RESUMO
Cerebral cavernous malformations (CCMs) are a diffuse cerebrovascular disease affecting approximately 0.5% of the population. A CCM is characterized by abnormally enlarged and leaky capillaries arranged in mulberry-like structures with no clear flow pattern. The lesion might predispose to seizures, focal neurological deficits or fatal intracerebral hemorrhage. However, a CCM can also remain neurologically silent. It might either occur sporadically or as an inherited disorder with incomplete penetrance and variable expressivity. Due to advances in imaging techniques, the incidence of CCM diagnoses are increasing, and the patient must be managed on a multidisciplinary basis: genetic counselling, treatment if needed, and follow-up. Advances have been made using radiological and pathological correlates of CCM lesions adding to the accumulated knowledge of this disease, although management of these patients is very variable among centers. This review is aimed at providing an update in genetic and molecular insights of this condition. Included are implications for genetic counselling, and possible approaches to prevention and treatment that derive from the understanding of pathogenetic mechanisms.
Assuntos
Encéfalo , Sistema Nervoso Central/patologia , Hemangioma Cavernoso do Sistema Nervoso Central , Proteínas Associadas aos Microtúbulos , Proteínas Proto-Oncogênicas , Encéfalo/metabolismo , Encéfalo/patologia , Sistema Nervoso Central/metabolismo , Hemorragia Cerebral/genética , Hemorragia Cerebral/patologia , Aconselhamento Genético , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico , Hemangioma Cavernoso do Sistema Nervoso Central/genética , Hemangioma Cavernoso do Sistema Nervoso Central/fisiopatologia , Hemangioma Cavernoso do Sistema Nervoso Central/terapia , Humanos , Proteína KRIT1 , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Terapia de Alvo Molecular , Mutação , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Convulsões/genética , Convulsões/patologiaRESUMO
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are represented by rare but life-threatening cutaneous adverse reactions to different drugs. Previous studies have found that in a Han Chinese population from Taiwan and other Asian Countries, a strong genetic association between HLA-class I alleles (B*15:02, B*58:01) and SJS and TEN was induced by carbamazepine and allopurinol, respectively. To identify genetic markers that covered the MHC region, we carried out a case-control association enrolling 20 Caucasian patients with SJS/TEN. Our patient series included 10 cases related to paracetamol, 7 to allopurinol and 3 to different drugs (plaquenil, itraconazol, nabumetone). Healthy controls were represented by 115 Caucasian bone marrow or stem cell donors. The HLA-A*, B*, C*, DRB1*, DQB1*, DQA1* and DPB1* genotyping were determined. The frequencies of HLA-A*33:03 as well as C*03:02 and C*08:01 were significantly higher in SJS/TEN patient subgroup showing allopurinol drug-induced severe cutaneous adverse reactions (SCAR) as compared to controls (28.6% vs 0%, P=0.00002, Pc=0.0011; 28.6% vs 0%, P=0.00002, Pc=0.001; 28.6% vs 0%, P=0.00002, Pc=0.001, respectively). In the same subgroup the frequencies of B*58:01, DRB1*15:02 and DRB1*13:02 alleles, although considerably higher than in control group (42.8% vs 5.2%, P=0.003; 28.6% vs 1.7%, P=0.005; 28.6% vs 3.5%, P=0.037, respectively), appeared no more statistically different after P correction (Pc=0.248; Pc=0.29; Pc=1.00, respectively). In addition, in 10 of the 20 SJS/TEN patient subgroup with paracetamol-induced SCAR no statistically significant association with HLA alleles could be found. However, in the same SJS/TEN patient subgroup showing allopurinol drug-induced SCAR, haplotype analysis indicated that B*58:01, DRB1*13:02 and DRB1*15:02 alleles, that in a single allele analysis lost statistical significance after P correction, may still confer susceptibility, because the B*58:01-DRB1*13:02 and DRB1*15:02-DQB1*05:02 are positively associated with the disease (14.2% vs 0.43%, P= 0.00001, Pc=0.00028; 14.2% vs 0.43%, P=0.00001, Pc=0.00028, respectively). Our results show that in contrast to SCAR-related to paracetamol, where HLA alleles do not appear to be involved, HLA molecules behave as a strong risk factor for SCAR-related to allopurinol even when a limited number of patients are considered.
