The prevalence of epilepsy in society is general knowledge; however the impact on social activity as well as other daily factors are not always fully recognised. Epilepsy frequently poses a problem with regard to work–related activities (Heaney, 1999:44). Moran et al. (2004:425) indicated that the major impacts of epilepsy on life were work and school difficulties, driving prohibition, psychological and social life of which restriction of work or schooling has the greatest impact on epileptic’s life. In all cases the type, severity, and frequency of the seizures as well as the age would be relevant. Davis et al. (2008:451) established that 39% of all epileptics were not adherent to their therapy and in patients over 65 this was even higher at 43 %. Non–adherence with antiepileptic medicine appears to be related to increased health care utilisation and costs and may also lead to an increased probable accidents or injuries The general objective was to investigate anti–epileptic medicine prescribing patterns and treatment cost in a section of the private health care sector by using a medicine claims database. A retrospective drug utilisation study was done on the data claims from a pharmacy benefit management company for the study period 1 January 2005 to 31 December 2008. Firstly epilepsy was investigated in order to understand the disease and to determine the prevalence and treatment thereof. It was found that epilepsy is still one of the most common neurological conditions and according to the findings, 2 out of every hundred patients were using anti–epileptic medicine in this section of the private health care sector. To make this condition socially more acceptable and understandable, public education for special target groups concerning the disorder must be conducted as well as employment training programmes for people with epilepsy themselves. The utilisation patterns of anti–epileptic drugs were reviewed, analysed and interpreted. It was determined that anti–epileptic medicine items are relatively expensive with regards to other medicine items on the total database. With regard to gender, more females are using anti–epileptic medicine than males on the database. The largest age group of patients using anti–epileptic medicine, is between > 40 years and <= 64 years of age. It was also clear that prevalence increase as age increase. With regard to the different prescribers, the number of items prescribed by a general practitioner was almost double that of the other prescribers. It was further established that newer anti–epileptic medicines are more expensive than older anti–epileptic medicine according to the cost per tablet in this section of the private health care sector. Carbamazepine and valproate were the two active ingredients that were most frequently prescribed as a single item on a prescription. After a cost–minimisation analysis was done, R134 685.66 could have been saved when generic substitution was implemented. The refill–adherence rate decreased as age increased. Only 30.46% of the trade names was refilled according to acceptable refill–adherence rates. The refill–adherence rate according to active ingredient showed that medicine items containing, phenobarbitone/vit B or gabapentin had the lowest unacceptable refill–adherence rate. The limitations for this study was stipulated and recommendations for further research regarding anti–epileptic medicine were also made. / Thesis (M.Pharm (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2011.

The prevalence of epilepsy in society is general knowledge; however the impact on social activity as well as other daily factors are not always fully recognised. Epilepsy frequently poses a problem with regard to work–related activities (Heaney, 1999:44). Moran et al. (2004:425) indicated that the major impacts of epilepsy on life were work and school difficulties, driving prohibition, psychological and social life of which restriction of work or schooling has the greatest impact on epileptic’s life. In all cases the type, severity, and frequency of the seizures as well as the age would be relevant. Davis et al. (2008:451) established that 39% of all epileptics were not adherent to their therapy and in patients over 65 this was even higher at 43 %. Non–adherence with antiepileptic medicine appears to be related to increased health care utilisation and costs and may also lead to an increased probable accidents or injuries The general objective was to investigate anti–epileptic medicine prescribing patterns and treatment cost in a section of the private health care sector by using a medicine claims database. A retrospective drug utilisation study was done on the data claims from a pharmacy benefit management company for the study period 1 January 2005 to 31 December 2008. Firstly epilepsy was investigated in order to understand the disease and to determine the prevalence and treatment thereof. It was found that epilepsy is still one of the most common neurological conditions and according to the findings, 2 out of every hundred patients were using anti–epileptic medicine in this section of the private health care sector. To make this condition socially more acceptable and understandable, public education for special target groups concerning the disorder must be conducted as well as employment training programmes for people with epilepsy themselves. The utilisation patterns of anti–epileptic drugs were reviewed, analysed and interpreted. It was determined that anti–epileptic medicine items are relatively expensive with regards to other medicine items on the total database. With regard to gender, more females are using anti–epileptic medicine than males on the database. The largest age group of patients using anti–epileptic medicine, is between > 40 years and <= 64 years of age. It was also clear that prevalence increase as age increase. With regard to the different prescribers, the number of items prescribed by a general practitioner was almost double that of the other prescribers. It was further established that newer anti–epileptic medicines are more expensive than older anti–epileptic medicine according to the cost per tablet in this section of the private health care sector. Carbamazepine and valproate were the two active ingredients that were most frequently prescribed as a single item on a prescription. After a cost–minimisation analysis was done, R134 685.66 could have been saved when generic substitution was implemented. The refill–adherence rate decreased as age increased. Only 30.46% of the trade names was refilled according to acceptable refill–adherence rates. The refill–adherence rate according to active ingredient showed that medicine items containing, phenobarbitone/vit B or gabapentin had the lowest unacceptable refill–adherence rate. The limitations for this study was stipulated and recommendations for further research regarding anti–epileptic medicine were also made. / Thesis (M.Pharm (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2011.

