Biomedical subjects

D P Becker

Publications and source records attributed to D P Becker.

At least 73 records · Page 4Linked to original sources

PubMed1992

Secondary injury and acidosis.

Following traumatic brain injury, cells that are not directly, and thereby irreversibly damaged are subjected to ionic fluxes including potassium and calcium. This injury-induced ionic flux is a result of both neuronal firing via direct mechanical stimulation of the neurons as well as the activation of ligand-gated ion channels primarily associated with excitatory amino acids (e.g. glutamate). This ionic destabilization places enormous energy demands on these cells in order to activate pumping mechanisms to reinstate normal ionic balance. The primary fuel used to acquire this energy is glucose, which results in a period of hyperglycolysis leading to the accumulation of lactate. This acute period of increased glucose metabolism lasts only during the acute period, after which these same cells exhibit a state of chronic metabolic depression for both glucose and oxygen. This metabolic derangement may prevent the necessary energy production for maintaining cellular protein synthesis which is inhibited following traumatic brain injury. This injury-induced metabolic derangement is not uniform throughout all regions. Some structures are more or less affected presumably due to their proximity to the site of trauma and/or to the extent to which they have a preponderance to being more vulnerable to insult. Within these affected regions, the metabolic dysfunction indicates that cells are functionally compromised in their ability to respond to both normal physiologic and pathophysiologic challenges. This results in the expression of neurological deficits and an enhanced vulnerability of these cells to a second insult, both of which dissipate as normal metabolic function returns over time.

Acidosis↗

PubMed1992

Chronic lymphocytic leukemia presenting as a pituitary mass lesion.

We describe a unique case of chronic lymphocytic leukemia (CLL) in a patient who presented with bitemporal hemianopsia, adrenal insufficiency, and gonadotrophin deficiency. Studies revealed an enhancing intrasellar mass with suprasellar extension and displacement of the optic chiasm. Peripheral blood and cerebrospinal fluid (CSF) studies disclosed a monoclonal IgM kappa expressing B-cell CLL. Biopsy of the pituitary mass revealed dense infiltration of the pituitary gland by leukemic cells. This is, to our knowledge, the first reported case of CLL presenting as a pituitary mass lesion.

Brain↗

PubMed1991

Inhibition of rapid potassium flux during cerebral ischemia in vivo with an excitatory amino acid antagonist.

Previous studies have demonstrated that microdialysis is capable of detecting an abrupt and massive increase in extracellular K+ concentration ([K+]e) and a concomitant increase in extracellular concentration of excitatory amino acids (EAAs) during cerebral ischemia in the rat hippocampus in vivo. Following in situ administration of kynurenic acid (KYN), a broad-spectrum antagonist of EAAs, through the dialysis probe (5-10 mM), a delay in reaching the maximum level of increased [K+]e was observed in a dose-dependent manner. The initial component of the rapid increase in [K+]e appears to be mediated by EAAs released from nerve terminals.

Amino Acids↗

PubMed1991

Diffuse prolonged depression of cerebral oxidative metabolism following concussive brain injury in the rat: a cytochrome oxidase histochemistry study.

Utilizing a lateral fluid percussion injury as a model of cerebral concussion, rats were studied histochemically measuring the degree of cytochrome oxidase activity present within different structures at different times following injury. After concussion, the cerebral cortex ipsilateral to the site of injury exhibited a diffuse decrease in its level of chromotome oxidase (CO) activity beginning at as soon as one day and lasting for up to 10 days after the insult. The ipsilateral dorsal hippocampus also exhibited an injury-induced decrease in CO activity, however, it was not as severe as in the cortex. These results indicate that oxidative metabolism is depressed primarily within the cerebral cortex and hippocampus for several days following a cerebral concussion. We propose that this period of metabolic depression may delineate a period of time during which the injured brain is unable to function normally and thus would be vulnerable to a second insult.

