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Biomedical subjects

M R Mayberg

Publications and source records attributed to M R Mayberg.

At least 55 records · Page 3Linked to original sources

Improved outcome after rupture of anterior circulation aneurysms: a retrospective 10-year review of 224 good-grade patients.

Several significant diagnostic and therapeutic advances in the management of subarachnoid hemorrhage have emerged during the last 10 years. The present study was undertaken to determine whether these advances have improved overall outcome in patients of low surgical risk and what factors predict outcome. The authors retrospectively reviewed the management of good-grade patients seen at the Harborview Medical Center at the University of Washington, who suffered ruptured anterior circulation aneurysms between 1983 and 1993. The results in this series demonstrate that favorable outcomes occurred in 96.8% of patients designated Hunt and Hess Grade I, 88.3% of those assigned Grade II, and 81.3% of those deemed Grade III after rupture of anterior circulation aneurysms. On the basis of clinical and radiographic factors present at admission, correct prediction can be made about all favorable, but only 17% of unfavorable outcomes. During the decade under investigation, the authors observed a significant (p = 0.002) increase in the number of favorable outcomes: 74.5% of patients treated during the first management period (1983-1987); 87% of patients treated during the second period (1987-1990); and 93.5% of patients treated during the third management period (1990-1993) experienced favorable outcomes. Improvements in critical-care techniques and the management of vasospasm may be associated with the improved outcome observed during this series.

Adult↗

Radiation inhibition of intimal hyperplasia after arterial injury.

To demonstrate the effect of gamma radiation on proliferating smooth muscle cells in vivo, a standardized bilateral carotid balloon catheter arterial injury was produced in 45 rats and doses from 0-20 Gy were delivered to the right carotid artery at 24 h after injury. At 20 days after injury, cross-sectional area of intima was determined from axial histological sections. Compared to contralateral, nonirradiated balloon-injured arteries, radiation produced a significant dose-dependent reduction in intimal cross-sectional area, with a 50% decrease at 5-7.5 Gy. To determine the effect of timing of irradiation on intimal hyperplasia, 30 rats with bilateral carotid injury received unilateral cervical irradiation at doses of 1, 5 or 10 Gy administered at either 1, 3 or 5 days after injury. The radiation dose (P = 0.0002), timing of irradiation (P = 0.003) and an interaction between timing and dose (P = 0.0278) were significantly associated with reduction in neointimal cross-sectional area. To determine the effects of radiation on intimal hyperplasia at later intervals, rats irradiated with 15 (n = 5) or 20 Gy (n = 5) were euthanized at 3 months after injury. A significant persistent reduction in intimal cross-sectional area for irradiated arteries at 3 months was associated with minimal apparent radiation effects upon adjacent tissue. These data suggest that external gamma irradiation at the single doses used effectively inhibits smooth muscle proliferation and intimal hyperplasia in the rat balloon catheter injury model in a time- and dose-dependent manner.

Angioplasty, Balloon↗

Unilateral vestibular schwannoma in a child with prior orbital rhabdomyosarcoma.

In the absence of neurofibromatosis, vestibular schwannomas (acoustic neuromas) are rarely found in children. We report a case of a 13-year-old boy who presented with unilateral vestibular schwannoma 11 years after resection of an orbital rhabdomyosarcoma. The coincidence of these tumors has not been previously reported.

Adolescent↗

Gamma irradiation inhibits neointimal hyperplasia in rats after arterial injury.