This study focuses on the way in which learners living with epilepsy, who attend mainstream schools in the rural areas of the Limpopo Province, experience epilepsy. The results of the study indicate that the needs of learners with epilepsy are not well-catered for in mainstream schools. They often experience fear, anxiety, humiliation, ostracisation, name-calling, scape-goating, blaming and suspicion. Recommendations were made regarding the measures which should be taken to address the needs of rural children living with epilepsy. These recommendations could be used by teachers and the Department of Education. / Educational Studies / M.Ed. (Guidance and Councelling)

These studies were completed to examine how status epilpeticus seizure characteristics are modulated during post-juvenile brain development. This may determine if postnatal age in rats is a better identifier of stages of post-juvenile brain development. The first study fully detailed the acute discrete seizure phase of the rat pilocarpine-SE model. Results for this study showed that Racine behavioral severity score, spike frequency, and seizure severity during the acute discrete seizure phase change in relation to post-juvenile brain developmental stages. The second study fully detailed early and late patterns of status epilepticus. Results for this study displayed modulation of time in pattern, spike frequency, and relative delta power for seizure pattern during post-juvenile ages. The third study displayed modulation of diazepam efficacy during post-juvenile ages. The data suggest characteristics in the acute discrete seizure pliase, chronic SE phase, and therapeutic window of SE change in relation to age during post-juvenile brain development. This establishes that age is a better estimator of developmental stage than animal bodyweight.

Les études cliniques montrent que l’incidence des crises épileptiformes est la plus forte durant la période néonatale. Ces crises ont de nombreux facteurs étiologiques : un traumatisme crânien, des épisodes anoxo-ischémiques, des infections périnatales, des hémorragies intracrâniennes, des troubles métaboliques et de la fièvre... Ces crises per se peuvent entrainer des conséquences délétères à long terme. Notamment, l’hypothèse que la propagation des crises répétées vers des structures cérébrales naïves peut conduire à la formation d’un foyer épileptique secondaire qui génère des crises spontanées a été longtemps suggérée comme étant un mécanisme de base dans l’épilepsie humaine. Par conséquent, il est nécessaire de traiter efficacement les crises néonatales. Cependant, les traitements de premier choix comme le phénobarbital et le diazépam qui ont été développés pour traiter les crises chez l’adulte, sont souvent inefficaces chez les nouveau-nés et peuvent même aggraver les crises. Les mécanismes à l’origine de cette différence sont actuellement mal connus. Récemment, à l’aide d’une préparation développée dans le laboratoire composée des deux hippocampes néonataux interconnectés, il a été montré pour la première fois que des crises induites dans un hippocampe qui se propagent vers l’hippocampe controlatéral pouvaient conduire à la formation d’un foyer épileptique secondaire - foyer miroir (« seizure beget seizure »). Ce modèle a permis de montrer qu’un des mécanismes clés de la formation d’un foyer épileptique était l’augmentation permanente du chlore intracellulaire résultant en une action GABAergique excitatrice favorisant la genèse de crises spontanées. Déterminer les mécanismes à l’origine de l’épileptogenèse secondaire est d’une importance clinique majeure, et permettra de développer de nouvelles stratégies de prévention des effets pathologiques des crises.La première partie de ce travail a été de définir l’implication du co-transporteur de chlore NKCC1 dans la genèse de crises et l’épileptogenèse secondaire. Nous avons montré que le blocage de NKCC1, à l’aide d’outils pharmacologiques ou génétiques, ne prévient ni la formation d’un foyer miroir par des crises propagées ni l’augmentation permanente de chlore intracellulaire. Par conséquent, NKCC1 n’est ni nécessaire ni suffisant à induire ces modifications. Dans la deuxième partie, utilisant des outils électrophysiologiques et immunochimiques, nous apportons un faisceau d’évidences montrant que le co-transporteur de chlore KCC2 est internalisé et altéré fonctionnellement par des crises suggérant que l’accumulation de chlore résulte essentiellement de l’incapacité des neurones à évacuer le chlore. Dans la troisième partie nous avons étudié les effets du phénobarbital (PB) et du diazépam (DZP) sur la genèse de crises et