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Biomedical subjects

F Velasco

Publications and source records attributed to F Velasco.

At least 55 records · Page 3Linked to original sources

Electrocortical and behavioral responses produced by acute electrical stimulation of the human centromedian thalamic nucleus.

Incremental, desynchronizing and spike-wave electrocortical responses and concomitant symptoms to acute electrical stimulation of the centromedian thalamic nucleus (CM) were studied in 12 patients with intractable complex partial and tonic-clonic generalized seizures. Low-frequency (6/s), 320-800 microA stimulation of the caudal-basal and central portions of CM elicited incremental recruiting and augmenting-like responses with a bilateral regional scalp distribution, with emphasis at the ipsilateral frontal (recruiting) and central (augmenting) regions, while ventral-basal CM stimulation elicited primary-like responses with a focal distribution at the ipsilateral parietal region. High-frequency (60/s), 320-800 microA stimulation of caudal-basal and central, but not ventral-basal CM, elicited EEG desynchronization and a slow negative shift of the EEG baseline with scalp distribution similar to that showed by recruiting- and augmenting-like responses. Neither incremental nor desynchronization EEG responses were accompanied by evident patient sensory or motor responses. Low-frequency (3/s), high-intensity (30 V = 2400 microA) combined stimulation of the right CM and left non-specific mesencephalic ascending pathways elicited a response similar to the typical absence attack with all EEG and clinical ingredients: S1, S2, P1 and W components of the individual spike-wave complex and generalized spike-wave discharges followed by sleep spindle EEG afterdischarges, accompanied by motionless stare, 3/s eye blinking, lip smacking and total failure to respond to visual stimuli in patients under a simple responding task.

Behavior↗

Temporo-spacial correlations between cortical and subcortical EEG spike-wave complexes of the Idiopathic Lennox-Gastaut syndrome.

All-night EEG recordings of the interictal 2/s spike-wave complexes (SKW) from different cortical and subcortical regions were performed in 5 patients with atypical absences of the Idiopathic Lennox-Gastaut syndrome (ILGS), in whom multicontact depth electrodes were implanted in the centromedian thalamic region as a part of a neuroaugmentive procedure for seizure control. Since during slow wave sleep III cortical spike (S2) and subcortical negative spike (NSK) consisting of simple monophasic negative potentials appeared together with a ratio of almost 1:1 and with fixed temporal relations, it was possible to determine visually the differences in peak-to-peak intervals of S2 and NSK, as well as their amplitude distribution in different cortical and subcortical structures. It was found that the peak of subcortical NSK preceded by 35 ms that of cortical S2. In addition, subcortical NSK and cortical S2 potentials attained maximal amplitude at the mesencephalic-thalamic reticular and frontal cortical regions, respectively, from which amplitude of NSK and S2 decreased with distance to other subcortical and cortical regions. These data suggest that interictal 2/s SKW of the ILGS result from ascending reticular impulses impinging upon the frontal cortical neurons.

Brain↗

C1-esterase inhibitor prevents early pulmonary dysfunction after lung transplantation in the dog.

The success of lung transplantation to a large extent depends on effective protection of the graft from ischemic injury after reperfusion. Although mechanisms have not been clarified, the pathologic findings of ischemic injury after reperfusion are similar to adult respiratory distress syndrome, a condition in which the blood coagulation contact system is activated. This study evaluates the effect of C1-esterase inhibitor (C1-INH), the main inhibitor of the blood coagulation contact system, on short-term lung function in a dog model of orthotopic lung transplantation. Twelve lung transplantations were performed after 24 h of ischemic time. Dogs were randomly assigned to receive either vehicle (Control) or C1-INH. After the lung transplantation in the control group, Pao2 decreased by 84% and both the AaPO2 and the Qs/Qt% increased (340 and 530%, respectively, p < 0.01); these parameters remained unchanged in the C1-INH group. The hypoxemia observed in control animals was associated with decreased blood coagulation contact factors, complement consumption, increased expression of adhesion glycoproteins in leukocytes, and extensive intraalveolar and interstitial neutrophil infiltration. In contrast, C1-INH administration prevented hypoxemia, the decrease in blood coagulation contact factors, the activation of the complement system, the increase in expression of leukocyte adhesion molecules, and inflammatory cell infiltrate. This study has demonstrated that in a dog model of lung transplantation, the administration of C1-INH prevents early pulmonary dysfunction, and it suggests that activation of blood coagulation contact system and complement are important mechanisms causing ischemic injury after reperfusion.

