PubMed Health⌕ Search

Biomedical subjects

M R Mayberg

Publications and source records attributed to M R Mayberg.

At least 19 recordsLinked to original sources
PubMed1992

Comparison of multicenter study designs for investigation of carotid endarterectomy efficacy.

BACKGROUND: Our report summarizes and compares the characteristics of six prospective, multicenter, randomized clinical trials of carotid endarterectomy underway in North America and Europe. SUMMARY OF REVIEW: Three trials are designed to evaluate the safety and efficacy of endarterectomy in patients with asymptomatic carotid artery stenosis. The other three trials enroll patients who have had transient ischemic attacks or a minor cerebral infarction in the distribution of the randomized artery. Considered together, these six clinical trials span the range of candidates for carotid endarterectomy. The inclusion and exclusion criteria, methodology, and statistical considerations of each study are detailed in tables. CONCLUSIONS: The results from these trials will be helpful in resolving some of the questions surrounding endarterectomy, provided the similarities and differences in the study designs are considered when interpreting the results.

Carotid Arteries↗
PubMed1992

Resolution of petrous internal carotid artery stenosis after transluminal angioplasty. Case report.

Percutaneous transluminal angioplasty is commonly used for treatment of peripheral vascular disease, but only recently has it been applied to craniocervical lesions. The successful use of percutaneous transluminal angioplasty for treatment of an isolated high-grade stenosis of the petrous internal carotid artery is described in a patient with progressive ischemic symptoms despite maximum medical management. At his 2-year follow-up examination, the patient remained asymptomatic with angiographic evidence of progressive resolution of the stenotic lesion and indirect evidence of improved hemispheric blood flow ipsilateral to the lesion. Percutaneous transluminal angioplasty may provide an effective means of treatment for selective intracranial artherosclerotic stenosis.

Aged↗
PubMed1992

Inhibition of delayed arterial narrowing by the iron-chelating agent deferoxamine.

The potential role of iron in cerebral vasospasm was examined in the rat femoral artery model by the perivascular application of deferoxamine, a ferric ion chelator and antioxidant. In 25 rats, platelet-rich plasma or fresh autologous whole blood containing deferoxamine at concentrations of 1, 5, 10, or 15 mg/ml was applied to the adventitial surface of the femoral artery in a Silastic cuff to insure chronic exposure to the vessel wall. At 7 days, contralateral femoral arteries exposed to whole blood showed a 70% reduction in luminal cross-sectional area and morphological changes associated with vasospasm. Application of platelet-rich plasma or whole blood containing deferoxamine at 25 mg/ml produced no significant arterial narrowing or structural changes; significant intermediate reductions in arterial narrowing were observed at deferoxamine concentrations of 5 and 10 mg/ml. Presaturation deferoxamine (10 mg/ml) with excess ferric ion prior to application eliminated the protective effect. In addition, deferoxamine chelated the ferric ion released from incubated whole blood in vitro over 7 days in a dose-dependent manner consistent with its protective effect in vivo. Ferric ion may influence the development of chronic arterial narrowing after subarachnoid hemorrhage by a variety of mechanisms.

Animals↗
PubMed1991

Carotid endarterectomy and prevention of cerebral ischemia in symptomatic carotid stenosis. Veterans Affairs Cooperative Studies Program 309 Trialist Group.