l’épileptogenèse durant la période néonatale. En particulier, nous montrons que le PB, mais pas le DZP, bloque des crises initiales induites et prévient l’induction d’un foyer épileptique secondaire. Cette différence est due à un blocage partiel des récepteurs AMPA/KA par le PB. Cependant, une fois le foyer miroir établi, le PB comme le DZP aggravent les crises spontanées en exacerbant les effets excitateurs du GABA. Ces résultats montrent que l’histoire des crises détermine les effets du PB. En outre, le bumétanide, un antagoniste de NKCC1 qui réduit le chlore intracellulaire, améliore l’action du PB et bloque les crises spontanées. En conclusion, nos observations plaident fortement pour un traitement rapide des crises néonatales afin de protéger autant que faire les capacités du neurone à réguler le chlore intracellulaire. / Clinical studies show that children, especially neonates are in a much higher risk than adults to develop seizures. Such seizures in the brain may be provoked by different factors: tumor, infection, anoxia, fever, trauma, cysts, vascular malformations... Seizures in neonates are also often resistant to treatments and available antiepileptic drugs (AEDs) are inefficient or even provoke and aggravate neonatal seizures. A fundamental concept in epilepsy is that the seizures generated in epileptogenic regions propagate to the other brain structures even to the contralateral side and may develop permanent epileptic focus in the naïve brain structures – secondary epileptic focus. Consequently, it is necessary to treat the neonatal seizures. Diazepam (DZP) and phenobarbital (PB) are extensively used as first and second line drugs to treat acute seizures in neonates and their actions are thought to be mediated by increasing the actions of GABAergic signals. Yet, their efficacy is different and variable with occasional failure or even aggravation of recurrent seizures questioning whether other mechanisms are not involved in their actions. We studied these issues in the intact interconnected hippocampal preparation from neonatal rats and mice. Using this preparation and three-compartment chamber we induced seizures in one hippocampus that propagated to the contralateral one. The propagation of recurrent seizures transformed the contralateral hippocampus into independent epileptogenic focus – mirror focus (MF) - that was capable of generating spontaneous seizures (« seizure beget seizure »). The formation of MF is associated with a permanent increase of the intracellular concentration of chloride and a shift of the actions of GABA from inhibitory to excitatory. Therefore determining how secondary epileptogenesis is induced will have major clinical impact as it will enable to develop tools that prevent selectively the pathogenic seizures.At first, we have determined the impact and the contribution of chloride co-transporter NKCC1 in seizure generation and secondary epileptigenesis. We have shown that the pharmacologically or genetically blockade of NKCC1 did not prevent neither the generation nor propagation of evoked seizures nor formation of MF. However, in the isolated MF, bumetanide effectively blocked spontaneous epileptiform activity. Bumetanide partially reduced DFGABA and therefore the excitatory action of GABA in epileptic neurons. Therefore, bumetanide is a potent anticonvulsive agent although it cannot prevent formation of the epileptogenic MF.Second using different electrophysiological and immunochemistry approaches we have demonstrated that the accumulation of chloride and the excitatory actions of GABA in mirror foci neurons are mediated by NKCC1 chloride importer and by a downregulation and internalisation of the chloride exporter KCC2.Finally using our MF model we have compared the actions of PB and DZP on neonatal seizures. We have revealed that PB but not DZP dramatically reduced initial propagating seizures and prevented formation of epileptogenic MF. We show that PB in contrast to DZP has a highly specific action on AMPA/kainate receptor mediated currents. This action underlies an important difference between the two AEDs as in contrast to PB, DZP aggravates early seizures reflecting the advantage of PB over DZP to prevent secondary epileptogenesis. Yet, after repeated seizures, once an epileptogenic MF has been formed, this difference is abolished because of the strong excitatory actions of GABA. Therefore, the history of seizures prior to GABA acting AED treatment determines its effects and rapid treatment of severe potentially epileptogenic neonatal seizures is recommended to prevent secondary epileptogenesis associated with KCC2 down regulation.

