Uso de membrana de celulosa oxidada post-gingivectomía en hiperplasia gingival inducida por fenitoína / Use of oxidized cellulose regenerated post-gingivectomy on ginigival hyperplasia induced by phenytoin

Introducción: La hiperplasia gingival es una condición benigna caracterizada por el aumento de volumen de la encía. Algunos fármacos, factores genéticos, aparatología y placa dentobacteriana son factores que pueden inducir esta condición. Objetivo: Devolver la anatomía a la encía brindando una mejor estética y permitiendo una óptima higiene oral. Material y métodos: Paciente masculino de 20 años de edad con antecedentes de fenitoína presenta aumento de volumen en la encía. Resultados: Se obtuvieron resultados estéticos y funcionales satisfactorios con el tratamiento quirúrgico y el uso de membrana de celulosa oxidada. Conclusión: En el manejo de la hiperplasia gingival es importante el enfoque no quirúrgico como control de placa dentobacteriana y medidas de higiene del mismo paciente (AU)

Introduction: Gingival hyperplasia is a benign condition characterized for the grown on the gingival volume. Some drugs, genetic, orthodontic and dental plaque are some factors that can induce this condition. Objective: To return the gingival anatomy, providing a better aesthetic allowing also good oral hygiene. Material and methods: A male 20 years of age with medical history of phenytoin display grown on the gingival volume. Results: Aesthetic and functional results were achieved with the surgical treatment and the oxidized cellulose membrane. Conclusion: In the gingival hyperplasia management is important de non-surgical approach, as dental plaque control and oral hygiene of the patient (AU)

Oral Use of Phenytoin to Reduce Calcification in Bovine Pericardium and Porcine Aortic Leaflets Implants in Rats

Abstract Introduction: This study aims to test the effect of phenytoin as an inhibitor of the process of dystrophic calcification in bovine pericardium and porcine leaflets implanted in the subcutaneous tissue of rats. Methods: Isolated segments of biomaterials were implanted subcutaneously in young rats. The study groups received 500 mg phenytoin per kilogram of diet per day. After 90 days, samples were collected and quantitative calcification assessment by optical microscopy, radiological studies with mammography, and atomic emission spectrometry were performed. Results: Inflammatory reaction was a frequent finding in all groups when analyzed by optical microscopy. The calcium level assessed by atomic absorption spectrophotometry was significantly lower in the study groups using phenytoin compared to the control groups (control bovine pericardium group X=0.254±0.280 µg/mg; study bovine pericardium group X=0.063±0.025 µg/mg; control porcine aortic leaflets group X=0.640±0.226 µg/mg; study porcine aortic leaflets group X=0.056±0.021 µg/mg; P<0.05). Radiologic studies revealed a statistically significant difference between the groups treated with and without phenytoin (not only regarding the bovine pericardium but also the porcine leaflets). Conclusion: The results obtained suggest that phenytoin reduces the calcification process of bovine pericardium segments and porcine aortic leaflets in subdermal implants in rats; also, the incidence of calcification in bovine pericardium grafts was similar to that of porcine aortic leaflets.

Síndrome DRESS asociado a fenitoína: informe de caso / DRESS syndrome associated with phenytoin: case report

El síndrome DRESS es una reacción adversa dermatológica que puede presentarse debido a diversos medicamentos, y constituye uno de los diagnósticos más importantes por encima del síndrome de Stevens-Johnson. Se trata de un caso relacionado con una reacción adversa de muy baja frecuencia, que está documentada en la literatura científica, a varios medicamentos, entre ellos la fenitoína. Por lo mencionado, la publicación de estos casos resulta escasa y limitada. Las principales preocupaciones del paciente relacionadas con su cuadro clínico radicaban en el gran compromiso cutáneo que lo llevó a hospitalización, dolor e incomodidad, por el cual recurrió al manejo tópico generalizado con vaselina. Los hallazgos clínicos relevantes fueron: eosinofilia severa, ulceraciones cutáneas, hepatitis química y fiebre. Con los hallazgos del cuadro clínico y la evaluación de la escala RegiSCAR se hace el diagnóstico de síndrome DRESS inducido por fenitoína. Se suspende la fenitoína, se inicia levetiracetam y se administran corticosteroides y acetaminofén con evolución favorable. (AU)

