Angiogenic competency of biodegradable hydrogels fabricated from polyethylene glycol-crosslinked tyrosine-derived polycarbonates.

Synthetic biomaterials can be used as instructive biological milieus to guide cellular behaviour and function. To further realize this application, we synthesized a series of structurally similar hydrogels and tested their ability to modulate angiogenesis. Hydrogels were synthesized from poly(DTE-co-x% DT carbonate) crosslinked by y% poly(ethylene glycol) (PEG). Hydrogel desaminotyrosyl tyrosine (DT) contents (x%) ranged from 10-100%, and crosslink densities (y% PEG-crosslinker) ranged from 5-80%. The hydrogels were fashioned into porous scaffolds with highly interconnected macro- and micro-pore (>100 and 10 mm in diameter, respectively) architecture using poly(DTE-co-10%DT carbonate% crosslinked with 8% PEG. Under physiological conditions (in vitro), the hydrogels degraded into three major products: desaminotyrosyl-tyrosine ethyl ester (DTE), desaminotyrosyl tyrosine (DT), and poly(ethylene glycol)-di-DT-hydrazide (PEG-di-DT hydrazide). Increasing either DT content or crosslink density brought quickened degradation. Because DT and DTE, two of the three major degradation products, have not demonstrated any noticeable cytotoxicity or angiogenic effect in previous studies, we measured the cytotoxicity of PEG-di-DT hydrazide, the third major degradation product. We found that PEG-di-DT hydrazide only displayed significant cytotoxicity at the high concentration of 100 mg/mL. Interestingly, PEG-di-DT hydrazide and its further degradation product PEG-dihydrazide stimulated in vitro endothelial cell migration and tubulogenesis, which is comparable to results found with FGF-beta treatment. Subcutaneous implantation of the PEG-crosslinked poly(DTE-co-10%DT carbonate) scaffolds into the backs of rats elicited greater tissue growth over time and superior vascularization than poly(DTE carbonate) implantation. These results show that this new class of biomaterials has a strong potential to modulate angiogenesis.

Recurrence of posterior polymorphous corneal dystrophy after penetrating keratoplasty.

Recurrence of a corneal dystrophy after keratoplasty can occur in multiple dystrophies, including macular, granular, and lattice dystrophies. We treated two unrelated patients who had documented posterior polymorphous dystrophy and who, in previously clear grafts, developed haziness in the zone of Descemet's membrane, which led to graft failure. Histologic examination of the keratoplasty specimen showed changes typical of posterior polymorphous dystrophy.

Congenital corneal keloid.

The clinical course and pathological findings in an infant with a congenital corneal opacity, aniridia, and cataract of the right eye and anophthalmia of the left orbit are reviewed. Although the lesion was thought to represent a dermoid pre-operatively, the keratoplasty specimen revealed disorganized and vascularized connective tissue, with thickened, keratinized epithelium. Bowman's and Descemet's membranes as well as the endothelium were absent. These histopathologic findings were felt to represent a congenital corneal keloid. The co-existence of aniridia in the involved eye and anophthalmia of the contralateral socket are hypothesized to be evidence that a primary ocular developmental disorder, rather than a reparative process, resulted in the corneal alteration. The difficulties of penetrating keratoplasty in lesions of this sort are examined.

Epithelial downgrowth: a 30-year clinicopathological review.

We performed a retrospective clinicopathological review of 124 patients with epithelial downgrowth seen over a 30-year-period at the Massachusetts Eye and Ear Infirmary. The purpose of this study was to determine predisposing factors in the development of epithelial downgrowth, diagnostic symptoms and signs, and the results of various types of treatments. The incidence of this condition after cataract surgery was 0.12%, decreasing to 0.08% over the latter decade. 82% of postsurgical patients with epithelial downgrowth presented to the ophthalmologist within one year following surgery, commonly complaining of decreasing visual acuity, red eye, and pain. The most common presenting signs of epithelial downgrowth were retrocorneal membrane, which was seen in 45% of patients, glaucoma in 43%, corneal oedema in 21%, and a positive Seidel test in 23%. We found that a variety of conditions predispose to epithelial downgrowth but that no one factor was present in all cases. Damage to the underlying endothelium, corneal stromal vascularisation, and stromal downgrowth appeared to be important events not emphasised in prior studies. The angle was partially or totally closed in 87% of enucleation specimens. Patients treated surgically underwent fewer enucleations than those treated medically or not treated.

Co-cultivation of retinoblastoma with fibroblasts, iris pigment epithelium, and retinal pigment epithelium in tissue culture.

Retinoblastoma cells of the Y79 line were co-cultivated with human fibroblasts and bovine iris and retinal pigment epithelium in tissue culture. The Y79 cells, which characteristically grow as a suspension culture, were found to attach directly to the fibroblasts and pigment epithelium on the flask surface. Electron microscopic examination of the fibroblast-retinoblastoma co-cultures revealed numerous pinocytotic vesicles lining the fibroblast cell borders that were in contact with the tumor cells. The retinoblastoma cells contained increased numbers of ribosomes, endoplasmic reticulum, and-mitochondria. Fibroblastic processes appeared to wrap around and engulf tumor cells. In both the iris and retinal pigment epithelium co-cultures with retinoblastoma cells, there were increased numbers of mitochondria in the tumor cells in areas adjacent to pigment epithelium but no pinocytotic vesicles were seen. The pigment epithelium attached to Y79 cells showed fewer processes than did the fibroblasts in co-culture. In summary, both fibroblast and pigment epithelium functioned as an effective carrier cell layer for retinoblastoma cells. In addition, we believe that the fibroblast layer removed substances secreted by the tumor cells via pinocytotic vesicles.

Adaptation to lateral displacement of vision in patients with lesions of the central nervous system.

The visual-motor adaptation to lateral displacement of vision by prism glasses was studied in normal individuals and patients with cerebellar dysfunction, Parkinson's disease, right or left cerebral hemisphere lesions, Alzheimer's disease, or Korsakoff's syndrome. Adaptation was analyzed in two phases, the return to normal pointing with prism glasses in place (the "error reduction portion") and the mispointing in the opposite direction after the glasses were removed (the "negative aftereffect portion"). Negative aftereffect, which seems to be the best measure of true adaptation, was significantly reduced only for the cerebellar patients. This poor performance supports the involvement of the cerebellum in motor learning.

Combination chemotherapy of malignant melanoma with imidazole carboxamide, BCNU and vincristine.

Forty patients with disseminated malignant melanoma were treated with triple combination chemotherapy consisting of Imidazole Carboxamide, BCNU and Vincristine. Seventeen of 40 patients (42.5%) showed significant responses including three complete responses. Responses were seen in cutaneous, lymph node and pulmonary metastases. Nine instances of hepatic metastases were unaffected by therapy but 68% of the skin and nodal patients responded. The median response duration was only 4 months and the median survival of responders was 9.5 months compared to a 2 month median survival of non-responders. Half of the responders died of CNS metastases. The short duration of response, the resistance of hepatic metastasis and the high incidence of cerebral recurrence necessitate additional therapeutic approaches to this disease.