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Biomedical subjects

D M Albert

Publications and source records attributed to D M Albert.

At least 109 records · Page 6Linked to original sources

Antiproliferative effect of retinoic acid in intravitreous silicone oil in an animal model of proliferative vitreoretinopathy.

PURPOSE: To evaluate, in vitro, the solubility and stability of all-trans RA in silicone oil (SiO) and, in vivo, the stability and the antiproliferative effect of all-trans RA in SiO on an experimental model of PVR. METHODS: The solubility and stability of RA in SiO, in vitro and in vivo, were evaluated by HPLC. Rabbits underwent unilateral gas-compression vitrectomy and gas-SiO exchange. Rabbits received 10 micrograms (n = 17), 5 micrograms (n = 11), and 2 micrograms (n = 9) of all-trans RA in SiO, and SiO only (n = 12). All rabbits received an intravitreous injection of 150,000 fibroblasts. RESULTS: RA is stable in SiO in vitro, but some isomerization from all-trans to 13-cis was observed under light exposure. In vivo, after 1 week, trace amounts of RA in SiO were observed in the controls and in the experimental animals, suggesting a steady state between the release of RA from the SiO and from the retina to the SiO. The rate of fractional retinal detachment was significantly lower in the animals that received 10 and 5 micrograms of RA than in the controls (P < 0.05). No statistical differences were found between the eyes treated with 10 and 5 micrograms of RA. Eyes that received 2 micrograms of RA showed no difference from the control group. CONCLUSIONS: The in vivo data suggest that retinoic acid might be useful as an antiproliferative agent in human eyes.

Animals↗

Investigation of the role of the ras protooncogene point mutation in human uveal melanomas.

PURPOSE: Genetic alterations have been observed in a wide variety of neoplastic processes, including Burkitt's lymphoma, chronic myelogenous leukemia, promyelocytic leukemia, and solid tumors of the colon, skin, and breast. The polymerase chain reaction (PCR), dot blotting, and direct double-stranded DNA sequencing were used to assess ras gene activation in human uveal melanomas for three candidate genes: c-Ha-ras1, c-Ki-ras2, and N-ras at codons 12, 13, and 61. METHODS: Samples of 49 human uveal melanomas were obtained. Amplifiable high molecular weight DNA was obtained from 39 of these. PCR amplification of regions centering on three candidate ras genes was performed. PCR-amplified DNA was evaluated by dot blot and double-stranded DNA sequencing utilizing standard methods. RESULTS: No point mutations were identified in screening the c-Ha-ras gene nor were any genetic alterations found in the c-Ki-ras2 gene at codons 12 and 13. Only wild-type sequences were found at codon 61. No ras mutations were detected in any uveal melanomas studied. CONCLUSIONS: This study provides no evidence to support an association between ras protooncogene mutations and human uveal melanomas at codons 12, 13, or 61.

Adult↗

Occupation and risk of uveal melanoma. An exploratory study.

BACKGROUND: Little is known about the cause of uveal melanoma, the most common primary intraocular malignant lesion in adults. This population-based case-control study evaluated occupational exposures. METHODS: One hundred ninety-seven newly diagnosed cases of uveal melanoma participated. Approximately two control subjects matched for age, sex, and telephone exchange area were selected for each case by random-digit dialing. Data were collected by a structured telephone interview. Two systems of occupational coding were used: an occupation-exposure linkage system and the Bureau of Census data. Conditional logistic regression for matched studies was used to examine various occupational exposures while controlling for previously reported potential confounders and for family income. The occupation-exposure matrix was used to define clusters of cases exposed to a particular chemical group from various occupations. RESULTS: Odds ratios were elevated for agriculture and farming work for both industry and occupation; this was consistent across both classification systems. Elevated odds ratios also were found for occupations involving machine operations, fabrication, assembling, equipment cleaning, and exposure to metal industries. Exposure to alkylating agents and phenols was associated with a lower risk compared with all other exposures. Several self-reported exposures also were studied. Exposures associated with elevated odds ratios were inks, insecticides, gases, radioactive substances, polybromated biphenyls, and chemical solvents. CONCLUSIONS: This exploratory study suggests various occupational associations for uveal melanoma and areas for future research.

