Least-squares finite-element scheme for the lattice Boltzmann method on an unstructured mesh.

A numerical model of the lattice Boltzmann method (LBM) utilizing least-squares finite-element method in space and the Crank-Nicolson method in time is developed. This method is able to solve fluid flow in domains that contain complex or irregular geometric boundaries by using the flexibility and numerical stability of a finite-element method, while employing accurate least-squares optimization. Fourth-order accuracy in space and second-order accuracy in time are derived for a pure advection equation on a uniform mesh; while high stability is implied from a von Neumann linearized stability analysis. Implemented on unstructured mesh through an innovative element-by-element approach, the proposed method requires fewer grid points and less memory compared to traditional LBM. Accurate numerical results are presented through two-dimensional incompressible Poiseuille flow, Couette flow, and flow past a circular cylinder. Finally, the proposed method is applied to estimate the permeability of a randomly generated porous media, which further demonstrates its inherent geometric flexibility.

The systemic production of cytotoxic lymphoid cells in corneal allograft reaction. 1. A quantitantitative study utilizing 51chromium release assay.

The purpose of the study was to determine whether the mechanism of corneal allograft rejection is systemic in nature. Utilizing a 51Cr release assay in which labelled donor and recipient corneal cells were used as targets, it was demonstrated that cytotoxic cells specific for antigens located in donor corneal cells were present in spleen and lymph nodes.

Vascular endothelial cell growth inhibitor of normal and pathologic human vitreous.

Normal and pathologic human vitreous have been analyzed for the presence of a low-molecular weight inhibitor of aortic endothelial cell proliferation. Vitreous was subjected to gel chromatography and the material appearing in the retarded volume (less than 13,000 daltons) was tested for its ability to inhibit tritiated thymidine incorporation into DNA by calf aortic endothelial cells. Depending on the sample of vitreous analyzed, one or more fractions showing inhibitory activity were identified in each case.

Ocular toxoplasmosis in three consecutive siblings.

Ocular toxoplasmosis in consecutive siblings is rare. We report positive ocular and serologic findings in three consecutive teenaged siblings. Results of immunologic studies that were performed on members of the family failed to reveal deficiencies.

The BB Wistar rat: an experimental model for the study of diabetic retinopathy.

Diabetic retinopathy was studied in the spontaneously diabetic BB Wistar rat with respect to qualitative and quantitative structural changes. Trypsin-digested retinal preparations revealed after 8 to 11 months of diabetes a decrease in the pericyte/endothelial cell ratio. Quantitative ultrastructural examinations showed no increase in the vascularity or in basement-membrane thickness in diabetic animals. However, retinal capillaries showed not infrequently occlusions by fibrin and platelet thrombi.

Contaminated renal allografts.

Bacterial contamination of a renal allograft may cause infection of the transplant with eventual loss of the graft and possibly death of the patient. We report two cases that illustrate these complications and that support the suggestion that culture of the transport medium is a valuable investigation prior to transplantation.

Changes of MK medium during storage of human cornea.

By comparing the composition of McCarey-Kaufman (MK) medium before and after corneal storage we attempted to identify specific physiological changes in the medium as predictors of tissue damage. We also tried to determine if hydrocortisone (a lysosomal membrane stabiliser) added to the medium could reduce tissue damage during storage. Corneas (human and rabbit) were stored in the MK medium with and without hydrocortisone for 4 days at 4 degrees C. The water and nitrogen contents of the stored cornea were compared with those of the fresh cornea. The medium was analysed before and after corneal storage to determine the concentrations of glucose, protein, and amino acids as well as pH and osmolarity. Scanning electron microscopy (SEM) was used to estimate the degree of the corneal endothelial cell damage. The nitrogen contents and dry weights of the steroid treated and untreated stored corneas were similar to those of the fresh unstored cornea. The steroid treated cornea contained a lesser amount of water than the untreated cornea. The cornea stored in medium without steroid took up a greater amount of glucose from the medium than the cornea stored in medium with steroid. As compared with their concentrations in the fresh unused medium the concentrations of leucine, lysine, and glycine were lower and that of glutamic acid was higher in both the media used for corneal storage. However, the steroid treated storage medium as compared with the untreated storage medium had a greater reduction in the lowering of leucine, lysine, and glycine, and a lesser reduction in the increase of glutamic acid. Steroid treated medium also had a lesser amount of protein released from the stored cornea. Changes in the pH and osmolarity of the media before and after corneal storage were not remarkable. SEM showed that the endothelial cells of the cornea stored in the medium containing steroid were less damaged than those of the cornea stored in the medium without steroid.

