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Biomedical subjects

U DeGirolami

Publications and source records attributed to U DeGirolami.

At least 55 records · Page 3Linked to original sources

Effect of mannitol on experimental focal ischemia in awake monkeys.

The effect of mannitol on focal cerebral ischemia in cynomolgus monkeys was studied. After the implantation of a snare ligature about the right middle cerebral artery (MCA) and of deep electrodes for measurement of cerebral blood flow, unanesthetized animals underwent 4-hour MCA occlusion. Ten monkeys were untreated, and 12 animals received mannitol (1.2 g/kg i.v.) 20 minutes after occlusion. The preocclusion and postocclusion deep hemispheric cerebral blood flows (mean CBFs) were similar in the treated and untreated groups. Occlusion produced an average decrease in flow of about 50% in both groups. In the mannitol-treated group the mean CBF of 30.0 fell to 15.8 ml/100 g/minute, and in the untreated group the mean CBF of 29.5 fell to 12.5 ml/100 g/minute. Several animals showed increased CBF after mannitol treatment, and there was an average 21% increase in CBF in the mannitol group after treatment, but this was not a statistically significant difference from the untreated group. With regard to clinical status, there was no significant difference between the mannitol group and the untreated group after MCA occlusion. In individual animals, mannitol treatment caused no significant improvement. Two weeks after occlusion, brains were evaluated for infarct size; there was no significant difference between the mannitol and the untreated groups. In this study, treatment with mannitol (1.2 g/kg) 20 minutes after MCA occlusion failed to modify significantly the mean hemispheric CBF, clinical status, or the pathological effects of 4-hour focal cerebral ischemia.

Animals↗

Experimental corticosteroid myopathy.

The steroids triamcinolone, dexamethasone, beta-methasone, and cortisone were administered i.p. to adult rats for 14-63 days. The extensor digitorum longus (EDL, white muscle) and soleus (SOL, red muscle) muscles were examined histologically and histochemically. Triamcinolone was the most potent lesion-producing drug. Selective involvement of muscles, and of the fiber types within them was observed: Necrotic changes were seen only in the type 1 fibers of the SOL; atrophic fibers were observed in the type 2 fibers of both the SOL and the EDL.

Adrenal Cortex Hormones↗

Variability and reversibility of focal cerebral ischemia in unanesthetized monkeys.

To assess reversibility of focal cerebral ischemia, we performed a neurologic and pathologic study of 27 monkeys subjected to temporary middle cerebral artery occlusion. An implanted snare ligature occluded the artery in awake monkeys for 30 minutes, 4 hours, 8 hours, 16 hours, 24 hours, or permanently. Serial neurologic observations were made for 2 weeks, and systematic neuropathologic examination estimated extent of infarction. Deficits from ischemia were commonly reversible at 30 minutes and 4 hours, but were rarely reversible after 8 hours. Neurologic deficit and infarct size showed remarkable variability. Maximum irreversible infarction evolved in about 4 to 8 hours in most awake monkeys. Variability and reversibility of focal ischemia were probably related to variable collateral circulation. The results suggested that emergency surgical revascularization might help some cases of acute ischemic stroke.

Animals↗

Thresholds of focal cerebral ischemia in awake monkeys.

An awake-primate model has been developed which permits reversible middle cerebral artery (MCA) occlusion during physiological monitoring. This method eliminates the ischemia-modifying effects of anesthesia, and permits correlation of neurological function with cerebral blood flow (CBF) and neuropathology. The model was used to assess the brain's tolerance to focal cerebral ischemia. The MCA was occluded for 15 or 30 minutes, 2 to 3 hours, or permanently. Serial monitoring evaluated neurological function, local CBF (hydrogen clearance), and other physiological parameters (blood pressure, blood gases, and intracranial pressure). After 2 weeks, neuropathological evaluation identified infarcts and their relation to blood flow recording sites. Middle cerebral artery occlusion usually caused substantial decreases in local CBF. Variable reduction in flow correlated directly with the variable severity of deficit. Release of occlusion at up to 3 hours led to clinical improvement. Pathological examination showed microscopic foci of infarction after 15 to 30 minutes of ischemia, moderate to large infarcts after 2 to 3 hours of ischemia, and in most cases large infarcts after permanent MCA occlusion. Local CBF appeared to define thresholds for paralysis and infarction. When local flow dropped below about 23 cc/100 gm/min, reversible paralysis occurred. When local flow fell below 10 to 12 cc/100 gm/min for 2 to 3 hours or below 17 to 18 cc/100 gm/min during permanent occlusion, irreversible local damage was observed. These studies imply that some cases of acute hemiplegia, with blood flow in the paralysis range, might be improved by surgical revascularization. Studies of local CBF might help identify suitable cases for emergency revascularization.

Anesthesia↗

Charcot-Marie-Tooth disease associated with hypertrophic neuropathy: a neuropathologic study of two cases.

