RESUMEN
BACKGROUND: To minimize the risk of progressive multifocal leucoencephalopathy (PML), treatment with natalizumab is often stopped after 2 years, but evidence upon rebound of disease activity is limited and controversial. OBJECTIVE: To evaluate effects of natalizumab discontinuation on clinical disease activity within twelve months after cessation. METHODS: We retrospectively analyzed data of 201 patients with MS who discontinued natalizumab between 2007 and 2012. Mean change scores of annualized relapse rate (ARR) and expanded disability status scale (EDSS) were calculated for detection of rebound disease activity after twelve months. RESULTS: Natalizumab exposure did not exceed 2 years in 50.2% of patients, and the most common reasons for discontinuation were a long treatment period and concern of PML (56%). A total of 11.9% experienced a rebound phenomenon within twelve months. Mean ARR prenatalizumab was lower (P = 0.001, 95% CI -1.0-0.000) and treatment response to natalizumab poorer (P < 0.001, 95% CI 0.4-1.3) in patients with rebound compared to those without, but rebound was not associated with brief exposure to natalizumab (P = 0.159, 95% CI -9.3-1.5). 86.1% of patients switched to another therapy. Patients without rebound were found more often in the group starting an alternative treatment early (P = 0.013). CONCLUSION: Our data suggest that rebound of MS disease activity affects a subgroup of patients (11.9%), especially those with low disease activity before natalizumab therapy and a longer treatment gap after its withdrawal.
Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Síndrome de Abstinencia a Sustancias/etiología , Adulto , Femenino , Humanos , Masculino , Esclerosis Múltiple/tratamiento farmacológico , Natalizumab , Estudios RetrospectivosRESUMEN
Isolated monarthritis caused by Tropheryma whipplei without involvement of the gastrointestinal tract is rare but is nowadays often described as an early manifestation of the disease. In a male patient with recurrent knee joint arthritis for several years, we could ultimately diagnose Whipple's disease based on PCR positive biopsies of synovial tissue and fluid. Furthermore, the patient was found to be an asymptomatic T. whipplei carrier. With adequate antibiotic therapy the patient has meanwhile fully recovered.
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Antibacterianos/uso terapéutico , Artritis/tratamiento farmacológico , Artritis/microbiología , Tropheryma , Enfermedad de Whipple/tratamiento farmacológico , Enfermedad de Whipple/microbiología , Artritis/diagnóstico , Diagnóstico Diferencial , Humanos , Articulación de la Rodilla , Masculino , Persona de Mediana Edad , Enfermedades Raras/diagnóstico , Enfermedades Raras/tratamiento farmacológico , Enfermedades Raras/microbiología , Resultado del Tratamiento , Enfermedad de Whipple/diagnósticoRESUMEN
Combined forearm fractures are identified according to their location as Galeazzi, Monteggia or Essex-Lopresti injuries. The feature common to these three forms is the combination of a forearm fracture with instability of the distal or proximal radio-ulnar joint. The combination of Galeazzi and Monteggia fractures in the same extremity is an exceedingly rare occurrence. It has been reported in eight cases including two pediatric patients worldwide. In this case report the rare occurrence of the combination of these injuries and the possibility of pitfalls in the operative treatment are presented.
Asunto(s)
Traumatismos del Antebrazo/diagnóstico por imagen , Traumatismos del Antebrazo/cirugía , Fijación Interna de Fracturas/instrumentación , Fracturas del Radio/diagnóstico por imagen , Fracturas del Radio/cirugía , Fracturas del Cúbito/diagnóstico por imagen , Fracturas del Cúbito/cirugía , Adulto , Fijación Interna de Fracturas/métodos , Humanos , Masculino , Radiografía , Resultado del TratamientoRESUMEN
We sequenced 61 patients with various idiopathic generalized epilepsy (IGE) syndromes for mutations in the EFHC1 gene. We detected three novel heterozygous missense mutations (I174V, C259Y, A394S) and one possibly pathogenic variant in the 3' UTR (2014t>c). The mutation I174V was also detected in 1 of 372 screened patients with temporal lobe epilepsy. We conclude that mutations in the EFHC1 gene may underlie different types of epilepsy syndromes.
