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Biomedical subjects

D P Becker

Publications and source records attributed to D P Becker.

At least 55 records · Page 3Linked to original sources

Radiosurgery of cavernous sinus tumors.

Stereotactic radiosurgery was applied to concentrate high dose of photon irradiation to tumors enclosed in the cavernous sinus. We have treated 10 meningiomas, five pituitary tumors, and three metastatic lesions in the past two years. Follow-up time ranges from 3 to 18 months with an average of 10 months. Tumor volume ranged from 0.92 to 53.31 cc with an average 10.79 cc. CT scans and MRIs were used to demonstrate the tumor relationship to cranial nerves and structures of the brain. One to 6 isocenters were used. Collimator size varied from 7 to 28 mm, and the dose to the margin of the tumor ranged from 1400 to 2500 cGy with an average of 1650 cGy. Maximal dose range of 1575 to 5000 cGy. The margin of the tumor was encompassed within the 50 to 95% isodose volume with an average treatment prescribed to the 57% isodose volume. Symptomatic response was seen in 12 patients, and stabilization of symptoms in three patients with progression of symptoms observed in three patients. Radiographic imaging revealed response in eight patients, unchanged in three patients and progression in three patients. This report shows the feasibility of applying linear accelerator radiosurgery to the treatment of cavernous sinus tumors. This form of therapy promises to play an important role in complementing tumor resection.

Adult↗

Comparison between radiosurgery and stereotactic fractionated radiation for the treatment of brain metastases.

This study evaluates the treatment of intracerebral brain metastases with single dose stereotactic radiosurgery in comparison to stereotactic fractionated radiotherapy (SFR). Twenty six patients with 41 lesions were evaluated. Thirty four lesions in 19 patients were treated with radiosurgery, and 7 lesions in 7 patients were treated with SFR. The radiosurgery group was treated with an average number of isocenters of 1.4, and an average of 9 arcs. The average dose was 2140 cGy delivered to the 70% isodose line. The average volume of the lesions was 5.22 cc. The SFR group lesions received a mean dose to the indicated area delivered by 4 to 6 coplanar fields. The dose was 600 cGy per fraction, 2 to 3 fractions were given. The average volume of the treated lesions was 21.2 cc. Follow-up extended from 2-18 months. Twenty five lesions of the radiosurgery group had image follow-up. The overall local control was seen in 92% of the patients. Six lesions of the SFR group had image follow-up, the local control was 83%. The small number in each group, the non-randomized nature of the study, and the relatively short follow-up preclude a definitive conclusion. SFR may be the method of choice for large lesions surrounded by significant edema. The delivery of the dose in large fractions may obviate the transient acute reactions seen when radiosurgical dose is delivered to large lesions surrounded by edema. However, both forms of therapy have proven to be effective in the control of brain metastases.

Adult↗

Clinical considerations in the reduction of secondary brain injury.

Craniocerebral trauma renders the brain vulnerable to a variety of secondary insults that must be prevented or promptly corrected before irreversible neurologic damage occurs. These secondary insults can include hypoxia, ischemia, or both, which result in significant cell loss. The trauma-induced state of vulnerability appears to be due to cellular ionic and metabolic alterations that make up the basic physiologic sequelae after brain injury. We discuss clinical aspects regarding these potentially devastating injuries in an effort to enhance their recognition and aid in their management.

Brain Injuries↗

Clinical trial of Serratia marcescens extract and radiation therapy in patients with malignant astrocytoma.

