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In this research, a UHPLC-MS/MS method was developed and validated for the determination of zonisamide in dried plasma spots (DPS) and dried blood spots (DBS). Detection of zonisamide and internal standard, 1-(2,3-dichlorphenyl)piperazine, was carried out in ESI+ mode by monitoring two MRM transitions per analyte. Total run time, less than 2.5 min, was achieved using Acquity UPLC BEH Amide (2.1 × 100 mm, 1.7 µm particle size) column with mobile phase comprising acetonitrile-water (85:15%, v/v) with 0.075% formic acid. The flow rate was 0.225 mL/min, the column temperature was 30 °C and the injection volume was 3 µL. Desolvation temperature, desolvation gas flow rate, ion source temperature and cone gas flow rate were set by the IntelliStart software tool in combination with tuning. All of the Guthrie cards were scanned, and DPS/DBS areas were determined by the image processing tool. The influence of hematocrit values (20-60%) on accuracy and precision was evaluated to determine the range within which method for DBSs is free from Hct or dependency is within acceptable limits. The validated method was applied to the determination of zonisamide levels in DPS and DBS samples obtained from patients confirming its suitability for clinical application. Finally, the distribution of zonisamide into the red blood cells was estimated by correlating its DPS and DBS levels.
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Teste em Amostras de Sangue Seco , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida/métodos , Teste em Amostras de Sangue Seco/métodos , Humanos , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos , ZonisamidaRESUMO
OBJECTIVES: Although the importance of the epigenetic changes in tumors, including oral squamous cell carcinomas (OSCCs), is now becoming apparent, the mechanisms that trigger or cause aberrant DNA methylation in cancer are still unrevealed. DNA methylation is regulated by a family of enzymes, DNA methyltransferases (DNMTs). DNMT gene expression analysis, as well as genetic polymorphisms, has not been previously evaluated in OSCC. MATERIALS AND METHODS: In 65 OSCC patients, SYBR Green real-time PCR method was assessed for relative quantification of DNMT1, DNMT3A, and DNMT3B mRNAs, normalized to TATA-binding protein (TBP) mRNA. The expression levels of all three genes were dichotomized as high or low, with a twofold change of normalized mRNA expression used as the cutoff value. Polymorphisms in DNMT1 (rs2228612) and DNMT3B (rs406193) were analyzed in 99 OSCCs by TaqMan SNPs genotyping assays. RESULTS: DNMT1, DNMT3A, and DNMT3B were overexpressed in 36.9, 26, and 23 % of the OSCC patients, respectively. DNMT1 overexpression was significantly associated with the overall survival, p = 0.029, and relapse-free survival of OSCC patients, p = 0.003. Patients with DNMT1 overexpression, as an independent prognostic factor, had a 2.385 times higher risk to relapse than those with lower expression. The DNMT1 A201G gene polymorphism was associated with a reduced overall survival in OSCC patients, p = 0.036. CONCLUSIONS: Our results suggest that DNMT1 could play an important role in modulating OSCC patient survival. CLINICAL RELEVANCE: DNMT gene expression could be a potential prognostic marker that might lead to an improvement in diagnosis, prognosis, and prospective use of epigenetic-targeted therapy of OSCC.
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Carcinoma de Células Escamosas/genética , DNA (Citosina-5-)-Metiltransferase 1/genética , DNA (Citosina-5-)-Metiltransferases/genética , Neoplasias Bucais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Metilação de DNA , DNA Metiltransferase 3A , Epigênese Genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo Genético , Prognóstico , RNA Mensageiro/genética , Fatores de Risco , Taxa de Sobrevida , DNA Metiltransferase 3BRESUMO
Holoprosencephaly is a complex malformation of the brain associated with the median facial defects. Variability of the clinical picture is the characteristic of this anomaly. In most cases, the degree of severity of the facial anomaly correlates with the degree of damage to the brain. This article aims to present a rare case of child with a milder form of brain anomaly combined with a severe form of facial anomaly. The article also presents the application of a feeding stimulator to improve the child's quality of life. The anomaly was diagnosed by postnatal sonography of the brain, magnetic resonance imaging of the endocranium, and three-dimensional computed tomography of the craniofacial skeleton.
