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Biomedical subjects

E S Flamm

Publications and source records attributed to E S Flamm.

At least 19 recordsLinked to original sources
PubMed1992

Percivall Pott: an 18th century neurosurgeon.

This paper examines neurosurgery in the 18th century and suggests that the origins of the specialty can be recognized at the time when surgeons began to use the neurological status of the patient as a guide for surgical intervention. Percivall Pott (1714-1788) was one of the leading surgeons in London in the 18th century. He is remembered through eponyms of Pott's puffy tumor, Pott's fracture, and Pott's disease. A review of his writings and those of his contemporaries indicates that these surgeons were aware of the importance of changes in level of consciousness after head injury. The recognition and significance of the lucid interval was described and understood as a neurosurgical sign in the 18th century. Because of Pott's pre-eminence in the surgery of his time through his writings and lectures, he should be considered one of the founders of neurosurgery as a separate surgical discipline.

History, 18th Century↗
PubMed1992

Anomalous arrangement of the origins of the anterior choroidal and posterior communicating arteries. Case report.

A case of anomalous origin of the anterior choroidal and posterior communicating arteries in a 36-year-old woman with aneurysmal subarachnoid hemorrhage is presented. Preoperative four-vessel angiography revealed a reverse relationship of these vessels, wherein the anterior choroidal artery origin was proximal to the origin of the posterior communicating artery. This arrangement is extremely rare; the only other reported case was in a patient undergoing angiography prior to acoustic neurinoma resection. It is believed that this is the first case reported in a patient with subarachnoid hemorrhage from rupture of an aneurysm arising from a vessel of such anomalous origin.

Adult↗
PubMed1990

Isolated one-and-a-half syndrome with pontine cavernous angioma: successful surgical removal.

We report a patient with a pathologically proven pontine cavernous angioma and a horizontal one and a half syndrome. Following recurrent hemorrhages, the vascular malformation was removed from the dorsal pons using microsurgical techniques with partial resolution of the motility disturbance. This case demonstrates that vascular malformations of the brainstem parenchyma may be removed, thereby precluding further hemorrhage and facilitating the return of neurologic function.

Adult↗
PubMed1989

The potential use of nicardipine in cerebrovascular disease.

The efficacy of intravenous nicardipine in the prevention of vasospasm after subarachnoid hemorrhage has been investigated in a dose escalation study in 67 patients admitted within 1 week of subarachnoid hemorrhage. Favorable outcomes were noted in 52 patients (78%). Vasospasm was found by arteriography in 31 patients (46%). A dose-related trend was noted. At the lower dose levels, angiographic spasm was observed in 68% and symptomatic vasospasm in 27% of 34 patients. Only eight of 33 patients (24%) treated at the highest dose level (approximately 10 mg/hr) developed arteriographic evidence of vasospasm. Symptomatic vasospasm was diagnosed in only two of 33 patients (6%) treated with this dose. No deaths from vasospasm occurred. Verification of changes in tissue calcium has been obtained from the rat middle cerebral artery occlusion model, and we concluded that nicardipine administered after permanent occlusion may offer protection against cerebral ischemia in this animal model. Nicardipine uptake was greater at the infarct site than in surrounding tissue, with the highest concentration in the area of maximal ischemia. Nicardipine appears to affect changes in Ca2+ more than other ions: it significantly reduced Ca2+ accumulation in the territory of the middle cerebral artery by 60% at 6 hours, and significantly reduced Na+ and K+ shifts in the same territory by 40% and 50%, respectively, at 6 hours. Although much research remains to be done, a wide role for the dihydropyridines in a number of cerebrovascular conditions is emerging.

Animals↗
PubMed1988

Combination of aminocaproic acid and nicardipine in treatment of aneurysmal subarachnoid hemorrhage.

Antifibrinolytic drugs reduce the risk of rebleeding during the first 2 weeks after aneurysmal subarachnoid hemorrhage. However, they do not lower overall mortality, largely because of an increased incidence of cerebral ischemia. The usefulness of antifibrinolytic drugs might be increased if a method to prevent or control vasospasm in patients were to be developed. We recently completed late Phase I and Phase II studies of the calcium ion blocking drug nicardipine in 67 patients treated within 1 week of subarachnoid hemorrhage. Of these 67 patients, 42 had delayed operations and were treated concomitantly with the antifibrinolytic drug aminocaproic acid (1.5 g/hr) for an average of 6 days before surgery. The outcome of these 42 patients is the subject of this report. Fifteen of 42 patients were treated with the lower dosage levels of nicardipine (0.4-4.5 mg/m2/hr), and 27 patients were treated at the highest dosage level (6.0 mg/m2/hr). Using the World Federation of Neurological Surgeons scale for subarachnoid hemorrhage, at admission 18 patients were Grade I, 15 were Grade II, 6 were Grade III, and 3 were Grade IV. Five patients (12%) developed clinical signs of deterioration suggestive of cerebral ischemia with concomitant evidence of vasospasm on arteriography. These patients were all treated with hypervolemic hypertensive therapy. Only one patient (2%) developed an infarction from vasospasm. Two patients developed symptomatic hydrocephalus requiring ventriculoperitoneal shunting, and a third patient required a temporary ventriculostomy. The 3-month postoperative outcomes were excellent. Three patients (7%) rebled. Three patients died, two from rebleeding of the aneurysm and one who never regained consciousness from the initial hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Nicardipine reduces calcium accumulation and electrolyte derangements in regional cerebral ischemia in rats.

