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PubMed2002

Detection and significance of focal, interictal, slow-wave activity visualized by magnetoencephalography for localization of a primary epileptogenic region.

OBJECT: Magnetoencephalography (MEG) is a novel noninvasive diagnostic tool used to determine preoperatively the location of the epileptogenic zone in patients with epilepsy. The presence of focal slowing of activity recorded by electroencephalography (EEG) is an additional indicator of an underlying pathological condition in cases of intractable mesial temporal lobe epilepsy (MTLE). In the present study the authors examined the significance of focal, slow-wave and interictal spike activity detected using MEG in 29 patients who suffered from MTLE that was not associated with structural brain lesions. METHODS: All patients underwent resective surgery after MEG and EEG monitoring. Equivalent single-dipole modeling was applied to focal low-frequency magnetic activity (LFMA) and interictal paroxysmal activity. Lateralized LFMA was defined as trains of rhythmic activity over the temporal area, with frequencies lower than 7 Hz, which were easily distinguished from background activity. Lateralized LFMA was found in 17 patients (58.6%); it always occurred on the side ipsilateral to the side of resection and displayed a maximum amplitude over the temporal area. Dipolar sources of magnetic flux computed during slow-wave trains were found in the majority of cases in the posterior superior temporal region and, occasionally, in mesial temporal structures that were subsequently resected. With respect to lateralization there was never disagreement between LFMA and MEG interictal spike sources. Thus, in patients with MTLE that is not associated with a mass lesion LFMA is topographically related to the epileptogenic area and, therefore, has value for reliable determination of the side and, possibly, the location of this area. CONCLUSIONS: Although focal slowing of EEG background activity is generally considered to be a nonspecific sign of functional disturbance, interictal LFMA in patients with MTLE should be conceptualized as a distinct electrographic phenomenon that is directly related to the epileptogenic abnormality. Analyzing the interictal MEG distribution of LFMA and sharp activity improves the diagnostic utility of MEG in patients with suspected TLE who are undergoing surgical evaluation.

Adolescent↗
PubMed1989

[The genetic architecture of emotionality in rats using Mendelian cross analysis].

Two inbred strains of Tsukuba Emotionality Rat (THE and TLE) and four hybrids derived from them were observed for ambulatory response in a novel environment as a measure of emotionality. The Runway Test (modified "timidity test") was run for successive three days. Mean transformed (square root) scores of ambulation for generation were subjected to Mendelian cross analysis. Total ambulation scores showed significant additive genetic effect, maternal effect and environmental effect. Directional dominance toward low level of response was present only for males. Daily ambulation scores showed changes in the genetic architecture over three days and the difference between males and females. For females, directional dominance occurred toward low level on Day 1, toward high level on Day 3, but no directional dominance was observed on Day 2. Males' directional dominance toward low level, on the other hand, declined with days. These findings on the genetic architecture of emotionality were discussed with reference to evolutionary adaptation.

Affective Symptoms↗
PubMed2004

Lupus tumidus: a variant of cutaneous lupus erythematosus.

Lupus tumidus is a rare sub-type of chronic cutaneous lupus erythematosus characterized by dermal plaques in which excessive mucin accumulates early in disease process. We report a middle aged women having succulent, edematous and persistent plaque over her face for five years that was not responding to various empirical treatments offered to her. Finally, on clinico-pathological basis, it was diagnosed as a case of tumid lupus erythematosus (TLE) and she responded satisfactorily to the treatment regimen including oral steroids, chloroquine and application of sun screen.

Adult↗
PubMed2000

[Recent advances of MEG].

The number of MEG(Magnetoencephalography) channels was rapidly increased from 14 to 306 in the past decade and the detection coil array with the whole-scalp coverage has become fairly common these days. Besides the advances of biomagnetometer itself, there are several important technical advances around MEG measurements. An active shielding technique can reduce the contamination of environmental magnetic noise in the frequency range below 10 Hz. Applying SSP(signal space projection) technique, which is known as a strong tool to resolve multiple current sources, can be another choice to reduce this contamination in the full frequency range. Recently the realistic head model reconstructed from MRI data was accomplished and we can apply this model, instead of the conventional spherical model, to the patients with TLE(temporal lobe epilepsy) expecting further accurate dipole estimation. These advances are quite important for the data acquisition with high S/N(signal to noise) ratio and the reliable three-dimensional localization of current sources in the brain.

