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1.
Gesundheitswesen ; 77(1): 16-23, 2015 Jan.
Artículo en Alemán | MEDLINE | ID: mdl-24566836

RESUMEN

INTRODUCTION: After the hospital discharge of older patients with multiple morbidities, GPs are often faced with the task of prioritising the patients' drug regimens so as to reduce the risk of overmedication. AIM: How do GPs prioritise such medications in multimorbid elderly patients at the transition between inpatient and home care? The experience by the GPs is documented in typical case vignettes. METHOD: 44 GPs in Sachsen-Anhalt were recruited--they were engaged in focus group discussions and interviewed using semi-standardised questionnaires. Typical case vignettes were developed, relevant to the everyday care that elderly patients would typically receive from their GPs with respect to their drug optimisation. RESULTS: According to the results of the focus groups, the following issues affect GPs' decisions: drug and patient safety, their own competence in the health system, patient health literacy, evidence base, communication between secondary and primary care (and their respective influences on each other). When considering individual cases, patient safety, patient wishes, and quality of life were central. This is demonstrated by the drug dispositions of one exemplary case vignette. CONCLUSIONS: GPs do prioritise drug regimens with rational criteria. Initial problem delineation, process documentation and the design of a transferable product are interlinking steps in the development of case vignettes. Care issues of drug therapy in elderly patients with multiple morbidities should be investigated further with larger representative samples in order to clarify whether the criteria used here are applied contextually or consistently. Embedding case vignettes into further education concepts is also likely to be useful.


Asunto(s)
Atención Ambulatoria/estadística & datos numéricos , Médicos Generales/estadística & datos numéricos , Asignación de Recursos para la Atención de Salud/estadística & datos numéricos , Prioridades en Salud/estadística & datos numéricos , Mal Uso de los Servicios de Salud/prevención & control , Prescripciones/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Recolección de Datos , Toma de Decisiones , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Femenino , Alemania , Asignación de Recursos para la Atención de Salud/métodos , Servicios de Salud para Ancianos/estadística & datos numéricos , Servicios de Atención de Salud a Domicilio , Humanos , Masculino , Administración del Tratamiento Farmacológico/estadística & datos numéricos , Persona de Mediana Edad , Alta del Paciente/estadística & datos numéricos , Transferencia de Pacientes/estadística & datos numéricos
2.
J Obstet Gynaecol ; 33(8): 798-801, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24219716

RESUMEN

Postpartum haemorrhage is an infrequent but potentially life-threatening obstetrical emergency amenable to simulation. An educational programme consisting of a lecture and high-fidelity simulation exercise was given to incoming obstetrics and gynaecology (OB) and family medicine (FM) residents. Residents reported pre- and post-intervention confidence scores on a 1-5 Likert scale and a subset completed a postpartum haemorrhage knowledge assessment. Residents reported significant improvements in confidence in parameters involved in diagnosis and management of postpartum haemorrhage. The postpartum haemorrhage test mean scores significantly increased (57.4 ± 9.6% vs 77.1 ± 7.9%, p < 0.01) and were significantly correlated to confidence scores (Spearman's coefficient of 0.651, p < 0.001). In conclusion, an education programme that incorporates high-fidelity simulation of postpartum haemorrhage improves the confidence and knowledge of incoming residents and appears to be an effective educational approach.


Asunto(s)
Obstetricia/educación , Hemorragia Posparto/terapia , Competencia Clínica , Femenino , Humanos , Internado y Residencia/estadística & datos numéricos , Simulación de Paciente , Embarazo
3.
Endocrinology ; 147(10): 4968-76, 2006 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16794011

RESUMEN

Ulcerative colitis is a multifactorial disease, with immunological, genetic, and environmental factors playing an important role in its pathogenesis. Here we investigated the consequences of exposure to chronic psychosocial stress on the severity of a dextran sulfate sodium (DSS)-induced colitis in male C57BL/6 mice. Chronic stress was induced by repeated exposure to social defeat (SD, 2 h) and overcrowding (OC, 24 h) during 19 consecutive days. SD/OC mice showed a diminished body weight gain, thymus-atrophy, and adrenal hypertrophy, but similar light-phase plasma corticosterone concentrations, compared with unstressed mice. In contrast, the rise in dark-phase corticosterone concentration was significantly attenuated in SD/OC mice, whereas plasma ACTH concentrations and hypothalamic CRH mRNA expression did not differ between stressed and nonstressed groups. Additionally, adrenal cells from SD/OC mice showed a decreased in vitro response to ACTH stimulation. Subsequent treatment with 1% DSS for 7 d resulted in a more severe intestinal inflammation in SD/OC mice, as reflected by an increase in body weight loss, histological damage scores, and secretion of IL-6, TNFalpha, and interferon-gamma from mesenteric lymph node cells and by decreased colon length. The impaired health status of stressed mice was also reflected by a significantly lower survival rate after termination of the DSS treatment. In conclusion, the present findings demonstrate that chronic intermittent exposure to a psychosocial stressor before the induction of acute DSS-colitis results in adrenal insufficiency, increases in the severity of the acute inflammation, and impairs the healing phase.