BACKGROUND AND PURPOSE: Restenosis complicates a significant proportion of endovascular and open vascular procedures such as carotid endarterectomy. In contrast to the primary atheroma, restenosis is characterized by intimal hyperplasia of vascular smooth muscle cells. We hypothesized that gamma radiation would reduce restenosis by limiting intimal hyperplasia after arterial injury. METHODS: To demonstrate the effect of gamma radiation on smooth muscle hyperplasia in vivo, a standardized bilateral carotid balloon catheter arterial injury was produced in 37 rats. A single dose of 750, 1500, or 2250 cGy (1cGy = 1 rad) gamma radiation was delivered to the right carotid artery at either 1 or 2 days after injury; the shielded contralateral carotid artery served as matched control. At 21 days after injury, vessels were perfusion-fixed in situ, and cross-sectional area of neointima was determined from axial sections using image analysis. RESULTS: Marked reductions in neointimal cross-sectional area were demonstrated in vessels subjected to 1500- and 2250-cGy radiation at both 1 and 2 days after injury. A less prominent effect was noted for 750 cGy, reaching statistical significance only at 2 days after injury. By two-way ANOVA, radiation dose (P = .0002), timing of radiation delivery (P = .003), and an interaction between timing and dose (P = .0278) were significantly associated with reduction in neointimal cross-sectional area. At 1500 cGy, delivery of radiation 1 day after injury inhibited neointimal hyperplasia more prominently than the same dose 2 days after injury; a dose-response relation was evident at 1 day. CONCLUSIONS: Radiation may be an important adjunctive therapy for reducing the incidence of restenosis after angioplasty or endarterectomy.

Animals↗

Stereotactic radiosurgery: a review and comparison of methods.

PURPOSE: Stereotactic radiosurgery (SRS) is an evolving modality for treating well-circumscribed intracranial lesions. Different physical methods have been developed to deliver highly localized dose distributions accurately. We review the different methods and the documented clinical results to present a coherent view of radiosurgery, and to aid physicians and physicists in the appropriate use of this modality. DESIGN: A review of the medical physics and clinical literature was conducted. The physical aspects of the different methods and their impact on treatment were summarized. Results were compiled from those individual clinical series with adequate follow-up data to compare the various modalities with respect to treatment outcome for benign tumors, metastases, and vascular malformations. RESULTS: The physical accuracy was comparable between radiosurgical methods. Differences between gamma radiation and linear accelerator methods had little effect on the dose distribution for single isocenter treatments. Charged particle methods could produce better dose localization for large lesions (> 25 cm3) than was possible with photon methods. Clinical results indicate similar lesion control rates between all radiosurgical methods. There was a progressive increase in the median size of treated lesions for gamma radiation, linear accelerator, and charged particle methods. CONCLUSION: For small lesions (< 5 cm3), physical dose distributions are similar for the photon methods, but linear accelerator methods offer more flexibility for the treatment of intermediate-sized (5 to 25 cm3) lesions in applying future technical developments. More clinical results are needed before firm conclusions can be drawn on the type of lesions to be treated, and the dose-volume parameters to be used.

Brain Neoplasms↗

Severe symptomatic vasospasm: the role of immediate postoperative angioplasty.

The clinical success of angioplasty for symptomatic vasospasm following subarachnoid hemorrhage (SAH) depends on early intervention and can best be achieved after the aneurysm is occluded. However, patients presenting with unsecured ruptured aneurysms and established clinical vasospasm offer a dilemma for the surgeon. The authors describe the cases of five such patients who underwent acute clipping of aneurysms followed by immediate postoperative angioplasty between 1988 and 1992. All were referred at least 5 days after SAH. Severe vasospasm compatible with the clinical presentation was confirmed by angiography. The patients met the department's criteria for angioplasty but, because of unclipped aneurysms, were first taken patients met the department's criteria for angioplasty but, because of unclipped aneurysms, were first taken to the operating room for a craniotomy and aneurysm obliteration. Angiography was repeated immediately after surgery. Arterial narrowing had progressed during surgery in two patients. In all patients, postoperative mechanical dilatation was achieved with the use of a silicone microballoon. Following angioplasty, transcranial Doppler ultrasound flow velocities and single-photon emission computerized tomography evaluation indicated improved cerebral perfusion compared to preoperative determinations. Four patients improved clinically and made a good recovery. In this subgroup of patients presenting with proven symptomatic vasospasm and an unclipped but ruptured aneurysm, urgent surgical obliteration of the aneurysm followed by immediate postoperative angioplasty may be a safe and reasonable means to improve outcome.