Assuntos
Alelos , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe I/genética , Síndrome de Stevens-Johnson/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Haplótipos , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Síndrome de Stevens-Johnson/imunologia , Adulto JovemRESUMO
BACKGROUND: Spontaneous intracranial hypotension (SIH) is characterized by orthostatic headache, diffuse pachymeningeal enhancement on brain magnetic resonance imaging (MRI) and low cerebrospinal fluid (CSF) pressure. Treatment ranges from conservative management, such as bed rest, overhydration and caffeine, to invasive procedures, such as the autologous epidural blood patch (EBP), computed tomography (CT)-guided fibrin glue injection at the site of the leak and open surgical intervention. EBP has emerged as the treatment of choice for SIH when initial conservative measures fail to bring relief. METHODS: Forty-two patients with SIH were treated with lumbar autologous EBP in Trendelenburg position preceded by pre-medication with acetazolamide. RESULTS: A complete recovery was obtained in all patients after one (90%), two (5%) or three (5%) EBPs. After EBP, two patients (5%) also performed evacuation of bilateral chronic subdural hematoma with mass effect. CONCLUSIONS: Spontaneous intracranial hypotension can be effectively cured by lumbar autologous EBP in Trendelenburg position pre-medicated with acetazolamide.
Assuntos
Acetazolamida/administração & dosagem , Placa de Sangue Epidural/métodos , Decúbito Inclinado com Rebaixamento da Cabeça/fisiologia , Hipotensão Intracraniana/tratamento farmacológico , Posicionamento do Paciente/métodos , Pré-Medicação/métodos , Derrame Subdural/tratamento farmacológico , Adulto , Idoso , Inibidores da Anidrase Carbônica/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Posicionamento do Paciente/normas , Recuperação de Função Fisiológica/fisiologia , Derrame Subdural/complicações , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: Since little is known about the role of gender in the course of Alzheimer's disease (AD), a prospective epidemiological study was conducted to detect gender differences in relation to AD evolution and outcome. METHODS: Six hundred AD patients, 214 men and 386 women, first seen between September 2000 and December 2003, were enrolled; the follow-up period lasted until December 2008. RESULTS: The men had greater comorbidity and higher mortality than the women, who instead recorded more disability and longer survival. Survival curves showed that women reach partial loss of autonomy faster than men. Higher Neuropsychiatric Inventory scores at baseline showed a predictive value for loss of autonomy regardless of gender. Pharmacological treatment seems to have a protective role on disability and mortality. CONCLUSIONS: Gender influences disease evolution not only directly but also through other factors such as comorbidity.
Assuntos
Doença de Alzheimer , Atividades Cotidianas/psicologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/fisiopatologia , Inibidores da Colinesterase/uso terapêutico , Feminino , Idoso Fragilizado/psicologia , Humanos , Testes de Inteligência , Itália , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores Sexuais , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Of the cases with nocturnal frontal lobe epilepsy (NFLE) approximately 30% are refractory to antiepileptic medication, with several patients suffering from the effects of both ongoing seizures and disrupted sleep. From a consecutive series of 522 patients operated on for drug-resistant focal epilepsy, 21 cases (4%), whose frontal lobe seizures occurred almost exclusively (>90%) during sleep, were selected. All patients underwent a comprehensive pre-surgical evaluation, which included history, interictal EEG, scalp video-EEG monitoring, high-resolution MRI and, when indicated, invasive recording by stereo-EEG (SEEG). There were 11 males and 10 females, whose mean age at seizure onset was 6.2 years, mean age at surgery was 24.7 years and seizure frequency ranged from <20/month to >300/month. Nine patients reported excessive daytime sleepiness (EDS). Prevalent ictal clinical signs were represented by asymmetric posturing (6 cases), hyperkinetic automatisms (10 cases), combined tonic posturing and hyperkinetic automatisms (4 cases) and mimetic automatisms (1 case). All patients reported some kind of subjective manifestations. Interictal and ictal EEG provided lateralizing or localizing information in most patients. MRI was unrevealing in 10 cases and it showed a focal anatomical abnormality in one frontal lobe in 11 cases. Eighteen patients underwent a SEEG evaluation to better define the epileptogenic zone (EZ). All patients received a microsurgical resection in one frontal lobe, tailored according to pre-surgical evaluations. Two patients were operated on twice owing to poor results after the first resection. Histology demonstrated a Taylor-type focal cortical dysplasia (FCD) in 16 patients and an architectural FCD in 4. In one case no histological change was found. After a post-operative follow-up of at least 12 months (mean 42.5 months) all the 16 patients with a Taylor's FCD were in Engel's Class Ia and the other 5 patients were in Engel's Classes II or III. After 6 months post-surgery EDS had disappeared in the 9 patients who presented this complaint pre-operatively. It is concluded that patients with drug-resistant, disabling sleep-related seizures of frontal lobe origin should be considered for resective surgery, which may provide excellent results both on seizures and on epilepsy-related sleep disturbances. An accurate pre-surgical evaluation, which often requires invasive EEG recording, is mandatory to define the EZ. Further investigation is needed to explain the possible causal relationships between FCD, particularly Taylor-type, and sleep-related seizures, as observed in this cohort of NFLE patients.