Animals↗

PubMed1991

Calcium-dependent component of massive increase in extracellular potassium during cerebral ischemia as demonstrated by microdialysis in vivo.

This study characterizes the physiological features and limitations of K(+)-free dialysis to detect changes in extracellular concentration of K+ ([K+]e) in the rat hippocampus in vivo. It also demonstrates the effects of Ca(2+)-free perfusate containing Co2+ or Mg2+, which blocks Ca2+ entry into the presynaptic nerve terminal, on the abrupt increase in [K+]e detected by this technique during cerebral ischemia. K(+)-free dialysis for 40 min caused no significant changes in the baseline [K+]e. In contrast, Ca(2+)-free dialysis for 40 min significantly reduced the extracellular Ca2+ concentration. Under this condition, together with addition of Co2+ or Mg2+ to the perfusate, the increase in [K+]e was delayed, and a delay in reaching the maximum level was observed in a dose-dependent manner. These results are consistent with the hypothesis that the initial increase in [K+]e during cerebral ischemia is related to the Ca(2+)-dependent exocytotic release of neurotransmitters from depolarized nerve terminals.

Animals↗

PubMed1991

Dynamic changes in local cerebral glucose utilization following cerebral conclusion in rats: evidence of a hyper- and subsequent hypometabolic state.

Following cerebral concussion, in which there is no evidence of direct morphological damage, cells are exposed to an increase in extracellular potassium as well as an accumulation of calcium. This concussion-induced ionic flux most likely alters the cellular energy demands thereby modifying metabolic processes. To investigate the metabolic changes after cerebral concussion, local cerebral metabolic rates for glucose (lCMRglc) utilizing [14C]2-deoxy-D-glucose were studied in rats (n = 98; 250-300 g) immediately, 30 min, 6 h, 1, 2, 3, 5 and 10 days following a unilateral frontoparietal fluid percussion (F-P) injury (3.7-4.3 atm). Compared to sham controls, animals exhibited bilateral hypermetabolism immediately following brain injury. However, this effect was more pronounced in structures ipsilateral to the site of F-P and was especially marked for the cerebral cortex (46.6-30.1% higher than control) and hippocampus (90.1-84.4% higher than control). By 30 min post-trauma many ipsilateral regions still showed evidence of hypermetabolism, although their lCMRglc had subsided. Beginning as early as 6 h following injury many regions within the ipsilateral cortex and hippocampus went into a state of metabolic depression (16.4-33.7% of control) which lasted for as long as 5 days. These results indicate that, although not mechanically damaged from the insult, cells exposed to concussive injury dramatically alter their metabolic functioning. This period of post-concussive metabolic dysfunction may delineate a period of time, following injury, during which cells are functionally compromised.

Animals↗

PubMed1991

Calcium-dependent glutamate release concomitant with massive potassium flux during cerebral ischemia in vivo.

The changes in extracellular glutamate ([Glu]e) and potassium ([K+]e) in the rat hippocampus during cerebral ischemia were determined simultaneously by microdialysis in vivo. Biphasic increases in [Glu]e, i.e. an earlier rapid increase concomitant with an abrupt increase in [K+]e followed by a later slow increase, were observed. Dialysis with Ca(2+)-free perfusate containing Co2+ blocked the earlier rapid increase completely but the later slow increase only partially. These findings suggest that Ca(2+)-dependent exocytotic release from the presynaptic nerve terminals is involved predominantly in the earlier rapid increase in [Glu]d. The later slow increase in [Glu]d may be due in part to a breakdown of membrane function resulting from several causes, including a loss of the electrogenic component of the glutamate gradients across the plasma membrane, and a loss of function of the glutamate uptake system.

Animals↗

PubMed1991

Peripheral benzodiazepine induces morphological changes and proliferation of mitochondria in glioma cells.

