Biomedical subjects
Publications and source records attributed to J T Hoff.
A patient with herniated thoracic discs in tandem is reported. The previous literature is reviewed. Difficulties with the preoperative diagnosis and the surgical approach to these lesions are discussed.
Does an open skull alter the fundamental biomechanical properties of normal brain tissue? This question was studied in 32 anesthetized cats, 16 of which underwent a standard craniectomy (2.5 X 2.0 cm) in the left frontoparietal region. Brain tissue pressure, regional cerebral blood flow (rCBF), and brain water content were measured from the same area of cortical gray and white matter, and intracranial pressure (ICP) was recorded from the cisterna magna. Brain tissue resistance, tissue compliance, and the pressure-volume index were analyzed in response to a bolus injection of saline into brain tissue or the cisterna magna. Cerebrovascular resistance was also calculated. In craniectomized animals 2 hours after surgery, ICP had fallen to 3.75 +/- 0.39 mm Hg, and cortical gray and white matter tissue pressure had fallen to 3.19 +/- 0.47 and 4.69 +/- 0.54 mm Hg, respectively (mean +/- standard error of the mean); these variables did not fall further over 4 hours. The pressure-volume index in the same animals increased significantly from 0.67 +/- 0.01 to 0.86 +/- 0.04 ml. Tissue compliance rose in the cortical gray matter but tissue resistance fell, approximating that found in subjacent white matter. There was no significant difference between animals with and without craniectomy in rCBF, cerebrovascular resistance, or brain water content in either gray or white matter. These findings indicate that in the cat craniectomy causes an increase in the compensatory capacity of the intracranial cavity to increased volume. The data also indicate that cortical tissue has high hydraulic conductivity and compliance when the skull is opened.
Leukotrienes are pharmacologically active compounds that promote vascular permeability. In this study we sought to determine whether tissue leukotriene-like immunoreactivity was increased in intracranial tumors associated with peritumoral edema. In 20 patients undergoing craniotomy tissue specimens were immediately frozen after removal and tissue leukotriene C4 levels were determined by radioimmunoassay. An index of peritumoral edema was estimated from preoperative contrast-enhanced computed tomographic scans. There was a significant correlation between brain edema and tissue leukotriene levels (p less than 0.003). Metastatic tumors (n = 8) had the highest leukotriene C4 level at 13.8 +/- 8.5 pg/mg tissue (mean +/- SE) and the highest index of edema 5.7 +/- 1.8. The mean leukotriene C4 level in the gliomas (n = 5) was 6.2 +/- 2.3 pg/mg tissue and the edema index was 2.1 +/- 0.6. There was no edema and no neoplasm in the temporal lobes removed for seizure (n = 2), and their level of leukotriene C4 was 0.4 +/- 0.1 pg/mg tissue. The formation of leukotriene C4 is stimulated by intracranial tumors. Leukotrienes increase blood-brain barrier permeability and may be important in the formation of vasogenic edema surrounding tumors.
A case of acute cervical epidural abscess is presented. The use of intraoperative spinal sonography is discussed as a valuable adjunct in the evaluation and treatment of these uncommon lesions.
We examined the role of ischemic brain edema, tissue pressure gradients, and regional CBF (rCBF) in adjacent regions of cerebral cortex in cats with middle cerebral artery (MCA) occlusion (MCAO). Tissue pressure, rCBF, and water content were measured from gray matter in the central core and the peripheral margin of the MCA territory over 6 h after MCAO. Ventricular fluid pressure and CSF pressure were recorded. Tissue pressure in the ischemic core, with a flow of approximately 5 ml/100 g/min, increased more than that in the periphery where flow was approximately 19 ml/100 g/min. Tissue pressure rose progressively to 14.8 +/- 1.0 mm Hg in the core over 6 h after MCAO, establishing a significant pressure gradient between that tissue and the lateral ventricle nearby or the subarachnoid space in the middle fossa within the first 3 h. The increase in tissue pressure was linearly related to the amount of edema fluid that developed until the edema reached a severe degree. This study shows that a hydrostatic tissue pressure gradient within ischemic cortex is associated with ischemic brain edema. The magnitude of the gradient that develops is related to the severity of ischemic edema in that tissue.
We studied whether a hydrostatic pressure gradient between arterial blood and brain tissue plays a role in the formation of early ischemic cerebral edema after middle cerebral artery (MCA) occlusion in cats. Tissue pressure, regional CBF, and water content were measured from the cortex in the core and the peripheral zone of brain normally perfused by the MCA. Intraluminal arterial pressure was altered at intervals by inflation of an aortic balloon to vary the blood-tissue pressure gradient in the ischemic zone. Brain water content in the ischemic core, where flow fell to 5.5 ml/100 g/min, increased within 1 h of occlusion. After occlusion tissue pressure rose from 7.95 +/- 0.72 mm Hg at 1 h to 13.16 +/- 1.13 mm Hg at 3 h. When intraluminal pressure was increased, water content increased further, but only at 1 h after occlusion. In the periphery where flow was 18.9 ml/100 g/min during normotension, neither water content nor tissue pressure rose within 3 h of occlusion. Increased intraluminal pressure was accompanied by increased water content only at 3 h. This study indicates that a hydrostatic pressure gradient is an important element in the development of ischemic brain edema, exerting its major effect during the initial phase of the edema process.
