Willem J. Kolff and artificial vision for the blind.
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Biomedical subjects
Publications and source records attributed to W H Dobelle.
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We report development of special macroporous semipermeable membranes and diffusion chambers made of polymerized 2-hydroxyethyl methacrylate (pHEMA), synthesized specifically to enclose living insulin-producing pancreatic islet cells for the treatment of diabetes. This material was selected to minimize the fibrotic encapsulation which has limited hybrid artificial pancreas efforts with other membranes, including Millipore and Nuclepore filters. The pore density and pore size distribution were dependent on the ratio of water to HEMA monomer and also on the crosslinker (EGDMA) concentration. A macroporous membrane resulted only when the ratio of water/HEMA monomer was greater than 50%. 125I-insulin permeability was studied in vitro. A technique is also described to fuse the membranes to form diffusion chambers used for implantation into diabetic rats.
A histological evaluation of the biocompatibility of a new porous hydrogel membrane made of 2-hydroxyethyl methacrylate (2-HEMA) was performed. Isolated membranes and diffusion chambers made of this material and filled with rabbit pancreas were implanted in diabetic rats for periods of up to 8 1/2 months. Histologic evaluation showed that this polymer elicits minimal tissue reaction within the first 7 weeks but some increase in granulation tissue and fibrosis thereafter. A component of this tissue reaction is neovascularization, and many blood vessels were noted immediately adjacent to the membrane's surface. Calcification of the membrane was also progressive but could be minimized by formulations resulting in the incorporation of acid groups throughout the hydrogel and on its surface. Diffusion chambers made of this new material show promise for use in a "hybrid" artificial pancreas for the treatment of diabetes.
The coronary arteries of the goat heart were studied using angiographic techniques and molds of the coronary vessel trees. Blood supplies to the left and right ventricles, interventricular septum, atrioventricular node, and apex of the caprine heart were studied. The goat possesses a left dominant pattern of coronary supply with relatively uniform coronary anatomy and may provide a good large animal model for testing cardiovascular assist devices.
Ninety-five porcine pancreases were incubated at temperatures of 0, 20, or 37 degrees C for periods of 1-32 h. After incubation at 37 degrees C for 2-4 h, islet cells retain their morphologic and functional integrity, whereas acinar cells become necrotic. Because of acinar destruction, the pancreas also becomes soft and amenable to mechanical separation with a simple new device. Temperature-controlled incubation therefore may be a useful first step in the isolation of islet cells from large animal pancreases.
From a research perspective, some of the primary problems created by the FDA regulations include: the amount of time necessary to comply with the regulations and to obtain FDA and IRB review of the studies. The cost of such delays may be great in terms of statistical death. Lack of understanding of the regulations on the part of investigators. Escalated costs and extra restrictions on the use of animals. Benefits of the regulations appear to be: better preclinical testing performed prior to initiating clinical trials, and improved testing protocols, both of which may result in lower risks to patients.
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Electrical stimulation of human visual cortex produces punctuate phosphenes in the visual field. This phenomenon, which is being explored as the basis for a visual prosthesis for the blind, also provides the first electrophysiological information about the retinocortical map in man. Stimulation of points clustered on the surface of the visual cortex produces phosphenes clustered in visual space. However, adjacent surface electrodes located on opposite sides of a sulcus can produce widely separated phosphenes, because the intervening cortex is buried and inaccessible to stimulation. Such electrodes can also produce multiple phosphenes by simultaneously stimulating both banks of the sulcus. Electrodes which are widely spaced on the brain can produce phosphenes close together in visual space providing they stimulate cortex corresponding to overlapping maps in areas 17 and 18. Analysis of the phosphene map indicates that successive stimulation of points further from the tip of the occipital pole produces phosphenes progressively more distant from the fixation point. Successive stimulation of points along the orthogonal dorsoventral dimension produces a progressive change in phosphene bearing. These results confirm the general view of cortical organization derived from field defect studies in man, and from anatomical and electrophysiological studies in monkeys, and provide a new tool for more detailed study of retinotopic projections in man.
Neuroprostheses research provides on application of percutaneous access. We have investigated a number of clinical situations requiring chronic percutaneous transmission of either fluid or electricity in man to explore other uses. Selection criteria for new models include the following considerations: 1) it should allow use of a skull mounted pedestal; 2) it should offer the potential of benefit to the patient with minimal extra risks; 3) it should be a common enough problem to provide sufficient clinical material; and 4) it should not require major new developments of technology. Other potential uses include the artifical pancreas, artificial heart, and hyperalimentation. With some modification, it might be possible to provide access to devices located in the chest via the jugular vein. Similarly, other uses for this percutaneous device warrant investigation. Our twenty man-years of experience with the device indicates that it provides successful chronic access when used with appropriate skill.
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