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Biomedical subjects

D P Becker

Publications and source records attributed to D P Becker.

At least 91 records · Page 5Linked to original sources
PubMed1990

Novel 21-aminosteroids prevent tumour associated neurological dysfunction.

The efficacy of the potent lipid peroxidation inhibitors U-74006F and U-78517F in the treatment of blood-tumour barrier permeability and tumour associated neurological dysfunction was evaluated. Rats with stereotactically implanted Walker 256 tumours were treated with methylprednisolone (MP), U-74006F, U-78517F, or vehicle. (0.05 N HCl) on days 6 through 10 following implantation. Neurologic function and vascular permeability was assessed on day 10. U-74006F and MP were equally effective at preventing neurologic dysfunction compared to control (p less than 0.01). U-78517F was slightly less effective than U-74006F and MP but was significantly better than vehicle in preventing neurological dysfunction. MP resulted in a significant decrease in tumour vascular permeability (p less than 0.006) while the lipid peroxidation inhibitors had no effect on permeability.

Animals↗
PubMed1990

Cellular swelling during cerebral ischaemia demonstrated by microdialysis in vivo: preliminary data indicating the role of excitatory amino acids.

When rapid cellular swelling occurs, water moves from the extracellular space (ECS) into the cells and the concentration of ECS markers which do not move into the cells increases. Cellular swelling during cerebral ischaemia has therefore been demonstrated in vivo as an increase in ECS markers which is measurable with intracerebral electrodes. We attempted to detect the cellular swelling by brain microdialysis employing a similar principle. Dialysis probes were placed in the hippocampus, and perfused for 20 min with 14C-sucrose as an ECS marker. The probes were subsequently perfused without 14C-sucrose and the dialysate concentration of 14C-sucrose was determined at 1-min intervals. The dialysate concentrations of 14C-sucrose suddenly became elevated 1-3 min after the onset of cerebral ischaemia, indicating the occurrence of cellular swelling. The present technique is useful because it enables the mechanism of cellular swelling to be analyzed by observing the effects of pharmacological agents administered through a dialysis probe. Preliminary data indicating the role of excitatory amino acids in producing cellular swelling during cerebral ischaemia are presented as an example.

Amino Acids↗
PubMed1990

Early cellular swelling in experimental traumatic brain injury: a phenomenon mediated by excitatory amino acids.

Early cellular swelling following fluid-percussion brain injury was demonstrated in vivo by means of microdialysis in the rat. When rapid cellular swelling occurs, water moves from the extracellular space (ECS) into the cells and the extracellular concentration of ECS marker which does not move into the cells increases. Cellular swelling was therefore demonstrated in vivo as an increase in the dialysate concentration of 14C-sucrose ([14C-sucrose]d) pre-perfused as an ECS marker. The increase in [14C-sucrose]d occurred concomitantly with an increase in the dialysate concentration of K+ ([K+]d) representing large ionic fluxes. The increases in [K+]d and [14C-sucrose]d were both inhibited by kynurenic acid, a broad spectrum antagonist of excitatory amino acids (EAAs), which was administered through the dialysis probe. These findings suggest that early cellular swelling following traumatic brain injury is a result of ionic fluxes mediated by EAAs.

Amino Acids↗
PubMed1990

Imaging peripheral benzodiazepine receptors in brain tumors in rats: in vitro binding characteristics.

Peripheral benzodiazepine binding constants for transplanted RG-2 gliomas and HD and LK Walker 256 tumors (metastatic breast carcinoma) were determined in Wistar rats using autoradiography. In addition, Kd and Bmax parameters for peripheral benzodiazepine receptors on RG-2 tumors were directly visualized using digital image analysis of autoradiograms. High specific binding of [3H]PK11195, a selective peripheral benzodiazepine ligand, had excellent topographical correlation to areas of histologically verified tumor. Scatchard analysis suggested a single class of peripheral binding sites with similar binding affinities in RG-2 and LK Walker 256 tumors and normal cortex. Bmax was 20-fold greater in glial tumors and 11.6- and 10.6-fold greater in LK and HK Walker 256 tumors, respectively, compared to normal cortex. The location of metastatic tumors, either intracerebrally or subcutaneously, did not effect their Kd or Bmax values. Kd and Bmax values for RG-2 tumors were similar whether determined densitometrically or by direct visualization with image analysis. Binding parameters within normal brain were difficult to visualize by image analysis due to the low level of specific binding. The ability to label specifically intracerebral tumor cells and to characterize the binding parameters shown in this study suggest that peripheral benzodiazepine receptor ligands could be utilized by PET to analyze directly a variety of tumors in humans.