Adult↗

Local application of calcium antagonists inhibits intimal hyperplasia after arterial injury.

The local effect of the calcium channel antagonist diltiazem and the protein kinase inhibitor 1-5-(isoquinoline sulfonyl)-5-homopiperazine HCL (HA1077) on neointimal formation after arterial injury were investigated by the use of a perivascular drug-delivery system. Bilateral carotid artery balloon injury was produced in 130 rats. In six groups of 10 rats each, diltiazem or HA1077 at three doses (low, 0.2 mg; medium, 1 mg; high, 5 mg) was mixed with the drug-delivery polymer poly(vinyl) alcohol and applied to the adventitial surface of the injured right carotid artery enclosed by a Silastic cuff; 10 control animals received polyvinyl alcohol only in the silastic cuff. In all animals, the contralateral injured artery without the cuff served as a control. At 10 and 20 days after the injury, the intimal cross-sectional area was determined from light microscopic sections for the injured segment of both carotid arteries. In six additional groups of 10 rats each, treated as above, levels of diltiazem and HA1077 in plasma were measured at periods from 1 hour to 5 days after perivascular application. At 10 days after endothelial injury, animals receiving high-dose diltiazem or HA 1077 (5 mg) demonstrated significant reductions in neointimal area compared with polyvinyl alcohol controls for both treated and contralateral untreated vessels. At 20 days after injury, neointimal hyperplasia was inhibited only on the treated side in both high-dose groups. Perivascular diltiazem and HA1077 at lower doses (1 or 0.2 mg) did not affect neointimal area at 10 or 20 days in either treated or untreated arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

Sequestration and secretion of insulin-like growth factor-I by bovine aortic endothelial cells.

Endothelial cells elaborate growth promoting activities in culture medium that support limited smooth muscle cell and fibroblast growth in vitro in the absence of serum. We investigated whether insulin-like growth factor-I (IGF-I) was synthesized and secreted by bovine aortic endothelial cells in vitro. Subconfluent endothelial cell cultures in serum-free medium secreted severalfold higher IGF-I levels than confluent cultures by acid-sizing chromatography and IGF-I radioimmunoassay. The IGF-I secretory level was not sustained during a second serum-free incubation. In contrast, secretion of IGF binding proteins persisted and was maintained at constant levels throughout the same observation periods. Analysis of poly(A+)RNA by northern blots revealed hybridization of an IGF-I cDNA to a 7.5- to 7.0-kb transcript and superinduction of the 7.5-7.0-kb mRNA by the translational inhibitor, cyclohexamide. However, no endogenously labeled IGF-I was detected in conditioned media after incubation of cultures with [35S]cysteine or [3H]leucine. When cultures were incubated in the presence of serum supplemented with IGF-I, subconfluent cultures sequestered and released more IGF-I than confluent cultures. We concluded that the majority of IGF-I secreted in vitro was sequestered from serum.

Animals↗

Basic fibroblast growth factor and transforming growth factor beta-1: synergistic mediators of angiogenesis in vitro.

We investigated the relative roles of basic fibroblast growth factor (bFGF) and transforming growth factor beta-1 (TGF-b) on bovine aortic endothelial cell mitogenesis and morphogenesis using two-dimensional Petri dish cultures and a three-dimensional hydrated collagen gel. bFGF alone stimulated endothelial cell proliferation with an EC50 of 0.5 ng/ml. At bFGF levels greater than 2.5 ng/ml, morphologic alterations in confluent monolayers predominated; cells changed from a cobblestone morphology to an elongated cell pattern and showed enhanced migration into a denuded area of a Petri dish. In the three-dimensional model, exposure of endothelial cell monolayers to high bFGF levels stimulated minor cell migration directly under the monolayer but no invasion into the gel matrix. In combination with bFGF, heparin potentiated morphogenic changes, but not mitogenesis. bFGF modification of the antiproliferative effect of TGF-b in confluent cultures was evidenced by induction of endothelial cell sprouting in response to 0.5 ng/ml TGF-b and 10-20 ng/ml bFGF in two-dimensional cultures. On collagen gels, endothelial cells migrated into the deep layers of the gel in a dose-dependent manner: invasion was maximal at 0.3-0.7 ng/ml TGF-b with decreased invasion at higher concentrations. The optimal collagen concentration that supported cell invasion was 0.075% collagen with the number of invading cells decreasing with increasing collagen gel density. By scanning electron microscopy, invading endothelial cells assumed a fibroblast-like appearance with slender cell extensions. We concluded that bFGF and TGF-b had independent effects on endothelial cell morphology and mitogenesis in culture. In combination at specific doses, these agents stimulated sprouting in the two-dimensional model and cell invasion in a collagen gel model. Morphogenic changes may be the primary event in determining angiogenesis.

