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Biomedical subjects

G Fernández

Publications and source records attributed to G Fernández.

At least 19 recordsLinked to original sources
PubMed2003

Intrasubject reproducibility of presurgical language lateralization and mapping using fMRI.

BACKGROUND: fMRI is becoming a standard tool for the presurgical lateralization and mapping of brain areas involved in language processing. However, its within-subject reproducibility has yet to be fully explored. OBJECTIVE: To evaluate within-test and test-retest reliability of language fMRI in consecutive patients undergoing evaluation for epilepsy surgery. METHODS: Thirty-four unselected patients were investigated once (within-test reliability) and 12 patients twice (test-retest reliability). The imaging series consisted of an alternating 25-second synonym judgment condition with a 25-second letter-matching condition repeated 15 times. Reproducibility of activation maps of the first and second half of session 1 or activation maps of sessions 1 and 2 was evaluated by comparing one global and three regional lateralization indexes (Broca's area, remaining prefrontal cortex, temporoparietal area) and on a voxel-by-voxel basis (intraclass correlation coefficient, percentage overlap, correlation of t-values). RESULTS: Global and regional language lateralization was achieved with high reliability within and across sessions. Reproducibility was evenly distributed across both hemispheres but not within each hemisphere. Frontal activations were more reliable than temporoparietal ones. Depending on the statistical threshold chosen, the voxel-by-voxel analysis revealed a mean overlap of activations derived from the first and second investigation of up to 48.9%. CONCLUSION: Language fMRI proved sufficiently reliable for the determination of global and regional lateralization of language representation in individual unselected patients with epilepsy.

Adolescent↗
PubMed2002

An evaluation of extubation failure predictors in mechanically ventilated infants and children.

OBJECTIVE: To assess the accuracy of traditional weaning indices in predicting extubation failure, and to compare their accuracy when indices are measured at the onset of a breathing trial (SBT) and at the end of the SBT before extubation. DESIGN: Prospective study. SETTING: Medical-surgical intensive care unit at a tertiary care hospital. PATIENTS: Four hundred eighteen consecutive infants and children who received mechanical ventilation for at least 48 h and were deemed ready to undergo a SBT by their primary physician. INTERVENTIONS: Respiratory frequency (RR), tidal volume (V(T)), maximal inspiratory pressure (P(imax)) and frequency-to-tidal volume ratio (f/V(T)) were obtained within the first 5 min of breathing through a T-piece. The primary physicians were unaware of those measurements and the decision to extubate a patient was made by them. RR, V(T), f/V(T) were remeasured before extubation by the respiratory therapists. Extubation failure was defined as needing re intubation within 48 h after extubation. The area under the receiver operating characteristic (ROC) curve was calculated for each index as a measure of the accuracy in predicting extubation outcome. MEASUREMENTS AND MAIN RESULTS: Three hundred twenty-three patients successfully underwent the SBT and were extubated, but 48 of them (14%) required re-intubation. The ROC curve for V(T), RR, P(imax) and f/V(T) measured within the first 5 min of breathing were 0.54, 0.56, 0.57 and 0.57, respectively. The ROC curve did not increase significantly when the above indices were remeasured before extubation. CONCLUSIONS: In a population which had passed SBT, the ability of the traditional weaning indices to discriminate between children successfully extubated and children re-intubated is very poor.

Adolescent↗
PubMed2002

Diagnostic delay in psychogenic nonepileptic seizures.

Delay to diagnosis was studied in 313 consecutive patients with psychogenic nonepileptic seizures (PNES). On average, patients with PNES were diagnosed 7.2 years after manifestation (SD 9.3 years). Younger age, interictal epileptiform potentials in the EEG, and anticonvulsant treatment were associated with longer delays. Other patient factors did not explain the great variability of the time to diagnosis, suggesting that physician factors contributed to delays.

Adolescent↗
PubMed2002

Evidence of brain abnormality in patients with psychogenic nonepileptic seizures.

