[Current status of epilepsy surgery in Spain. Compendium and awareness]. / Estado actual de la cirugía de la epilepsia en España. Compendio y conciencia.

INTRODUCTION: Drug-resistant epilepsy affects between a third and a quarter of patients with epilepsy. Within this group, with a poorer quality of life and high healthcare costs, there is a considerable proportion of patients with potentially surgical causes of epilepsy, and epilepsy surgery is a proven therapeutic option. In Spain, we do not know the actual number of patients who are treated in relation to the total number of cases of refractory epilepsy that could benefit from surgical treatment. AIM: To analyse the number of epilepsy surgical interventions performed and published in relation to the potential cases of refractory epilepsy who are candidates for surgery in our country. METHOD: A review was carried out through a literature search in PubMed and Cochrane of articles published between 1990 and 2020, combining the following words and Boolean operators: 'epilepsy surgery IN Spain'. The evidence and recommendations were classified according to the prognostic criteria of the Oxford Centre for Evidence Based Medicine (2001) and of Neurological Societies (2004) for therapeutic actions. RESULTS: The majority (75.6%) of the publications came from the autonomous communities of Madrid and Catalonia and 46.4% of the articles published were short series. We counted 2,113 surgical interventions (resections, palliative interventions, implantation of deep electrodes and implantation of neurostimulators), which represents 8.7% of the estimated population with refractory epilepsy. CONCLUSION: Epilepsy surgery in our country is an underused therapeutic indication that is not offered or administered to the majority of potential beneficiaries.

TITLE: Estado actual de la cirugía de la epilepsia en España. Compendio y conciencia.Introducción. La epilepsia refractaria al tratamiento médico afecta a entre un tercio y una cuarta parte de los pacientes con epilepsia. Dentro de este grupo, con peor calidad de vida y altos costes sanitarios, existe una considerable proporción de pacientes con causas de epilepsia potencialmente quirúrgicas, y la cirugía de la epilepsia es una opción terapéutica comprobada. En España no sabemos el número real de pacientes que llegan a tratarse en relación con el total de los casos con epilepsia refractaria que podrían beneficiarse del tratamiento quirúrgico. Objetivo. Analizar el número de cirugías de epilepsia realizadas y publicadas en relación con los potenciales casos de epilepsia refractaria candidatos a cirugía en nuestro país. Método. Se realizó una revisión mediante la búsqueda bibliográfica en PubMed y Cochrane de artículos publicados entre 1990 y 2020, combinando las siguientes palabras y operadores booleanos: 'epilepsy surgery IN Spain'. Se clasificaron las evidencias y recomendaciones según los criterios pronósticos del Oxford Center for Evidence Based Medicine (2001) y de la European Federation of Neurological Societies (2004) para actuaciones terapéuticas. Resultados. El 75,6% de las publicaciones se originó en las comunidades autónomas de Madrid y Cataluña. El 46,4% de los artículos publicados son de series cortas. Contabilizamos 2.113 intervenciones quirúrgicas (resecciones, cirugías paliativas, implantación de electrodos profundos e implantación de neuroestimuladores), lo que representa el 8,7% de la población estimada con epilepsia refractaria. Conclusión. La cirugía de la epilepsia en nuestro medio es una indicación terapéutica infrautilizada y que no se ofrece o no se administra a la mayoría de los potenciales beneficiarios.

Sex differences on the electrocardiographic pattern of cardiac repolarization: possible role of testosterone.

BACKGROUND: Cardiac repolarization has been shown to be shorter and faster in men compared with women. In this study, we examined the electrocardiographic pattern of repolarization in patients with abnormal plasma levels of testosterone to gain insight into the role that this hormone plays in modulating repolarization. METHODS AND RESULTS: Repolarization was measured in 27 castrated men, 26 women with virilization, and 53 control subjects pair-matched for age and sex. Repolarization in castrated men was slower and longer than that of normal men. Women with virilization exhibited a shorter and faster repolarization than normal women and castrated men. These differences are the opposite of those found in the normal population. Finally, the changes observed in castrated men may be reverted by testosterone. CONCLUSIONS: We conclude that testosterone plays an important role in modulating cardiac repolarization.

Inhibition of interferon gamma production by peripheral blood mononuclear leukocytes of patients with sarcoidosis. Pathogenic implications.

Interferon gamma (IFN-gamma) production by stimulated peripheral mononuclear leukocytes of 30 patients with sarcoidosis was studied. A significant inhibition (64 percent, 5 to 330 IU/ml vs normal individuals = 1,000 +/- 250 IU/ml) in the IFN-gamma synthesis was found. The inhibition is due to a defect in the circulating monocytes and not in the peripheral T lymphocytes of these patients. This defect in the peripheral IFN-gamma production could be involved in the pathogenesis of this disease.

