RESUMEN
OBJECTIVE: This study investigated inter-rater agreement (IRA) among EEG experts for the identification of electrographic seizures and periodic discharges (PDs) in continuous ICU EEG recordings. METHODS: Eight board-certified EEG experts independently identified seizures and PDs in thirty 1-h EEG segments which were selected from ICU EEG recordings collected from three medical centers. IRA was compared between seizure and PD identifications, as well as among rater groups that have passed an ICU EEG Certification Test, developed by the Critical Care EEG Monitoring Research Consortium (CCEMRC). RESULTS: Both kappa and event-based IRA statistics showed higher mean values in identification of seizures compared to PDs (k=0.58 vs. 0.38; p<0.001). The group of rater pairs who had both passed the ICU EEG Certification Test had a significantly higher mean IRA in comparison to rater pairs in which neither had passed the test. CONCLUSIONS: IRA among experts is significantly higher for identification of electrographic seizures compared to PDs. Additional instruction, such as the training module and certification test developed by the CCEMRC, could enhance this IRA. SIGNIFICANCE: This study demonstrates more disagreement in the labeling of PDs in comparison to seizures. This may be improved by education about standard EEG nomenclature.
Asunto(s)
Electroencefalografía/normas , Unidades de Cuidados Intensivos/normas , Convulsiones/diagnóstico , Convulsiones/fisiopatología , Humanos , Variaciones Dependientes del Observador , Estudios RetrospectivosRESUMEN
BACKGROUND: Selective amygdalohippocampectomy (SelAH) is increasingly performed in patients with mesial temporal lobe epilepsy and hippocampal sclerosis. To determine whether visual field defects are less pronounced after SelAH than after standard temporal lobectomy (StTL), we retrospectively analyzed postoperative quantitative visual fields after the 2 procedures. METHODS: Humphrey visual field analysis was obtained postoperatively in 18 patients who had undergone SelAH and in 33 patients who had undergone StTL. The SelAH was performed via a transcortical approach through the middle temporal gyrus and included the amygdala, 3 cm of the hippocampus, and the parahippocampal gyrus. The visual field pattern deviation was used for analysis. We considered a defect clinically significant if there were 3 contiguous coordinates affected at the 5% level or 2 at the 1% level. RESULTS: All but 2 of 18 patients who had undergone SelAH had homonymous superior quadrantic visual field defects contralateral to the side of the surgery. One patient had no defects by our criteria, and one had a mild defect that reached significance only in the ipsilateral eye. The averaged defect affected mostly coordinates close to the vertical meridian with relative sparing of points close to the horizontal meridian. All but 3 of the 33 patients who had undergone StTL had homonymous superior quadrantic visual field defects. One patient had no defects; 2 had defects that reached significance in only one eye. The averaged defect involved all points in the affected quadrant, but was also greater near the vertical meridian. Of 13 tested visual field coordinates, 4 were significantly less affected by SelAH in the ipsilateral eye and 3 in the contralateral eye. The coordinates close to the horizontal meridian were significantly spared by SelAH. CONCLUSIONS: Visual field defects are very common after SelAH but are significantly less pronounced than after StTL. In particular, the visual field close to the horizontal meridian is relatively spared in SelAH.
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Epilepsia del Lóbulo Temporal/cirugía , Procedimientos Neuroquirúrgicos/efectos adversos , Complicaciones Posoperatorias/etiología , Lóbulo Temporal/cirugía , Baja Visión/etiología , Vías Visuales/lesiones , Adolescente , Adulto , Amígdala del Cerebelo/fisiopatología , Amígdala del Cerebelo/cirugía , Niño , Femenino , Hemianopsia/etiología , Hemianopsia/patología , Hemianopsia/fisiopatología , Hipocampo/patología , Hipocampo/fisiopatología , Hipocampo/cirugía , Humanos , Enfermedad Iatrogénica/prevención & control , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos/métodos , Complicaciones Posoperatorias/prevención & control , Estudios Retrospectivos , Lóbulo Temporal/patología , Lóbulo Temporal/fisiopatología , Baja Visión/patología , Baja Visión/fisiopatología , Campos Visuales/fisiología , Vías Visuales/patología , Vías Visuales/fisiopatología , Adulto JovenRESUMEN
GABA(A) receptor alpha subunit subtypes have distinct CNS distributions and confer different pharmacological and biophysical properties to alphabetagamma receptor isoforms. However, the alpha subtype-dependent properties of alphabetadelta receptor isoforms that may be targeted to extrasynaptic sites remain poorly understood. We investigated the properties of alpha1beta3delta and alpha6beta3delta receptor currents evoked by concentration jumps using a saturating GABA concentration (1 mM). alpha1beta3delta receptor currents desensitized slowly, deactivated rapidly and displayed voltage-dependence only of peak amplitude. In contrast, alpha6beta3delta receptor currents had voltage-dependent increased desensitization and slower deactivation, but did not show rectification. The neurosteroid THDOC (1 microM) enhanced alpha1beta3delta more than alpha6beta3delta currents, but increased the extent of desensitization and prolonged deactivation for both receptor isoforms. alpha1-alpha6 and alpha6-alpha1 chimeras (spliced in transmembrane domain 1) suggested that differences in deactivation rate and its voltage-dependence correlated with N-terminal domains, while the extent of desensitization and its voltage-dependence correlated with C-terminal domains. Both chimeras showed outward rectification. alpha1 subunit-like THDOC enhancement was observed with the alpha1-alpha6 chimera, but the alpha6-alpha1 chimera did not confer alpha6 subunit-like enhancement, suggesting that multiple alpha1 subunit domains contributed to neurosteroid efficacy. Thus, alpha subunit subtypes may regulate the kinetic and pharmacological properties of tonic neuronal inhibition.