OBJECTIVE: To determine whether carotid endarterectomy provides protection against subsequent cerebral ischemia in men with ischemic symptoms in the distribution of significant (greater than 50%) ipsilateral internal carotid artery stenosis. DESIGN: Prospective, randomized, multicenter trial. SETTING: Sixteen university-affiliated Veterans Affairs medical centers. PATIENTS: Men who presented within 120 days of onset of symptoms that were consistent with transient ischemic attacks, transient monocular blindness, or recent small completed strokes between July 1988 and February 1991. Among 5000 patients screened, 189 individuals were randomized with angiographic internal carotid artery stenosis greater than 50% ipsilateral to the presenting symptoms. Forty-eight eligible patients who refused entry were followed up outside of the trial. OUTCOME MEASURES: Cerebral infarction or crescendo transient ischemic attacks in the vascular distribution of the original symptoms or death within 30 days of randomization. INTERVENTION: Carotid endarterectomy plus the best medical care (n = 91) vs the best medical care alone (n = 98). RESULTS: At a mean follow-up of 11.9 months, there was a significant reduction in stroke or crescendo transient ischemic attacks in patients who received carotid endarterectomy (7.7%) compared with nonsurgical patients (19.4%), or an absolute risk reduction of 11.7% (P = .011). The benefit of surgery was more profound in patients with internal carotid artery stenosis greater than 70% (absolute risk reduction, 17.7%; P = .004). The benefit of surgery was apparent within 2 months after randomization, and only one stroke was noted in the surgical group beyond the 30-day perioperative period. CONCLUSIONS: For a selected cohort of men with symptoms of cerebral or retinal ischemia in the distribution of a high-grade internal carotid artery stenosis, carotid endarterectomy can effectively reduce the risk of subsequent ipsilateral cerebral ischemia. The risk of cerebral ischemia in this subgroup of patients is considerably higher than previously estimated.

Aged↗
PubMed1991

Symptomatic cerebral vasospasm following tumor resection: report of two cases.

The authors report two cases of symptomatic cerebral vasospasm following resection of an acoustic neuroma and a left sphenoid wing meningioma. Vascular spasm was documented by transcranial Doppler and angiography studies. Both patients responded to hypervolemic therapy. Possible mechanisms contributing to this rare complication are discussed.

Adult↗
PubMed1991

Lack of sympathetic and cholinergic influences on cerebral vasodilation caused by sciatic nerve stimulation in the rat.

We studied the influences of sympathetic and cholinergic mechanisms on pial arteriolar responses during cortical activation in the rat. Adult male Sprague-Dawley rats were anesthetized with alpha-chloralose and urethane and mechanically ventilated. Pial arterioles on the somatosensory cortex were visualized on a video monitor through a closed cranial window. Changes in arteriolar diameter induced by sciatic nerve stimulation (0.2 V, 5 Hz, 5 ms, for 20 s) were measured before and after (a) ipsilateral superior cervical ganglionectomy (n = 5), (b) intravenous (0.5 mg/kg) administration and topical (10(-5) M) application of atropine (n = 5), and (c) lesion of the nucleus basalis magnocellularis (the major source of intracerebral acetylcholine neurons, n = 7). Unilateral nucleus basalis magnocellularis lesions were performed stereotactically by injection of ibotenic acid (25 nmol/microliter). Sensory cortex cholinergic denervation was confirmed histologically. These treatments had no significant effect on arteriolar responses to sciatic nerve stimulation. Thus, the present results suggest that neither sympathetic nor cholinergic mechanisms play a significant role in somatosensory evoked cerebral vasodilation.

Animals↗
PubMed1990

Prevention of microvascular thrombosis with controlled-release transmural heparin.

The use of controlled local-release heparin was studied as a means to prevent thrombosis in microvascular surgery, using a rat arterial inversion graft as a model. Polyvinyl alcohol embedded with heparin was placed around the outside of inversion graft anastomoses in 16 animals. Results were compared with control group animals in which polyvinyl alcohol alone was placed around the graft or systemic heparin was given. Vessel patency rates were significantly higher for animals receiving either systemic or transmural heparin than for animals in the control group. Controlled local delivery of heparin did not cause measurable systemic anticoagulation. However, the complication of local hematoma formation occurred as frequently as in the systemic heparin group. Controlled transmural release of heparin has an effective local antithrombotic effect and may hold promise for use in clinical practice.

Anastomosis, Surgical↗
PubMed1990

A rat femoral artery model for vasospasm.