Animals↗

Tissue factor (TF) and urokinase plasminogen activator receptor (uPAR) and bleeding complications in leukemic patients.

Tissue factor (TF) and urokinase receptor (uPAR) are key cellular receptors triggering, respectively, coagulation and fibrinolysis. Bleeding complications among leukemic patients have been related to an abnormal expression of TF by blast cells and/or to an abnormal fibrinolytic response. In this study the expression of TF and uPAR has been assessed in 18 acute non-lymphoblastic and 8 lymphoblastic leukemic blast cells using several methodological approaches. TF mRNA was evaluated by in situ hybridization and TF and uPAR antigen were evaluated immunologically in cell lysates and on the cell surface by flow cytometry. In addition, TF-procoagulant activity was measured in coagulation-based assays. The reliability of these methods was corroborated in six leukemic cell lines of different lineages and states of maturation. Disseminated intravascular coagulation was detected in two M3 leukemia patients whose blast cells expressed high amounts of TF. Hyperfibrinolysis was detected in one M1 and two M2 patients, whose blast cells displayed a high content of uPAR antigen, but no TF. Furthermore, M5 leukemia blast cells expressed both TF and uPAR, although no hemostatic defects or bleeding complications were detected in these patients. Taken together, although a limited number of patients was included in this study, these data suggest that in leukemia patients exhibiting bleeding, either TF or uPAR are expressed by their blast cells. However, the presence of these receptors does not necessarily imply the existence of a hemostatic disorder.

Acute Disease↗

Polygraphic characterization of the sleep-epilepsy patterns in a hydranencephalic child with severe generalized seizures of the Lennox-Gastaut syndrome.

This is the report of a hydranencephalic child with severe generalized seizures of the Lennox-Gastaut Syndrome (LGS) who lacked the development of the entire cerebral hemispheres and had preserved the brain stem, cerebellum, hypothalamus and a portion of the thalamus as evidenced by radiological and/or physiological studies. Conventional polygraphic sleep studies in these patients showed presence of scalp EEG and other peripheral, somatic and vegetative signs characterizing the wakefulness, quiet sleep and active sleep stages. Absence of the vertex waves and disrupted sleep spindles were the major qualitative EEG abnormalities. In contrast, quantitative abnormalities in duration, latency and number of sleep cycles found in this patient were similar to those found in other children with Idiopathic Lennox-Gastaut Syndrome (ILGS). A substantial reduction in the number of interictal EEG spikes and a shortening of the ictal clonic EEG activities without concomitant EMG jerks were the most distinct epileptiform abnormalities in this child. In contrast, his basic polygraphic patterns of the tonic and apneic seizures were similar to those found in other children with ILGS. Data obtained from this child suggest that both the sleep stages and the generalized seizures of the ILGS basically depend more on the integrity of the brain stem than on the telencephalic structures.

Brain Stem↗

Reduction of thrombotic and hemorrhagic complications after stent implantation.

This study compared two consecutive antithrombotic strategies after Palmaz-Schatz stent implantation and involved 918 patients. Patients treated between May 1991 and May 1994 (group 1; n = 379) received aspirin, dipyridamole, and intravenous unfractionated heparin until oral anticoagulation was effective, between June 1994 and August 1995, 539 patients (group 2) were treated for 1 month with subcutaneous low-molecular-weight heparin (Fragmin), ticlopidine, and aspirin. There were no differences between the groups in terms of sex, clinical condition, vessel diameter, and severity and location of stenosis. Patients in group 1 were younger than those in group 2 (4% were > 70 years old compared with 12%, respectively; p < 0.01). Group 1 patients had more frequent unplanned stenting (48% vs 18%, respectively; p < 0.01) and fewer endoprostheses in the same artery than those in group 2 (1.1 +/- 0.5 vs 1.2 +/- 0.5, respectively; p < 0.01). Among group 2 patients, there was a significant reduction in thrombotic and hemorrhagic complications compared with group 1 patients. No subacute thrombosis occurred in patients in group 2 in contrast with a 5.8% incidence in patients in group 1 (p < 0.01). In addition, a lower incidence of groin and systemic bleeding was observed in patients in group 2 compared with patients in group 1 (2.6% vs 15%, respectively; p < 0.01). The association of low-molecular-weight heparin and antiplatelets provides a simpler antithrombotic strategy in patients treated with intracoronary stents and reduces the incidence of stent thrombosis and hemorrhagic complications. Our findings suggest that this antithrombotic regimen may prevent or completely avoid stent thrombosis.

