✓ This article details the errors in compliance with federal rules and regulations relating to the healthcare benefits programs at the University of Washington Department of Neurological Surgery from 1996 through 2002. University faculty members, regardless of the organization to which they belong, will be identified by the federal government as the individual responsible in healthcare finance inquiries. A full understanding of all regulations and an active compliance program are necessary to avoid problems, including criminal prosecution.
H. Richard Winn
Natural history of unruptured intracranial aneurysms
H. Richard Winn
H. Richard Winn
H. Richard Winn
✓ Arthur A. Ward, Jr., the former Professor and founding Chairman of the Department of Neurological Surgery at the University of Washington, died on December 23, 1997. He was a former member (1963–1973) and Chairman (1971–1973) of the Editorial Board of the Journal of Neurosurgery.
Warren R. Selman and H. Richard Winn
Ralph G. Dacey Jr., David Pitkethly, and H. Richard Winn
✓ The management of intracranial aneurysms in elderly patients remains controversial, since the natural history of these lesions is not well understood. The authors describe the case of a 76-year-old woman with documented enlargement of an internal carotid artery aneurysm over 3 years. The management of intracranial aneurysms in elderly patients is discussed.
David D. Weaver, H. Richard Winn, and John A. Jane
✓ Four patients with unilateral mass lesions are presented in whom bilateral supratentorial subarachnoid pressures were continuously recorded. A significant pressure differential between the ipsi- and contralateral side was documented in each case. The possible relationship of this phenomenon to various factors involved in producing increased intracranial pressure, including cerebrospinal fluid flow dynamics, vascular reactivity, elasticity, and brain tissue pressure, are discussed. This study suggests that supratentorial subarachnoid pressure should be measured ipsilateral to the site of a focal mass lesion.
Daniel L. Silbergeld, Francis Ali-Osman, and H. Richard Winn
✓ Endothelial cell proliferation is a significant biological feature of malignant astrocytomas. The ability of the cells of these tumors to elaborate mitogenic angiogenesis factors has been well documented. However, less is known about the transformational effects that neoplastic astrocytes may have on the endothelial cells within malignant astrocytomas. In this study, the hypothesis that humoral factors elaborated by cells derived from malignant astrocytomas induce transformational changes in normal endothelial cells in vitro is investigated. Conditioned medium (CM) was prepared from exponentially growing cultures of a human glioblastoma cell line (UW18) and from two rat brain-tumor cell lines: an anaplastic astrocytoma (R175A) and a glioblastoma with sarcomatous elements (9L). Subconfluent target bovine aortic arch endothelial cells (BAEC's) were exposed for 48 hours to varying concentrations of CM prepared from each of these tumors, and then evaluated for transformational changes. Different molecular weight (MW) fractions of UW18 CM were prepared by molecular ultrafiltration, and each fraction was tested for transforming activity. Transformation endpoints included changes in cellular deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) content and distribution (measured by differential flow cytometry) and changes in de novo DNA synthesis determined by 3H-thymidine incorporation.
Significant changes in the amount and distribution of DNA and RNA were observed in the BAEC's treated with UW18 CM compared to untreated BAEC's. At 10% concentrations of UW18 CM, changes in the RNA profile of target BAEC's were evident, and at 30% concentrations of UW18 CM, an irregular bimodal distribution was well established. Patterns of DNA were also altered in a concentration-dependent manner, with significant aneuploidy developing at UW18 CM concentrations of 20%. The DNA synthesis in BAEC's increased with increasing CM concentrations, up to a maximum of about 250% of control values at 30% concentrations of UW18 CM. The transformational changes induced after exposure of BAEC's to CM prepared from R175A and 9L were significantly less than those observed with UW18 CM. Molecular ultrafiltration was used to prepare UW18 CM fractions with MW cutoffs of less than 10 kD, 10 to 30 kD, and greater than 30 kD. Transformational activity was significant only in CM's with an MW of 10 to 30 kD.
It is concluded that the UW18 human glioblastoma cell line elaborates a soluble factor, or group of factors, with an MW in the 10- to 30-kD range, capable of inducing transformational alterations in target normal endothelial cells, and that such transformation may account for some of the abnormal endothelial cell changes associated with malignant astrocytomas.