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Biomedical subjects

D de Wolff-Rouendaal

Publications and source records attributed to D de Wolff-Rouendaal.

At least 19 recordsLinked to original sources

Immunophenotypic markers to differentiate between benign and malignant melanocytic lesions.

BACKGROUND/AIMS: The authors investigated the expression of S100A1, S100A6, S100B, MelanA, and CEA in conjunctival naevi, primary acquired melanosis (PAM), conjunctival melanoma, and uveal melanoma in order to assess their potential usefulness in the pathological differential diagnosis of these entities. METHODS: Paraffin embedded sections of 18 conjunctival naevi, 14 PAM, 16 conjunctival melanomas, and 20 uveal melanomas were immunostained for S100A1, S100A6, S100B, MelanA, and CEA, and expression was scored semiquantitatively. RESULTS: Expression of S100A1 differed significantly between conjunctival naevi and conjunctival melanoma, with percentages of positive cells of 30.6% and 71.4%, respectively. Conjunctival melanomas had high average scores for S100A1 and S100B (71.4%, 62.9%, respectively), while uveal melanomas also had high S100A1 but low S100B scores (88.5%, 18.5%, respectively). MelanA was highly variable; naevi and uveal melanoma had higher average scores than conjunctival melanoma. CEA was hardly detectable in all four groups. CONCLUSION: S100A1 seems to be a possible candidate to differentiate conjunctival naevi from conjunctival melanoma. S100B seems to differentiate between uveal melanoma and conjunctival melanoma. However, the study size was small and therefore the data have to be confirmed by others.

Antigens, Neoplasm↗

Ciliary tissue transplantation in the rabbit.

Irreversible damage of the ciliary body can be responsible for prolonged ocular hypotony and phthisis bulbi, which, currently, cannot be treated. The aim of this study was to achieve survival of morphologically normal ciliary tissue (CT) transplants in the anterior chamber of a rabbit's eye. Outbred female New Zealand albino rabbits received CT allografts, which were placed on to the surface of the host iris. We evaluated the influence of ciclosporin (CsA), VEGF and donor perfusion on graft survival. Operated eyes were assessed clinically and histologically, and revascularization of the grafts was determined by fluorescein angiography. All grafts became dark and ischemic during the first five to seven days after transplantation. Reperfusion of the grafted tissue was complete at approximately ten days after transplantation. In untreated animals, transplants became infiltrated by inflammatory cells, which led to destruction of the tissue. This was prevented by systemic use of CsA. Transplants treated with VEGF prior to transplantation had fewer ischemic areas but epithelial cell survival was not improved. Whole body donor perfusion prior to preparation of the grafts resulted in less inflammation and, histologically, in a better quantity and quality of the epithelial cells in the CT transplants. Ciliary tissue can be successfully transplanted but the ciliary epithelium suffers from ischemia and in untreated animals the whole transplant is rejected in the classical fashion. If the donor is perfused and the host immunosuppressed, histologically normal ciliary epithelium can be preserved together with rapid revascularization, minimal inflammation and good survival of the transplant, although fibrosis continued to occur during the two months after transplantation.

Animals↗

Topical alpha-interferon in recurrent conjunctival papilloma.

PURPOSE: To report the effect of topical alpha-interferon (alpha-IF) in two cases of recurrent conjunctival papillomas. METHODS: One patient with a conjunctival papilloma and one patient with a limbus-based papilloma were treated with excision and cryotherapy. Recurrences included one in situ carcinoma. Retreatment included systemic and topical alpha-IF. RESULTS: In Case 1, the papillomas regressed with systemic alpha-IF followed by topical application of alpha-IF (2.8 x 106 U) for 1 year against recurrence. In Case 2, the papillomas disappeared with topical alpha-IF over 1 year. No recurrences were seen during follow-up (84 and 91 months, respectively). The possible side effect of topical alpha-IF was superficial keratitis. Retrospective polymerase chain reaction tests for HPV were positive and showed type 6 in Case 1 and type 33 in Case 2. CONCLUSION: Topical alpha-IF can be used as adjuvant therapy in recurrent conjunctival papillomas.

