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1.
Oecologia ; 196(4): 1139-1152, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34331568

RESUMEN

Invasive species are a major cause of biodiversity loss worldwide, but their impact on communities and the mechanisms driving those impacts are varied and not well understood. This study employs functional diversity metrics and guilds-suites of species with similar traits-to assess the influence of an invasive tree (Tamarix spp.) on riparian plant communities in the southwestern United States. We asked: (1) What traits define riparian plant guilds in this system? (2) How do the abundances of guilds vary along gradients of Tamarix cover and abiotic conditions? (3) How does the functional diversity of the plant community respond to the gradients of Tamarix cover and abiotic conditions? We found nine distinct guilds primarily defined by reproductive strategy, as well as growth form, height, seed weight, specific leaf area, drought and anaerobic tolerance. Guild abundance varied along a covarying gradient of local and regional environmental factors and Tamarix cover. Guilds relying on sexual reproduction, in particular, those producing many light seeds over a long period of time were more strongly associated with drier sites and higher Tamarix cover. Tamarix itself appeared to facilitate more shade-tolerant species with higher specific leaf areas than would be expected in resource-poor environments. Additionally, we found a high degree of specialization (low functional diversity) in the wettest, most flood-prone, lowest Tamarix cover sites as well as in the driest, most stable, highest Tamarix cover sites. These guilds can be used to anticipate plant community response to restoration efforts and in selecting appropriate species for revegetation.


Asunto(s)
Ríos , Árboles , Biodiversidad , Especies Introducidas , Plantas
2.
Epilepsy Behav ; 20(2): 334-7, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21195032

RESUMEN

We describe 17 children with nocturnal or early-morning seizures who were switched to a proportionally higher evening dose of antiepileptic drugs and were retrospectively reviewed for seizure outcome and side effects. Of 10 children with unknown etiology, clinical presentation was consistent with nocturnal frontal lobe epilepsy (NFLE) in 5 and benign epilepsy with centrotemporal spikes (BECTS) in 3. After a mean follow-up of 5.3 months, 15 patients were classified as responders; 11 of these became seizure free (5 NFLE, 1 BECTS, 5 with structural lesions) and 4 (2 BECTS, 2 with structural lesions) experienced 75-90% reductions in seizures. Among two nonresponders, seizures in one had failed to resolve with epilepsy surgery. Nine subjects (53%) received monotherapy after dose modification, and none presented with worsening of seizures. Two complained of transient side effects (fatigue/somnolence). Differential dosing led to seizure freedom in 64.7% (11/17) of patients, and 88.2% (15/17) experienced ≥ 50% reductions in seizures.


Asunto(s)
Anticonvulsivantes/administración & dosificación , Cronoterapia de Medicamentos , Convulsiones/tratamiento farmacológico , Convulsiones/fisiopatología , Adolescente , Anticonvulsivantes/farmacocinética , Niño , Preescolar , Dietilcarbamazina/administración & dosificación , Dietilcarbamazina/farmacocinética , Relación Dosis-Respuesta a Droga , Electroencefalografía , Registros Electrónicos de Salud/estadística & datos numéricos , Femenino , Humanos , Lactante , Levetiracetam , Masculino , Piracetam/administración & dosificación , Piracetam/análogos & derivados , Piracetam/farmacocinética , Convulsiones/sangre , Estadísticas no Paramétricas , Resultado del Tratamiento
3.
Epilepsy Behav ; 20(2): 344-8, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21233024

RESUMEN

OBJECTIVE: The purpose of this study was to determine the safety and efficacy of rufinamide for treatment of epileptic spasms. METHODS: We retrospectively reviewed patients treated with rufinamide for epileptic spasms from January 2009 to March 2010. Age, presence of hypsarrhythmia, change in seizure frequency following rufinamide initiation, and side effects were assessed. Patients who had a ≥ 50% reduction in spasm frequency were considered responders. RESULTS: Of all 107 children treated with rufinamide during the study period, 38 (36%) had epileptic spasms. Median patient age was 7 years (range: 17 months to 23). One patient had hypsarrhythmia at the time of treatment with rufinamide, and 9 other patients had a history of hypsarrhythmia. Median starting dose of rufinamide was 9 mg/kg/day (range: 2-18) and median final treatment dose was 39 mg/kg/day (range: 8-92). All patients were receiving concurrent antiepileptic drug therapy, with the median number of antiepileptic drugs being 3 (range: 2-6). Median duration of follow-up since starting rufinamide was 171 days (range: 10-408). Responder rate was 53%. Median reduction in spasm frequency was 50% (interquartile range=-56 to 85%, P<0.05). Two patients (5%) achieved a >99% reduction in spasms. Rufinamide was discontinued in 7 of 38 patients (18%) because of lack of efficacy, worsening seizures, or other side effects. Minor side effects were reported in 14 of 38 patients (37%). CONCLUSIONS: Rufinamide appears to be a well-tolerated and efficacious adjunctive therapeutic option for children with epileptic spasms. A prospective study is warranted to validate our observations.


