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Biomedical subjects

B Mickey

Publications and source records attributed to B Mickey.

At least 19 recordsLinked to original sources
PubMed2005

Gliosarcoma cell death after radiosurgery in a rat model.

Therapeutic radiation and subsequent detection of tumor cell death has been performed mainly in vitro systems, making it difficult to accurately characterize the mechanisms of tumor cell death after radiosurgery. To better characterize what occurs to glioma cells after radiation therapy, we developed a rat model using the 9L gliosarcoma cell line implanted reproducibly to the caudate nucleus in rats. After 1 Gy radiation, 9L tumors in vivo induced mainly necrosis (determined by trypan blue exclusion) of 10 - 74 % at 6 - 72 hours post-radiation. This is in contrast to a previous in vitro study which demonstrated that 18 Gy of radiation induces considerably less cell death as determined by trypan blue exclusion (approximately 20 - 25 % at 6 - 72 hours post-radiation). However, significant amounts of apoptosis were detected as early as 6 hours after radiation. Apoptosis determination was by annexin V (marker of early apoptosis) and propidium iodide (marker of membrane stability) staining followed by flow cytometry detection. When caspase 3 and caspase 8 enzymatic activities (mediators of apoptosis) were measured from freshly explanted tumor cells, peak activity was found 6 hours after 1 Gy radiation (p < 0.01). Taken together, these data indicate the presence of apoptosis early after radiation therapy (1 Gy) which progressed to necrosis in a unique in vivo model of gliosarcoma that may prove useful in determining new therapeutic approaches to radiation therapy and tumor cell biology.

Animals↗
PubMed2005

Detection of experimentally induced brain tumors in rats using high resolution computed tomography.

OBJECTIVE: The feasibility of high resolution CT imaging for evaluating experimentally-induced brain tumors in rats was assessed. METHODS: The gliosarcoma cell line (9 L/lacZ) was inoculated in 34 male Fischer 344 rats and CT studies were performed prior to and at 4, 7, 9, 12 and 14 days post-tumor cell implantation. Brain imaging pre- and post-contrast was performed and correlated with autopsy findings. RESULTS: Tumors were identified by CT in 19 of the 34 animals after contrast administration and their presence was confirmed at autopsy. Tumors were present at autopsy and not identified by CT scanning in eight additional animals and in the remaining seven animals, the CT scan was normal and no tumors were present at autopsy. The sensitivity and specificity of CT scanning with contrast in detecting tumors in this rat model of gliosarcoma was 70 and 100%, respectively. CONCLUSION: The improved CT technology currently available can be used to identify and follow tumor burden in a rat model of gliosarcoma, and be a good tool to utilize in determining treatment outcomes experimentally, especially when MR imaging is not available.

Animals↗
PubMed2004

Image-guided robotic radiosurgery in a rat glioma model.

Despite the proven efficacy of radiosurgery for the treatment of brain tumors, limited histological information is available after treatment that might allow a better understanding of the relationship between radiation dose, the volume treated, and the response of the surrounding brain to the delivered radiation. The use of an animal model could provide the opportunity to clarify these relationships and answer several other key questions arising in clinical practice. We show here that treatment of small animals with radiosurgery is feasible using a robotically controlled linear accelerator, which offers the advantages of radiosurgery and preserves the potential for fractionated regimens without rigid immobilization. Specifically, we demonstrate the use of a robotically driven linear accelerator to provide radiosurgical treatment to a rat brain tumor model.

Animals↗
PubMed2000

Neurophysiologic and neuroradiologic features of intractable epilepsy after traumatic brain injury in adults.