Acute Disease↗

Aortic thrombosis in a neonate with hereditary antithrombin III deficiency: successful outcome with thrombolytic and replacement treatment.

We report the case of a newborn male who presented an aortic thrombosis during the neonatal period and was subsequently diagnosed as having antithrombin III (AT III) hereditary deficiency type I. This hypercoagulable condition is known to predispose young adults to venous thrombosis, but in our patient the primary thrombotic incident affected the arterial vessels within the first few days of life. Combined treatment with thrombolytic agents and AT III concentrates recovered aortic permeability, suggesting that the use of AT III may be beneficial for the treatment of thrombotic complications during the first few days of life.

Angiography, Digital Subtraction↗

Monounsaturated fatty acid-enriched diet decreases plasma plasminogen activator inhibitor type 1.

An increase in levels of plasma plasminogen activator inhibitor type 1 (PAI-1) is one of the main hemostatic alterations in patients with coronary heart disease. Despite growing interest in the fibrinolytic system, few studies have been undertaken to determine the effect exerted on it by the different dietary fatty acids. We investigated the effect of a monounsaturated fat (MUFA)-rich diet in comparison with a low-fat diet (National Cholesterol Education Program step 1 diet) (NCEP-1) on factors involved in blood coagulation and fibrinolysis. We also determined the effect of dietary cholesterol on these blood parameters. Twenty-one young, male, healthy volunteers followed two low-fat/high-carbohydrate diets (< 30% fat, < 10% saturated fat, 14% MUFA) for 24 days each, with 115 or 280 mg of cholesterol per 1000 kcal per day, and two oleic acid-enriched diets (38% fat, 24% MUFA) with the same dietary cholesterol as the low-fat/high-carbohydrate diets. Plasma levels of fibrinogen, thrombin-antithrombin complexes, prothrombin fragments 1+2, plasminogen, alpha 2 antiplasmin, and tissue plasminogen activator were not significantly different among the experimental diets used in this study. Consumption of the diet rich in MUFA resulted in a significant decrease in both PAI-1 plasma activity (P < .005) and antigenic PAI-1 (P < .04) compared with the carbohydrate-rich diet (NCEP-1). The addition of dietary cholesterol to each of these diets did not result in any significant additional effect. Changes in insulin levels and PAI-1 activity were positively correlated (r = .425; P < .02). In conclusion, consumption of diets rich in MUFAs decreases PAI-1 plasma activity, which is accompanied by a parallel decrease in plasma insulin levels.

Adult↗

Distinct patterns of urokinase receptor (uPAR) expression by leukemic cells and peripheral blood cells.

The urinary type plasminogen activator, urokinase (uPA) is localized on the cell surface through the binding of a specific receptor, the uPA receptor (uPAR). The uPA localization enhances plasmin formation on the cell surface and facilitates cell migration. The cellular and tissue distribution of uPAR is not fully established. We have analyzed uPAR expression in nine leukemic cell lines of distinct lineages and maturational states and correlated this with expression of plasminogen receptors, tissue-type plasminogen activator (tPA) receptors and LDL receptor-related protein (LRP). The most immature and least differentiated cell line (an erythro-myeloid cell line) and cells of lymphoid lineage, did not express uPAR, whereas cells differentiated along the myelo-monocytic pathway displayed this receptor. Plasminogen and tPA receptors were expressed by all leukemic cell lines and by all nucleated peripheral blood cells but B and T lymphocytes were negative for cell surface expression of both uPAR and LRP while monocytes and neutrophils were positive for expression of both uPAR and LRP. PMA stimulation induced surface expression of uPAR in lymphocytes but did not induce expression of LRP by these cells. In contrast, lymphoid cell lines were negative for uPAR expression even after PMA stimulation, indicating differences in regulation of uPAR expression between lymphocytes and lymphoid cell lines. The pattern of uPAR expression on leukemic cell lines was also studied on bone marrow blast cells from leukemic patients. Only the most mature myeloid cells expressed uPAR on their surfaces. In contrast, M3 leukemic cells and other blast cells displaying lymphoid markers such as TdT (+) and/or CD2 (+) did not express intracellular or cell-surface associated uPAR, indicating an heterogeneity among these promyelocytic cells and suggesting that uPAR may be a useful marker for leukemia typing. Myeloid blast cells from some patients contained intracellular pools of uPAR but displayed no receptor on the cell surface, suggesting that translocation may be a mechanism regulating uPAR expression in these cells. The comparison of uPAR expression between these cell lines and peripheral blood cells and it correlation with plasminogen receptors, tPA receptors and LRP expression offers new insights regarding potential mechanisms for regulation of uPA-uPAR-mediated pericellular proteolysis.