Chloride current in toad skeletal muscle and its modification by the histidine-modifying reagent diethylpyrocarbonate.

Cl- currents were measured in short fibres in the toad lumbricalis muscle with a two-microelectrode voltage clamp. Membrane Cl- conductance increased markedly when external pH was raised. At pH 7 or higher, the Cl- current fell during a hyperpolarizing voltage pulse and the rate of inactivation was directly proportional to the voltage change. The histidinemodifying reagent diethylpyrocarbonate (DEPC, 1 mM) which carbethoxylates histidil residues in proteins, suppressed the inactivation of Cl- currents at pH 7.5. On the other hand, no apparent changes in the kinetics of the currents at pH 5 were seen. No3- currents, which are independent of the extracellular pH and time, were not affected by DEPC. Our results support the notion that the inactivation of Cl- currents at pH 7.5 represents a membrane permeability change and that DEPC interferes with this process. Protonation of histidine groups associated with Cl- channels may be the controlling reaction for the pH -dependent Cl- response.

Blockade of the inward rectifier potassium currents by zinc and nickel ions in voltage-clamped toad muscles.

The inward rectifier is one of the voltage-sensitive K+ channels present in several tissues: Its conductance increases under hyperpolarization and decreases with depolarization. In this work we studied the effects of Zn2+ and Ni2+ (5-30 mM) on the macroscopic K+ current through the inward rectifier system. The experiments were performed in the short muscle fibers of the lumbricalis muscle of toads with a two-microelectrode voltage clamp technique. The fibers were equilibrated in a control solution containing 68 mM K2SO4 and then exposed to Zn2+ or Ni2+. We found that both cations reduced in a reversible manner the current carried by K+ ions, and this reduction was prevented by decreasing the external pH of the solution (pH 5). The blockade of current was slightly dependent on the membrane potential and time independent. Two mechanisms may be involved in the blocking action of these cations: Zn2+ and Ni2+ may either be blocking the pore of the channels or acting at a regulatory binding site on the extracellular surface in an unspecified manner.

Barium resistant potassium current in mammalian skeletal muscle following denervation.

Inward rectifier potassium channels are thought to be related to resting membrane potential and in innervated skeletal muscle they are specially sensitive to the blocking action of Ba2+ ions. After denervation other channels are known to become resistant to their blockers. We study the effect of Ba2+ upon the inward rectifier potassium channels after denervation. Rat extensor digitorum longus fibers were equilibrated for 150 minutes in 150 mM KCl; when they were returned to 5 mM KCl the resting potential went back to its original level with a half time of 35 minutes. This repolarization was blocked by 5 mM BaCl2 in innervated muscles and in muscles denervated for 7 days, but failed to do so after 14 days of denervation. Voltage-clamp experiments performed in lumbricalis denervated muscle showed a lack of effect of Ba2+ upon potassium current after 18 days of denervation. This results suggest that the inward rectifier potassium channels become resistant to Ba2+ ions after denervation, indicating a neural influence.

Internal features of graphite in cast irons. Confocal microscopy: useful tool for graphite growth imaging.

Spherulitic crystallisation is a mode of growth of crystals from the melt. Considerable attention has been given to spheroidal graphite formation, providing detailed information about the internal microstructure of the spherulites in spheroidal (SG irons) and compacted graphite irons (CG irons) (Stefanescu, D., 1990. Cast Irons. ASM Handbook, 10th ed., vol. 1). Nevertheless, the mechanisms responsible for this mode of crystallisation are not fully understood. This study deals with the inoculation mechanisms, with particular emphasis on the study of the inclusions for the heterogeneous nucleation of graphite. It is shown that the graphite nuclei are sulfide products of the nodularizing treatment. It has been observed that when rare-earth treatment is applied, the central nucleus consists of a core and an envelope from which the graphite grows. Confocal Scanning Laser Microscopy (CSLM), in reflection mode, was used to study the internal features of the spheroidal graphite growth. Confocal reflection imaging, which has a capacity for optical sectioning of the sample, provides high-resolution images of surface and subsurface regions of interest contained within a semi-transparent sample. Furthermore, three-dimensional reconstruction of these optical sections can provide insight into the mechanism of graphite growth mechanism interpretation. With CSLM the radial growth of graphite was seen. Other techniques, such as TEM, SEM-EDS, WDS, AES and SAM were also used to corroborate the results.

Effect of electrode impedance in improved buffer amplifier for bioelectric recordings.

