Use of coronary Palmaz-Schatz stent in the percutaneous treatment of vertebral artery stenoses.

A case of chronic vertebrobasilar insufficiency due to severe stenoses at the origins of both vertebral arteries was treated with percutaneous transluminal angioplasty and coronary Palmaz-Schatz stents. Use of stents led to a better angiographic result than angioplasty alone. The patient is improved 8 mo later.

Multiple sclerosis mimicking primary brain tumor.

Surgical biopsy specimens of multiple sclerosis plaques have been only infrequently reported, and the scanty descriptions of these specimens have generally emphasized the inflammatory nature of the lesion. We present surgical specimens from four patients with multiple sclerosis on whom biopsies were performed because of clinical features mimicking brain tumor. Both general pathologists and neuropathologists involved with these cases experienced difficulty in arriving at the correct diagnosis. In all four cases, the lesions were remarkably uniform in microscopic appearance, consisting of monotonous sheets of gemistocytic astroglia interspersed by numerous foamy macrophages. In sections stained with hematoxylin-eosin, the most helpful diagnostic features were the even distribution of the foamy macrophages and the absence of associated necrosis. In each case, the diagnosis was confirmed with special stains that disclosed total destruction of myelin sheaths with relative preservation of axons. Significant inflammatory infiltration was present in only one of five biopsy specimens.

The effect of tocopherol and dimethyl sulfoxide on focal edema and lipid peroxidation induced by isocortical injection of ferrous chloride.

Addition of iron salts to suspensions of subcellular organelles or polyunsaturated fatty acids results in the formation of oxidative free radicals with subsequent initiation of lipid peroxidation. Pretreatment of rats with anti-oxidants prevents peroxidation following isocortical ferrous chloride injection, and increases the rate of resolution of iron-induced focal edema. In this experiment, treatment of rats at the time of injection of 5 microliters of 100 mM FeCl2 with tocopherol and DMSO caused decreased formation of brain peroxidation at the injection site, as measured by formation of MDA. Tocopherol failed to change the quantity of tissue fluid accumulation. However, DMSO alone, or combined with tocopherol, hastened the resolution of brain edema. Tocopherol may terminate peroxidation reactions by donation of a phenolic hydrogen, forming a quinone of tocopherol. DMSO has many pharmacologic effects; however, inhibition of initiation reactions by scavenging hydroxyl radicals, and direct and indirect effects on focal edema accumulation may account for our observations.

Effects of antiperoxidants on FeCl2-induced lipid peroxidation and focal edema in rat brain.

Head trauma with contusion or cortical laceration and hemorrhage causes focal edema with encephalomalacia and gliosis. Because cerebral hemorrhage ultimately results in deposition of heme compounds and iron into the neuropil, we injected an aqueous solution of iron salts to simulate the decompartmentalization of iron after trauma. We pretreated animals with saline or with 600 mg/kg alpha-tocopherol plus 5 ppm selenium added to the drinking water. Formation of lipid peroxidation products was significantly inhibited within the iron injection site in the antiperoxidant-pretreated rats at 30, 60, and 120 min after injection of iron into the isocortex. The antiperoxidants failed to prevent formation of focal brain edema at the injection site between 1 and 8 h after injection; however, significantly less edema was present in the alpha-tocopherol + selenium-pretreated animals 24 and 48 h after injection. The efficacy of antiperoxidants in preventing lipid peroxidation, and enhancing the resolution of ferrous-induced focal brain edema suggest that tocopherol + selenium administration caused free radical quenching and termination of lipid peroxidation, and increased membrane stabilization, an effect similar to the action of glucocorticoids.

Formation of malonaldehyde and focal brain edema induced by subpial injection of FeCl2 into rat isocortex.

Subpial injection of iron salts or iron-containing blood products into rat isocortex induces recurrent epileptiform discharges coupled with cavitary necrosis and gliosis. Since aqueous iron or heme compounds cause formation of superoxide radicals and peroxidation of membrane lipids, we studied the rate of formation of malonaldehyde (MDA) after subpial injection of 5 microliters of various concentrations of FeCl2 and CoCl2. Injection of CoCl2 failed to alter isocortical MDA levels. However, significant formation of MDA occurred after injection of 25, 50 and 100 mM FeCl2 into rat isocortex. Formation of peak MDA levels of 13.4 +/- 1.0 nmol.mg protein-1 occurred at 15 in to 1 h after 100 mM FeCl2 injection; levels returned to equal control by 12 h. Tissue fluid accumulation occurred by 2 h after FeCl2 injection and persisted for 38 h. Histopathologic assessment using Nissl staining of tissue from the injection site showed loss of cellular staining, coagulation necrosis, and accumulation of macrophages and glial cells. Although these experiments showed the initiation of lipid peroxidation and formation of focal isocortical edema by injection of aqueous solutions of iron salts, we speculate that decompartmentalization of iron red blood cells after trauma, cerebral hemorrhage or infarction may be important in the propagation of tissue damage from such injuries.

Changes in [3H]lysine incorporation into protein in a seizure focus in rat isocortex.