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Desoxicorticosterona/análogos & derivados , Antagonistas del GABA/farmacología , Neurotransmisores/farmacología , Receptores de GABA-A/metabolismo , Secuencia de Aminoácidos , Animales , Desoxicorticosterona/farmacología , Estimulación Eléctrica , Electrofisiología , Antagonistas de Receptores de GABA-A , Isomerismo , Potenciales de la Membrana/fisiología , Datos de Secuencia Molecular , Técnicas de Placa-Clamp , Ratas , Receptores de GABA-A/química , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes/química , Ácido gamma-Aminobutírico/farmacologíaRESUMEN
Fast IPSCs in the brain are predominantly caused by presynaptic release of GABA that activates GABA(A) receptor (GABA(A)R) channels. The IPSCs are shaped by the gating and desensitization properties of postsynaptic GABA(A)Rs. Specifically, fast desensitization has been suggested to decrease IPSC amplitude and to increase IPSC duration by slowing deactivation; however, the mechanisms underlying desensitization, deactivation, and their coupling are poorly understood. Consistent with this suggestion, alpha1beta3gamma2L GABA(A)Rs desensitize with a prominent fast phase and deactivate slowly, whereas alpha1beta3delta GABA(A)Rs desensitize without a fast phase and deactivate rapidly. Using the concentration-jump technique applied to excised patches, we studied GABA(A)Rs containing chimeras or exchange mutants between delta and gamma2L subunits to gain insight into the structural bases for fast desensitization and its coupling to deactivation. We demonstrated that the N terminus and two adjacent residues (V233, Y234) in the first transmembrane domain (TM1) of the delta subunit were both required to abolish fast desensitization. Additionally, these residues in TM1 of the gamma2L subunit (Y235, F236) were critical for desensitized states to prolong deactivation after removal of GABA, because mutations resulted in accelerated deactivation despite unaltered desensitization time course. Interestingly, control of desensitization and deactivation was independent of the identity (gamma2L or delta subunit sequence) of TM2, indicating that structures related to the putative channel gate may play a less direct role in desensitization than previously suggested.
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Receptores de GABA-A/genética , Receptores de GABA-A/metabolismo , Animales , Línea Celular , Relación Dosis-Respuesta a Droga , Fibroblastos/citología , Fibroblastos/metabolismo , Humanos , Riñón/citología , Riñón/metabolismo , Ratones , Mutagénesis Sitio-Dirigida , Inhibición Neural/fisiología , Técnicas de Placa-Clamp , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Subunidades de Proteína , Ratas , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Relación Estructura-Actividad , Ácido gamma-Aminobutírico/metabolismo , Ácido gamma-Aminobutírico/farmacologíaRESUMEN
To understand the mechanisms underlying activation and deactivation of GABA(A) receptor (GABAR) channels, we studied the properties of an identified GABAR isoform under conditions similar to those present at central GABAergic synapses. Recombinant alpha5beta3gamma2L GABARs were expressed in L929 fibroblasts and studied using patch-clamp recording techniques. Brief application of a high GABA concentration to outside-out membrane patches elicited transient currents that resembled those reported for miniature inhibitory postsynaptic currents (mIPSCs), as well as native GABAR currents recorded under similar conditions. Characteristic of these currents was a rapid activation phase followed by a prolonged biphasic deactivation phase that far outlasted GABA application. Single-channel recordings revealed unique patterns of channel activity with two channel conductance states of 22 and 16 pS. The prolonged deactivation phase appeared to be sustained by entry into and reopening from long-lasting closures or desensitized states. Agonist affinity determined the time course of deactivation, indicating that occupied receptors drove the channel activity underlying the decay of current. The time course of deactivation was also longer at depolarized membrane potentials. The similarities between transient activation kinetics of recombinant alpha5beta3gamma2L GABARs to activation of synaptic GABARs (rapid activation and prolonged, voltage-dependent deactivation) suggest that intrinsic channel properties determine much of the response patterns of native GABARs.