Animals↗

Pituitary oncocytomas: clinical features, characteristics in cell culture, and treatment recommendations.

To determine whether there are significant differences between oncocytomas and pituitary adenomas, we evaluated clinical features, treatment regimens and outcome in 23 males and 9 females (average age 64 years, range 43-81 years) with the histologic diagnosis of pure pituitary oncocytomas (> 95% oncocytes). Symptom duration was six to twelve months in 6 cases (19%) and more than one year in 19 cases (59%). Three patients presented with sudden onset of symptoms, and were found to have hemorrhage within their tumors. Visual loss (69%) and symptoms of hypopituitarism (44%) were the most common presenting complaints. Preoperative endocrine profiles revealed abnormalities in most cases, including pituitary insufficiency in 56% and hyperprolactinemia in 59%. The tumors were typically large at presentation; all but one had suprasellar extension. 28 patients underwent transsphenoidal tumor resections; 4 underwent subfrontal craniotomies. Gross dural invasion was found at surgery in 11 cases. At a mean followup of 31 months (range 2-68 months), recurrent tumor was identified in 4 patients (12.5%). Tumor size, dural invasion, preoperative endocrine profile, and postoperative radiotherapy did not correlate with recurrence. Among seven oncocytomas grown in culture, five demonstrated two distinct cell types consisting of oncocytes and typical adenoma cells, respectively. Oncocytomas often have a different clinical presentation than functional pituitary adenomas.

Adenoma, Oxyphilic↗

Crescendo transient ischemic attacks: a surgical imperative. Veterans Affairs trialists.

PURPOSE: In a randomized, prospective, multicenter trial at 16 medical centers, 189 of 5000 patients screened with cerebrovascular disease were identified as having angiographic internal carotid artery stenosis (> 50%) corresponding to presenting symptoms of transient ischemic attacks (TIAs), transient monocular blindness, or recent, minor completed stroke. METHODS: Patients were randomly assigned to carotid endarterectomy plus the best medical care (n = 91) versus the best medical care alone (n = 98). RESULTS: After 1 year there was a significant reduction in stroke or crescendo attacks in the 91 patients who received carotid endarterectomy (7.7%) compared with 98 patients who did not undergo operation (19.4%) (p = 0.011). Twelve (12%) of the 98 patients with symptomatic carotid stenosis treated medically had crescendo TIAs, four had minor strokes, and three had major strokes. Crescendo TIAs were defined as disabling, recurrent transient cerebral or retinal ischemia characterized by an increased frequency, duration, or severity of events. The average time from randomization until the onset of crescendo TIAs was 2 months. Seven of the 12 patients in whom crescendo TIAs developed had stenosis greater than 90%, one had greater than 80% stenosis, and four had between 70% and 80% stenosis, with one of these four having contralateral occlusion. Another three patients had 50% or greater contralateral occlusion. Patients with crescendo TIAs were offered carotid endarterectomy, and all 12 had an uncomplicated, urgent procedure. On follow-up the 12 patients were symptom free at the study conclusion. CONCLUSIONS: Crescendo TIAs are disabling symptoms that occur in patients with high-grade carotid stenoses often within 3 months of the initial symptoms of ischemic cerebrovascular disease. The 12% of medically treated patients in whom crescendo TIAs developed had carotid endarterectomy, which abolished symptoms on follow-up.