Humans↗
PubMedDate not supplied

[Neurotic symptoms frequency].

The analysis of symptom checklists completed by 3196 patients before treatment--1970 females and 1226 males starting the therapy due to neurotic disorders--revealed that 12 symptoms occur im more than 80% of patients; 9 symptoms in 70-80%, 18 dysfunctions in 70-60% and 17 other dysfunctions in 60-50% of examined population. This means that a large number of symptoms including tension, mood depression an anxiety as well as difficulties in concentration, lack of self-confidence, sense of tiredness, loss of energy, persistent thoughts and images, constant fear, absent-mindedness, motor tensions, pessimism, thought flood, the sense of difficulty in thinking and tachycardia occur in almost all patients suffering from neurotic disorders, mo matter what these disorders are. Tle largest group consisted of patients with the diagnosis of anxiety disorders like phobias and the like (ca. 25%). Results of the study suggest the necessity of verification of the present views on the picture of dysfunctions combining into neurotic disorders. A similar occurrence rate of ca. 30% of the 95 analysed dysfunctions in the subgroups of females and males as well as a higher occurrence rate of 10% of the dysfunctions in the male group also make it necessary to verify the prevalent convictions about the sex-dependent differences in the picture and course of neurotic disorders.

Adult↗
PubMed2000

PET: cholinergic neuroreceptor mapping.

The application of PET with NMPB has provided useful information toward understanding the pathogenesis of mesial TLE, and can be used as a tool in the presurgical evaluation. Many other patient populations have yet to be studied with cholinergic neuroreceptor imaging. The use of NAChR radioligands in the study of ADNFLE may be especially rewarding.

Benzilates↗
PubMed2001

Clinical fluoroscopic fiducial-based registration of the vertebral body in spinal neuronavigation.

We present a system involving a computer-instrumented fluoroscope for the purpose of 3D navigation and guidance using pre-operative diagnostic scans as a reference. The goal of the project is to devise a computer-assisted tool that will improve the accuracy, reduce risk, minimize the invasiveness, and shorten the time it takes to perform a variety of neurosurgical and orthopedic procedures of the spine. For this purpose we propose an apparatus that will track surgical tools and localize them with respect to the patient's 3D anatomy and pre-operative 3D diagnostic scans using intraoperative fluoroscopy for in situ registration and embedded fiducials. Preliminary studies have found a fiducial registration error (FRE) of 1.41 mm and a Target Localization Error (TLE) of 0.48 mm. The resulting system leverages equipment already commonly available in the operating room (OR), providing an important new functionality that is free of many current limitations, while keeping costs contained.

Artificial Intelligence↗
PubMed2002

Preclinical evaluation of a new, stabilized neurotensin(8--13) pseudopeptide radiolabeled with (99m)tc.

UNLABELLED: The rapid degradation of neurotensin (NT) limits its clinical use in cancer imaging and therapy. Thus, a new NT(8--13) pseudopeptide, NT-VIII, was synthesized. Some changes were introduced in the sequence of NT(8--13) to stabilize the molecule against enzymatic degradation: Arg(8) was N-methylated, and Lys and Tle replaced Arg(9) and Ile(12), respectively. Finally, (NalphaHis)Ac was coupled to the N-terminus for (99m)Tc(CO)(3) labeling. This peptide was characterized both in vitro and in vivo. METHODS: The new analog was labeled with (99m)Tc(CO)(3). Its metabolic stability was analyzed both in human plasma and in HT-29 cells. Binding properties, receptor downregulation, and internalization were tested with HT-29 cells. Biodistribution was evaluated in nude mice with HT-29 xenografts. RESULTS: (99m)Tc(CO)(3)NT-VIII showed a high stability in plasma, where most of the peptide remained intact after 24 h of incubation at 37 degreesC. However, the degradation in HT-29 cells was more rapid (46% of intact (99m)Tc(CO)(3)NT-VIII after 24 h at 37 degreesC). Binding to NT1 receptors (NTR1) was saturable and specific. Scatchard analysis showed a high affinity for (99m)Tc(CO)(3)NT-VIII, with a dissociation constant similar to (125)I-NT (1.8 vs. 1.6 nmol/L). After interacting with NTR1, (99m)Tc(CO)(3)NT-VIII was rapidly internalized, with more than 90% internalized after 30 min. It also distributed and cleared rapidly in nude mice bearing HT-29 xenografts. The highest rates of accumulation were found in kidney and tumor at all time points tested. Tumor uptake was highly specific because it could be blocked by coinjection with a high dose of (NalphaHis)Ac-NT(8--13). Tumors were clearly visualized in scintigraphy images. CONCLUSION: The changes that were introduced stabilized the molecule against enzymatic degradation without affecting binding properties. Moreover, the increase in stability enhanced tumor uptake, making this derivative a promising candidate for clinical use.