Asunto(s)
Proteínas de Unión al Calcio/genética , Epilepsia Generalizada/genética , Fenotipo , Regiones no Traducidas 3'/genética , Adulto , Femenino , Variación Genética , Humanos , Masculino , Mutación Missense , SíndromeRESUMEN
Mutations in the chloride channel gene CLCN2 have been reported in families with generalized and focal epilepsy syndromes. To evaluate the contribution of mutations in the CLCN2 gene to the etiology of epilepsies in our population, we screened 96 patients with different epilepsy syndromes and a putative genetic background. No definite mutations were found in our study population. We conclude that mutations in the CLCN2 gene are only a rare cause of idiopathic generalized epilepsy.
Asunto(s)
Canales de Cloruro/genética , Epilepsia Generalizada/genética , Mutación Puntual , Canales de Cloruro CLC-2 , Pruebas Genéticas , Variación Genética , HumanosRESUMEN
Glatiramer acetate (GA; Copaxone) is a random sequence polypeptide used in the treatment of relapsing remitting multiple sclerosis (RR MS). We have recently demonstrated that prior to treatment, GA induces proliferation of resting T cells and is not cross-reactive with myelin antigens. Daily GA injections induce a significant loss of this GA responsiveness, which is associated with the induction of highly cross-reactive Th2-type T cells potentially capable of suppressing inflammatory responses. The mechanism of action by which GA induces T cell nonresponsiveness leading to T cell receptor degeneracy in patients with RR MS is unknown. Here, we examined the effects of daily GA administration on the induction of T cell hyporesponsiveness. The frequency of GA-reactive T cells in peripheral blood of seven patients with RR MS was measured by limiting dilution analysis prior to and during 6 months of treatment. In addition, a model in which GA-reactive T cells were stimulated in vitro was developed to better characterize the selection of T cell populations over time. In vivo treatment with GA induced a decrease in GA-reactive T cell frequencies and hyporesponsiveness of CD4(+) T cell reactivity to GA in vitro that was only partially reversed by the addition of IL-2. These data suggest that T cell peripheral tolerance to GA was achieved in vivo during treatment. Thus, our in vitro data suggest that the underlying changes in GA-reactive CD4(+) T cell reactivity could be explained by the induction of T cell anergy and clonal elimination.
Asunto(s)
Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Péptidos/farmacología , Linfocitos T/efectos de los fármacos , Adulto , Presentación de Antígeno/efectos de los fármacos , Citocinas/biosíntesis , Relación Dosis-Respuesta a Droga , Femenino , Acetato de Glatiramer , Humanos , Tolerancia Inmunológica/efectos de los fármacos , Inyecciones Subcutáneas , Interleucina-2/farmacología , Masculino , Esclerosis Múltiple Recurrente-Remitente/inmunología , Péptidos/administración & dosificación , Proteínas Recombinantes/farmacología , Linfocitos T/inmunologíaRESUMEN
Automated analysis of submicron particles by computer-controlled scanning electron microscopy is generally possible. The minimum diameter of the detectable particles is dependent on the mean atomic number of the particles and the operating parameters of the scanning microscope. The main limitation with regard to particle size is set by the quality of the particle detection system, which generally is the backscatter electron detector. The accuracy of the results of the x-ray analyses is very often strongly affected by specimen damage, omnipresent especially for environmental particles even at low electron energies and probe currents. With the exception for light elements, the detection limit is approximately 1 wt%. Device-related limitations to automated analysis may be specimen drift and an unreliable autofocus function.
