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T J O'Brien

Publications and source records attributed to T J O'Brien.

At least 19 recordsLinked to original sources
PubMed2002

Insertion of depth electrodes with or without subdural grids using frameless stereotactic guidance systems--technique and outcome.

Over recent years frameless stereotactic systems have begun replacing framed systems for many neurosurgical procedures. However, little has been published regarding the use of these systems to guide intracranial electrode implantation for epilepsy surgery patients. Here we report our experience utilising such a system to insert depth electrodes and subdural grid electrodes. The SteathStation Image-Guided System (SSIGS) (Sofamor Danek, Memphis TN.) was used to insert bilateral depth electrodes in 13 patients, of whom 5 also underwent the insertion of subdural grids or strip electrodes. Initially, a surgical plan based on an entry and target point on axial and sagittal images was performed for the insertion of electrodes. Navigational views, using three-planar images, were then performed to determine which structures the electrodes would pass through to be correctly placed in the amygdala and hippocampus. The correct site of electrode implantation was confirmed post-operatively by spiral CT scans in 4 patients (which were then co-registered to the pre-implantation MRI using a surface matching technique) and the other 9 patients by post-implantation MRI. The SSIGS was found to have a mean registration error of 2.0 mm (range 1.8-2.5) in 10 cases; in the 3 cases where the error was greater than 2.5 mm a surfacemerge technique was used with a mean error 0.9 (0.8-1.00). The post-implantation MRI or CT-MRI co-registration confirmed an accurate electrode placement in the mesial temporal region in all cases. Seizure onset lateralisation was achieved in 11 patients, all of whom went onto formal resections based on these results. The only long-term complication was a case of osteomyelitis which required removal of the bone flap. 73% of patients had an excellent seizure outcome. Frameless stereotactic systems can be safely used to intracranial electrodes, avoid the disadvantages of the framed system and have the added advantage of the surgeon being able to visualise the trajectory and to adjust this to avoid vital structures. As well they eliminate surgical obstruction to the insertion of subdural grids at the same operation, which may be caused by a framed system.

Adult↗
PubMed2002

Novel immunotherapeutic strategies in gynecologic oncology. Dendritic cell-based immunotherapy for ovarian cancer.

The recognition of tumor antigen loaded dendritic cells as one of the most promising approaches to induce a tumor specific immune response in vivo has recently generated widespread interest in the use of these natural adjuvants for the therapy of human malignancies refractory to standard treatment modalities. However, many cancer patients may not benefit from current strategies of cancer vaccination because an effective tumor antigen associated with their cancer has not yet been identified or because sufficient amounts of tumor tissue cannot be obtained for antigen preparation. The recent identification and cloning of a group of preferentially expressed serine proteases as novel ovarian tumor-associated antigens may offer the opportunity to test in a large group of patients the potential of DC-based immunotherapy. In this review, we describe these ovarian tumor antigens and assess the potential for therapeutic DC vaccination for the treatment of chemotherapy-resistant ovarian cancer.

Adult↗
PubMed2001

Prospective study of local cutaneous reactions in patients receiving IV phenytoin.

The authors prospectively examined the occurrence of subacute local cutaneous reactions (LCR) in patients receiving IV phenytoin over a 12-month period at a general hospital. LCR were detected in 29 of 115 patients (25.2%; 22 mild and seven moderate). All resolved within 3 weeks. Patients with LCR were older (median 68 versus 54.5 years, p = 0.004), were more likely to be in a general ward (86% versus 66%, p = 0.04), and had larger catheters (median 16 G versus 18 G, p = 0.05). The authors conclude that LCR are common in routine hospital practice, but are generally mild and benign.

Adult↗
PubMed2001

Advances in neuroimaging: non-substrate-directed partial epilepsy.