Administration, Topical↗

Late ophthalmological complications after total body irradiation in non-human primates.

PURPOSE: To investigate the long-term effects of total body irradiation (TBI) on the incidence and time course of ocular complications. MATERIALS AND METHODS: Rhesus monkeys treated with TBI photon doses up to 8.5 Gy and proton doses up to 7.5 Gy were studied at intervals up to 25 years post-irradiation. They were compared with control groups with a similar age distribution. Cataract formation and ocular fundus lesions were scored according to a standardized protocol. Fluorescein angiography and histopathology was performed in selected animals. RESULTS: Cataract formation occurred after a latent period of 3-5 years. Significant cataract induction was observed for photon-doses of 8 and 8.5 Gy and beyond 20 years after proton irradiation. The severity of the lesions represents significant impairment of vision and would require cataract surgery if similar results occurred in human bone marrow transplant patients. Fluorescein angiography demonstrated a normal pattern of retinal vessels in 13 out of 14 animals (93%) from the irradiated group and in eight out of nine animals (89%) from the control group. No additional lesions apart from age-related degenerative changes could be demonstrated. Histological evaluation revealed no radiation-associated vasculopathy. CONCLUSIONS: Radiation alone for doses up to 8.5 Gy of photons does not carry a potential risk for fundus pathology, whereas clinically important cataract induction should be anticipated within 5 years after photon doses of 8.0 and 8.5 Gy and proton doses in excess of 2.5 Gy.

Age Factors↗

Histopathological findings in human choroidal melanomas after transpupillary thermotherapy.

AIMS: The effect of transpupillary thermotherapy (TTT) on human choroidal melanomas was investigated by means of histopathology. METHODS: Before enucleation TTT was performed in 11 eyes with a xenon are photocoagulator with a red filter or a diode laser at 810 nm. The exposure time was 1 minute; the estimated temperature at the top of the tumour was about 65 degrees C. RESULTS: Seven of 11 tumours developed necrosis to a maximum depth of 3.9 mm with a sharp demarcation between the necrotic and the viable part of the tumour. The depth correlated with penetration of heat into the tumour. Scattered small haemorrhages in the transitional zone between the necrotic and the viable part of the tumour were observed in three eyes but large haemorrhages were absent. Ocular media were not affected owing to the low rate of absorption of radiation at 810 nm. TTT did not cause significant scleral damage. Intrascleral tumour cells with a viable appearance were observed in one eye, where the tumour was almost totally necrotic. CONCLUSION: Results show that TTT has potential as a conservative therapeutic treatment for choroidal melanomas.

Choroid Neoplasms↗

A histopathological, ultrastructural and immunohistochemical study of congenital hereditary retinoschisis.

OBJECTIVE: To confirm our earlier histopathological and electron microscopic findings in congenital hereditary retinoschisis (CHRS) in two additional globes and to further evaluate the nature and origin of the intraretinal filaments by means of immunohistochemical analysis. PATIENTS: Three white men with CHRS, aged 83 years (patient I) (two globes), 55 years (patient 2) (two globes) and 33 years (patient 3, nephew of patient 2) (one globe). OUTCOME MEASURES: Findings on histopathological study and electron microscopy (patient I) and immunohistochemical analysis (all five globes). RESULTS: Histopathological examination showed extensive extracellular deposition of amorphous material positive for periodic acid-Schiff reagent in the outer schisis layer and focally in the macula. Ultrastructurally, the amorphous material represented filaments measuring 8 to 12 nm in diameter within degenerated Müller cells, with accumulation of these filaments in adjacent extracellular spaces. Similar, less severe changes were seen in the superonasal retina. Immunohistochemical studies showed focal reactivity for glial fibrillary acidic protein (GFAP) in the retina adjacent to the schisis cavity in all five globes, focal reactivity for S-100 protein in four retinas, rare focal staining for vimentin and neurofilaments in two retinas each and no reactivity for type I keratin or actin. CONCLUSIONS: The present study corroborates our previous work and provides pathological evidence that the retinal disorder extends beyond the limits of the schisis. The results of the immunohistochemical analysis are consistent with a glial cell origin of the filaments. We postulate that defective Müller cells produce GFAP and possibly S-100 protein, which accumulate within the retina and secondarily result in degeneration of these cells and schisis formation.