We analysed the effects of electrode impedance on the transfer response of a one-stage improved buffer amplifier. The electrode DC resistance (R(d)) modifies the one-stage buffer transfer response. We found a limit electrode resistance (R(d(lim))) which depends on the transfer damping factor (epsilon). If R(d) is lower than 86.5 komega, the transfer response of the buffer fulfils American Heart Association (AHA) recommendations, but when R(d) is greater than R(d(lim)) it must be cautiously weighed up because its influence in the transfer response becomes appreciable. The maximum R(d) that can be driven by the buffer is 1.2 Momega. Higher values do not fulfil AHA recommendations. Therefore, electrodes with higher impedance should not be used with this kind of buffer. In contrast, when this buffer is used to build in an instrumentation amplifier (IA) for bipolar recording, the common-mode rejection ratio (CMRR) is sensitive to the electrode type used.

[Ion channels in non excitable cells]. / Canales iónicos en células no excitables.

Several distinct types of voltage-gated and second-messenger-operated K+, Ca2+, Na+ and Cl- channels exist in electrically non excitable cells such as those of the hematopoietic lineage. In these cells ion channels mediate cellular functions involving intracellular biochemical responses, rather than rapid electrical signaling. The presence of the channels is required for several basic functions, such as activation, secretion of lymphokines, mitogenesis, the regulation of cell volume and the mechanisms of resistance to chemotherapeutic agents. Here IN we review the patch-clamp method for studying many characteristics of these ionic channels, particularly in blood cells.

Chloride currents in skeletal muscles of Bufo arenarum.

C1- currents (ICl) were measured in short fibers (1-2 mm) from the lumbricalis muscle of toads (Bufo arenarum) with two microelectrodes (15 degrees C). Initially the fibers were equilibrated in a high (K+)-containing solution: (mM) K2SO4 68; Na2SO4 20; KCl 60; CaSO4 8; MgSO4 1; HEPES 2.5. Constant pulses were applied when all the external K+ was replaced by Cs+: Cs2SO4 68; Na2SO4 20; CsCl 60; CaSO4 8; HEPES 2.5 (pH 7.5). Under these conditions about 80-90% of the current is carried by Cl-. The current-voltage relation is almost linear implying constant conductance and hence voltage-independent permeability. The voltage dependence of the net C1- current could be fitted by constant field equation with a PCl of 3.3 x 10-6 cm/sec. In a separate group of experiments a two-pulse technique was used to estimate the availability and the inactivation of the initial ICl during a test pulse. After returning the potential to the holding potential for various times, test pulses of the same amplitude and duration of the prepulses were applied. The initial current during the test pulse was 70% of the initial current during the prepulse and the recovery was complete in less than 300 msec with a linear relationship between the current during the test pulse and the amplitude of the preceding prepulse. When the test pulses were preceded by a positive prepulse, the initial current for any given test pulse was larger than with a negative prepulse. If we assumed that the initial current during the test pulse is a measure of the number of channels open at the end of the prepulse, these results suggest that hyperpolarizing pulses inactivate and depolarizing prepulses activate the ICl.

Chloride channels in toad skeletal muscle fibers.

Chloride currents were measured in short lumbricalis fibers of toads (Bufo arenarum) with voltage and patch clamp techniques. For the availability of chloride currents we applied a double-pulse technique in voltage-clamped fibers. When the test pulse was preceded by a positive prepulse, the initial current was larger than with a negative prepulse and exhibited a different rate of decline to its steady-state value. At the single-channel level we found that in most of the experiments with symmetrical 110 mM NaCl solutions, two levels of conductance, 20 ("small channel") and 360 pS ("maxi channel"), occurred with the highest probabilities. The openings of the maxi channels were more frequent at potentials close to 0 mV, whereas for the small channels the openings were at negative potentials. In contrast with the results with the macroscopic currents, a change of 2 orders of magnitude in the pH, from 7.3 to 5, had only minor effects on the channels' conductance. As with some other anion channels, the selectivity of the channels described here is low, the p(Cl)/p(Na) ratio being 1.9 and 3.7 for the small and maxi Cl(-) channels, respectively. The behavior of these Cl(-) channels with a relative high Na(+) permeability could contribute to the relatively low resting membrane potential of the lumbricalis fibers measured in the standard 110 mM NaCl solution.

Effects of amiodarone and desethylamiodarone on the inward rectifying potassium current (IK1) in rabbit ventricular myocytes.