Blindness↗

Risks of anticoagulation therapy after experimental corticectomy in the rat.

To determine the optimal postoperative interval after which heparin therapy can be safely initiated, a rat model for experimental craniotomy and corticectomy was developed. In 50 rats (100 lesions), heparin therapy was initiated 1, 2, 3, 5, or 7 days after standardized bilateral frontal corticectomy and was continued for 7 days. Intraperitoneally administered heparin, 75 to 100 U/kg.h, was continuously given to maintain the activated partial thromboplastin time in one of two ranges: therapeutic (1.5-3 times control) or supratherapeutic (> 3 times control). The size of intracranial hemorrhage was determined from coronal brain sections by automated image analysis. No significant hemorrhage was observed in control (saline infusion) animals or in rats receiving therapeutic doses of heparin beginning more than 24 hours after surgery. Small (10-50 mm3) and large (> 50 mm3) hemorrhages were frequent at all intervals up to 5 days in animals with supratherapeutic activated partial thromboplastin time (P < 0.01). Judicious heparin therapy may be safely initiated at 48 hours after craniotomy and corticectomy in rats, whereas supratherapeutic anticoagulation is associated with intracranial hemorrhage at intervals of up to 5 days.

Animals↗

Prevention of postoperative intracerebral hemorrhage with topical recombinant factor XIII in the rat.

Factor XIII is an endogenous clotting factor that retards thrombus degradation by cross-linking fibrin. To determine the efficacy of Factor XIII as a topical clot-stabilizing agent in preventing postoperative hemorrhage associated with coagulopathy, a rat model of experimental craniotomy and standardized bilateral frontal corticectomy was developed. In 25 rats (50 lesions), recombinant human Factor XIII or placebo solution was topically applied to corticectomy cavities after hemostasis was achieved; each animal served as its own control. In 20 rats, heparin sulfate (100 U/kg.h) was initiated intraperitoneally 3 days after surgery and was continually administered by an Alzet pump for 7 days, compared with a control group of 5 rats receiving saline intraperitoneally. The volume of intracranial hemorrhage was quantitatively determined from coronal sections by use of automated image analysis. Large (> 50 mm3) intracerebral hemorrhages were significantly more frequent in placebo (60%)- compared with recombinant Factor XIII (15%)-treated lesions (P < 0.01) in animals receiving heparin. The topical application of clot-stabilizing agents such as Factor XIII may reduce the risk of postoperative intracranial hemorrhage, especially in high-risk patients with coagulopathy.

Administration, Topical↗

Paragangliomas of the sellar region: report of two cases.

Two cases of paraganglioma arising from the parasellar region are presented. Both occurred in middle-aged women who sought treatment of headaches but who had no endocrinological dysfunction; one case was associated with ophthalmoplegia from cavernous sinus involvement. Diagnosis in both cases was confirmed by typical histological appearance and cytochemical demonstration of immunoreactive chromogranin in tumor cells. The pathological features and possible pathogenesis of parasellar paragangliomas are discussed.

Adult↗

Detection of proliferating cell nuclear antigen in gliomas and adjacent resection margins.

We describe a technique for estimating the number of proliferating cells in gliomas and adjacent resection cavities after tumor removal. Proliferating cell nuclear antigen (PCNA) is a nuclear protein associated with the cell cycle. Anti-PCNA antibody staining provides a semiquantitative estimate of the number of proliferating cells found in fixed tissue embedded in paraffin. The extent of the staining of tumor cells of glioblastoma multiforme, anaplastic astrocytomas, low-grade gliomas, and other lesions of the brain with anti-PCNA antibody is correlated with the histological diagnosis. In addition, the labeling of the margins after resection of gliomas and other lesions with anti-PCNA antibody is also associated with the histological diagnosis of the lesion. This technique may be useful in estimating the "biological" extent of resection and in predicting the recurrence patterns of gliomas.

Adolescent↗