Adenocarcinoma↗
PubMed2001

Neuropsychological changes after surgical treatment for temporal lobe epilepsy.

PURPOSE: The effect of unilateral temporal lobectomy on seizure frequency is well recognized, but little is known about the neuropsychological changes that occur after surgical treatment. We assessed neuropsychological status in 26 patients with an average age of 35 years before and after unilateral temporal lobectomy for medically intractable TLE. METHODS: Neuropsychological examination to assess cognitive function, memory, attention, visuospatial analysis, language, and emotional functions was performed preoperatively and at 1 month and 1 year after the surgery. RESULTS: At both 1 month and 1 year after the surgery, the patients had improved scores, compared with the preoperative scores, on the Wechsler Adult Intelligence Scale-Revised (WAIS-R: verbal IQ, performance IQ, and full-scale IQ), Wechsler Memory Scale-Revised (WMS-R: verbal, general, and delayed paired associates memory), and Raven Colored Progressive Matrices. In the Minnesota Multiphasic Personality Inventory (MMPI), significant decreases were observed at 1 year after the surgery in the scores for infrequency, hypochondriasis, psychasthenia, and schizophrenia. Patients in whom the seizures had been relieved postoperatively also had improved scores on the WAIS-R, WMS-R, and Raven Colored Progressive Matrices. CONCLUSIONS: These data suggest that neuropsychological improvement postoperatively is influenced by the reduction in the frequency of seizures after surgery.

Adult↗
PubMed2002

[Effect of flumazenil on the regional cerebral blood flow measured by [15O]-butanol PET scan and transcranial Doppler ultrasonography].

The authors investigated the role of the cBZD/GABA-A receptor-complex in the regulation of rCBF by simultaneously applying [15O]-butanol-PET and TCD in therapy-resistant TLE patients. It is known that the density of the cBZD/GABA-A-receptors is reduced in the epileptogenic area of the temporal lobe, but there are no data available about the impact of this phenomenon on rCBF. FMZ is a well-known BZD-receptor antagonist which can be used to inhibit the effect mediated by cBZD/GABA-A-receptors, offering a way to study the contribution of these receptors in the determination of rCBF. The authors examined the possible correlation between the rCBF values obtained by PET and the blood flow speed readings measured by TCD in MCAs. The results show that FMZ does not cause any change in rCBF on the side of the epileptogenic focus but it significantly raises rCBF (p < 0.001) in the intact brain tissue on the other side. The TCD measurements showed no significant differences between the blood flow in the MCAs supplying the affected and the contralateral lobe.

Adult↗
PubMed2001

[A case with left mesial temporal lobe epilepsy characterized by abnormal massive salivation].

A 26-year-old woman was admitted because of a 12-year history of intractable epileptic seizures. Every seizure began with an upper abdominal discomfort, and often followed by massive salivation. Whenever the epileptic salivation happened, the patient lost consciousness, and sometimes she developed generalized convulsions. In terictal sphenoidal EEG recordings revealed abnormal discharges in the left mesial temporal region. MRI demonstrated left hippocampal atrophy. Since her seizures were medically intractable, left temporal lobectomy was performed. Neuropathologic examination revealed hippocampal sclerosis. After the operation, she became completely seizure-free with no episode of massive salivation. From the literature, epileptic salivation can originates from the rolandic area; fronto-orbital cortex & cingulate gyrus; insula & operculum; and mesial temporal structures. The abnormal massive salivation in our patient might be attributable to the activation of frontal limbic system triggered by hippocampal abnormal firing during the ictal period of TLE.

Adult↗
PubMed2002

Effect of electroporation and iontophoresis on skin permeation of Defibrase--a purified thrombin-like enzyme from the venom of Agkistrodon halys ussuriensis Emelianov.