Cell Differentiation↗

Electrical stimulation of the centromedian thalamic nucleus in control of seizures: long-term studies.

Five patients with chronic incapacitating seizures averaging 15-5,000/month were selected for study. All patients had more than one seizure type and had received maximal doses of antiepileptic drugs (AEDs). The centromedian thalamic nucleus (CM) was stimulated electrically through bilateral multicontact platinum electrodes stereotaxically placed in CM and connected to internalized pulse generators. Electrophysiologic confirmation of electrode position included thalamically elicited recruiting responses and EEG desynchronization recorded at the scalp. Stimulation parameters were adjusted individually in the range of 450-800-microA intensity, 65 pps, 0.09 ms, in 1-min trains, alternating right and left side stimulation and with 4-min intervals delivered for 2 h/day. Quantitative evaluation included frequency of seizures/month, number of maximal interictal paroxysmal discharges, and frequency of background activities counted in selected scalp EEG samples, taken throughout the observation period (7-33 months). Significance of changes was evaluated by parametric Student's t test. Generalized tonic-clonic seizures (GTC) decreased dramatically, almost disappearing in all cases (p < 0.001), with a significant reduction in interictal paroxysmal discharges (p < 0.01) and a tendency toward an increase in EEG background frequency. Other generalized seizures (atypical absences) decreased significantly, but there was no change in the number of complex partial seizures (CPS). CM stimulation is useful in control of GTC, but its beneficial effect on other seizure types has not been established.

Adult↗

Persistence of the typical spike-wave EEG pattern after surgical excision of a temporal lobe astrocytoma and apical lobectomy.

This is a report on a patient with intractable 'primary' generalized seizures and typical spike-wave EEG patterns, in whom an unexpected temporal lobe astrocytoma was detected by MRI studies. Clinical and electrophysiological studies were performed before and after surgical excision of the tumor and apical temporal lobectomy in an attempt to determine whether 'primary' generalized seizures and EEG patterns and the temporal lobe tumor were only coincident neurological disorders or were indeed related. Before resection, the patient consistently showed a typical spike-wave EEG pattern with no background and paroxysmal activities suggestive of 'secondary' bilateral synchrony in 10 consecutive conventional EEG recordings; neither spontaneous interictal nor ictal ECoG activities suggested focal temporal lobe epileptogenesis. After resection, the patient showed increased pentylenetetrazol (PTZ) convulsive threshold, and reduction in the number of 'primary' generalized seizures, although typical spike-wave EEG discharges persisted. These observations suggest that 'primary' generalized seizures, EEG patterns and the temporal tumor were physiopathologically interrelated, and that both reticulocortical and corticoreticular mechanisms may participate together in the genesis of 'primary' generalized clinical and EEG activities.

Adult↗

Sleep-epilepsy interactions in patients with intractable generalized tonic seizures and depth electrodes in the centro median thalamic nucleus.

Sleep-epilepsy interactions were studied in ten patients with Lennox-Gastaut Syndrome (LGS) suffering intractable generalized tonic seizures associated with generalized ictal fast spikes and interictal slow spike-wave complexes, where electrodes were implanted in the centromedian thalamic nucleus (CM) as part of a neuroaugmentive procedure for seizure control. In these patients, continuous all night recordings according to International Guidelines were performed to quantitatively determine changes in sleep patterns produced by the epileptic condition and changes in ictal and interictal surface and CM EEG activities produced by sleep stages. LGS patients showed significantly longer wakefulness (W) and shorter slow wave sleep (SWS) II than normals. Patients with seizures during the night showed shorter latency and larger number of paradoxical sleep (PS) periods than those patients without seizures. Ictal and interictal spike-wave EEG activities appeared together in surface and CM regions during all sleep stages with a ratio SURFACE/CM almost equal to one and PS did not focalize ictal and interictal activities in thalamic or cortical regions. Occurrence and duration of "myoclonic" ictal EEG component and number of interictal spike-wave complexes were higher during SWSII while they were smaller during PS than during W.

