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Biomedical subjects

M S Grady

Publications and source records attributed to M S Grady.

106 records · Page 6Linked to original sources

Evaluation of brain death using transcranial Doppler.

Cerebral blood flow velocities in the middle cerebral arteries were measured using transcranial Doppler in 12 patients with conditions that ultimately resulted in brain death. All patients had sustained closed head injury, gunshot wounds to the head, or spontaneous intracerebral hemorrhages. When clinical criteria for brain death were met, a characteristic pattern was found with transcranial Doppler. This pattern consisted of reverberating flow, with forward flow in systole and retrograde flow in diastole. When this pattern was seen, there was arrest of cerebral flow, as measured by radionuclide scanning using technetium, in all patients studied. Transcranial Doppler is a useful technique for easily assessing the arrest of the cerebral circulation.

Adolescent↗

Intracerebral drug delivery in rats with lesion-induced memory deficits.

Pharmacological treatments directed at increasing cortical acetylcholine activity in patients with Alzheimer's disease have largely been disappointing, perhaps because denervated areas of brain may not be exposed to adequate amounts of drug. A new method has been developed to enable localized intracerebral delivery of neurotransmitter substances using a polymeric drug delivery system. Microspheres of a polyanhydride sebacic acid copolymer were impregnated with bethanechol, an acetylcholinesterase-resistant cholinomimetic. Twenty rats received bilateral fimbria-fornix lesions, producing cholinergic denervation of the hippocampus and marked impairment in spatial memory. The animals were trained for 2 weeks to run after which they received bilateral intrahippocampal implants of saline (five rats), blank polymer (five rats), or bethanechol-impregnated polymer (10 rats). Following implantation, spatial memory was assessed by radial-maze performance testing for 40 days. Untreated lesioned rats showed persistently poor spatial memory, entering maze arms with near random frequency. Similarly, animals treated with saline and blank polymer did not improve after implantation. Rats treated with bethanechol-impregnated microspheres, however displayed significant improvement within 10 days after implantation; this improvement persisted for the duration of the experiment (p less than 0.05, Student's t-test). Histological analysis of regional acetylcholinesterase staining showed widespread loss of activity throughout the hippocampus bilaterally in all animals. The microsphere implants were visible within the hippocampus, with minimal reactive changes in surrounding brain. It is concluded that intracerebral polymeric drug delivery successfully reversed lesion-induced memory deficits, and has potential as a neurosurgical treatment method for Alzheimer's disease and other neurodegenerative disorders.

Anhydrides↗

Synaptic reorganization within the human central nervous system following injury.

Behavioral recovery following brain injury in humans is well recognized; however, the anatomical basis for such recovery has not been demonstrated. Two cases are presented that show reorganization of synaptic connections (plasticity) in the dentate gyrus of human brain following uncal herniation. The neurohistological appearance of these cases is very similar to a well-described animal model of anatomical, physiological, and behavioral recovery following experimental surgical injury.

Acetylcholinesterase↗

Angioplasty for the treatment of symptomatic vasospasm following subarachnoid hemorrhage.

Angioplasty of narrowed cerebral arteries was performed in 10 patients who became symptomatic from vasospasm following subarachnoid hemorrhage. This procedure was accomplished with a microballoon catheter via percutaneous transfemoral insertion. Patients were selected for treatment if they had delayed neurological deficits due to vasospasm which were not responsive to hypervolemic hypertensive therapy. Eight patients (80%) showed sustained improvement in neurological function following the procedure. In two patients transcranial Doppler ultrasound recordings were obtained which revealed decreased mean blood flow velocities following angioplasty. Two patients died, one from an aneurysmal rebleed, and one secondary to diffuse vasospasm. There was one case of delayed stroke 6 weeks following the procedure. The overall results of this series indicate that in selected cases percutaneous balloon angioplasty can offer marked improvement to patients with ischemic deficits due to vasospasm following subarachnoid hemorrhage.

Adult↗

Arteriovenous malformations of the dura mater.

The presentation, angiographic findings, and treatment of eight dural arteriovenous malformations is reviewed. The majority presented as intracranial hemorrhage, one of which was an intracerebral hemorrhage, and an aneurysm was found in conjunction with two of the eight. Preoperative embolization of one of the malformations was used with an excellent result. Five of eight were treated surgically with a good outcome. Patient outcome, whether surgically treated or not, was good in all cases though follow-up is a maximum of 3 years, except for one case of 23 years.

Aged↗

Ectopic pituitary gland simulating a suprasellar tumor.