Contemporary neuroimaging studies using structural and functional techniques are critical in the evaluation of patients with localization-related epilepsy. Imaging procedures may be used to localize the epileptic brain tissue or determine the likely pathologic findings underlying the epileptogenic zone, or both. The diagnostic yield of magnetic resonance imaging (MRI) has been demonstrated in patients with partial epilepsy. The identification of an MRI epileptogenic lesion is almost invariably a reliable indicator of the site of seizure onset. Peri-ictal single photon emission computed tomography (SPECT) may be of particular benefit in patients with normal MRI studies. The use of neuroimaging in the care and management of patients with partial epilepsy is discussed here.

Epilepsies, Partial↗
PubMed2001

Multimodality image-guided epilepsy surgery.

Co-registration of imaging modalities in the diagnosis of epilepsy is now commonly used in major epilepsy centres. However, the incorporation of these registrations into an image-guided system has only recently been developed. Using techniques of segmentation, surface matching and/or voxel-based matching, we have been able to co-register FLAIR MRI, SPECT, PET, and subdural grids into the 3-D space of the volumetric MRI and use these images on the StealthStation Image-Guided System to resect these foci. This greatly aids the surgeon in performing a more precise tailoring of the cortical resection so as to maximize the excision of the epileptogenic zone while minimizing the impact on eloquent cortex and epileptogenic foci.

Adult↗
PubMed2001

Underexpression of cyclin-dependent kinase inhibitor p27 is associated with poor prognosis in serous ovarian carcinomas.

Reduced expression of a cyclin-dependent kinase inhibitor, p27, has been reported to be associated with poor prognosis in several human cancers. The aim of this study was to investigate the potential role of p27 in ovarian cancer development and progression. Immunohistochemical expression of p27 was determined using 117 epithelial ovarian tumor tissues and 8 normal ovaries. p27 mRNA expression was examined by semi-quantitative PCR amplification using 26 ovarian cancer samples. Nuclear staining of p27 was commonly observed in the normal ovarian surface epithelium and the epithelial cells of germinal inclusion cysts. Positive p27 staining rates were significantly higher in serous adenomas (p=0.006) and in serous LMP tumors (p=0.013) than that in serous carcinomas (Fisher's exact test). In serous ovarian cancers, positive p27 staining rate was significantly higher in early stage (stage1/2) than that in advanced stage (stage 3/4) diseases (p=0.030, Fisher's exact test). Log-rank testing showed that negative p27 expression significantly correlates with poor survival in serous ovarian cancer patients (p=0.041). Considerable levels of p27 mRNA were detected in all ovarian cancer samples examined. These results suggest that the underexpression of p27 caused by post-translational mechanism may contribute to the development and progression and result in poor prognosis of serous ovarian cancers.

Cell Cycle Proteins↗
PubMed2001

The utility of a 3-dimensional, large-field-of-view, sodium iodide crystal--based PET scanner in the presurgical evaluation of partial epilepsy.