BACKGROUND: There is controversy regarding the precise mechanism by which epilepsy results after traumatic brain injury (TBI). Previous reports have suggested that mesial temporal lobe epilepsy may result from TBI only in young children, while neocortical epilepsy arises from TBI in later life. These conclusions were based on surgical series and may be biased because of patient selection. OBJECTIVE: To determine the frequency of mesial temporal lobe as opposed to neocortical epilepsy in patients with intractable epilepsy resulting from TBI after the age of 10 years. PATIENTS AND METHODS: We identified 23 patients with intractable epilepsy who had TBI after the age of 10 years, preceding the onset of epilepsy. Patients were studied by simultaneous videotape and scalp electroencephalographic recording of typical seizures; magnetic resonance imaging; neuropsychologic studies; and, when appropriate, intracarotid amobarbital testing. Two patients underwent anterior temporal lobectomies. RESULTS: Of the 23 patients, 8 (35%) had mesial temporal lobe epilepsy, based on the finding of hippocampal sclerosis on a magnetic resonance imaging scan, consistent interictal and ictal electroencephalographic recordings, evidence of temporal lobe dysfunction on neuropsychologic testing, and characteristic seizure semiology. Two of these patients underwent anterior temporal lobectomies with clinical benefit, and hippocampal sclerosis was confirmed pathologically. In 2 cases, patients were not treated surgically because of bilateral temporal lobe dysfunction noted on intracarotid amobarbital testing. Eleven patients had neocortical epilepsy; 1 had primary generalized epilepsy; and, in 3, the site of seizure onset was not localized. CONCLUSIONS: Mesial temporal lobe epilepsy can result from TBI in adolescents and adults as well as in children, and can often be bilateral and associated with multifocal injury. This information may be useful in developing prophylactic therapy for posttraumatic epilepsy.

Adult↗
PubMed2000

Molecular advances to treat cancer of the brain.

Malignant primary and metastatic brain tumours continue to be associated with poor prognosis. Nevertheless, recent advances in molecular medicine, specifically in the strategies of gene therapy, targeting tumour cells, anti-angiogenesis and immunotherapy, have created novel tools that may be of therapeutic value. To date, gene therapy trials have not yet demonstrated clinical efficacy because of inherent defects in vector design. Despite this, advances in adenoviral technology, namely the helper-dependent adenoviral constructs (gutless) and the uncovering of brain parenchymal cells as effective and necessary targets for antitumour benefits of adenoviral-mediated gene transfer, suggest that developments in vector design may be approaching the point of clinical utility. Targeting tumour cells refers to strategies that destroy malignant but spare normal cells. A new assortment of oncolytic viruses have emerged, capable of specific lysis of cancer tissue while sparing normal cells and propagating until they reach the tumour borders. Furthermore, peptides have been transformed into bullets that specifically seek and destroy cancer cells. The concept of tumour angiogenesis has been challenged by new but still very controversial findings that tumour cells themselves may form blood channels. These results may lead to the redirecting of the molecular targets toward anti-angiogenesis in some tumours including glioblastoma multiform. Unfortunately, our knowledge regarding the immunological ignorance of the tumour is still limited. Even so, newly discovered molecules have shed light on novel pathways leading to the escape of the tumour from the immune system. Finally, significant limitations in our current experimental tumour models may soon be overcome by firstly, the development of models of reproducible organ-specific tumours in non-inbred animals and secondly applying genomics to individualize therapy for a particular tumour in a specific patient.

Angiogenesis Inhibitors↗
PubMed1998

Surgical treatment of cerebrospinal fluid fistulae involving lateral extension of the sphenoid sinus.