Assuntos
Epilepsia do Lobo Frontal/cirurgia , Sono , Adolescente , Adulto , Anticonvulsivantes/uso terapêutico , Mapeamento Encefálico/métodos , Criança , Ritmo Circadiano , Resistência a Medicamentos , Eletroencefalografia/métodos , Epilepsia do Lobo Frontal/tratamento farmacológico , Epilepsia do Lobo Frontal/patologia , Epilepsia do Lobo Frontal/fisiopatologia , Feminino , Seguimentos , Lobo Frontal/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Microcirurgia/métodos , Estudos Retrospectivos , Resultado do Tratamento , Gravação em VídeoRESUMO
A substantial genetic contribution in the etiology of developmental dyslexia (DD) has been well documented with independent groups reporting a susceptibility locus on chromosome 15q. After the identification of the DYX1C1 gene as a potential candidate for DD, several independent association studies reported controversial results. We performed a family-based association study to determine whether the DYX1C1 single nucleotide polymorphisms (SNPs) that have been associated with DD before, that is SNPs '-3GA' and '1249GT', influence a broader phenotypic definition of DD. A significant linkage disequilibrium was observed with 'Single Letter Backward Span' (SLBS) in both single-marker and haplotype analyses. These results provide further support to the association between DD and DYX1C1 and it suggests that the linkage disequilibrium with DYX1C1 is more saliently explained in Italian dyslexics by short-term memory, as measured by 'SLBS', than by the categorical diagnosis of DD or other related phenotypes.
Assuntos
Dislexia/genética , Memória de Curto Prazo/fisiologia , Proteínas do Tecido Nervoso/genética , Proteínas Nucleares/genética , Criança , Proteínas do Citoesqueleto , DNA/genética , Dislexia/psicologia , Feminino , Marcadores Genéticos , Genótipo , Haplótipos , Humanos , Inteligência/fisiologia , Testes de Inteligência , Desequilíbrio de Ligação/genética , Masculino , Testes Neuropsicológicos , Fenótipo , Desempenho Psicomotor/fisiologia , LeituraRESUMO
The ability to process and identify human faces matures early in life, is universal and is mediated by a distributed neural system. The temporal dynamics of this cognitive-emotional task can be studied by cerebral visual event-related potentials (ERPs) that are stable from midchildhood onwards. We hypothesized that part of individual variability in the parameters of the N170, a waveform that specifically marks the early, precategorical phases of human face processing, could be associated with genetic variation at the functional polymorphism of the catechol-O-methyltransferase (val(158)met) gene, which influences information processing, cognitive control tasks and patterns of brain activation during passive processing of human facial stimuli. Forty-nine third and fourth graders underwent a task of implicit processing of other children's facial expressions of emotions while ERPs were recorded. The N170 parameters (latency and amplitude) were insensitive to the type of expression, stimulus repetition, gender or school grade. Although limited by the absence of met- homozygotes among boys, data showed shorter N170 latency associated with the presence of 1-2 met158 alleles, and family-based association tests (as implemented in the PBAT version 2.6 software package) confirmed the association. These data were independent of the serotonin transporter promoter polymorphism and the N400 waveform investigated in the same group of children in a previous study. Some electrophysiological features of face processing may be stable from midchildhood onwards. Different waveforms generated by face processing may have at least partially independent genetic architectures and yield different implications toward the understanding of individual differences in cognition and emotions.