UNLABELLED: (18)F-FDG PET is an accurate and reliable technique for localizing medically refractory temporal lobe epilepsy, but widespread use has been hindered by limited reimbursement in many countries because of the high cost of traditional PET equipment and radioisotopes. Additionally, the place of FDG PET as a cost-effective tool for presurgical evaluation of epilepsy has been questioned because of limited data showing that FDG PET provides localization information incremental to that provided by more established techniques, particularly MRI and ictal electroencephalography (EEG). Three-dimensional (3D), large-field-of-view, sodium iodide crystal-based scanners have lower equipment and running costs and better multiplanar resolution than traditional 2-dimensional bismuth germinate (BGO) systems but have not yet been validated for evaluation of epilepsy. Our purpose was to investigate the localization rate, accuracy, and prognostic value of FDG PET images acquired on a 3D, large-field-of-view, sodium iodide crystal-based PET scanner in the presurgical evaluation of intractable partial epilepsy. We also wanted to establish the incremental value of FDG PET over established MRI and ictal EEG techniques. METHODS: Fifty-five patients who were surgical candidates because of medically refractory partial epilepsy were examined. For most of these patients, the lesions had not been clearly localized on conventional assessment. The FDG PET scans were reviewed independently by 2 reviewers who were unaware of the patients' clinical details, ictal EEG findings, and volumetric MRI results, and the FDG PET results were correlated with those of MRI and EEG and with postsurgical outcome. RESULTS: Forty-two patients (76%) had localizing FDG PET images (37 temporal, 5 extratemporal). The ictal EEG recordings were localizing in 66%, and the MRI findings were localizing in 27% (which increased to 35% after the MRI findings were reviewed again after PET). Concordance between the site of the PET localizations and the site of the MRI or EEG localizations was 100%. The PET images were localizing in 63% and 69% of patients with nonlocalizing ictal EEG and MRI findings, respectively. Twenty-one of 24 patients who subsequently underwent epilepsy surgery had localizing FDG PET images; of these 21 patients, 18 (86%) had a class I outcome. Multiple regression analysis showed the FDG PET results to be predictive of postsurgical outcome independently of the MRI findings. CONCLUSION: For intractable partial epilepsy, FDG PET using a 3D, large-field-of-view, sodium iodide crystal-based scanner provided clinically useful localizing information that was at least as accurate as the results reported for traditional BGO-based scanners. The PET images provided prognostically significant localization information incremental to that provided by volumetric MRI and ictal EEG, particularly if 1 of these studies was nonlocalizing.

Adolescent↗
PubMed2001

Mechanism of apoptosis and determination of cellular fate in chromium(VI)-exposed populations of telomerase-immortalized human fibroblasts.

The cellular responses to carcinogen exposure influence cellular fate, which in turn modulates the neoplastic response. Certain hexavalent chromium [Cr(VI)] compounds are implicated as occupational respiratory carcinogens at doses that are both genotoxic and cytotoxic. We examined the mechanism of Cr(VI)-induced apoptosis in normal human fibroblasts (BJ) immortalized by human telomerase gene transfection (BJ-hTERT), and we assessed the spectrum of cumulative cellular fates [(a) regaining of replicative potential; (b) terminal growth arrest; or (c) apoptosis] for a narrow range of increasingly genotoxic doses of Cr(VI). Exposure of BJ-hTERT cells to Cr(VI) resulted in a dose-dependent increase in apoptosis that involved mitochondrial disruption as evidenced by mitochondrial membrane depolarization and cytochrome c release. The initial response to Cr(VI) exposure was inhibition of cell cycle progression. At the lowest dose tested (1 microM; 32% clonogenic survival), the cell cycle inhibition led to terminal growth arrest but no apoptosis. The fraction of terminally growth arrested cells increased as the dose was increased to 3 microM but then decreased at 4, 5, and 6 microM as apoptosis became the predominant cell fate. Our results suggest that cell populations exposed to Cr(VI) have a different spectrum of responses, depending on the extent of DNA damage, and that the regaining of replicative potential after relatively higher genotoxic exposures may be attributable to either escape from, or resistance to, terminal growth arrest or apoptosis.

Apoptosis↗
PubMed2000

Subtraction peri-ictal SPECT is predictive of extratemporal epilepsy surgery outcome.