We studied the effects of the calcium channel blocker nicardipine on regional tissue Ca2+, Na+, K+, and water shifts in the brains of seven Sprague-Dawley rats after permanent occlusions of the middle cerebral artery. We also assessed the entry of [14C]nicardipine into the brains of five rats; the highest concentrations of [14C]nicardipine were in the infarcted area. Nicardipine treatment significantly reduced Ca2+ accumulation in the middle cerebral artery territory by 60% compared with six untreated rats 6 hours after arterial occlusion. Eight 125-micrograms/kg boluses of nicardipine given every 30 minutes starting 5 minutes after arterial occlusion also significantly reduced the Na+ and K+ shifts in the middle cerebral artery territory by 40% and 50%, respectively, 6 hours after arterial occlusion. Nicardipine appears to reduce Ca2+ accumulation more than it reduces Na+ and water accumulation and K+ loss. Our results suggest that a calcium channel blocker can protect brain tissues in a model of focal cerebral infarction by directly reducing Ca2+ entry into ischemic cells.

Animals↗
PubMed1988

In vivo metabolism of radiolabeled putrescine in gliomas: implications for positron emission tomography of brain tumors.

The in vivo uptake and metabolism of radiolabeled putrescine was examined in two glioma models: (a) the T9 gliosarcoma in the CD Fischer rat and (b) the U-87 MG human glioblastoma in the athymic (nude) mouse. Autoradiography after parenteral administration of [14C]putrescine revealed rapid and selective uptake by both tumors compared with normal brain. Polyamine analysis of the rat gliosarcoma demonstrated minimal conversion of labeled putrescine to its metabolites, spermidine and spermine, at 5 and 30 minutes after intravenous injection. The human glioblastoma also exhibited minimal polyamine conversion at 5 minutes, although there was a trend toward significant metabolism at longer time periods (30 and 45 minutes). In addition, the human glioblastoma produced nonpolyamine metabolites that suggest an alternative pathway of putrescine metabolism via gamma-aminobutyric acid. These in vivo findings are discussed in relation to the usefulness of putrescine as a marker for positron emission tomography of human gliomas.

Animals↗
PubMed1988

Dose-escalation study of intravenous nicardipine in patients with aneurysmal subarachnoid hemorrhage.

A dose-escalation study of the calcium ion entry blocking drug nicardipine was performed using large dose infusions in 67 patients with recent aneurysmal subarachnoid hemorrhage (SAH). A safe, potentially therapeutic dose of the drug was determined. Patients admitted within 7 days of SAH from a documented cerebral aneurysm were entered into the study if no spasm was present on the initial angiogram. Nicardipine was administered as a continuous intravenous infusion throughout the 14-day period after SAH, regardless of the timing of surgery. To determine the safest possible dose, nicardipine was administered at seven dose levels from 0.01 to 0.15 mg/kg/hr. The total daily doses ranged from 27.7 mg to 375.0 mg. A follow-up angiogram was carried out on all 67 patients 7 to 10 days after SAH. Computerized tomography and neurological examinations were used to determine the presence of cerebral infarction. No major adverse effects, unexpected reactions, or permanent sequelae could be attributed to nicardipine. A decline in blood pressure was noted following administration of the drug. This occurred more frequently among patients given the largest dose but did not produce clinical problems or require discontinuation of the drug. Favorable outcomes were noted in 52 patients (78%). Vasospasm was found by arteriography in 31 patients (46%). A dose-related trend was noted: only eight (24%) of 33 patients treated at the highest dose level (approximately 10 mg/hr) developed arteriographic evidence of vasospasm. Symptomatic vasospasm was diagnosed in only two (6%) of 33 patients treated with this dose. Of the 34 patients receiving the lower dose levels, angiographic spasm was observed in 68% and symptomatic vasospasm in 27%. No deaths due to vasospasm occurred. Nicardipine appears to prevent both vasospasm and cerebral ischemia after SAH. A multicenter randomized double-blind trial to test this hypothesis is planned.