DRESS syndrome is a dermatological adverse reaction can occur due to various medications, being one of the most important diagnoses above Steven-Johnson syndrome. This is a case related to a very low frequency adverse reaction that is documented in the scientific literature to several medicines among those, the phenytoin. Therefore, the publication of these cases is scarce and limited. The main concerns of the patients related to their clinical picture were due to the great cutaneous compromise that lead to hospitalization, pain and discomfort for which they resorted to generalized topical management with vaseline (petrolatum). Relevant clinical findings were severe eosinophilia, skin ulcerations, chemical hepatitis and fever. With clinical picture findings and evaluation of the RegiSCAR scale, the diagnosis of Phenytoin-induced DRESS syndrome is made. Phenytoin is discontinued, levetiracetam is started and corticosteroids and acetaminophen are administrated with favorable evolution. (AU)

Trends in prescribing patterns of antiepileptic drugs among older adult inpatients in a Brazilian tertiary center / Tendências no padrão de prescrição de drogas antiepilépticas em idosos internados em um centro terciário brasileiro

ABSTRACT Background: Data on prescribing patterns of antiepileptic drugs (AEDs) to older adult inpatients are limited. Objective: To assess changes in prescribing patterns of AEDs to older adult inpatients with late-onset epilepsy between 2009-2010 and 2015-2019, and to interpret any unexpected patterns over the 2015-2019 period. Methods: Patients aged ≥60 years with late-onset epilepsy from a tertiary center were selected. Demographic data, seizure characteristics and etiology, comorbidities, and comedications were analyzed, in addition to prescription regimens of inpatients taking AEDs to treat epilepsy. AED regimens were categorized into two groups: group 1 included appropriate AEDs (carbamazepine, oxcarbazepine, valproic acid, gabapentin, clobazam, lamotrigine, levetiracetam, topiramate, and lacosamide); and group 2 comprised suboptimal AEDs (phenytoin and phenobarbital). Multivariate logistic regression analysis was performed to identify risk factors for prescription of suboptimal AEDs. Results: 134 patients were included in the study (mean age: 77.2±9.6 years). A significant reduction in the prescription of suboptimal AEDs (from 73.3 to 51.5%; p<0.001) was found; however, phenytoin remained the most commonly prescribed AED to older adult inpatients. We also found an increase in the prescription of lamotrigine (from 5.5 to 33.6%) and levetiracetam (from 0 to 29.1%) over time. Convulsive status epilepticus (SE) and acute symptomatic seizures associated with remote and progressive etiologies were risk factors for the prescription of suboptimal AEDs. Conclusions: Phenytoin was the main suboptimal AED prescribed in our population, and convulsive SE and acute symptomatic seizures associated with some etiologies were independent risk factors for phenytoin prescription. These results suggest ongoing commitment to reducing the prescription of suboptimal AEDs, particularly phenytoin in Brazilian emergence rooms.

RESUMO Introdução: Os dados referentes à prescrição de drogas antiepilépticas (DAE) em pacientes idosos hospitalizados são limitados. Objetivo: Avaliar as mudanças no padrão de prescrição de DAE em idosos hospitalizados com epilepsia de início tardio, entre 2009-2010 e 2015-2019, e interpretar quaisquer padrões inesperados no período de 2015-2019. Métodos: Foram selecionados pacientes com ≥60 anos com epilepsia de início tardio admitidos em um centro terciário. Analisamos os dados demográficos, as características e etiologia das crises, as comorbidades e as comedicações. Foram avaliados os esquemas de prescrição das DAE no tratamento de epilepsia para pacientes internados. Os regimes de DAE foram categorizados em dois grupos: o grupo 1 incluiu as DAE apropriadas (carbamazepina, oxcarbazepina, ácido valproico, gabapentina, clobazam, lamotrigina, levetiracetam, topiramato e lacosamida); e o grupo 2 compreendeu as DAE subótimas (fenitoína e fenobarbital). A análise de regressão logística multivariada foi realizada para identificar fatores de risco para prescrição de DAE subótimas. Resultados: Foram incluídos 134 pacientes (idade média: 77,2±9,6 anos). Encontramos uma redução significativa do uso das DAE subótimas (73,3 para 51,5%; p<0.001); entretanto, a fenitoína permaneceu sendo a DAE mais prescrita para os idosos hospitalizados. Também encontramos um aumento na prescrição da lamotrigina (5,5 para 33,6%) e do levetiracetam (0 para 29,1%) no período. O estado de mal epiléptico (EME) convulsivo e as crises agudas sintomáticas que estiveram associadas a etiologias remotas e progressivas foram fatores de risco para prescrição de DAE subótimas. Conclusões: A fenitoína foi a principal DAE subótima prescrita em nossa população, e o EME convulsivo e as crises agudas sintomáticas associadas a algumas etiologias foram fatores independentes de risco para a prescrição da fenitoína. Esses resultados sugerem a necessidade de compromisso contínuo para reduzir a prescrição de DAE subótimas, particularmente a fenitoína nas salas de emergência brasileiras.

