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Biomedical subjects

T J O'Brien

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

At least 55 records · Page 3Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

Subtraction ictal SPET co-registered to MRI in partial epilepsy: description and technical validation of the method with phantom and patient studies.

Computer-aided subtraction of the co-registered and normalized interictal from the ictal single photon emission tomography (SPET) scan, followed by co-registration to the magnetic resonance image, may improve the utility of ictal SPET in the localization of partial epilepsy. This paper describes and technically validates our method. The SPET to SPET co-registration was tested using six sequential 99Tc(m) brain phantom SPET images of different known positions (15 matches). The registration error was determined by multiplying the calculated match transformation matrix by the inverse of the known transformation matrix. The 'worst case' co-registration error was less that one voxel diameter in all cases (median 3.2 mm, range 1.2-4.8 mm). For interictal to ictal SPET registrations in 10 consecutive intractable partial epilepsy patients, a similar root mean square distance (RMSD) between corresponding points on the matched scans was found as for the phantom studies (median 2.2 vs 2.6 mm). The appropriateness of our normalization was studied by comparing the pixel intensity distributions between the matched scans, and by analysing the subtraction pixel intensity distribution. The pixel intensity distribution for both the normalized phantom, and paired normalized patient studies, were closely matched to each other except for the extreme values, which in clinical situations likely represent regions of ictal activation or depression. The subtraction image intensity distributions were symmetrically centred on zero for all values up to at least within the 5th to 95th centile range, confirming good normalization for the 'non-activated' pixels. Also, a linear relationship was demonstrated between the measured pixel intensity on the phantom scans and the true changes in 99Tc(m) activity based on its decay constant. The results of this study demonstrate that our method produces accurate SPET to SPET co-registration, and appropriate SPET normalization, thereby allowing a valid ictal subtraction image to be derived.

Brain↗

Cerebellar changes in partial seizures: clinical correlations of quantitative SPECT and MRI analysis.

PURPOSE: To determine the frequency and patterns of periictal cerebellar hyperperfusion, whether it is associated with increased cerebellar atrophy, and whether cerebellar hyperperfusion and cerebellar atrophy are associated with predisposing clinical factors or with the outcome of epilepsy surgery. METHODS: Periictal and interictal SPECT scans and volumetric brain magnetic resonance imaging (MRI) were quantitatively analyzed in 54 consecutive patients with medically refractory partial epilepsy. Their histories were reviewed and their postsurgical outcomes assessed. RESULTS: Significant periictal cerebellar hyperperfusion was found in 26 (48.1%) patients, of whom 18 had CCH, two had homolateral cerebellar hyperperfusion (HCH), and six had symmetrical bilateral hyperperfusion (BCH). No relation found between the site of the SPECT seizure localization and the presence or type of cerebellar hyperperfusion. CCH was more common when the injected seizure involved unilateral clonic motor activity (p < 0.05). A smaller MRI relative cerebellar volume (cerebellar volume/cerebral volume) was correlated with a greater seizure frequency (Rs = -0.30; p < 0.05) but not with the duration of epilepsy. There was no difference in the cerebellar volumes between the different patterns of cerebellar perfusion (p > 0.05). However, patients without a focal structural MRI lesion had significantly smaller cerebellar volumes (p < 0.05). In patients who underwent epilepsy surgery (n = 31), there was a trend for those without excellent outcomes to have smaller relative cerebellar volumes than did those with excellent outcome (10.6 vs. 11.8%; p = 0.08). CONCLUSIONS: Periictal changes in cerebellar perfusion, particularly CCH, are common in patients with intractable partial epilepsy. However, periictal hyperperfusion does not appear to be a major contributor to the development of cerebellar atrophy.

Adolescent↗

Subtraction ictal SPECT co-registered to MRI improves clinical usefulness of SPECT in localizing the surgical seizure focus.