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Fenda Labial/diagnóstico por imagem , Fissura Palatina/diagnóstico por imagem , Holoprosencefalia/diagnóstico por imagem , Doenças Raras/diagnóstico por imagem , Feminino , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , UltrassonografiaRESUMO
Evidence-based guidelines, or recommendations, for the management of infants with seizures are lacking. A Task Force of the Commission of Pediatrics developed a consensus document addressing diagnostic markers, management interventions, and outcome measures for infants with seizures. Levels of evidence to support recommendations and statements were assessed using the American Academy of Neurology Guidelines and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The report contains recommendations for different levels of care, noting which would be regarded as standard care, compared to optimal care, or "state of the art" interventions. The incidence of epilepsy in the infantile period is the highest of all age groups (strong evidence), with epileptic spasms the largest single subgroup and, in the first 2 years of life, febrile seizures are the most commonly occurring seizures. Acute intervention at the time of a febrile seizure does not alter the risk for subsequent epilepsy (class 1 evidence). The use of antipyretic agents does not alter the recurrence rate (class 1 evidence), and there is no evidence to support initiation of regular antiepileptic drugs for simple febrile seizures (class 1 evidence). Infants with abnormal movements whose routine electroencephalography (EEG) study is not diagnostic, would benefit from video-EEG analysis, or home video to capture events (expert opinion, level U recommendation). Neuroimaging is recommended at all levels of care for infants presenting with epilepsy, with magnetic resonance imaging (MRI) recommended as the standard investigation at tertiary level (level A recommendation). Genetic screening should not be undertaken at primary or secondary level care (expert opinion). Standard care should permit genetic counseling by trained personal at all levels of care (expert opinion). Genetic evaluation for Dravet syndrome, and other infantile-onset epileptic encephalopathies, should be available in tertiary care (weak evidence, level C recommendation). Patients should be referred from primary or secondary to tertiary level care after failure of one antiepileptic drug (standard care) and optimal care equates to referral of all infants after presentation with a seizure (expert opinion, level U evidence). Infants with recurrent seizures warrant urgent assessment for initiation of antiepileptic drugs (expert opinion, level U recommendation). Infantile encephalopathies should have rapid introduction and increment of antiepileptic drug dosage (expert opinion, level U recommendation). There is no high level evidence to support any particular current agents for use in infants with seizures. For focal seizures, levetiracetam is effective (strong evidence); for generalized seizures, weak evidence supports levetiracetam, valproate, lamotrigine, topiramate, and clobazam; for Dravet syndrome, strong evidence supports that stiripentol is effective (in combination with valproate and clobazam), whereas weak evidence supports that topiramate, zonisamide, valproate, bromide, and the ketogenic diet are possibly effective; and for Ohtahara syndrome, there is weak evidence that most antiepileptic drugs are poorly effective. For epileptic spasms, clinical suspicion remains central to the diagnosis and is supported by EEG, which ideally is prolonged (level C recommendation). Adrenocorticotropic hormone (ACTH) is preferred for short-term control of epileptic spasms (level B recommendation), oral steroids are probably effective in short-term control of spasms (level C recommendation), and a shorter interval from the onset of spasms to treatment initiation may improve long-term neurodevelopmental outcome (level C recommendation). The ketogenic diet is the treatment of choice for epilepsy related to glucose transporter 1 deficiency syndrome and pyruvate dehydrogenase deficiency (expert opinion, level U recommendation). The identification of patients as potential candidates for epilepsy surgery should be part of standard practice at primary and secondary level care. Tertiary care facilities with experience in epilepsy surgery should undertake the screening for epilepsy surgical candidates (level U recommendation). There is insufficient evidence to conclude if there is benefit from vagus nerve stimulation (level U recommendation). The key recommendations are summarized into an executive summary. The full report is available as Supporting Information. This report provides a comprehensive foundation of an approach to infants with seizures, while identifying where there are inadequate data to support recommended practice, and where further data collection is needed to address these deficits.
