Scleral plug of biodegradable polymers containing ganciclovir for experimental cytomegalovirus retinitis.

PURPOSE: To evaluate the efficacy of a biodegradable scleral plug containing ganciclovir (GCV) in a rabbit model of human cytomegalovirus (HCMV) retinitis. METHODS: To develop a rabbit model for HCMV retinitis, HCMV solution was injected once into the vitreous cavity of pigmented rabbits. The treated animals were divided into three groups: group A received no treatment, group B was treated once with GCV solution, and group C was treated with a scleral plug containing GCV. Rabbits in group B received an intravitreal injection of GCV solution 1 week after HCMV inoculation. In group C, the scleral plug containing GCV was implanted in the vitreous of the rabbits 1 week after HCMV inoculation. Ophthalmoscopically, vitreoretinal findings in each group were graded from 0+ to 4+ every week for 4 weeks after HCMV injection. RESULTS: Eyes of group A rabbits showed whitish retinal exudates and vitreous opacities 3 days after HCMV inoculation. These materials increased gradually until 3 weeks after HCMV inoculation. Scores for vitreoretinal lesions were significantly lower in eyes of group B rabbits compared with those of group A at 1 week after GCV injection (P < 0.05). However, vitreoretinal inflammation in eyes of group B rabbits increased again thereafter, and no significant difference in inflammation between groups A and B was found 2 weeks after GCV injection. In eyes of group C, scores for vitreoretinal lesions were significantly lower compared with those in both group A and group B at 3 weeks after HCMV inoculation (P < 0.01). CONCLUSIONS: The results demonstrated that sustained release of GCV into the vitreous cavity with biodegradable scleral plugs was effective for the treatment of experimentally induced HCMV retinitis in rabbits.

Replacement of myocardium with a Dacron prosthesis for complications of acute myocardial infarction.

From July 1983 to April 1986, four patients (three with ventricular septal perforations and one with left ventricular free-wall rupture) underwent replacement of the myocardium with a Dacron prosthesis for complications of acute myocardial infarction. There were three males and one female, ages ranging from 53 to 70 years (mean 63.3). Three of the four patients survived; the one with the ventricular septal perforation died of severe cardiac failure five days after operation. Replacement of the infarcted myocardium with a Dacron prosthesis seems to be an excellent operative technique for the treatment of complications of acute myocardial infarction when the left ventricular cavity is predicted to be small after resection of the myocardium.

Effect of particle size of polymeric nanospheres on intravitreal kinetics.

In this study, we injected nanospheres containing a fluorescein derivative into the vitreous cavity of pigmented rabbit eyes and evaluated their intraocular kinetics as drug carriers in vivo. Polystyrene nanospheres (2 microm, 200 nm and 50 nm in diameter) containing a fluorescein derivative were used in this study. A suspension of each particle was prepared by diluting with distilled water at a concentration of 10 microg/ml equivalent to sodium fluorescein. The suspension of nanospheres was injected once into the vitreous cavity of unilateral eyes of pigmented rabbits. A sodium fluorescein solution of the same concentration was injected once into the vitreous cavity of the other eye as the control. The intraocular kinetics of nanospheres was evaluated by measuring vitreous fluorescence using a scanning fluorophotometer. To investigate elimination pathways of nanospheres in detail, serial cross-sections of the eyes were examined with a fluorescence microscope. The fluorescence derived from nanospheres was observed in the vitreous cavity for over 1 month (2 microm: t(1/2) = 5.4 +/- 0.8 days, 200 nm: t(1/2) = 8.6 +/- 0.7 days, 50 nm: t(1/2) = 10.1 +/- 1.8 days), whereas that in the control eyes completely disappeared within 3 days (t(1/2) = 7.8 +/- 0.7 h). The elimination half-life from the vitreous cavity correlated well with the particle diameter (r = -0.997, p = 0.007). Histological studies using a fluorescence microscope revealed that nanospheres with a diameter of 2 microm were seen in the vitreous cavity and trabecular meshwork, while nanospheres with a diameter of smaller than 200 nm were also observed in the retina as well as these tissues. Our findings indicated that nanospheres may be beneficial as a drug carrier to the retina, vitreous and trabecular meshwork.

Chemical characterization of eumelanins with special emphasis on 5,6-dihydroxyindole-2-carboxylic acid content and molecular size.

Mammalian melanins exist in two chemically distinct forms; the brown to black eumelanins and the yellow to reddish pheomelanins. Eumelanins are derived from copolymerization of 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA). Eumelanins can be quantified by HPLC analysis of the oxidation product pyrrole-2,3,5-tricarboxylic acid (PTCA) and by our spectrophotometric method (Sp.EM). We also developed a spectrophotometric method for assaying the total amount of eu- and pheomelanins by dissolving them in Soluene-350 (TM). In addition, we previously showed that Sp.EM/TM and PTCA/TM ratios are significant parameters in characterizing eumelanins produced in follicular melanocytes. The objectives of this study were (1) to clarify the significance of Sp.EM/TM and PTCA/TM ratios in synthetic eumelanins and (2) to apply these methods to characterizing natural eumelanins with various DHI/ DHICA ratios and molecular sizes. The results obtained show that (1) the Sp.EM/TM ratio of synthetic eumelanins increases as polymerization proceeds, (2) the Sp.EM/TM and PTCA/TM ratios in copolymers of DHI and DHICA correlate to the percentage content of DHICA-derived units, and (3) combination of the Sp.EM/TM and PTCA/TM ratios serves to estimate the DHICA content and the degree of polymerization in natural eumelanins.

Anomalies associated with Axenfeld-Rieger syndrome.

BACKGROUND: To detect the associated anomalies in patients with Axenfeld-Rieger syndrome is clinically important, because early treatment for such anomalies is crucial to both visual and systemic development. This study was conducted to clarify the associated anomalies in the syndrome. METHODS: We evaluated 21 patients with Axenfeld-Rieger syndrome encountered at Nagoya City University Hospital over a 16-year period. Patients who presented with a prominent Schwalbe's line accompanying the iris strands were diagnosed as having Axenfeld-Rieger syndrome. RESULTS: The series consisted of 9 males and 12 females, ranging in age from 1 month to 41 years, mean 15.4+/-12.7 (SD) years. The syndrome was bilateral in 17 cases and unilateral in 4 cases. Hypoplasia of the iris was observed in 10 eyes of 6 patients. The associated ocular anomalies included sclerocornea in 6 eyes of 3 patients, developmental glaucoma in 5 eyes of 3 patients, persistent pupillary membrane in 4 eyes of 2 patients, microphthalmos in 3 eyes of 2 patients, and typical iris coloboma in 1 eye. Of 10 eyes with hypoplasia of the iris, 5 exhibited glaucoma. The accompanying systemic anomalies included 9 cases of dental anomalies, 5 of facial anomalies, and 3 of Alagille syndrome. CONCLUSIONS: All of the associated ocular and systemic anomalies appeared to arise from the maldevelopment of the neural crest cells. Patients with Axenfeld-Rieger syndrome should therefore be examined for the presence of anomalies in the tissues of neural crest origin. Patients with hypoplasia of the iris should be checked for glaucoma.