Adult↗
PubMed1987

Aneurysms of the distal anterior cerebral artery and associated vascular anomalies.

Between July 1975 and July 1985, 20 patients with 24 congenital distal anterior cerebral artery (DACA) aneurysms were admitted to our institution and underwent microsurgical clipping of their aneurysms. This group composes 4% of the 588 aneurysms managed surgically during this period. The clinical presentations included subarachnoid hemorrhage, transient ischemic attacks, headaches, and seizures. Fourteen patients had additional vascular anomalies documented by angiography: multiple aneurysms, bilateral DACA aneurysms, arteriovenous malformation distal to incidental DACA aneurysms, and azygous DACA. Computed tomography was performed in 19 patients and was valuable in preoperative planning and prognosis: intracerebral hematoma and intraventricular hemorrhage were associated with poor preoperative grade and the development of vasospasm. Operative management, case morbidity/mortality, and the high incidence of multiple aneurysms and other vascular anomalies associated with DACA aneurysms are discussed. Because of the devastating effects of subarachnoid hemorrhage from these aneurysms, they should be carefully searched for and treated before hemorrhage occurs.

Adult↗
PubMed1986

Putrescine metabolism in human brain tumors.

The metabolism of the polyamines, putrescine, spermidine and spermine, was studied in human brain and brain tumors. Samples of brain and tumors were incubated with 3H-putrescine and the amounts of labeled polyamines were measured. The amount of putrescine conversion was found to be greater in tumors that in normal brain samples. Furthermore, the metabolism of putrescine in brain tumors was related to tumor type and appeared to correlate with the degree of malignancy. The significance of these findings with regard to positron emission tomographic scanning and therapy of patients with malignant gliomas is discussed.

Astrocytoma↗
PubMed1986

Tissue Na, K, and Ca changes in regional cerebral ischemia: their measurement and interpretation.

A simple and reliable method of quantifying tissue damage is described. This method, based on atomic absorption spectroscopic determinations of Na, K, and Ca concentrations in small brain samples, was applied to the rat middle cerebral artery occlusion model (MCAo). At the infarct site by 24 hours, Na concentration more than doubled, Ca concentration increased by greater than 70%, and K concentration fell nearly 80%; these changes are consistent with a greater than 80% disruption of cells. A remarkable acceleration of ionic shifts occurred between 4 and 6 hours after MCAo. At 4 hours, only 20-30% of the ionic shifts found at 24 hours had occurred; by 6 hours, 80-100% of the ionic shifts found at 24 hours had taken place. Since the measurements reflect ionic movement into and out of the tissue, they are likely to represent irreversible tissue damage. Although blood brain barrier breakdown may have contributed to an increased rate of ionic shifts, large ionic gradients must have been present between the extracellular space and the vascular compartment at 4-6 hours to drive the ionic shifts. Our results suggest an upper time limit of 4 hours for treatments of acute ischemic tissue damage in the rat MCAo model. The methods and analytical approach described may be useful for determining the time window for therapeutic intervention in acute CNS injuries, as well as for evaluating treatment effects.

Acute Disease↗
PubMed1986

Effect of difluoromethylornithine on the antiglioma therapeutic efficacy of intra-arterial BCNU.

In an attempt to improve glioma management, an animal model was developed to evaluate the therapeutic efficacy of intra-arterial 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Furthermore, the model was used to study the antitumor activity of D,L-alpha-difluoromethylornithine (DFMO), a polyamine-biosynthesis inhibitor, used both as a single agent and in combination with intra-arterial BCNU. An N-methylnitrosourea-induced gliosarcoma (T9) was transplanted stereotaxically into the right caudate nucleus of male Fischer 344 rats. Animals receiving a single low-dose (5 mg/kg) intracarotid injection of BCNU 9 days following tumor implantation had a 57% increase in life span compared with untreated control rats (p less than 0.001). Intracarotid drug delivery was more effective than systemic (intraperitoneal) administration of the same dose of BCNU. When given as a single agent, DFMO demonstrated dose-dependent effectiveness. As part of a combined regimen, DFMO enhanced the antitumor therapeutic activity of both systemic (intraperitoneal) and intra-arterial BCNU. Survival times of animals receiving combined DFMO and intra-arterial BCNU were almost double those of untreated controls, and were significantly better than survival times of animals receiving combined DFMO and intraperitoneal BCNU. These findings suggest methods to optimize current clinical chemotherapy for glioma.

Animals↗