The purpose of this study was to investigate electroporation and iontophoresis as a means for in vitro delivery of Defibrase--a thrombin-like enzyme (TLE) from Agkistrodon halys ussuriensis Emelianov snake venom--through human epidermis membrane (HEM). Electroporation was carried out using an exponential decay pulse generator (BioR-ad Genepulser, USA) for a period of 0.5 h, followed by a period of 5.5 h passive diffusion or iontophoresis. The results indicated that the combined use of electroporation and anodal iontophoresis in pH 6.4 permeation medium could effectively enhance the skin permeation of Defibrase, whose apparent permeability coefficient was 1.6 +/- 0.8 x 10(-4) cm.h-1. The delivery of Defibrase by the combined use of electroporation and anodal iontophoresis was more effective than by electroporation alone (P < 0.01) or by the combined use of electroporation and cathodal iontophoresis (P < 0.01). Moreover, when the pH of the permeation medium was raised from 6.4 to 7.4 the permeation of Defibrase caused by a combined use of electroporation and anodal iontophoresis showed a tendency to increase. These results implied that electroosmotic flow effect might be important for the iontophoretic (following electroporation) skin permeation of Defibrase.

Batroxobin↗
PubMed2002

[Interictal brain SPECT in patients with medically refractory temporal lobe epilepsy].

The objective of this study was to evaluate the utility of interictal brain SPECT in localizing the epileptogenic focus in a population of patients of Epilepsy Clinic of Hospital Universitário Clementino Fraga Filho (HUCFF/UFRJ), with medically refractory temporal lobe epilepsy (TLE) and normal computed tomography (CT) scans, studying the correlation between SPECT, electroencephalogram (EEG) and, in 11 cases, brain magnetic resonance imaging (MRI), and to compare the results to the other six literature series. Twelve (52.2%) patients presented abnormal SPECT. Among these, five (41.6% of abnormal SPECTs) presented unilateral SPECT changes at the same side of EEG (hypoperfusion in four and hyperperfusion in one), three (25% of abnormal SPECTs) presented bilateral hypoperfusion and bilateral EEG changes too, and four (33.3%) presented unilateral hypoperfusion and bilateral EEG changes. The statistical analysis was based on fuzzy logic. The correlation index among SPECT X EEG, SPECT X MRI and SPECT X EEG X MRI were highly significant, with significance levels at 0.01, p < 0.0005 and trust interval at 99% in all correlations. The correlation studies between the series presented similar results.

Adolescent↗
PubMed2002

The role of the temporal pole in auditory processing.

Experiments in animals have shown that the temporal pole and the amygdala are involved in auditory processing. Comparable data are scarce in humans. It is only known that after temporal lobectomy, hearing may be impaired and dichotic listening scores reduced on the ear contralateral to the operated temporal lobe. Middle-latency auditory evoked potentials (MLAEPs) and late auditory evoked potentials (LAEPs) have been recorded in 14 patients before and after temporal lobectomy for the treatment of drug-resistant temporal lobe epilepsy. The Na and Pa components of MLAEPs were significantly delayed and the Pa component amplitude reduced before and after surgery as compared to a group of 21 healthy subjects. Data in pre- and postoperative period were not statistically different. N100 and P200 component of LAEPs were similarly altered. It is concluded that in humans the amygdala and probably the temporal pole may be involved in the process of auditory activation-inhibition. The possible role of auditory processing impairment in cognitive deficits in TLE patients can also be questioned.

Adult↗
PubMed2003

Runx2/Cbfa1 functions: diverse regulation of gene transcription by chromatin remodeling and co-regulatory protein interactions.

Development of the osteoblast phenotype requires transcriptional mechanisms that regulate induction of a program of temporally expressed genes. Key components of gene activation, repression, and responsiveness to physiologic mediators require remodeling of the chromatin structure of a gene that renders promoter elements competent for the assembly of macromolecular transcriptional complexes. Here we review evidence that the Runx transcription factors support tissue-specific gene expression and bone formation by contributing to promoter structure, chromatin remodeling, and the integration of independent signaling pathways. In addition, we discuss the role of Runx2 in both activation and negative regulation of gene promoters (osteocalcin, bone sialoprotein, and Runx2/Cbfa1) in relation to the interaction of Runx with co-regulatory proteins in distinct subnuclear foci. The modifications in chromatin organization and transcription of the osteocalcin gene that are influenced by the activities of Runx2/Cbfa1 mediated by interacting proteins (YAP, TLE, SMAD, C/EBP) are emphasized. These functional properties of Runx2 provide novel insights into the requirements for multiple levels of transcriptional control within the context of nuclear architecture to support the convergence of regulatory signals that control tissue-specific gene expression.