A new animal model for vasospasm using rat femoral artery has been developed. Whole blood, washed erythrocytes, or leukocytes in platelet-rich plasma were selectively applied to the adventitial surface of the femoral artery for 7 days in 15 rats, after which the vessels were perfusion-fixed and examined by light and transmission electron microscopy and immunohistochemistry. As compared with matched control arteries, there was a prominent reduction in luminal cross-sectional area after 7 days in vessels exposed to whole blood or washed erythrocytes, but not in those exposed to leukocytes in platelet-rich plasma. In arteries with luminal narrowing, light and transmission electron microscopy demonstrated marked morphological changes throughout the vessel wall similar to those seen in cerebral vasospasm after subarachnoid hemorrhage. Immunohistochemistry disclosed a prominent loss of immunoreactive actin in smooth muscle cells of arteries exposed to whole blood or erythrocytes. To assess the time course of arterial narrowing in this model, whole blood was selectively applied to the adventitial surface of femoral arteries in 23 rats for periods from 2 to 20 days. As compared with control arteries, arterial narrowing was variably present at 2 days, progressively increased by 5 days, was maximal at 7 to 10 days, and returned to near control levels by 20 days. The presence and severity of ultrastructural changes in vessel wall corresponded to the degree of arterial narrowing over time. These results suggest that chronic narrowing in rat femoral artery exposed to periadventitial blood is analogous to that observed in cerebral arterial vasospasm after subarachnoid hemorrhage. This new model represents a simple and reliable means to investigate pathogenic mechanisms and potential therapies for vasospasm.

Animals↗
PubMed1990

The significance of morphological changes in cerebral arteries after subarachnoid hemorrhage.

A porcine model was developed to allow quantitative assessment of morphological changes in cerebral arteries after subarachnoid hemorrhage and to determine the significance of structural changes in producing arterial narrowing. Whole blood was selectively applied to the middle cerebral artery (MCA) of seven pigs. After 10 days, vessels were perfusion-fixed and examined by light and transmission electron microscopy and immunohistochemistry. The MCA's exposed to whole blood for 10 days showed prominent luminal narrowing associated with profound ultrastructural changes affecting all layers of the vessel wall. Morphometric analysis, however, demonstrated that significant reductions in the luminal cross-sectional area (-55.8% +/- 12.5%, p less than 0.005) and increases in radial wall thickness (75.1% +/- 10.5%, p less than 0.005) were associated with only minimal increase in the cross-sectional area of the vessel wall (12.5% +/- 15%, p less than 0.025). By stereological analysis, the volume density of individual components of the arterial wall was unchanged in MCA's exposed to blood. Vessels exposed to blood showed a 44% reduction in smooth-muscle cell immunoreactive actin and increased collagen in the extracellular matrix of the vessel wall. These data suggest that structural changes in cerebral arteries after subarachnoid hemorrhage do not directly contribute to vessel narrowing through increases in wall mass. Nevertheless, such changes may reflect pathological mechanisms which act to augment prolonged vasoconstriction or inhibit the maintenance of normal vascular tone.

Animals↗
PubMed1990

The role of hemoglobin in arterial narrowing after subarachnoid hemorrhage.

A porcine model for subarachnoid hemorrhage has been developed to allow the selective application of blood and its components to cerebral arteries. Whole blood was centrifuged to produce two fractions consisting of washed erythrocytes (red blood cells, RBC's) and white blood cells (WBC) plus platelet-rich plasma (PRP); the RBC fraction was subsequently separated into hemoglobin (Hb)-containing cytosol and erythrocyte membranes. Each fraction was selectively applied to the middle cerebral artery (MCA) of pigs for 10 days; after which, vessels were perfusion-fixed and examined by light and transmission electron microscopy and immunohistochemical studies. By morphometric analysis, a marked reduction in the MCA lumen cross-sectional area was observed after selective application of RBC's or Hb/cytosol but not of WBC/PRP or erythrocyte membranes. In both RBC- and Hb/cytosol-treated vessels, luminal narrowing was associated with a differential increase in vessel wall thickness of the ventral (subarachnoid) compared to the dorsal (brain) aspect of the artery, but no significant change in cross-sectional area of the vessel wall. After 10 days of exposure to RBC's or Hb/cytosol, there was a spectrum of ultrastructural changes in the vessel wall comparable to those seen after periadventitial application of whole blood. Selective application of commercially available Hb to MCA produced similar structural and morphometric changes. The degree of luminal narrowing after exposure to whole blood or RBC's was proportional to the volume of the erythrocyte mass adjacent to the vessel at sacrifice. These data suggest that arterial narrowing after SAH is mediated by mechanisms related to prolonged exposure of the vessel wall to hemoglobin or its catabolites from lysing subarachnoid erythrocytes.