Asunto(s)
Anticonvulsivantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Espasmos Infantiles/tratamiento farmacológico , Triazoles/uso terapéutico , Adolescente , Niño , Preescolar , Electroencefalografía/métodos , Epilepsia/complicaciones , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Estudios Retrospectivos , Espasmos Infantiles/complicaciones , Resultado del Tratamiento , Adulto Joven
4.
Obes Rev ; 19(9): 1177-1188, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30035381

RESUMEN

Humans expend energy at rest (REE), and this major energy exchange component is now usually estimated using statistical equations that include weight and other predictor variables. While these formulas are useful in evaluating an individual's or group's REE, an important gap remains: available statistical models are inadequate for explaining underlying organ-specific and tissue-specific mechanisms accounting for resting heat production. The lack of such systems level REE prediction models leaves many research questions unanswered. A potential approach that can fill this gap began with investigators who first showed in animals and later in humans that REE reflects the summated heat production rates of individual organs and tissues. Today, using advanced imaging technologies, REE can be accurately estimated from the measured in vivo mass of 10 organ-tissue mass components combined with their respective mass-specific metabolic rates. This review examines the next frontier of energy expenditure models and discusses how organ-tissue models have the potential not only to better predict REE but also to provide insights into how perturbations in organ mass lead to structure-function changes across other interacting organ systems. The introductory ideas advanced in this review provide a framework for future human energy expenditure modelling research.


Asunto(s)
Metabolismo Basal/fisiología , Composición Corporal/fisiología , Metabolismo Energético/fisiología , Modelos Biológicos , Humanos
5.
AJNR Am J Neuroradiol ; 28(8): 1486-8, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17846196

RESUMEN

Distinguishing propagated epileptic activity from primary epileptic foci is of critical importance in presurgical evaluation of patients with medically intractable focal epilepsy. We studied an 11-year-old patient with complex partial epilepsy by using simultaneous magnetoencephalography (MEG) and electroencephalography (EEG). In EEG, bilateral interictal discharges appeared synchronous, whereas MEG source analysis suggested propagation of spikes from the right to the left frontal lobe.


Asunto(s)
Potenciales de Acción , Epilepsia Parcial Compleja/diagnóstico , Epilepsia Parcial Compleja/fisiopatología , Magnetoencefalografía , Niño , Sincronización Cortical , Electroencefalografía , Femenino , Lóbulo Frontal/fisiopatología , Humanos , Imagen por Resonancia Magnética
6.
Eur J Clin Nutr ; 71(3): 294-300, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-27876807

RESUMEN

Energy exchange is fundamental to life and is a cornerstone in the study of human physiology, metabolism and nutrition. A global effort is underway to further our understanding of human energy exchange and its components as a means of establishing the mechanistic underpinnings of the evolving obesity and chronic disease epidemics. The current report establishes a conceptual historical framework for examining the evolution of energy exchange concepts and measurement methods. We review developments taking place over more than 2000 years during which humans endeavored to establish the source of body heat, the 'fire of life'. Major conceptual and methodological advances over the past three centuries have incrementally advanced the field and created the energy exchange paradigm within which we now work. As in the past, innovative experimental ideas and measurement methods are now needed to answer important questions brought to light by the obesity and chronic disease epidemics. Nevertheless, older classical measurement methods based on calorimetry techniques still hold a strong position in the field as many diet and weight-related questions remain unanswered.


