RESUMEN
BACKGROUND: The pathophysiology of ascending/descending myelomalacia (ADMM) after canine intervertebral disk (IVD) extrusion remains poorly understood. Vasoactive molecules might contribute. HYPOTHESIS/OBJECTIVES: To investigate the immunoreactivity of endothelin-1 (ET-1) in the uninjured and injured spinal cord of dogs and its potential association with intramedullary hemorrhage and extension of myelomalacia. ANIMALS: Eleven normal control and 34 dogs with thoracolumbar IVD extrusion. METHODS: Spinal cord tissue of dogs retrospectively selected from our histopathologic database was examined histologically at the level of the extrusion (center) and in segments remote from the center. Endothelin-1 immunoreactivity was examined immunohistochemically and by in situ hybridization. Associations between the immunoreactivity for ET-1 and the severity of intramedullary hemorrhage or the extension of myelomalacia were examined. RESULTS: Endothelin-1 was expressed by astrocytes, macrophages, and neurons and only rarely by endothelial cells in all dogs. At the center, ET-1 immunoreactivity was significantly higher in astrocytes (median score 4.02) and lower in neurons (3.21) than in control dogs (3.0 and 4.54) (P < .001; P = .004) irrespective of the grade of hemorrhage or myelomalacia. In both astrocytes and neurons, there was a higher ET-1 immunoreactivity in spinal cord regions remote from the center (4.58 and 4.15) than in the center itself (P = .013; P = .001). ET-1 mRNA was present in nearly all neurons with variable intensity, but not in astrocytes. CONCLUSION AND CLINICAL IMPORTANCE: Enhanced ET-1 immunoreactivity over multiple spinal cord segments after IVD extrusion might play a role in the pathogenesis of ADMM. More effective quantitative techniques are required.
Asunto(s)
Enfermedades de los Perros/diagnóstico por imagen , Endotelina-1/inmunología , Hematoma Subdural/veterinaria , Desplazamiento del Disco Intervertebral/veterinaria , Animales , Estudios de Casos y Controles , Enfermedades de los Perros/inmunología , Perros , Femenino , Hematoma Subdural/diagnóstico por imagen , Hematoma Subdural/inmunología , Inmunohistoquímica/veterinaria , Desplazamiento del Disco Intervertebral/diagnóstico por imagen , Desplazamiento del Disco Intervertebral/inmunología , Masculino , Índice de Severidad de la EnfermedadRESUMEN
UNLABELLED: ESSENTIALS: An IgA paraprotein with anti-thrombin activity was not associated with a severe bleeding phenotype. This observation challenges the paradigm that anticoagulant therapy necessarily increases bleeding risk. Characterization of the antibody showed that it specifically binds to thrombin exosite I. A therapeutic drug with the properties of this antibody might be an antithrombotic that doesn't cause bleeding. BACKGROUND: We report the case of a 54-year-old female who presented with a traumatic subdural hemorrhage. Coagulation tests were markedly prolonged due to the presence of an anti-thrombin IgA paraprotein at 3 g L(-1) . The patient made a complete recovery and has had no abnormal bleeding during a 7-year follow-up, despite the persistence of the paraprotein. OBJECTIVES: To determine how the paraprotein prolonged clotting tests by defining its target and its epitope. METHODS: The paraprotein was purified and added to normal pooled plasma for in vitro clotting assays. Binding studies were conducted to determine the affinity of the IgA for thrombin. The Fab was isolated and crystallized with thrombin. RESULTS: The purified IgA was sufficient to confer the patient's in vitro coagulation profile in normal pooled plasma, and was found to bind specifically and with high affinity to thrombin. A crystal structure of the Fab fragment in complex with thrombin revealed an exosite I interaction involving CDRH3 of the antibody. CONCLUSIONS: Although the patient originally presented with a subdural bleed, the hematoma resolved without intervention, and no other bleeding event occurred during the subsequent 7 years. During this period, the patient's IgA paraprotein levels have remained constant at 3 g L(-1) , suggesting that the presence of a high-affinity, exosite I-directed antibody is consistent with normal hemostasis. A therapeutic derivative of this antibody might therefore permit antithrombotic dose escalation without an associated increase in the risk of bleeding.