PURPOSE: A clinical trial was undertaken to determine the safety and efficacy of combining a biologic response modifier derived from the bacterium Serratia marcescens (ImuVert) and radiation therapy (RT) in patients with newly diagnosed anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM). PATIENTS AND METHODS: Fifteen patients who had undergone either a gross total resection, a partial resection, or a biopsy were treated concurrently with ImuVert and RT. Safety and tolerance were examined by assessment of symptomatic reactions recorded at each ImuVert treatment. Efficacy of treatment was examined in terms of time to progression of tumor and survival. RESULTS: All patients experienced local reactions at the injection sites that consisted of erythema and induration. The majority of patients experienced flu-like symptoms. Hypotension was responsible for the most significant morbidity (which required fluid resuscitation and extended observation) and dose deescalation. No patients were removed from the study because of toxicity. There were no on-study deaths related to ImuVert treatment. Median time to progression was 33.4 weeks, and median survival was 78 weeks. CONCLUSION: These results compare favorably with those of recent studies in patients with malignant astrocytomas who received multimodality therapy.

Adult↗

Drilling the posterior wall of the petrous pyramid: a microneurosurgical anatomical study.

Posterior approaches to the petroclival area requiring extensive drilling of the posterior pyramidal wall have been described in the last 10 years. If hearing is to be preserved, damage to the inner-ear structures must be avoided; however, the fine points of this pyramidal drilling technique have never been reported in detail. A microneurosurgical anatomical study was undertaken in 15 cadavers to determine the relationships between bone landmarks and labyrinthine structures that could be used to give some practical drilling guidelines. Drilling of the posterior pyramidal wall is facilitated on identification of the intersection of the petrous ridge with the most anterior portion of the bone ledge covering the sigmoid sinus (petrosigmoid intersection), the bony operculum of the endolymphatic sac, and the petrous ridge. Drilling may proceed rather safely at a minimum depth of 2.5 mm in an area 0.9 cm anterior and 1 cm inferior to the petrosigmoid intersection and petrous ridge, respectively. From there, identification of the vestibular aqueduct, genu, and horizontal portion is necessary to safely open the posterior wall of the internal auditory canal. The vestibular aqueduct represents the lateral and superior limits of drilling. The bone between these areas may then be safely drilled to a depth of at least 2.5 mm. A microneurosurgical dissection of the posterior pyramidal wall conducted in cadaveric material according to these guidelines did not violate any inner-ear structures.

Ear, Middle↗

The mandibular swing-transcervical approach to the skull base: anatomical study. Technical note.

This report describes in a stepwise fashion the surgical anatomy of an approach to the midline and lateral compartments of the skull base (clivus, infralabyrinthine/infratemporal regions). The salient features of this procedure are represented by a mandibulotomy and by detachment of the pharynx from the skull base through a combined oral and cervical approach. There is full neurovascular control of the internal carotid artery and lower cranial nerves with the possibility of complete exposure of the intrapetrous and intracavernous segments of the internal carotid artery on the side of the exposure. This approach, which may be regarded as an expansion of the original work of Krespi, should be considered when dealing aggressively with extensive skull-base lesions invading the midline and lateral compartments of the skull base.

Cadaver↗

The petrosal approach with hearing preservation.

Twenty-six patients with petroclival lesions were operated on via a petrosal approach designed to preserve hearing. The surgical pathology included 14 meningiomas, three chordomas, three epidermoid cysts, four vertebrobasilar aneurysms, and two pontine cavernous malformations. The approach allowed complete resection of 14 of 20 tumors and definitive treatment of all six vascular lesions. Complications included cerebrospinal fluid leakage in three patients, high-frequency sensorineural hearing loss in three, meningitis in one, and cranial nerve palsies (which were usually transient). This approach allows a wide exposure of the petroclival region with decreased operating distance. Cerebellar and temporal lobe retraction are minimized, dural sinus patency is maintained, and the inner ear structures are not sacrificed. The approach is suitable for neoplastic or vascular lesions involving the petroclival region, the ventral pons, or the basilar artery trunk. The surgical technique, indications, and neuro-otological considerations are discussed.

Adolescent↗

Magnetoencephalographic localization of a language processing cortical area adjacent to a cerebral arteriovenous malformation. Case report.