Adolescent↗

Nucleolar organizer regions in iris nevi and melanomas.

The silver staining of nucleolar organizer region-associated proteins is an objective method that has been used to differentiate benign from malignant neoplasms. Recently this method was used to distinguish benign choroidal nevi from malignant choroidal melanomas. We studied 24 iris melanocytic lesions to assess the applicability of this technique for differentiating benign from neoplastic iris tumors. Masked observers determined the number of silver-stained nucleolar organizer region dots per cell for silver-stained specimens. Iris nevi contained a mean of 1.6 silver-stained nucleolar organizer region dots per cell, whereas iris (spindle A and B, spindle B, epithelioid, mixed cell) malignant melanomas contained a mean of at least 3.5 silver-stained nucleolar organizer region dots per cell (P less than .0001). All iris nevi demonstrated counts lower than 1.9, whereas all iris melanomas demonstrated counts greater than 2.8. Silver-stained nucleolar organizer region counts were also compared with the clinicopathologic variables of gender, age, and largest specimen dimension. Only the largest specimen dimension correlated with silver-stained nucleolar organizer region counts (P less than .0029). The silver-stained nucleolar organizer region method is a simple technique for differentiating iris nevi from iris melanomas. The silver-stained nucleolar organizer region technique may aid in the assessment and treatment of iris lesions by confirming the malignancy of biopsy specimens.

Female↗

Histopathology of proton beam-irradiated vs enucleated uveal melanomas.

The histopathology of eyes with uveal melanoma was compared in a masked fashion in 47 eyes whose primary treatment was enucleation and a matched series of 47 eyes enucleated after proton beam irradiation. Irradiated tumors were more likely to show signs of necrosis (P less than .001) and fibrosis (P = .005) and to have balloon cells present (P = .002). In the irradiated group, mitotic figures were fewer in 40 high-power fields (P = .020), and the prevalence of tumor blood vessel damage (P less than .001) was higher. Changes in the retina were more common in the irradiated series, but damage was usually overlying or in close proximity to the tumor. Based on characteristic changes, the pathologist distinguished irradiated from nonirradiated eyes in 85% of the cases. These findings suggest that irradiation damages tumor cells and blood vessels, and alters the tumor's capacity for cellular reproduction.

Adult↗

'Black cornea' after long-term epinephrine use.

Fifteen years after a partial maxillectomy and radiation therapy for left antral carcinoma, a 53-year-old woman presented to the Eye Plastics and Orbit Service of the Massachusetts Eye and Ear Infirmary, Boston, with phthisis and a large, black corneal lesion in the left eye. She had been treated for unilateral glaucoma in the left eye for more than 10 years with topically administered epinephrine borate, timolol maleate, and pilocarpine hydrochloride. Clinically, the lesion was smooth, black, and homogeneous, and was thought to represent uveal prolapse covered by a thin layer of epithelium. An eyelid-sparing anterior exenteration was performed. Histopathologic examination revealed an acellular, homogeneous substance that stained positively with the Fontana Masson stain for melanin and bleached with potassium permanganate, findings consistent with corneal adrenochrome deposition. Since adrenochrome can be easily dissected free from the cornea, this case illustrates that misdiagnosing adrenochrome deposition may lead to unnecessary surgery.

Cornea↗

Acquired heterochromia with horner syndrome in two adults.