OBJECTIVES: To determine whether localization of extratemporal epilepsy with subtraction ictal SPECT coregistered with MRI (SISCOM) is predictive of outcome after resective epilepsy surgery, whether SISCOM images provide prognostically important information compared with standard tests, and whether blood flow change on SISCOM images is useful in determining site and extent of excision required. BACKGROUND: The value of SISCOM in predicting surgical outcome for extratemporal epilepsy is unknown, especially if MRI findings are nonlocalizing. METHODS: SISCOM images in 36 consecutive patients were classified by blinded reviewers as "localizing and concordant with site of surgery," "localizing but nonconcordant with site of surgery," or "nonlocalizing." SISCOM images were coregistered with postoperative MRI, and reviewers visually determined whether cerebral cortex underlying the SISCOM focus had been completely resected, partially resected, or not resected. RESULTS: Twenty-four patients (66.7%) had localizing SISCOM, including 13 (76.5%) of those without a focal MRI lesion. Eleven of 19 patients (57.9%) with localizing SISCOM concordant with the surgical site, compared with 3 of 17 (17.6%) with nonlocalizing or nonconcordant SISCOM, had an excellent outcome (p < 0.05). With logistic regression analysis, SISCOM findings were predictive of postsurgical outcome, independently of MRI or scalp ictal EEG findings (p < 0.05). The extent of resection of the cortical region of the SISCOM focus was significantly associated with the rate of excellent outcome (100% with complete resection, 60% with partial resection, and 20% with nonresection, p < 0.05). CONCLUSION: SISCOM images may be useful in guiding the location and extent of resection in extratemporal epilepsy surgery.

Adolescent↗
PubMed2000

Ovarian tumor cells express a novel multi-domain cell surface serine protease.

Serine proteases serve many functions in normal biological processes. These functions are often usurped by cancer cells to allow progression of tumors by increasing the growth and metastatic potential of the neoplasia. Here, we have used a polymerase chain reaction (PCR)-based strategy to clone Tumor Associated Differentially-expressed Gene-12 (TADG-12), a new serine protease from ovarian carcinoma. This technique also revealed a variant splicing form of TADG-12 that could lead to a truncated protein product. Semi-quantitative PCR showed that TADG-12 is overexpressed in 41 of 55 ovarian cancer specimens relative to normal expression, and the variant form, TADG-12V is found at increased levels in 8 of 22 carcinomas examined. Northern blot revealed three transcripts, the largest of which is approximately 2.4 kb. An ovarian tumor cDNA library was screened, and the entire cDNA of TADG-12 has been identified. This sequence encodes a putative protein of 454 amino acids which includes a potential transmembrane domain, an LDL receptor-like domain, a scavenger receptor cysteine-rich domain, and a serine protease domain. These features imply that TADG-12 will be at the cell surface, and it may be useful as a molecular target for therapy or a diagnostic marker.

Amino Acid Sequence↗
PubMed2000

Evaluation of SPECT in the assessment and treatment of intractable childhood epilepsy.

The authors retrospectively examined the role of SPECT in 65 children undergoing video-EEG telemetry. SPECT was concordant in most children whose lesions were already localized by MRI and epilepsy syndrome and provided localizing data in more than half not localized by these modalities. Ictal SPECT provided no additional prognostic benefit in patients undergoing epilepsy surgery (n = 23) who have a localized MRI lesion. In patients without lesions, however, ictal SPECT provides useful additional localization that may be used as a guide to intracranial implantation.

Brain↗
PubMed2000

Induction of matrix metalloprotease-7 is common in mucinous ovarian tumors including early stage disease.

Matrix metalloproteases are known to play an important role in tumor invasion by mediating degradation of the extracellular matrix. In this study, we have investigated the immunohistochemical expression of matrix metalloprotease -7 (MMP-7) in 44 mucinous ovarian tumors (9 adenomas, 13 low malignant potential tumors, 22 adenocarcinomas) and 6 normal ovaries. Positive staining of MMP-7 is observed in all mucinous ovarian tumors, whereas little or no staining was observed in surface epithelium as well as the epithelial cells of germinal inclusion cyst of the normal ovary. Positive immunostaining of MMP-7 is also observed in the secreted mucin in the tumor glands, which suggests the secretion of the MMP-7 protein from tumor cells. mRNA expression of MMP-7 was confirmed using RT-PCR. The MMP-7 gene was amplified in parallel with an internal control gene beta-tubulin using a thermal cycler. mRNA expression levels of MMP-7 were significantly elevated in mucinous tumor samples compared with that in normal ovaries. Our results suggest that MMP-7 is frequently overexpressed in mucinous ovarian tumors and secreted with the mucin which is produced from the tumor cells. MMP-7 may therefore contribute to mucinous ovarian tumor development or enhanced growth capacity of mucinous ovarian tumors. MMP-7 may also serve as a target for therapeutic intervention in the down regulation of tumor progression.