The retrolabyrinthine section of the vestibular nerve is an effective procedure for the ablation of unilateral vestibular function while preserving hearing. Although this procedure has been most frequently used for the control of unilateral Meniere's disease, it may also be effective in the control of unilateral vestibular dysfunction of other etiologies. A 2-year experience with the indications for and the surgical results in a series of patients who underwent this procedure is presented. Brief case histories of a variety of etiologies of unilateral vestibular dysfunction are discussed.
The effect of standard parenteral nutritional formulas on cold-induced vasogenic edema formation in cats was examined and compared to the effects of 5% dextrose, 0.9% saline, and 40.5% mannitol. The amount of vasogenic edema formed during a 3-hour period of fluid infusion following cold injury was quantified by a computerized graphics tablet determination of the volume of Evans blue-dyed white matter. Specific gravity measurements were taken as a measure of white matter water content. Serum osmolality, urine output, arterial blood gases, hematocrit, body temperature, and systolic blood pressure were measured periodically throughout the infusion period. Parenteral nutritional formulas and a 40.5% mannitol solution produced greater changes in serum osmolality than did 5% dextrose or 0.9% saline. Greater changes in serum osmolality were associated with larger calculated volumes of edema in the injured hemisphere and lower water contents in the uninjured hemisphere. The data indicate that hyperosmolar solutions may potentiate vasogenic edema formation when the blood-brain barrier is open.
Acute arterial hypertension was studied in normal cats to determine its role in the formation of brain edema. Arterial hypertension was induced for 30 minutes by inflation of a balloon catheter situated in the descending aorta. Cerebral edema was evaluated by gross and microscopic observations, tissue water content by wet/dry weights, and blood-brain barrier (BBB) permeability by extravasation of horseradish peroxidase (HRP) and Evans blue dye. For 1 hour after the hypertensive insult, tissue pressure and regional cerebral blood flow (rCBF) were measured from the arterial boundary zone and from a non-boundary region, and intracranial pressure was recorded from the lateral ventricle as ventricular fluid pressure. Focal lesions with increased BBB permeability to Evans blue dye or HRP were usually located symmetrically in the cortex, corresponding to the occipitoparietal parts of the arterial boundary zones. The increase in water content was found only in areas of increased permeability. Tissue pressure increased simultaneously with the abrupt rise in blood pressure, and an increase in rCBF paralleled the elevation of blood pressure. Tissue pressure and rCBF returned to a steady state when blood pressure returned to normal. There were no differences in tissue pressure or rCBF between the arterial boundary zone and the non-boundary zone, even during arterial hypertension. In cerebral hemispheres examined 48 hours after the hypertensive challenge, brain edema had not continued to develop. The data indicate that acute arterial hypertension may produce focal brain edema with increased permeability of the BBB in the cortex of normal brain, particularly in the arterial boundary zones. The authors postulate that increased cerebral blood volume, high intraluminal pressure, and breakthrough of autoregulation play an important role in the formation of hypertensive brain edema.
Cerebral protection from an ischemic/hypoxic insult implies that tissue injury can be controlled or even prevented by certain therapeutic maneuvers. For example, physiological thresholds may be altered so that tissue vulnerability to the insult is reduced, or the intensity of an insult may be blunted by enhancing brain homeostasis. Such a therapeutic maneuver is carotid endarterectomy to improve blood flow in the disordered hemisphere. Alternatively, drugs with protective properties can be used before or even after the insult to "stabilize" injured tissue and prevent the harmful secondary effects that often follow. Various past and present approaches to cerebral protection employing physiological, pharmacological, and surgical intervention are reviewed. The mechanisms by which each allegedly protects the brain from ischemia and hypoxia are discussed briefly. Promising, but not always successful, approaches used in the past have pointed the way for new and more rational therapies. Truly effective protection of the brain from ischemia and hypoxia depends directly upon our capability to explore basic mechanisms of injury and our willingness to measure accurately and objectively the outcome of newly developed protective measures.
To examine whether leukotrienes could increase blood-brain barrier permeability, rats were anesthetized and injected intravenously with Evans blue. Ten microliters of vehicle, of leukotrienes B4, C4, or E4, or of arachidonic acid was injected over 1 hour directly into the brain parenchyma. The percentage of the total surface area of Evans blue extravasation in a coronal section of brain centered on the injection site was then determined as an estimate of blood-brain barrier permeability. Leukotrienes B4, C4, and E4, and arachidonic acid all increased blood-brain barrier permeability, but this effect was lost when the total dose was reduced to 20 ng. Increased blood-brain barrier permeability induced by arachidonic acid could be prevented by pretreatment with the lipoxygenase inhibitor BW755C, but not with indomethacin. Leukotrienes may play a role in the development of increased blood-brain barrier permeability after cerebral injury.