Asunto(s)
Antitrombinas/inmunología , Hemorragia/inmunología , Inmunoglobulina A/inmunología , Trombina/química , Anticoagulantes/química , Antitrombinas/química , Coagulación Sanguínea , Pruebas de Coagulación Sanguínea , Epítopos/química , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/química , Hematoma Subdural/inmunología , Hemostasis/inmunología , Humanos , Inmunoglobulina A/química , Fragmentos Fab de Inmunoglobulinas/química , Persona de Mediana Edad , Fenotipo , Trombina/inmunologíaRESUMEN
OBJECT: The aim of this study was to make a preliminary evaluation of whether microdialysis monitoring of cytokines and other proteins in severely diseased neurosurgical patients has the potential of adding significant information to optimize care, thus broadening the understanding of the function of these molecules in brain injury. METHODS: Paired intracerebral microdialysis catheters with high-cutoff membranes were inserted in 14 comatose patients who had been treated in a neurosurgical intensive care unit following subarachnoidal hemorrhage or traumatic brain injury. Samples were collected every 6 hours (for up to 7 days) and were analyzed at bedside for routine metabolites and later in the laboratory for interleukin (IL)-l and IL-6; in two patients, vascular endothelial growth factor and cathepsin-D were also checked. Aggregated microprobe data gave rough estimations of profound focal cytokine responses related to morphological tissue injury and to anaerobic metabolism that were not evident from the concomitantly collected cerebrospinal fluid data. Data regarding tissue with no macroscopic evidence of injury demonstrated that IL release not only is elicited in severely compromised tissue but also may be a general phenomenon in brains subjected to stress. Macroscopic tissue injury was strongly linked to IL-6 but not IL- lb activation. Furthermore, IL release seems to be stimulated by local ischemia. The basal tissue concentration level of IL-lb was estimated in the range of 10 to 150 pg/ml; for IL-6, the corresponding figure was 1000 to 20,000 pg/ml. CONCLUSIONS: Data in the present study indicate that catheters with high-cutoff membranes have the potential of expanding microdialysis to the study of protein chemistry as a routine bedside method in neurointensive care.
Asunto(s)
Conmoción Encefálica/diagnóstico , Lesiones Encefálicas/diagnóstico , Cuidados Críticos , Hematoma Subdural/diagnóstico , Interleucina-1beta/líquido cefalorraquídeo , Interleucina-6/líquido cefalorraquídeo , Microdiálisis/instrumentación , Monitoreo Fisiológico/instrumentación , Complicaciones Posoperatorias/diagnóstico , Hemorragia Subaracnoidea/diagnóstico , Encéfalo/inmunología , Conmoción Encefálica/inmunología , Conmoción Encefálica/cirugía , Lesiones Encefálicas/inmunología , Lesiones Encefálicas/cirugía , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/inmunología , Catepsina D/líquido cefalorraquídeo , Ensayo de Inmunoadsorción Enzimática , Ácido Glutámico/líquido cefalorraquídeo , Glicerol/líquido cefalorraquídeo , Hematoma Subdural/inmunología , Hematoma Subdural/cirugía , Complicaciones Posoperatorias/inmunología , Pronóstico , Valores de Referencia , Análisis de Regresión , Hemorragia Subaracnoidea/inmunología , Hemorragia Subaracnoidea/cirugía , Factor A de Crecimiento Endotelial Vascular/líquido cefalorraquídeoAsunto(s)
Hematoma Subdural/etiología , Hematoma Subdural/inmunología , Inmunización , Hemorragia Retiniana/etiología , Hemorragia Retiniana/inmunología , Distribución por Edad , Causalidad , Francia/epidemiología , Hematoma Subdural/epidemiología , Humanos , Esquemas de Inmunización , Japón/epidemiología , Hemorragia Retiniana/epidemiología , Estados Unidos/epidemiologíaAsunto(s)
Síndrome de Guillain-Barré/fisiopatología , Hematoma Subdural/inmunología , Anciano , Enfermedad Crónica , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/etiología , Síndrome de Guillain-Barré/terapia , Hematoma Subdural/diagnóstico , Hematoma Subdural/patología , Hematoma Subdural/cirugía , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Masculino , Procedimientos Neuroquirúrgicos/efectos adversosRESUMEN
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Asunto(s)
Humanos , Masculino , Anciano , Síndrome de Guillain-Barré/fisiopatología , Hematoma Subdural/inmunología , Inmunoglobulinas Intravenosas/uso terapéutico , Procedimientos Neuroquirúrgicos , Enfermedad Crónica , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/etiología , Síndrome de Guillain-Barré/terapia , Hematoma Subdural/diagnóstico , Hematoma Subdural/patología , Hematoma Subdural/cirugíaRESUMEN
OBJECTIVES: Macrophages are an inherent component of the dura mater, and can be characterised in cases of subdural hematoma (SDH) by their progressive and varying accumulation within areas of damage. Gross and histological methods used to determine the age of SDH are inexact. These are in part due to the active nature of such lesions and the diverse manner in which trauma victims respond to injury. Correct diagnosis has obvious medico-legal implications. However, there is as yet no specific diagnostic method that allows the age of SDH to be reliably determined. This study investigated the progressive and orderly pattern of reactivity of resident and infiltrating dural macrophages that occurs in response to injury associated with SDH. MATERIALS: 26 postmortem cases of traumatic SDH were examined with survival times (onset of trauma to death) ranging from a few hours and up to 31 days. METHODS: Macrophage reactivity associated with the dura mater and the underlying hematoma was determined using CD68 and MHC class II immunohistochemistry and the qualitative