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Guias de Prática Clínica como Assunto , Convulsões Febris/terapia , Espasmos Infantis/terapia , Comitês Consultivos , Anticonvulsivantes , Gerenciamento Clínico , Eletroencefalografia , Epilepsia/diagnóstico , Epilepsia/terapia , Humanos , Lactente , Recém-Nascido , Neuroimagem , Convulsões Febris/diagnóstico , Espasmos Infantis/diagnósticoRESUMO
OBJECTIVE: To examine the prevalence of temporomandibular disorders (TMD) after orthodontic-surgical treatment in patients with mandibular prognathism and analyze psychosocial variables related to TMD. MATERIALS AND METHODS: The case-control study comprised 40 patients with mandibular prognathism who underwent combined orthodontic-surgical treatment (orthognathic surgery group). Forty-two patients with untreated mandibular prognathism served as a control group. Research diagnostic criteria for temporomandibular disorders was used in order to assess the clinical diagnosis of TMD (Axis I) and to estimate depression, somatization and patient's disability related to chronic pain (Axis II). RESULTS: The overall prevalence of TMD was not significantly different between the groups. Myofascial pain was significantly higher, while arthralgia, arthritis and arthrosis was significantly lower in the orthognathic group compared with the controls (90.5% vs 50.0%, 0.0% vs 27.8%, respectively) (p < 0.05). Females in orthognathic surgery group showed higher prevalence of TMD (p < 0.05) and myofascial pain (p < 0.01) and increased level of chronic pain (p < 0.05) in comparison with post-operative males. No significant difference in chronic pain, somatization and depression scores was found between investigated groups. With respect to presence of TMD within the groups depression was higher in untreated subjects with dysfunction (p < 0.05). CONCLUSION: Prevalence of TMD immediately after completion of orthodontic-surgical treatment for mandibular prognathism is similar to frequency of dysfunction in untreated subjects, is significantly higher in females and is most commonly myogenic. Furthermore, females show an increased level of chronic pain post-operatively. Somatization and depression levels do not differ between patients with corrected prognathism and untreated prognathic patients.
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Depressão/etiologia , Má Oclusão Classe III de Angle/complicações , Má Oclusão Classe III de Angle/cirurgia , Procedimentos Cirúrgicos Ortognáticos/efeitos adversos , Prognatismo/complicações , Prognatismo/cirurgia , Transtornos da Articulação Temporomandibular/etiologia , Adulto , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Dor Crônica/etiologia , Estudos Transversais , Feminino , Humanos , Masculino , Mandíbula/anormalidades , Mandíbula/cirurgia , Fatores de Risco , Fatores Sexuais , Fatores Socioeconômicos , Transtornos Somatoformes/etiologia , Estatísticas não Paramétricas , Transtornos da Articulação Temporomandibular/diagnóstico , Síndrome da Disfunção da Articulação Temporomandibular/diagnóstico , Síndrome da Disfunção da Articulação Temporomandibular/etiologia , Adulto JovemRESUMO
Lafora progressive myoclonus epilepsy is characterized by pathognomonic endoplasmic reticulum (ER)-associated polyglucosan accumulations. We previously discovered that mutations in EPM2A cause Lafora disease. Here, we identify a second gene associated with this disease, NHLRC1 (also called EPM2B), which encodes malin, a putative E3 ubiquitin ligase with a RING finger domain and six NHL motifs. Laforin and malin colocalize to the ER, suggesting they operate in a related pathway protecting against polyglucosan accumulation and epilepsy.
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Proteínas de Transporte/genética , Mutação , Epilepsias Mioclônicas Progressivas/genética , Proteínas Tirosina Fosfatases/genética , Sequência de Bases , Estudos de Coortes , Feminino , Homozigoto , Humanos , Doença de Lafora/genética , Masculino , Dados de Sequência Molecular , Epilepsias Mioclônicas Progressivas/enzimologia , Linhagem , Proteínas Tirosina Fosfatases não Receptoras , Deleção de Sequência , Ubiquitina-Proteína LigasesRESUMO
BACKGROUND: Genetic polymorphisms of vitamin D receptor gene (VDR) and genes involved in vitamin D metabolism pathway, CYP27B1 and CYP24B1, may affect individual susceptibility to oral squamous cell carcinoma. The purpose of this study was to evaluate the associations between VDR, CYP27B1 and CYP24A1 gene polymorphisms with oral cancer risk and survival. METHODS: Study cohort consisted of 110 patients with oral cancer and 122 healthy controls. The genotypes of the analysed genes were determined by PCR-RFLP or real-time PCR method. RESULTS: The significant decrease of oral cancer risk was observed in individuals with heterozygote genotype of CYP24A1 gene (rs2296241) (odds ratio 0.281, P = 0.000) in comparison with wild type. Patients with VDR FokI ff wild type genotype had significantly worse overall survival (P = 0.012, log rank) compared with heterozygous and mutated genotype combined. A stratified analysis by the lymph node involvement and tumour stage showed that ff is associated with poor survival in groups with and without lymph node involvement (P = 0.025, P = 0.040, respectively) and in stage III tumours (P = 0.026). Multivariate Cox's regression analysis revealed that VDR FokI could be considered an independent prognostic factor. CONCLUSION: Our findings indicate that CYP24A1 gene polymorphism might have an influence on the susceptibility to oral cancer. VDR FokI polymorphism was associated with worse survival and could be considered as an independent prognostic marker.