Animals↗
PubMed1990

Three-dimensional comparison of peripheral benzodiazepine binding and histological findings in rat brain tumor.

Experiments were undertaken to determine the in vivo utility of the mixed benzodiazepine ligand [3H]flunitrazepam and the selective peripheral benzodiazepine ligand [3H]PK 11195 [1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide] to outline the borders of rat C6 glial tumors in three dimensions. Intravenous injection of [3H]flunitrazepam resulted in a tumor/cortex ratio of radioactive densities between 2.7 and 1.5 within the first 60 minutes after injection. [3H]PK 11195 demonstrated a higher tumor/cortex ratio (5.3) than [3H]flunitrazepam. For three-dimensional studies, images were generated from thionin-stained histological sections and autoradiograms. The mixed type benzodiazepine ligand [3H]flunitrazepam was superior in showing some of the normal anatomical structures surrounding the tumor, whereas [3H]PK 11195, a specific peripheral ligand, demonstrated higher tumor/brain contrast and superior topographical correlation between histological and autoradiographic images. Implications of peripheral benzodiazepine receptor ligands for positron emission tomography are discussed.

Animals↗
PubMed1990

Focal functional anatomy of dorsolateral frontocentral seizures.

We compared 6 patients with dorsolateral frontocentral seizures to 7 patients with temporal lobe seizures. We determined general seizure location by structural lesions in 7 patients, bilateral depth electrodes in 4, and EEG and semiology in 2. We then mapped seizure cortex and essential cortex using chronic ECoG arrays. Two ECoG patterns were similar in frontal and temporal seizures. Focal patterns were near lesions and resections. Regional patterns were distant from lesions but not associated with worse surgical outcome. "Dipolar" seizure patterns occurred in one-half of frontal patients with maps like somatosensory evoked responses, consistent with focal seizure anatomy and involvement of sensorimotor cortex. Dipole location estimates were near centers of seizure cortex determined by lesions, semiology, and outcome. Six temporal patients had focal excisions that gave significant seizure reduction in all. All frontocentral patients had focal excisions that significantly reduced seizures except in 1 patient with progressive disease. We conclude that dorsolateral frontocentral seizures have focal functional anatomy that can be predicted by ictal ECoG.

Adult↗
PubMed1990

Massive increases in extracellular potassium and the indiscriminate release of glutamate following concussive brain injury.

An increase in extracellular K+ concentration ([K+]c) of the rat hippocampus following fluid-percussion concussive brain injury was demonstrated with microdialysis. The role of neuronal discharge was examined with in situ administration of 0.1 mM tetrodotoxin, a potent depressant of neuronal discharges, and of 0.5 to 20 mM cobalt, a blocker of Ca++ channels. While a small short-lasting [K+]c increase (1.40- to 2.15-fold) was observed after a mild insult, a more pronounced longer-lasting increase (4.28- to 5.90-fold) was induced without overt morphological damage as the severity of injury rose above a certain threshold (unconscious for 200 to 250 seconds). The small short-lasting increase was reduced with prior administration of tetrodotoxin but not with cobalt, indicating that neuronal discharges are the source of this increase. In contrast, the larger longer-lasting increase was resistant to tetrodotoxin and partially dependent on Ca++, suggesting that neurotransmitter release is involved. In order to test the hypothesis that the release of the excitatory amino acid neurotransmitter glutamate mediates this increase in [K+]c, the extracellular concentration of glutamate ([Glu]c) was measured along with [K+]c. The results indicate that a relatively specific increase in [Glu]c (as compared with other amino acids) was induced concomitantly with the increase in [K+]c. Furthermore, the in situ administration of 1 to 25 mM kynurenic acid, an excitatory amino acid antagonist, effectively attenuated the increase in [K+]c. A dose-response curve suggested that a maximum effect of kynurenic acid is obtained at a concentration that substantially blocks all receptor subtypes of excitatory amino acids. These data suggest that concussive brain injury causes a massive K+ flux which is likely to be related to an indiscriminate release of excitatory amino acids occurring immediately after brain injury.

Animals↗
PubMed1990

Thallium-201 SPECT imaging of brain tumors: methods and results.

Recent studies suggest that thallium-201 (201Tl) planar scans of brain tumors more accurately reflect viable tumor burden than CT, MRI, or radionuclide studies with other single-photon emitting compounds. We have previously reported the utility of 201Tl SPECT index in distinguishing low- from high-grade gliomas elsewhere. Here we describe the technical considerations of deriving a simple 201Tl index, based on uptake in the tumor normalized to homologous contralateral tissue, from SPECT images of brain tumors. We evaluated the importance of consistently correcting for tissue attenuation, as it may achieve better lesion discrimination on qualitative inspection, and the methodologic limitations imposed by partial volume effects at the limits of resolution.