Peripheral benzodiazepine (PBD) receptors are localized on the mitochondrial membrane and are highly expressed in brain tumors compared to normal brain. To elucidate the biological role of the PBD receptor on mitochondria, we examined the effect of PBDs on mitochondrial morphology in C6 and T98G glioma cells using rhodamine 123 and quantitative electron microscopy. In cells incubated in serum-free medium alone, mitochondria were distributed in a filamentous pattern throughout the cytoplasm. By contrast, the mitochondria aggregated in the perinuclear region in PK11195 or Ro5-4864 (10 nM) treated cells. Quantitative electron micrography revealed a 250% increased in the number of mitochondria with elongated cristae and a fivefold increase in dividing mitochondria in PK11195-treated cells compared with cells incubated in serum-free medium alone. PBD treatment also resulted in vacuolation within the matrix and mitochondrial swelling. These data suggest that PBDs influence mitochondrial morphology and induce mitochondrial replication in cultured glioma cells.

Animals↗

PubMed1991

Intracarotid infusion of leukotriene C4 selectively increases blood-brain barrier permeability after focal ischemia in rats.

Intracarotid infusions of leukotriene C4 (LTC4) were used to open selectively the blood-brain barrier (BBB) in ischemic tissue after middle cerebral artery (MCA) occlusion in rats. BBB permeability was determined by quantitative autoradiography using [14C]aminoisobutyric acid. Seventy-two hours after MCA occlusion, LTC4 (4 micrograms total dose) infused into the carotid artery ipsilateral to the MCA occlusion selectively increased the unidirectional transfer constant for permeability Ki approximately threefold within core ischemic tissue and tissue adjacent ot the ischemic core. No effect on BBB permeability was seen within nonischemic brain tissue or in ischemic tissue after only 24 h after MCA occlusion. gamma-Glutamyl transpeptidase (gamma-GTP) activity was decreased in capillaries in ischemic tissue at 48 and 72 h after infarction, compared to high gamma-GTP in normal brain capillaries and moderate gamma-GTP in capillaries in the ischemic tissue at 24 h after infarction. These findings suggest that normal brain capillaries resist the vasogenic effects of LTC4. In contrast, LTC4 increases permeability in capillaries of ischemic tissue, where gamma-GTP is decreased. gamma-Glutamyl transpeptidase, an enzyme that inactivates LTC4 to LTD4 and LTE4 to LTF4, may act as an "enzymatic barrier" in normal brain capillaries to leukotrienes.

Animals↗

PubMed1991

Middle cranial fossa transtemporal approach to the intrapetrous internal carotid artery.

Diseases involving the proximity of the internal carotid artery at the skull base require identification of this vessel in the temporal bone to gain vascular control for any maneuver in its vicinity. This article details the technique of surgical dissection and exposure of the internal carotid artery within the skull base through a transtemporal middle cranial fossa approach. The anatomic landmarks important in utilizing this procedure include the greater superficial petrosal nerve, the mandibular branch of the trigeminal nerve, and the middle meningeal artery. With this approach, the internal carotid artery can be followed throughout the carotid canal and beyond the formen lacerun to the region of the cavernous sinus. The indications and limitations of this procedure are described and several clinical applications are provided.

Journal Article↗

PubMed1991

Meckel cave lesions: percutaneous fine-needle-aspiration biopsy cytology.

The authors describe the novel combination of two traditional methods to facilitate diagnosis of Meckel cave lesions, which may otherwise require craniotomy to obtain adequate tissue samples. Fine-needle-aspiration biopsy cytology was performed on tissue obtained with a percutaneous approach via the foramen ovale with use of fluoroscopic guidance and intravenous analgesia during an outpatient procedure. This new application of fine-needle-aspiration biopsy cytology results in decreased patient morbidity and significant cost reduction.

Adult↗

PubMed1991

Nonneoplastic enhancing lesions mimicking intracanalicular acoustic neuroma on gadolinium-enhanced MR images.