Effect of hydrocortisone on the mobilisation of leucocytes in corneal wounds.

We have studied in rabbits the effect of subconjunctivally injected hydrocortisone on the polymorphonuclear leucocyte invasion of corneal wounds at different times after an injury. One group of rabbits was treated with the steroid (hydrocortisone group) and the other not (control group). After making nonpenetrating trephine incisions on the cornea we obtained cellular samples by the impression technique at a given postoperative period (2, 4, or 6 hours), and then the animal was killed. The cornea was processed for histological study of the infiltrating cells. At any postoperative period the number of polymorphonuclear leucocytes in the corneal wounds of the hydrocortisone group was significantly less than the number in the identical wounds of the control group (p less than 0.01 to 0.001).

A morphometric study of endothelial cells of human corneas stored in MK media and warmed at 37 degrees C.

No study has yet been done to investigate the changes in endothelial cell size, perimeter, and density that may result from the warming of corneas in MK (McCarey-Kaufman) medium for specular microscopy. In the present investigation eye bank eyes were stored in MK medium at 4 degrees C and rewarmed daily for six days at 37 degrees C before specular photography of the endothelium was performed. These photographs were compared with wet mount preparations stained with trypan blue and alizarin red made from the same corneas and those stored without rewarming for six days. In addition all corneas were qualitatively analysed with the scanning electron microscope (SEM). The data from serial specular photography were insufficient to allow significant conclusions to be drawn about day to day changes in cell morphology. However, analysis of wet mount preparations revealed that cell density and perimeter varied significantly between those corneas rewarmed daily and those held in cold storage for six days. SEM studies showed an intact cell monolayer with cell loss along the folds of corneal endothelium. We therefore concluded that repeated rewarming at 37 degrees C of corneas stored in MK medium at 4 degrees has a deleterious effect on cell morphology and that folds induced by swelling of corneal tissue result in endothelial cell damage with some loss.

Effects of cigarette smoking on intraocular pressure and vision.

In a survey of 426 patients of Toronto ophthalmologists the correlations of reported smoking habits with (1) intraocular pressure and (2) visual acuity were examined. Average tonometer readings were closely similar in smokers, ex-smokers, and non-smokers, and multiple regression analysis showed similar age coefficients for the 3 categories. However, in women (but not in men) there was also a significant coefficient related to total cigarette exposure (puff-pack-years). It is suggested that this was due to recent smoking rather than a permanent effect on tonometer pressures, pointing the need to standardise this aspect of ocular pressure measurements. Visual acuity showed similar age coefficients in smokers, ex-smokers, and non-smokers, with no independent effect of exposure to cigarette smoke.

Ocular complications of systemic steroid after renal transplantation and their association with HLA.

The eyes of 62 patients who had received allogenic renal transplants were examined for eye disease. Thirty-six patients were found to have steroid induced cataract. Six patients had ocular hypertension. Twelve patients showed arteriosclerotic changes in their fundi relating to their previous hypertensin. There was no significant difference in HLA type in patients who developed cataract and those who did not. 83.3% of the 6 patients with ocular hypertension had HLA B12 in common. None of the patients had cytomegalic retinitis.

Quantitative analysis of collagen content and amino acids in trabecular meshwork.