RESUMEN
The capacity of glatiramer acetate (GA), a random copolymer of alanine, lysine, glutamic acid, and tyrosine to stimulate primary in vitro human and murine T cell proliferation was examined. PBMCs isolated from healthy humans and relapsing remitting multiple sclerosis patients and spleen cells from inbred strains of mice, expressing different H-2 haplotypes, were used as sources of non-GA-primed lymphocytes. GA functioned as a universal Ag, inducing dose-dependent proliferation of all non-GA-primed human and murine T cell populations tested. Moreover, GA stimulated PBMCs derived ex vivo from human cord blood, strongly suggesting that GA can activate both naive and memory T cells. The human T cell proliferative responses to GA were HLA class II DR-restricted by virtue of the ability of anti-class II Ab to inhibit T cell proliferation, and the demonstration that individual GA specific human T cell clones were HLA class II DR-restricted by either restriction element but not both. Furthermore, GA-reactive T cells secreted Th0 cytokines and expressed a diverse repertoire of TCR. Limiting dilution analysis indicated that the T cell precursor frequency among the healthy human adults tested ranged from 1:5,000 to 1:125,000. Given that all of the T cell populations tested were isolated from non-GA-primed donors, it appears that virtually all humans and murine strains contain significant numbers of T cell populations cross-reactive with GA. These findings may explain the recent clinical finding that daily s.c. administration of GA ameliorates the progression of multiple sclerosis.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Activación de Linfocitos , Péptidos/inmunología , Péptidos/metabolismo , Adulto , Animales , Linfocitos T CD4-Positivos/citología , Línea Celular Transformada , Separación Celular , Células Clonales , Relación Dosis-Respuesta Inmunológica , Femenino , Acetato de Glatiramer , Antígenos HLA-DR/genética , Antígenos HLA-DR/metabolismo , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/inmunología , Humanos , Inmunización , Memoria Inmunológica/genética , Separación Inmunomagnética , Recién Nacido , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/inmunología , Activación de Linfocitos/genética , Recuento de Linfocitos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Esclerosis Múltiple Recurrente-Remitente/inmunología , Péptidos/síntesis química , Péptidos/farmacología , Bazo/citología , Bazo/inmunología , Células TH1/citología , Células TH1/inmunología , Células TH1/metabolismo , Células Th2/citología , Células Th2/inmunología , Células Th2/metabolismoRESUMEN
We examined the effect of glatiramer acetate, a random copolymer of alanine, lysine, glutamic acid, and tyrosine, on antigen-specific T-cell responses in patients with multiple sclerosis (MS). Glatiramer acetate (Copaxone) functioned as a universal antigen, inducing proliferation, independent of any prior exposure to the polymer, in T-cell lines prepared from MS or healthy subjects. However, for most patients, daily injections of glatiramer acetate abolished this T-cell response and promoted the secretion of IL-5 and IL-13, which are characteristic of Th2 cells. The surviving glatiramer acetate-reactive T cells exhibited a greater degree of degeneracy as measured by cross-reactive responses to combinatorial peptide libraries. Thus, it appears that, in some individuals, in vivo administration of glatiramer acetate induces highly cross-reactive T cells that secrete Th2 cytokines. To our knowledge, glatiramer acetate is the first agent that suppresses human autoimmune disease and alters immune function by engaging the T-cell receptor. This compound may be useful in a variety of autoimmune disorders in which immune deviation to a Th2 type of response is desirable.