The neuropathologic features of two cases of Charcot-Marie-Tooth disease associated with hypertrophic neuropathy are described. The peripheral nerves had a loss of myelinated fibers, endoneurial fibrosis, and numerous onion-bulb formations. The most severe changes were seen in the distal nerves. In the older of the two patients, advanced changes were also observed in the proximal nerves and anterior roots and were associated with neuronal degeneration in the anterior horns and dorsal root ganglia. The muscles were the site of chronic denervation atrophy, which was most severe in the distal portions of the lower extremities. In one of the cases, the autopsy findings were complemented by sural nerve biopsy studies, which confirmed the presence of segmental demyelination and remyelination, axonal degeneration, and Schwann cell proliferation in the form of onion bulbs. Our observations support the concept of a primary neuronal abnormality in the hypertrophic type of Charcot-Marie-Tooth disease (HN-CMT). The disorder appears to initially involve the distal axonal processes but, with progression of the disease, also involves the proximal axons, eventually leading to degeneration and loss of neurons in the anterior horns and dorsal root ganglia. Onion-bulb formation generally parallels nerve fiber degeneration, suggesting that segmental demyelination and onion bulbs may occur secondary to axonal degeneration. The possibility of a concomitant Schwann cell abnormality cannot be excluded, however, on the basis of our postmortem studies.

Adult↗

Regional cerebral blood flow thresholds during cerebral ischemia.

The development of methods of determining regional cerebral blood flow (rCBF) has made possible the determination of thresholds for the appearance of cerebral ischemia. These thresholds vary depending on the method used for assessing cerebral ischemia. The following thresholds have been determined in man and nonhuman primates: 20 cc/100 g per min, electroencephalogram (EEG) and evoked cortical potential abnormalities appear, paralysis seen in waking monkeys; 15 cc/100 g per min. EEG and evoked cortical potential are lost; 12 cc/100 g per min, flows at this level in excess of 120 min produce infarction in waking animals; and 6 cc/100 g per min, massive loss of intracellular [K+]. The residual rCBF and the duration of ischemia determine the appearance of infarction in waking Macaca irus monkeys.

Animals↗

Effect of occlusion on large vessels. I. A study of the rat carotid artery.

The effect of permanent occlusion on the carotid artery of the rat was studied by light and by electron microscopy. A segment between two ligatures was examined at times from 2 minutes to 1 year. Between 2 and 15 minutes after occlusion, the red blood cells adjacent to the wall formed radially arranged rouleaux; within 24 hours the endothelium disappeared, while platelets (despite the lack of flow) accumulated against the denuded elastica. This behavior of formed blood elements may have been the result of electric forces (injury potential). By 3 days, undifferentiated cells were found lining the elastica interna or free in the lumen; they apparently were derived from medial smooth muscle.In the media, by 3 days some smooth muscle cells had become necrotic, while "undifferentiated" cells appeared; strong circumstantial evidence suggested that these were smooth muscle cells which had lost their specific characteristics and had thus become dedifferentiated (a phenomenon also known to occur in striated muscle cells); by 1 month they had matured into smooth muscle, but the media from then on contained fewer cells and more collagen than normal.In the lumen, the undifferentiated cells also matured into typical smooth muscle cells from 15 days onward, while collagen and elastin appeared between them. After 1 month these cells began to accumulate droplets of fat, which thereafter increased in number (at 6 months they were associated with cholesterol clefts) and then declined. This accumulation of fat in smooth muscle cells (also seen in atherosclerosis) was interesting because it occurred in the absence of blood flow.

Arterial Occlusive Diseases↗

Craniopharyngiomas: a clinical and pathological review.

Two hundred and forty-five cases of craniopharyngiomas were obtained from the files of the AFIP and reviewed statistically with reference to their gross and microscopic appearance and clinical data. The majority of the tumors were cystic and microscopically, cysts were formed by squamous epithelial maturation, by degeneration of the stellate cells at the centers of adamantinomatous nests, or by degeneration of the stroma. Transitional forms were seen between adamantinomatous and squamous epithelium and keratohyaline granules and keratin were present in some cases. Because of this overlap, differentiation between craniopharyngiomas and suprasellar epidermoid cysts often is not possible. Significantly increased acturial survival rates were associated with absence of calcification in plain skull films in adults, negative CSF examination, and tumor size under 3.0 cm.

Calcinosis↗

Spinal cord infarction: a highly reproducible stroke model.

The study of focal central nervous system ischemia has been impeded by the lack of animal models that are both reproducible and simulate human ischemic strokes. To circumvent these problems, we have developed a rabbit spinal cord infarction model. Infarction of the caudal lumbar cord is produced by temporary occlusion of the abdominal aorta below the renal arteries. One hour of ischemia causes all of the animals to develop spinal cord infarctions in a highly reproducible pattern. These animals can be maintained alive for at least 2 weeks post-operatively. We believe that the tissue changes in spinal cord infarction are qualitatively similar to infarction of most areas of the central nervous system. This model has numerous features which make it particularly useful for neurochemical, neuropathological, and neurophysiological studies.

Animals↗