Adult↗

Hamster Greene melanoma in the rabbit eye: immunosuppressive treatment to improve this tumor model.

BACKGROUND: The hamster Greene melanoma (HGM) implanted in the anterior chamber of the rabbit eye has been used to study experimental therapies for human uveal melanoma. However, the occurrence of spontaneous necrosis limits the value of this model for long-term evaluation of experimental treatments. In the present study we tested the hypothesis that an immune response is the cause of this necrosis and that prevention of the immune response can prolong the experimentation time METHODS: HGM was implanted in the anterior chamber of control, presensitized and immunosuppressed rabbits. The effects of sensitization and immunosuppression were assessed by clinical and histological observation RESULTS: Sensitization led to a significant slowing down of tumor growth, but not to a difference in necrosis. Immunosuppressive treatment with cyclosporin A improved the success rate of implantation and decreased the amount of necrosis in the tumor CONCLUSION: The immune response plays a role in the occurrence of necrosis. However, although immunosuppressive treatment with cyclosporin A decreased the amount of necrosis, significant necrosis still occurred, suggesting that other factors like angiogenesis play a part as well and still limit the usefulness of this model in the long-term evaluation of experimental therapies.

Animals↗

Tapioca melanoma of the iris.

Clinical identification of tapioca melanoma of the iris is important because its medical treatment may differ from that of other malignant iris melanomas. The characteristic iris nodules must be differentiated from granulomatous uveitis, metastases, and Lisch nodules (neurofibromatosis). We will discuss the anterior segment findings, secondary glaucoma, and fluorescein iris angiographic and histopathologic data from two patients, one with a single nodular type and one with a seeding type of tapioca melanoma of the iris.

Adolescent↗

Possible relation between HLA and ABO type and prognosis of uveal melanoma.

Not only local parameters but also genetic determinants like the HLA genes may play a role in the development and clinical behavior of malignant tumors. In skin melanoma the presence of HLA-B40 is associated with a poor prognosis. We tested the hypothesis that the clinical behavior of uveal melanoma is influenced by the HLA type of the patient. The HLA types of 44 patients with uveal melanoma had been determined before operation with a view to using the cornea of the enucleated eye for an HLA-matched corneal transplantation. We compared the ABO and HLA types of the patients with the development of metastases and with the ten-year patient survival. An association was observed between the presence of HLA-B40 and death due to metastasis of uveal melanoma. We conclude that the HLA type of the patient may influence the clinical behavior not only of skin melanoma but also of uveal melanoma.

ABO Blood-Group System↗

Transpupillary thermotherapy (TTT) by infrared irradiation of choroidal melanoma.

We studied the destructive effect of hyperthermia at sub-photocoagulation level of 45-60 degrees C on melanomas. Optimal conditions for spreading of heat into tissue are a wavelength of 700-900 nm, a temperature of 45-60 degrees C, an exposure time of 1 minute or more, and a beam diameter of several millimeters. In hamsters with subcutaneous melanomas we obtained a tumour necrosis of 6 mm depth at 60 degrees C and one minute exposure time. We performed transpupillary thermotherapy (TTT) with a diode laser at 810 nm in patients with choroidal melanomas prior to enucleation. Treatment is based on the fortunate situation that irradiation at this wavelength combines optimal tissue penetration with a low absorption by clear ocular media of 5% or less. In 3 TTT-treated eyes histopathology showed a depth of necrosis of 0.9, 3.4, and 3.9 mm. TTT may become a new useful treatment modality for choroidal melanoma but its ultimate value has yet to be assessed.

Animals↗

Hamster Greene melanoma implanted in the anterior chamber of a rabbit eye: a reliable tumor model?

The hamster Greene melanoma (HGM), implanted into the anterior chamber (AC) of a rabbit eye, has previously been used as a model for testing experimental therapies against human uveal melanomas. Even without therapy, the tumor showed necrosis and hemorrhages 8-10 days after inoculation. These changes could interfere with the interpretation of the results of experimental therapies. In 8 rabbits, a piece of HGM was implanted subcutaneously, and after 4 weeks, HGM was also implanted in the AC of the eye. In these eyes, tumor growth in the AC slowed down, and more necrosis and hemorrhages were found clinically and histologically as compared to 8 rabbits without previous subcutaneous implantation of HGM. In spite of the long use of this tumor and frequent transfer, the tumor cells did not lose their antigenic potential.