Assuntos
Catecol O-Metiltransferase/genética , Potenciais Evocados Visuais/genética , Expressão Facial , Reconhecimento Visual de Modelos/fisiologia , Tempo de Reação/genética , Criança , Discriminação Psicológica/fisiologia , Emoções/fisiologia , Feminino , Genótipo , Humanos , Masculino , Processos Mentais/fisiologia , Percepção SocialAssuntos
Agenesia do Corpo Caloso/genética , Agenesia do Corpo Caloso/patologia , Oxigenases de Função Mista/genética , Mutação , Paraparesia Espástica/genética , Paraparesia Espástica/patologia , Idade de Início , Sequência de Aminoácidos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Linhagem , IrmãosRESUMO
OBJECTIVE: The aim of this study was to assess efficacy and toxicity of temozolomide given alone or in combination with thalidomide, an anti-angiogenetic drug, in patients with newly diagnosed glioblastoma multiforme (GBM). PATIENTS AND METHODS: 46 patients with histologically proven GBM were eligible for inclusion. Twenty-three patients (15 males and 8 females) received temozolomide on a conventional schedule; 23 patients (12 males and 11 females) received temozolomide on the same schedule and thalidomide was dose-adjusted in each individual patient based on their tolerance. RESULTS: The median survival time was 12 months for temozolomide and 13 months for temozolomide + thalidomide. CONCLUSION: The administration of temozolomide in association with thalidomide after radiotherapy (RT) does not offer an advantage over temozolomide alone in adults with newly diagnosed GBM. The two therapeutic strategies produce similar results for survival, but the latter regimen shows a moderate increase in toxicity.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Dacarbazina/análogos & derivados , Glioblastoma/tratamento farmacológico , Adulto , Idoso , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Terapia Combinada , Dacarbazina/administração & dosagem , Dacarbazina/uso terapêutico , Feminino , Glioblastoma/radioterapia , Glioblastoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Temozolomida , Talidomida/administração & dosagemRESUMO
OBJECTIVE: Even if the majority of patients with Guillain-Barré syndrome (GBS) have a favourable functional outcome some residual motor and sensory signs and symptoms may remain. The aim of this study was to evaluate the long-term effect of GBS on daily life,working activities, hobbies and social status and the presence of residual symptoms. PATIENTS AND METHODS: Seventy patients with GBS enrolled in a case-control study were examined. Information on signs or symptoms during the acute phase of the disease was retrieved from medical records and an ad-hoc questionnaire administered during hospitalization. Patients were interviewed by phone 3 to 5 years after disease onset about residual symptoms and changes in daily living. Disability and handicap were assessed using the Hughes, Rankin and Rotterdam 9-items scale. RESULTS: At follow-up 45 patients (64 %) made a complete functional recovery; 19 patients (27%) had some minor limitations in daily life although they were able to perform all their activities independently while 6 (9 %) needed aid for some hours or continuously during the day. Nineteen patients (27 %) had, however, to make substantial changes in their job, hobbies or social activities. There was no significant correlation between clinical and laboratory features during the acute phase of GBS and outcome. CONCLUSIONS: Although over 90% of our GBS patients had a more or less complete functional recovery, almost 30% of them had to make substantial changes in daily life. These findings indicate that GBS still has a significant impact on patients' life which may go beyond their residual disability or impairment. Treatment of GBS should not be only aimed at improving patients' disability but also at limiting the impact of the disease on their social life.
Assuntos
Pessoas com Deficiência/psicologia , Síndrome de Guillain-Barré/fisiopatologia , Síndrome de Guillain-Barré/psicologia , Mudança Social , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Avaliação da Deficiência , Progressão da Doença , Feminino , Seguimentos , Síndrome de Guillain-Barré/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
UNLABELLED: AIM. The aim of this study is to show the compliance and the test-retest reliability of the questionnaire. METHODS: Construction of a structured questionnaire to perform a phone follow-up in 511 persons with traumatic spinal cord injury (SCI) 4 years after discharge from the first rehabilitative hospitalization. The questionnaire is structured in 24 items, comprising exclusion (closed questions) answers and 3 analogic scale answers, divided into 7 aspects: clinical conditions, sentimental relationships, quality of life, autonomy, mobility, occupation, social reintegration. A pilot survey on 20 subjects with SCI, hospitalized in different periods in 2 rehabilitation centers, was performed to check the questionnaire's feasibility and reproducibility. The persons were interviewed twice by telephone, with an interval of about one month, by a psychologist. The questionnaire was completed during one single phone conversation. RESULTS: No missing answers were recorded. The test run for this questionnaire showed high reproducibility based on the large numbers of questions with 100% correspondence between the answers ''before'' and ''after''. For most of the other questions this factor ranged between 80% and 99%, and for 2 questions on the analogic scale between 30% and 50%. CONCLUSIONS: The data collected by this pilot survey show the reliability of this questionnaire for all answers, save for the quantification of subjective variables.