Prevalence of Gingival Hyperplasia Induced by Anticonvulsants: A Systematic Review / Prevalência da Hiperplasia Gengival Induzida pelo uso de anticonvulsivantes: Revisão sistemática

Objective: Gingival hyperplasia (GH) is one of the side effects of anticonvulsant drugs. The aim of this study was to verify the prevalence of GH associated with the use of anticonvulsant, through a systematic review. Material and Methods: Systematic search was done at databases Pubmed and Embase between January 1984 and March of 2020 for identification of articles addressing the prevalence of GH associated with the use of anticonvulsant drugs. The methodological index for non-randomized studies (MINORS) was independently assessed for quality in the selected papers. Results: The search identified 4.471 references. Nine articles were selected and evaluated 632 participants. All of the studies included in the systematic review showed a low risk of bias. The anticonvulsants used by patients were carbamazepine, ethosuximide, phenytoin, primidone, phenobarbital, sodium valproate. The studies showed a correlation between different types of anticonvulsants and GH prevalence, with a range from 0% to 73%. Among the anticonvulsants used, phenytoin showed the greatest incidence of GH, varying between 15.61% and 73% in patients. Conclusion: In the analysis of the results obtained in the literature, it is possible to notice that the great majority of studies presented incidence of GH associated with anticonvulsant use. However, further studies are necessary to understand the anticonvulsant action mechanism inducing GH, as well as the prevention forms, given that GH is a significant side effect. (AU)

Objetivo: Hiperplasia gengival (HG) é um dos efeitos colaterais das drogas anticonvulsivantes. O objetivo deste estudo foi verificar a prevalência de HG associada ao uso de anticonvulsivantes, por meio de uma revisão sistemática. Material e Métodos: A busca sistemática foi realizada nas bases de dados Pubmed e Embase entre janeiro de 1984 e março de 2020 para identificação de artigos que abordassem a prevalência de HG associada ao uso de drogas anticonvulsivantes. Foi avaliado independentemente, o risco de viés através do "Methodological index for non-randomized studies" (MINORS), para análise da qualidade dos trabalhos selecionados. Resultados: A pesquisa identificou 4.471 referências. Nove artigos foram selecionados e avaliaram 632 participantes. Todos os estudos incluídos na revisão sistemática mostraram baixo risco de viés. Os anticonvulsivantes utilizados pelos pacientes foram carbamazepina, etossuximida, fenitoína, primidona, fenobarbital e valproato de sódio. Os estudos mostraram correlação entre os diferentes tipos de anticonvulsivantes e a prevalência de HG, com variação entre 0% a 73%. Entre os anticonvulsivantes utilizados, a fenitoína apresentou a maior incidência de HG, variando entre 15,61% e 73% em pacientes. Conclusão: Na análise dos resultados obtidos na literatura, é possível notar que a grande maioria dos estudos apresentou incidência de HG associada ao uso de anticonvulsivantes. No entanto, estudos adicionais são necessários para compreender o mecanismo de ação do anticonvulsivante para a indução da HG, bem como as formas de prevenção, dado que a HG é um efeito colateral significativo (AU)

Fotobiomodulação na síndrome de stevens-johnson: relato de caso / Photobiomodulation for stevens-johnson syndrome: case report

Introdução: A Síndrome Stevens-Johnson (SSJ) é uma doença causada por hipersensibilidade a imunocomplexos e pode ser desencadeada por distintos fármacos, dentre eles a fenitoína. Devido sua complexidade e raridade, ainda nãohá consenso de tratamento padrão ouro, porém sabese da necessidade da atuação multidisciplinar. Para os cuidados com as feridas, pode-se citar os curativo se a fotobiomodulação (FBM). Objetivo: Relatar o uso da FBM como terapia complementar em um caso de SSJ no Hospital Universitário Regional dos Campos Gerais (HU-UEPG). Métodos: Paciente sexo feminino, 26 anos, deu entrada na unidade de terapia intensiva (UTI) com diagnóstico de SSJ secundária ao uso de fenitonína, escore de SCORTEN 1, com área sem epitélio íntegro 10- 30% e área acometida por lesões de 94,5%, poupando apenas o couro cabeludo. Foi abordada e tratada por uma equipe multidisciplinar e solicitado vaga em centro de especializado em queimados. No sétimo dia de UTI foi iniciado tratamento com FBM, 2 J por ponto, distância entre pontos de 2cm, comprimento onda vermelho (660nm), nas feridas que não apresentavam secreção, foram cinco sessões com intervalo de três dias entre a terceira e a quarta. Resultados: A paciente apresentou melhora visível das lesões cutâneas e recebeu alta hospitalar 5 dias após cessação da FBM. Conclusão: O uso da FBM pode ser efetiva no tratamento complementar da fase aguda SSJ desencadeada por fenitoína.