Astrocytoma↗
PubMed1989

Relationship between CT attenuation changes and post-traumatic CSF-CKBB-activity after severe head injury in man.

In order to evaluate if it is practically possible to assess the volume of contused brain tissue from the CT pictures, a comparison has been carried out between the size of the cerebral contusion(s)--as estimated from the CT scans--and the post-traumatic CSF-CKBB activity, in a series of 29 patients with severe head injury. A clearance curve for the elimination of CKBB from the CSF was constructed. The relation between contusion volume and CSF-CKBB-activity was not statistically significant, while the relationships between contusion volume and outcome, and between CSF-CKBB, as estimated at 6 hours after from the clearance curve, and outcome, were.

Adolescent↗
PubMed1989

Use of thallium-201 SPECT to quantitate malignancy grade of gliomas.

A quantitative preoperative technique using thallium-201 single-photon emission computerized tomography is described which predicts whether specific gliomas are of high- or low-grade malignancy. An index, based on the ratio of thallium uptake in the tumor versus the homologous contralateral brain, was calculated and compared with tumor histology. The index in 14 patients with low-grade malignant gliomas was 1.27 +/- 0.40 in contrast to an index of 2.40 +/- 0.61 in 11 patients with high-grade malignant gliomas (p less than 0.0005). Whether gliomas were of low- or high-grade malignancy could be predicted with 89% accuracy using a threshold of 1.5. Low-grade gliomas with an index higher than 1.5 acted biologically more like high-grade tumors, and no tumor histologically classified as being of high-grade malignancy had an index lower than 1.7. This technique could help to reduce unrecognized sampling errors during needle biopsies of brain tumors, particularly of high-grade lesions classified in error as low-grade tumors due to inadequate biopsy material.

Aged↗
PubMed1988

The magnetic and electric fields agree with intracranial localizations of somatosensory cortex.

We measured the magnetoencephalogram (MEG), electroencephalogram (EEG), and electrocorticogram (ECoG) after stimulation of contralateral median nerve in four patients with partial epilepsy evaluated for surgery. Quantitative localization estimates from equivalent source modeling were compared with locations of central fissure in hand sensorimotor area determined by cortical stimulations, intraoperative photographs, and examination after excision in frontal lobe. We also measured MEG and EEG in nine control subjects. MEG and EEG localizations were within 2.5 cm of the estimated location of central fissure in all 13 subjects. In the three patients who had complete mapping of all three fields, the average distance of localizations from central fissure was approximately 4 mm in both MEG and EEG, 3 mm in ECoG, and 3 mm in combined MEG and EEG. MEG was simpler than EEG, which was simpler than ECoG. MEG resolved ambiguities in both EEG and ECoG. The combination of the three fields added information about the spatiotemporal activity of somatosensory cortex. Localization of central fissure was essential to surgical treatment.

Brain Mapping↗
PubMed1988

Value of skull radiography, head computed tomographic scanning, and admission for observation in cases of minor head injury.

A retrospective review of 373 adult patients admitted to Harbor General Hospital between 1980 and 1984 for minor closed head injury (Glasgow coma scale 13-15) was performed to determine the benefits of skull radiography, computed tomographic (CT) scanning of the head, and admission for observation. Variables reviewed were mental status, neurological examination, presence or absence of loss of consciousness, clinical evidence of basilar skull fracture, and fracture on skull radiography. The neurological examination (including mental status and Glasgow coma scale) in the emergency room was the best predictor of subsequent deterioration or the presence of an operative hematoma. The only patients with Glasgow coma scale scores of 15 who required surgical evacuation of an extraaxial hematoma had focal neurological deficits referable to hemispheric compression, with or without an abnormal mental status. A Glasgow coma scale score of 13 or 14 places the patient at risk either of having a hematoma requiring surgery or of deteriorating. We recommend that a head CT scan be obtained on all patients with Glasgow coma scale scores of less than 15, abnormal mental status, or hemispheric neurological deficits. If no operative lesion is found on the CT scan, the patient should be admitted for observation because there is still a risk of deterioration. Those with a Glasgow coma scale score of 15, a normal mental status, and no hemispheric neurological deficit may be discharged to be observed at home by a competent observer despite basilar or calvarial skull fracture, loss of consciousness, or cranial nerve deficit. No benefit was gained from skull radiography in any group.

Adolescent↗
PubMed1988

Brain cellular injury and recovery--horizons for improving medical therapies in stroke and trauma.