Assuntos
25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , Predisposição Genética para Doença , Neoplasias Bucais/genética , Receptores de Calcitriol/genética , Esteroide Hidroxilases/genética , Idoso , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/mortalidade , Razão de Chances , Polimorfismo de Nucleotídeo Único , Valores de Referência , Vitamina D3 24-HidroxilaseRESUMO
PURPOSE: The aim of the study was to evaluate the outcome of status epilepticus (SE) in children and to define predictors for morbidity, mortality, and SE recurrence. METHODS: The study included 302 children (age 2 months to less than 18 years; mean age ± SD 4.7 ± 4.2 years) with 489 episodes of SE. Etiology, treatment, and clinical and electroencephalography (EEG) features of SE and their impact on the outcome were analyzed. The outcome was classified into three categories: unchanged neurologic status, neurologic consequences, and lethal outcome. Univariate and multivariate Cox hazard regression analyses were used to define predictors of mortality, morbidity, and SE recurrence. KEY FINDINGS: Neurologic status was unchanged in 235 children (77.8%) and neurologic consequences occurred in 39 patients (12.9%); case-fatality ratio was 9.3% and recurrence rate was 21%. Mortality was related to progressive encephalopathy, preexisting neurologic abnormalities, specific EEG findings, and generalized convulsive type of SE. Neurologic consequences were associated with younger age, progressive encephalopathy, duration of SE >24 h, prior epilepsy, and specific EEG findings. Multivariate analyses showed that etiology of SE and prior neurologic abnormalities were independent predictors of mortality, whereas younger age, etiology, and very long duration of SE were predictors of morbidity. SIGNIFICANCE: Outcome of SE in children is favorable in most of the cases, but mortality and morbidity rates are still high. Etiology and prior neurologic abnormalities were the main predictors of mortality, whereas the main predictor of morbidity was underlying etiology.
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Cuidados Críticos , Estado Epiléptico/terapia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Eletroencefalografia , Feminino , Humanos , Lactente , Unidades de Terapia Intensiva , Modelos Logísticos , Masculino , Doenças do Sistema Nervoso/epidemiologia , Prognóstico , Recidiva , Fatores de Risco , Convulsões/fisiopatologia , Estado Epiléptico/etiologia , Estado Epiléptico/mortalidade , Resultado do TratamentoRESUMO
Various inflammatory diseases of central nervous system, including subacute sclerosing panencephalitis, could cause epilepsia partialis continua. Two boys with epilepsia partialis continua with onset in terminal phase of atypical subacute sclerosing panencephalitis have been reported. Children were not vaccinated against measles, and the second case had history of measles at an early age. In both cases, the onset of subacute sclerosing panencephalitis was characterized by altered behavior and cognitive decline with very fast mental and neurological deterioration. One boy was suffering from complex partial seizures and myoclonic jerks synchronous with periodic electroencephalographic pattern. Diagnosis was proved by increased titers of antimeasles antibodies in both serum and cerebrospinal fluid. In terminal phase of the disease, epilepsia partialis continua of localized group of the muscles was diagnosed, with good response to intravenous infusion of midazolam. Surface electroencephalographic recordings during epilepsia partialis continua did not show the epileptic discharges. During the terminal phase of the disease, no other type of seizures and movement disorders were recognized, except epilepsia partialis continua. In spite of the treatment, period from the onset of disease to death lasted less than 3 months, suggesting very fulminant course of subacute sclerosing panencephalitis.