Markers of brain abnormalities in patients with psychogenic nonepileptic seizures (PNES) were studied to explore whether physical brain disorder is associated with an increased risk of PNES. Evidence of epileptiform EEG changes, MRI abnormalities, and neuropsychological (NPS) deficits was obtained from the records of 329 consecutive patients in whom the diagnosis of PNES was established at our center between 1991 and 2001. Two hundred six patients had PNES alone, and 123 PNES and epilepsy (PNES+E). In the PNES-only group, at least one marker of brain disorder was detected in 22.3% of patients (epileptiform potentials in 8.7%, MRI changes in 9.7%, NPS deficits in 9.7%). The actual prevalence of abnormalities is likely to be higher because 54.9% of the patients with only psychogenic seizures did not undergo MRI or neuropsychological testing. Evidence of brain abnormality was found more frequently in the PNES+E group (epileptiform potentials in 70.7%, MRI changes in 60.2%, NPS deficits in 52.8%). Although markers of brain abnormality were detected much less commonly in the PNES than in the PNES+E group, they were still found in a substantial proportion of patients with PNES alone. This suggests that physical brain disease plays a role in the development of PNES. Markers of physical abnormality were not more common in the right hemisphere.

Journal Article↗
PubMed2002

Interleukin-1beta induces in vivo tolerance to lipopolysaccharide in mice.

Endotoxin or lipopolysaccharide (LPS) tolerance may be partially due to the secretion of potent anti-inflammatory cytokines following severe Gram-negative infections, or by low doses of LPS. In this work, we describe the effects of interleukin-1 (IL-1) and tumour necrosis factor alpha (TNF-), two early cytokines secreted after LPS exposure, in the induction of LPS tolerance. Our results demonstrate that mice treated with three daily doses of 100 ng of IL-1 were tolerant to LPS-induced shock. However, TNF- was unable to induce an LPS refractory state. Given the fact that 100 ng of IL-1 increase the plasma levels of glucocorticoids, we evaluated whether a daily injection of dexamethasone (DEX) alone was able to reproduce the LPS-like tolerant state. However, no signs of LPS refractoriness were detected, except when DEX was administered concomitantly with a dose of IL-1 that does not induce corticosterone secretion (12 ng/mouse). This dose was found to induce in vitro up-regulation of the glucocorticoid receptors (GcR) of peritoneal macrophages following 24 h of treatment. In addition, we demonstrate that IL-1 is capable of inducing the down-regulation of Toll-like receptor 4 (TLR4), a crucial molecule in the signal transduction of LPS. Taken together, our results indicate that IL-1 can generate tolerance to LPS in vivo, and suggest that the regulation of mechanisms of the down-regulation of TLR4, as well as those involved in the expression of GcR and/or in the secretion of glucocorticoids, would be crucial for these effects.

Animals↗
PubMed2002

Standard magnetic resonance imaging is inadequate for patients with refractory focal epilepsy.

OBJECTIVES: Patients with intractable epilepsy may benefit from epilepsy surgery especially if they have a radiologically demonstrable cerebral lesion. Dedicated magnetic resonance imaging (MRI) protocols as performed at epilepsy surgery centres can detect epileptogenic abnormalities with great sensitivity and specificity. However, many patients with epilepsy are investigated with standard MRI sequences by radiologist outside epilepsy centres ("non-experts"). This study was undertaken to compare standard MRI and epilepsy specific MRI findings in patients with focal epilepsy. METHODS: Comparison of results of standard MRI reported by "non-expert" radiologists, standard MRI evaluated by epilepsy "expert" radiologists, and epilepsy specific MRI read by "expert" radiologists in 123 consecutive patients undergoing epilepsy surgery evaluation between 1996 and 1999. Validation of radiological findings by correlation with postoperative histological examination. RESULTS: Sensitivity of "non-expert" reports of standard MRI reports for focal lesions was 39%, of "expert" reports of standard MRI 50%, and of epilepsy dedicated MRI 91%. Dedicated MRI showed focal lesions in 85% of patients with "non-lesional" standard MRI. The technical quality of standard MRI improved during the study period, but "non-expert" reporting did not. In particular, hippocampal sclerosis was missed in 86% of cases. Neuropathological diagnoses (n=90) were predicted correctly in 22% of "non-expert" standard MRI reports but by 89% of dedicated MRI reports. CONCLUSIONS: Standard MRI failed to detect 57% of focal epileptogenic lesions. Patients without MRI lesion are less likely to be considered candidates for epilepsy surgery. Patients with refractory epilepsy should be referred to an MRI unit with epileptological experience at an early point.