Traditional side-by-side visual interpretation of ictal and interictal single-photon emission computed tomography (SPECT) scans can be difficult in identifying the surgical focus, particularly in patients with extratemporal or otherwise unlocalized intractable epilepsy. Computer-aided subtraction ictal SPECT co-registered to MRI (SISCOM) may improve the clinical usefulness of SPECT in localizing the surgical seizure focus. We studied 51 consecutive intractable partial epilepsy patients who had interictal and ictal scans. The SPECT studies were blindly reviewed and classified as either localizing to 1 of 16 sites in the brain or as nonlocalizing. SISCOM images were localizing in 45 of 51 (88.2%) compared with 20 of 51 (39.2%) for traditional side-by-side inspection of ictal and interictal SPECT images (p < 0.0001). Inter-rater agreement for two independent reviewers was better for SISCOM (84.3% versus 41.2%, kappa = 0.83 versus 0.26; p < 0.0001). Concordance of seizure localization with the more established tests was also higher for SISCOM. Late injection of the radiotracer (> 45 seconds), but not secondary generalization of the seizure, was associated with a falsely localizing or nonlocalizing SISCOM. Epilepsy surgery patients whose SISCOM localization was concordant with a falsely localizing or nonlocalizing SISCOM. Epilepsy surgery patients whose SISCOM localization was concordant with the surgical site were more likely to have excellent outcome than patients with nonconcordant or nonlocalizing findings (62.5% [10/16] versus 20% [2/10]; p < 0.05). On the other hand, seizure localization by the traditional method of SPECT inspection had no significant association with postsurgical outcome. We conclude that SISCOM improves the sensitivity and the specificity of SPECT in localizing the seizure focus for epilepsy surgery. Concordance between SISCOM localization and site of surgery is predictive of postsurgical improvement in seizure outcome.

Brain↗

Incidence and clinical consequence of the purple glove syndrome in patients receiving intravenous phenytoin.

OBJECTIVE: To determine the incidence, risk factors, and long-term sequelae of the purple glove syndrome (PGS) in hospital patients receiving IV phenytoin. BACKGROUND: PGS is a poorly understood, potentially serious local complication of IV phenytoin administration characterized by progressive distal limb edema, discoloration, and pain. METHODS: The pharmacologic records of the Mayo Foundation hospitals were reviewed to identify 179 consecutive patients who had IV phenytoin ordered during a 3-month period. Their hospital records were then reviewed to confirm IV phenytoin treatment, the frequency of PGS (defined as the progressive development of edema, discoloration, and pain in the limb after administration of IV phenytoin), and the outcome of PGS. RESULTS: A total of 152 patients received IV phenytoin, and nine (5.9%) developed PGS. PGS patients received a greater median initial dose of phenytoin, total 24-hour dose, and total number of doses (all p < 0.05). In addition, the median age of the PGS patients was older, their infusion was more often given for acute seizures, it was less likely to be administered in the operating room, and the length of their hospital stay was longer (all p < 0.05). One patient required surgical therapy, and all other patients resolved within 3 weeks with conservative management. CONCLUSIONS: PGS is not rare and elderly patients and individuals receiving large, multiple doses are particularly at risk. This iatrogenic complication may be preventable by substituting fosphenytoin for IV phenytoin.

Adolescent↗

Acute postoperative seizures following anterior temporal lobectomy for intractable partial epilepsy.

OBJECT: Recurrence of seizures immediately following epilepsy surgery can be emotionally devastating, and raises concerns about the chances of successfully attaining long-term seizure control. The goals of this study were to investigate the frequency of acute postoperative seizures (APOS) occurring in the 1st postoperative week following anterior temporal lobectomy (ATL) to identify potential risk factors and to determine their prognostic significance. METHODS: One hundred sixty consecutive patients who underwent an ATL for intractable nonlesional temporal lobe epilepsy were retrospectively studied. Acute postoperative seizures occurred in 32 patients (20%). None of the following factors were shown to be significantly associated with the occurrence of APOS: age at surgery, duration of epilepsy, side of surgery, extent of neocortical resection, electrocorticography findings, presence of mesial temporal sclerosis, and hippocampal volume measurements (p > 0.05). Patients who suffered from APOS overall had a lower rate of favorable outcome with respect to seizure control at the last follow-up examination than patients without APOS (62.5% compared with 83.6%, p < 0.05). The type of APOS was of prognostic importance, with patients whose APOS were similar to their preoperative habitual seizures having a significantly worse outcome than those whose APOS were auras or were focal motor and/or generalized tonic-clonic seizures (excellent outcome: 14.3%, 77.8%, and 75%, respectively, p < 0.05). Only patients who had APOS similar to preoperative habitual seizures were less likely to have an excellent outcome than patients without APOS (14.3% compared with 75%, p < 0.05). Timing of the APOS and identification of a precipitating factor were of no prognostic importance. CONCLUSIONS: The findings of this study may be useful in counseling patients who suffer from APOS following ATL for temporal lobe epilepsy.