Asunto(s)
Colitis/inducido químicamente , Colitis/prevención & control , Aglomeración/psicología , Sulfato de Dextran , Regeneración/fisiología , Predominio Social , Estrés Psicológico/fisiopatología , Enfermedad Aguda , Glándulas Suprarrenales/anatomía & histología , Glándulas Suprarrenales/crecimiento & desarrollo , Hormona Adrenocorticotrópica/sangre , Animales , Corticosterona/sangre , Hormona Liberadora de Corticotropina/metabolismo , Citocinas/metabolismo , Sistema Hipotálamo-Hipofisario/fisiología , Hipotálamo/metabolismo , Ganglios Linfáticos/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Sistema Hipófiso-Suprarrenal/fisiología , ARN Mensajero/biosíntesis , Estrés Psicológico/psicología , Timo/anatomía & histología , Timo/crecimiento & desarrollo
4.
Anat Embryol (Berl) ; 210(5-6): 525-37, 2005 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-16180018

RESUMEN

Recent advances in our understanding of the basic mechanisms of epilepsy have derived, to a large extent, from increasing ability to carry out detailed studies on patients surgically treated for intractable epilepsy. Clinical and experimental perioperative studies divide into three different phases: before the surgical intervention (preoperative studies), on the intervention itself (intraoperative studies), and on the period when the part of the brain that has to be removed is available for further investigations (postoperative studies). Before surgery, both structural and functional neuroimaging techniques, in addition to their diagnostic roles, could be used to investigate the pathophysiological mechanisms of seizure attacks in epileptic patients. During epilepsy surgery, it is possible to insert microdialysis catheters and electroencephalogram electrodes into the brain tissues in order to measure constituents of extracellular fluid and record the bioelectrical activity. Subsequent surgical resection provides tissue that can be used for electrophysiological, morphological, and molecular biological investigations. To take full advantage of these opportunities, carefully designed experimental protocols are necessary to compare the data from different phases and characterize abnormalities in the human epileptic brain.


Asunto(s)
Encéfalo/patología , Encéfalo/fisiopatología , Epilepsia/cirugía , Encéfalo/cirugía , Electroencefalografía , Epilepsia/patología , Epilepsia/fisiopatología , Humanos , Microdiálisis
5.
Neuroreport ; 15(7): 1141-4, 2004 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-15129162

RESUMEN

Reduction of the melanin precursor DOPA associated with albinism leads to spatiotemporal disturbances in retinal neurogenesis and thus seems to be responsible for numerous neuronal alterations found in albino retinae. To investigate whether these cellular alterations are reflected in retinal neurotransmitter concentrations we compared the levels of GABA and glutamate in the retina of adult pigmented Long Evans and albino Wistar rats using reversed phase-liquid chromatography (RP-HPLC). When normalized to retinal weight, GABA levels showed a statistically insignificant trend to be lower and glutamate values to be higher in albinos than in pigmented animals. The ratio of glutamate to GABA was significantly higher in albino than in pigmented retinae. As numerous studies have shown that the balance between GABA and glutamate plays a crucial role for establishing direction selectivity, these results are discussed in relation to direction selectivity and defects in the optokinetic system of albinos.


Asunto(s)
Albinismo/genética , Albinismo/metabolismo , Retina/metabolismo , Ácido gamma-Aminobutírico/genética , Ácido gamma-Aminobutírico/metabolismo , Animales , Femenino , Ácido Glutámico/genética , Ácido Glutámico/metabolismo , Masculino , Ratas , Ratas Long-Evans , Ratas Wistar , Especificidad de la Especie
6.
J Neurosci Res ; 75(6): 807-16, 2004 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-14994341