The purpose of this study was to compare collagen content in the TM of normal and glaucomatous eyes, and to establish whether collagen levels change with age. Collagen content was measured in 30 normal and 27 age matched glaucoma trabeculectomy specimens by the sirius red dye binding technique, and in 14 normal and 15 age matched glaucoma specimens by amino acid analysis. Both dye binding data and amino acid analysis showed no statistical difference between normal and glaucoma samples. Age had no significant effect on mean optical densities or on the collagen-specific amino acids proline, hydroxyproline, and hydroxylysine. Amino acid variability, however, was statistically different between the two groups. These results indicate that mean collagen levels in the trabecular meshwork of glaucomatous eyes do not differ from those in normal eyes.

Is there any difference in the photobiological properties of melanins isolated from human blue and brown eyes?

Investigations were carried out to determine whether the melanin present in the blue and brown eyes were eumelanin, the melanin present in black hair and dark skin, or pheomelanin, the melanin present in red hair and the skin of people with red hair. Our results showed that UV-visible irradiation of blue or brown eye melanin did not produce any superoxide. Irradiation of 51Cr-labelled Ehrlich ascites carcinoma cells in the presence of blue or brown eye melanin did not produce significant cell lysis. The electron spin resonance (ESR) signals of blue and brown eye melanins were very similar to those of eumelanin. Comparison of these findings with our previous results indicated that the blue and brown eye melanins are essentially eumelanin. The ESR signals further suggested that in the case of both blue and brown eye melanins the iris, ciliary body, choroid, and retinal pigment epithelium did not differ.

Experimental and clinical studies on corneal grafts from donors dying of drug overdose: a review.

In order to determine whether or not corneal tissues from donors dying of drug overdose are safe to be used as grafts, animal experiments and a small retrospective clinical study (in which the patients received corneal grafts from donors dying of drug overdose) were done. In rabbits, the drug (ethanol, phenobarbital, pentobarbital, methyprylon, salicylate, or morphine) was injected intravenously in one lethal or sublethal dose. The quantity of the agent was determined in various eye tissues using appropriate techniques. Rabbits were also grafted interlamellarly with full-thickness corneas from animals dying from drug overdose. Concentrations of the agent that reduced cellular proliferation and protein synthesis to 50% were determined using corneal cell culture. Chemical analysis of some eyes of Coroner's cases was done. In animals, all grafts carried the drug to the recipient eye, but none of them (except a few from donors killed with phenobarbital) became opaque or produced any abnormal eye reaction. Only salicylate was found in the cornea and aqueous humor of the drugged animals in a cytotoxic concentration, but only for a short time. Ethanol was found in human eyes for up to 4 days. Clinical investigation revealed no obvious relationship between graft failure and drug content of the donor's blood.

Donor eyes. A comparison of characteristics and outcomes for Eye Bank and local tissue.

The Corneal Recipient Registry was begun in 1985 to collect information on all recipients of corneal grafts in the province of Ontario, Canada, and on the donors providing tissue. While most of the tissue is handled by the Eye Bank of Canada (Ontario Division), ophthalmologists in centers away from the Eye Bank often use local tissue when it is available. Comparison of the donor characteristics of local tissue with that obtained through the Eye Bank revealed that local donors were 9-10 years younger (p less than 0.01), their times to enucleation were an hour less (p less than 0.02), and they were much more likely to be the victims of trauma than the donors of Eye Bank eyes. Prognosis of the graft, assessed using life table methods, suggested that success of local eyes was 89% after 6 months, compared with 80% for Eye Bank eyes in the same period, but this was not a significant difference (p greater than 0.05). While the Eye Bank is a more common source of tissue, eyes obtained locally are more likely to represent the "ideal" tissue for many corneal surgeons.

Phototoxicity of chlorpromazine on retinal pigment epithelial cells.

