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Biomedical subjects

R Folberg

Publications and source records attributed to R Folberg.

At least 19 recordsLinked to original sources

The morphologic characteristics of tumor blood vessels as a marker of tumor progression in primary human uveal melanoma: a matched case-control study.

Nine morphologic patterns of tumor vessels were identified in eyes removed for ciliary body or choroidal melanoma by the examination of tissue sections stained with fluorescein-conjugated Ulex europaeus I using laser scanning confocal microscopy. This technique also highlights intravascular tumor invasion. Each of these nine morphologic patterns of tumor vessels also may be demonstrated by a modification of the periodic acid-Schiff reaction, viewed with a green narrow band pass filter, but this modified histochemical technique does not accurately identify intravascular tumor invasion. Most tumors have a heterogeneous distribution of vascular patterns. Melanomas in two groups of 20 tumors each were matched by tumor size and location (one group of tumors from patients who survived at least 15 years free of metastatic melanoma after enucleation and one group of tumors from patients who died of metastatic melanoma). A matched case-control analysis indicates that the presence of at least one closed vascular loop in a uveal melanoma is the most significant vascular pattern associated with death from metastatic melanoma after enucleation. Closed loops are associated with other histologic features that are predictive of an unfavorable outcome after enucleation: epithelioid cells and mitotic figures. In this preliminary study the formation of closed vascular loops is a marker of tumor progression in ciliary body and choroidal melanomas.

Adult

Retinal hemorrhages: replicating the clinician's view of the eye.

The authors describe a technique for the gross examination of postmortem eyes of children who are suspected to have been the victims of deliberate trauma. By removing the anterior segment (cornea, iris, lens and pars plicata of the ciliary body) en bloc by a coronal incision through the pars plana just anterior to the ora serrata, the pathologist may view and photograph the fundus exactly as it would have been seen clinically. The photographs obtained with this technique correlate more closely with antemortem clinical examinations and photographs than conventional gross examination procedures and have been introduced as evidence in trials concerning the issue of retinal hemorrhages in injured children. The anterior segment and optic nerve are also examined to facilitate a comprehensive description of ocular findings.

Child

Avellino corneal dystrophy. Clinical manifestations and natural history.

PURPOSE: The pathologic features of a variant of granular corneal dystrophy has been described in which the presence of lattice changes in addition to characteristic granular lesions has been documented. The authors investigated the mode of inheritance, natural history, and clinical manifestations of this dystrophy. METHODS: A family with this condition was investigated, and a pedigree was established. Family members underwent ophthalmic examination, and ophthalmic history was obtained. In addition, pathologic examination of corneal tissue from affected patients was performed. RESULTS: Similar to the four previously described cases, this family also traced its origins to Avellino, Italy. This autosomal dominant condition affected 27 of 92 family members, ranging in age from 5 to 77 years. Granular deposits were the earliest and most common manifestations. Lattice lesions were present in some patients with granular lesions. Older patients had anterior stromal haze between deposits, which impaired visual acuity. Recurrent granular deposits were noted in donor corneal tissue after penetrating keratoplasty for this condition. Pathologic examination of corneal tissue from affected patients confirmed the presence of hyaline material seen in granular dystrophy as well as fusiform deposits of amyloid, similar to those seen in lattice dystrophy type I. CONCLUSION: This study establishes the natural history and clinical manifestations of this condition.

Adolescent

Clinicopathologic spectrum of primary uveal melanocytic lesions in an animal model.

