RESUMEN
Two patients, 14 and 46 years of age, presented with diffuse, rapidly growing intracerebral tumors leading to death 6 1/2 and 9 1/2 months, respectively, after diagnosis. Histological examination showed sheets of moderate-sized tumor cells with clear cytoplasm and central nuclei interrupted by delicate arciform vasculature, an appearance distinctly different from that of neuroblastoma. Malignant features were present in the form of significant nuclear pleomorphism, numerous mitotic figures, and small foci of necrosis with some suggestion of adjacent pseudo-palisading in one case. Ultrastructural examination showed neuronal differentiation, including prominent neuritic processes, microtubules, dense-core neurosecretory-type granules, and synaptic bouton-like structures containing small, empty-appearing synaptic-type vesicles and synapse-like membrane "thickenings." Immunohistochemistry showed focal immunopositivity for synaptophysin, neurofilaments, neuron-specific enolase, and S100 protein. Immunoreactivity for glial fibrillary acidic protein (GFAP) was found at the margins of the tumors adjacent to some intratumoral blood vessels and in some tumor cells. These tumors seem to occupy a nosological "middle ground" between neuroblastoma and central neurocytoma.
Asunto(s)
Neoplasias Encefálicas/patología , Neuroblastoma/patología , Neurocitoma/patología , Adolescente , Neoplasias Encefálicas/química , Femenino , Proteína Ácida Fibrilar de la Glía/análisis , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Neuroblastoma/química , Neurocitoma/química , Proteínas de Neurofilamentos/análisis , Fosfopiruvato Hidratasa/análisis , Proteínas S100/análisis , Sinaptofisina/análisis , Vimentina/análisisRESUMEN
An unusual pleomorphic tumor was resected from the cerebellopontine angle of a 40-year-old man with no stigmata of neurofibromatosis. The tumor showed multinucleated giant cells scattered amid smaller, slightly elongated cells. The tumor showed a rudimentary fascicular pattern containing some looser areas but no nuclear palisading. A diagnosis of Schwann cell tumor was made based on ultrastructural findings and on immunoreactivity for S100 protein. Malignancy was suggested by the extreme pleomorphism of the tumor, by the presence of tripolar mitotic figures, and by flow cytometric demonstration of aneuploidy and of a significant proportion of S-phase tetraploid nuclei (9%). Ten months after the first operation, the tumor had regrown to its original size, and was again resected. The histologic and ultrastructural appearances were similar to those of the first specimen, but flow cytometric analysis now showed a double aneuploid population of nuclei and showed 12% of the nuclei in tetraploid S phase. Within 11 months of the second operation, the tumor had regrown to an estimated size of 22 cm3. Four months of radiotherapy subsequently halted tumor growth, but additional lesions appeared in the cervical and high thoracic areas.
Asunto(s)
Neurilemoma/patología , Neuroma Acústico/patología , Adulto , Citometría de Flujo , Humanos , Imagen por Resonancia Magnética , Masculino , Microscopía Electrónica , Neurilemoma/diagnóstico , Neurilemoma/cirugía , Neuroma Acústico/diagnóstico , Neuroma Acústico/cirugía , Ploidias , Reoperación , Fase SRESUMEN
Restoration of coronary artery flow following a period of ischemia often results in further ultrastructural damage to cardiac fibers, a phenomenon known as reperfusion injury. We have compared the ultrastructural effects of uncontrolled reperfusion in vivo of ischemic pig myocardium with the ultrastructural effects of reperfusion controlled at flow rates comparable to preischemia levels. Myocardial ischemia was produced for 60 minutes in 9 pigs by means of a reversible coronary artery occlusion, after which coronary artery flow was restored for 120 minutes. This restoration of flow was complete in four pigs (resulting in uncontrolled reperfusion) and partial in five pigs, with constant monitoring and adjustment of flow to maintain rates near preischemia values (controlled reperfusion). Myocardial samples from the ischemic, reperfused region were examined by electron microscopy. Ischemic damage to nuclei, mitochondria, and myofibrils and ischemic depletion of glycogen were graded independently and blindly by two investigators using a simple, nonparametric three-point scale. Ischemic damage was greater in pigs receiving uncontrolled reperfusion than in animals receiving controlled reperfusion, and these differences were significant for ischemic effects on nuclei (p less than 0.01), glycogen (p less than 0.02), and myofibrils (p less than 0.05) but not for ischemic effects on mitochondria (p = 0.095). We conclude that uncontrolled, hyperemic flow during reperfusion of ischemic myocardium is responsible, in part, for the phenomenon of reperfusion injury.
