion of saline (control group, five animals) or L-arginine (10(-3) M; six animals) on the occurrence and degree of cerebral vasospasm was examined in monkeys. The degree of vasospasm in all experiments was assessed by cerebral arteriography, which was performed preoperatively and on postoperative Days 7 (short and long-term infusion experiments) and 14 (long-term infusion experiment). In the long-term infusion experiment, plasma levels of L-arginine were measured at these times in the monkeys to confirm L-arginine availability. Vasospasm was not affected by the intracarotid infusion of L-arginine (shown by the reduction in the right MCA area on an anteroposterior arteriogram compared with preoperative values). However, intracarotid L-arginine infusion increased rCBF by 21% (p < 0.015; PCO2 38-42 mm Hg) in all vasospastic monkeys compared with rCBF measured during the saline infusions. In the long-term infusion experiment, vasospasm of the right MCA occurred with similar intensity with or without continuous intravenous administration of L-arginine on Day 7 and had resolved by Day 14. The mean plasma L-arginine level increased during infusion from 12.7+/-4 microg/ml on Day 0 to 21.9+/-13.1 microg/ml on Day 7 and was 18.5+/-3.1 microg/ml on Day 14 (p < 0.05). CONCLUSIONS: Brief intracarotid and continuous intravenous infusion of L-arginine did not influence the incidence or degree of cerebral vasospasm. After SAH, intracarotid infusion of L-arginine markedly increased rCBF in a primate model of SAH. These findings discourage the use of L-arginine as a treatment for vasospasm after SAH.
Effect of hematocrit on calculation of cerebral blood flow and lambda in xenon CT.
Knowledge of the patient's hematocrit is necessary for calculation of cerebral blood flow (CBF) with xenon CT, and is a potential source of error. This study quantifies the effect of hematocrit on the calculation of CBF and lambda, and determines if the magnitude of the effect is dependent on actual CBF or lambda. The effect of hematocrit was measured empirically using software employing the numerical calculation method. CBF and lambda were found to be inversely related to hematocrit. The percent error produced by an inaccurate hematocrit is greater for lower actual CBF values.
The role of performance assessment in the regulation of underground disposal of radioactive wastes: an international perspective.
Much has been written about the development and application of quantitative methods for estimating under uncertainty the long-term radiological performance of underground disposal of radioactive wastes. Until recently, interest has been focused almost entirely on the technical challenges regardless of the role of the organization responsible for these analyses. Now the dialogue between regulators, the repository developer or operator, and other interested parties in the decision-making process receives increasing attention, especially in view of some current difficulties in obtaining approvals to construct or operate deep facilities for intermediate or high-level wastes. Consequently, it is timely to consider the options for regulators' review and evaluation of safety submissions, at the various stages in the site selection to repository closure process, and to consider, especially, the role for performance assessment (PA) within the programs of a regulator both before and after delivery of such a submission. The origins and broad character of present regulations in the European Union (EU) and in the OECD countries are outlined and some regulatory PA reviewed. The issues raised are discussed, especially in regard to the interpretation of regulations, the dangers from the desire for simplicity in argument, the use of regulatory PA to review and challenge the PA in the safety case, and the effects of the relationship between proponent and regulator. Finally, a very limited analysis of the role of PA in public hearings is outlined and recommendations are made, together with proposals for improving the mechanisms for international collaboration on technical issues of regulatory concern.
Distance learning for hospital managers.
Telemedicine technology enabled this class to meet. The Chapel Hill instructor could not have traveled to Scotland Neck for the classes, and the class members could not have taken time away from their jobs to travel to Chapel Hill. The technology allowed the participants to fit the classes into their schedules. For the group of managers at this small, isolated hospital, the experience of participating in a management class with an expert was a positive one. They were introduced to standard management practices, learned new skills, and formed a support group/team onsite. The students felt close to the leader, yet the physical distance made her an outsider in a way that encouraged frankness. The technology seemed to foster the best of both worlds--intimacy, yet physical distance and, thus, safety. These new managers were able to take part in a course that taught tangible skills for improving their job performance and, more important, afforded access to resources outside of Halifax County. They were able to step away from their daily routine and interact with outsiders and each other in new ways, without the stress and expense of travel. The results of this pilot study indicate that distance learning is feasible for courses of this kind. Staff burnout and turnover are chronic problems in rural facilities, with isolation contributing to job dissatisfaction. Distance learning offers exciting possibilities for addressing these problems in healthcare settings across the country.