Animals↗
PubMed2003

Temporal and spatial parameters of skeletal gene expression: targeting RUNX factors and their coregulatory proteins to subnuclear domains.

Key components of the basal transcription machinery and several tissue-specific transcription factor complexes are functionally compartmentalized as specialized subnuclear domains. We have identified a unique 31-38 amino acid targeting signal (NMTS) that directs the Runx (Cbfa/AML) transcription factors to distinct nuclear matrix-(NM) associated sites within the nucleus that support gene expression. Our determination of the NMTS crystal structure, yeast 2 hybrid screens to identify NM interacting proteins, and in situ colocalization studies with Runx interacting factors (YAP, Smad, TLE) suggest that localization of Runx transcription factors at intranuclear sites facilitates the assembly and activity of regulatory complexes that mediate activation and suppression of target genes. Mice homozygous for the deletion of the intranuclear Runx2 targeting signal in a homologous recombination (Runx2 deltaC) do not form bone due to maturational arrest of osteoblasts, demonstrating the importance of fidelity of subnuclear localization for tissue-differentiating activity. These results provide evidence that Runx2 subnuclear targeting and the associated regulatory functions are essential for a spatiotemporal placement that facilitates activation of Runx-dependent genes involved in tissue differentiation during embryonic development.

Animals↗
PubMedDate not supplied

Emerging importance of Pneumocystis carinii among indian immunosuppressed patients.

Pneumocystis carinii is known to cause both significant morbidity and mortality in immunosuppressed individuals. In a six and a half year period starting with 1992, a total of 204 samples including bronchial aspirates, induced sputum and suction catheter tips were examined for P. carinii by direct microscopic examination of Giemsa's and toluidine 'O' stained smears. At a later stage of the investigation, immunofluorescent staining using monoclonal reagent (Meriflour, USA) was also used for examination of the specimens. In all 24 (11.8%) of 204 samples were positive for P. carinii. In addition, Pneumocystis carinii pneumonia (PCP) was diagnosed in five (33%) of 15 patients of acquired immunodeficiency syndrome (AIDS) with opportunistic infections. All these 15 patients had CD4 T cell counts of less than 500 T lymphocyte equivalent (TLE) /ml as measured by a Trax ELISA assay. Laboratories in India have to be better equipped for an early and correct diagnosis of PCP that is bound to rise with the increase in the number and variety of immunosuppressed patients.

Enzyme-Linked Immunosorbent Assay↗
PubMed1992

[Efficacy and limitations of antiepileptic drug monotherapy for temporal lobe epilepsy].

To evaluate the efficacy of antiepileptic drug (AED) monotherapy, we studied 147 patients with temporal lobe epilepsy (TLE) aged 15 or older who had been undergoing treatment at our hospital for at least five consecutive years. We divided the treatment time into Period I which included one year beginning six months after the initial diagnosis, and Period II which was the two years from January, 1987 to December, 1989. The efficacy of therapy was evaluated for the two periods based on the following standards: effective, if seizures had been controlled, and ineffective, if at least one seizure had occurred during each period. Patients in whom monotherapy was effective increased by a factor of 1.7 over the period of observation, from 38 cases (28%) in Period I to 65 cases (44%) in Period II. The total number of effectively treated cases (including those on polytherapy) also rose from 58 cases (40%) in Period I to 79 cases (54%) in Period II. The average number of AEDs used was reduced from 3.0 +/- 1.3 at the time of initial diagnosis to 1.8 +/- 0.8 in Period I and 1.6 +/- 0.8 in Period II. When compared with the 68 ineffectively treated cases, significant background factors for the 65 effectively treated cases on monotherapy included: higher age at ictal onset, fewer histories of any previous treatment at initial diagnosis, or of encephalitis or febrile seizures, fewer psychological impairments such as cognitive degeneration or personality disorders, lower frequency of seizures, fewer histories of secondary generalization or automatism, and a higher rate of normal findings of background EEG and cerebral CT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