In order to accurately estimate the risk of surgery for dominant perisylvian arteriovenous malformations, the topographical relationship of the lesion to language cortex must be determined. A case is presented in which a magnetoencephalographic (MEG) study was used to map preoperatively and noninvasively an intracortical source of speech-receptive cortex in a 25-year-old right-handed man with a dominant left temporal lobe arteriovenous malformation. The speech-evoked magnetic field was analyzed at 36 positions over the left hemisphere in response to presentations of the consonant-vowel syllables "da" and "ga." A topographical map of the magnetic component evoked at 110 msec after stimulus onset, which was negative going to the vertex in concurrent electrical recordings, was congruent with a superficial cortical neuronal current source. This source was displaced from that usually observed in normal individuals to tonal or click stimuli, being superior to the probable location of auditory cortex, and superior and anterior to the probable location of Wernicke's area as conventionally described. The MEG results were in accord with the determination of position of a language-processing cortical area as assessed by direct electrical stimulation of the cortex during surgery under local anesthesia, and by superselective Amytal (amobarbital) injection during angiography. The MEG recordings and exposed brain stimulation sites were coordinated by cranial measurements, skull x-ray landmarks, and angiographic anatomy. Investigations such as this, which compare MEG findings with those from established clinical procedures, are an essential step in determining the physiological and anatomical utility of magnetoencephalography for noninvasive clinical functional localization.

Adult↗

Early cellular swelling during cerebral ischemia in vivo is mediated by excitatory amino acids released from nerve terminals.

This study demonstrates ischemic cellular swelling in vivo detected as changes in the concentration of 14C-sucrose pre-perfused into the extracellular space (ECS) as an ECS marker. Microdialysis was utilized as a means of perfusion and measurement of the extracellular concentration of 14C-sucrose ([14C-sucrose]e). Concomitant with an abrupt increase in [K+]e at 1-3 min following the ischemia induction, [14C-sucrose]e was also rapidly elevated. Since sucrose is not taken up by either cells or capillaries, the absolute amount of 14C-sucrose in the ECS must be unchanged. The increase therefore appears to represent a relative decrease in water volume in the ECS resulting from a movement of water into the cells, i.e. cellular swelling. Ca(2+)-free perfusate containing Co2+, which has been shown to block excitatory amino acid release during cerebral ischemia, significantly delayed the increase in [14C-sucrose]e and [K+]e. Kynurenic acid, a broad-spectrum antagonist of excitatory amino acids, administered in situ through the dialysis probe also significantly delayed the increase in [14C-sucrose]e and [K+]e. These findings indicate that the early cellular swelling occurring during cerebral ischemia is a result of massive ionic fluxes mediated by excitatory amino acids which are released by a Ca(2+)-dependent exocytotic process from the nerve terminals.

Amino Acids↗

Topographic mapping of somatosensory evoked potentials helps identify motor cortex more quickly in the operating room.

Median nerve somatosensory evoked potentials were recorded from exposed cerebral cortex during craniotomies. This technique is valuable when knowledge of the motor cortex location can influence surgical decisions about resection limits or biopsy sites. Two different recording techniques were compared: strips of electrodes and arrays of electrodes. The arrays recorded electrical potentials suitable for topographic mapping. We found that motor cortex could be identified more quickly when using the topographic mapping of SEPs from arrays. We conclude that topographic mapping of SEP from sensorimotor regions during craniotomies works well in general and can be done more quickly than the traditional electrode strip technique.

Adolescent↗

Hippocampal CA3 lesion prevents postconcussive metabolic dysfunction in CA1.