Asunto(s)
Inmunosupresores/farmacología , Esclerosis Múltiple/inmunología , Péptidos/farmacología , Células Th2/efectos de los fármacos , Adulto , Secuencia de Aminoácidos , División Celular , Células Cultivadas , Reacciones Cruzadas , Epítopos de Linfocito T/inmunología , Femenino , Acetato de Glatiramer , Humanos , Epítopos Inmunodominantes/inmunología , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéutico , Interferón gamma/metabolismo , Interleucina-5/metabolismo , Leucocitos Mononucleares/citología , Ligandos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Esclerosis Múltiple/tratamiento farmacológico , Proteína Básica de Mielina/inmunología , Vaina de Mielina/inmunología , Fragmentos de Péptidos/inmunología , Péptidos/administración & dosificación , Péptidos/uso terapéutico , Toxoide Tetánico/inmunología , Células Th2/inmunologíaRESUMEN
OBJECTIVE: To investigate the effects of vaccinations and steroids on disease progression and mood in patients with multiple sclerosis (MS). MATERIAL AND METHODS: Twenty-three patients with clinically definite MS were questioned with respect to vaccination history and the cumulative dose of steroids given during their life-time. EDSS scores and MRI scans of the brain were obtained and used to quantify clinical and MRI disease progression. Mood was assessed by using a self-estimated adjective mood scale. RESULTS: The number of vaccinations showed no effect on disease progression or mood. High cumulative steroid doses were associated with rapid MRI disease progression and the number of supratentorial MRI lesions. The absence of band-like MRI lesions was correlated with rapid clinical and MRI disease progression. Self-estimated mood tended to be worse in patients with chronic-progressive MS compared to those with relapsing-remitting MS. CONCLUSION: Neither clinical nor MRI-documented disease progression nor mood are influenced by the total number of vaccinations whereas high cumulative steroid doses and the absence of band-like MRI lesions indicate rapidly progressive MS. Self-estimated mood tends to be worse in patients with chronic-progressive MS compared to patients with relapsing-remitting MS.
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Afecto , Inmunoterapia/estadística & datos numéricos , Esclerosis Múltiple/diagnóstico , Esteroides/administración & dosificación , Adulto , Progresión de la Enfermedad , Femenino , Humanos , Esquemas de Inmunización , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
The psychiatric services of the Swiss region of Basel-Landschaft observed an increasing deterioration and shortage of accommodation offers for mentally ill persons. At the same time, it grew temporarily more and more difficult to let single rooms in flat-sharing communities. Therefore a psychiatric services research project aimed at evaluating the wishes and needs of specialists in the housing sphere, and of about 600 in- and outpatients, as well as for their caregivers. The results showed, similar to other studies, on the one hand patients' predominant wish to live independently, whereas on the other hand there was a great difference between the views of patients and their caregivers. The latter view this aspiration for independence rather skeptically. The striking disagreement between patients and caregivers may be fruitful for the therapeutic process; however, this applies only if both partners are aware of this fact.
Asunto(s)
Servicios Comunitarios de Salud Mental/provisión & distribución , Vivienda/estadística & datos numéricos , Trastornos Mentales/rehabilitación , Actividades Cotidianas , Adulto , Anciano , Estudios Transversales , Desinstitucionalización/estadística & datos numéricos , Femenino , Humanos , Incidencia , Masculino , Trastornos Mentales/epidemiología , Persona de Mediana Edad , Satisfacción del Paciente , Calidad de Vida , Deseabilidad Social , Suiza/epidemiologíaRESUMEN
Apoptosis plays a crucial role in natural recovery from T cell-mediated autoimmune disorders of the nervous system. Whether apoptosis also occurs in human inflammatory myopathies is unclear. In this study we examined muscle biopsy specimens from untreated patients with polymyositis (n = 12), dermatomyositis (n = 12), and inclusion body myositis (n = 12) for the presence of apoptosis using morphological criteria and DNA fragmentation by in situ tailing. In all these disorders, only rare T cells exhibited signs of apoptosis by nuclear morphology and in situ labeling techniques. Although Fas-expression was upregulated in a few inflammatory cells, increased apoptosis of the surrounding T cells was not observed. Further, nuclei of degenerating muscle fibers did not show morphological signs of apoptosis and were not labeled by the tailing reaction. We conclude that in the inflammatory myopathies, T cell inflammation is not cleared by apoptosis and affected muscle fibers do not die by apoptosis. The observations are consistent with the non-self-limited nature of these disorders and suggest that, in contrast to the nervous system, the local microenvironment in muscle does not deliver pro-apoptotic stimuli.
