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T J O'Brien

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

At least 37 records · Page 2Linked to original sources
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↗
PubMed2000

Subtraction ictal SPECT coregistered to MRI for seizure focus localization in partial epilepsy.

Peri-ictal single-photon emission computed tomography (SPECT) of the brain is increasingly used in localizing the seizure focus in presurgical evaluation of patients with partial epilepsy. However, traditional side-by-side visual interpretation of ictal and interictal SPECT films is hampered by differences in slice location and tracer activity. Precise correlation of the seizure focus with a high-quality image of the underlying brain anatomy can improve the physician's understanding of seizure neurophysiology and assist in surgical planning. Computer-based methods have been developed for aligning, normalizing, and subtracting digital ictal and interictal SPECT images of the patient's brain to produce a map of the blood flow changes occurring between the seizure and resting states. These maps are then aligned with a high-resolution magnetic resonance image (MRI) of the patient's brain anatomy and fused to identify anatomical regions involved in the seizure. The purpose of this article is to review the technical components and clinical implementation of subtraction ictal SPECT, as well as to discuss recent technological advances that could extend and improve the diagnostic and localizing capacity of this method.

Acute Disease↗
PubMed1999

The stratum corneum chymotryptic enzyme that mediates shedding and desquamation of skin cells is highly overexpressed in ovarian tumor cells.

BACKGROUND: Proteases play essential roles in the process of tumor invasion and metastasis. The serine protease stratum corneum chymotryptic enzyme (SCCE) has been purified from human stratum corneum and is known to contribute to the cell shedding process by catalyzing the degradation of intercellular cohesive structures at the skin surface. The presence of SCCE on the surface of tumor cells suggests it also may contribute to the process of tumor cell shedding, resulting in early metastasis of carcinoma. METHODS: Gene expression of SCCE was investigated in 44 ovarian tumors (12 low malignant potential tumors and 32 carcinomas) and 10 normal ovaries by quantitative polymerase chain reaction (PCR). The PCR product was labeled with (32)P and a phosphoimager was used to determine the relative expression of SCCE compared with an internal control Beta-tubulin. mRNA transcripts were studied by Northern blot hybridization and protein expression and localization was examined by Western blot analysis and immunohistochemistry. RESULTS: mRNA expression levels of SCCE were elevated significantly in 66.7% of 12 low malignant potential tumors and 78.1% of 32 carcinomas. Furthermore, SCCE protein was abundant in tumor cells and tumor cell lines that overexpressed the mRNA transcript. CONCLUSIONS: The results of the current study suggest that SCCE frequently is overexpressed in ovarian tumors and therefore may contribute to tumor cell growth, tumor spread, and the metastatic potential of ovarian tumor cells.

Blotting, Northern↗
PubMed1999

Cloning of tumor-associated differentially expressed gene-14, a novel serine protease overexpressed by ovarian carcinoma.

The family of enzymes known as serine proteases supports many biological functions for cancer cells, including activation of growth and angiogenic factors and activation of other proteases for invasion and metastasis. In addition, many of these serine proteases are secreted by cells into the extracellular space to serve these functions. Therefore, serine proteases are excellent candidate tumor markers. To examine serine proteases expressed by ovarian carcinoma, we designed degenerate PCR primers corresponding to the conserved regions of these genes and used them in reverse transcriptase-PCR experiments with normal and tumor cDNA as a template. The PCR products were subcloned and sequenced, and one of these clones was found to encode a novel serine protease, named tumor-associated differentially expressed gene-14 (TADG14). Northern blot analysis indicated that the mRNA for TADG14 is 1.4 kb long and that it is highly overexpressed in ovarian carcinoma compared with normal ovary. The entire cDNA has been obtained, and based on sequence homology, it encodes a 260-amino acid serine protease. Semiquantitative PCR indicates that TADG14 is overexpressed in 24 of 40 tumors studied. Northern blot data confirm this overexpression, and immunohistochemical staining suggests that this protein is secreted. As such, the TADG14 protease may be useful as a diagnostic tool or as a molecular target for therapy.

Amino Acid Sequence↗
PubMed1999

Determination of lamotrigine in human plasma by high-performance liquid chromatography.