Animals↗
PubMed1990

Thrombospondin deposition in rat carotid artery injury.

The balloon catheter injury model was used to determine the relative contributions of vascular smooth muscle cells (SMC) and platelets to thrombospondin (TSP) antigen deposition in the artery wall. Rat carotid arteries were denuded of endothelium, exposing the thrombogenic subendothelial extracellular matrix (ECM) to the circulation. Rats were killed after 1 hour, or 5, 10, or 20 days. Thrombospondin antigen deposition in the injured arteries was assessed using a specific polyclonal antiserum raised in rabbit against rat platelet TSP and a sensitive silver-enhanced immunogold staining method. Faint immunostaining for TSP antigen was detected, associated mostly with cells, in the media of the carotid artery of the nonoperated controls. One hour after balloon catheter injury, however, prominent cell-associated immunostaining was evident in the media; extracellular matrix staining was negligible. At this time, large foci of immunostaining were present on the lumenal surface of the vessel. Intimal proliferation was evident on most stained sections of tissue taken 5 days after balloon injury. Thrombospondin antigen immunostaining was markedly increased compared to nonoperated controls in all sections, regardless of the degree of intimal thickening. Thrombospondin immunostaining remained associated with cells in the neointima and media; extracellular matrix staining remained negligible. Ten days after endothelial injury, immunostaining for TSP antigen was detected in all layers of the artery, but was greater in the neointima and media. Reaction product was still associated only with cells. Thrombospondin antigen levels, as detected by this procedure, remained high in the injured tissue through 10 days of observation but appeared less prominent 20 days after injury. At this time extracellular matrix staining was obvious and cell-associated staining was reduced. These data support the hypotheses that thrombospondin (TSP) expression by vascular smooth muscle cells is an early response to injury and that the primary source of TSP antigen in injured artery is the vascular smooth muscle cells (SMC). These results support data derived from in vitro studies of TSP secretion.

Animals↗
PubMed1990

Morphologic changes in cerebral arteries after subarachnoid hemorrhage.

The premise of this article is that morphologic changes observed in cerebral arteries after subarachnoid hemorrhage play an important role in the pathogenesis of associated ischemic deficits observed in this disorder. Secondly, the arteriopathic response of cerebral arteries to subarachnoid blood is similar in many respects to that observed in systemic vessels under various pathologic conditions, and common pathogenic mechanisms may exist. The data supporting these premises may be summarized as follows: 1. Morphologic changes in human and animal cerebral arteries after subarachnoid hemorrhage are temporally associated with angiographic and clinically significant vasospasm. 2. Profound morphologic changes in cerebral arteries after subarachnoid hemorrhage do not contribute to structural narrowing of the lumen through increases in vessel wall mass. Nevertheless, structural changes may act in concert with contractile mechanisms to alter normal physiologic responses and maintain a narrowed lumen. 3. The agent responsible for arterial narrowing and morphologic changes in cerebral arteries after subarachnoid hemorrhage is contained in the erythrocyte component of whole blood and is most likely hemoglobin. 4. The volume and duration of exposure of subarachnoid blood to the artery appears to be significant in the development of the angiopathic response. 5. Ultrastructural abnormalities in systemic vessels associated with hypertension, atherogenesis, and endothelial damage are similar in many respects to those seen after subarachnoid hemorrhage.

Animals↗
PubMed1989

Localized release of perivascular heparin inhibits intimal proliferation after endothelial injury without systemic anticoagulation.