Acute Disease↗

Anterior cruciate ligament reconstruction in the military patient.

This study prospectively evaluates the likelihood of a return of military personnel to full duty after anterior cruciate ligament reconstruction. We report the results of 120 active duty military patients who underwent anterior cruciate ligament reconstruction with autogenous patella tendon. Mean follow-up was 29 months (range, 24-65 months). Time from injury to reconstruction was > 6 months in 90% of patients. Final Lysholm scores averaged 89 (range, 29-100). We found that 77% of patients returned to full duty, whereas 23% of patients were medically discharged from military service. The patient age, military rank, time from injury to surgery, and KT-1000 measurements did not correlate with either the Lysholm score or return to duty (p = 0.05). Severe chondromalacia (Outerbridge III or IV) did correlate with poor result (p = 0.043), and Lysholm score did correlate with return to duty (p = 0.003). Anterior cruciate ligament reconstruction offers a higher likelihood of return to full military duty than nonoperative treatment in a similar study.

Adult↗

Hepsin, a cell surface serine protease identified in hepatoma cells, is overexpressed in ovarian cancer.

Extracellular proteases mediate the digestion of neighboring extracellular matrix components in initial tumor growth, allow shedding or desquamation of tumor cells into the surrounding environment, provide the basis for invasion of basement membranes in target metastatic organs, and are required for release and activation of many growth and angiogenic factors. We identified overexpression of the serine protease hepsin gene in ovarian carcinomas and investigated the expression of this gene in 44 ovarian tumors (12 low malignant potential tumors and 32 carcinomas) and 10 normal ovaries. Quantitative PCR was used to determine the relative expression of hepsin compared to that of beta-tubulin. The mRNA expression levels of hepsin were significantly elevated in 7 of 12 low malignant potential tumors and in 27 of 32 carcinomas. On Northern blot analysis, the hepsin transcript was abundant in carcinoma but was almost never expressed in normal adult tissue, including normal ovary. Our results suggest that hepsin is frequently overexpressed in ovarian tumors and therefore may be a candidate protease in the invasive process and growth capacity of ovarian tumor cells.

Carcinoma, Hepatocellular↗

Expression of the farnesyltransferase beta-subunit gene in human ovarian carcinoma: correlation to K-ras mutation.

The ras signaling protein requires a posttranslational modification to localize it to the inner surface of plasma membrane. In this state it can behave as a signal transduction mediator. Farnesyltransferase plays an important role in this posttranslational processing of ras by attaching a farnesyl group to the cysteine of the ras C-terminal tetrapeptide. In this study, we investigated the relationship of K-ras expression and mutation with farnesyltransferase beta-subunit expression in 20 ovarian tumors (17 carcinomas and 3 low malignant potential tumors) and 4 normal ovaries. The expression level of mRNA was determined by using quantitative PCR and mutation analysis was performed by direct cDNA sequencing. K-ras mutations were found in 1 of 3 low malignant potential tumors and in 4 of 17 carcinoma cases. K-ras mRNA overexpression was found in 1 of 3 low malignant potential tumors (one with mutated ras) and in only 1 of 17 carcinoma cases. Farnesyltransferase beta-subunit mRNA overexpression was found in 2 of 3 low malignant potential tumors and in 7 of 17 carcinoma cases. Interestingly, all K-ras mutation cases showed farnesyltransferase beta-subunit overexpression. These findings suggest that there may be a direct relationship between K-ras (ras dysfunction) mutation and expression of farnesyltransferase beta-subunit gene.