An edited summary of an Interdepartmental Conference arranged by the Department of Medicine of the UCLA School of Medicine, Los Angeles. The Director of Conferences is William M. Pardridge, MD, Professor of Medicine. After ischemic and traumatic brain injury, many cells may be rendered dysfunctional but are not irreversibly damaged or disrupted. The brain tissue may become metabolically deranged, and neurons, while still alive, are paralyzed and cannot create an action potential or conduct an electrical impulse. This injured brain tissue is in a precarious state of increased vulnerability. If the milieu of the favorable, they may recover; if it is slightly unfavorable, they may die. There is now evidence that reversibly injured brain tissue will die from an ischemic or hypoxic insult ordinarily tolerated by the normal brain. The major challenge of modern research in stroke and trauma is to define the chemical and metabolic milieu in which the injured brain exists and to define an ideal milieu for healing.

Adult↗
PubMed1987

Brain tissue pH in severely head-injured patients: a report of three cases.

It is well established that low cerebrospinal fluid (CSF) pH and high CSF lactate concentration indicate the development of brain acidosis after severe human head injury. However, there is no direct evidence that tissue acidosis actually occurs. We measured brain extracellular pH (pHe) in three patients undergoing operation for the evacuation of acute subdural hematomas. A pH-sensitive polymer membrane electrode was inserted 500 micron into the cerebral cortex close to the damaged area. The pHe values obtained were correlated with ventricular CSF acid-based parameters and extension of the brain lesion. The CSF pH was higher than the pHe in all cases; the pHe was particularly low in areas of contusion or compression by mass lesion. The effect of focal brain tissue acidosis on clinical course after severe head injury is discussed.

Acid-Base Equilibrium↗
PubMed1987

Transient suppression of event-related evoked potentials produced by mild head injury in the cat.

Studies in humans have shown that sensory stimuli, presented in the context of certain tasks, can elicit a late positive component (LPC), namely P300, in the scalp-recorded evoked potential believed to reflect neural activity related to attentional processes. A similar LPC has been reported in cats and monkeys. In this study, the LPC of the auditory evoked potential (AEP) in the cat was used to detect impairment in attention to a relevant stimulus after low levels of cerebral concussion produced by a fluid percussion device. A hollow screw (for fluid percussion) and stainless steel screws (for AEP recording) were surgically placed in the skull. After recovery from surgery, animals were trained in the paradigm to obtain an LPC. Pupillary dilation was conditioned to tones. A random sequence of two discriminable tones was presented. The lower tone had a probability of 0.1 and was followed by a tail shock (tone-shock). After 400 to 1000 tone-shock presentations, animals attended to the lower tone stimulus as inferred by selective pupillary dilation. In the AEP an early positive component at 50 to 120 msec related to an alerting response was enhanced, and an LPC at 250 to 450 msec appeared in response to the paired tone-shock. Animals were then subjected to cerebral concussion. Complete recovery of normal reflexes, motor coordination, and orienting response was seen within 2 hours after injury. The LPC was suppressed for a period of at least 3 days, suggesting that low magnitudes of brain injury can disrupt higher-order neural activities. This disruption can persist despite recovery of other neurological functions.

Animals↗
PubMed1986

Induced hypertension for the treatment of cerebral ischemia after subarachnoid hemorrhage. Direct effect on cerebral blood flow.

The best treatment for symptomatic cerebral ischemia from presumed vasospasm after aneurysmal subarachnoid hemorrhage remains a matter of controversy. A direct effect of any treatment modality on regional cerebral blood flow has never been documented. In a series of 43 patients operated on for ruptured anterior circulation aneurysms, five patients (11.6%) developed clinical signs of cerebral ischemia postoperatively. In four of those patients, the diagnosis of "vasospasm" was made with measurements of cerebral blood flow (133Xe inhalation or intravenous injection, 10-16 detectors, cerebral blood flow infinity). Treatment with induced arterial hypertension with phenylephrine was instituted. Hemodilution was instituted in one patient; the other three patients already had hematocrits in the range of 33. Within 1 hour, the cerebral blood flow measurement was repeated to document the effect of treatment. The average pretreatment hemispherical blood flow on the operated side was 18.8 mL/100 g per minute, on the contralateral side 21.0 mL/100 g per minute. With treatment these flows increased to 30.8 and 35.8 mL/100 g per minute, respectively. There was also an immediate and obvious positive clinical effect in all patients. The role of measurement of cerebral blood flow in the clinical management of vasospasm is discussed. We stress the theoretical and practical advances of measurements of cerebral blood flow over cerebral angiography, especially in comatose patients.

Adult↗