BACKGROUND: Heterochromia iridis, asymmetry of iris pigmentation, has been well described with congenital Horner syndrome. Acquired heterochromia associated with lesions in the ocular sympathetic pathways in adulthood, however, is rare. METHODS: Two cases are reported in which sympathectomy in adults resulted in ipsilateral Horner syndrome with heterochromia. In each case, pharmacologic testing with cocaine and hydroxyamphetamine was performed. RESULTS: In both cases, sympathectomy occurred at the level of the second order neuron, but hydroxyamphetamine testing suggested at least partial third order neuron involvement. CONCLUSION: Acquired heterochromia can occur in adults. The partial response to hydroxyamphetamine in the two cases presented may reflect trans-synaptic degeneration of the postganglionic neuron. A reduction in trophic influences on iris melanocytes may have contributed to the observed heterochromia.

Aged↗

Adult extrarenal rhabdoid tumor of the lacrimal gland.

A 50-year-old man presented with a rapidly growing mass in the area of the right lacrimal gland. An initial erroneous histopathologic diagnosis of a pleomorphic adenoma made on a small-incisional biopsy was later corrected to a malignant rhabdoid tumor when a wide local excision of the tumor was performed. The tumor was composed predominantly of dyscohesive, globoid, and eosinophilic cells, which frequently contained cytoplasmic inclusions. These were demonstrated to be composed of whorls of intermediate vimentin filaments. The tumor cells expressed epithelial membrane antigen as well as cytokeratin. Ultrastructurally, they displayed intercellular junctions and interrupted segments of linear basement membrane material. These findings, together with the development of the lesion within the parenchyma of the lacrimal gland, are suggestive of an epithelial origin. The patient was treated with radical surgery and adjunctive radiotherapy and chemotherapy, which are the recommended treatment modalities for this highly malignant tumor.

Antigens, Neoplasm↗

Laryngeal candidiasis: a cause of airway obstruction in the immunocompromised child.

Laryngeal involvement with candida is usually secondary to pulmonary candidiasis and is seen in patients with impaired immunity. We report a case of isolated laryngeal candidiasis involving the vestibular folds and presenting with stridor in a one-year-old child with Down's syndrome and hypogammaglobulinaemia. Vestibular fold reduction and fluconazole achieved resolution of the disease. Candidiasis should be considered in any potentially immunodeficient child presenting with symptoms of laryngeal disease.

Airway Obstruction↗

Photometrics: a new method of measuring the cross-sectional area of the subglottis.

A new endoscopic method of measuring the cross-sectional area of a subglottic stenosis is presented. The method was tested against existing techniques using a model. By standardizing the distance from the objective of the endoscope to the stenotic area we were able to measure the cross-sectional area using a graduated grid held against the video screen. This technique was then compared with the standard one of estimating the diameter of a stenosis from the external diameter of the bronchoscope which can be passed through the stenosis. The methods were found to be equally accurate in measuring the lumen diameter. However, when measuring the minimum cross-sectional area, three of five observers were significantly better (P less than 0.01) using the photometric method rather than the standard method (Wilcoxon's rank sum test for paired data). The photometric technique of measuring the cross-sectional area of the subglottis is easily performed, non-traumatic, and allows a visual record to be kept.

Bronchoscopes↗

Ocular manifestations of pigmentary disorders.

Disorders of pigmentation can result from either an abnormal number of melanocytes, as in nevus of Ota and vitiligo, or an abnormal amount of melanin production, as in albinism. Melanin-producing cells are found in the skin, mucous membranes, uveal tract, and retinal pigment epithelium of the eye and the stria vascularis of the inner ear. Thus, many of the hereditary or congenital pigmentary disorders of the skin are associated with similar pigmentary abnormalities in the eye, such as iris heterochromia or changes in pigmentation of the fundus; however, more commonly, the associated eye finding is a defect in ocular motility, i.e., strabismus and nystagmus, suggesting a concomitant defect in neurologic development. In albinos, the observed neurologic abnormality in the visual pathway and foveal hypoplasia are hypothesized to be related directly to the lack of melanin in the pigment epithelium during development. In acquired disorders of pigmentation, in particular, vitiligo, Vogt-Koyanagi-Harada syndrome, and onchocerciasis, there is a frequent association with uveitis, suggesting an inflammatory cause for the cutaneous pigmentary changes.