Immediately following fluid-percussion (F-P) brain injury, the hippocampus exhibits a marked increase in its local CMRglc (LCMRglc; mumol/100 g/min) as determined using [14C]2-deoxy-D-glucose autoradiography. This injury-induced increase in metabolism is followed in 6 h by a subsequent decrease in LCMRglc. These two postinjury metabolic states may be the result of ionic disruptions following trauma via stimulation of glutamate-gated ion channels. To determine if endogenous glutamate innervation to the CA1 region of the hippocampus can provide an anatomical basis for this proposed mechanism, it was removed by kainic-acid-induced destruction of CA3, and the effect on CA1 metabolism following concussive injury was studied. Five days before a lateral F-P injury (3.5-4.5 atm), kainic acid (0.5 microgram) or vehicle was stereotaxically injected into the left ventricle of 65 rats. Histological inspection indicated that kainic acid produced severe cell loss primarily in the CA3 region of the hippocampus ipsilateral to the injection. The metabolic results indicated that immediately following injury, animals with an intact hippocampus exhibited an increase in LCMRglc to 84.6 +/- 5 within the CA1 region, representing a 81.5% increase over controls. However, in the CA3-lesioned animals, CA1 showed no evidence of an injury-induced hypermetabolism, with LCMRglc remaining at control levels (51.4 +/- 3.9). At 6 h postinjury, the intact hippocampus exhibited a reduction of LCMRglc to rates of 40.7 +/- 4.7 within the CA1 region, representing a 17.9% reduction compared with controls. In contrast, CA3-lesioned animals exhibited less of an injury-induced decrease in LCMRglc within the CA1 region, exhibiting a mean rate of 43.4 +/- 4.5, representing only a 12.5% reduction compared with controls. These results indicate that the removal of the CA3 projection to CA1 protects the CA1 cells from the metabolic dysfunction typically seen following injury. This supports our previous work indicating the important role glutamate plays in the ionic flux and subsequent metabolic changes that follow traumatic brain injury.

Animals↗

Administration of excitatory amino acid antagonists via microdialysis attenuates the increase in glucose utilization seen following concussive brain injury.

Immediately following concussive brain injury, cells exhibit an increase of energy demand represented by the activation of glucose utilization. We have proposed that this trauma-induced hypermetabolism reflects the effort of cells to restore normal ionic balance disrupted by massive ionic fluxes through transmitter-gated ion channels. In the present study, changes in local CMRglc following fluid-percussion concussive injury were determined using [14C]2-deoxy-D-glucose autoradiography, and the effects of in situ administration (via microdialysis) of excitatory amino acid (EAA) antagonists [kynurenic acid (KYN), 2-amino-5-phosphonovaleric acid (APV; 100 microM, 1 mM, and 10 mM), and 6-cyano-7-nitroquinoxaline-2,3-dine (CNQX; 300 microM, 1 mM, and 10 mM] on glucose utilization were investigated. Animals that did not receive dialysis showed a remarkable increase (up to 181% of normal control) in cortical glucose utilization following injury. In contrast, this high demand for glucose was reduced in areas infiltrated with KYN, APV, and CNQX. These results indicate that EAA-activated ion channels are involved in the posttraumatic increase in glucose utilization, reflecting the energy demand of cells required to drive pumping mechanisms against an ionic perturbation seen immediately following the concussive injury. The effects of KYN, APV, and CNQX suggest that although all subtypes of the glutamate receptor appear to be involved in this phenomenon, N-methyl-D-aspartate-activated channels may play a major role.

2-Amino-5-phosphonovalerate↗

Histochemical evaluation of energy metabolism in rat glioma.

The key enzymes of oxidative phosphorylation and glycolysis were evaluated histochemically in rat-implanted C6 gliomas using spot densitometry. Hexokinase, the initial enzyme for the glycolysis pathway, was 40% higher within tumour than the contralateral cerebral cortex. A similar increase within tumours for 2-deoxyglucose was observed by autoradiography. Glucose-6-phosphate dehydrogenase (G6PDH), which is the first enzyme in the pentose phosphate pathway, shunting glucose towards nucleic acid synthesis, was more than 300% higher in gliomas compared with the normal cortex. In contrast, enzymes in the energy producing tricarboxylic acid cycle (succinate-, isocitrate-, and malate-dehydrogenase) and in the electron-transport system (cytochrome c oxidase) were significantly reduced in tumour (58% less than the contralateral cortex). Lactate dehydrogenase activity, which converts pyruvate to lactate, was 50% higher within tumour. Significant reductions of enzymatic activities also occurred in non-neoplastic tissue in ipsilateral hemisphere, with larger tumours. Some enzymes showed heterogeneous activity within tumours, especially G6PDH. These results suggest that: (1) energy production is more dependent on lactate production than on oxidative phosphorylation in C6 glioma, and (2) a significant part of the increased glucose utilization in glioma cells is due to increased activity of the pentose phosphate shunt for increased DNA synthesis, and not energy production.