BACKGROUND: Currently, there are no animal models of primary uveal melanoma in an eye large enough to allow documentation of the clinical evolution of the lesion by either funduscopy or fundus photography. METHODS: The authors induced primary uveal melanocytic lesions in the eyes of Dutch (pigmented) rabbits using a two-stage carcinogenesis protocol involving initiation with 4 weekly topical applications of 10 microliters of a 1% solution of 7,12-dimethyl-benz[a]anthracene (DMBA) in acetone (21 eyes) followed by 12 weekly topical applications of a 10 microliters solution of either 0.25% or 0.5% croton oil in acetone. They also investigated the effect of initiation with DMBA without promotion and the effects of chronic topical exposure to acetone and proparacaine. RESULTS: Exposure to DMBA followed by promotion with croton oil in either concentration was the most effective means of inducing clinically detectable fundus lesions. Histologically, a spectrum of melanocytic proliferations developed including benign nevi, nevi with varying grades of cytologic atypia, and clusters of confluent atypical melanocytes that may represent early melanomas. Although clinical regression of fundus lesions was noted in eight eyes after promotion had been stopped, five of these eyes showed unequivocal histologic evidence of a residual uveal melanocytic lesion. Chronic ocular irritation is capable of inducing cytologically benign subclinical uveal melanocytic proliferations. CONCLUSIONS: The conventional classification of human uveal melanocytic lesions includes only nevi and melanomas, but a comparison of the results of this study with descriptions of human uveal melanocytic nevi suggests the existence of a spectrum of intermediate atypical precursor lesions in humans.

9,10-Dimethyl-1,2-benzanthracene

Paraneoplastic pemphigus, cicatricial conjunctivitis, and acanthosis nigricans with pachydermatoglyphy in a patient with bronchogenic squamous cell carcinoma.

A 77-year-old man with chronic conjunctivitis, acanthosis nigricans with pachydermatoglyphy, and pemphigus-like mucocutaneous lesions was found to have a well-differentiated bronchogenic squamous cell carcinoma. Histopathologic and immunofluorescence studies confirmed the diagnosis of paraneoplastic pemphigus. Skin lesions resolved with oral prednisone and azathioprine therapy, but the conjunctivitis and mucous membrane erosions persisted. The conjunctiva later became scarred with foreshortening of the fornices and development of symblepharon. External beam irradiation arrested the growth of the tumor but did not have any effect on the diseased conjunctiva and other mucous membranes. This case demonstrates that cicatrizing conjunctivitis with bullous mucocutaneous lesions may be a clinical sign associated with an occult neoplasm.

Acanthosis Nigricans

Congenital macronodular juvenile xanthogranuloma of the eyelid.

A large congenital eyelid mass prevented an infant from elevating his eyelid successfully. A small punch biopsy was initially interpreted as "consistent with a dermatofibrosarcoma protuberans." On the basis of this diagnosis, radical surgery was advised. Dermatofibrosarcoma protuberans, however, rarely affects children and seldom appears in the head and neck area. Because of the discrepancy between clinical and pathologic diagnoses, additional biopsies were performed, which disclosed the lesion to be a juvenile xanthogranuloma. The mass regressed after intralesional injections of corticosteroids. This is the first clinicopathologic description of congenital macronodular juvenile xanthogranuloma affecting the eyelids. The variability in the histologic composition of this large lesion may lead to a mistaken diagnosis of an aggressive condition that may provoke unnecessary radical surgery.

Adrenal Cortex Hormones

Vitreoretinal traction and perimacular retinal folds in the eyes of deliberately traumatized children.

The pathophysiology of perimacular folds in eyes of deliberately traumatized children is disputed. The authors reviewed the clinical and forensic records and systemic and ocular findings at autopsy of three children with perimacular retinal folds who died after being violently shaken. Two of the children suffered direct head trauma in addition to being shaken; one patient was violently shaken without any physical or forensic evidence of direct head trauma. No direct ocular trauma was detected. In each case, the vitreous had partially separated from the retina but remained attached to the internal limiting membrane at the apices of the folds and the vitreous base, implicating traction in the pathogenesis of these folds. Although some intraocular findings in deliberately traumatized children may be explained by direct head injury, the possibility of both direct head trauma and shaking must be considered. Perimacular folds may develop without direct ocular or head trauma and may constitute evidence supporting violent shaking.

Battered Child Syndrome

Murine cytomegalovirus ocular infection in immunocompetent and cyclophosphamide-treated mice. Potentiation of ocular infection by cyclophosphamide.