Asunto(s)
Apoptosis/inmunología , Enfermedades Autoinmunes/inmunología , Dermatomiositis/inmunología , Antígenos de Histocompatibilidad Clase I/inmunología , Fibras Musculares Esqueléticas/inmunología , Miositis por Cuerpos de Inclusión/inmunología , Polimiositis/inmunología , Subgrupos de Linfocitos T/inmunología , Adulto , Anciano , Enfermedades Autoinmunes/patología , Dermatomiositis/patología , Humanos , Hibridación in Situ , Persona de Mediana Edad , Miositis por Cuerpos de Inclusión/patología , Polimiositis/patología , Receptor fas/análisisRESUMEN
The adrenocortical response is central to recovery from experimental allergic encephalomyelitis (EAE) in the Lewis rat, as reflected by the increased severity of the disease in adrenalectomized animals. The protection conferred by glucocorticoids is related to the immunosuppressive effects of the steroid, which may include apoptosis of immunocompetent cells. Here we describe T-cell infiltration and apoptosis in spinal cord lesions of intact (INT) and adrenalectomized (ADX) rats during the course of EAE. The normal disease course (peak clinical score 3) was induced following intra-peritoneal transfer of 4 x 10(7) myelin basic protein (MBP)-sensitized spleen lymphocytes to INT rats. Maximum apoptosis of infiltrating T cells (32%) was evident on day 7 and was associated with the expected increase in circulating corticosterone levels and the onset of disease remission. ADX rats, which have no corticosterone response, administered 4 x 10(7) cells displayed rapid and fatal EAE with only minimal signs of T-cell apoptosis (1.9-3.8%). In order to delay the onset and prolong the disease in ADX rats, a lower cell dose was used. In ADX rats injected with 1 x 10(6) cells, disease onset was comparable to INT 4 x 10(7) rats but disease progression was equally rapid and T-cell apoptosis (1.4-8.5%) was similarly low to that seen in ADX rats given the higher dose of cells. Transfer of the lower number of splenocytes (1 x 10(6) cells) to INT rats resulted in only mild EAE (clinical score 0.5-1) which was reflected both in low T cell apoptosis (1.7-16%) and circulating corticosterone levels. In all treatment groups very few apoptotic macrophages were detected ( < 1% of all macrophages) and no differences between groups were apparent. The results suggest that glucocorticoid-mediated T-cell apoptosis, whether initiated directly or indirectly, may contribute to the recovery phase of EAE in Lewis rats.
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Apoptosis , Sistema Nervioso Central/inmunología , Encefalomielitis Autoinmune Experimental/inmunología , Macrófagos/inmunología , Linfocitos T/inmunología , Adrenalectomía , Animales , Apoptosis/efectos de los fármacos , Recuento de Células , Sistema Nervioso Central/patología , Corticosterona/farmacología , Modelos Animales de Enfermedad , Femenino , Cobayas , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/inmunología , Proteína Básica de Mielina/farmacología , Ratas , Ratas Endogámicas LewRESUMEN
In this study we have characterized apoptotic cell death of autoreactive T cells resulting from their interaction with astrocytes and the modulatory effect of steroid hormones. Time kinetics of T-cell activation by interferon (IFN)-gamma-treated astrocytes from neonatal Lewis rats and by professional antigen presenting cells (APCs) from bulk suspensions of thymus or spleen were performed. [3H]Thymidine incorporation of neuritogenic P2- and encephalitogenic myelin basic protein (MBP)-specific T-cell lines declined after 48 h in culture with astrocytes. A similar suppressive effect was observed when T cells were cocultured with thymic APCs and astrocytes. This effect disappeared when astrocytes were separated by a transwell system. After 72 h of culture with astrocytes a mean of 17.5 +/- 12.4% T cells exhibited morphological signs of apoptosis. Apoptosis was identified by light microscopy, and confirmed by electron microscopy, by in situ tailing reaction and by agarose gel electrophoresis. Glucocorticosteroids and oestrogen specifically enhanced T-cell apoptosis within 8 h (69.8 +/- 23.1% and 69 +/- 17.1%, respectively) when added after 72 h to the astrocyte system, but not at earlier time points of T-cell activation or when thymic APCs were used. Glucocorticoid-mediated T-cell apoptosis was inhibited by the steroid-receptor antagonist RU 486. Pregnenolone, lipocortin-1, indomethacin and transforming growth factor-beta did not induce apoptosis in this system. The steroid effect was not associated with CD28, IL-2 receptor, or transferrin-receptor expression, which were equally upregulated on T cells activated by astrocytes or thymic APC as shown by fluorescence activated cell sorting (FACS) analysis. We conclude that astrocytes as CNS-specific APC may render T cells susceptible for induction of apoptotic cell death. Some steroid hormones can markedly enhance this process in vitro and may augment an additional effect of a systemic corticosteroid response in vivo during recovery from autoimmune encephalomyelitis.