The management of closed head injury has improved recently. Mortality rates for severe trauma are lower and outcomes are more favorable. Advances are related to improved diagnostic tools, such as computerized tomography scanning, aggressive supportive care, standardized evaluation criteria, and program-oriented rehabilitation. Further progress depends on sophisticated triage, including delivery of the patient to an experienced head-injury unit, as well as successful manipulation of cellular and subcellular processes to maintain brain homeostasis. Recent developments in the pathophysiology, diagnosis, and treatment of closed head injury are reviewed, and promising research avenues are discussed.
Posttraumatic progressive myelopathy (PTPM) was studied in nine patients and grouped into three categories on the basis of characteristic radiographic findings and response to therapy: (a) myelomalacia with no cystic degeneration, which has poor response to therapy; (b) small cysts, with poor response to therapy; and (c) large cysts, which are effectively treated by decompression. One type dominated in each patient, although a mixture of types was present in each. Magnetic resonance (MR) imaging gave slightly improved resolution and specificity of type, decreased morbidity, and simplification of procedure in comparison with imaging by delayed computed tomographic metrizamide myelography (DCTM). DCTM and MR imaging results correlated nearly equally with those of intraoperative sonography (IOS) and pathologic study at surgery. IOS was superior to DCTM or MR imaging in detecting septations and small additional cysts. IOS also was helpful in myelotomy positioning, shunt placement, and verification of cyst decompression. MR imaging may replace DCTM in the preoperative evaluation of PTPM, followed by IOS imaging as indicated. Patients with nonmyelopathic signs and symptoms (e.g., radiculopathy) probably still require study with conventional and/or CT myelography.
Twenty-three anesthetized cats underwent permanent middle cerebral artery occlusion in a study of the relationships of regional cerebral blood flow, ventricular fluid pressure, brain tissue pressure, and ischemic edema formation. A pressure gradient of 8 mm Hg developed between ischemic tissue and normally perfused tissue during a 4-hour observation period after occlusion. Brain water accumulated as tissue pressure rose, while blood flow in the same area fell. The data suggest, but do not prove, that ischemic brain edema causes tissue pressure to rise focally, and that blood flow to the ischemic zone is compromised further by the resultant hydrostatic pressure gradient.
Eicosapentaenoic acid is converted by cyclo-oxygenase to the prostacyclin, PGI3. Consequently eicosapentaenoic acid might protect the brain from the impairment in cerebral blood flow that follows temporary cerebral arterial occlusion. We studied the effect of 90% pure eicosapentaenoic acid, given intravenously, on cerebral blood flow, brain water and prostaglandins after ischemia in gerbils. Ischemia was produced by bilateral carotid occlusion for 15 min followed by reperfusion for 2 h. In experimental gerbils, 0.833 mg or 0.167 mg of eicosapentaenoic acid (Na salt) was given intravenously followed by a continuous infusion of 1 mg h-1. Control gerbils were given 0.167 mg of linoleic acid (Na salt) intravenously followed by a continuous infusion of 1 mg h-1 or a saline infusion. Regional cerebral blood flow was measured by the hydrogen clearance method and brain water by the specific gravity technique. Brain diene prostaglandins were measured by radioimmunoassay. In control gerbils cerebral blood flow decreased significantly during reperfusion and remained depressed after 2 h of reperfusion. In eicosapentaenoic acid treated gerbils blood flow decreased initially but after 2 h of reperfusion blood flow was significantly higher than in control gerbils. Brain edema and brain diene prostaglandins were not significantly different between control and experimental groups. Our study indicates that eicosapentaenoic acid, given intravenously, improves cerebral blood flow after ischemia and reperfusion. We speculate that this effect may be due to the formation of the prostacyclin, PGI3.
Lumbar myelography was performed in 38 patients; 19 received iohexol (an investigational aqueous contrast agent) and 19 received metrizamide. Iohexol is stable in solution, which is not the case with metrizamide. There was no other significant difference in diagnostic utility or quality between the two media. However, there was considerable postmyelography morbidity in the metrizamide group, but no postmyelography morbidity in the iohexol group. Preliminary clinical evidence suggests that iohexol is significantly superior to metrizamide as a contrast agent for lumbar myelography.
Lumbar myelography was performed in 50 patients; 25 received iohexol (an investigational aqueous contrast agent) and 25 received metrizamide. The two media produced radiographs of equal quality. However, iohexol is stable in solution, while metrizamide is not. Further, markedly less morbidity resulted from iohexol. These features indicate that iohexol may be superior to metrizamide as a contrast agent for lumbar myelography.
This study of direct tissue pressure measurement from brain parenchyma in 25 anesthetized cats focuses on steady-state observations and responses to some common physiological manipulations. Tissue pressure recording by a needle system can be done accurately without significant alterations of the blood-brain barrier, brain water content, regional cerebral blood flow, and cerebrovascular reactivity to changes in PaCO2 and cerebral perfusion pressure. Methodological details, including in vitro and in vivo validation, are described.