Segmental endothelial desquamation of the common carotid artery was produced in 30 rats using a balloon catheter technique which produces consistent proliferation of intimal smooth muscle cells from 5 to 20 days after injury. Immediately after endothelial injury, 15 animals were treated with periadventitial application of heparin contained in a continuous-release drug-delivery system using the polymer polyvinyl alcohol (PVA) and PVA alone applied in a similar fashion to 15 control rats. Animals were killed at 5, 10 and 20 days, respectively, after surgery by intracardiac perfusion-fixation, and vessels were prepared for light microscopy, scanning electron microscopy, and immunohistochemistry with antibodies directed against actin. At all time periods, there was a significant reduction in intimal cross-sectional area in heparin/PVA-treated vessels compared to control vessels. Scanning electron microscopy showed complete absence of endothelial cells from the luminal surface in both control and treated arteries at all time periods without evidence of significant platelet aggregation. Immunohistochemistry demonstrated the presence of immunoreactive actin in the proliferating myointimal cells. Femoral venous prothrombin time and partial thromboplastin time were unchanged in heparin/PVA-treated animals compared to controls at 1, 5, and 10 days. Continuous-release polymer drug delivery can be used to apply heparin selectively to the adventitial surface of vessels and effect changes in the vessel wall over periods of up to 3 weeks. By this means, smooth muscle proliferation and subsequent vessel narrowing after endothelial injury were inhibited without systemic anticoagulation. This technique may be applicable to both clinical and research applications related to the pathophysiology of arterial injury.

Animals↗
PubMed1989

Intracerebral drug delivery in rats with lesion-induced memory deficits.

Pharmacological treatments directed at increasing cortical acetylcholine activity in patients with Alzheimer's disease have largely been disappointing, perhaps because denervated areas of brain may not be exposed to adequate amounts of drug. A new method has been developed to enable localized intracerebral delivery of neurotransmitter substances using a polymeric drug delivery system. Microspheres of a polyanhydride sebacic acid copolymer were impregnated with bethanechol, an acetylcholinesterase-resistant cholinomimetic. Twenty rats received bilateral fimbria-fornix lesions, producing cholinergic denervation of the hippocampus and marked impairment in spatial memory. The animals were trained for 2 weeks to run after which they received bilateral intrahippocampal implants of saline (five rats), blank polymer (five rats), or bethanechol-impregnated polymer (10 rats). Following implantation, spatial memory was assessed by radial-maze performance testing for 40 days. Untreated lesioned rats showed persistently poor spatial memory, entering maze arms with near random frequency. Similarly, animals treated with saline and blank polymer did not improve after implantation. Rats treated with bethanechol-impregnated microspheres, however displayed significant improvement within 10 days after implantation; this improvement persisted for the duration of the experiment (p less than 0.05, Student's t-test). Histological analysis of regional acetylcholinesterase staining showed widespread loss of activity throughout the hippocampus bilaterally in all animals. The microsphere implants were visible within the hippocampus, with minimal reactive changes in surrounding brain. It is concluded that intracerebral polymeric drug delivery successfully reversed lesion-induced memory deficits, and has potential as a neurosurgical treatment method for Alzheimer's disease and other neurodegenerative disorders.

Anhydrides↗
PubMed1989

Angioplasty for the treatment of symptomatic vasospasm following subarachnoid hemorrhage.

Angioplasty of narrowed cerebral arteries was performed in 10 patients who became symptomatic from vasospasm following subarachnoid hemorrhage. This procedure was accomplished with a microballoon catheter via percutaneous transfemoral insertion. Patients were selected for treatment if they had delayed neurological deficits due to vasospasm which were not responsive to hypervolemic hypertensive therapy. Eight patients (80%) showed sustained improvement in neurological function following the procedure. In two patients transcranial Doppler ultrasound recordings were obtained which revealed decreased mean blood flow velocities following angioplasty. Two patients died, one from an aneurysmal rebleed, and one secondary to diffuse vasospasm. There was one case of delayed stroke 6 weeks following the procedure. The overall results of this series indicate that in selected cases percutaneous balloon angioplasty can offer marked improvement to patients with ischemic deficits due to vasospasm following subarachnoid hemorrhage.

Adult↗