Asunto(s)
Antígenos/inmunología , Apoptosis , Astrocitos/inmunología , Linfocitos T/inmunología , Análisis de Varianza , Animales , Células Cultivadas , Relación Dosis-Respuesta a Droga , Interferón gamma/farmacología , Modelos Inmunológicos , Ratas , Ratas Endogámicas LewRESUMEN
There is no cure for multiple sclerosis (MS). Many therapeutic strategies are known. With exception of high dose corticosteroids for the treatment of acute exacerbations most of the concepts are not generally accepted. Reasons are the variable, often unpredictable natural course of MS, the incomplete understanding of the pathophysiology and the difficult trial design. Yet, new therapeutic agents give hope at least to slow the course of the disease.
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Esclerosis Múltiple/terapia , Azatioprina/administración & dosificación , Cladribina/administración & dosificación , Ciclofosfamida/administración & dosificación , Acetato de Glatiramer , Humanos , Interferón beta/administración & dosificación , Metotrexato/administración & dosificación , Mitoxantrona/administración & dosificación , Péptidos/administración & dosificación , Plasmaféresis , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
After major head trauma, a 28-year-old male patient developed tetraparesis with marked left-sided contractions of the leg adductors. Spasticity was resistant to antispastic drugs and intensive physiotherapy. Therefore, we injected 12.5 ng botulinum A toxin (Dysport) in the left adductor longus and adductor magnus. Eight measurements of the post-micturition residual urine of the bladder before botulinum-A-toxin administration gave no evidence for urinary retention. Between day 5 and 14 after injection we measured pathologically increased urinary volumes up to 130 ml at five different points of time. This case report indicates possible subclinical side effects on the autonomic nervous system of the urinary bladder.