Assuntos
Traumatismos da Medula Espinal/reabilitação , Inquéritos e Questionários , Atividades Cotidianas , Adulto , Idoso , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Psicometria , Qualidade de Vida , Reprodutibilidade dos Testes , Traumatismos da Medula Espinal/fisiopatologiaRESUMO
Cerebral cavernous malformations (CCMs) are vascular abnormalities that may cause seizures, headaches, intracerebral hemorrhages, and focal neurological deficits; they can also be clinically silent and occur as a sporadic or an autosomal dominant condition. Three genes have been identified as causing familial CCM: KRIT1/CCM1, MGC4607/CCM2, and PDCD10/CCM3, mapping, respectively, on chromosomes 7q, 7p, and 3q. Here, we report an Italian family affected by CCM due to a MGC4607 gene mutation, on exon 4. All the affected subjects suffered from seizures, and some of them underwent surgery for removal of a cavernous angioma. Brain MRI showed multiple lesions consistent with CCMs in all patients. Spinal and cutaneous cavernous angiomas were present too. This report underlines the need for a careful interdisciplinarity among neurologists, neuroradiologists, neurosurgeons, geneticists, ophthalmologists, and dermatologists for a total evaluation of the different manifestations of familial CCM. This points out that only referral centers are organized to offer a multidisciplinary management of this disease.
Assuntos
Proteínas de Transporte/genética , Neoplasias do Sistema Nervoso Central/genética , Hemangioma Cavernoso do Sistema Nervoso Central/genética , Mutação , Neoplasias Cutâneas/genética , Adolescente , Adulto , Idoso , Neoplasias do Sistema Nervoso Central/diagnóstico , Criança , Éxons , Feminino , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico , Humanos , Masculino , Linhagem , Neoplasias Cutâneas/diagnósticoRESUMO
Sixteen cerebrospinal fluid (CSF) specimens serially obtained during long-term follow-up of two patients with Devic's neuromyelitis optica (DNO) were compared with 65 CSF samples from patients with multiple sclerosis (MS). By statistical analysis, the CSF profile in DNO was found to differ from that observed in MS, mainly showing pleocytosis, blood-brain barrier damage, and absence of persistent immunoglobulin G synthesis within the central nervous system. Oligoclonal bands, detected with isoelectric focusing, were present in CSF of 92% of the patients with MS, and in three CSF specimens from one patient with DNO during the first 6 months after disease onset. The bands disappeared in two subsequent samples. This finding has never been described in MS. One patient with DNO had an apparent chronic-relapsing course probably due to steroid dependence. The clinical and CSF features of our cases favour the nosographic independence of DNO and MS.
Assuntos
Doenças Desmielinizantes/fisiopatologia , Neuromielite Óptica/fisiopatologia , Adulto , Barreira Hematoencefálica , Feminino , Seguimentos , Humanos , Imunoglobulina G/líquido cefalorraquidiano , Imunoglobulinas/líquido cefalorraquidiano , Linfocitose/patologia , Neuromielite Óptica/líquido cefalorraquidiano , Neuromielite Óptica/metabolismo , Bandas Oligoclonais , Albumina Sérica/líquido cefalorraquidianoRESUMO
The 9139 follow-up records of 438 myasthenia gravis (MG) patients were reviewed. Excluding those patients who were diagnosed 5 or more years after symptom onset (n = 37) and those who experienced only oculomotor symptoms throughout follow-up (n = 21), there were 380 patients. A survival analysis approach was used to assess the influence of prognostic factors on the following endpoints: (a) stable complete remission, (b) complete remission of at least 6 months and (c) pharmacological remission of at least 6 months. Early diagnosis was associated with a better prognosis with respect to all endpoints. Thymectomy also improved the prognosis but only for those patients without thymoma. Later MG onset was associated with a higher tendency to achieve pharmacological remission.