A focus of epileptiform discharge was induced in rat isocortex by subpial injection of 5 microliters of 100 mM FeCl3. Control animals were prepared with saline injections. Protein synthesis was estimated by uptake of [3H]lysine and its incorporation into protein at the site of iron injection, in the contralateral homotopic isocortex, and in the midline cerebellum. We found diminished uptake of [3H]lysine into all regions of rat brain in the interictal or nonseizing iron-injected animals, whereas the corrected rate of incorporation of [3H]lysine into protein was not significantly different from control rates. Actively seizing animals showed no inhibition of uptake of [3H]lysine, but [3H]lysine incorporation into protein relative to the uptake was significantly inhibited within the epileptic focus but not in the other areas examined. This decreased incorporation of amino acids into protein parallels that found in animals convulsing after electroshock or pentylenetetrazol injection.

Antiperoxidant pretreatment and iron-induced epileptiform discharges in the rat: EEG and histopathologic studies.

Iron causes formation of superoxide radicals resulting in peroxidation of membranous components of tissue. Hemosiderin deposition in human brain often accompanies chronic posttraumatic seizures induced by trauma. We injected an aqueous solution of iron salts, the principal metallic iron of whole blood, into rat isocortex. Serial electroencephalographic recording showed than 94% of untreated animals developed epileptiform discharges. Pretreatment with alpha-tocopherol and with 2 ppm selenium prevented development of iron-induced epileptiform activity in 72% of animals. Histopathologic assessment of serial sections stained with Nissl, hematoxylin and eosin, and prussian blue showed cavitation, neuronal pyknosis and loss, and astrogliosis in untreated animals. The site of iron injection in animals treated with antiperoxidants contained only an area of neuronal pyknosis. The efficacy of antioxidants in preventing development of iron-induced cavitation, gliosis, and epileptiform discharges suggests that peroxidative injury may be important in the development of experimental epilepsy induced by isocortical injection of ferrous chloride.

Dendritic alterations in rat isocortex within an iron-induced chronic epileptic focus.

Ferrous chloride was injected into the rat isocortex in 5-microliters volumes as an aqueous solution with a concentration of 100 mM. Bursts of epileptiform discharges were sustained throughout the 6 weeks of observation. Nissl and Golgi-Cox stains showed gliosis and neuronal loss within the injection site. Neurons adjacent to the cavitory lesion showed deformity of dendrites, dendritic nodularity, loss of spines, and string-of-beads deformity. These changes are identical to those found in human epileptogenic foci.

A study of cyclic nucleotide metabolism and the histology of rat liver during 3'-methyl-4-dimethylamino-azobenzene carcinogenesis. II. Cyclic AMP metabolism.

We have studied cAMP metabolism in rat livers undergoing carcinogenesis induced by dietary 3'-methyl-4-dimethylaminoazobenzene. A correlation between the biochemical and the histological changes described in the companion paper has been made. In this study, we saw 100% incidence of cholangiocarcinoma by 10 weeks. During weeks 1--10, the biochemistry of tumor-free areas of the livers only was studied; during weeks 11-13, the increased size of the tumors made possible a biochemical study of the tumor tissue as well as the non-tumor tissue, and a comparison between the two was made. Alterations in all parameters of cAMP metabolism were seen from the earliest stages of treatemnt. Most striking were those of adenylate cyclase activity which preceded and accompanied tumor formation, and were seen in both non-tumor and tumor tissue. In the first few weeks of treatment, small acidophilic glycogen-deficient hepatocytes appeared in the periportal areas of the liver lobules. During this time, there was an increase in maximal isoproterenol stimulation of adenylate cyclase and to a lesser extent in the basal activity of the enzyme; increases in phosphodiesterase activity were seen, and were greatest in weeks 1, 2; cAMP levels were diminished in weeks 1, 2 and slightly but not significantly elevated at week 3. From week 4 onwards an even smaller glycogen-deficient cell population appeared in perilobular areas amongst the acidophilic hepatocytes, and tumors began to appear elsewhere in the livers; at this time, there were further marked increases in the basal activity and isoproterenol responsiveness of adenylate cyclase, and the appearance of increased Gpp(NH)p responsiveness of the enzyme; the increase in phosphodiesterase activities seen at week 3 (smaller than that seen in weeks 1, 2) was sustained but did not further increase; cAMP levels were now significantly elevated also, but they did not rise steadily as did the activity of adenylate cyclase. There was a marked difference between the adenylate cyclase activities in non-tumor tissue from tumor-bearing and non-tumor-bearing livers in weeks 4--10, but there was no difference between the phosphodiesterase activities or cAMP levels in these two groups. Adenylate cyclase activity was extremely high in both non-tumor tissue of tumor-bearing livers from weeks 4--10 and tumors from weeks 11--13. Although phosphodiesterase activities were most elevated in the tumors, there were extremely high cyclic AMP levels in these tissues. The difference between the cAMP levels of tumor and non-tumor tissue was striking. Our findings are discussed with respect to the two-state model of carcinogenesis...