The method involves precipitation of plasma proteins with acetonitrile and analysis of the supernatant by high-performance liquid chromatography using a 5 microm Zorbax C8 column. Quantitation was performed by measurement of the UV absorbance at a wavelength of 306 nm. The method was linear in the range of 1-20 microg/ml, with a mean coefficient of determination (r2=0.998). The limit of detection was 0.6 microg/ml and the lower limit of quantitation was 1 microg/ml using 200 microl of plasma. Within- and between-day accuracy and precision were below 6% at all analysed concentrations except at the limit of quantitation. No interfering peaks were found by commonly monitored antiepileptic drugs. Recovery was found to be > or =99%. Satisfactory performance was obtained in the evaluation of epileptic patient samples, whose results of plasma concentration measurements are briefly discussed. We conclude that this is a reliable method for the routine monitoring of lamotrigine concentration in plasma in the clinical setting.

Adult↗
PubMed1999

Subtraction SPECT co-registered to MRI improves postictal SPECT localization of seizure foci.

OBJECTIVE: To determine whether the detection of focal hypoperfusion by subtraction SPECT co-registered to MRI (SISCOM) improves the sensitivity and specificity of postictal SPECT in intractable partial epilepsy. BACKGROUND: Postictal SPECT injections are easier to perform than are ictal injections, but the images are more difficult to interpret and have been reported to have lower sensitivity and specificity. METHODS: Thirty-five consecutive intractable partial epilepsy patients who had postictal SPECT studies were evaluated. The following sets of SPECT images were separately interpreted by three blinded reviewers and classified as either localizing to 1 of 16 possible sites in the brain or as nonlocalizing: unsubtracted postictal and interictal images for conventional side-by-side comparison, SISCOM images of hyperperfusion, SISCOM images of hypoperfusion, and both sets of SISCOM hyperperfusion and hypoperfusion images (combined SISCOM evaluation). RESULTS: Significantly higher proportions of the hyperperfusion SISCOM images (65.7%), the hypoperfusion SISCOM images (74.3%), and the combined SISCOM evaluation (82.9%) were localizing than were the conventional method of side-by-side comparison of unsubtracted images (31.4%; p < 0.0001). Concordance with the discharge diagnosis was higher for the combined SISCOM evaluation than it was for either the hyperperfusion or the hypoperfusion SISCOM images alone (both p < 0.05). For the hypoperfusion SISCOM and the combined SISCOM evaluations, concordance of the localization with the site of epilepsy surgery was associated with a greater probability of an excellent outcome than were nonconcordant/nonlocalizing images (both p < 0.05). CONCLUSION: The use of SISCOM to detect focal cerebral hypoperfusion, in addition to focal hyperperfusion, improves the sensitivity and specificity of postictal SPECT in intractable partial epilepsy.

Adolescent↗
PubMed1999

Comparative study of 99mTc-ECD and 99mTc-HMPAO for peri-ictal SPECT: qualitative and quantitative analysis.

OBJECTIVES: Most studies that clinically validated peri-ictal SPECT in intractable partial epilepsy had used technetium-99m-hexamethylpropylene amine oxime (99mTc-HMPAO or 99mTc-exametazime) as the radiopharmaceutical. Because of some theoretical advantages, technetium-99m-ethyl cysteinate diethylester (99mTc-ECD or 99mTc-bicisate) is increasingly being used instead. This study compares unstabilised 99Tc-HMPAO and 99mTc-ECD in the performance of peri-ictal SPECT in partial epilepsy. METHODS: The injection timing and localisation rates in 49 consecutive patients with partial epilepsy who had peri-ictal injections with unstabilised 99mTc-HMPAO were compared with 49 consecutive patients who had peri-ictal injections with 99mTc-ECD. Quantitative cortical/subcortical and cortical/extracerebral uptake ratios were also compared. Subtraction SPECT coregistered to MRI (SISCOM) was performed in patients whose interictal SPECTS were available. RESULTS: In the 99mTc-ECD patients, the latency from seizure commencement to injection was shorter (median 34 v 80 seconds, p<0.0001) and there was a lower rate of postictal injections (16.3% v 57.1%, p<0.0001). The cortical/extracerebral and cortical/subcortical uptake ratios were greater in the 99mTc-ECD images (median 5.0 v 3.6, and 2.5 v 2.2 respectively; both p<0.005), but the relative peri-ictal increase in uptake in the cortical focus did not differ significantly (median 37.0% v 37.0%; p>0.05). Blinded review of the SISCOM images were localising in a higher proportion of the 99mTc-ECD patients (40/45 (88.9%) v 25/37 (67.6%), p<0.05), and had a better concordance with EEG, MRI, and with the discharge diagnosis. CONCLUSION: 99mTc-ECD compares favourably with unstabilised 99mTc-HMPAO as a radiopharmaceutical for peri-ictal SPECT studies. Its use results in earlier injections and less frequent postictal injections than unstabilised 99mTc-HMPAO, thereby enhancing the sensitivity and the specificity of peri-ictal SPECT for the localisation of intractable partial epilepsy.