Introduction: Stevens-Johnson Syndrome (SJS) is a disease caused by hypersensitivity to immune complexes and can be triggered by different drugs, including phenytoin. Due to its complexity and rarity, there is still no consensus on gold standard treatment, but the need for multidisciplinary action is known. For wound care, dressings and photobiomodulation (PBM) can be mentioned. Objective: This study is to report the use of PBM as complementary therapy in a case of SJS at Hospital Universitário Regional dos Campos Gerais (HU-UEPG). Methods: A 26-year-old female patient was admitted to the intensive care unit (ICU) diagnosed with SJS secondary to the use of phenytoin, SCORTEN score 1, with an area without intact epithelium 10-30% and an area affected by injuries of 94.5 %, saving only the scalp. She was approached and treated by a multidisciplinary team which requested a place in a specialized burn center. On the seventh day of ICU, treatment with PBM, 2J per point was started, distance between points of 2cm, red wave length (660nm), in wounds that did not present secretion, with a total of five sessions with an interval of three days between the third and fourth. Results: The patient showed a visible improvement of skin lesions and was discharged from hospital 5 days after cessation of PBM. Conclusion: Use of PBM can be effective in complementary treatment of acute SJS phase triggered by phenytoin.

Efficacy and safety of levetiracetam versus phenytoin as second-line drugs for the treatment of children with convulsive status epilepticus: a Meta analysis / 中国当代儿科杂志

OBJECTIVE@#To systematically evaluate the efficacy and safety of levetiracetam (LEV) versus phenytoin (PHT) as second-line drugs for the treatment of convulsive status epilepticus (CSE) in children.@*METHODS@#English and Chinese electronic databases were searched for the randomized controlled trials comparing the efficacy and safety of LEV and PHT as second-line drugs for the treatment of childhood CSE. RevMan 5.3 software was used for data analysis.@*RESULTS@#Seven studies with 1 434 children were included. The Meta analysis showed that compared with the PHT group, the LEV group achieved a significantly higher control rate of CSE (@*CONCLUSIONS@#LEV has a better clinical effect than PHT in the treatment of children with CSE and does not increase the incidence rate of adverse events.

Agrandamiento gingival inducido por fenitoínas / Phenytoin induced gingival enlargement

Se entiende por agrandamiento gingival el incremento en masa y volumen del tejido gingival. Se considera una condición benigna de la cavidad oral, por lo general de manejo rutinario, que logra regularse con medidas simples de control del biofilm microbiano. El agrandamiento gingival puede ser producido por diversas condiciones clínicas, hereditarias, deficiente higiene oral o fármacos. La epilepsia afecta a 1% de la población mundial y requiere el uso de fármacos antiepilépticos o anticonvulsivantes para lograr su control, dentro de éstos la fenitoína actúa como un bloqueador selectivo de los canales de sodio sensibles al voltaje y constituye uno de los fármacos más empleados por su capacidad en el control de crisis focales y generalizadas. La fenitoína se ha relacionado con los agrandamientos gingivales como uno de sus efectos adversos, los cuales se incluyen dentro de las enfermedades por fármaco inducidas en la cavidad oral. El objetivo de este artículo es brindar la información necesaria sobre el manejo correcto de pacientes con agrandamiento gingival producido por fenitoínas y a la vez poder conocer las consecuencias de estos fármacos en la cavidad oral (AU)

Gingival enlargement means the increase in mass and volumen of the gingival tissue. It is considered a benign condition of the oral cavity, usually of routine management, wich can be regulated with simple measures of biofilm control. The gingival enlargement can be produced by diverse clinical conditions, hereditary deficient oral higiene or drugs. Epilepsy affects 1% of the world population and requires the use of antiepileptic or anticonvulsant drugs to achieve its control, within these phenytoin acts as selective blocker or voltage ­ sensitive sodium channels and is one of the most used grugs for its ability to control focal and generalized crises. Phenytoin has been linked to gingival enlargement as one of its adverse effects which is included within the drug diseases induced in the oral cavity. The objective of this article is to provide the necessary information on the correct managment of patients with gingival enlargemen produced by phenytoins and at the same time to know the consequences of these drugs in the oral cavity (AU)