As it is known that chlorpromazine (CPZ) can bind to melanins as well as cause ocular phototoxicity, we investigated the cytotoxic effects of UV-visible irradiation of melanotic and amelanotic retinal pigment epithelial (RPE) cells in the presence of CPZ. At low concentrations (5 micrograms/ml) of CPZ a photosensitization reaction took place which lysed the cells as measured by the release of 51Cr from cells labelled with chromium. At concentrations of CPZ less than 5 micrograms/ml, no significant cell lysis occurred when the cells were incubated at 37 degrees C in the dark. As the concentration of CPZ was increased to 25 micrograms/ml or more, high percentages of cells were lysed. When the melanotic RPE cells were exposed to different concentrations of CPZ and grown in culture, the cell growth (multiplication) diminished drastically with low concentrations (less than 2 micrograms/ml CPZ). Vitamin E decreased the cell lysis both in the dark and upon irradiation. Oxygen radical scavengers such as glutathione, B-carotene, mannitol, D-penicillamine as well as superoxide dismutase and catalase did not decrease cell lysis. The phototoxic effects of CPZ was found not to be due to stable photoproducts formed during irradiation of CPZ.

The BB-rat--an authentic model of human diabetic retinopathy.

The pathogenesis of diabetic retinopathy has not been fully explained. The earliest histological lesion is the loss of intramural pericytes and thickening of the basement membrane. Increased activity of the polyol pathway is a probable mechanism for these two abnormalities. Investigations have suffered from the lack of an exact animal model simulating the human condition. Examination of the retina in the spontaneously diabetic BB-rat demonstrated degeneration and loss of intramural pericytes, a progressive increase in basement membrane thickness, and microinfarctions with areas of non-perfusion. Therefore, this model may be used to clarify the biochemical mechanism(s) linking the metabolic abnormalities of diabetes and the retinopathy.

The toxic effects of pilocarpine gel and drops on rabbit cornea.

Pilocarpine drops and gel were applied daily for 3 months to rabbit cornea to determine their cytotoxic effects. The corneas were examined clinically with slit lamp biomicroscopy and histologically with scanning and transmission electron microscopy. The gel-treated corneas developed edema and desquamation of the superficial epithelial layers. Vacuoles, swollen mitochondria and amorphous deposits were detected in the basal epithelial layers. The drop-treated corneas developed endothelial cell damage characterised by cytoplasmic vacuoles, swelling and degeneration of the intracellular organelles. The study confirms the clinical impression that pilocarpine gel can produce anterior corneal damage. The toxic effect of pilocarpine gel on the corneal endothelium was much less than the effect produced with pilocarpine drops.

Potential value of collagen shields as a subconjunctival depot release system.

Collagen shields are fabricated from dissoluable porcine scleral tissue and have been used as an ocular drug delivery system. The aim of the present study was to determine the time and extent of shield absorption when implanted subconjunctivally, and the absorption and release of 5-fluorouracil in vitro. Thirty New Zealand white rabbit eyes were employed. BioCor 72 hour collagen shields were surgically implanted in the subconjunctival space. Rabbits were sacrificed at 7, 14 and 21 days after shield implantation, and the remaining shields removed. Remaining shields were measured by both dry weight and protein assay. The absorption and release of 5-FU from collagen shields was determined in vitro using tritiated 5-FU. The collagen shields were not fully absorbed for at least 14 days in the subconjunctival space. In vitro, 5-FU absorbed by the shields reached saturation levels at approximately 15 minutes. Nearly 100% of the 5-FU was released within 15 minutes. Although the time for subconjunctival shield absorption may be useful for antifibroblast drugs, the rate of 5-FU release from these shields is not optimal for enhancing bleb formation when shields are soaked in solutions of 5-FU.

Least-squares finite-element lattice Boltzmann method.

A new numerical model of the lattice Boltzmann method utilizing least-squares finite element in space and Crank-Nicolson method in time is presented. The new method is able to solve problem domains that contain complex or irregular geometric boundaries by using finite-element method's geometric flexibility and numerical stability, while employing efficient and accurate least-squares optimization. For the pure advection equation on a uniform mesh, the proposed method provides for fourth-order accuracy in space and second-order accuracy in time, with unconditional stability in the time domain. Accurate numerical results are presented through two-dimensional incompressible Poiseuille flow and Couette flow.