Adult↗

Long-term effects of medical and surgical treatments on Parkinson's disease.

Three groups of patients with Parkinson's disease (PD) were studied: (1) PD patients treated medically with L-Dopa and anticholinergics, (2) PD patients treated with thalamo-subthalamotomies plus medical treatment, and (3) PD patients treated with autologous adrenal medullary transplantation to right caudate nucleus plus medical treatment. Evaluations prior and 1, 6 and 12 months after treatment were accomplished with PD scales (NYPDS, UPDS, Schwab and England and Hoehn and Yahr scales). No attempt was made to compare one PD after treatment in each group. Statistical analysis was performed with the Friedman-Anova test. Group 1 did not show significant improvement at any time but deterioration at 12 months. Group 2 showed significant improvement at 1 month but at 12 months deterioration occurred mainly in the mental condition and akinesia. Group 3 did not show significant improvement at any time but at 12 months there was a tendency of improvement in self-sufficiency.

Adrenal Medulla↗

Neurotransmitter levels in cerebrospinal fluid in relation to severity of symptoms and response to medical therapy in Parkinson's disease.

Determinations of biopterin (BP), homovanilic acid (HVA), glutamic acid (GTA), and glutamine (GT) levels in cerebrospinal fluid (CSF) obtained through a lumbar tap were performed in 20 parkinsonian patients in different stages of evolution and without medication. In patients with motor symptoms not related to Parkinson's disease (dystonia, dyskinesia and essential tremor) (n = 4). In 7 other neurological patients subjected to spinal tap for diagnostic procedures neurotransmitters were also determined and taken as control groups. In 14 of the patients with Parkinson's disease, the symptoms were evaluated using conventional scales (UPDS, NYPDS, NWPDS, Schwab and England, and Hoehn and Yahr scale). The amplitude and the frequency of tremor were quantitatively evaluated through a single plane accelerometer Grass SP-1, akinesia was measured through reaction time to auditory stimuli, and rigidity through the speed of lineal movement. Evaluations were performed with the patient not on any medication for 1 week and repeated 1 h after the intake of 250 mg of 200/50 L-dopa/carbidopa preparation (Sinemet) and on a different day after the intake of biperiden (Akineton) 6 mg/day. Differences in neurotransmitter or metabolites levels between Parkinson's disease and control groups were determined through an independent Student's t test. Correlation between severity of symptoms in the scales and for each individual symptom measured through the quantitative tests and the levels of neurotransmitters in CSF were evaluated through the Pearson correlation analysis test. Modifications in the motor performance after administration of Sinemet and Akineton, and the levels of neurotransmitters were indirectly determined. RESULTS. (1) There were significant differences between the levels of BP and GT in patients with Parkinson's disease and control groups, (2) lower GTA levels correlated with more severe rigidity and akinesia, and with the best response to the administration of L-dopa and may be an important marker for prognosis, and (3) lower levels of GT correlated with least akinesia, but not with tremor, which may indicate that the akinesia depends on other biochemical abnormalities besides dopamine depletion.

Adult↗

Role of the centromedian thalamic nucleus in the genesis, propagation and arrest of epileptic activity. An electrophysiological study in man.

Twenty-eight patients underwent electrical stimulation of the centromedian (CM) thalamic nucleus as a neuro-augmentative procedure to control intractable seizures of various types. To assess the correct placement of electrodes, electrical stimulation at 3 and 6 Hz, 1.0 msec and 600-2000 uA pulses in trains of 30-60 sec were used while the EEG was recorded by scalp electrodes. Spontaneous seizure activities of various types were simultaneously recorded. In cases of focal epilepsy depth electrodes were used in order to study the sequence of activation of different structures. Three Hz electrical stimulation induced spike-and-wave complexes accompanied by a typical absence. Eight Hz induced recruiting-like responses with ipsilateral predominance and no clinical manifestations. Interictal spike activity was recorded in the CM in cases of generalized tonic-clonic convulsions (GTCC) and ictal spike pattern in the CM preceded discharges in other areas. In atypical absences cortical and CM discharges occurred simultaneously. It is concluded that the CM participates in the onset of GTCC and typical absences, in the propagation of secondary GTCC but not in myoclonic convulsions.

Electric Stimulation↗