A case report of ectopic pituitary gland in the suprasellar region of a normal 39-year-old woman with persistent headaches is presented. The embryological development of the pituitary gland is briefly reviewed, with a discussion of the relevant literature. No previous report of normal pituitary tissue in a suprasellar location in the absence of tumor could be found.

Adult↗

Use of the Philadelphia collar as an alternative to the halo vest in patients with C-2, C-3 fractures.

We analyzed retrospectively 27 individuals with C-2, C-3 fractures, 8 of whom were treated with a Philadelphia collar rather than the more commonly used halo vest. Successful fusion without neurological deficit occurred in all cases whether treatment was by Philadelphia collar (n = 8), halo apparatus (n = 16), or prolonged bed rest (n = 3). There was an increase in subluxation in 3 patients in both the Philadelphia collar group and the halo apparatus group. However, 1 of the 3 in the collar group was uncooperative and discarded his collar during treatment. If he is excluded, the subluxation rate in the Philadelphia collar group is 27%; the rate in the halo group is 19%. The Philadelphia collar seems to be an acceptable means of stabilizing the neck in C-2, C-3 fractures, but one must consider the degree of cervical movement in the collar (as detected by dynamic x-ray films), patient reliability, and patient age. The presence of subluxation did not preclude successful fusion in either the Philadelphia collar or the halo vest groups.

Adolescent↗

Long term survival of a patient with an intracranial ependymoma: case report.

A patient with a posterior fossa ependymoma who has survived for over 49 years is presented. Inspection of the original specimen from 1936 and comparison to subsequent biopsies show no change in the benign morphology of the tumor. This case is unique not only in the patient's length of survival, but also in the sequential histological examination of the tumor.

Brain Neoplasms↗

Profound cerebral vasospasm without radiological evidence of subarachnoid hemorrhage: case report.

Profound clinical and radiographic arterial vasospasm in all major intracerebral vessels was identified in a patient with an intraparenchymal hemorrhage that extended into the lateral, 3rd, and 4th ventricles. By computed tomographic criteria and on early cerebrospinal fluid examination, no subarachnoid blood was detected. The temporal appearance of vasospasm was consistent with that typically seen in subarachnoid hemorrhage. Despite hypervolemia and iatrogenic hypertension, cerebral infarction occurred contralateral to the hemorrhage. We conclude that patients without significant subarachnoid hemorrhage (as determined by computed tomographic scanning) may still be at risk for developing vasospasm.

Adult↗

Pharmacokinetics of intraventricular vancomycin in hydrocephalic rats.

An animal model was developed for studying the pharmacokinetics of antibiotics administered intraventricularly in hydrocephalus. Obstructive hydrocephalus was consistently produced in craniectomized adult rats by injecting kaolin into the cisterna magna. After induction of hydrocephalus, vancomycin was injected into the right lateral ventricle of each rat. Bilateral ventricular cerebrospinal fluid (CSF) and brain parenchymal samples were obtained at 0.5, 1, 2, 4, 8, and 12 hours and the concentration of vancomycin in these samples was determined. Brain tissue was also analyzed histologically. The results show: (a) vancomycin is rapidly distributed within the CSF, including the contralateral ventricle, within 30 minutes; (b) vancomycin concentrations were nearly identical in both ventricles at all time points; (c) mean peak CSF vancomycin concentrations occurred at 2 hours and were 23.8 and 21.3 micrograms/ml for the left and right lateral ventricles, respectively; (d) elimination from CSF was slow (T1/2 beta = 2.22 hours, T1/2 gamma = 19.65 hours); (e) no vancomycin was detected (less than or equal to 2 micrograms/g) in the samples of periventricular white matter; (f) histological changes observed were consistent with untreated obstructive hydrocephalus and did not seem to be related to vancomycin treatment. The clinical significance of these results and the usefulness of the experimental model are discussed.

Animals↗

Changes in superior sagittal sinus pressure in children with head elevation, jugular venous compression, and PEEP.

Air embolism is a potential hazard during craniotomy whenever intracranial venous pressure is subatmospheric. In order to better understand both the risk of air embolism and its treatment in neurosurgical patients, the authors have investigated the relationship of superior sagittal sinus pressure (SSP) to head position in 15 children and examined the effects of both jugular venous compression and positive end-expiratory airway pressure (PEEP) on SSP. Progressive head elevation significantly decreased mean SSP and, in five patients, SSP was less than 0 mm Hg at 90 degrees torso elevation. A PEEP of 10 cm H2O was ineffective in significantly increasing SSP at any degree of head elevation, whereas bilateral internal jugular compression always caused a significant increase in SSP. The authors conclude that children are at risk for venous air embolism when undergoing suboccipital craniectomy in the sitting position because intracranial venous pressure is often subatmospheric when the head is elevated. Furthermore, maintaining PEEP does not appear to be a reliable treatment for increasing SSP, whereas bilateral internal jugular compression is effective.