Estudio del índice nivel/dosis de la fenitoína en pacientes epilépticos voluntarios de Mérida / Study of the level/dose index of phenytoin in volunteer epileptic patients from Mérida

INTRODUCCIÓN La fenitoína es usada con mucha frecuencia en nuestro medio, por lo que se requiere hacer estudios de monitorización terapéutica, que contribuya a minimizar los efectos adversos y optimizar la terapia farmacológica. En ese contexto, nuestro objetivo ha sido determinar el índice nivel/dosis de la fenitoína en pacientes epilépticos voluntarios de Mérida. MÉTODOS Se realizó un estudio descriptivo, observacional y por reclutamiento consecutivo concurrente, conformado por 30 pacientes voluntarios con diagnóstico de epilepsia. Las muestras de suero se obtuvieron en niveles mínimos de pacientes que estaban en tratamiento con fenitoína durante 1 mes. Los niveles del fármaco se cuantificaron por el método de Inmunoensayo de enzima donante clonada en el equipo Indiko Thermo Scientific. RESULTADOS El índice nivel/dosis fue de 1,4 y 1,6, la concentración plasmática de 4,8mg/l y 8,0mg/l, la capacidad metabólica de 388,4 y 462,9mg/día, respectivamente en mujeres y hombres. Mientras que el nivel de la concentración plasmática en el estado estacionario fue de 6,5mg/l y 5,5mg/l, la dosis de carga máxima de 237,3mg y de 395,6mg, respectivamente en mujeres y hombres con epilepsia de la ciudad de Mérida. CONCLUSIONES Nuestros resultados sugieren que se debe individualizar la dosis en base al índice nivel/dosis de cada paciente, ya que no se puede extrapolar para todos los pacientes con epilepsia, debido a diversos factores como al fenotipo metabólico y al uso de fármacos inductores e inhibidores enzimáticos.

INTRODUCTION Phenytoin is used very frequently in our environment, so it is necessary to do studies of therapeutic monitoring, which helps to minimize adverse drug reaction and optimize pharmacological therapy. In this context, our objective was to determine the level/dose index of phenytoin in volunteer epileptic patients from Mérida. METHODS A descriptive, observational and consecutive concurrent recruitment study was carried out, consisting of 30 volunteer patients with a diagnosis of epilepsy. The serum samples were obtained in minimum levels from patients who were in treatment with phenytoin for 1 month. The levels of the drug were quantified by the method of donor enzyme immunoassay cloned in the Indiko Thermo Scientific equipment. RESULTS The level/dose index was 1,4 and 1,6, the plasma concentration of 4,8mg/l and 8,0mg/l, the metabolic capacity of 388,4 and 462,9mg/day, respectively in women and men. While the level of plasma concentration at steady state was 6,5mg/l and 5,5mg/l, the maximum loading dose of 237,3mg and 395,6mg, respectively in women and men with epilepsy of the city of Mérida. CONCLUSIONS Our results suggest that the dose should be individualized based on the level/dose index of each patient, since it can not be extrapolated for all patients with epilepsy, due to various factors such as the metabolic phenotype and the use of enzyme-inducing drugs and inhibitors.

Uso de testosterona en mujeres: un comentario sobre el consenso global sobre el uso de la terapia de testosterona para mujeres / Global consensus position statement on the use of testosterone therapy for women

Las mujeres han sido tratadas por décadas con testosterona intentando aliviar una gran variedad de síntomas con riesgos y beneficios inciertos. En la mayoría de los países, la testosterona se prescribe "off-label", de modo que las mujeres están utilizando compuestos y dosis ideadas para tratamientos en hombres. En este sentido, varias sociedades médicas de distintos continentes adoptaron recientemente por consenso una toma de posición sobre los beneficios y potenciales riesgos de la terapia con testosterona en la mujer, explorar las áreas de incertidumbre e identificar prácticas de prescripción con potencial de causar daño. Las recomendaciones con respecto a los beneficios y riesgos de la terapia con testosterona se basan en los resultados de ensayos clínicos controlados con placebo de al menos 12 semanas de duración. A continuación se comentan las recomendaciones. (AU)