Asunto(s)
Toxinas Botulínicas/efectos adversos , Traumatismos Cerrados de la Cabeza/rehabilitación , Espasticidad Muscular/rehabilitación , Cuadriplejía/rehabilitación , Retención Urinaria/inducido químicamente , Urodinámica/efectos de los fármacos , Adulto , Sistema Nervioso Autónomo/efectos de los fármacos , Toxinas Botulínicas/administración & dosificación , Terapia Combinada , Humanos , Inyecciones Intramusculares , Masculino , Modalidades de Fisioterapia , Vejiga Urinaria/inervación , Retención Urinaria/diagnósticoRESUMEN
BACKGROUND: A number of enzymatic techniques have recently been developed to detect DNA fragmentation in apoptosis at the cellular level. However, since DNA fragmentation also occurs in cellular necrosis, we studied to which extent the use of DNA polymerase (nick translation) or terminal transferase (tailing) allows the differentiation between internucleosomal DNA degradation, typical for apoptosis, and the more random DNA destruction in necrosis. EXPERIMENTAL DESIGN: We compared these techniques on in vitro and in vivo models for apoptotic or necrotic cell death. Apoptosis of thymocytes in vitro was induced by gamma-irradiation, necrosis by the cytotoxic action of antibody and complement. Cell death in vivo was examined on paraffin-embedded tissue material from animals with autoimmune encephalomyelitis that served as a model for apoptosis, or in kainic acid-induced nerve cell degeneration as a model for necrosis. RESULTS: DNA fragmentation was visualized by the incorporation of labeled nucleotides into the nuclei of affected cells utilizing tailing or nick translation techniques. In the early stages of cell degeneration in vitro, cells undergoing apoptosis were preferentially labeled by tailing, whereas necrotic cells were identified by nick translation. Similarly, early stages of necrosis in vivo were preferentially detected by nick translation, whereas tailing was slightly more sensitive for the detection of apoptosis. Results obtained with these enzymatic techniques were in accord with the assessment of cell death by morphologic criteria. Both techniques could be applied in tissue samples even after prolonged fixation in paraformaldehyde if the sections were pretreated with proteinase K digestion. CONCLUSIONS: Our studies show that both in situ nick translation and in situ tailing are useful in detecting DNA fragmentation in cell suspensions and tissue sections. These techniques may help to define the molecular mechanisms leading to cell death in experimental conditions and eventually in human tissue.
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Apoptosis/genética , ADN Polimerasa Dirigida por ADN , Técnicas Genéticas , Transferasas , Animales , Muerte Celular/genética , Daño del ADN , Citometría de Flujo , Masculino , Necrosis , Neuronas/patología , Ratas , Ratas Endogámicas Lew , Ratas Sprague-Dawley , Sensibilidad y Especificidad , Timo/patologíaRESUMEN
The neuropathology of demyelinating lesions in multiple sclerosis was studied in specimens obtained by diagnostic needle biopsy during early stages of the disease. The lesions were characterized by a chronic inflammatory reaction dominated by lymphocytes and macrophages, plaque-like demyelination, and astroglial sclerosis. Oligodendrocytes within the lesions were studied by immunocytochemistry using antibodies against various myelin and oligodendroglia components. The expression of messenger RNA for proteolipid protein was determined by in situ hybridization. Our studies revealed that myelin-oligodendrocyte glycoprotein is a sensitive and reliable marker for identification of oligodendrocytes in demyelinated plaques. The results suggest that in the early course of the disease in some patients, oligodendrocytes may largely be preserved, whereas in others oligodendroglial loss is pronounced. Loss of oligodendrocytes was only marginally related to the stage of demyelinating activity within the lesions. These findings indicate that the pathogenesis of demyelination may vary within different multiple sclerosis patients.
Asunto(s)
Esclerosis Múltiple/patología , Oligodendroglía/patología , Adolescente , Adulto , Encéfalo/metabolismo , Encéfalo/patología , Femenino , Humanos , Inmunohistoquímica , Hibridación in Situ , Masculino , Esclerosis Múltiple/metabolismo , Proteínas de la Mielina/metabolismo , Vaina de Mielina/patología , Oligodendroglía/metabolismo , Factores de TiempoRESUMEN
The highly potent neurotoxins produced by Clostridium botulinum lead to botulism when ingested in appreciable amounts. However, botulinum toxin injections delivered intramuscularly in very small quantities can produce a therapeutically intended focal paresis while producing only negligible local or systemic side effects. Over the past several years, various neurological disorders, especially those involving increased muscle tone and/or abnormal movements, have been successfully treated with local botulinum A toxin injections. The success of this method has led to a general change in the management of blepharospasm, torticollis spasmodicus, hemifacial spasm, and other disorders. Treatment is usually effective for 4 to 12 weeks; if symptoms recur, the injections can be repeated over a period of several years, usually with the same success. Side effects depend on the site of the injections, and are rare at the optimal dosage and always reversible. For optimum therapeutic results, this treatment must be restricted to specialized centers.