Assuntos
Miastenia Gravis/mortalidade , Adulto , Idade de Início , Bases de Dados Factuais , Oftalmopatias/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Regressão , Estudos Retrospectivos , Taxa de Sobrevida , Timectomia , Timoma , Neoplasias do TimoRESUMO
The sensitivities and predictive values of visual, somatosensory, and brain auditory evoked potentials (EPs), cerebrospinal fluid oligoclonal banding (CSF-OB) and magnetic resonance imaging (MRI) were evaluated for the early diagnosis of clinically definite multiple sclerosis (CDMS). Paraclinical evidence of asymptomatic lesions allows a diagnosis of CDMS. Eighty-two patients in whom MS was suspected but diagnosis of CDMS was not possible entered the study prospectively. Paraclinical examinations were performed at entry. Patients were examined and underwent EPs every 6 months, and MRI yearly. After a mean follow-up of 2.9 years, 28 patients (34%) had developed CDMS (McDonald-Halliday criteria). The initial MRI was strongly suggestive of MS in 19 of these (68%), while 27 (96%) had at least one MS-like abnormality in the initial MRI. CSF-OB and EPs had lower sensitivities. CDMS developed during follow-up in 19 of the 36 patients (53%) who had an initial MRI strongly suggestive of MS but in only 1 of the 25 who had normal MRI when first studied. These results support previous conclusions that MRI is the most sensitive test for detecting white matter asymptomatic lesions, and the most predictive for the diagnosis of CDMS.
Assuntos
Encéfalo/patologia , Potenciais Evocados Visuais , Imageamento por Ressonância Magnética , Esclerose Múltipla/diagnóstico , Adolescente , Adulto , Anticorpos/líquido cefalorraquidiano , Proteínas do Líquido Cefalorraquidiano/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/complicações , Neurite Óptica/etiologia , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
A recent study reported an association between left-handedness and some pathologies, such as autoimmune diseases, including myasthenia gravis (MG). We studied hand preference in 102 patients with a generalized autoimmune form of myasthenia gravis and in a control group of 178 subjects. We employed Oldfield's inventory with a few minor modifications. The questionnaire also asked the hand preference of patients' and controls' relatives. For each subject, the laterality quotient (LQ) was calculated and submitted to ANOVA. The frequency of left-handedness in controls was similar to that reported in the literature. Although left-handedness occurred less often in myasthenics, the difference between the two groups was not significant. Also the frequency of left-handedness in relatives of myasthenic patients did not differ from that observed in controls.
Assuntos
Lateralidade Funcional , Miastenia Gravis/psicologia , Humanos , Testes Neuropsicológicos , Caracteres SexuaisRESUMO
Following previous work on the modification and inversion of electroendoosmotic flow (EOF) of naked silica by a cyclic diamine [1-(4-iodobutyl)-1,4-dimethylpiperazin-1-ium iodide] [J. Chromatogr. A 894 (2000) 53], the present report considerably expands previous data by describing additional compounds of the same series of omega-iodoalkylammonium salts. Four of them are able to instantaneously reverse the EOF, thus producing a cationic surface with a highly stable reverse EOF. All these compounds are believed to become covalently attached to the silica surface via alkylation occurring by nucleophilic substitution of ionized silanols on the silica wall by the omega-iodo functionality in the modifier. The unique advantage of such compounds, as compared to adsorbed polymers or oligoamine EOF quenchers, is that they are not needed any longer in the background electrolyte, after the initial conditioning step inducing the covalent bond. It is additionally demonstrated, by running a mixture of cinnamic acid compounds, that some of the omega-iodoalkylammonium salts can act as modulators of analyte migration, thus inducing separations of otherwise identical compounds, such as isomeric species. Such interactions can only occur when the analytes drift close to the silica wall, and must be rapidly reversible, since no peak tailing or broadening is experienced.