Brain↗
PubMed2001

Integrated brain activity in medial temporal and prefrontal areas predicts subsequent memory performance: human declarative memory formation at the system level.

After an era in which lesion studies have identified the declarative memory system and its essential anatomical structures, functional imaging and event-related potential studies have begun to delineate the neural underpinnings of declarative memory formation at the system level. By memory formation, we refer to those mnemonic processes present during encoding that transform perceptual representations into enduring memories. Recent studies have revealed that distinct regions in medial temporal and prefrontal areas exhibit more neural activity during successful than unsuccessful memory formation. We attempt to identify the nature of the processes underlying these subsequent memory effects. Reviewed data suggest specific mnemonic operations in the medial temporal lobe that may be integrated with semantic/perceptual operations and subserving operations in the prefrontal cortex. The formation of relational and non-relational memories may be supported by distinct subregions within these two brain regions. While the medial temporal lobe may have a serial organizational structure, with a processing hierarchy, interactions between medial temporal and prefrontal areas seem to occur in a parallel and bi-directional fashion. Interacting with this system, emotionally arousing events enhance neural activity in the amygdala, which in turn may modulate processing in other brain regions responsible for declarative memory formation.

Animals↗
PubMed2001

Tolerance to lipopolysaccharide (LPS) regulates the endotoxin effects on Shiga toxin-2 lethality.

It has been suggested that Shiga toxin (Stx) is necessary but not sufficient for hemolytic uremic syndrome (HUS) development, and pro-inflammatory stimuli such as lipopolysaccharide (LPS) from Gram negative bacteria are needed. Taking into account that LPS is present in the natural infection during HUS development, detoxification or regulation of LPS activity could be crucial to define the course of the disease. The objective of the present study was to investigate whether tolerance to LPS and/or antibodies to LPS, are able to modify the LPS-induced modulation of Stx type-2 (Stx2) lethality in a mouse model. Our results demonstrate that the high levels of IgG anti-LPS antibodies in immunized mice did not modify the dual effects of LPS (enhancement or protection) on Stx2 action. This could be attributed to the fact that antibodies do not recognize the active portion of LPS molecule (lipid A). However, the enhancement of Stx2 toxicity exerted by LPS was inhibited in tolerant mice. This effect could be ascribed to the inhibition of LPS-induced TNF-alpha and IL-1beta secretion in tolerant animals, two cytokines known to be involved in the overexpression of Stx receptors. The phenomenon of LPS-induced protection on Stx2 toxicity was also inhibited in tolerant animals, although the mechanism involved in this effect is not clear. This is the first description which shows the influence of endotoxin tolerance on the evolution of experimental HUS. However, like in Gram negative infections, further knowledge on tolerance mechanism is necessary in order to achieve a comprehensive view of this phenomenon.

Animals↗
PubMed2001

Inferior temporal stream for word processing with integrated mnemonic function.

The participation of the inferior temporal cortex in visual word perception and recognition raises several questions: Is there a directed processing stream proceeding anteriorly by continuous cortical processing? How fast are words processed within such an inferior temporal stream? Does this stream support implicit or explicit memory? To answer these questions, we analyzed the spatio-temporal relationship of event-related potentials, recorded directly from the inferior temporal cortex in epilepsy patients performing a continuous visual word recognition paradigm. Event-related potentials elicited an inferior temporal positivity in a strip along the left collateral sulcus. This potential exhibited a linear (r = 0.74) peak latency progression from posterior to anterior inferior temporal regions (approximately 15 cm/sec), indicating a directed, intracortical processing stream. Peak amplitudes and latencies showed reliable old/new effects with smaller amplitudes and shorter latencies for old as opposed to new words. Although the amplitude-old/new-effect occurred for all repeated words (e.g., implicit memory), the latency-old/new-effect occurred for correctly recognized old words only (e.g., explicit recognition). These results seem to dissociate two distinct mnemonic processes. The graded decrease of mean ITP peak amplitudes and latencies, however, does not allow us to exclude a single trace model as assumed for explicit recognition memory based on familiarity (Mandler [1980]: Psychol Rev 87:252-271). Regardless whether there is a dissociation between implicit and explicit memory in inferior temporal cortex or not, our findings are in accordance with an integrated inferior temporal processing stream for words that performs continuously semantic and mnemonic operations supporting both implicit and explicit memory.