Cystadenocarcinoma, Mucinous↗
PubMed2000

Localization of the epileptic focus by low-resolution electromagnetic tomography in patients with a lesion demonstrated by MRI.

Patients with medically intractable partial epilepsy and well-defined symptomatic MRI lesions were studied using phase-encoded frequency spectral analysis (PEFSA) combined with low-resolution electromagnetic tomography (LORETA). Ten patients admitted to the epilepsy monitoring unit with MRI-identified lesions and intractable partial epilepsy were studied using 31-electrode scalp EEG. The scalp electrodes were located in three-dimensional space using a magnetic digitizer and coregistered with the patient's MRI. PEFSA was used to obtain a phase-encoded scalp map for the ictal frequencies. The ictal generators were obtained from the scalp map using LORETA. In addition, the generators of interictal epileptogenic spikes were identified using time-domain LORETA. The LORETA generators were rostral to the MRI lesion in 87% (7/8) of patients with temporal lobe lesions, but all were located in the mesial temporal lobe in concordance with the patients' MRI lesions. In patients with frontal lobe epilepsy, the ictal generators at the time that the spectral power was maximal localized to the MRI lesions. Eight of 10 patients had interictal spikes, of which 4 were bilateral independent temporal lobe spikes. Only generators of the interictal spikes that were ipsilateral to seizure onset correlated with the ictal generators. LORETA combined with PEFSA of the ictal discharge can localize ictal EEG discharges accurately and improve correlation with brain anatomy by allowing coregistration of the ictal generator with the MRI. Analysis of interictal spikes was less useful than analysis of the ictal discharge.

Brain↗
PubMed2000

The EEG evaluation of single photon emission computed tomography abnormalities in epilepsy.

Single photon emission computed tomography (SPECT) has increasingly been used as a diagnostic procedure for localizing epileptic seizure foci and as a research tool for investigating the physiologic mechanisms underlying seizure activity. With increasing use of SPECT in localizing the seizure focus for epilepsy surgery, there arises a need to critically assess its current role in the evaluation of patients for epilepsy surgery, especially as it relates to other clinical and laboratory data used in presurgical evaluation. Ictal EEG discharge has traditionally been used as the "gold standard" against which SPECT studies are compared in assessing the latter's localizing value. However, this practice presents a major challenge because SPECT studies are often reserved for patients with nonlocalizing EEG or magnetic resonance imaging findings. Nonetheless, SPECT studies in evaluation for epilepsy surgery should always be performed with the knowledge of the patient's EEG activity preceding, during, and after the injection of the radiotracer. The advent of techniques such as subtraction SPECT with co-registration on magnetic resonance imaging (SISCOM) and computer image-guided surgery has great potential in enhancing the clinical electrophysiologic evaluation of SPECT-detected abnormalities in epilepsy. These techniques permit accurate spatial correlation between intracranial EEG activity and SPECT perfusion patterns. The techniques can also be used to evaluate the effect of the extent of EEG focus resection compared with that of SISCOM focus resection to determine which has more prognostic importance in postsurgical control of seizures. Both animal and human studies are warranted to advance our knowledge of the electrophysiology associated with the various SPECT perfusion patterns.

Adult↗
PubMed2000

Voxel significance mapping using local image variances in subtraction ictal SPET.

