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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

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↗
PubMed1999

Progressive hippocampal atrophy in chronic intractable temporal lobe epilepsy.

We report on a 28-year-old man with long-standing intractable complex partial and secondary generalized seizures, whose magnetic resonance imaging scans 4 years apart documented progressive decrease in the left hippocampal volume. Left anterior temporal lobectomy with amygdalohippocampectomy rendered the patient seizure free at 12 months' follow-up. The findings demonstrate that patients with uncontrolled temporal lobe seizures may develop progressive atrophy of the hippocampus, in the absence of status epilepticus.

Adult↗
PubMed1999

Biomechanical comparison of plates and rods in the unstable thoracic spine.

Thoracic spine stabilization after trauma or in tumor reconstruction cases frequently is performed with hook and rod internal fixation systems, the use of which is not always possible. Pelvic reconstruction plates with pedicle screw fixation offer an alternative to hooks and rods. In this study, we biomechanically compared a plate construct with a hook and rod system in an acute postoperative, unstable thoracic spine model. We found that the hook and rod system offered more resistance to flexion and extension bending than the plate construct; the opposite was true for lateral bending and axial torsion. We further determined that the addition of pars interarticularis screws to the plate construct provided increased resistance to all loading modes. Our study indicates that plate constructs can effectively stabilize the thoracic spine.

Biomechanical Phenomena↗
PubMed1999

Quantitative and clinical analysis of SPECT image registration for epilepsy studies.

UNLABELLED: This study reports quantitative measurements of the accuracy of two popular voxel-based registration algorithms--Woods' automated image registration algorithm and mutual information correlation--and compares these with conventional surface matching (SM) registration. METHODS: The registration algorithms were compared (15 different matches each) for (a) three-dimensional brain phantom images, (b) an ictal SPECT image from a patient with partial epilepsy matched to itself after modification to simulate changes in the cerebral blood flow pattern and (c) ictal/interictal SPECT images from 15 patients with partial epilepsy. Blinded visual ranking and localization of the subtraction images derived from the patient images were also performed. RESULTS: Both voxel-based registration methods were more accurate than SM registration (P < 0.0005). Automated image registration algorithm was more accurate than mutual information correlation for the computer-simulated ictal/interictal images and the patient ictal/interictal studies (P < 0.05). The subtraction SPECTs from SM were poorer in visual ranking more often than the voxel-based methods (P < 0.05). CONCLUSION: Voxel intensity-based registration algorithms provide significant improvement in ictal/interictal SPECT registration accuracy and result in a clinically detectable improvement in the subtraction SPECT images.

Algorithms↗
PubMed1998

The practical utility of performing peri-ictal SPECT in the evaluation of children with partial epilepsy.

Peri-ictal brain single-photon emission computed tomography (SPECT) is increasingly being established as a useful test in localizing partial epilepsy in adults. However, obtaining an ictal injection and acquiring the SPECT images poses a greater challenge in pediatric patients, and few reports have specifically addressed the practical use of this technique in children. The Mayo Clinic experience of peri-ictal SPECT in the evaluation of children with partial epilepsy is reported here. Peri-ictal SPECT was attempted during 71 admissions involving 59 patients (median age 12 years, range 1 year 6 months-17 years). A peri-ictal SPECT injection was performed on 48 (67.6%) of these admissions in 43 (72.9%) patients, and only two patients could not be scanned. Of the 46 peri-ictal images successfully obtained, 30 (65.2%) were from ictal injection and 16 (34.8%) from post-ictal injections. Forty-two (91.3%) of the successfully obtained SPECT images, in 38 patients (92.3%), were classified as localizing (15 temporal, 24 extratemporal). We conclude that, with the appropriate unit setup and well-trained staff, peri-ictal SPECT scans can be obtained in most pediatric partial epilepsy patients. Moreover, the procedure provides specific localizing information in a high proportion of these patients.

Adolescent↗
PubMed1998

Scalp-recorded EEG localization in MRI volume data.

Scalp-recorded EEG is a noninvasive and widely available tool for studying normal and dysfunctional human neurophysiology with unsurpassed temporal resolution. However, scalp-recorded EEG data is difficult to correlate with anatomy, and most current display and neural source estimation algorithms are based on unrealistic spherical or elliptical models of the head. It is possible to measure the positions of electrodes on the patient's scalp, and to register those electrode positions into the space of a high-resolution MRI volume, and to then use the patient-specific anatomy as the basis for display and estimation of neural sources. We use a surface matching algorithm to register digitized electrode and scalp surface coordinates to a three-dimensional MRI volume. This study uses fiducial markers in phantom and volunteer studies to quantitatively estimate the accuracy of the electrode registration method. Our electrode registration procedure is accurate to 2.21 mm for a realistic head phantom and accurate to 4.16 mm on average for five volunteers. This level of accuracy is considered within acceptable limits for clinical applications.

Algorithms↗
PubMed1998

Subclinical rhythmic electrographic discharges of adults (SREDA) revisited: a study using digital EEG analysis.

Previous descriptions of the subclinical rhythmic electrographic discharges of adults (SREDA) have been based entirely on visual analysis of analog electroencephalographic (EEG) recordings. The introduction of digital electroencephalograms (EEGs) and advances in digital signal processing provide an opportunity to restudy in more depth the nature of SREDA. We identified nine patients who had SREDA diagnosed on a routine EEG recording since the introduction of digital EEG to our laboratory in August 1995. Following careful rereview using standard montages, six of these patients were determined to fulfill the traditional requirements for the diagnosis of SREDA, whereas three were believed to have other benign discharges. Review with Laplacian montages demonstrated that the site of the SREDA activity was maximal in the parietal region or parietocentrotemporal regions, whereas it was maximal in the temporal or frontotemporal regions in the non-SREDA discharges. Frequency analysis, using both the conventional fast Fourier transform (FFT) and time-frequency mapping with the Wigner FFT variant, demonstrated that the SREDA consisted of a complex mixture of multiple rapidly shifting frequencies which showed little spatial and temporal correlation. In contrast, the non-SREDA all consisted of a single dominant well-organized rhythmic frequency spectrum that remained stable throughout space and time.

Adult↗