[pt] Em economias competitivas com mercados incompletos e horizonte infinito, quando a tomada de garantias previamente constituídas é o único mecanismo que dá incentivos contra a inadimplência em operações de crédito, esquemas de Ponzi são evitados e há equilíbrio independemente da escolha destas garantias. Nestas economias, adiciono mecanismos contra inadimplência que são efetivos, isto é, induzem os credores a efetuarem pagamentos além do valor das garantias. Neste contexto, provo que a escolha das exigências de garantias se tornam relevantes para assegurar a existência planos individuais ótimos. Enfatizo também que este resultado não depende de tipos de mecanismos contra inadimplência específicos, contanto que os tomadores de empréstimos se deparem com pagamentos adicionais ao valor das garantias como uma porcentagem da dívida remanescente. / [en] In infnite horizon incomplete market economies, when the seizure of collateral guarantees is the only mechanism enforcing borrowers not to entirely default on their promises, equilibrium exists independently of the choice of collateral bundles. In these economies, we add default enforcement mechanisms that are effective, i.e. induce payments besides the value of collateral guarantees. We prove that the choice of collateral requirements become relevant to assure the existence of individual's optimal plans. This result does not depend on specific types of such mechanisms, as long lenders face payments besides the value of collateral guarantees as a percentage of the remaining debt.

A Eletroconvulsoterapia (ECT) é o tratamento biológico mais eficaz para quadros depressivos. Os estudos de seus aspectos técnicos são fundamentais tanto para compreensão dos mecanismos da ECT quanto para maximizar a eficácia e minimizar seus efeitos cognitivos. Existem muitos métodos para o cálculo da dose do estímulo elétrico e não há consenso em relação ao melhor. Sabe-se que doses muito elevadas tendem a ser eficazes, mas à custa de efeitos na memória. Embora o método de titulação seja recomendado pela Associação Psiquiátrica Americana, muitos profissionais tem preocupação sobre a segurança cardiovascular deste procedimento, devido aos sucessivos estímulos frustros que levam a um aumento na incidência de bradicardia e/ou assistolia. O objetivo deste trabalho foi traçar o perfil dos pacientes submetidos ao método da titulação do limiar, verificando sua segurança cardiovascular. Para isso foi feito um estudo retrospectivo e 113 casos foram revistos no ano de 2007. A maioria (70,3%) recebeu aplicação bilateral e (62,8%) eram mulheres. O diagnóstico de depressão apareceu com mais freqüência (50,5%). A maioria (57,5%) necessitou de dois estímulos, (12,4%) necessitou de apenas um, (28,3%) necessitou de três e (1,8%) realizou quatro estímulos. A média de frequência cardíaca inicial foi de 79,6 bpm (DP = 17). O limiar convulsígeno variou de 16mC a 128mC (média = 58,9; DP 25,4). A relação do limiar convulsígeno foi significativamente menor com o posicionamento unilateral dos eletrodos (p < 0,001), mas não com sexo ou idade. Não foi encontrada associação com a medicação concomitante. A incidência de bradicardia aumentou com os estímulos frustros, mas não foi significante a relação entre o primeiro e segundo estímulos. Não houve complicações cardíacas significativas e nenhum paciente apresentou assistolia. Conclui-se que o método da titulação do limiar pode ser uma estratégia segura e mais precisa, uma vez que os fatores (sexo, idade e uso de medicamentos) não foram relacionados com o LCT; a baixa incidência de complicações cardiovasculares reforça-o como método de escolha. Não se pode descartar um efeito protetor do uso da atropina. / Electroconvulsive therapy (ECT) is the most effective biological treatment for depression. Studies of the technical aspects are fundamental for understanding the mechanisms of ECT and to maximize efficiency and minimize their cognitive effects. There are many methods to determine the dose of electrical stimulation and there is no consensus on which is the best one. It is known that very high doses are effective, but at the expense of effects on memory. Although the method of limits (titration method) is generally accepted, being encouraged by the American Psychiatric Association, many practitioners have