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Receptores de GABA-A/efectos de los fármacos , Ácido gamma-Aminobutírico/farmacología , Animales , Línea Celular , Relación Dosis-Respuesta a Droga , Electrofisiología , Agonistas del GABA/farmacología , Isoxazoles/farmacología , Cinética , Potenciales de la Membrana/efectos de los fármacos , Isoformas de Proteínas/efectos de los fármacos , Isoformas de Proteínas/genética , Isoformas de Proteínas/fisiología , Receptores de GABA-A/genética , Receptores de GABA-A/fisiología , Proteínas Recombinantes de Fusión/efectos de los fármacos , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/fisiología , Factores de TiempoRESUMEN
Physiological properties of GABAA receptors from acutely dissociated rat dentate granule cells. Study of fast, GABAA receptor-mediated, inhibitory postsynaptic currents (IPSCs) in hippocampal dentate granule cells has suggested that properties of GABAA receptors influence the amplitude and time course of the IPSCs. This study describes the physiological properties of GABAA receptors present on hippocampal dentate granule cells acutely isolated from 18- to 35-day-old rats. Rapid application of 1 mM GABA to outside-out macropatches excised from granule cells produced GABAA receptor currents with rapid rise time and biexponential decay of current after removal of GABA. After activation, granule cell GABAA receptor currents desensitized incompletely. During a 400-ms application of 1 mM GABA, peak current only desensitized approximately 40%. In symmetrical chloride solutions there was no outward rectification of whole cell current. Activation rates and peak currents elicited by rapid application of GABA to macropatches were also similar at positive and negative holding potentials. However, deactivation of GABAA receptor currents was slower at positive holding potentials. When whole cell currents were recorded without ATP in the pipette, current run-down was not apparent for 30 min in 50% of neurons, but run-down appeared to start soon after access was established in the remaining neurons. When 2 mM ATP was included in the recording pipette no run-down was apparent in 30 min of recording. The efficacy and potency of GABA were lower in cells recorded with no ATP in the pipette and during run-down compared with those recorded with 2 mM ATP and no run-down.
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Giro Dentado/metabolismo , Neuronas/metabolismo , Receptores de GABA-A/fisiología , Adenosina Trifosfato/farmacología , Animales , Giro Dentado/citología , Giro Dentado/efectos de los fármacos , Conductividad Eléctrica , Electrofisiología , Femenino , Masculino , Neuronas/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Receptores de GABA-A/efectos de los fármacos , Ácido gamma-Aminobutírico/farmacologíaRESUMEN
1. To determine their contributions to the rapid kinetic properties of GABAA receptor (GABAR) currents, alpha1 and beta3 subunit subtypes without or with delta or gamma2L subtypes were transiently coexpressed in mouse L929 fibroblasts to produce alpha1beta3, alpha1beta3delta, or alpha1beta3gamma2L GABAR isoforms. 2. Brief (2-3 ms) applications of 1 mM GABA to outside-out membrane patches containing alpha1beta3, alpha1beta3delta, or alpha1beta3gamma2L isoforms elicited currents that activated rapidly with monophasic time courses and deactivated rapidly with biphasic time courses. alpha1beta3gamma2L currents exhibited a slower mean deactivation rate (76.1 ms) than alpha1beta3 (34.1 ms) or alpha1beta3delta currents (42.8 ms). 3. During 1 mM GABA applications, alpha1beta3gamma2L currents activated more rapidly (0.46 ms) than alpha1beta3 currents (1.7 ms) or alpha1beta3delta currents (2.4 ms). During 4000 ms GABA applications, alpha1beta3 and alpha1beta3gamma2L currents desensitized with triphasic time courses to similar extents (alpha1beta3, 94.6 %; alpha1beta3gamma2L, 92.4 %) and with similar mean rates (alpha1beta3, 352 ms; alpha1beta3gamma2L, 462 ms). In contrast, alpha1beta3delta currents desensitized only 55.6 % with a biphasic time course and slower mean rate (1260 ms). 4. These experiments demonstrated that the alpha1beta3 heterodimer formed a GABAR channel with rapid deactivation and rapid and nearly complete desensitization. Addition of the delta subunit did not alter the activation rate, but produced a receptor with slower and less complete desensitization. Addition of the gamma2L subtype increased activation rate, prolonged deactivation and changed the pattern of rapid desensitization. 5. Rapid kinetic and steady-state single-channel data were used to construct kinetic models that predicted the behaviour of the alpha1beta3gamma2L and alpha1beta3delta currents. These models represent a reconciliation of macroscopic and steady-state single-channel data for GABARs and provide a framework for systematically assessing the functional significance of different GABAR isoforms.
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Activación del Canal Iónico/fisiología , Receptores de GABA-A/genética , Receptores de GABA-A/metabolismo , Animales , Relación Dosis-Respuesta a Droga , Fibroblastos/química , Fibroblastos/fisiología , Activación del Canal Iónico/efectos de los fármacos , Isomerismo , Cinética , Ratones , Modelos Químicos , Técnicas de Placa-Clamp , Receptores de GABA-A/química , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transfección , Ácido gamma-Aminobutírico/farmacologíaRESUMEN
Poly(L-lactic acid) (PLLA) monofilaments were evaluated for use as intravascular polymeric stents. The PLLA monofilaments were extruded and drawn to different draw ratios. They were then subjected to different thermal treatments and their mechanical properties characterized. Stents constructed with similar monofilaments were tested under hydrostatic pressure, and the results correlated with the properties of the monofilaments. Stent collapse pressure was a decreasing function of stent diameter and filament draw ratio.