Asunto(s)
Metabolismo Energético , Peso Corporal , Calorimetría , Ingestión de Energía , Humanos
7.
Eur J Clin Nutr ; 71(11): 1329-1335, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28876331

RESUMEN

BACKGROUND/OBJECTIVES: Recent advances have extended anthropometry beyond flexible tape measurements to automated three-dimensional optical devices that rapidly acquire hundreds of body surface dimensions. Three new devices were recently introduced that share in common inexpensive optical cameras. The design, and thus potential clinical applicability, of these systems differ substantially leading us to critically evaluate their accuracy and precision. SUBJECTS/METHODS: 113 adult subjects completed evaluations by the three optical devices (KX-16 (16 stationary cameras), Proscanner (1 vertically oscillating camera), and Styku scanner (1 stationary camera)), air displacement plethysmography (ADP), dual-energy X-ray absorptiometry (DXA) and a flexible tape measure. Optical measurements were compared to reference method estimates that included results acquired by flexible tape, DXA and ADP. RESULTS: Optical devices provided respective circumference and regional volume estimates that overall were well-correlated with those obtained from flexible tape measurements (for example, hip circumference: R2, 0.91, 0.90, 0.96 for the KX-16, Proscanner, and Styku scanner, respectively) and DXA (for example, trunk volume: R2, 0.97, 0.97, and 0.98). Total body volumes measured by the optical devices were highly correlated with those from the ADP system (all R2s, 0.99). Coefficient of variations obtained from duplicate measurements (n, 55) were larger in optical than in reference measurements and significant (P<0.05) bias was present for some optical measurements relative to reference method estimates. CONCLUSIONS: Overall, the evaluated optical imaging systems differing in design provided body surface measurements that compared favorably with corresponding reference methods. However, our evaluations uncovered system measurement limitations, such as discrepancies in landmarking, that with correction have the potential to improve future developed devices.


Asunto(s)
Antropometría/instrumentación , Composición Corporal , Absorciometría de Fotón , Adolescente , Adulto , Anciano , Diseño de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dispositivos Ópticos , Pletismografía , Reproducibilidad de los Resultados , Adulto Joven
8.
Epilepsy Res ; 69(1): 80-6, 2006 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-16516443

RESUMEN

OBJECTIVE: To evaluate the sensitivity of a simultaneous whole-head 306-channel magnetoencephalography (MEG)/70-electrode EEG recording to detect interictal epileptiform activity (IED) in a prospective, consecutive cohort of patients with medically refractory epilepsy that were considered candidates for epilepsy surgery. METHODS: Seventy patients were prospectively evaluated by simultaneously recorded MEG/EEG. All patients were surgical candidates or were considered for invasive EEG monitoring and had undergone an extensive presurgical evaluation at a tertiary epilepsy center. MEG and EEG raw traces were analysed individually by two independent reviewers. RESULTS: MEG data could not be evaluated due to excessive magnetic artefacts in three patients (4%). In the remaining 67 patients, the overall sensitivity to detect IED was 72% (48/67 patients) for MEG and 61% for EEG (41/67 patients) analysing the raw data. In 13% (9/67 patients), MEG-only IED were recorded, whereas in 3% (2/67 patients) EEG-only IED were recorded. The combined sensitivity was 75% (50/67 patients). CONCLUSION: Three hundred and six-channel MEG has a similarly high sensitivity to record IED as EEG and appears to be complementary. In one-third of the EEG-negative patients, MEG can be expected to record IED, especially in the case of lateral neocortical epilepsy and/or cortical dysplasia.


Asunto(s)
Electroencefalografía , Epilepsias Parciales/patología , Magnetoencefalografía , Cuidados Preoperatorios , Adolescente , Adulto , Niño , Epilepsias Parciales/fisiopatología , Epilepsias Parciales/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sensibilidad y Especificidad
9.
Ann Fr Anesth Reanim ; 25(5): 535-8, 2006 May.
Artículo en Francés | MEDLINE | ID: mdl-16516435