Conventional virologic and in situ nucleic acid hybridization methods were used to study immunocompetent and immunosuppressed 3-week old BALB/c mice inoculated intravitreally with 10(4) plaque-forming units (pfu) of murine cytomegalovirus (MCMV). Immunocompetent mice experienced a self-limited ocular infection with peak virus titers of 10(3.5) pfu/ml in the retina-choroid fraction on day 4 of infection. Using biotinylated MCMV DNA probes, MCMV DNA was detected in cells of the iris, ciliary body, and rarely, the retina or choroid on days 4 and 7 of infection. With few exceptions, retinal architecture was preserved. By contrast, mice immunosuppressed with cyclophosphamide (200 mg/kg on day 0 and 100 mg/kg on days 5 and 11 after MCMV inoculation) had progressive ocular infection that culminated in a necrotizing retinitis. Virus titers in the retina-choroid fraction rose progressively (nearly 10(5) pfu/ml in cyclophosphamide-treated mice on day 11 versus 10(1.5) pfu/ml in immunocompetent mice). The MCMV DNA was detected in the iris and ciliary body of the immunosuppressed mice on days 4 and 7 and in the retina, on days 7, 11, and 14. On day 14 abundant MCMV DNA was found in most retinal layers, and extensive retinal necrosis was observed. These studies indicate that immunosuppression with cyclophosphamide potentiates MCMV ocular disease in mice, a finding analogous to CMV retinitis in immunosuppressed humans.

Animals

Ocular manifestations of patients with circulating antineutrophil cytoplasmic antibodies.

Antineutrophil cytoplasmic antibodies are seen in patients with systemic vasculitides, especially Wegener's granulomatosis. Antineutrophil cytoplasmic antibodies are helpful laboratory markers for these disease. We report on the ocular findings of six patients with systemic vasculitis who had antineutrophil cytoplasmic antibodies. Four patients had systemic Wegener's granulomatosis, one had microscopic polyarteritis, and in one a specific histopathologic diagnosis could not be made. Two patients were first evaluated for systemic vasculitis because of their ocular manifestations. Ocular findings included ptosis, bilateral lacrimal gland masses, proptosis, choroidal folds, episcleritis, phlebitis, retinal and vitreous hemorrhage, keratitis sicca, and bilateral central scotomas. It was difficult to make a systemic diagnosis in all cases. If systemic vasculitis is in the differential diagnosis of a patient with suggestive ocular findings, antineutrophil cytoplasmic antibody testing should be considered. A prospective study of antineutrophil cytoplasmic antibody testing should be considered in patients with ocular findings that suggest the possibility of vasculitis.

Adolescent

Histoplasma capsulatum endophthalmitis after cataract extraction.

A 60-year-old white man from an area endemic for Histoplasma capsulatum presented with a vitreous wick, hypopyon iritis, and dense vitreitis 2 months after removal of an anterior chamber intraocular lens (IOL) for chronic iritis. A diagnostic vitrectomy was performed and H. capsulatum was cultured and identified 2 weeks later. Despite intravitreal and intravenous amphotericin as well as repeat vitrectomies, the inflammation worsened and the eye was removed. Results of histopathologic examination showed Histoplasma organisms along the vitreous wick, over the surface of the iris and ciliary body, and over the retina. No organisms were found in the choroid. Dalen-Fuchs-type nodules similar to those of sarcoid also were noted, but there was no evidence of granulomatous inflammation in the uvea. Because of his unilateral disease with Histoplasma in the vitreous wick, negative serology, and an absence of systemic infection, the authors believe that this patient had a previously unreported form of ocular Histoplasma, exogenous postoperative Histoplasma endophthalmitis.

Cataract Extraction

The pathology of posterior amorphous corneal dystrophy.

The youngest affected member of a family with a five-generation history of posterior amorphous corneal dystrophy underwent penetrating keratoplasty. The corneal button was studied by light and electron microscopy, representing the first pathologic description of this condition. Light microscopy demonstrated fracturing of the most posterior collagen layers of the stroma and focal attenuation of endothelial cells. Electron microscopy showed the collagen fibers in the most posterior stromal lamellae to be disorganized. Descemet's layer was interrupted by a band of collagen fibers resembling stroma, and there was loss of endothelial cells. These findings suggest a developmental abnormality in the formation of the posterior stroma and Descemet's membrane in posterior amorphous corneal dystrophy.

Child, Preschool

An autosomal dominant form of low-tension glaucoma.