Assuntos
Epilepsia Parcial Contínua/etiologia , Panencefalite Esclerosante Subaguda/complicações , Criança , Eletroencefalografia , Humanos , MasculinoRESUMO
The objective of this study is to report cases of unexpected deaths in Unverricht-Lundborg disease (ULD) patients, a comparatively benign form of progressive myoclonus epilepsy. We performed a multicentric study of the circumstances of death in ULD patients seen in the last 16 years. We assessed age, sex, severity and duration of disease, antiepileptic drugs, circumstances and presumed cause of death. Nineteen observations (12 females, 7 males) were collected from four centers (Tunis, Marseille, Milan, Belgrade). The most common causes of death are (1) SUDEP (six cases, all female), with 4/6 on phenobarbital alone, and (2) complications of severe ULD (six cases). Two patients committed suicide. Only one death was clearly unrelated to ULD (car accident), while four patients died of stroke, drowning, complications of chronic alcoholism and Wernicke encephalopathy, respectively. In conclusion, although the prognosis of ULD has progressed, there are still spontaneously severe forms and high risk of early death, including SUDEP.
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Síndrome de Unverricht-Lundborg/mortalidade , Adolescente , Adulto , Idade de Início , Anticonvulsivantes/uso terapêutico , Causas de Morte , Criança , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Estado Epiléptico/etiologia , Suicídio , Inquéritos e Questionários , Síndrome de Unverricht-Lundborg/genética , Adulto JovemRESUMO
â¢We report the successful treatment of a boy with hypothalamic tumor, gelastic seizures, drug-resistant epilepsy and ADHDâ¢The use of methylphenidate significantly reduced symptoms of ADHD while seizure frequency remained unchanged.
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PURPOSE: Evaluation of the etiology, clinical characteristics and outcome of the first status epilepticus (fSE) event in children. METHOD: The patients with fSE hospitalized in our Institute from 1995 to 2011 were included. The etiology was characterized as either known (symptomatic) or unknown (cryptogenic). Outcome was assessed at the end of hospitalization. Logistic regression analyses were used to assess predictors of the outcome, with odds ratio adjusted by age as a measure effect. RESULTS: The study included 236 patients with a median age of 2.0 years (IQR 4.0). Etiology was identified as secondary to: defined electroclinical syndromes 108 (45.8), acute symptomatic conditions 63 (26.7%), unknown 24 (10.1%), progressive encephalopathy 23 (9.7%), or remote symptomatic 18 (7.6%). Recurrence rate was 16.9%, neurological consequences were in 24.6% and case-fatality ratio was 4.7%. The main predictors were for: a) death - progressive encephalopathy (ORâ¯=â¯14.68, 95% CI 4.06-23.11. pâ¯=â¯0.001); b) neurological sequelae - acute symtomatic (OR 3.44, 95% CI 4.82-6.47) pâ¯=â¯0.001, remote symptomatic (ORâ¯=â¯13.84, 95% CI 4.34-44.12. pâ¯=â¯0.001), progressive encephalopathy (ORâ¯=â¯3.94, 95% CI 1.64-9.56. pâ¯=â¯0.002), seizure duration >60â¯min (ORâ¯=â¯0.44, 95% CI 0.24-0.81. pâ¯=â¯0.001); c) seziure recurrence - acute symptomatic etiology (ORâ¯=â¯3.59, 95% CI 41.76-7.21. pâ¯=â¯0.001), seizure duration >60â¯min (ORâ¯=â¯0.30, 95% CI 0.15-0.61. pâ¯=â¯0.001). CONCLUSIONS: In children with fSE, exploring acute disorders and immediate etiological treatment is essential. The outcome of fSE is favorable concerning the recurrence rate, while neurological sequelae are seen in one quarter of the patients. The etiology and fSE duration are the main determinants of outcome.