Use of hydroxyapatite bone cement to prevent cerebrospinal fluid leakage through the frontal sinus: technical report.
OBJECTIVE: To test the efficacy of a simple technique of frontal sinus obliteration during low frontal craniotomy using hydroxyapatite cement instead of more traditional methods, such as pericranial flaps, free muscle or adipose grafts, lumbar drainage, or fibrin glue. METHODS: Eight patients undergoing low frontal craniotomy for intradural surgery had the frontal sinus obliterated by careful removal of mucosa followed by filling of the sinus with hydroxyapatite bone cement. No other adjuncts for preventing cerebrospinal fluid leakage through the sinus were used. RESULTS: At an average follow-up of 9 months, there were no cerebrospinal fluid leaks, infections, instances of resorption, or cosmetic deformities. CONCLUSION: Hydroxyapatite bone cement seems to be a simple and effective method for frontal sinus obliteration and prevention of cerebrospinal fluid leakage.
Basilar artery perforation as a complication of endoscopic third ventriculostomy.
The morbidity and mortality associated with third ventriculostomy has decreased significantly over the past 75 years since its introduction by Walter Dandy. Now more commonly performed using an endoscopic method, the significant morbidity of third ventriculostomy has dropped to approximately 5%; essentially that associated with ventriculoscopy in general. However, the possible complication of massive subarachnoid hemorrhage resulting from perforation of the basilar artery or its branches in the course of fenestration of the floor of the third ventricle has only recently been reported. In our case, subsequent to a vascular injury, a pseudoaneurysm developed at the site of vascular perforation, which was then appropriately controlled. The patient has since made a full recovery. Our goal is to remind the endoscopist of this unusual complication and to discuss our management strategies.
Surgical exposure of the petrous internal carotid artery: practical application for skull base surgery.
When exposing the horizontal petrous carotid artery in preparation for intrapetrous carotid bypass, the surgeon has no definite landmarks to localize the perimeter of the cochlea. The results of this study provide a practical, consistent, and safe method to maximize carotid artery exposure while minimizing cochlear injury. We measured the carotid-cochlea distance (mean, 4.3 mm) and the carotid-cochlear angle (mean, 10.8 degrees) in 33 temporal bones in which the extended middle fossa approach had been performed. We correlated this distance to the width of a Sheehy weapon knife, which can be easily measured intraoperatively. Twenty-five temporal bones were imaged prior to surgical exposure using a new computed tomography (CT) protocol that can be used for preoperative assessment of the carotid-cochlear anatomy. The carotid-cochlea distance and carotid-cochlear angle measured on CT are compared with postsurgical measurements.
Nine reasons why healthcare delivery using advanced communications technology should be reimbursed.
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Nitric oxide mediation of chemoregulation but not autoregulation of cerebral blood flow in primates.
The authors sought to develop a model for assessing in vivo regulation of cerebral vasoregulation by nitric oxide (NO), originally described as endothelial-derived relaxing factor, and to use this model to establish the role of NO in the regulation of cerebral blood flow (CBF) in primates. By using regional intraarterial perfusion, the function of NO in cerebral vasoregulation was examined without producing confounding systemic physiological effects. Issues examined were: whether resting vasomotor tone requires NO; whether NO mediates vasodilation during chemoregulation and autoregulation of CBF; and whether there is a relationship between the degree of hypercapnia and hypotension and NO production. Twelve anesthetized (0.5% isoflurane) cynomolgus monkeys were monitored continuously for cortical CBF, PaCO2, and mean arterial pressure (MAP), which were systematically altered to provide control and experimental curves of chemoregulation (CBF vs. PaCO2) and autoregulation (CBF vs. MAP) during continuous intracarotid infusion of 1) saline and 2) an NO synthase inhibitor (NOSI), either L-n-monomethyl arginine or nitro L-arginine. During basal conditions (PaCO2 of 38-42 mm Hg) NOSI infusion of internal carotid artery (ICA) reduced cortical CBF from 62 (saline) to 53 ml/100 g/per minute (p<0.01), although there was no effect on MAP. Increased CBF in response to hypercapnia was completely blocked by ICA NOSI. The difference in regional (r)CBF between ICA saline and NOSI infusion increased linearly with PaCO2 when PaCO2 was greater than 40 mm Hg, indicating a graded relationship of NO production, increasing PaCO2, and increasing CBF. Diminution of CBF with NOSI infusion was reversed by simultaneous ICA infusion of L-arginine, indicating a direct role of NO synthesis in the chemoregulation of CBF. Hypotension and hypertension were induced with trimethaphan camsylate (Arfonad) and phenylephrine at constant PaCO2 (40 +/- 1 mm Hg). Autoregulation in response to changes in MAP from 50 to 140 mm Hg was unaffected by ICA infusion of NOSI. In primates, cerebral vascular tone is modulated in vivo by NO; continuous release of NO is necessary to maintain homeostatic cerebral vasodilation; vasodilation during chemoregulation of CBF is mediated directly by NO production; autoregulatory vasodilation with hypertension is not mediated by NO; and increasing PaCO2 induces increased NO production.