We examined the effects of amiodarone (AMI) and desethylamiodarone (DAM) on whole-cell inward rectifying potassium current (IK1) in freshly isolated adult rabbit ventricular myocytes by using the whole-cell voltage-clamp technique, as an index of their effects on resting membrane resistance (Rm). Under control conditions, the current showed a strong inward rectification with a maximal inward current measured at -130 mV of -26.4 +/- 1.3 pA/pF and a maximal outward current measured at -50 mV of 3.5 +/- 0.3 pA/pF The current also exhibit a time-dependent activation, with a time constant of activation (tau(a)) that increased with depolarization. The maximal slope conductance normalized to cell capacitance was 0.509 +/- 0.019 nS/pE After exposure to both DAM (50 microM; n = 8) and AMI (50 microM; n = 7), rapid decrease in inward IK1 was observed. Block was restricted almost exclusively to the inward component. DAM caused a significant reduction of the maximal inward current (-20.0 +/- 2.0 pA/pF; p < 0.05), whereas AMI induced an even greater reduction of the same component (-14.1 +/- 1.2 pA/pF; p < 0.05 with respect to control and to DAM). The outward component of IK1 was not changed by either AMI or DAM (4.0 +/- 0.3 pA/pF and 3.4 +/- 0.4 pA/pF, respectively). AMI and DAM also decreased the maximal slope conductance significantly (0.297 +/- 0.019 nS/pF and 0.421 +/- 0.038 nS/pF, respectively). In addition, AMI but not DAM significantly increased the tau(a). However, the voltage dependence of the acceleration of tau(a) remained unchanged after both AMI and DAM exposure. These results allow us to conclude that AMI may induce a greater increase in the resting Rm than its main metabolite. This effect may counterbalance, at least in part, the conduction slowing due to its sodium channel-blocking properties.

Differential modulation of electrocardiographic indices of ventricular repolarization dispersion depending on the site of pacing during premature stimulation.

INTRODUCTION: Dispersion of ventricular repolarization has been shown to increase with premature stimulation. Moreover, a straight correlation between the amount of dispersion of repolarization and the vulnerability to ventricular fibrillation was reported. On the other hand, differences between right ventricular (RV) and left ventricular (LV) fibrillation threshold have been reported. However, no data exist regarding the influence of the site of stimulation on modulation of dispersion of repolarization. METHODS AND RESULTS: In the present study, several ECG indices of dispersion of repolarization, as a function of the coupling interval and the site of stimulation, were evaluated in a modified Langendorff-perfused rabbit heart (n = 12), with a 5 x 8 array of a simulated body surface unipolar lead system. As the coupling interval was shortened, a biphasic modulation of dispersion of repolarization was found when stimuli were elicited at the LV. In contrast, when the heart was paced from the RV, the dispersion increased monotonically as coupling interval was shortened. CONCLUSION: A differential behavior of the modulation of dispersion of repolarization was found as a function of the site of stimulation.

Influence of filtering techniques on the time-domain analysis of signal-averaged P wave electrocardiogram.

INTRODUCTION: The advent of signal-averaged ECG (SAECG) systems for P wave analysis has made it important to determine if the use of different filtering techniques in these systems is diagnostically equivalent. METHODS AND RESULTS: Three different high-pass filtering techniques and two cutoff frequency values were used: 29- and 40-Hz Butterworth bidirectional filter (BB29, BB40), 29- and 40-Hz Butterworth unidirectional filter (UB29, UB40), and 29- and 40-Hz least mean square filter (LMS29, LMS40). Normal healthy volunteers (n = 36) and patients with documented paroxysmal atrial fibrillation (n = 23) were analyzed. A custom-built SAECG system and standard bipolar orthogonal leads were used. Noise was reduced to < 0.3 microV. P wave total duration, root mean square voltage of the terminal 20, 30, and 40 msec of the filtered vector magnitude, and the area under the curve between the onset and offset of averaged unfiltered and filtered P wave vector magnitude were analyzed. Only the duration of the P wave showed statistically significant differences between groups, being longer in the PAF group for all filters and cutoff frequencies studied. A bias increment of approximately 20 msec was detected in unidirectional and least mean square filters as compared to the bidirectional filter. Sensitivity, specificity, and predictive accuracy were > 70% for all filters; the BB40 filter yielded the best performance. CONCLUSION: The normality limits derived from one filter cannot be applied directly to recordings obtained from the other filters. Critical limits must be established individually for different software settings.

Sex-dependent electrocardiographic pattern of cardiac repolarization.

BACKGROUND: Although sex-dependent differences in cardiac repolarization have been known for many years, few attempts have been carried out to define the individual contribution of each electrocardiographic (ECG) repolarization variable to the sex-dependent pattern. METHOD AND RESULTS: We analyzed several ECG repolarization variables that reflect both the duration and the rate of repolarization in 500 normal healthy subjects between the ages of 20 and 80 years (250 men and 250 women) and distributed into 5 groups according to age. Cardiac repolarization, measured in the precordial lead exhibiting the highest T-wave amplitude, was found to be shorter and faster in normal men compared with normal women (P <.001). The parameters with the highest individual weight in determining these sex differences were the J point and the ST angle, as indicated by nonlinear (logistic) multivariate regression analysis. CONCLUSION: We conclude that changes in the duration and rate of early repolarization are determinants for these sex-dependent ECG pattern differences.