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T J O'Brien

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

At least 55 records · Page 3Linked to original sources

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↗

Terra firma-forme dermatosis.

Terra firma-forme dermatosis (TFFD) is a relatively common but usually unrecognized clinical problem. The cause is unknown. The changes usually occur on the neck in childhood as dirty brown patches that cannot be removed with soap but are easily removed with alcohol. Terra firma-forme dermatosis may be mistaken for acanthosis nigricans.

Acanthosis Nigricans↗

Hippocampal atrophy is not a major determinant of regional hypometabolism in temporal lobe epilepsy.

PURPOSE: The pathophysiologic basis for the [18F]fluorodeoxyglucose positron-emission tomography (FDG-PET) temporal lobe hypometabolism in patients with hippocampal sclerosis (HS) is uncertain. We tested the hypothesis that hippocampal atrophy, which is strongly correlated with hippocampal cell loss, is largely responsible for the regional hypometabolism in HS. METHODS: Regions of interest (ROIs) on FDG-PET scanning were determined in the medial, lateral, and posterior temporal lobe, thalamus, and basal ganglia. A right/left asymmetry index for each ROI was calculated. These results were correlated with hippocampal magnetic resonance imaging (MRI) volume ratios. RESULTS: There was no correlation between the magnitudes of the FDG-PET asymmetry index and the MRI volume ratio for the mesial or lateral temporal regions (r = -0.09, r = -0.04). When the right/left asymmetry index was compared with the right/left hippocampal volume ratio, correlations for the mesial temporal ROI (r = 0.79, p < 0.0001) and lateral temporal ROI (r = 0.57, p < 0.0005) were found. These, however, simply indicated that both tests accurately reflect the side of the epileptogenic region. The concordance of the side of relative hypometabolism of the FDG-PET with the side of the hippocampal atrophy was higher for the mesial temporal region (100%) than for the lateral (77.5%). CONCLUSIONS: The lack of correlation between the magnitudes of the ratios argues against hippocampal atrophy and cell loss having a central role in the FDG-PET temporal hypometabolism.

Adult↗

Resection of frontal encephalomalacias for intractable epilepsy: outcome and prognostic factors.

PURPOSE: Because focal encephalomalacia is an important cause of medically intractable partial epilepsy and few studies have evaluated the efficacy and the safety of resecting focal-encephalomalacias to improve seizure control, we studied a cohort of 17 consecutive patients who underwent resection of encephalomalacias in the frontal lobes as a treatment of their intractable epilepsy. METHODS: We evaluated several factors for their value in predicting postsurgical seizure control. Pre- and postsurgical magnetic resonance imaging (MRI) scans were reviewed independently by 2 blinded investigators. RESULTS: At a median of 3 years of follow-up (range 0.6-7.5 years), 12 patients (70%) were seizure-free or had only rare seizures. The presence of a focal fast frequency discharge (focal ictal beta pattern) at the beginning of seizures on scalp EEG was predictive of seizure-free outcome (p = 0.017), even among patients who had complete resection of their encephalomalacias (p = 0.016). There was no significant differences in outcome with regard to age at the time of the injury that caused encephalomalacia, interval between injury and onset of seizures, duration of presurgical seizure history, presurgical seizure frequency, age at surgery, or the completeness of encephalomalacia resection. The analysis regarding completeness of encephalomalacia resection almost reached significance, suggesting that it may also be an important predictive factor (p = 0.051). CONCLUSIONS: We conclude that surgery is a very effective treatment for intractable frontal lobe epilepsy (FLE) secondary to encephalomalacias. Patients are more likely to become seizure-free if they have a focal ictal beta discharge on their scalp EEG. Complete resection of the encephalomalacia should be attempted, since our results suggest that this may be a favorable predictive factor. Moreover, the operative strategy for our patients entailed, whenever possible, complete resection of the encephalomalacias and of the adjacent electrophysiologically abnormal tissues.

Adolescent↗

CA125 phosphorylation is associated with its secretion from the WISH human amnion cell line.