concerns regarding cardiac safety of this method. Due to repetitive subthreshold stimuli until the seizure is elicited, an increased risk of bradiarrhythmia and/or asystole is believed to be present. The objective of this study was to establish the profile of patients undergoing the method of titration of the threshold, checking their cardiovascular safety. A retrospective study was performed including 113 cases that receive their treatment in the year of 2007. The majority (70.3%%) received bilateral ECT, (62.8%) were women. The diagnosis of depression appeared more frequently (50.5%). The majority (57.5%) needed two stimuli; 12.4% needed only one; 28.3% needed three and 1.8% required four stimuli. The average initial heart rate was 79.6 bpm (SD = 17). The seizure threshold ranged from 16mC to 128mC (mean = 58.9, SD 25.4). The ratio seizure threshold was significantly lower with unilateral electrode placement (p <0.001) but not with sex or age. No association was found with concomitant medication. There was an increased incidence of bradycardia with subthreshold stimuli , but there was not a relationship between the first and second stimuli. There were no significant cardiac complications and no patient had asystole. In conclusion, the method of titration of the threshold seems to be a safe and more precise to determined electrical dose, since the factors usually used to predict the threshold (gender, age and medication use) were not related to the LCT The low incidence of cardiovascular complications adds up to its use as the method of choice.. A protective effect of atropine cannot be ruled out.

À luz do princípio da presunção de inocência, construiu-se o entendimento de que no processo penal seriam lícitas apenas as medidas cautelares, em respeito ao status de inocência do acusado, vedando quaisquer outras medidas que revelassem uma antecipação do juízo condenatório. Partindo dessa premissa, as medidas de busca e apreensão passaram a ser entendidas e aceitas apenas como medidas cautelares, destinadas a assegurar a marcha processual ou a eficácia e a utilidade do provimento jurisdicional final. Entretanto, com a promulgação da Lei nº 10.695/2003 que modificou a proteção penal da propriedade imaterial e criou um novo procedimento especial para os crimes de ação penal de iniciativa pública , foi introduzida no sistema uma nova modalidade de apreensão, permitindo o apossamento de todos os bens ilicitamente produzidos ou reproduzidos, com o escopo de tornar o combate à pirataria mais eficiente. Assim, a nova medida deixou de ser um instrumento a serviço do processo e passou a ter um novo objetivo: dar resposta à sociedade com a apreensão, antes mesmo da produção da prova pericial, dos bens contrafeitos, revelando natureza jurídica de medida de antecipação de tutela (satisfativa). Entretanto, apesar de ter natureza jurídica satisfativa, a medida de apreensão prevista no artigo 530-B do Código de Processo Penal se justifica no nosso sistema e não representa violação ao princípio da presunção de inocência, por se referir a capítulo da sentença distinto do capítulo da autoria e da culpabilidade do acusado: refere-se ao capítulo das coisas que não podem ser restituídas. Nessa situação, tanto em casos de condenação quanto em casos de absolvição, impronúncia ou arquivamento, as coisas não podem ser restituídas porque o fabrico, a alienação, o porte ou a detenção constitui por si só fato ilícito autônomo. Logo, a antecipação de tutela determinando a apreensão de tais coisas não representa violação ao princípio da presunção de inocência. Por outro lado, o procedimento deve ser modificado para alcançar o justo equilíbrio entre a eficiência e o garantismo, introduzindo a obrigação de que a ilicitude seja constatada, por perito ou pessoa tecnicamente habilitada, logo após a apreensão e de que a medida seja sempre precedida de ordem judicial ou, nos casos de prisão em flagrante, seja imediatamente submetida à apreciação judicial, para que seja convalidada ou revogada / Under the light of assumption of innocence, it was understood that in the criminal suits there would only be acceptable caution measures regarding the status of innocence of the accused, prohibiting any other measures revealing an advanced position of the condemning judgment. As of this