Eye↗

The antineoplastic effect of vitamin D in transgenic mice with retinoblastoma.

Vitamin D has been shown to inhibit growth of human retinoblastoma in tissue culture and nude mouse heterografts. We have described a heritable transgenic mouse model of retinoblastoma. The in vivo efficacy of 1,25-dihydroxycholecalciferol (vitamin D3) was examined by administering this agent to transgenic mice with retinoblastoma. Forty-six 8-10-week-old transgene-bearing mice were injected intraperitoneally for 5 wk. Experimental animals received 0.05 microgram (15 animals) or 0.025 microgram (15 animals) of vitamin D. Sixteen control animals received only a mineral oil vehicle. Eyes were enucleated at 5 mo and were examined histologically by two investigators in a masked fashion. All control animals demonstrated bilateral involvement of retinoblastoma. Four eyes in the low-dose group and six eyes in the high-dose group had no evidence of retinoblastoma. Eyes treated with vitamin D3 showed less extensive involvement of the retina by retinoblastoma. Vitamin D-treated animals demonstrated tumors confined to the retina, whereas control animals demonstrated larger tumors, more often invading the vitreous, anterior chamber, and choroid. Thus, Vitamin D inhibited the growth and local extension in a dose-dependent fashion.

Animals↗

Retinal manifestations of neurofibromatosis. Diagnosis and management.

Five patients presented with vision-threatening retinal tumors and systemic signs of neurofibromatosis, including neurofibromatosis type 1 (four patients) and familial cafe-au-lait spots (one patient). These tumors included large retinal astrocytic hamartomas, multiple retinal capillary hemangiomas, and combined hamartomas of the retina and retinal pigment epithelium, which resulted in rubeotic glaucoma, vitreous hemorrhage, and retinal detachment. Surgical therapy included retinal cryopexy, xenon and argon photocoagulation, scleral buckling, and pars plana vitrectomy with excisional retinal biopsy. Retinal tumors may result in marked visual loss in patients with neurofibromatosis, and vitreoretinal surgery may restore useful vision in some of these patients.

Adolescent↗

Clinical, neurophysiological, biochemical and morphological features of eyes in Persian cats with mannosidosis.

The clinical, neurophysiological, morphological and biochemical manifestation of eyes from Persian kittens affected with alpha-mannosidosis were studied. Clinically the disease is characterized by progressive corneal and lenticular opacification. In addition there is asymmetry in shape and latency of signal conductions which were demonstrated by visual evoked potential studies. Morphological and histochemical studies revealed vacuolization of various ocular cell types which stained positively with Concanavalia ensiformis agglutinin (Con A) and wheat germ agglutinin (WGA). Biochemical studies illustrated low activity of acid alpha-mannosidase in cultured keratocytes and abnormal storage of partially degraded oligosaccharides in these cells, in vitreous humor and lens. This comprehensive study of ocular alpha-mannosidosis demonstrates enzyme deficiency which leads to abnormal storage of oligosaccharides in affected cells and is manifested by morphological alterations and functional impairment.

Animals↗

Mitogenic effects of excitatory amino acids in the adult rat retina.

We studied the retinas of adult rats after the intravitreal injection of excitatory amino acids and ouabain. Kainic acid, domoic acid, N-methyl D-asparate and ouabain produced swelling and vacuolization of the outer plexiform, inner nuclear and inner plexiform layers and pyknosis. Mitoses were present in retinas treated with all agents other than N-methyl D-asparate. Rompun ketamine anesthesia blocked the mitogenic effects. Immunohistochemical labeling of both glial fibrillary acidic protein and S100 protein would indicate that the mitoses are occurring in glial cells. We suggest that the mitogenic effects are mediated through action on glial cationic channels, and might account for the reactive gliosis observed in some retinal lesions.

Animals↗