Evidence is presented suggesting that CA125 is a serine and/or threonine phosphoprotein and that its secretion from the human amnion WISH cell line is closely linked to its phosphorylation. It is also indicated that regulation of CA125 secretion requires protein(s) tyrosine phosphorylation. WISH cells treated with a tyrosine phosphatase inhibitor, vanadate/ H2O2, resulted in increased levels of CA125 secretion. Exposure of vanadate-treated cells to epidermal growth factor further enhanced this secretory activity. Immunohistochemistry of vanadate-treated cells resulted in a substantial increase in not only cytoplasmic tyrosine phosphoproteins but also in membrane-associated CA125 when stained with the PY20 anti-phosphotyrosine and M11 anti-CA125 monoclonal antibodies, respectively. M11 immunoprecipitation of CA125 from cells labelled with [32P]-orthophosphate was analyzed by SDS-PAGE and autoradiography. Immunoprecipitates from cell lysates demonstrated that a phosphoprotein of > 200 kD was isolated and immunoreacted with both the OC125 and M11 anti-CA125 monoclonal antibodies by Western blotting. CA125 immunoprecipitated from vanadate-treated cells showed a marked increase in cell-associated CA125 phosphorylation. Although CA125 could be immunoprecipitated from WISH cell media incubated with [32P]-orthophosphate in the presence or absence of vanadate as detected by Western blotting, autoradiographic analysis of the Western blots revealed no [32P]-labelled CA125 co-migrating with the 200-kD plus molecule detected by M11. When the PY20 anti-phosphotyrosine monoclonal antibody was used as the probe, no tyrosine-phosphorylated CA125 was detected in cell lysates.

Amnion↗

Efficacy of prophylactic antibiotics in arthroscopic surgery.

A prospective, randomized, double-blind study of 437 patients undergoing arthroscopic diagnostic and operative procedures found that no deep infections occurred in any patient and only one superficial infection occurred in a patient who did not receive prophylactic antibiotics. One patient had a mild allergic reaction to the antibiotic that resolved after treatment with Benadryl. These results suggest that the routine use of prophylactic antibiotics is not indicated for patients undergoing arthroscopic surgery and that the slight risk of infection is outweighed by the cost of the antibiotics and the slight risk of allergic reaction.

Adolescent↗

Complications when using the cannulated 3.5 mm screw system.

Five patients with breakage of instrumentation when using the cannulated 3.5 mm screw system for fracture fixation are reported. Four 1.25 mm guide wires were sheared off by the cannulated drill and one 3.5 mm cannulated tap sleeve fractured. This article presents potential dangers when using the cannulated 3.5 mm screw system for general fracture care.

Adolescent↗

Biochemical evidence of impaired trophoblastic invasion of decidual stroma in women destined to have preeclampsia.

OBJECTIVE: Reduced trophoblastic migration into the decidua during the first half of pregnancy is a fundamental abnormality in preeclampsia. CA 125 and insulin-like growth factor binding protein-1 are major endometrial proteins whose primary sources are decidual epithelial and stromal cells, respectively. We hypothesized that reduced trophoblastic invasion in pregnancies destined for preeclampsia would affect the maternal vascular deportation of these decidual proteins. STUDY DESIGN: CA 125 and insulin-like growth factor binding protein-1 concentrations were analyzed by radioimmunoassays of plasma from preeclamptic and matched control patients in a longitudinal, nested case-control study. RESULTS: CA 125 concentrations did not differ with respect to pregnancy outcome or trimester. Midtrimester plasma insulin-like growth factor binding protein-1 concentrations were significantly lower in women who later had preeclampsia compared with normal pregnant controls. CONCLUSION: These findings provide biochemical evidence that abnormalities of trophoblastic invasion affect the maternal vascular deportation of a decidual stromal protein. Lower circulating concentrations of insulin-like growth factor binding protein-1 in women destined to have preeclampsia were observed 12 to 26 weeks before the onset of clinical signs of this syndrome.

Adult↗