Subtraction ictal SPET co-registered to MRI (SISCOM) has been shown to aid epileptogenic localization and improve surgical outcome in partial epilepsy patients. This paper reports a method of identifying significant areas of epileptogenic activation in the SISCOM subtraction image, taking into account normal variation between sequential 99Tcm-ethyl cysteinate diethylester SPET scans of single individuals, and attempts to assess the clinical value of statistical mapping in subtraction SPET. Non-linear inter-subject registration is used to combine a group of subtraction images into a common anatomical framework. A map of the pixel intensity standard deviation values in the subtraction images is created, and this map is non-linearly registered to a patient's SISCOM subtraction image. Pixels in the patient subtraction image were then evaluated based upon the statistical characteristics of corresponding pixels in the atlas. SISCOM images created with the voxel variance method were rated higher in quality than the conventional image variance method in 15 patients. No difference in localization rate was observed between the voxel variance mapping and image variance methods. The voxel significance mapping method was shown to improve the quality of clinical SISCOM images.

Brain↗
PubMed2000

Factors predictive of the outcome of frontal lobe epilepsy surgery.

PURPOSE: To identify factors that predict the outcome in seizure control after frontal lobe epilepsy surgery (FLES). FLES is the second most frequent type of epilepsy surgery, but the results are generally not as good as those after anterior temporal lobectomy. METHODS: Our cohort consisted of 68 consecutive patients whose first epilepsy surgery involving the frontal lobe occurred between 1987 and 1994. Clinical history and results of imaging and electroencephalographic studies were reviewed in detail. Excellent outcome was defined as being seizure free or having only nondisabling seizures at last follow up. RESULTS: Forty of the 68 patients (58.8%) had an excellent outcome; none of the patients with a history of childhood febrile seizures had an excellent outcome, whereas outcome was excellent in 63% of those without that history (p </= 0.01). The other significant presurgical factor was the presence of a potentially epileptogenic lesion in the frontal lobe on neuroimaging (excellent outcome in 72% when present versus 41% when absent, p </= 0.001). The only significant postsurgical factor was early postoperative seizure control in the first year (excellent outcome in 96% with early control versus 25% without, p </= 0.01). CONCLUSIONS: History of childhood febrile seizures is a poor prognostic factor in FLES patients. It may suggest that the structural basis of all or some of the patients' intractable seizures is mesial temporal sclerosis. On the other hand, neuroimaging detection of a potentially epileptogenic frontal lobe lesion and early postoperative seizure control are associated with subsequent excellent outcome.

Adult↗
PubMed2000

Significance of cerebellar atrophy in intractable temporal lobe epilepsy: a quantitative MRI study.

PURPOSE: To determine the incidence of cerebellar atrophy (CA) in patients with intractable temporal lobe epilepsy, whether any clinical factors are significantly associated with CA, whether CA is unilateral or asymmetric and whether this feature has any relationship to the side of epileptogenicity, and whether the presence of CA is related to epilepsy surgery outcome. METHODS: We developed a magnetic resonance imaging method of measuring the presurgical volumes of the cerebellar hemispheres of 185 patients who underwent temporal lobectomy for intractable epilepsy and of 80 control subjects. In addition, cerebellar volumes were normalized to the total brain volumes. CA was determined as being present when the measured volume was smaller than two standard deviations from the mean value found in control subjects. RESULTS: Both absolute and normalized cerebellar volumes were found to be significantly reduced in the epilepsy patients compared with the control subjects. Without normalization of the cerebellar volumes, CA was present in 25.9% of the epilepsy patients; with normalization, it was present in only 16.2%. The atrophy was symmetric between the cerebellar hemispheres, and there was no significant difference in volume between the hemisphere ipsilateral and the hemisphere contralateral to the side of the temporal lobectomy. The duration of epilepsy was significantly longer and the age at onset of epilepsy was younger in patients with CA than in those without CA. The presence of CA was not associated with the outcome of temporal lobectomy. CONCLUSIONS: CA is symmetric and common in patients with intractable temporal lobe epilepsy. However, the results suggest that the atrophy in one third of patients with CA also proportionately affects the cerebral hemispheres. The duration of epilepsy and the age at onset of epilepsy are associated with the occurrence of CA. Seizure control after temporal lobectomy is not influenced by the presence of CA.

Adult↗