RESUMEN

A-type currents powerfully modulate discharge behavior and have been described in a large number of different species and cell types. However, data on A-type currents in human brain tissue are scarce. Here we have examined the properties of a fast transient outward current in acutely dissociated human neocortical neurons from the temporal lobe of epilepsy patients by using the whole-cell voltage-clamp technique. The A-type current was isolated with a subtraction protocol. In addition, delayed potassium currents were reduced pharmacologically with 10 mM tetraethylammonium chloride. The current displayed an activation threshold of about -70 mV. The voltage-dependent activation was fitted with a Boltzmann function, with a half-maximal conductance at -14.8 +/- 1.8 mV (n = 5) and a slope factor of 17.0 +/- 0.5 mV (n = 5). The voltage of half-maximal steady-state inactivation was -98.9 +/- 8.3 mV (n = 5), with a slope factor of -6.6 +/- 1.9 mV (n = 5). Recovery from inactivation could be fitted monoexponentially with a time constant of 18.2 +/- 7.5 msec (n = 5). At a command potential of +30 mV, application of 5 mM 4-aminopyridine or 100 microM flecainide resulted in a reduction of A-type current amplitude by 35% or 22%, respectively. In addition, flecainide markedly accelerated inactivation. Current amplitude was reduced by 31% with application of 500 microM cadmium. All drug effects were reversible. In conclusion, neocortical neurons from epilepsy patients express an A-type current with properties similar to those described for animal tissues.


Asunto(s)
Epilepsia/fisiopatología , Neocórtex/patología , Neuronas/fisiología , Valina/análogos & derivados , Adolescente , Adulto , Anestésicos Locales/farmacología , Antiarrítmicos/farmacología , Cadmio/farmacología , Preescolar , Femenino , Flecainida/farmacología , Humanos , Técnicas In Vitro , Masculino , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Persona de Mediana Edad , Técnicas de Placa-Clamp/métodos , Bloqueadores de los Canales de Potasio/farmacología , Canales de Potasio/fisiología , Tetraetilamonio/farmacología , Tetrodotoxina/farmacología , Valina/farmacología
7.
Neuroscience ; 121(3): 587-604, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-14568020

RESUMEN

Stimulus-induced pattern of bioelectric activity in human neocortical tissue was investigated by use of the voltage sensitive dye RH795 and a fast optical recording system. During control conditions stimulation of layer I evoked activity predominantly in supragranular layers showing a spatial extent of up to 3000 microm along layer III. Stimulation in white matter evoked distinct activity in infragranular layers with a spatial extent of up to 3000 microm measured along layer V. The mean amplitude of optical signals close to the stimulated sites in layer I and white matter determined 25 ms following the stimulus, decreased by 50% at a lateral distance of approximately 900 microm and 1200 microm, respectively. Velocity of spread along the vertical stimulation axis reached 0.24 m/s in the supragranular layers (layers I to III) and then decreased to 0.09 m/s following layer I activation; stimulation of white matter induced a velocity of spread in layer V of 0.38 m/s, which slowed down to 0.12 m/s when passing the lower border of lamina IV. The horizontal velocities of spread determined from the stimulation site to a lateral distance of 500 microm reached 0.26-0.28 m/s and 0.28-0.35 m/s for layer I and white matter stimulation, respectively. At larger distances velocity of spread decreased. Increased excitability (Mg(2+)-free solution) had no significant effect on the spatio-temporal distribution of evoked activity as compared with control conditions. There were also no obvious differences between the results obtained in slices, which generated spontaneously sharp waves and those which were not spontaneously active. About 30% of the slices (n=7) displayed a greatly different response pattern, which seemed not to be related in a simple way to the stimulation as was the case in the majority of the investigated slices. The activity pattern of those slices appeared atypical in regard to their deviations of the vertical and horizontal extent of activity, to their reduced spatial extent of activity during increased excitability, to their layer-related distribution of activity, and to the appearance of afterdischarges.Concluding, in 30% of the human temporal lobe slices atypical activity pattern occurred which obviously reflect intrinsic epileptiform properties of the resected tissue. The majority of slices showed stereotyped activity pattern without evidence for increased excitability.


Asunto(s)
Potenciales Evocados/fisiología , Neocórtex/fisiología , Adolescente , Adulto , Mapeo Encefálico , Niño , Preescolar , Diagnóstico por Imagen/métodos , Relación Dosis-Respuesta en la Radiación , Conductividad Eléctrica , Estimulación Eléctrica , Electrofisiología , Epilepsia del Lóbulo Temporal/metabolismo , Epilepsia del Lóbulo Temporal/fisiopatología , Epilepsia del Lóbulo Temporal/cirugía , Femenino , Colorantes Fluorescentes/farmacocinética , Humanos , Técnicas In Vitro , Magnesio/metabolismo , Masculino , Persona de Mediana Edad , Neocórtex/anatomía & histología , Neocórtex/metabolismo , Tiempo de Reacción , Estirenos/farmacocinética , Factores de Tiempo
8.
Brain Res ; 975(1-2): 129-34, 2003 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-12763600