RESUMEN

In winter, French Medicalised Ambulance Service rescued a 50-year-old patient after suicide attempts by jump from a bridge in the Seine. The body was discovered after more than 10 minutes of immersion. She was unconscious and in deep hypothermia with circulatory arrest. Basic CPR was started immediately and oral intubation and 100% oxygen ventilation was performed. Ventricular fibrillation appeared but repeated defibrillation failed due to profound hypothermia (rectal temperature: 28 degrees C). The patient was immediately transported to hospital. CPR and mechanical ventilation was continued during transport. The patient was taken in emergency room. The oesophageal temperature was 22 degrees C. Rewarming using extracorporeal circulation was immediately initiated after insertion of femoral access. At 27 degrees C, ventricular fibrillation started and was converted by external defibrillation to a pulse-generating cardiac rhythm. At 360 minutes, the patient's rectal temperature had reached 36 degrees C and she was disconnected from cardiopulmonary bypass with inotropic support. She was transferred to the intensive care unit after 9 hours of resuscitation, rewarming and stabilisation. Mechanical ventilation was needed for 15 days because of adult respiratory distress syndrome. Renal failure, pneumonia also occurred. She was successfully extubated on day 15 and was discharged from intensive care unit on day 21, suffering no neurological side effects.


Asunto(s)
Apoyo Vital Cardíaco Avanzado , Primeros Auxilios , Paro Cardíaco/terapia , Hipotermia/terapia , Inmersión/efectos adversos , Resucitación/métodos , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia , Apoyo Vital Cardíaco Avanzado/métodos , Puente Cardiopulmonar , Cardiotónicos/uso terapéutico , Manejo de Caso , Terapia Combinada , Cuidados Críticos , Cardioversión Eléctrica , Circulación Extracorporea , Femenino , Paro Cardíaco/etiología , Humanos , Hipotermia/etiología , Persona de Mediana Edad , Respiración Artificial , Síndrome de Dificultad Respiratoria/etiología , Síndrome de Dificultad Respiratoria/terapia , Recalentamiento/métodos , Intento de Suicidio , Fibrilación Ventricular/etiología , Fibrilación Ventricular/terapia
10.
J Neurosci ; 21(9): 3175-83, 2001 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-11312302

RESUMEN

Electrode grids on the cortical surface of epileptic patients provide a unique opportunity to observe brain activity with high temporal-spatial resolution and high signal-to-noise ratio during a cognitive task. Previous work showed that large-amplitude theta frequency oscillations occurred intermittently during a maze navigation task, but it was unclear whether theta related to the spatial or working memory components of the task. To determine whether theta occurs during a nonspatial task, we made recordings while subjects performed the Sternberg working memory task. Our results show event-related theta and reveal a new phenomenon, the cognitive "gating" of a brain oscillation: at many cortical sites, the amplitude of theta oscillations increased dramatically at the start of the trial, continued through all phases of the trial, including the delay period, and decreased sharply at the end. Gating could be seen in individual trials and varying the duration of the trial systematically varied the period of gating. These results suggest that theta oscillations could have an important role in organizing multi-item working memory.


Asunto(s)
Relojes Biológicos/fisiología , Cognición/fisiología , Memoria a Corto Plazo/fisiología , Ritmo Teta , Adolescente , Adulto , Mapeo Encefálico , Corteza Cerebral/fisiología , Señales (Psicología) , Electrodos Implantados , Epilepsia , Femenino , Análisis de Fourier , Humanos , Masculino , Modelos Neurológicos , Pruebas Neuropsicológicas , Estimulación Luminosa , Tiempo de Reacción/fisiología , Procesamiento de Señales Asistido por Computador , Conducta Verbal/fisiología
11.
Ann Fr Anesth Reanim ; 24(6): 640-2, 2005 Jun.
Artículo en Francés | MEDLINE | ID: mdl-15921882

RESUMEN

A chronically depressed 44-year-old man was rescued by the French medicalised ambulance service four hours after the ingestion of Nerium oleander leaves in a suicide attempt. Cardiotoxicity was evidenced by the presence of bradycardia with mental confusion and vomiting. The patient was empirically treated in the prehospital phase with a single dose of digoxin-specific Fab antibody fragments (Digidot). In spite of this treatment, the patient presented a new episode of important bradycardia (25 b/minute). Thereafter, the patient's rhythm stabilized and neurological signs and vomiting resolved. The patient recovered uneventfully and was discharged from the intensive care unit two days later.


