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Nicholas T. Zervas

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Akira Shintani and Nicholas T. Zervas

✓ A case requiring ligation of the vertebral artery to treat an aneurysm of that vessel is reported. Review of the literature reveals that vertebral artery ligation is far less hazardous than ligation of the carotid artery as long as the opposite vertebral artery is functioning.

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Outcome 1 year after SAH from cerebral aneurysm

Management morbidity, mortality, and functional status in 112 consecutive good-risk patients

Allan H. Ropper and Nicholas T. Zervas

✓ A group of 112 consecutive patients who initially had no neurological deficits after subarachnoid hemorrhage (SAH) was followed intensively for at least 1 year. Ninety-four were in neurological Grade I or II (Hunt and Hess classification) on arrival. A hundred patients underwent late surgery but, despite excellent surgical results, major morbidity and mortality rates were observed related to preoperative complications. In the preoperative period, 14 (13%) rebled, 41 (37%) had symptomatic cerebral vasospasm, and 24 (21%) had hydrocephalus that required treatment. Of the 100 surgical patients, 73 were in Grade I or II, 26 in Grade III, and one in Grade IV. Six patients had intraoperative neurological complications, and two had delayed postoperative cerebral infarction. Six patients died during hospitalization, but only one as a result of operation. Six others died during the year following discharge of causes unrelated to the operation. The ultimate functional outcome at 1 year of these initially good-risk patients was poor. Only 46% were fully recovered, and 25% reported emotional or psychological disturbances that interfered with their daily lives. Forty-four percent could return to their previous jobs or a comparable position, and 20% obtained lesser employment. Management mortality at 1 year was 11%, and morbidity related to persistent neurological deficits (mainly strokes from vasospasm) was 20%. Thus, management mortality and morbidity at 1 year was 31%, and the number of patients returning to useful life was disappointing. The authors support the suggestion by previous workers that an analysis of at least the 6-month and perhaps the 1-year outcome (especially management mortality for all patients) provides the most important parameter for judging outcome and comparing different management protocols for SAH.

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Richard J. Wurtman and Nicholas T. Zervas

✓ The authors, at the invitation of the Editorial Board, have outlined their general interpretation of the role of monoamine neurotransmitters following injury to the central nervous system. Their work on experimental stroke is discussed, and its relevance to spinal cord injuries accompanied by comparable hemorrhage and ischemia involving neurons is implied.

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Glyn R. Wellum, Thomas W. Irvine Jr. and Nicholas T. Zervas

✓ Dose responses in vitro of the basilar arteries of the dog, rabbit, and man to human hemoglobin are reported. For each species, the response occurred over a range of 10−9M to greater than 10−5M hemoglobin. When compared to a maximum serotonin contraction, the relative constriction induced by 10−5M hemoglobin was greater in the rabbit than in the dog, which in turn was greater than in man. The comparatively weak response of the human arteries is probably attributable to postmortem changes.

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Cerebral vasoactivity of heme proteins in vitro

Some mechanistic considerations

Glyn R. Wellum, Thomas W. Irvine Jr. and Nicholas T. Zervas

✓ The dose responses of canine basilar arteries to human hemoglobin, rabbit hemoglobin, horse-heart myoglobin, and human methemoglobin and cyanomethemoglobin are compared in this paper. The in vitro arterial segments responded similarly to the hemoglobins and myoglobin when doses were based on the hemoglobin dimer rather than on the tetramer. Superoxide free radicals produced by the autoxidation of hemoglobin to methemoglobin do not seem to be involved in the mechanism of hemoglobin-induced vasocontraction, as the contraction cannot be blocked by superoxide dismutase or other agents known to react with superoxide-generated products. Nonspecific uptake of hemoglobin into the smooth-muscle cells by pinocytosis is also discounted.

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Anne Klibanski, E. Chester Ridgway and Nicholas T. Zervas

✓ The authors describe six patients with pituitary macroadenomas hypersecreting only the alpha subunit of the glycoprotein hormones. These patients had been previously diagnosed as having “non-functioning chromophobe adenomas.” All of the patients had visual field abnormalities and partial hypopituitarism. The elevated serum alpha concentrations showed a variable response to stimulation by thyrotropin-releasing hormone, and could not be suppressed by thyroid hormone administration. Immunological, gel chromatographic, and immunocytochemical studies documented that only the alpha subunit was present. Following pituitary surgery and radiotherapy, serum alpha levels decreased. These patients represent a new subset of functioning pituitary tumors. Determination of alpha subunit concentration is useful in managing some patients with pituitary tumors previously thought to have non-functioning chromophobe adenomas.

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Anne Klibanski, Nicholas T. Zervas, Kalman Kovacs and E. Chester Ridgway

✓ Hypersecretion of growth hormone (GH) was found in three women aged 25 to 35 years old, with somatotroph adenomas without clinical stigmata of acromegaly. The patients had previously been diagnosed as having nonfunctioning pituitary macroadenomas, with extrasellar extension. Concentrations of GH were elevated preoperatively in all subjects and could not be suppressed during oral glucose tolerance testing. Somatomedin-C concentrations were elevated in two patients. Immunocytochemical studies of surgically obtained tumor tissue demonstrated sparse positive staining for GH in all subjects. Gel-chromatographic analysis of serum and tumor tissue samples demonstrated that the immunoactive GH was authentic GH. On pathological examination, the tumor was cellular in all cases, consisting of partly acidophilic and partly chromophobic cells. Electron microscopic analysis of one tumor showed a cell composition not previously described. These studies further characterize GH hypersecretion in a subset of patients with clinically nonfunctioning pituitary macroadenomas.

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Takakazu Kawamata, John W. Peterson, Takao Bun and Nicholas T. Zervas

✓ Although phorbol esters, synthetic activators of protein kinase C (PKC), can stimulate large increases in the binding of cytosolic PKC to form membrane-bound PKC (PKCm, an indicator of PKC activation), the authors report that even small increases in PKCm induced by phorbol esters (8–12% of total PKC content) can be associated with significant PKC-mediated contractions in vitro (50–85% of maximum) in normal canine cerebral arteries. Increases in PKCm of similarly small magnitude were found in vitro when control artery segments were exposed to hemolysate, but only if the arterial smooth-muscle cells were first slightly depolarized by increased extracellular potassium to values of membrane potential similar to those observed in canine cerebral arteries during chronic cerebral vasospasm. These increases in PKCm (6–8% of total PKC content) coincided with a greatly augmented contractile response to hemolysate. These results show that the previous observation of only a small increase in PKCm (approximately 7% of total PKC content) after experimental subarachnoid hemorrhage in the canine model does not preclude a potentially important role for PKC-mediated contraction in the pathogenesis of cerebral vasospasm.