RESUMEN

Spreading depression (SD) is characterized by a transient breakdown of neuronal function concomitant with a massive failure of ion homeostasis. It is a phenomenon that can be induced in neocortical tissue by raising excitability, e.g. injection of K(+), application of glutamatergic agonists, or blocking Na(+)/K(+) ATPase. Here we report a novel method of SD induction using minimal disinhibition with application of low concentrations (5 microM) of the GABA(A) receptor blocker bicuculline. This procedure-while subthreshold for epileptiform activity-readily induced spontaneous SDs in native rat neocortical slices, accompanied by typical depolarizations of neurons and glial cells. In contrast, in human neocortical preparations obtained from epilepsy surgery, in approximately 20% of the slices spontaneous epileptiform activity appeared with this bicuculline dosage without SDs. Raising the concentration of bicuculline to an epileptogenic dose (10 microM) in human tissue also resulted in the generation of epileptiform activity only. Likewise, in slices from pilocarpine-treated, chronically epileptic rats, bicuculline also only induced epileptiform activity without eliciting SDs. The experiments indicate that chronic epilepsy causes a differential sensitivity to partial GABA(A) receptor blockade with regard to induction of SD.


Asunto(s)
Depresión de Propagación Cortical/fisiología , Epilepsia/fisiopatología , Neocórtex/fisiología , 2-Amino-5-fosfonovalerato/farmacología , Animales , Bicuculina/farmacología , Enfermedad Crónica , Relación Dosis-Respuesta a Droga , Estimulación Eléctrica , Epilepsia/inducido químicamente , Antagonistas del GABA/farmacología , Humanos , Técnicas In Vitro , Potenciales de la Membrana/efectos de los fármacos , Microelectrodos , Neuroglía/efectos de los fármacos , Neuroglía/fisiología , Neuronas/efectos de los fármacos , Neuronas/fisiología , Parasimpaticomiméticos/farmacología , Pilocarpina/farmacología , Ratas , Receptores de GABA-A/efectos de los fármacos , Receptores de N-Metil-D-Aspartato/efectos de los fármacos
9.
Brain Res ; 908(2): 130-9, 2001 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-11454323

RESUMEN

Extra- and intracellular recording techniques were used to study the epileptiform activity generated by guinea-pig hippocampal slices perfused with low potassium containing artificial cerebrospinal fluid. Extracellular field potentials were recorded in CA1 and CA3 regions along with intracellular recordings in CA3 subfield. Reduction of the extracellular potassium concentration [K(+)](o) from 4 to 2 mM caused a transient neuronal hyperpolarisation which was followed by a repolarisation and subsequent depolarisation period. Paroxysmal depolarisation shifts occurred during the transient hyperpolarisation period while epileptic field potentials (EFP) appeared in the late repolarisation or early depolarisation phase. EFP elicited by reduction of [K(+)](o) were neither affected by blockade of N-methyl-D-aspartate (NMDA) glutamate-subreceptor or gamma aminobutyric acid receptor, nor by application of the organic calcium channel blocker nifedipine or the anticonvulsant drugs carbamazepine and valproic acid. Upon application of non-NMDA glutamate-subreceptor blocker the EFP were abolished in all trials, while application of the organic calcium channel blocker verapamil only suppressed the EFP in some cases. The results point to a novel mechanism of epileptogenesis and may provide an in vitro model for the development of new drugs against difficult-to-treat epilepsy.


Asunto(s)
Epilepsia/metabolismo , Espacio Extracelular/metabolismo , Hipocampo/metabolismo , Potenciales de la Membrana/fisiología , Neuronas/metabolismo , Deficiencia de Potasio/metabolismo , Potasio/metabolismo , Animales , Anticonvulsivantes/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio Tipo L/efectos de los fármacos , Canales de Calcio Tipo L/metabolismo , Epilepsia/fisiopatología , Antagonistas de Aminoácidos Excitadores/farmacología , Espacio Extracelular/efectos de los fármacos , Antagonistas del GABA/farmacología , Cobayas , Hipocampo/efectos de los fármacos , Hipocampo/fisiopatología , Potenciales de la Membrana/efectos de los fármacos , Neuronas/efectos de los fármacos , Técnicas de Cultivo de Órganos , Deficiencia de Potasio/fisiopatología , Receptores de GABA/efectos de los fármacos , Receptores de GABA/metabolismo , Receptores de Glutamato/efectos de los fármacos , Receptores de Glutamato/metabolismo
10.
Brain Res ; 906(1-2): 74-83, 2001 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-11430863

RESUMEN

Cortical spreading depression (CSD) occurrence has been suggested to be associated with seizures, migraine aura, head injury and brain ischemia-infarction. Only few studies identified CSD in human neocortical slices and no comprehensive study so far evaluated this phenomenon in human. Using the neocortical tissue excised for treatment of intractable epilepsy, we aimed to investigate CSD in human. CSD was induced by KCl injection and by modulating T-type Ca(2+) currents in incubated human neocortical tissues in an interphase mode. The DC-fluctuations were recorded by inserting microelectrodes into different cortical layers. Local injection of KCl triggered single CSD that propagated at 3.1+/-0.1 mm/min. Repetitive CSD also occurred spontaneously during long lasting application (5 h) of the T-type Ca(2+) channel blockers amiloride (50 microM) or NiCl(2) (10 microM) which was concomitant with a reversible extracellular potassium increase up to 50 mM. CSD could be blocked by the N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonovaleric acid in all cases. The results demonstrate that modulation of the Ca(2+) dynamics conditioned human neocortical slices and increased their susceptibility to generate CSD. Furthermore, these data indicate that glutamatergic pathway plays a role in CSD phenomenon in human.