Adolescent↗
PubMed1999

Cerebral topography of rectal stimulation using single photon emission computed tomography.

Central processing of visceral information in humans is incompletely understood. We aimed to demonstrate the feasibility of single photon emission computed tomography (SPECT) and to quantitate the changes in regional cerebral blood flow during rectal distension. Ten healthy volunteers underwent randomized sham and active rectal distensions on separate days, during which cerebral blood flow was assessed by intravenous technetium-99m ethyl cysteinate dimer ((99m)Tc-ECD) SPECT. Three-dimensional coregistration of brain images was used to quantitate activation in four preselected cerebral foci and two control regions. Paired analysis compared blood flow during sham and active distensions. There was increased right anterior cingulate gyrus activity (6.5 +/- 2.9%, P = 0.03) with active rectal distension. A 5.4 +/- 2.4% reduction in blood flow in the superior parieto-occipital control region (P = 0.04) suggested blood "redistribution" during stimulation. Marked variability in activation of the frontal cortex, thalamus/basal ganglia complex, and mesiotemporal lobe was noted. Thus rectal distension increases activity in the right anterior cingulate gyrus on average; other foci of cerebral activation are quite variable, suggesting a lack of specific cerebral projections during rectal stimulation.

Adolescent↗
PubMed1999

Anterior cervical graft and plate load sharing.

Anterior discectomy and fusion with an interbody bone graft and anterior plate is a common procedure in cervical spine surgical management. However, the graft may be shielded from some mechanical loading by the plate. Mechanical testing was performed on six cadaveric calf spines that were subjected to a simulated anterior cervical discectomy and fusion with an interbody bone graft alone and with an anterior plate to determine the amount of load sharing between the graft and plate. The load-displacement data were used to compute the amount of load sharing between the graft and the plate as a continuous function of the applied axial compression load. Although the percent load transmitted through the graft decreased (53 to 41%) as the axial load increased (45 to 90 N), the magnitude of load transmitted through the graft increased (24 to 37 N), with corresponding intervertebral strains <6%. In a single-level procedure, an anterior cervical plate serves as a load-sharing device rather than a load-shielding device, enabling graft consolidation as observed in clinical studies.

Animals↗
PubMed1999

Dual-isotope SPECT using simultaneous acquisition of 99mTc and 123I radioisotopes: a double-injection technique for peri-ictal functional neuroimaging.

UNLABELLED: The acquisition of multiple radiotracer studies at different time points during a neurological event permits the study of different functional activation states in humans. Peri-ictal SPECT is a promising technique for localizing the epileptogenic zone and would be enhanced by the ability to acquire sequentially coregistered ictal and postictal SPECT images of a single seizure. This study was designed to develop and validate an accurate method for the simultaneous acquisition of 99mTc and 123I SPECT images of the brain. METHODS: A multicompartment, transaxial Hoffman brain-slice phantom was filled with 99mTc, 123I or a 3:1 mixture of the two isotopes. Planar and SPECT images were acquired by a dual-head gamma camera system equipped with parallel and fanbeam collimators, respectively. Thirty-two energy windows (2 keV width) were acquired over the energy range 120-184 keV. From the planar data, the signal-to-noise characteristics and crosstalk were measured for each energy window and used to devise an energy window acquisition strategy that was then applied to the SPECT data. Three summed energy windows were created: a primary 99mTc image (130-146 keV), a primary 123I image (152-168 keV) and a secondary 99mTc crosstalk image (134-140 keV). A fraction (0.041) of the 99mTc crosstalk image was subtracted from the 123I image. No crosstalk correction was performed on the primary 99mTc image. RESULTS: (a) Planar images: results showed 1.3% crosstalk in the 123I image compared with 19.7% for a 10% asymmetric energy window alone. 123I crosstalk into the 99mTc window was 2.79% and was relatively constant with changes in the location of the 99mTc energy window. (b) Tomographic images: results showed 1.51% 99mTc crosstalk in the 123I image compared with 12.44% for the uncorrected image and 3.70% 123I crosstalk in the 99mTc image. CONCLUSION: An effective technique for the simultaneous acquisition of 99mTc and 123I radiotracer distributions in the brain has been developed and validated in a phantom model and should have clinical application in peri-ictal functional activation studies of the brain.

Brain↗