Asunto(s)
Daño por Reperfusión Miocárdica/prevención & control , Reperfusión Miocárdica/métodos , Miocardio/ultraestructura , Animales , Núcleo Celular/ultraestructura , Circulación Coronaria/fisiología , Microscopía Electrónica , Mitocondrias Cardíacas/ultraestructura , Daño por Reperfusión Miocárdica/patología , Porcinos , Factores de TiempoRESUMEN
Reperfusion of ischemic myocardium may result in further ultrastructural damage to cardiac fibers, a phenomenon known as reperfusion injury. We have recently shown that controlled reperfusion, with maintenance of reperfusion flow rates near preischemia levels, prevents much of this reperfusion damage. This observation suggests that mechanical damage to the myocardial microvasculature is important in the pathogenesis of reperfusion injury. In this study, we have used electron microscopy to examine the microcirculation of ischemic, reperfused pig myocardium under conditions of uncontrolled and controlled reperfusion. Animals receiving uncontrolled reperfusion (reperfusion flow 3-4 times preischemia levels) showed ultrastructural damage to myocardial capillaries after 1 hour of ischemia and 2 hours of reperfusion. This damage was manifested as depletion of endothelial cell pinocytotic vesicles, plugging of capillaries by erythrocytes, leukocytes, and fibrin-containing microthrombi, and perivascular microhemorrhages. None of these changes were found in animals receiving controlled coronary artery reperfusion. We conclude that mechanical damage to the myocardial microvasculature is important in the pathogenesis of reperfusion injury and that such damage is obviated under conditions of controlled coronary artery flow during reperfusion.
Asunto(s)
Daño por Reperfusión Miocárdica/prevención & control , Reperfusión Miocárdica/métodos , Miocardio/ultraestructura , Animales , Circulación Coronaria , Microcirculación/ultraestructura , Microscopía Electrónica , Daño por Reperfusión Miocárdica/etiología , Daño por Reperfusión Miocárdica/patología , Porcinos , Factores de TiempoRESUMEN
Coronary reperfusion following myocardial ischemia may result in further damage to injured myocytes, as judged by their ultrastructural appearance. Calcium entry into myocytes has been implicated in this effect, and calcium channel-blocking agents have been used in attempts to prevent or limit such damage. In this study, we produced myocardial ischemia in pigs by means of reversible coronary artery occlusion. The pigs were infused with either nifedipine or verapamil (both clinically employed calcium channel-blocking agents) prior to and during coronary reperfusion. During reperfusion, nifedipine produced a lowering of mean arterial pressure, while mean arterial pressure was constant in verapamil-treated pigs and rose in pigs not receiving drugs. Myocardial samples from the ischemic, reperfused region were examined by electron microscopy. Ischemic damage to nuclei, mitochondria, and myofibrils and glycogen depletion were independently graded on a three-point scale by two investigators. For each of the organelles studied, ischemic damage was significantly less for nifedipine-treated animals than for controls. Ischemic damage in verapamil-treated pigs was not different from that seen in control animals, except for a slight improvement in myofibrillar appearance. We conclude that nifedipine, administered prior to and during reperfusion of myocardium, protects against reperfusion injury. The mechanism of this protective effect may be attributable, in part, to afterload reduction and, in part, to inhibition of transmembrane calcium flux in cardiac fibers.