Asunto(s)
Depresión de Propagación Cortical/fisiología , Epilepsia/metabolismo , Neocórtex/metabolismo , Neuronas/metabolismo , Adolescente , Adulto , Amilorida/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio/efectos de los fármacos , Canales de Calcio/metabolismo , Señalización del Calcio/efectos de los fármacos , Señalización del Calcio/fisiología , Niño , Depresión de Propagación Cortical/efectos de los fármacos , Diuréticos/farmacología , Epilepsia/inducido químicamente , Epilepsia/fisiopatología , Antagonistas de Aminoácidos Excitadores/farmacología , Femenino , Ácido Glutámico/metabolismo , Humanos , Masculino , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Persona de Mediana Edad , Neocórtex/efectos de los fármacos , Neocórtex/fisiopatología , Neuronas/efectos de los fármacos , Níquel/farmacología , Potasio/metabolismo , Cloruro de Potasio/farmacología , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/metabolismo
11.
Epilepsy Res ; 44(2-3): 155-65, 2001 May.
Artículo en Inglés | MEDLINE | ID: mdl-11325571

RESUMEN

The antiepileptic effects of the novel antiepileptic drug retigabine (D-23129) [N-(2-amino-4-(4-flurobenzylamino)phenyl) carbamid acid ethyl ester] were tested in neocortical slice preparations (n=23) from 17 patients (age, 3-42 years) who underwent surgery for the treatment of intractable epilepsy. Epileptiform events consisted of spontaneously occurring rhythmic sharp waves, as well as of epileptiform field potentials (EFP) elicited by superfusion with Mg(2+)-free solution without or with addition of 10 micromol/l bicuculline. (1) Spontaneous rhythmic sharp waves (n=6), with retigabine application, the repetition rate was decreased down to 12-47% of initial value (10 micromol/l, n=3) after 180 min or suppressed completely within 12 min (50 micromol/l, n=3). (2) Low Mg(2+) EFP (n=9), with retigabine application, the repetition rate was decreased down to 50 and 65% of initial value (10 micromol/l; n=2) after 180 min or suppressed completely after 9-55 min (10, 50 and 100 micromol/l; n=2 in each case). In one slice only a transient reduction of the repetition rate was seen with 10 micromol/l retigabine. (3) Low Mg(2+) EFP with addition of bicuculline (n=8), with retigabine application, the repetition rate was decreased down to 12-55% of initial value (10 micromol/l; n=4) after 180 min or suppressed completely after 6-30 min (50 and 100 micromol/l; n=2 in each case). The depressive effect of retigabine was reversible in all but one slice. The results show a clear antiepileptic effect of retigabine in human neocortical slices on spontaneously occurring rhythmic sharp waves and different types of induced seizure activity.


Asunto(s)
Potenciales de Acción/efectos de los fármacos , Anticonvulsivantes/farmacología , Carbamatos/farmacología , Neocórtex/efectos de los fármacos , Fenilendiaminas/farmacología , Potenciales de Acción/fisiología , Adolescente , Adulto , Anticonvulsivantes/uso terapéutico , Bicuculina/farmacología , Carbamatos/uso terapéutico , Niño , Preescolar , Epilepsias Parciales/tratamiento farmacológico , Epilepsias Parciales/patología , Femenino , Antagonistas del GABA/farmacología , Humanos , Magnesio/farmacología , Masculino , Neocórtex/fisiología , Fenilendiaminas/uso terapéutico
12.
Eur J Neurosci ; 13(3): 639-40, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11168573

RESUMEN

The increase in the extracellular potassium concentration ([K(+)](o)) is a well-established model of epilepsy (the so-called high potassium model). Therefore, it is generally accepted that for the prevention of abnormal excitability and seizure generation, increases of [K(+)](o) must be avoided. In this paper, however, we show that on the contrary, a reduction of [K(+)](o) also elicits epileptic activity in brain slices of man.