and quantitative findings compared with the presence of iron detected using conventional Perl's Prussian blue method. RESULTS: The results show that CD68 and MHC class II are differentially expressed within the dura mater and hematoma in SDH, and that the expression of MHC class II is markedly upregulated in the inner aspect of the dura mater within the initial 24 hours following injury. CD68 expression can be detected quantitatively in the hematoma, 24-48 hours after SDH, and within the dura following this period. Linear regression analysis further revealed a significant and positive association between the expression of MHC class II or CD68 antigens and the progressive survival of SDH up to 31 days post-injury, which was not seen with Perl's histochemical method. The expression of MHC class II antigen was a distinguishing, and quantifiable feature particularly localized within the inner aspect of the dura from a very early stage in the progression of SDH. Widespread, diffuse and cellular MHC class II reactivity was particularly noted within the inner aspect of the dura mater in cases of SDH with survival > 10 days. Since only a proportion of this widespread immunoreactivity was accounted for by macrophages (considering CD68 immunoreactivity), a large component of this activity was more likely to be due to the reorganisation and activation of fibroblasts within inner dural layers (dural border layer), known to upregulate expression of MHC class II molecules. CONCLUSIONS: The expression of CD68 and MHC class II antigens provides a more informative picture of the progression of pathology associated with SDH, and may be used in conjunction with other clinicopathological factors, in further investigations that attempt to date SDH according to defined histopathological characteristics.
Asunto(s)
Duramadre/inmunología , Duramadre/patología , Hematoma Subdural/inmunología , Hematoma Subdural/patología , Macrófagos/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Duramadre/irrigación sanguínea , Femenino , Hemosiderina/metabolismo , Antígenos de Histocompatibilidad Clase II/metabolismo , Humanos , Macrófagos/metabolismo , Masculino , Microcirculación/inmunología , Microcirculación/patología , Persona de Mediana EdadRESUMEN
BACKGROUND AND PURPOSE: Patients with lupus anticoagulants do not typically have a bleeding tendency. However, a few reports of hemorrhage in patients with lupus anticoagulants in the absence of known risk factors for bleeding have been published, raising the question of an etiologic connection between lupus anticoagulants and certain types of hemorrhage. The presentation of three patients with subdural hematoma and lupus anticoagulants within only 1 year at our institutions and the report of two such patients in the literature led us to conduct a retrospective study to determine whether patients with lupus anticoagulants may have an increased risk for the development of subdural hematoma. CASE DESCRIPTIONS: All patients with a discharge diagnosis of nontraumatic subdural hematoma and lupus anticoagulant at three medical institutions between 1985 and 1996 were identified, and their medical histories and laboratory evaluations were reviewed. Of 733 patients with a discharge diagnosis of nontraumatic subdural hematoma, 5 were diagnosed as having a lupus anticoagulant (0.7%). All had known risk factors for the development of subdural hematoma: thrombocytopenia, hypoprothrombinemia, intracerebral venous hemorrhage, warfarin therapy, and advanced age with a history of a fall. CONCLUSIONS: This study suggests that presence of a lupus anticoagulant by itself is not associated with an increased incidence of nontraumatic subdural hematoma.
Asunto(s)
Hematoma Subdural/sangre , Hematoma Subdural/epidemiología , Inhibidor de Coagulación del Lupus/sangre , Adulto , Anciano , Anticuerpos Antifosfolípidos/sangre , Femenino , Hematoma Subdural/inmunología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Non-specific immune responses, cell-mediated immunity, and humoral immunity were analyzed in 35 patients with acute subdural hematomas vs. 55 healthy controls. The importance of prophylactic immunomodulation in prevention of infections and other clinically significant long-term complications after head trauma was demonstrated.
Asunto(s)
Reacciones Antígeno-Anticuerpo/inmunología , Conmoción Encefálica/inmunología , Hematoma Subdural/inmunología , Enfermedad Aguda , Adyuvantes Inmunológicos/uso terapéutico , Adulto , Formación de Anticuerpos , Conmoción Encefálica/tratamiento farmacológico , Conmoción Encefálica/cirugía , Terapia Combinada , Hematoma Subdural/tratamiento farmacológico , Hematoma Subdural/cirugía , Humanos , Inmunidad Celular , Inmunidad Innata , Persona de Mediana Edad , Periodo Posoperatorio , Timopoyetinas/uso terapéutico , Factores de TiempoRESUMEN
Acquired inhibitors of factor V are rare causes of clinical bleeding, whose severity ranges from mild to life-threatening. Optimal treatment of patients with factor V inhibitors is uncertain. We report on our successful treatment approach in a patient with spontaneous, life-threatening intracranial bleeding caused by a factor V inhibitor. The patient deteriorated after initial treatment with fresh-frozen plasma and platelet transfusions. He was subsequently treated with a combination of plasma exchange and chemotherapy, which led to complete recovery. Our experience suggests that plasma exchange may be life-saving in cases of severe bleeding caused by factor V inhibitors. The use of plasmapheresis in conjunction with chemotherapy is an efficacious and well-tolerated treatment and should be considered in patients with factor V inhibitors.