Animals↗

Inflammatory leukocytes associated with increased immunosuppression by glioblastoma.

In order to determine the in vivo immune response in glioblastoma, monoclonal and polyclonal antibodies specific for inflammatory leukocytes and immunoregulatory products were utilized to stain tissue from four surgical specimens. The more activated the inflammatory cells, the more activated the tumors appeared to be. In the tumor with the largest infiltration (Case 3), inflammatory cells were stained for interferon-gamma, interleukin-2, interleukin-1 beta, lymphotoxin, tumor necrosis factor-alpha, and transforming growth factor-beta. The tumor cells also expressed interleukin-1 beta, interleukin-6, transforming growth factor-beta, tumor necrosis factor-alpha, and prostaglandin E. In contrast, in the tumor with the least inflammatory response (Case 1), the tumor cells did not express any cytokines. Expression of cytokines by glioma cells was modest in the two cases with modest inflammatory responses. Cellular inflammation, primarily consisting of T cells and macrophages with few or no B cells or natural killer cells, was two- to 15-fold greater outside the tumor than within. In contrast to leukocytes outside the tumor, which were activated and expressing class II major histocompatibility antigens, leukocytes within the tumor parenchyma or at the tumor's edge were negative for these antigens. In the four specimens studied here, the tumor cells themselves were also negative for class II major histocompatibility antigens. These findings, although preliminary, suggest that inflammatory cells within gliomas are inactivated and that glioma cells may increase the expression of immunosuppressive cytokines in response to an increased lymphocyte infiltrate. This observation, if corroborated by more extensive studies, may help to explain the failure of immune treatments in glioblastoma multiforme.

Adult↗

Posttraumatic cerebral arterial spasm: transcranial Doppler ultrasound, cerebral blood flow, and angiographic findings.

Thirty patients admitted after suffering closed head injuries, with Glasgow Coma Scale scores ranging from 3 to 15, were evaluated with transcranial Doppler ultrasound monitoring. Blood flow velocity was determined in the middle cerebral artery (MCA) and the intracranial portion of the internal carotid artery (ICA) in all patients. Because proximal flow in the extracranial ICA declines in velocity when arterial narrowing becomes hemodynamically significant, the extracranial ICA velocity was concurrently monitored in 19 patients. To assess cerebral perfusion, cerebral blood flow (CBF) measurements obtained with the intravenous 133Xe technique were completed in 16 patients. Vasospasm, designated as MCA velocity exceeding 120 cm/sec, was found in eight patients (26.7%). Severe vasospasm, defined as MCA velocity greater than 200 cm/sec, occurred in three patients, and was confirmed by angiography in all three. Subarachnoid hemorrhage (SAH) was documented by computerized tomography in five (62.5%) of the eight patients with vasospasm. All cases of severe vasospasm were associated with subarachnoid blood. The time course of vasospasm in patients with traumatic SAH was similar to that found in patients with aneurysmal SAH; in contrast, arterial spasm not associated with SAH demonstrated an uncharacteristically short duration (mean 1.25 days), suggesting that this may be a different type of spasm. A significant correlation (p less than 0.05) was identified between the lowest CBF and highest MCA velocity in patients during the period of vasospasm, indicating that arterial narrowing can lead to impaired CBF. Ischemic brain damage was found in one patient who had evidence of cerebral infarction in the territories supplied by the arteries affected by spasm. These findings demonstrate that delayed cerebral arterial spasm is a frequent complication of closed head injury and that the severity of spasm is, in some cases, comparable to that seen in aneurysmal SAH. This experience suggests that vasospasm is an important secondary posttraumatic insult that is potentially treatable.

Adolescent↗