Asunto(s)
Epilepsia Parcial Compleja/fisiopatología , Epilepsia Generalizada/fisiopatología , Neocórtex/fisiopatología , Potasio/farmacología , Adolescente , Adulto , Niño , Preescolar , Epilepsia Parcial Compleja/inducido químicamente , Epilepsia Parcial Compleja/metabolismo , Epilepsia Generalizada/inducido químicamente , Epilepsia Generalizada/metabolismo , Espacio Extracelular/metabolismo , Femenino , Humanos , Técnicas In Vitro , Lactante , Masculino , Persona de Mediana Edad , Neocórtex/metabolismo
13.
Neuroscience ; 100(3): 445-52, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-11098107

RESUMEN

The antiepileptic effect of the dihydropyridine calcium channel blocker nifedipine was tested in neocortical slice preparations (n=27) from patients ranging in age from four to 46 years (mean=25) who underwent surgery for the treatment of intractable epilepsy. Epileptiform events consisted of spontaneously occurring rhythmic sharp waves as well as of untriggered epileptiform field potentials induced by omission of Mg(2+) from the superfusate, or epileptiform field potentials elicited by application of bicuculline and triggered by single electrical stimuli. (1) Spontaneous rhythmic sharp waves (n=6): with nifedipine (40micromol/l), the repetition rate was decreased down to 30% of initial value, whereas the area under the field potential remained nearly unchanged. (2) Untriggered low Mg(2+) epileptiform field potentials (n=6): with nifedipine (40micromol/l) the area under the field potentials was reduced while the action on the repetition rate was ambiguous. (3) Triggered bicuculline epileptiform field potentials (n=15): with nifedipine (40micromol/l; n=4), no antiepileptic effect was found. There was, however, a marked increase in the area under the epileptiform field potentials. The area under the field potentials was reduced only at a dosage of 60micromol/l (n=11). This effect was stronger when nifedipine was applied with a K(+) concentration raised from 4 to 8mmol/l. The results show that the calcium channel blocker nifedipine is able to reduce differential epileptiform discharges in human neocortical tissue. These observations are in line with previous findings, suggesting that calcium flux into neurons is involved in epileptogenesis. The present results therefore support the idea that some organic calcium antagonists may be useful in human epilepsy therapy, although the etiology of epileptic seizures seems to be a critical factor for the efficacy of the drug.


Asunto(s)
Bloqueadores de los Canales de Calcio/farmacología , Neocórtex/fisiología , Nifedipino/farmacología , Periodicidad , Adolescente , Bicuculina , Niño , Preescolar , Convulsivantes , Relación Dosis-Respuesta a Droga , Electrofisiología , Epilepsia/inducido químicamente , Epilepsia/fisiopatología , Humanos , Técnicas In Vitro , Lactante , Recién Nacido , Magnesio/administración & dosificación
14.
J Neurophysiol ; 84(4): 2161-5, 2000 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11024103

RESUMEN

Functional changes in neuronal circuitry reflected in spontaneously occurring synchronous sharp field potentials (SSFP) have been reported to occur in human brain suffering from chronic epileptogenicity but not in primary nonepileptic tissue from peritumoral resectates. Voltage sensitive dyes and fast imaging were used to visualize spontaneously occurring rhythmic depolarizations correlated to SSFP in chronically epileptic human neocortical slices obtained during epilepsy surgery. Localized and spatially inhomogeneous neuronal depolarizations were found to underlie spontaneous SSFP, which remained unchanged and spatially restricted to foci <750 micrometer diam even under epileptogenic (low-Mg(2+)) conditions. In cases where ictaform paroxysmal activity occurred in low-Mg(2+) medium, neuronal depolarizations were wide-spread but still spatially inhomogeneous, and the events were preferentially initiated at distinct foci. The findings suggest that small neuronal networks are able to establish and maintain synchronous rhythmic and epileptiform activity.


Asunto(s)
Epilepsia/fisiopatología , Neocórtex/fisiopatología , Neuronas/fisiología , Potenciales de Acción , Enfermedad Crónica , Relación Dosis-Respuesta a Droga , Epilepsia/patología , Humanos , Técnicas In Vitro , Magnesio/administración & dosificación , Magnesio/farmacología , Neocórtex/efectos de los fármacos , Neocórtex/patología , Red Nerviosa/fisiopatología , Óptica y Fotónica , Periodicidad
15.
J Neurosci Methods ; 102(1): 1-9, 2000 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-11000406