Adolescent↗
PubMed2001

Language mapping in less than 15 minutes: real-time functional MRI during routine clinical investigation.

Neurosurgical interventions often require the presurgical determination of language dominance or mapping of language areas. Results obtained by fMRI are closely correlated with invasive procedures such as electrical stimulation mapping or the intracarotid amobarbital test. However, language fMRI is not used routinely, because postprocessing is time-consuming. We utilized a real-time analysis software installed directly on the MR console computer and SPM99 as reference postprocessing software. We assessed the reliability of the immediate determination of language dominance based on individual activation maps by comparing the results of the visual analysis of images derived from conventional postprocessing with those produced by the real-time tool. All images were rated independently by six senior neurologists blinded to other data. We validated the robustness of the real-time method statistically by comparing global and regional lateralization indices derived from real-time and postprocessing analysis. Functional MRI was performed with a standard 1.5-T whole-body scanner. Brain activity was contrasted between an alternating semantic judgment and letter matching task. Twelve right-handed, healthy control subjects and 12 consecutive patients with drug-resistant, localization-related epilepsy were investigated. The semantic condition induced almost invariably left hemispheric activations in Broca's area, the premotor cortex, the dorsolateral prefrontal cortex, and the temporoparietal region. Although real-time analysis reduced noise less effectively than SPM99, visual ratings and lateralization indices produced highly concordant results with both methods. In conclusion, real-time fMRI, as used here, allowed reliable language lateralization and mapping in less than 15 min during routine clinical MRI investigation with no need for postprocessing.

Adult↗
PubMed2001

Human memory formation is accompanied by rhinal-hippocampal coupling and decoupling.

In humans, distinct processes within the hippocampus and rhinal cortex support declarative memory formation. But do these medial temporal lobe (MTL) substructures directly cooperate in encoding new memories? Phase synchronization of gamma-band electroencephalogram (EEG) oscillations (around 40 Hz) is a general mechanism of transiently connecting neural assemblies. We recorded depth-EEG from within the MTL of epilepsy patients performing a memorization task. Successful as opposed to unsuccessful memory formation was accompanied by an initial elevation of rhinal-hippocampal gamma synchronization followed by a later desynchronization, suggesting that effective declarative memory formation is accompanied by a direct and temporarily limited cooperation between both MTL substructures.

Action Potentials↗
PubMed2001

Influence of endothelium in dose-dependent inhibition and potentiation by isoniazid of isosorbide dinitrate relaxation of rat aorta.

The influence of in vivo administration of isoniazid on the relaxant effect of isosorbide dinitrate was determined by pretreating rats with various doses of isoniazid and obtaining concentration-response curves to isosorbide dinitrate in aortic rings from these animals. In rings with endothelium, isoniazid potentiated responses to isosorbide dinitrate at doses of 10, 30, and 100 mg/kg; 3 and 300 mg/kg were without effect. In endothelium-denuded preparations, potentiation was present only at 10 mg/kg; 3 and 300 mg/kg inhibited relaxation. Other experiments indicated that isoniazid potentiation was prevented by pyridoxine, was reproduced with theophylline, and did not occur with 3-morpholinosydnonimine or papaverine. These results were deemed compatible with the hypothesis that isoniazid inhibits transsulfuration of homocysteine and causes its accumulation in vascular smooth muscle and endothelial cells, where it functions as a thiol intermediate and leads to enhanced bioactivation of isosorbide dinitrate. Potentiation appeared to occur only with moderate increases of homocysteine.

Animals↗
PubMed2000

Epileptic vertigo: evidence for vestibular representation in human frontal cortex.

The authors report a 5-year-old boy with episodes of epileptic rotational clockwise vertigo without nystagmus. Video-EEG monitoring showed a left frontocentral onset of epileptic discharges accompanied by complaints of vertigo. MRI showed a small low-grade astrocytoma in the left frontal middle gyrus. After lesionectomy, vertiginous seizures ceased. The patient's vertigo seems to be induced by epileptic discharges in a vestibular representation area within the frontal cortex.

Child, Preschool↗
PubMed2000

Study of Ligand Substitution Reactions at Pentacyanoferrates(II) in Aqueous Salt and Micellar Solutions.