Asunto(s)
Autoanticuerpos/inmunología , Enfermedades Autoinmunes/inmunología , Deficiencia del Factor V/inmunología , Factor V/inmunología , Hematoma Subdural/inmunología , Inmunoglobulina G/inmunología , Anciano , Autoanticuerpos/aislamiento & purificación , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/terapia , Terapia Combinada , Ciclofosfamida/uso terapéutico , Factor V/antagonistas & inhibidores , Deficiencia del Factor V/terapia , Úlcera del Pie/complicaciones , Hematoma Subdural/cirugía , Hemorragia/etiología , Hemorragia/inmunología , Humanos , Inmunoglobulina G/aislamiento & purificación , Inmunosupresores/uso terapéutico , Masculino , Paraplejía/complicaciones , Plasma , Intercambio Plasmático , Plasmaféresis , Prednisona/uso terapéutico , Úlcera por Presión/complicaciones , Infecciones Urinarias/complicaciones , Vincristina/uso terapéuticoRESUMEN
In order to estimate the contribution of platelet-activating factor (PAF) to the formation of chronic subdural haematomas (CSH), we measured plasma PAF and anti-PAF antibody levels in head-injured patients with and without CSH and normal volunteers. Plasma PAF and anti-PAF IgG levels were higher in patients with CSH than in patients without CSH or in normal volunteers. Furthermore, plasma PAF and anti-PAF IgG levels increased in a time-dependent manner over the first 35 days following head injury. These data suggest that PAF may be involved in the generation of CSH.
Asunto(s)
Autoanticuerpos/sangre , Hematoma Subdural/inmunología , Inmunoglobulina G/sangre , Factor de Activación Plaquetaria/inmunología , Factor de Activación Plaquetaria/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Valores de ReferenciaRESUMEN
A 62-year-old Norwegian male was found to have a leucocytosis (20 X 10(9)/l blood). About 80% of the leucocytes were T-lymphocytes with markedly convoluted, often cerebriforme nuclei. There were generalized pea-sized lymph nodes. The liver was enlarged and was found to be infiltrated with the same type of lymphocytes as were found in the blood. A bone marrow biopsy showed massive infiltration with the same kind of cells. The patient had a non-specific rash, but no generalized exfoliative dermatitis. A double set of markers was found on the T-lymphocytes, with a membrane phenotype T4+ and T8+ on practically all cells.
Asunto(s)
Transformación Celular Neoplásica/patología , Leucemia Linfoide/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Reguladores/inmunología , Anticuerpos Monoclonales/inmunología , Núcleo Celular/patología , Núcleo Celular/ultraestructura , Transformación Celular Neoplásica/ultraestructura , Hematoma Subdural/inmunología , Hematoma Subdural/patología , Humanos , Leucemia Linfoide/ultraestructura , Hígado/inmunología , Masculino , Persona de Mediana Edad , Fenotipo , Linfocitos T Colaboradores-Inductores/ultraestructura , Linfocitos T Reguladores/ultraestructuraRESUMEN
The leukocyte reactions of 106 neurosurgical cases, including 63 brain tumors, 10 intracerebral hematomas, 10 cerebral infarctions, 10 subarachnoidal hemorrhages, 8 cerebral injuries and 5 chronic subdural hematomas, against the extracts of gliomas and normal brain tissues were tested by capillary migration (LMI) and adherence inhibition (LAI) assays. Both tests showed specific responses with autochthonous and allogeneic glioma extracts in glioma patients. The sensitivity of LAI was superior to that of LMI, although LAI also showed adherence enhancement in the presence of weakly sensitized leukocytes or weak antigenic stimuli. Leukocytes from glioma patients showed positive inhibition with normal brain tissues from patients with glioma and intracerebral hematoma. Positive leukocyte reactions with normal brain tissues were also confirmed in patients with intracerebral hematomas, cerebral infarctions and severe cerebral lacerations, but not in those with subarachnoidal hemorrhages, minor cerebral contusions and chronic subdural hematomas. These results suggest that the leukocytes of patients with destructive brain lesions were autosensitized by normal brain antigens. The autosensitization has some advantages in that destroyed brain tissues are eliminated, but the hyperimmune state might cause postictal brain edema and should be properly controlled by steroids.