RESUMEN

Living brain slices are usually cut with razor blades, which compress a ca. 50-microm-thick layer of tissue. This results in cell debris and lesioned cells which, e.g. form diffusion barriers between the bath and living neurons underneath, thereby prolonging response times of neurons to drugs in the bath saline and impeding the experimental access to intact neurons. To avoid such drawbacks, a macromingotome was developed which cuts nervous tissue with water jets. Physiological saline under pressures of 100-1800 bar was ejected through nozzles of 35-100 microm to cut 300-500-microm-thick hippocampal slices. Systematic variations of pressure and nozzle diameter revealed best results at 400-600 bar and with nozzle diameters of 60-80 microm. Under these conditions, intact CA1- and CA3-neurons as well as granule cells were detected with infrared microscopy at less than 10 microm underneath the surface of the slice. Superficial neurons with intact fine structures were also seen when the slices were studied by light-microscopy. Intra- and extracellular recordings from superficial neurons showed normal membrane- and full action potentials and the development of stable epileptiform discharges in 0 Mg(2+)-saline. These results indicate that the macromingotome offers an alternative way of cutting slices which may facilitate electrophysiological/neuropharmacological or fluorometric studies on superficial neurons.


Asunto(s)
Técnicas de Cultivo/métodos , Hipocampo/citología , Microtomía/instrumentación , Microtomía/métodos , Presión , Agua , Potenciales de Acción/fisiología , Animales , Cobayas , Hipocampo/fisiología , Neuronas/citología , Neuronas/fisiología , Ratas
16.
Neurobiol Dis ; 7(4): 471-82, 2000 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10964616

RESUMEN

Organic calcium channel antagonists block epileptiform activity in adult tissue, suggesting an essential role of L-type channels in epileptogenesis in the mature CNS. By contrast, this remains doubtful for neonatal tissue, as the density of calcium channels changes markedly with ontogenesis. The paper addresses this question by exploring the antiepileptic efficacy of the L-type calcium channel blockers verapamil and nifedipine in low-Mg(2+)-epilepsy in rat hippocampal slices of different postnatal (PN) ages. Field (CA3, CA1) and membrane potentials (CA3) were recorded. Washout of Mg(2+) induced epileptiform potentials, which were blocked age-dependently: Verapamil suppressed activity in all preparations of PN1-5 and PN13-30+, but only in 70% of PN6-12. Nifedipine depressed activity in >75% of slices of PN13-30+, but only in 33% of PN1-12. The findings indicate a role of L-type calcium channels in epileptogenesis from PN13 onwards, with phenylalkylamine-sensitive calcium channels also being involved during PN1-5.


Asunto(s)
Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio Tipo L/efectos de los fármacos , Epilepsia , Potenciales de la Membrana/efectos de los fármacos , Nifedipino/farmacología , Verapamilo/farmacología , Factores de Edad , Animales , Animales Recién Nacidos , Bloqueadores de los Canales de Calcio/uso terapéutico , Canales de Calcio Tipo L/fisiología , Epilepsia/tratamiento farmacológico , Hipocampo/efectos de los fármacos , Hipocampo/fisiología , Potenciales de la Membrana/fisiología , Nifedipino/uso terapéutico , Células Piramidales/efectos de los fármacos , Células Piramidales/fisiología , Ratas , Verapamilo/uso terapéutico
17.
Neuroscience ; 95(1): 63-72, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-10619462

RESUMEN

The aim of the present investigation was to compare the antiepileptic efficacy of the specific L-type calcium channel blocker nifedipine in hippocampal and neocortical slice preparations in the Mg2+-free model of epilepsy. The main findings were as follows. (1) In hippocampal slices, in general, nifedipine (20-80 micromol/l) exerted a suppressive effect both on repetition rate and on area under epileptiform field potentials. This effect was clearly dose dependent. In the majority of cases, this suppression was preceded by an increase, which was transient in nature. Only in the lowest concentration (20 micromol/l) used, in normal K+, instead of a depression, a persistent increase occurred. (2) In neocortical slices, in the majority of experiments, nifedipine (20-80 micromol/l) showed a depressive action only on the area under the epileptiform field potentials. The depressive effect of nifedipine on the area was dose dependent, although to a lesser extent than in the hippocampus. In nearly half of the slices this suppression was preceded by a transient increase. By contrast, the repetition rate of epileptiform field potentials increased transiently in about 20% of the slices followed by a decrease. In the remaining 80% of the slices the repetition rate increased persistently. (3) An elevation of the K+ concentration accentuated the depressive actions of nifedipine only in the hippocampus. In contrast to elevated K+, in both the hippocampus and the neocortex, epileptiform field potentials were not suppressed in all experiments in normal K+. (4) The reversibility of the depressive effects of nifedipine was differential in the two tissue types. In the hippocampus, after suppression of epileptiform field potentials they reappeared in the overwhelming majority of slices. In the neocortex, this was the case in only one experiment. These findings may indicate the existence of L-type calcium channels with a differential functional significance for epileptogenesis and/or the existence of different forms of L-type channels in hippocampal and neocortical tissue. As a whole, the differential effects of L-type calcium channel blockade in the hippocampus and neocortex point to differences in the network properties of the two tissue types.