Loss of nitric oxide synthase immunoreactivity in cerebral vasospasm.
To determine the distribution of nitric oxide synthase (NOS) in the primate cerebral artery nervi vasorum and to examine the potential role of NOS in cerebral vasospasm after subarachnoid hemorrhage (SAH) in primates, the distribution of NOS immunoreactivity (NOS-IR) in the major cerebral arteries was examined immunohistochemically in cynomolgus monkeys by the use of whole, mounted preparations of the circle of Willis. In four normal monkeys, NOS-IR was localized to the endothelial and adventitial layers of the large cerebral arteries. On the abluminal side, NOS-IR staining was densely concentrated in perivascular nerve fibers (nervi vasorum) of the anterior circulation. Staining was less prominent in the posterior circulation. In six monkeys with vasospasm on Day 7 after placement of preclotted arterial blood to form an SAH around the right middle cerebral artery (MCA) (42% +/- 8.3% decrease of MCA area, mean +/- standard deviation), NOS-IR was virtually absent in nerve fibers around the spastic right MCA but was normal on the contralateral side. In five monkeys in which vasospasm resolved by Day 14 after SAH (36% +/- 14% decrease of right MCA area on Day 7, and 5% +/- 14% decrease on Day 14), NOS-IR was also absent in the right MCA adventitial nerve fibers and remained normal in the left MCA. Adventitial NOS-IR was also normal in cerebral vessels of a sham-operated, nonspastic monkey. These findings provide further evidence that nitric oxide (NO) functions as a neuronal transmitter to mediate vasodilation in primates and indicate a role for adventitial NO in the pathogenesis of cerebral vasospasm after SAH in humans.
Telemedicine and geriatrics: back to the future.
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Effect of intracarotid nitric oxide on primate cerebral vasospasm after subarachnoid hemorrhage.
The continuous release of nitric oxide (NO) is required to maintain basal cerebrovascular tone. Oxyhemoglobin, a putative spasmogen, rapidly binds NO, implicating loss of NO in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). If vasospasm is mediated by depletion of NO in the vessel wall, it should be reversible by replacement with NO. To investigate this hypothesis, the authors placed blood clots around the right middle cerebral artery (RMCA) of four cynomolgus monkeys; four unoperated animals served as controls. Arteriography was performed before and 7 days after surgery to assess the presence and degree of vasospasm, which was quantified in the anteroposterior (AP) projection by computerized image analysis. On Day 7, cortical cerebral blood flow (CBF) in the distribution of the right MCA was measured during four to six runs in the right internal carotid artery (ICA) of brief infusions of saline followed by NO solution. Arteriography was performed immediately after completing the final NO infusion in three of the four animals with vasospasm. Right MCA blood flow velocities were obtained using transcranial Doppler before, during, and after NO infusion in two vasospastic animals. After ICA NO infusion, arteriographic vasospasm resolved (mean percent of preoperative AP area, 55.9%); that is, the AP areas of the proximal portion of the right MCA returned to their preoperative values (mean 91.4%; range 88%-96%). Compared to ICA saline, during ICA NO infusion CBF increased 7% in control animals and 19% in vasospastic animals (p < 0.002) without significant changes in other physiological parameters. During NO infusion, peak systolic right MCA CBF velocity decreased (130 to 109 cm/sec and 116 to 76 cm/sec) in two vasospastic animals. The effects of ICA NO on CBF and CBF velocity disappeared shortly after terminating NO infusion. Intracarotid infusion of NO in a primate model of vasospasm 1) increases CBF, 2) decreases cerebral vascular resistance, 3) reverses arteriographic vasospasm, and 4) decreases CBF velocity in the vasospastic artery without producing systemic hypotension. These findings indicate the potential for the development of targeted therapy to reverse cerebral vasospasm after SAH.
