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Biomedical subjects

I J Constable

Publications and source records attributed to I J Constable.

At least 199 records · Page 11Linked to original sources

Physical properties of experimental vitreous membranes. I. Tensile strength.

The tensile strength of vitreous membranes, induced by silk sutures imbedded in the vitreous body and removed one to two weeks later, was investigated in rabbits. Three types of membranes were distinguished by their appearance under an operating microscope; dense, opaque, cylindrical membranes, (Type 1), broken with 2 to 16 Gm. of force and elongated from 127 to 200 per cent before breaking; thin, cylindrical membranes, (Type 2), broken with 200 mg. to 2 Gm. of force and elongated from 51 to 152 per cent before breaking; and thin film-like membranes imbedded in formed vitreous gel, (Type 3), broken with 200 mg. to 5.5 Gm. of force and elongated from 53 to 186 per cent before breaking. Vitreous membranes formed two to eight weeks after surgery resisted forces greater than those required to detach rabbit retina. The results of the experiment are relevant in the design of vitrectomy instruments.

Animals↗

Vitreous structure, IV. Chemical composition of the insoluble residual protein fraction from the rabbit vitreous.

Analysis of the structural proteins in the rabbit vitreous showed that the hydroxyproline content was 3.1 per cent w/w compared to a value of 10.9 per cent w/w for equivalent samples obtained from cattle. In contrast to the discreet fibers in bovine vitreous, the rabbit constituents occur as an aggregate of fibrils with a diameter of 15 to 20 å. The amino acid and carbohydrate composition was similar to vascular basement membrane and isolated fractions contained significant amounts of palmitic and stearic acids. The data indicate that the variability of vitreous structure in different species is not only quantitative, but also qualitative. It is suggested that in the rabbit the structural proteins may be derived primarily from the atrophied hyaloid system and that little, if any, secondary vitreous formation occurs in this animal.

Amino Acids↗

Optimized underwater diathermy for vitreous surgery.

The properties of radio frequency (RF) diathermy currents are briefly reviewed. The inadequacy of damped currents is stressed. The recommended machine generates a frequency of 13.56 MHz. It has a power amplifier, crystal control, coaxial lead from machine to handle, and an impedance of 200 ohms. The two types of electrodes and handles described are shielded from the electrode tip to the diathermy machine. One has a short handle, and an electrode angulated at 35degrees, used in open-sky vitrectomies. The other has a longer handle and straight probe, and is provided with a system for saline infusion. It is used in closed transscleral operations. Electrodes require 35 to 50% more current when used underwater than when used on dry sclera. If charring of tissue is to be avoided, it is advisable to keep the intensity near the level at which gas bubbles form at the electrode tip. Blood vessels can be closed reliably and safely with these electrodes.

Animals↗

Proton irradiation of simulated ocular tumors.

Silicone sponges were sutured to the sclera of owl monkeys to create an indentation which would simulate a tumor of the posterior segment of the eye. A tantalum clip inserted in the silicone sponge served as a marker for radiographic localization of the simulated tumors. The acute lesions obtained on the retina and choroid after moderately high doses of proton irradiation suggest that this method of aiming the proton beam will be adquate for human clinical trials.

Animals↗

Keratoprostheses: advancing toward a true artificial cornea.

Keratoprosthesis surgery is carried out in very few centers. Elaborate surgical techniques and high complication rates limit the application of currently available keratoprostheses (KPros). However, the clinical need for an alternative to donor tissue has sparked considerable research interest in the development of new KPros. This paper charts the evolution of KPros from the earliest devices to those currently used, describes their drawbacks and discusses the specifications of an ideal device. Recent research focuses upon the use of porous polymers as the skirt component of core-and-skirt KPros in order to obtain improved biological integration of the prosthetic material. Developments in biomaterials technology make a KPro analogous to a donor corneal button an increasingly realistic goal. However, two particular problems still need to be addressed. First, it must be demonstrated that secure long-term fixation that is able to withstand trauma is achievable in a full-thickness artificial cornea. Second, an ideal artificial cornea for a wet eye requires an epithelialized surface, and this has yet to be achieved.

Animals↗

Generation and characterization of a recombinant adenovirus expressing vascular endothelial growth factor for studies of neovascularization in the eye.

There is accumulating evidence that an increased expression of vascular endothelial growth factor from retinal pigment epithelial cells may be important in choroidal neovascularization. In vivo studies have demonstrated that subretinal injection of recombinant adenovirus vectors produces long-term transgene expression specifically within retinal pigment epithelial cells. A recombinant adenovirus encoding of vascular endothelial growth factor (Ad.RSV.VEGF) was therefore produced and characterized in order to determine whether an upregulation of vascular endothelial growth factor expression is sufficient to induce choroidal neovascularization. Ad.RSV.VEGF was produced by homologous recombination and its identity confirmed by restriction enzyme analysis. Ad.RSV.VEGF was characterized in vitro by the transduction of cultured retinal pigment epithelial cells. The in vitro characterization confirmed vascular endothelial growth factor mRNA and protein expression from Ad.RSV.VEGF and demonstrated the biological activity of the vascular endothelial growth factor protein. A preliminary in vivo study suggested that the subretinal injection of Ad.RSV.VEGF induced vascular leakage.

Adenoviridae↗

Models for assessing scar tissue inhibitors.

The main purpose of animal models for proliferative vitreoretinopathy (PVR) is to develop pharmacologic therapies for this common cause of blindness. A very large number of pharmacologic agents appear to have potential use in this application by preventing cell proliferation and/or contraction. In practice, however, it has been found that prohibitively extensive numbers of animals and laboratory services are required to establish drug efficacy, safety, and dosage regimes. To lessen this work load and to accelerate drug screening programs, the authors have developed an in vitro model for PVR based on chorioretinal fibroblast growth in three-dimensional collagen lattices. This model yields precise data on the effect of drugs on cell proliferation and contractility. Trifluoperazine, colchicine, 5-fluorouracil, dexamethasone, and penicillamine were screened in this model. The first three agents were found to be inhibitory; on the basis of the pharmacokinetic data, obtained dosage regimes for animal testing were developed. The results obtained are discussed in terms of the in vitro model and the biochemical action of these drugs on the cellular events in PVR. In vitro screening of drugs prior to animal testing offers a significant advance in the quest for a pharmacologic prevention of blindness due to PVR.

Animals↗

Models for assessing scar tissue inhibitors.

The main purpose of animal models for proliferative vitreoretinopathy (PVR) is to develop pharmacologic therapies for this common cause of blindness. A very large number of pharmacologic agents appear to have potential use in this application by preventing cell proliferation and/or contraction. In practice, however, it has been found that prohibitively extensive numbers of animals and laboratory services are required to establish drug efficacy, safety, and dosage regimes. To lessen this work load and to accelerate drug screening programs, the authors have developed an in vitro model for PVR based on chorioretinal fibroblast growth in three-dimensional collagen lattices. This model yields precise data on the effect of drugs on cell proliferation and contractility. Trifluoperazine, colchicine, 5-fluorouracil, dexamethasone, and penicillamine were screened in this model. The first three agents were found to be inhibitory; on the basis of the pharmaco kinetic data, obtained dosage regimes for animal testing were developed. The results obtained are discussed in terms of the in vitro model and the biochemical action of these drugs on the cellular events in PVR. In vitro screening of drugs prior to animal testing offers a significant advance in the quest for a pharmacologic prevention of blindness due to PVR.

Animals↗