Asunto(s)
Canales de Calcio Tipo L/fisiología , Epilepsia/fisiopatología , Hipocampo/fisiopatología , Neocórtex/fisiopatología , Animales , Bloqueadores de los Canales de Calcio/farmacología , Relación Dosis-Respuesta a Droga , Femenino , Cobayas , Hipocampo/efectos de los fármacos , Técnicas In Vitro , Masculino , Neocórtex/efectos de los fármacos , Nifedipino/farmacología
18.
Cephalalgia ; 20(8): 740-7, 2000 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11167905

RESUMEN

Spreading depressions (SD) occur in association with ischaemia, epilepsy and migraine. Intracellular calcium oscillations have been suggested to be involved in the generation and propagation of SD. The present study was performed to study the mechanism of conditioning guinea pig hippocampal slices by the T-type calcium channel blockers NiCl2 and amiloride. SD-like fluctuations of DC potential were recorded by inserting microelectrodes into the CA1 and CA3 regions. The SD occurrence was significantly greater with 10 micromol/l NiCl2 as well as with 25 and 50 micromol/l amiloride than with other concentrations of these substances. The concentration response curve was inversely U-shaped with the maximum repetition rates of SDs being achieved at 10 micromol/l NiCl2 as well as at 25 and 50 micromol/l amiloride. SD occurrence could be completely blocked by the NMDA antagonist APV (10 micromol/l) in all cases. These data demonstrate that modulation of the Ca2+ dynamics conditioned guinea pig hippocampal slices and increased their susceptibility to generate SD.


Asunto(s)
Amilorida/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Depresión de Propagación Cortical/fisiología , Hipocampo/efectos de los fármacos , Hipocampo/fisiología , Níquel/farmacología , Valina/análogos & derivados , Animales , Canales de Calcio Tipo T/efectos de los fármacos , Depresión de Propagación Cortical/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Electrofisiología , Cobayas , Técnicas In Vitro , N-Metilaspartato/antagonistas & inhibidores , Valina/farmacología
19.
Epilepsy Res ; 32(1-2): 224-32, 1998 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-9761323

RESUMEN

The spatio-temporal distribution of epileptiform activity was investigated in slices from human temporal neocortex resected during epilepsy surgery. Activity was recorded by use of a voltage-sensitive dye and an optical recording system. Epileptiform activity was induced with 10 microM bicuculline and electrical stimulation of layer I. In 10 slices from six patients investigated, epileptiform activity spread across most of the slice. Largest amplitudes were located in layer II/III. Epileptiform activity was characterized by long-lasting potentials with slow rising phases and a low velocity of spread in the horizontal direction (0.044 m/s). This spatio-temporal pattern of epileptiform activity in human slices was similar to that found previously in neocortical slices from guinea pigs with bicuculline. In four of nine human slices investigated under control bath conditions (in non-epileptogenic medium), the spatio-temporal activity patterns were similar to those of guinea pigs in non-epileptogenic medium. In the remaining five human slices, however, the spread in the horizontal direction was significantly larger (4188 microm) in non-epileptogenic medium than that found in slices from guinea pigs (2171 microm). Activity in human slices showing such 'wide spread' in control bath conditions occasionally had characteristic features of epileptiform activity. Further work will have to clarify whether these epileptiform features reflect intrinsic epileptiform properties in human tissue slices.


Asunto(s)
Mapeo Encefálico , Epilepsia del Lóbulo Temporal/fisiopatología , Potenciales Evocados/fisiología , Neocórtex/fisiopatología , Neuronas/fisiología , Animales , Bicuculina/farmacología , Colorantes , Estimulación Eléctrica , Epilepsia del Lóbulo Temporal/cirugía , Potenciales Evocados/efectos de los fármacos , Cobayas , Humanos , Técnicas In Vitro , Neocórtex/efectos de los fármacos , Neocórtex/fisiología , Neuronas/efectos de los fármacos
20.
MCN Am J Matern Child Nurs ; 23(5): 262-5, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-9747089

RESUMEN

In response to several women who presented with postpartum depression in 1 year, a group of nurses developed a task force made up of hospital nurses, obstetricians, psychiatrists, pediatricians, family practitioners, lactation specialists, home care nurses, and mental health counselors. The purposes of this task force were to educate health care professionals about postpartum depression, to help identify women who might be affected, and to develop interventions for adjusting to parenthood. This article details the evolution of that task force, and how it has assisted not only the women but also the health care providers involved.


Asunto(s)
Enfermería en Salud Comunitaria , Depresión Posparto/prevención & control , Educación en Salud/organización & administración , Grupo de Atención al Paciente , Participación de la Comunidad , Depresión Posparto/enfermería , Femenino , Humanos , Idaho
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