OBJECTIVE AND IMPORTANCE: Four cases of spontaneous cerebrospinal fluid rhinorrhea caused by communication between the subarachnoid space of the middle cranial fossa and a lateral extension of the sphenoid sinus are presented. The cause and management of this unique type of cranial base defect are discussed. CLINICAL PRESENTATION: During the past 10 years, four patients referred to our institution with atraumatic cerebrospinal fluid fistulae were observed to have temporal encephaloceles (encephalomeningoceles) traversing the floor of the middle cranial fossa. Three of the patients had previously undergone unsuccessful transnasal attempts to repair their fistulae by obliteration of the sphenoid sinus. The fourth patient presented before undergoing any treatment. No patient had associated hydrocephalus or tumor. Preoperative computed tomographic cisternograms revealed that all fistulae involved a lateral extension of the sphenoid sinus into the floor of the middle cranial fossa. INTERVENTION: After definitive localization, each patient was operated on transcranially through an anterior middle cranial fossa approach with extradural and/or intradural exploration. The associated temporal encephalocele was amputated or disconnected, and the dehiscent dura and middle cranial fossa floor defect were oversewn and packed with autogenous tissue, respectively. CONCLUSION: The surgical treatment of cerebrospinal fluid rhinorrhea secondary to middle fossa encephalocele associated with lateral extension of the sphenoidal sinus differs from the surgical strategy for more medial sphenoidal fistulae. Fistulae involving a lateral extension of the sphenoid sinus require a transcranial approach for direct visualization and obliteration of the defect, whereas fistulae involving the central portion of the sinus may be successfully obliterated transsphenoidally.

Adult↗
PubMed1995

Rigidity of microtubules is increased by stabilizing agents.

Microtubules are rigid polymers that contribute to the static mechanical properties of cells. Because microtubules are dynamic structures whose polymerization is regulated during changes in cell shape, we have asked whether the mechanical properties of microtubules might also be modulated. We measured the flexural rigidity, or bending stiffness, of individual microtubules under a number of different conditions that affect the stability of microtubules against depolymerization. The flexural rigidity of microtubules polymerized with the slowly hydrolyzable nucleotide analogue guanylyl-(alpha, beta)-methylene-diphosphonate was 62 +/- 9 x 10(-24) Nm2 (weighted mean +/- SEM); that of microtubules stabilized with tau protein was 34 +/- 3 x 10(-24) Nm2; and that of microtubules stabilized with the antimitotic drug taxol was 32 +/- 2 x 10(-24) Nm2. For comparison, microtubules that were capped to prevent depolymerization, but were not otherwise stabilized, had a flexural rigidity of 26 +/- 2 x 10(-24) Nm2. Decreasing the temperature from 37 degrees C to approximately 25 degrees C, a condition that makes microtubules less stable, decreased the stiffness of taxol-stabilized microtubules by one-third. We thus find that the more stable a microtubule, the higher its flexural rigidity. This raises the possibility that microtubule rigidity may be regulated in vivo. In addition, the high rigidity of an unstabilized, GDP-containing microtubule suggests that a large amount of energy could be stored as mechanical strain energy in the protein lattice for subsequent force generation during microtubule depolymerization.

Animals↗
PubMed1993

Flexural rigidity of microtubules and actin filaments measured from thermal fluctuations in shape.

Microtubules are long, proteinaceous filaments that perform structural functions in eukaryotic cells by defining cellular shape and serving as tracks for intracellular motor proteins. We report the first accurate measurements of the flexural rigidity of microtubules. By analyzing the thermally driven fluctuations in their shape, we estimated the mean flexural rigidity of taxol-stabilized microtubules to be 2.2 x 10(-23) Nm2 (with 6.4% uncertainty) for seven unlabeled microtubules and 2.1 x 10(-23) Nm2 (with 4.7% uncertainty) for eight rhodamine-labeled microtubules. These values are similar to earlier, less precise estimates of microtubule bending stiffness obtained by modeling flagellar motion. A similar analysis on seven rhodamine-phalloidin-labeled actin filaments gave a flexural rigidity of 7.3 x 10(-26) Nm2 (with 6% uncertainty), consistent with previously reported results. The flexural rigidity of these microtubules corresponds to a persistence length of 5,200 microns showing that a microtubule is rigid over cellular dimensions. By contrast, the persistence length of an actin filament is only approximately 17.7 microns, perhaps explaining why actin filaments within cells are usually cross-linked into bundles. The greater flexural rigidity of a microtubule compared to an actin filament mainly derives from the former's larger cross-section. If tubulin were homogeneous and isotropic, then the microtubule's Young's modulus would be approximately 1.2 GPa, similar to Plexiglas and rigid plastics. Microtubules are expected to be almost inextensible: the compliance of cells is due primarily to filament bending or sliding between filaments rather than the stretching of the filaments themselves.