There are currently no clear established indications for testosterone replacement therapy for women. Nonetheless, clinicians have been treating women with testosterone to alleviate a variety of symptoms for decades with uncertainty regarding its benefits and risks. In most countries, testosterone therapy is prescribed off-label, which means that women are using testosterone formulations or compounds approved for men with a modified dose for women. Due to these issues, there was a need for a global Consensus Position Statement on testosterone therapy for women based on the available evidence from placebo randomized controlled trials (RCTs). This Position Statement was developed to inform health care professionals about the benefits and potential risks of testosterone therapy intended for women. The aim of the Consensus was to provide clear guidance as to which women might benefit from testosterone therapy; to identify symptoms, signs, and certain conditions for which the evidence does not support the prescription of testosterone; to explore areas of uncertainty, and to identify any prescribing practices that have the potential to cause harm. (AU)

Adverse Skin Reactions with Antiepileptic Drugs Using Korea Adverse Event Reporting System Database, 2008–2017

Predictive factors for seizures and efficacy of antiepileptic drugs in patients with Aneurysmal Subarachnoid Hemorrhage

Objectives@#To identify factors that predict the occurrence of seizures in patients with aneurysmal subarachnoid hemorrhage (SAH) and to evaluate the efficacy of antiepileptic drugs (AEDs) in preventing in-hospital seizures among patients who undergo clip occlusion of ruptured intracranial aneurysms.@*Methods@#In this retrospective study, the medical charts of 205 patients admitted for aneurysmal SAH in Philippine General Hospital (PGH) and who underwent craniotomy and clipping of aneurysm from January 2011 to June 2014 were reviewed. Demographic, radiologic, and clinical factors were converted into categorical variables and their association with the occurrence of seizures analyzed. The incidence of seizures among patients who received an AED (AED cohort) and those who did not receive an AED (No AED cohort) were compared. Secondarily, the effects of seizures and AED use on early postoperative outcomes were determined using the Glasgow Outcome Scale (GOS) on the day of discharge. @*Results@#Among 205 patients with aneurysmal SAH, 31 (15.1%) developed seizures. 21 (10.2%) had seizures at onset of SAH and only seven (3.4%) had in-hospital seizures. Aneurysm re-rupture (OR 5.26, p-value 0.045) and the presence of a parenchymal clot (OR 2.90, p-value 0.043) were independent predictors for seizure occurrence. There was no significant difference in the incidence of seizures in the AED cohort and in the No AED cohort (4/100, 4% vs. 3/99, 3%, p-value 0.714). AED use was associated with a higher proportion of patients with a discharge GOS score of 3 or less (28.0% vs 12.1%, p-value 0.005). @*Conclusion@#The results of the study do not support the routine use of AEDs in patients with aneurysmal SAH.

Effects of cyclosporin, nifedipine and phenytoin on gingival myofibroblast transdifferentiation in monkeys

Abstract Objective: Myofibroblasts have been associated with the development of several pathologic fibrotic conditions. This longitudinal study aims to assess the proliferative and antiapoptotic effects of cyclosporin, nifedipine and phenytoin on gingival connective tissue cells of nonhuman primate, as well as to analyze a possible role of myofibroblasts in gingival overgrowth. Materials and Methods: Gingival samples from the right superior canine area were obtained from 12 male monkeys ( Sapajus spp ) to comprise the control group. After one week, the animals were randomly assigned to three groups, which received daily oral doses of cyclosporin, nifedipine or phenytoin for 120 days. Gingival samples were collected from the left superior canine area of two animals of each group at 52 and 120 days. Histological sections were stained with hematoxylin and eosin, and immunoreacted against α-SMA, Ki- 67 and bcl-2. Results: α-SMA immunoreaction was negative in the control and experimental groups. Similarly, no difference between groups concerning immunostaining against Ki-67 and bcl-2 was observed in connective tissue cells. Conclusion: Based on this methodology, it may be concluded that gingival overgrowths induced by cyclosporin, nifedipine and phenytoin are not associated with neither myofibroblast transdifferentiation, proliferation nor apoptosis of gingival connective cells in monkeys.