Assuntos
Estado Epiléptico/epidemiologia , Estado Epiléptico/etiologia , Pré-Escolar , Feminino , Hospitalização , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Estado Epiléptico/terapiaRESUMO
Lafora disease (LD) is a fatal neurodegenerative disorder caused by loss-of-function mutations in either laforin glycogen phosphatase gene (EPM2A) or malin E3 ubiquitin ligase gene (NHLRC1). LD is associated with gradual accumulation of Lafora bodies (LBs). LBs are aggregates of polyglucosan, a long, linear, poorly branched, hyperphosphorylated, insoluble form of glycogen. Loss-of-function mutations either in the EPM2A or in the NHLRC1 gene lead to polyglucosan formation. One hypothesis on LB formation is based on findings that laforin-malin complex downregulates glycogen synthase (GS) through malin-mediated ubiquitination, and the other one is based on findings that laforin dephosphorylates glycogen. According to the first hypothesis, polyglucosan formation is a result of increased GS activity, and according to the second, an increased glycogen phosphate leads to glycogen conformational change, unfolding, precipitation, and conversion to polyglucosan, while GS remains bound to the precipitating glycogen. In this review, we summarize all the recent findings that have important implications for the treatment of LD, all of them showing that partial inhibition of GS activity may be sufficient to prevent the progression of the disease. The current perspective in LD is high-throughput screening for small molecules that act on the disease pathway, that is, partial inhibitors of GS, which opens a therapeutic window for potential treatment of this fatal disease.
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PURPOSE: The study investigated the pattern of p53 gene mutations and human papillomavirus (HPV) infection concerning their relation to overall survival in patients with oral squamous cell carcinomas of the tongue and floor of the mouth. PATIENTS AND METHODS: The presence of HPV infection in 50 patients, and p53 gene mutations (42 patients from the same group) in the tumour specimens were analysed by polymerase chain reaction and single-stranded conformational polymorphism method. The follow-up period ranged from 12 to 48 (median 29) months. RESULTS: p53 mutations were identified in 11/42 tumours. HPV infection was detected in 32/50 cases, mostly HPV16 (10/32), HPV18 and HPV31 (6/32). A significantly higher incidence of HPV infection was found among smokers (p<0.05) and among patients with poor oral hygiene (p<0.01). The highest incidence of p53 mutations was detected in tumours of histological grade I and nuclear grade III. Patients with p53 mutation or with HPV infection had significantly shorter overall survival when compared with those that were without p53 mutations (p<0.01) or HPV infection (p<0.05). HPV-infected patients with p53 mutation had the worst prognosis when compared with patients with HPV infection only (p<0.01) or with patients negative for both HPV and p53 (p<0.01). CONCLUSION: The results stress once more the importance of HPV for the prognosis of survival of patients with squamous cell carcinoma of lower parts of the oral cavity. The presence of p53 mutations in HPV-infected tumours was associated with an even poorer prognosis for the patients.
Assuntos
Carcinoma de Células Escamosas/terapia , Genes p53/genética , Neoplasias Bucais/terapia , Mutação/genética , Papillomaviridae/fisiologia , Infecções por Papillomavirus/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/virologia , Éxons/genética , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Soalho Bucal/patologia , Neoplasias Bucais/genética , Neoplasias Bucais/virologia , Estadiamento de Neoplasias , Higiene Bucal , Fumar , Taxa de Sobrevida , Neoplasias da Língua/genética , Neoplasias da Língua/terapia , Neoplasias da Língua/virologia , Resultado do TratamentoRESUMO
The Christian miracle tales strongly support the identification of Sts. Cosmas and Damian as doctors. The most famous of the saints' posthumous miracles, is that of the Black Leg. The main source of this story is the Golden Legend by Jacobus da Varagine, collection of fanciful hagiographies compiled in the 13th century. Saints Cosmas and Damian miraculously transplanted the black leg of the Ethiopian man onto the white body of the verger with "cancerous" leg. Saints appeared to the patient in a dream, amputated his diseased leg and replaced it with the leg of a recently died man. This dramatic cure was attractive for many western artists. The iconography of this miracle was depicted for the first time in a Florentine panel of ca.1370. The color of the leg later attracted special attention. Since the 1990's the Miracle of the Black Leg, presented in a (neo) Byzantine style, appeared in Greece. The miracle of Holy Unmercenaries has no proper historical foundation in the Books of the lives of the Saints in the Orthodox Churches. Action focused on replacement of the affected leg with one from cadaveric donor was unknown to the eastern Christianity. Exploration of available orthodox hagiographical sources related to the healing powers of Sts. Cosmas and Damian showed remarkable neglect of that miracle. Some contemporary Greek authors find appropriate to disregard it.