Development of a CELSS bioreactor: oxygen transfer and micromixing in parabolic flight.
The gas exchange portion of a phase-separated loop bioreactor was tested with respect to oxygen mass transfer and micromixing in accelerations of 0.01g, 1g, and 2g. A plot of the overall mass transfer coefficient versus gravity indicates the rate of oxygen transfer does not change as a function of acceleration. Also, it was determined that the micromixing did not exhibit significant changes in the various gravitational fields. These observations indicate the loop bioreactor should function independent of acceleration.
Are the calcium antagonists really useful in cerebral aneurysmal surgery? A retrospective study.
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Treatment of cranial dural arteriovenous fistulae by interruption of leptomeningeal venous drainage.
Cranial dural arteriovenous fistulae (AVF's) of the tentorial incisura or the dura of the middle fossa have a much higher incidence of draining via leptomeningeal veins than do AVF's of the transverse-sigmoid sinuses or the cavernous sinus. Such a drainage pattern is associated with an increased incidence of intracranial hemorrhage and progressive focal neurological deficits. Patients with cranial dural AVF's often undergo surgical excision and/or endovascular embolization for elimination of the AVF. Since these lesions are frequently large and involve the skull base or adjacent dural sinuses, extensive surgery is often required. In contrast, spinal dural AVF's with only intradural venous drainage to the medullary venous system are treated successfully by simply interrupting the vein that drains the dural AVF as it enters the subarachnoid space. The authors identified a subgroup of patients with cranial dural AVF's in whom the AVF was drained only by leptomeningeal veins, and sought to establish whether simple interruption of the vein draining the blood from the AVF into the subarachnoid space is effective and lasting treatment in this subgroup of patients, as it is in patients with spinal dural AVF's. Four adult patients with symptomatic cranial dural AVF's (two petrotentorial, one middle fossa floor, and one posterior fossa base) were identified on arteriography as having fistulae that were supplied by the internal and/or external carotid arteries and drained only via leptomeningeal veins (two entered the petrosal vein, one a cerebellar hemispheric vein, and one a mesencephalic vein). All patients underwent interruption of the vein draining the dural AVF as it penetrated the dura to enter the subarachnoid space, and experienced neurological improvement after surgery. Repeat arteriography at 1 to 2 weeks (three patients), 3 months (3 patients), 12 to 15 months (three patients), and 4 years (two patients) revealed no residual AVF and no evidence of abnormal blood flow. Many cranial dural AVF's with leptomeningeal venous drainage (the type with the most aggressive behavior) are drained only by leptomeningeal veins. This subgroup of patients can be identified by selective arteriography and requires only interruption of the draining vein as it enters the subarachnoid space for successful, lasting elimination.
Stereotactic radiosurgery of small intracranial tumors: neuropathological correlation in three patients.
The mechanism by which radiosurgery can stop the growth of some tumors is poorly understood, in part because postmortem neuropathological findings in patients have been reported only rarely. To define further the effects of radiosurgery, we present the correlation among clinical, neuroimaging, and neuropathological data in three patients with different intracranial tumors who died between 2 and 39 weeks after radiosurgery. The target volumes in two patients with malignant tumors showed sharply demarcated coagulative necrosis. In the third patient, who had a benign acoustic nerve tumor, neuropathological examination found intratumoral hemorrhage and cyst formation, but no necrosis. Radiosurgery appears to cause acute necrosis of malignant cells, although its effectiveness may be limited by the infiltrative nature of some tumors. In benign tumors, necrosis following radiosurgery is relatively delayed, and may not be required for growth arrest.