Asunto(s)
Anticuerpos Bloqueadores/uso terapéutico , Digoxina/inmunología , Nerium/envenenamiento , Adulto , Bradicardia/inducido químicamente , Bradicardia/terapia , Servicios Médicos de Urgencia , Cardiopatías/inducido químicamente , Cardiopatías/fisiopatología , Humanos , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Masculino , Intento de Suicidio , Vómitos/inducido químicamente , Vómitos/terapia
12.
Ann Otolaryngol Chir Cervicofac ; 122(4): 181-6, 2005 Sep.
Artículo en Francés | MEDLINE | ID: mdl-16230938

RESUMEN

UNLABELLED: Firstly reported after stapedectomy, perilymph fistula (PLF), may occur due to trauma. AIM: Preoperative symptoms and therapeutic results are described and analyzed after exploratory tympanotomy for traumatic PLF. MATERIAL AND METHODS: Traumatic PLF was investigated in 90 patients (97 examinations) by exploratory tympanotomy at the Nantes University Hospital from 1995 to 1999. Preoperative symptoms were recorded and compared to results of tympanotomy to determine their diagnostic value. Similarly post-operative recovery was compared to results of tympanotomy. RESULTS: This study showed the value of two symptoms: aural fullness and balance disturbance. During each surgical procedure, systematic grafting was performed even if fistulization was unapparent. The best results were achieved for vestibular symptoms and concerned more vertigo than auditory symptoms. There was no significant difference in postoperative symptoms, between patients with a leak and patients without a leak. CONCLUSION: This demonstrates that the oval and round window should be grafted with connective tissue when an exploratory tympanotomy is performed.


Asunto(s)
Fístula/etiología , Enfermedades del Laberinto/etiología , Ventilación del Oído Medio/métodos , Perilinfa , Adulto , Anciano , Niño , Traumatismos Craneocerebrales/complicaciones , Femenino , Fístula/diagnóstico , Fístula/cirugía , Humanos , Enfermedades del Laberinto/diagnóstico , Enfermedades del Laberinto/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
13.
Arch Neurol ; 55(9): 1181-3, 1998 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-9740111

RESUMEN

The current developments in the availability of new antiepileptic drugs (AEDs) are unprecedented. After a period of many years during which no new AED became available, 5 new AEDs were introduced in the United States between 1993 and 1997, and 2 more are expected to be approved soon. These new drugs are a most welcome addition to the therapeutic options in the treatment of epilepsy, but they also create a dilemma for the clinician because their individual places and their optimal use in the treatment of various forms of epilepsy are yet to be determined. This review serves to summarize the main characteristics of the newer AEDs.


Asunto(s)
Aminas , Anticonvulsivantes/uso terapéutico , Ácidos Ciclohexanocarboxílicos , Acetatos/uso terapéutico , Carbamazepina/análogos & derivados , Carbamazepina/uso terapéutico , Aprobación de Drogas , Epilepsia/tratamiento farmacológico , Felbamato , Fructosa/análogos & derivados , Fructosa/uso terapéutico , Gabapentina , Humanos , Lamotrigina , Ácidos Nipecóticos/uso terapéutico , Oxcarbazepina , Fenilcarbamatos , Glicoles de Propileno/uso terapéutico , Tiagabina , Topiramato , Triazinas/uso terapéutico , Estados Unidos , Vigabatrin , Ácido gamma-Aminobutírico/análogos & derivados , Ácido gamma-Aminobutírico/uso terapéutico
14.
Neurology ; 55(11 Suppl 3): S11-6, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-11147563

RESUMEN

The pharmacokinetics of antiepileptic drugs (AEDs) largely determine their ability to achieve and maintain concentrations that maximize their efficacy and safety. The term "pharmacokinetics" encompasses the quantitative assessment of changes of drug concentrations over time as a function of absorption, distribution, and elimination. Interaction among AEDs, and between AEDs and other classes of drugs, can result in undesirable drug levels. The pharmacokinetic properties of AEDs considered to be clinically most relevant include complete or constant bioavailability, availability of a parenteral formulation, elimination half-life or preparation suitable for once- or twice-daily dosing, linear elimination kinetics, no autoinduction of enzymatic biotransformation, and lack of pharmacokinetic interactions with other drugs. Both established AEDs (carbamazepine, phenytoin, valproate, phenobarbital, and primidone) and newer AEDs (oxcarbazepine, felbamate, gabapentin, lamotrigine, topiramate, tiagabine) are evaluated in terms of these properties. None of the currently marketed AEDs combines all of these desirable pharmacokinetic characteristics. However some of the newer AEDs have more favorable pharmacokinetic profiles. The main improvements needed are limited or no pharmacokinetic interactions, preparations suitable for once- or twice-daily administration, and availability of parenteral formulations.