The authors describe five patients with nonneoplastic lesions of the facial and/or vestibulocochlear nerves that demonstrated focal enhancement within the internal auditory canal on magnetic resonance (MR) images. MR and surgical findings for four patients with unilateral sensorineural hearing loss and one with Ramsay Hunt syndrome were reviewed. Three patients with hearing loss underwent surgical exploration and decompression of the internal auditory canal. The MR findings in all four patients with hearing loss were similar: Focal enhancement of the internal auditory canal was depicted on postcontrast T1-weighted images. Nonneoplastic lesions of the seventh and eighth cranial nerves may show focal enhancement on MR images, which mimics the appearance of a small intracanalicular neuroma. This potential for misdiagnosis may have important therapeutic implications.

Cranial Nerve Diseases↗

PubMed1991

Tumor-associated neurological dysfunction prevented by lazaroids in rats.

The efficacy of U-74006F and U-78517F in the treatment of blood-tumor barrier permeability and tumor-associated neurological dysfunction was evaluated in a brain-tumor model in rats. U-74006F is a 21-aminosteroid and U-78517F is a 2-methylamino chroman. Rats with stereotactically implanted Walker 256 tumors were treated with methylprednisolone, U-74006F, U-78517F, or vehicle (0.05 N HCl) on Days 6 through 10 following implantation. Neurological function and vascular permeability were assessed on Day 10. Methylprednisolone and U-74006F were equally effective at preventing neurological dysfunction compared to the control group (p less than 0.01); U-78517F was slightly less effective than U-74006F and methylprednisolone but was significantly better than vehicle in preventing neurological dysfunction. Delivery of methylprednisolone resulted in a significant decrease in tumor vascular permeability (p less than 0.006) while U-74006F and U-78517F had no effect on permeability. This suggests that U-74006F and U-78517F prevented tumor-associated neurological dysfunction by a mechanism other than decreasing permeability in tumor capillaries, and that U-74006F or U-78517F could prove useful in the treatment of brain tumors.

Animals↗

PubMed1991

Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial.

There is still controversy over whether or not patients should be hyperventilated after traumatic brain injury, and a randomized trial has never been conducted. The theoretical advantages of hyperventilation are cerebral vasoconstriction for intracranial pressure (ICP) control and reversal of brain and cerebrospinal fluid (CSF) acidosis. Possible disadvantages include cerebral vasoconstriction to such an extent that cerebral ischemia ensues, and only a short-lived effect on CSF pH with a loss of HCO3-buffer from CSF. The latter disadvantage might be overcome by the addition of the buffer tromethamine (THAM), which has shown some promise in experimental and clinical use. Accordingly, a trial was performed with patients randomly assigned to receive normal ventilation (PaCO2 35 +/- 2 mm Hg (mean +/- standard deviation): control group), hyperventilation (PaCO2 25 +/- 2 mm Hg: HV group), or hyperventilation plus THAM (PaCO2 25 +/- 2 mm Hg: HV + THAM group). Stratification into subgroups of patients with motor scores of 1-3 and 4-5 took place. Outcome was assessed according to the Glasgow Outcome Scale at 3, 6, and 12 months. There were 41 patients in the control group, 36 in the HV group, and 36 in the HV + THAM group. The mean Glasgow Coma Scale score for each group was 5.7 +/- 1.7, 5.6 +/- 1.7, and 5.9 +/- 1.7, respectively; this score and other indicators of severity of injury were not significantly different. A 100% follow-up review was obtained. At 3 and 6 months after injury the number of patients with a favorable outcome (good or moderately disabled) was significantly (p less than 0.05) lower in the hyperventilated patients than in the control and HV + THAM groups. This occurred only in patients with a motor score of 4-5. At 12 months posttrauma this difference was not significant (p = 0.13). Biochemical data indicated that hyperventilation could not sustain alkalinization in the CSF, although THAM could. Accordingly, cerebral blood flow (CBF) was lower in the HV + THAM group than in the control and HV groups, but neither CBF nor arteriovenous difference of oxygen data indicated the occurrence of cerebral ischemia in any of the three groups. Although mean ICP could be kept well below 25 mm Hg in all three groups, the course of ICP was most stable in the HV + THAM group. It is concluded that prophylactic hyperventilation is deleterious in head-injured patients with motor scores of 4-5.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed1991

Changes in the treatment of head injury.