A condition causing glaucomatous optic atrophy and visual field loss at normal or borderline intraocular pressure affected eight members of a family of consecutive generations. The disease was detectable in early adulthood and progressed slowly throughout life. The pattern of inheritance is autosomal dominant. One affected individual died of a myocardial infarction, and his eyes were obtained post mortem. Light and electron microscopic examination demonstrated glaucomatous optic atrophy with loss of ganglion cells. The trabecular meshwork, choroidal and optic nerve vasculature, retinal pigment epithelium, and photoreceptors were normal in appearance. We believe this family has an autosomal dominant genetic condition that is a distinct type of low-tension glaucoma.

Adolescent

Early retinal adhesion from laser photocoagulation.

Histopathologic examination of eight cynomolgus monkey eyes and one human eye revealed that both argon and krypton laser photocoagulation cause adhesion between the neurosensory retina and the retinal pigment epithelium (RPE) within 24 hours of treatment. The neurosensory retina remained attached at the sites of laser burns despite surrounding retinal detachment in untreated areas. This early adhesion with the laser is useful for the treatment of eyes in which the retina has been recently reattached such as at the end of a vitrectomy for a retinal detachment with proliferative vitreoretinopathy (PVR) or after a pneumatic retinopexy. It is also useful for the treatment of retinal breaks without detachment.

Adhesiveness

Temporal artery biopsies. Correlation of light microscopy and immunofluorescence microscopy.

Immunopathologic studies are done routinely on biopsy specimens from tissues affected by many autoimmune diseases. To evaluate the role of direct immunofluorescence microscopy (DIFM) in identifying temporal arteritis, the authors reviewed all temporal artery biopsies done over a 30-month period (100 consecutive biopsies). The DIFM, using antibodies to IgG, IgM, IgA, complement, and fibrinogen, had a diagnostic sensitivity rate of 93% and a specificity rate of 87% compared with light microscopy. In biopsy specimens showing arteritis by light microscopy, IgG was demonstrated by DIFM in 85% of cases, IgM in 69%, and IgA in 15%. In one patient, a DIFM staining pattern highly suspicious of temporal arteritis identified a patient with features of clinical temporal arteritis despite negative findings by light microscopy. The demonstration of immunoglobulin by DIFM supports the possible role of humoral immunity in the pathogenesis of temporal arteritis.

Aged

Animal model of conjunctival primary acquired melanosis.

A condition clinically identical to human conjunctival primary acquired melanosis (PAM) was induced in 16 of 20 Dutch (pigmented) rabbits after weekly topical 60-microliters applications of a 1% solution of 7,12-dimethylbenz[a]anthracene (DMBA) in acetone. Pigment stippling appeared in the conjunctiva as early as 5 weeks after the initial carcinogen application. Confluent patches of flat pigmentation appeared over the palpebral conjunctiva 18 weeks after the onset of treatment and showed progressive lateral enlargement and darkening. Histologically, a spectrum of changes from increased melanin production and melanocytic hyperplasia without atypia (resembling the human condition of PAM without atypia) through atypical melanocytic hyperplasia (resembling human PAM with atypia) was identified. The development of this model permits further investigations to explore and explain the clinically observed phenomenon of waxing and waning of PAM and its promotion to conjunctival malignant melanoma.

9,10-Dimethyl-1,2-benzanthracene

The treatment of serous macular detachment secondary to choroidal melanomas and nevi.

The authors successfully treated with laser photocoagulation five patients who had a serous macular detachment secondary to leakage from a pigmented choroidal tumor. Three patients had dye leakage on fluorescein angiography from a choroidal neovascular membrane. The subretinal fluid resolved in all three patients after the neovascular membrane was obliterated by either krypton red (2 patients) or argon green (1 patient) laser photocoagulation. The other two patients had prominent leakage from a localized choroidal neovascular membrane as well as mild diffuse leakage over the entire tumor. Focal argon laser treatment to the neovascular membrane alone did not cause permanent resolution of the subretinal fluid. The fluid did resolve, however, after the entire area of diffuse leakage was retreated with photocoagulation. In one of the patients who received both focal and confluent laser treatment, the choroidal tumor grew in a collar-button fashion through Bruch's membrane at the original site of focal treatment. This eye was enucleated, and results of histopathologic examination showed a choroidal melanoma.

Aged