Adolescent↗

Transplantation of embryonic chick spinal cord into transection adult chicken spinal cords: a useful model for transplantation research.

Adult chicken spinal cords were completely transected under direct visualization. One week later, embryonic chick spinal cords 6 days, 9 days, or 11 days old were implanted into the site of transection. The animals were allowed to survive for 2 months and then killed and the spinal cords were prepared for histologic analysis. The survival and outgrowth of the embryonic transplants were compared with regard to the age of the implant, and its effects on the host tissue. Six-day embryonic tissue survived and integrated far better than 9-day or 11-day, and adult spinal cord subjacent to the early age embryo showed fewer degenerative changes. The chick embryo may provide a model for use in CNS transplantation.

Aging↗

Preliminary experimental investigation of in vivo magnetic manipulation: results and potential application in hyperthermia.

The first in vivo experiments in support of a new technique for delivering stereotaxic hyperthermia have been conducted at the Experimental Surgery Facility of the University of Virginia's Medical Center. We call this technique the "Video Tumor Fighter." In each of twelve trials a single, small permanent magnet or train of small permanent magnets was implanted on the brain surface of adult canine models. In three of the trials, this "seed" (typically 6-mm diameter X 6-mm long) was moved by magnetic manipulation to different locations within the brain. In two other trials, the seed moved along the interface between the brain and the inner vault of the skull. The noncontact magnetic manipulation was accomplished by coupling the permanently magnetized seed to the large dc magnetic field gradient created by a water-cooled coil surrounding the animal's head. The seed's motions were monitored with x-ray fluoroscopy; its rate of movement was found to be approximately 0.8 mm s-1. The forces required to produce these motions were on the order of 0.07 N. We document here the instrumentation used in these trials, describe the experimental procedures employed, and discuss the technical aspects of the results.

Animals↗

Nonlinear magnetic stereotaxis: three-dimensional, in vivo remote magnetic manipulation of a small object in canine brain.

In a series of in vivo experiments on five adult canines, a small cylindrical permanent magnet (approximately 5-mm diameter x 5 mm long) was magnetically moved under fluoroscopic guidance from an occipital-lobe burr hole to a predetermined destination within the brain and then removed. On three of the animals, dorsal and temporal skull markers were used to establish a coordinate system against which the motions of the seed were referenced. These procedures were sufficiently accurate to permit the guided motion of the seed along nonlinear paths within the brain, including traversal of the midline through the corpus callosum. For removal, the seed could be steered either to a frontal lobe location for extraction through an auxiliary burr hole, or back to the same burr hole through which it had been inserted. This article discusses the way in which stereotactic motions were obtained, the performance limits of the instrumentation and the precision of motion achieved.

Animals↗

Thermodynamics of movable inductively heated seeds for the treatment of brain tumors.

A thermodynamic study is presented of temperature distributions created by an inductively heated 6-mm-diam Ni sphere imbedded in vivo and in vitro into porcine brain tissue. This study was performed in support of the development of a system that creates localized heat-induced lesions in deep-seated brain tumors. In this system, a magnetic "seed" will be remotely repositioned within the brain by an externally produced magnetic field. Convective effects of a hot moving seed will produce a different thermodynamic situation than that arising from an array of static implants. In this work, a study is presented of part of the expected change, in which a static sphere is heated to high temperature. Measurements were made of the temporal and spatial dependence of the temperature rise in the vicinity of the heated sphere, in vivo in four animals and in one that was euthanized immediately prior to experimentation. These results are used for parameter estimation with a theoretical model based on a point source solution to a form of the thermal diffusion equation, i.e., the "bioheat transfer equation." With this model thermal distributions from a power source of arbitrary geometry can be found using appropriate integration methods, and the method has widespread applicability. Estimates of blood flow rates, tissue thermal conductivity, and seed power absorption were found using the parameter estimation algorithm. The estimated blood perfusion exhibits a step increase following the first heating in multiple heating experiments. Thermal conductivity estimated using data from the nonperfused (in vitro) animal is 0.6 W/m degrees C. Seed power absorption is estimated correspondingly to be 0.9 W, a result confirmed independently with calorimetry. Statistical uncertainty is established for the radial decrease of the tissue temperature rise created by this method. This result allows estimation of a cell death boundary uncertainty of 0.6 mm, caused by fluctuations in power delivered to the seed, uncertainty in the temperature probe placements, and thermal properties such as blood perfusion and tissue thermal conductivity.

Animals↗