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  • Author or Editor: Rafael J. Tamargo x
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Irving J. Sherman, Ryan M. Kretzer and Rafael J. Tamargo

✓ Walter Edward Dandy (1886–1946) began his surgical training at the Johns Hopkins Hospital in 1910 and joined the faculty in 1918. During the next 28 years at Johns Hopkins, Dandy established a neurosurgery residency training program that was initially part of the revolutionary surgical training system established by William S. Halsted but eventually became a separate entity. Dandy’s residents were part of his “Brain Team,” a highly efficient organization that allowed Dandy to perform over 1000 operations per year, not counting ventriculograms. This team also provided rigorous training in the Halsted mold for the neurosurgical residents. Although exacting and demanding, Dandy was universally admired by his residents and staff. This article describes Dandy’s neurosurgical residency program at Johns Hopkins, and provides personal recollections of training under Walter Dandy.

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Ryan M. Kretzer, Alexander L. Coon and Rafael J. Tamargo

Although Walter E. Dandy (1886–1946) is appropriately credited with the first surgical clipping of an intracranial aneurysm in 1937—a procedure that established the modern field of vascular neurosurgery—his numerous other contributions to this specialty are not as well known. Dandy can be credited with the first detailed description of the vein of Galen malformation, the first description of x-ray visualization of an intracranial aneurysm, the first characterization of basilar artery dolichoectasia, and the publication of the first comprehensive operative case series of arteriovenous malformations, cavernous malformations, and developmental venous anomalies. In addition, Dandy performed the first surgical trapping of a cavernous internal carotid artery (ICA) aneurysm by clipping the supraclinoid ICA and ligating the cervical ICA, and he also executed the first intracranial surgical clipping of the ICA to treat a carotid-cavernous fistula. In this article the authors describe Dandy's contributions to the field of vascular neurosurgery.

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Ryan M. Kretzer, Ranice W. Crosby, David A. Rini and Rafael J. Tamargo

✓ Dorcas Hager Padget was a pioneer in the fields of neurosurgical illustration and neuroembryology who practiced during the early 20th century at The Johns Hopkins University. Without a college degree, she trained as a medical illustrator in the Johns Hopkins School of Medicine's Department of Art as Applied to Medicine under Max Brödel. She began her career working for Walter Dandy as his medical artist, gaining worldwide recognition for her neurosurgical illustrations. With Dandy's encouragement, Hager Padget undertook her own scientific research, studying neurodevelopment and aneurysm formation in the circle of Willis by using human embryos from the world-renowned Carnegie Collection. She made lasting contributions to the field of neuroembryology, publishing the first major work on neurodevelopment of the cerebral arterial and venous systems. Following Dandy's death in 1946, Hager Padget began a full-time career as a scientific researcher, first at the Department of Embryology at the Carnegie Institution of Washington in Baltimore and later at the University of Maryland School of Medicine. She continued to make contributions to the field of congenital malformations of the brain and spine, coining the term “neuroschisis” to describe a possible mechanism of neural tube damage leading to the creation of a myelomeningocele. The authors describe Dorcas Hager Padget's contributions to neurosurgical illustration and neuroembryology, as well as her remarkable career.

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Veit Rohde and Uzma Samadani

Object

Currently no adequate surgical treatment exists for spontaneous intracerebral hemorrhage (ICH). Implantable polymers can be used effectively to deliver therapeutic agents to the local site of the pathological process, thus reducing adverse systemic effects. The authors report the use of stereotactically implanted polymers loaded with tissue plasminogen activator (tPA) to induce lysis of ICH in a rabbit model.

Methods

Ethylene vinyl acetate (EVAc) polymers were loaded with bovine serum albumin (BSA) only or with BSA plus tPA. In vitro pharmacokinetic (three polymers) and thrombolysis (12 polymers) studies were performed. For the in vivo study, 12 rabbits were fixed in a stereotactic frame, and 0.2 ml of clotted autologous blood was injected into the right frontal lobe parenchyma. After 20 minutes, control BSA polymers were stereotactically implanted at the hemorrhage site in six rabbits, and experimental BSA plus tPA polymers were implanted in six rabbits. Animals were killed at 3 days, and blood clot volume was assessed.

The pharmacokinetic study showed release of 146 ng of tPA over 3 days. The tPA activity correlated with in vitro thrombolysis. In the in vivo study, the six animals treated with tPA polymers had a mean (±standard error of the mean [SEM]) thrombus volume of 1.43 ±0.29 mm3 at 3 days, whereas the six animals treated with blank (BSA-only) polymers had a mean (±SEM) thrombus volume of 19.99 ±3.74 mm3 (p <0.001).

Conclusions

Ethylene vinyl acetate polymers release tPA over the course of 3 days. Stereotactic implantation of tPA-loaded EVAc polymers significantly reduced ICH volume. Polymers loaded with tPA may be useful clinically for lysis of ICH without the side effects of systemic administration of tPA.

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Quoc-Anh Thai, Gustavo Pradilla, Federico G. Legnani, Ryan M. Kretzer, Wesley Hsu and Rafael J. Tamargo

Object

Currently no adequate surgical treatment exists for spontaneous intracerebral hemorrhage (ICH). Implantable polymers can be used effectively to deliver therapeutic agents to the local site of the pathological process, thus reducing adverse systemic effects. The authors report the use of stereotactically implanted polymers loaded with tissue plasminogen activator (tPA) to induce lysis of ICH in a rabbit model.

Methods

Ethylene vinyl acetate (EVAc) polymers were loaded with bovine serum albumin (BSA) only or with BSA plus tPA. In vitro pharmacokinetic (three polymers) and thrombolysis (12 polymers) studies were performed. For the in vivo study, 12 rabbits were fixed in a stereotactic frame, and 0.2 ml of clotted autologous blood was injected into the right frontal lobe parenchyma. After 20 minutes, control BSA polymers were stereotactically implanted at the hemorrhage site in six rabbits, and experimental BSA plus tPA polymers were implanted in six rabbits. Animals were killed at 3 days, and blood clot volume was assessed.

The pharmacokinetic study showed release of 146 ng of tPA over 3 days. The tPA activity correlated with in vitro thrombolysis. In the in vivo study, the six animals treated with tPA polymers had a mean (± standard error of the mean [SEM]) thrombus volume of 1.43 ± 0.29 mm3 at 3 days, whereas the six animals treated with blank (BSA-only) polymers had a mean (± SEM) thrombus volume of 19.99 ± 3.74 mm3 (p < 0.001).

Conclusions

Ethylene vinyl acetate polymers release tPA over the course of 3 days. Stereotactic implantation of tPA-loaded EVAc polymers significantly reduced ICH volume. Polymers loaded with tPA may be useful clinically for lysis of ICH without the side effects of systemic administration of tPA.