assumption, the search and seizure measures started to be understood and accepted only as caution measures, destined to assure the procedural progress or the effectiveness and usefulness of the final jurisdictional decision. However, with the enactment of Law 10695/2003 which modified the criminal protection of intangible property and created a new special process for criminal suits of public initiative a new kind of seizure was introduced, allowing the possession of all assets produced or reproduced illicitly, with the scope of rendering more efficient the fighting against piracy. Thus, the new measure stopped being an instrument to serve the suit and evidenced a new purpose, of providing answers to the society with the seizure of the infract assets, even before the production of the expert\'s evidence, revealing legal nature of advanced protection (satisfactory). However, in spite of having the legal nature of satisfaction, the seizure measure provided by article 530-B of the Criminal Procedures Code is justified in our system and does not represent infringement of the principle of assumption of innocence, since it refers to a chapter of the sentence different from the chapter of authorship and guilt of the accused, i.e., refers to chapter of things which cannot be returned. In these cases of things which cannot be returned, both in case of condemnation and acquittance, lack of judgment or filing, the things cannot be returned because the manufacture, disposal, possession or holding thereof, in itself, constitutes and independent illicit fact. Therefore, the advanced protection determining the seizure of such things does not represent infringement of the principle of assumption of innocence. On the other hand, the procedure must be modified to achieve fair balance between the efficiency and the guaranteeism, introducing the obligation of the forgery being evidenced by official expert or technically qualified person, straight after the seizure; and that the measure is always preceded by judicial order, or in cases of imprisonment in flagrant, that it is immediately submitted to judicial analysis, for the measure to be validated or revoked.

Over time astrocytes have been thought to function in an auxiliary manner, providing neurons with metabolic and structural support. However, recent research suggests they may play a fundamental role in the generation and propagation of focal epileptic seizures by causing synchronized electrical bursts in neurons. It would be helpful to have a simple mathematical model that represents this dynamic and incorporates these updated experimental results. We have created a two-compartment model of a typical neuron found in the hippocampal CA1 region, an area often thought to be the origin of these seizures. The focus is on properly modeling the astrocytic input to examine the pathological excitation of these neurons and subsequent transmission of the signals. In particular, we consider the intracellular astrocytic calcium fluctuations which are associated with slow inward currents in neighbouring neurons. Using our model, a variety of experimental results are reproduced, and comments are made about the potential differences between graded and “all-or-none” astrocytes.

Over time astrocytes have been thought to function in an auxiliary manner, providing neurons with metabolic and structural support. However, recent research suggests they may play a fundamental role in the generation and propagation of focal epileptic seizures by causing synchronized electrical bursts in neurons. It would be helpful to have a simple mathematical model that represents this dynamic and incorporates these updated experimental results. We have created a two-compartment model of a typical neuron found in the hippocampal CA1 region, an area often thought to be the origin of these seizures. The focus is on properly modeling the astrocytic input to examine the pathological excitation of these neurons and subsequent transmission of the signals. In particular, we consider the intracellular astrocytic calcium fluctuations which are associated with slow inward currents in neighbouring neurons. Using our model, a variety of experimental results are reproduced, and comments are made about the potential differences between graded and “all-or-none” astrocytes.