Assuntos
Eletroforese Capilar/métodos , Compostos de Amônio Quaternário/química , Sais/química , Estrutura MolecularRESUMO
A novel compound ¿quaternarized piperazine [(N-methyl,N-4-iodobutyl)-N'-methylpiperazine] (QPzI)¿ for the coating of a silica capillary able to reduce or invert the electroosmotic flow (EOF) in capillary zone electrophoresis is reported. Unlike standard oligoamines (like spermine and tetraethylene pentamine) which are very efficient in quenching macromolecule interaction with the silica wall, but only in acidic pH ranges, QPzI acts all along the pH scale, including alkaline pH ranges. It is believed that QPzI behaves like a trifunctional derivative: it forms ionic bonds with dissociated silanols via its quaternary nitrogen, hydrogen bonds via its tertiary nitrogen and, most importantly, a covalent bond via alkylation of ionized silanols through the terminal iodine atom in the butyl chain. Excellent separations are obtained with a variety of organic compounds, such as aromatic carboxylic acids, tryptophan metabolites and arylalkanoic acids. Such separations could not be obtained in naked capillaries in the presence of oligoamines and on some occasions not even with capillaries coated with a covalent layer of neutral polymers. In separations taking place in alkaline media, QPzI is not added to the background electrolyte, but is used simply in the capillary pre-conditioning step, a unique feature strongly supporting the hypothesis of its covalent binding to the silica surface. In difficult separations, such as in the case of o-/p-OMe-phenylacetic acids or nicotinic/picolinic acid, which would not normally occur under standard conditions, it is believed that QPzI acts as a discriminator, thus playing an active role in the separation process, rather than simply modulating the EOF.
Assuntos
Diaminas/química , Eletroforese Capilar/instrumentação , Dióxido de Silício/química , Espectroscopia de Ressonância Magnética , OsmoseRESUMO
Notwithstanding the use of acidic, amphoteric, isoelectric buffers with isoelectric points (pI) in the pH 2-3 range, adsorption of proteins to the naked silica wall can be non-negligible. Two such buffers have been tested: iminodiacetic acid (IDA; pI 2.23, apparent pH 3.2 in 7 M urea) and aspartic acid (pI 2.77, apparent pH 3.7 in 7 M urea). Three potential quenchers of such interactions have been tested: hydroxyethylcellulose (HEC; number average molecular mass, Mr 27,000), TEPA (tetraethylenepentamine) and a novel, quatemarized piperazine [N(methyl-N-omega-iodobutyl)-N'-methylpiperazine] (Q-Pip), either alone or in binary and ternary mixtures. Human alpha- and beta-globin chains have been used as test proteins in capillary electrophoresis separations. It has been found that mixtures of these compounds are the worst possible remedy. E.g., a ternary mixture comprising 0.5% HEC, 0.5 mM TEPA and 1 mM Q-Pip still leaves behind 4.5% adsorbed protein onto the silica surface in runs in IDA buffer and 7 M urea (pH 3.2). Conversely, 0.5 mM TEPA or 1 mM Q-Pip, when used alone, minimize adsorption down to only 1.8% and 0.5%, respectively. When the same globin chain separations are performed in Asp and 7 M urea (pH 3.7), the situation is much worse: 44% protein is adsorbed in a ternary mixture of 0.5% HEC, 1 mM Q-Pip and 0.5 mM TEPA. However, when used alone, 0.5 mM TEPA and 1 mM Q-Pip reduce globin adsorption to levels of 8% and 5%, respectively. TEPA and Q-Pip are found to be in all cases the best quenchers of protein interaction to naked fused-silica; in addition they exhibit the unique property of smoothing the base-line and giving reproducible runs. The best method for desorbing bound protein was found to be an electrophoretic step consisting in driving sodium dodecylsulphate micelles from the cathodic reservoir.
Assuntos
Eletroforese Capilar , Globinas/metabolismo , Soluções Tampão , Humanos , Ponto Isoelétrico , Ligação ProteicaRESUMO
The acute and chronic antihypertensive effects of nifedipine were investigated in patients with chronic renal insufficiency (CRI). The acute effects were assessed after the administration either of a fast-release nifedipine capsule or a slow-release nifedipine tablet in 10 and 15 patients respectively. Both the preparations induced prompt and marked reduction of systolic and of diastolic blood pressure, but the capsules showed a shorter antihypertensive effect (2 hours) than tablets (more than 6 hours). The chronic effects of nifedipine tablets given in addition to the previous therapy was assessed in 25 patients with CRI and resistant hypertension. Both systolic and diastolic blood pressure values promptly fell and maintained within the normal range over the whole period of the study (12 months).