Asunto(s)
Anticonvulsivantes/farmacocinética , Epilepsia/metabolismo , Humanos
15.
Neurology ; 33(2): 173-8, 1983 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-6681658

RESUMEN

We measured the apparent half-life (t50%) of phenytoin (PHT) 30 times in 16 infants (aged 2 to 36 days) who had seizures. During the first week of life, the t50%s ranged from 6 to 140 hours. After the first week, the concentration dependence of PHT elimination was demonstrated; the t50% was related to the initial concentration (Ci). The t50% also decreased with postnatal age. Controlling for a Ci of 18 mg per liter, the average t50% decreased threefold between the first (57.3 +/- 48.2 hours) and fourth weeks (19.7 +/- 1.31). In newborns, both age-related changes and the concentration dependence of PHT elimination can cause PHT levels to decrease when constant doses are given.


Asunto(s)
Enfermedades del Recién Nacido/metabolismo , Fenitoína/metabolismo , Convulsiones/metabolismo , Factores de Edad , Semivida , Humanos , Recién Nacido , Enfermedades del Recién Nacido/sangre , Cinética , Fenitoína/sangre , Convulsiones/sangre , Convulsiones/tratamiento farmacológico
16.
Neurology ; 33(3): 283-90, 1983 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-6681871

RESUMEN

Neurotoxicity and protection against maximal electroshock and Metrazol seizures from primidone (PRM), phenobarbital (PB), and phenylethylmalonamide (PEMA) were determined in mice for each drug separately and expressed in terms of brain concentrations. Compared with PB, PEMA was 16 times less potent against electroshock and Metrazol seizures but only 8 times less toxic. Primidone was markedly less neurotoxic than PB and equally potent against electroshock, but PRM had no effect against Metrazol or bicuculline. PRM is a relatively nontoxic anticonvulsant with a different action than PB, and PEMA is both a weak and a relatively toxic anticonvulsant.


Asunto(s)
Química Encefálica , Malonatos/uso terapéutico , Fenobarbital/uso terapéutico , Feniletilmalonamida/uso terapéutico , Primidona/uso terapéutico , Convulsiones/tratamiento farmacológico , Animales , Bicuculina , Encéfalo/efectos de los fármacos , Electrochoque , Femenino , Ratones , Ratones Endogámicos , Pentilenotetrazol , Fenobarbital/toxicidad , Feniletilmalonamida/toxicidad , Primidona/toxicidad , Convulsiones/inducido químicamente
17.
Neurology ; 33(3): 291-5, 1983 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-6681872

RESUMEN

Neurotoxicity and protection against maximal electroshock (MES) and pentylenetrazol (Metrazol) seizures were determined in mice for various combinations of primidone (PRM), phenobarbital (PB), and phenylethylmalonamide (PEMA). The results suggest that PRM and PB together are superior to either one alone in terms of spectrum of activity and relative toxicity. The protection against Metrazol and the toxicity of PB are both potentiated by PEMA at low concentrations. PEMA also potentiates the toxicity of combined PRM plus PB, without altering their protection against MES, thus lowering their therapeutic index. We conclude that PRM and PB together have an advantage over PB alone, especially when their brain concentration ratio is at or above 1 and PEMA concentrations are low. These conditions are usually not present at steady state in patients treated with PRM.


Asunto(s)
Química Encefálica , Malonatos/administración & dosificación , Fenobarbital/administración & dosificación , Feniletilmalonamida/administración & dosificación , Primidona/administración & dosificación , Convulsiones/tratamiento farmacológico , Animales , Encéfalo/efectos de los fármacos , Sinergismo Farmacológico , Quimioterapia Combinada , Electrochoque , Femenino , Ratones , Ratones Endogámicos , Pentilenotetrazol , Fenobarbital/toxicidad , Feniletilmalonamida/toxicidad , Primidona/toxicidad , Convulsiones/inducido químicamente
18.
Neurology ; 32(10): 1122-26, 1982 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-6214728

RESUMEN

The effect of nicotinamide on the conversion of primidone to phenobarbital was studied in mice and in three epileptic patients. In mice, 200 mg per kilogram of nicotinamide increased the half-life of primidone by 47.6%, and the conversion to phenobarbital and phenylethylmalonamide was decreased by 32.4% and 14.5%, respectively. Nicotinamide also decreased the conversion of primidone to phenobarbital in patients. The dose of nicotinamide correlated directly with the primidone-phenobarbital ratio (r = 0.861, p less than 0.01). Nicotinamide also increased carbamazepine levels in two patients treated with this drug. The data demonstrate that nicotinamide inhibits metabolism of primidone in mice and metabolism of primidone and carbamazepine in humans. This probably occurs by inhibition of cytochrome P-450 by nicotinamide.