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Religião e Medicina , Santos/história , Cristianismo , Grécia , História Medieval , Humanos , Médicos , Transplante/históriaRESUMO
In this paper, novel LC-MS/MS methods for the determination of antiepileptic drug pregabalin in dried matrix spots (DMS) are presented. This attractive technique of sample collection in micro amount was utilized in the form of dried blood spots (DBS) and dried plasma spots (DPS). Following a pre-column derivatization procedure, using n-propyl chloroformate in the presence of n-propanol, and consecutive liquid-liquid extraction, derivatized pregabalin and its internal standard, 4-aminocyclohexanecarboxylic acid, were detected in positive ion mode by applying two SRM transitions per analyte. A YMC-Pack Octyl column (50mm×4.0mm, 3µm particle size) maintained at 30°C, was utilized with running mobile phase composed of acetonitrile: 0.15% formic acid (85:15, v/v). Flow rate was 550µL/min and total run time 2min. Established methods were fully validated over the concentration range of 0.200-20.0µg/mL for DBS and 0.400-40.0µg/mL for DPS, respectively, while specificity, accuracy, precision, recovery, matrix-effect, stability, dilution integrity and spot homogeneity were found within acceptance criteria. Validated methods were applied for the determination of pregabalin levels in dried blood and plasma samples obtained from patients with epilepsy, after per os administration of commercial capsules. Comparison of drug level in blood and plasma, as well as correction steps undertaken in order to overcome hematocrit issue, when analyzing DBS, are also given.
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Anticonvulsivantes/sangue , Pregabalina/sangue , Adolescente , Adulto , Calibragem , Criança , Cromatografia Líquida de Alta Pressão , Feminino , Hematócrito , Humanos , Masculino , Espectrometria de Massas , Controle de Qualidade , Padrões de Referência , Reprodutibilidade dos Testes , Adulto JovemRESUMO
PURPOSE: Oxidative stress is recognized as an important factor in progressive myoclonus epilepsy (PME). Genetic polymorphism of glutathione S-transferases (GSTs), which are involved in both protection from oxidative damage and detoxification, might alter the capacity for protecting tissues from exogenous and endogenous oxidants. We aimed to assess a possible association between GST polymorphism and PME, as well as, correlation between GST genotypes and oxidative phenotype in PME patients. METHODS: GSTA1, GSTM1, GSTP1 and GSTT1 genotypes were determined in 26 patients with PME and 66 controls. Byproducts of protein oxidative damage (thiol groups (P-SH) and nitrotyrosine), superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities were determined. RESULTS: The frequency of GSTA1, GSTM1 and GSTP1 genotypes was not significantly different between PME patients and controls, while individuals with GSTT1-null genotype were at 5.44-fold higher risk of PME than carriers of GSTT1-active genotype. Moreover, significant risk of PME was obtained in carriers of both GSTT1-null and GSTM1-null genotypes. Carriers of combined GSTA1- active and GSTT1-null genotype were at highest, 7.55-fold increased risk of PME. Byproducts of protein damage did not reach statistical significance, while SOD and GPX activities were significantly higher in PME patients then in controls. When stratified according to GST genotype, P-SH groups were significantly lower only in patients with GSTT1-null genotype in comparison to carriers of active genotype. Only SOD activity was increased in GSTT1-null when compared to corresponding active genotype. CONCLUSIONS: GSTT1-null genotype might be associated with the increased risk and enhanced susceptibility to oxidative stress in PME patients.