Antiepileptic drug-induced severe cutaneous adverse reactions and HLA alleles: A report of five cases with lymphocyte activation test

Antiepileptic drugs (AEDs) can induce severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. We performed HLA genotyping and lymphocyte activation tests (LATs) for five AED-induced SCAR patients (three males and two females; aged 40–66 years old). Three patients were treated with carbamazepine (CBZ) for pain control, one was treated with phenytoin (PHT) for seizure prevention, and one was treated with valproic acid (VPA) for seizure prevention. One patient was diagnosed with CBZ-induced DRESS syndrome and the remaining patients were diagnosed with SJS. All patients recovered from SCARs after stopping suspicious drugs and supportive care. LATs were conducted to confirm the culprit drug responsible for inducing SCARs; and LAT results were positive for the suspected culprit drugs, in all except in one case. HLA-A,

Clinical Efficacy and Safety of Injectable Levetiracetam Versus Phenytoin as Second-Line Therapy in the Management of Generalized Convulsive Status Epilepticus in Children: An Open-Label Randomized Controlled Trial

BACKGROUND AND PURPOSE: There is sparsity of quality evidence for the use of drugs after first-line benzodiazepines in convulsive status epilepticus in children. The aim of the study was to compare the clinical efficacy and safety of intravenous levetiracetam versus intravenous phenytoin as second-line drugs in the management of generalized convulsive status epilepticus in children. METHODS: This open-label randomized controlled trial was conducted in the Emergency Department of The Children's Hospital and The Institute of Child Health, Multan, Pakistan over a period of 4 years and 6 months from January 2014 to June 2018. This study included 600 children with generalized convulsive status epilepticus: 300 in the 40 mg/kg levetiracetam group, and 300 in the 20 mg/kg phenytoin group. Cessation of a clinical seizure (seizure cessation rate) within 30 minutes after the end of drug administration was the primary outcome in this study, and the presence or absence of adverse effects was noted as the secondary outcome. Data were analyzed using SPSS (version 20.0). RESULTS: The children in the levetiracetam and phenytoin were aged 3.5±0.2 and 3.4±0.2 years (mean±SD), respectively, their seizure durations before the start of treatment were 25.1±0.6 and 23.8±0.4 minutes, and their treatment efficacies were 278/300 (92.7%) and 259/300 (83.3%). Levetiracetam was significantly more effective than phenytoin (p=0.012), with no significant difference in safety. Adverse events were observed in eight children in the phenytoin group. CONCLUSIONS: Levetiracetam is significantly more effective than phenytoin for the treatment of convulsive status epilepticus in children who have failed to respond to benzodiazepines.

Synergistic effect of honey and Nigella sativa on wound healing in rats

Abstract Purpose: To investigate the therapeutic potential of honey, Nigella sativa (N. sativa) and their combination in rat model of excisional wound healing. Methods: A circular excision wound was established in the back region of 50 Wistar rats. Subsequently, they were divided into 5 groups and daily topical administration of lanolin in the control group, honey in the honey group, cold-pressed N. sativa seed oil in the N. sativa groups, mix of 1:1 ratio of honey and N. sativa seed oil in the mix group, and phenytoin cream in the phenytoin group were used. Then, wound surface areas were evaluated using digital camera immediately after the injury and at post excision days 5, 10, 15 and 20. Results: Significant reduction in wound surface area was observed within and between the groups (P < 0.001). In the post excision days 5, 10, 15 and 20 the wound surface areas in the mix group were significantly lower than the other groups followed by the phenytoin, honey, N. sativa, and control groups. Conclusion: The wound healing may be improved and accelerated by using topical solutions of honey, N. sativa seed oil and especially their mixture.

Paroxysmal Ataxia and Dysarthria in a Patient with Demyelinating Disease

Paroxysmal dysarthria and ataxia is characterized by abrupt onset of dysarthria and ataxia of unilateral limbs for seconds. We present a 45-year-old female patient with paroxysmal symptoms of dysarthria, right-sided ataxia, and a persistent symptom of upbeating nystagmus. Her brain fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging indicated potential diagnosis of demyelinating disease. The paroxysmal and persistent symptoms have recovered after phenytoin administration. Sodium channel blocker may play a role in reducing the ephaptic transmission in a demyelinated or re-myelinated lesion.

HLA DRB1*04:03 and Drug Reaction with Eosinophilia and Systemic Symptoms Induced by Oxcarbazepine: A Case Report / 대한소아신경학회지