The ligand substitution reactions Fe(CN)(5)(4-(t)bupy)(3-) + 4-CNpy and Fe(CN)(5)(4-(t)bupy)(3-) + pzCO(2)(-) (4-(t)Bupy = 4-tert-butylpyridine; 4-CNpy = 4-cyanopyridine; pzCO(2)(-) = pyrazinecarboxylate) were studied in several aqueous salt and micellar solutions. Kinetic data in aqueous solutions showed that the two processes follow a dissociative mechanism, D, and the dependence of the first-order rate constants on [salt] on electrolyte aqueous solutions allow the estimation of the activation volumes corresponding to both reactions. Under true first-order conditions no kinetic micellar effects were found in anionic (SDS) and nonionic (Triton X-100) aqueous micellar solutions. In cationic micellar solutions (CTAB, CTAC, and TTAB) small kinetic micellar effects were found. These were related to the different ionic concentrations and the different polarity and structure of the Stern layer surrounding the cationic micellar aggregates, where the reactions take place, with respect to pure water. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

[Orthostatic hypotension in the aged and its association with antihypertensive treatment].

BACKGROUND: To assess the prevalence of orthostatic hypotension (OH) in an elderly population and to evaluate the influence of hypertension control and of the type of antihypertensive drug used. METHODS: 2,700 elderly patients (> 65 years) from the EPICARDIAN study were included. Blood pressure (BP) was measured twice with the patient seated and once again 1 to 3 minutes afterwards with the patient standing. Hypertension is defined as BP > or = 140/90 mmHg or if the patient received antihypertensive treatment. Orthostatic hypotension was defined as a fall of SBP > or = 20 mmHg and/or DBP > or = 10 mmHg 1 to 3 minutes after the postural change. RESULTS: 71.6% of the patients were classified as hypertensive and 57.1% were receiving pharmacological treatment. The overall prevalence of OH was 6.8% among hypertensive patients, 8.1% and 3.4% in normotensives patients (p < 0.05). No significant difference was found in the prevalence of OH between those receiving (7.7%) or not (8.6%) antihypertensive medication. No association was found either between the prevalence of OH and the type or number of antihypertensive drugs used. 17.6% of the patients reached hypertension optimal control (SBP < 140 and DBP < 90 mmHg), the prevalence of OH in these patients was 5.3%, among the uncontrolled the prevalence was 8.9% (p < 0.05). The adjusted OR was 1.91 (1.1-3.3) for the prevalence of OH in the uncontrolled patients versus the controlled. CONCLUSIONS: The prevalence of OH in the elderly is not very high, being greater among hypertensive than normotensive patients. No association was found between the prevalence of OH and the number of drugs received. Reaching hypertension control reduces the prevalence of OH.

Adrenergic alpha-Antagonists↗
PubMed2000

Single trial analysis of event related potentials: non-linear de-noising with wavelets.

We present and apply a method for single trial analysis of event related potentials (ERPs) that combines techniques from non-linear time series analysis with the wavelet transform. For this method, convincing results have already been achieved for simulated data as well as for intracranially recorded ERPs (Physica D 140 (2000) 257). However, ERPs are affected by a variety of external and internal experimental parameters, which makes the appropriate configuration of single trial analysis difficult. Thus, several pitfalls may occur in realistic applications. In this paper, we applied the method of non-linear de-noising with wavelets to both intra- and extracranially recorded ERPs, and show examples of how and where this single trial analysis can be used to obtain additional information on dynamic neural processes.

Brain↗
PubMed2000

Synthesis and herbicidal activity of N-oxide derivatives.

As part of an ongoing program on the chemistry and biological activity of N-oxide-containing molecules, a number of novel 1,2, 5-oxadiazole N-oxide, benzo[1,2-c]1,2,5-oxadiazole N-oxide, and quinoxaline N,N'-dioxide derivatives were synthesized and evaluated for their herbicidal activity. Many of these compounds exhibited moderate to good herbicidal pre-emergence activity against Triticum aestivum. Dose-response studies were done on the more representative compounds (12, 20, and 26). The most active compound, butylcarbamoylbenzo[1,2-c]1,2,5-oxadiazole N-oxide, 26, displayed herbicidal activity at concentrations as low as 24 g/ha.

Dose-Response Relationship, Drug↗