Assuntos
Predisposição Genética para Doença , Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Epilepsias Mioclônicas Progressivas/genética , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Técnicas de Genotipagem , Heterozigoto , Humanos , Masculino , Epilepsias Mioclônicas Progressivas/sangue , Epilepsias Mioclônicas Progressivas/enzimologia , Estresse Oxidativo/genética , Estresse Oxidativo/fisiologia , Polimorfismo Genético , Adulto JovemRESUMO
INTRODUCTION: Juvenile myoclonic epilepsy is considered to be a chronic disease requiring lifelong antiepileptic treatment. The aim of this study was both to identify factors predicting the kind of seizure control and to investigate the outcome in patients after therapy withdrawal. MATERIAL AND METHODS: The study included 87 patients (49 female, 38 male), aged from 17.5 to 43.5 years, referred to our Department between 1987 and 2008, with the seizure onset at the age of 14.3±2.9, and followed up for 13.3±5.8 years on average (from 5 to 23 years). RESULTS: Sixty seven (77.0%) patients were fully controlled; whereas 13.8% had persistent seizures and 9.2% showed pseudoresistance. The combination of three seizure types and focal electroencephalogram features were independent factors of poor seizure control. Therapy was discontinued in 34 patients either by the treating physician (in 21 patients) or by the patients themselves (in 13 cases). In 18 subjects, all seizure types relapsed after 1.1 year on average (from 7 days to 4 years) and therapy was resumed in them. All patients but three (10/13), who stopped the treatment themselves, experienced recurrences. Seizure freedom off drugs was recorded in 10.3% patients. Nonintrusive myoclonic seizures recurred in 0.5-3 years as their only seizure type in four patients, but without reintroducing medication in three patients. CONCLUSION: Combination of seizure types and focal electroencephalogram features are significant factors of pharmacoresistancy. Continuous pharmacotherapy is required in majority of patients, although about 10% of them appear to have permanent remission without therapy in adolescence.
Assuntos
Epilepsia Mioclônica Juvenil/terapia , Adolescente , Adulto , Anticonvulsivantes/uso terapêutico , Eletroencefalografia , Feminino , Humanos , Masculino , Epilepsia Mioclônica Juvenil/diagnóstico , Indução de Remissão , Estudos Retrospectivos , Adulto JovemRESUMO
INTRODUCTION: L-2-Hydroxyglutaric aciduria (L-2-HGA) is an autosomal recessive neurometabolic disease with a slowly progressive course and characterized by increased levels of hydroxyglutaric acid in urine, cerebrospinal fluid and plasma. In this condition clinical features mainly consist of mental deterioration, ataxia and motor deficits. CASE OUTLINE: The patient is a 16-year-old girl, the first and only child of healthy, non-consanguineous parents of Serbian origin. At the age of 4 years her walk became unsteady and ataxic. Other signs of cerebellar involvement were soon observed. Head circumference was above two standard deviations (55 cm). Mild mental retardation was revealed by formal intelligence testing (IQ 60). MR examination of the brain showed confluent subcortical white matter lesions spread centripetally, and atrophy of the cerebellar vermis with involvement of dentate nuclei, without deep white matter abnormalities. Laboratory investigation revealed increased amounts and a very large peak of HGA in urine and plasma. Enantiomeric analysis confirmed the L-configuration (> 90%) establishing the diagnosis of L-2-HGA. The first epileptic seizure, partial with secondary generalization, occurred at age of 8 years. Favorable seizure control was achieved. A slow progression of neurological impairment was noted. Therapeutic trials with oral coenzyme Q10 and with oral riboflavin showed no biochemical and clinical effects. Recently, the diagnosis was proven by the presence of a mutation in the L-2-HGA gene. CONCLUSION: To our knowledge, this is the first report of L-2-HGA in Serbia. L-2-HGA must be considered in the differential diagnosis based on specific findings in cranial MRI.
Assuntos
Encefalopatias Metabólicas Congênitas/diagnóstico , Adolescente , Encéfalo/patologia , Encefalopatias Metabólicas Congênitas/complicações , Diagnóstico Diferencial , Epilepsia/diagnóstico , Epilepsia/etiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , SérviaRESUMO
INTRODUCTION: Cleft lips and palates are the most common congenital orofacial anomaly. This type of clefts is the most severe from the orthodontic-surgical therapy aspect. CASE REPORT: A female newborn with a complete cleft of the primary and the secondary palate was admitted to the clinic, where a multiple-role orthodontic device was specially designed and applied to primarily manage the closure of the existing cleft and help to improve the suckling ability of the baby. Besides the fact that it allows breastfeeding, it has a significant orthodontic effect, too. CONCLUSION: Specificity of this device is the lack of extraoral fixation. What can easily be observed is a progressive reduction of the cleft between the separated segments and the premaxilla retrusion. It, thus, allows the creation of much better conditions for further surgical management of the said defect.