Actin Cytoskeleton↗
PubMed1992

Transcranial resection of ethmoid sinus cancer involving the anterior skull base.

We present 11 cases of ethmoid sinus careinoma treated primarily by transcranial surgical resection and followed 1(1/2) to 7 years. Morbidity and mortality following surgery has proved acceptable. Local disease control and survival prognosis of the patients have been determined primarily by the histopathologic classification of the cancer rather than by invasion of dura or orbit. Good to excellent control has been achieved in cases of adenocarcinoma, adenoid cystic carcinoma, and squamous cell careinoma, but could not be demonstrated for undifferentiated carcinoma. Alternate means of treatment, including adjuvant chemotherapy and radiation therapy, are recommended for such anaplastic malignancies.

Journal Article↗
PubMed1992

Complications of lumbar spinal fluid drainage.

Cerebrospinal fluid fistula is an unfortunate, yet well-recognized, complication of basilar skull fracture, skull base surgery, and neurotologic procedures. Treatment commonly involves the use of continuous lumbar drainage. A retrospective chart review of 32 consecutive patients who required placement of lumbar drain by the otorhinolaryngology and neurosurgical services from March 1988 through July 1991 was undertaken to assess possible complications. The complications found were readily separated into minor and major categories on the basis of the possibility of permanent morbidity or mortality. Minor complications, including subjective complaints of headache, nausea, vomiting, etc., were noted in 59% of patients. Major complications were observed in four of 32 patients (12.5%), including unilateral occlusion of the posterior cerebral artery and unilateral true vocal cord paralysis. Alleviation of all complications was achieved by cessation of lumbar drainage. These cases are presented with discussion of pathogenesis. These findings demonstrate the possibility of potentially serious complications that mandate close monitoring of patients who require continuous lumbar drainage.

Adult↗
PubMed1991

Management of the external auditory canal in skull base surgery.

Transtemporal approaches to the skull base are being used with increasing frequency. When the external auditory canal is transected in the course of these operations, the risk of cerebrospinal fluid fistula is created. When hearing is to be sacrificed, we use a modification of the technique developed by Rambo for closure of the external auditory canal. This technique permits a cosmetically acceptable reliable watertight closure. When hearing is to be salvaged, we use a "conchal flap technique," which prevents circumferential scarring and stenosis and permits a watertight suture closure.

Journal Article↗
PubMed1991

Modified Rambo meatoplasty in translabyrinthine tumor removal.

Spinal fluid otorrhea and otorhinorrhea are morbid complications that occur in up to 18% of patients after removal of translabyrinthine tumor. Both of these problems can be significantly reduced if, during the initial surgery, the posterior canal wall is taken down and the tympanic membrane and external auditory canal skin are removed for better exposure of the eustachian tube orifice. The external auditory meatus can then be sealed by a previously described modification of the Rambo procedure. This additional procedure adds about 20 minutes to the surgery and presents a small risk of retained squamous epithelium. Fifty consecutive patients were divided into two equal groups and studied retrospectively. In group I, the patients underwent a modified Rambo meatoplasty at the time of the removal of their translabyrinthine tumor, whereas patients in group II had the tympanic orifice of their eustachian tube obstructed through the facial recess. Review of the postoperative course of these fifty patients indicated that the addition of the modified Rambo meatoplasty was justified by the overall reduction in morbidity and expense it provided.

Adult↗
PubMed1988

A combined frontotemporal and lateral infratemporal fossa approach to the skull base.