Asunto(s)
Carbamazepina/uso terapéutico , Epilepsia/tratamiento farmacológico , Niacinamida/uso terapéutico , Primidona/uso terapéutico , Animales , Carbamazepina/metabolismo , Niño , Preescolar , Interacciones Farmacológicas , Quimioterapia Combinada , Epilepsia/metabolismo , Femenino , Semivida , Humanos , Lactante , Masculino , Ratones , Ratones Endogámicos , Niacinamida/metabolismo , Fenobarbital/metabolismo , Fenobarbital/uso terapéutico , Feniletilmalonamida/metabolismo , Primidona/metabolismo
19.
Neurology ; 43(4): 693-6, 1993 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-8469324

RESUMEN

We studied the efficacy and safety of felbamate, an investigational antiepileptic drug, in a unique, double-blind, placebo-controlled trial. Sixty-four patients with refractory partial-onset seizures who completed a routine evaluation for epilepsy surgery met seizure frequency entry criteria. Each patient received felbamate or placebo in addition to the anticonvulsant regimen present at the conclusion of the presurgical evaluation. The treatment phase consisted of an 8-day inpatient period and a 21-day outpatient period. The efficacy variable was time to fourth seizure. The difference in time to fourth seizure was statistically significant (p = 0.028) in favor of felbamate. Eighty-eight percent of the patients in the placebo group had a fourth seizure during the treatment phase compared with 46% of the patients in the felbamate group (p = 0.001). Adverse experiences with felbamate were generally mild or moderate in severity. This trial demonstrated the ability of felbamate to quickly and safely reduce the occurrence of frequent partial-onset seizures and maintain effective seizure control following reductions in the dosages of standard antiepileptic drugs.


Asunto(s)
Anticonvulsivantes/uso terapéutico , Epilepsias Parciales/tratamiento farmacológico , Glicoles de Propileno/uso terapéutico , Adolescente , Adulto , Anticonvulsivantes/efectos adversos , Método Doble Ciego , Epilepsias Parciales/diagnóstico , Felbamato , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Examen Neurológico , Fenilcarbamatos , Examen Físico , Glicoles de Propileno/efectos adversos , Recurrencia , Análisis de Supervivencia , Resultado del Tratamiento
20.
Am J Med ; 84(1A): 29-33, 1988 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-3146222

RESUMEN

Valproate is often administered with other antiepileptic drugs, a practice that can lead to clinically significant pharmacologic interactions. Concomitant administration of such enzyme-inducing antiepileptic drugs as carbamazepine, phenobarbital, primidone, or phenytoin will markedly accelerate the metabolic conversion of valproate, particularly in children. In response to the effects of enzyme induction, valproate dosage may need to be doubled to maintain therapeutic serum levels. Valproate does not appear to induce enzymatic drug metabolism, but rather acts as a metabolic inhibitor. Because of this inhibition, phenobarbital dosage must often be reduced after valproate is added to the therapeutic regimen. Valproate also may markedly increase concentrations of the active epoxide metabolite of carbamazepine. The interaction between phenytoin and valproate results primarily from displacement from plasma proteins. The resulting increase in the free fraction of phenytoin alters the relationship between total phenytoin concentration and the drug's pharmacologic effect. Thus, clinical evidence of toxicity may be present at concentrations usually considered to be in the therapeutic range.


Asunto(s)
Anticonvulsivantes/farmacología , Ácido Valproico/farmacocinética , Carbamazepina/farmacología , Interacciones Farmacológicas , Etosuximida/farmacología , Humanos , Fenobarbital/farmacología , Fenitoína/farmacología , Primidona/farmacología , Ácido Valproico/farmacología
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