Alkyl and Aryl Transferases↗

Mechanisms whereby propofol mediates peripheral vasodilation in humans. Sympathoinhibition or direct vascular relaxation?

BACKGROUND: Anesthetic induction and maintenance with propofol are associated with decreased blood pressure that is, in part, due to decreased peripheral resistance. Several possible mechanisms whereby propofol could reduce peripheral resistance include a direct action of propofol on vascular smooth muscle, an inhibition of sympathetic activity to the vasculature, or both. This study examined these two possibilities in humans by measuring the forearm vascular responses to infusions of propofol into the brachial artery (study 1) and by determining the forearm arterial and venous responses to systemic (intravenous) infusions of propofol after sympathetic denervation of the forearm by stellate blockade (study 2). METHODS: Bilateral forearm venous occlusion plethysmography was used to examine forearm vascular resistance (FVR) and forearm vein compliance (FVC). Study 1 used infusion of intralipid (time control) and propofol at rates between 83 and 664 micrograms/min into the brachial artery of 11 conscious persons and compared responses to arterial infusions of sodium nitroprusside (SNP) at 0.3, 3.0, and 10 micrograms/min. Venous blood from the infusion arm was assayed for plasma propofol concentrations. In study 2, after left stellate block (12 ml 0.25% bupivacaine + 1% lidocaine), six participants were anesthetized and maintained with propofol infusions of 125 and 200 micrograms.kg-1.min-1. Simultaneous right forearm (unblocked) blood flow dynamics served as the time control. In three additional conscious participants, intrabrachial artery infusions of SNP and nitroglycerin, both at 10 micrograms/min, were performed before and after stellate blockade of the left forearm to determine whether the sympathetically denervated forearm vessels could dilate beyond the level produced by denervation alone. RESULTS: In study 1, infusion of intralipid or propofol into the brachial artery did not change FVR or FVC. Sodium nitroprusside significantly decreased FVR in a dose-dependent manner by 22 +/- 5%, 65 +/- 3%, and 78 +/- 2% (mean +/- SEM) but did not change FVC. During the incremental propofol infusions, plasma propofol concentrations increased from 0.2 to 10.1 micrograms/ml and averaged 7.4 +/- 1.1 micrograms/ml during the highest infusion rate. In study 2, stellate ganglion blockade decreased FVR by 50 +/- 6% and increased FVC by 58 +/- 10%. Propofol anesthesia at 125 and 200 micrograms.kg-1.min-1 progressively reduced mean arterial pressure. In the arm with sympathetic denervation, FVR and FVC showed no further changes during propofol anesthesia, whereas in the control arm FVR significantly decreased by 41 +/- 9% and 42 +/- 7%, and FVC increased significantly by 89 +/- 27% and 85 +/- 32% during 125 and 200 micrograms.kg-1.min-1 infusions of propofol, respectively. In the three additional conscious participants, intraarterial infusion of SNP and nitroglycerin (TNG) after the stellate blockade resulted in a further decrease of FVR and a further increase of FVC. CONCLUSIONS: In contrast to SNP infusions, propofol infusions into the brachial artery of conscious persons caused no significant vascular responses, despite the presence of therapeutic plasma concentrations of propofol within the forearm. The effects of propofol anesthesia on FVR and FVC are similar to the effects of sympathetic denervation by stellate ganglion blockade. Thus the peripheral vascular actions of propofol appear to be due primarily to an inhibition of sympathetic vasoconstrictor nerve activity.

Adult↗

Melasma of the forearms.

Melasma of the forearms seems to be a relatively common sign which is, to our knowledge, not reported in the literature. It seems that it may be more common in older patients and especially in postmenopausal women on supplementary oestrogen. The pigmentary change is macular and may be confluent or speckled. Like facial chloasma there is a sharp line of demarcation at the margins. In some, there seems to be an element of erythema.

Adult↗