Drug reaction with eosinophilia and systemic symptoms(DRESS), which occurs 2–8 weeks after taking a medication is a rare and potentially life-threatening drug-induced hypersensitivity reaction, which includes skin eruption, hematologic abnormalities, lymphadenopathy, and internal organ such as liver, lung, kidney involvement. Antiepileptic agents (e.g., carbamazepine, lamotrigine, phenytoin, and phenobarbital) and allopurinol are the most commonly reported causes. However, new antiepileptic agents, such as oxcarbazepine, rarely cause drug reaction with eosinophilia and systemic symptoms. A 11-year-old boy who was administered oxcarbazepine for 34 days developed widespread rashes, facial edema, fever, cough, nasal stuffiness, tonsillitis, and cervical lymphadenopathy. Laboratory test results showed leukocytosis, eosinophilia, thrombocytosis, elevated c-reactive protein, and elevated liver transaminase levels. As we suspected drug reaction with eosinophilia and systemic symptoms, we immediately withdrew oxcarbazepine and commenced corticosteroid therapy. The patient's skin lesions and abnormal laboratory results slowly improved. Before change the antiepileptic agents, we performed human leukocyte antigen (HLA) typing to assess the genetic risk factors of the drug reaction and the result was positive for HLA DRB1*04:03 known to cause severe acute drug hypersensitivity, such as Stevens-Johnson syndrome by oxcarbazepine in Koreans. We have presented the first report of drug reaction with eosinophilia and systemic symptoms associated with oxcarbazepine in a patient with HLA DRB1*04:03. Although DRESS by oxcarazepine is extremely rare and unpredictable, when suspected clinical symptoms occur, it is necessary to interrupt the causative drug rapidly and confirming the patient's HLA typing may help to select a safer alternative drug.

MDR1 gene polymorphism and phenytoin pharmacokinetics in epilepsy

Background: Pharmacokinetics is a widely used anti-epileptic drug phenytoin, which exhibits noticeable inter-individual variations in efficacy. Genetic factors, such as MDR1 gene polymorphism may play a crucial role in drug response

Objective: To investigate the influence of MDR1 variant genotypes on Phenytoin Pharmacokinetics in epileptic patients

Design: A Case-Control Genetic Study

Setting: College of Medicine and Pharmacy, King Khalid University, Abha, Saudi Arabia

Method: Twenty-five epileptic patients non-responders to phenytoin monotherapy and 25 epileptic patients' responders to phenytoin monotherapy were recruited. DNA was isolated by conventional phenol-chloroform method. MDR1 [3435C>T] gene polymorphism was assessed using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphisms [PCR-RFLP] method. Allelic and genotypic frequency were calculated. Reversed-phase High-Performance Liquid Chromatography [HPLC] method was used to determine the plasma levels of Phenytoin drug. PK Solutions was used for non-compartmental analysis to estimate the pharmacokinetic parameters

Result: The MDR1 [3435C>T] polymorphism was found to be in Hardy-Weinberg equilibrium and displayed significant allelic and genotypic association between non-responders and responders to phenytoin [P<0.01]. The finding of pharmacokinetics analysis demonstrated that longer halflife [t1/2 = 33.26 hours] and less clearance rate [CL = 0.42 L/hour] in the homozygous variant group compared to wild-type genotype group [t 1/2 = 19.2hrs, CL = 0.8 L/hour]

Conclusion: The finding suggests that the genetic polymorphism in the C3435T location of MDR1 gene might determine pharmacokinetics variability of phenytoin drug. Therefore, pharmacokinetics parameters along with genotyping of MDR1 [C3435T] genotype might be valuable in the perspective of personalized medicine in epileptic patients

Controversias sobre el rastreo de los niveles séricos de vitamina D y su suplementación / Controversies about serum vitamin D levels screening and its supplementation

Si bien los niveles bajos de vitamina D se han asociado con varios resultados de interés en salud, aún resulta motivo de controversia qué significa un nivel bajo, cual es la utilidad de su suplementación y cuales son sus potenciales efectos adversos. En ese contexto, se realizó en el Servicio de Medicina Familiar y Comunitaria del Hospital Italiano un taller de discusión denominado "Actividad ECCO" (Evidencia Científica en la Clínica Cotidiana) en la que fueron presentados los resulta-dos de estudios identificados que hubieran comparado el uso de vitamina D (con o sin suplementación de calcio) ver-sus placebo, con el objetivo de discutir cuál es la evidencia actual para el rastreo de deficiencia de vitamina D y para, eventualmente, recomendar o no su suplementación. Este artículo resume la evidencia identificada y las conclusiones consensuadas en dicha actividad. (AU)

Although low levels of vitamin D have been associated with several health outcomes, it is controversial what a low level means, the usefulness of its supplementation and its potential adverse effects. In this context, a workshop called "ECCO Activity" (Scientific Evidence in the Daily Clinic) was held in the Family and Community Medicine Division of Hospital Italiano de Buenos Aires, where the results of identified studies that compared the use of vitamin D (with or without calcium supplementation) versus placebo, with the aim of discussing what is the current evidence for screening of vitamin D deficiency and to, eventually, recommend or not its supplementation. This article summarizes the identified evidence and the agreed conclusions in that activity. (AU)