A brief description of the fundamental concepts of the biology and pathophysiology of excitatory amino acids, lactic acidosis, and free radicals in brain injury have been presented. For a comprehensive review of these topics, the references provide access to an extensive body of research in each of these areas. They represent a complex series of interrelated events that are set into motion at the initial injury. Some neurons are destined to die despite all therapeutic endeavors, but further investigation into the mechanisms responsible for delayed neuronal demise are in the early stages of human investigation or very close to clinical trials. Efforts directed at providing a favorable extracellular milieu for those neurons that are salvageable provide promise for continued improvements in outcome for patients with head injury.

Amino Acids↗

PubMed1991

Brain tumors.

Recent advances in experimental tumor biology are being applied to critical clinical problems of primary brain tumors. The expression of peripheral benzodiazepine receptors, which are sparse in normal brain, is increased as much as 20-fold in brain tumors. Experimental studies show promise in using labeled ligands to these receptors to identify the outer margins of malignant brain tumors. Whereas positron emission tomography has improved the dynamic understanding of tumors, the labeled selective tumor receptors with positron emitters will enhance the ability to specifically diagnose and greatly aid in the pretreatment planning for tumors. Modulation of these receptors will also affect tumor growth and metabolism. Novel methods to deliver antitumor agents to the brain and new approaches using biologic response modifiers also hold promise to further improve the management of brain tumors.

Brain Chemistry↗

PubMed1990

Specific high-affinity binding of peripheral benzodiazepine receptor ligands to brain tumors in rat and man.

Two types of benzodiazepine receptors have been identified in mammalian tissues: a central type which is localized to neuronal elements in the brain, and a peripheral type which is present on glial cells and in tissues outside the central nervous system such as kidney. The authors report an increase in specific binding of peripheral benzodiazepine receptor ligands in certain human brain tumors using computer assisted quantitative image analysis of autoradiograms. Higher densities of binding sites to a 3H-labeled selective peripheral benzodiazepine ligand, PK11195 [1-(2-chlorophenyl-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide] were observed in human gliomas as the malignancy of these tumors increased. Specific binding was also present in some non-glial tumors but little binding was demonstrated in necrotic tissue or normal brain. In in vitro binding studies in rats, there was a significant increase in Bmax (1089.3 +/- 232.2 fmol/mg tissue) in C6 glial tumors and LK Walker 256 metastatic tumors (924.2 +/- 183.7) compared with normal brain (62.1 +/- 12.8 fmol/mg tissue). Binding affinities were, however, similar (Kd = 2.09, 2.17, and 2.04 nmol/l, respectively). These findings suggest that the number of peripheral benzodiazepine receptors are increased in brain tumors. These receptors could be utilized in positron emission tomography to image brain tumors.

Animals↗

PubMed1990

The increase in local cerebral glucose utilization following fluid percussion brain injury is prevented with kynurenic acid and is associated with an increase in calcium.

Immediately following a lateral fluid percussion brain injury, the cerebral cortex and hippocampus ipsilateral to the percussion show a marked accumulation of calcium and a pronounced increase in glucose metabolism. To determine if this increase in glucose metabolism was related to the indiscriminate release of the excitatory amino acid (EAA) glutamate, kynurenic acid (an EAA antagonist) was perfused into the cerebral cortex through a microdialysis probe for 30 min prior to injury. The results show that adding kynurenic acid to the extracellular space prior to trauma prevents the injury-induced increase in glucose utilization. These results indicate that calcium contributes to the ionic fluxes that are typically seen following brain injury and supports the concept of an increased energy demand upon cells to drive pumping mechanisms in order to restore membrane ionic balance.

Animals↗