A variety of neoplasms involve both the infratemporal fossa and the base of the middle cranial fossa, in medial proximity to the cavernous sinus and orbital apex. To provide simultaneous access to both the intracranial and extracranial aspects of these tumors, a temporal or frontotemporal craniotomy may be combined with a lateral exposure of the infratemporal fossa. The approach, which is readily achieved by a neurosurgeon and an otolaryngologist acting as a team, involves a unilateral frontotemporal incision extended inferiorly onto the neck, a lateral facial flap reflected anteriorly, and transection of the zygoma followed by its reflection inferolaterally with the temporalis muscle. This exposure provides excellent visualization of both the intradural and extradural aspects of the anterior portion of the cavernous sinus, allowing for an aggressive resection of neoplasms involving this region. Experience with this procedure is reported here in the management of nine patients: three with nasopharyngeal angiofibromas, three with low-grade malignancies of the upper aerodigestive tract, and three with sphenoid ridge meningiomas.

Adenocarcinoma↗
PubMed1988

Improvement in regional cerebral blood flow and cerebral vasoreactivity after extracranial-intracranial arterial bypass.

Regional cerebral blood flow was measured with xenon-133 inhalation single photon emission computed tomography in a patient who developed a neurological deficit after carotid ligation. Hemispheric hypoperfusion was noted in resting studies and impaired vasoreactivity was suggested by lack of symmetrical flow augmentation after acetazolamide administration. Because of progressive neurological deterioration, an extracranial-intracranial bypass was performed. After prompt neurological improvement, repeat cerebral blood flow measurements at 1 and 9 weeks postoperatively confirmed improvement in resting flow and vasoreactivity. It is possible that decreased cerebrovascular reserve implied by measurements of vasoreactivity can identify patients who will benefit from surgical revascularization.

Aged↗
PubMed1987

Enlargement and rupture of distal basilar artery aneurysm after iatrogenic carotid occlusion.

A case of angiographic enlargement and fatal rupture of a previously asymptomatic distal basilar aneurysm in a 12-year-old girl is reported. She had been treated by carotid sacrifice for a giant intracavernous carotid aneurysm. After superficial temporal-middle cerebral artery bypass, this patient underwent a trapping procedure and decompression of her symptomatic giant aneurysm. Despite postoperative patency of her bypass graft, the involved middle cerebral circulation was irrigated substantially by retrograde flow through her posterior communicating artery. An incidental distal basilar aneurysm involving the origin of her superior cerebellar arteries, posterior cerebral arteries, and multiple perforators was treated by a wrapping procedure. Eleven days after carotid ligation, she suffered a fatal subarachnoid hemorrhage from her basilar aneurysm. This catastrophe was undoubtedly produced by our failure to consider the additional hemodynamic stress placed upon the distal basilar artery by carotid sacrifice and may have been preventable by a more aggressive attack on this previously asymptomatic lesion.

Basilar Artery↗
PubMed1986

Potential roles for early revascularization in patients with acute cerebral ischemia.

The risk of carotid endarterectomy in acute cerebral ischemic situations is well documented. By using the superficial temporal or occipital artery, it is possible to provide relatively low flow revascularization conduits, potentially avoiding the risk of postoperative hemorrhage. Eighteen patients at The University of Texas Health Science Center at Dallas, Texas, have been treated recently with extracranial to intracranial bypass in the setting of acute neurological deficit, stroke in evolution, or recent completed infarction. Angiographic causes of these deficits included cervical carotid occlusion in 5 patients, carotid siphon disease in 2 patients, middle cerebral stenosis or occlusion in 3 patients, and delayed cerebral ischemia following subarachnoid hemorrhage in 8 patients. Neurological improvement was demonstrated within 24 hours following revascularization in 15 cases (83%); 3 patients were unchanged following bypass, and no patient's condition was worsened. The only case of postoperative intracerebral hemorrhage occurred 1 week following a long saphenous vein graft from the subclavian to the middle cerebral artery. After an average follow-up of 19 months, 7 patients are neurologically normal, 8 patients have mild to moderate deficits, and 3 patients have died. Low flow revascularization procedures appear to be safe in the setting of acute cerebral ischemia and may in selected patients boost regional cerebral blood flow from levels of symptomatic ischemia into a range compatible with normal neuronal function.

Acute Disease↗