Animals↗

Echographic differentiation of histological types of intraocular melanoma.

The aim of this study was to assess the differentiation of histologically different types of choroidal melanomas by means of clinical and quantitative acoustic/texture parameters of echograms. Clinical parameters were graded by morphological, kinetic and quantitative statements about the A- and B-mode echograms by a skilled diagnostician. Acoustic/texture parameters were obtained by processing and analysing radio frequency, AM-demodulated and FM-demodulated echograms. The data were preprocessed to remove influences induced by beam diffraction and focusing. The correlations between the clinical parameters were lower than 0.5 but significant in a few cases. The best set of four clinical echographic parameters enabled a retrospective classification of spindle type melanomas vs. mixed + epithelioid type melanomas with an accuracy of 77% (area under the ROC-curve of 86%). These figures do not enable, however, a prospective diagnosis. The correlations of the clinical parameters with the acoustic/texture parameters were investigated. The mutual correlations between the latter parameters were also assessed, the most significant (0.70) being between the speckle size and the slope of the linearized backscattering spectrum. The discriminant analysis performed with the best four acoustic/texture parameters (n = 30) yielded a sensitivity of 89%, a specificity of 92% and an area under the ROC-curve corresponding to a probability of correct classification of 96.6%. When using these data prospectively to classify tumours of unknown cell type (n = 21), this classification could be performed in 86% of cases.

Algorithms↗

Morphologic effects of bacteriochlorin a and light in vivo on intraocular melanoma.

To study the development of tissue and cell damage, the early morphologic changes induced by photodynamic therapy (PDT) with the new photosensitizer bacteriochlorin a (BCA) were investigated in Greene hamster melanoma implanted in the anterior eye chamber of white rabbits up to 24 hr after BCA-PDT, using light and electron microscopy. Immediately after BCA-PDT, intracellular spaces were enlarged, and blood vessels were clotted with swollen erythrocytes. By electron microscopy, it was found that some mitochondria had fused inner and outer membranes, and the cristae mitochondriales were affected. With time, the severity of the tissue and cell damage increased, leading to almost complete tumor necrosis after 24 hr. The direct mitochondrial damage and the vascular damage induced by BCA-PDT probably both contribute to tumor necrosis.

Animals↗

Clinical course and pathologic features of conjunctival non-Hodgkin's lymphoma. A report of six cases.

Six patients with conjunctival non-Hodgkin's lymphoma (NHL) were evaluated. In all six cases the conjunctiva was the primary site of clinical presentation; four cases involved low-grade malignancy and two, intermediate-grade malignancy, according to the International Working Formulation. The disease developed within a short period of time to stage IV. The poor response to therapy revealed a worse prognosis than would be expected according to the histopathologic classification. Four of the six patients died of NHL, three of them within 15 months. Comparison of these 6 cases with a group of 15 patients with orbital NHL revealed a much better prognosis in the latter patients. In spite of the fact that 4 of the 15 orbital cases showed NHL of high-grade malignancy, only 2 of them died of the lymphoma. Therefore, conjunctival NHL requires a fast and adequate diagnostic and therapeutic approach.

Adrenal Cortex Hormones↗

Tumor destruction by intermediate level hyperthermia.

The tumoricidal effect of hyperthermia was studied in Greene's amelanotic hamster melanoma transplanted into the anterior chamber of rabbit eyes. To achieve optimal depth penetration, hyperthermia was induced with near infrared light of 820-870 nm, during 15 minutes, at a beam diameter of 2.5-6.0 mm resulting in an intermediate level hyperthermia of 45-60 degrees C. At 45 degrees C no tumor destruction occurred, at 50 degrees C the effect varied from no destruction to total thickness tumor destruction. At 55-60 degrees C total tumor destruction with additional lens damage occurred. In comparison photocoagulation with white light revealed only necrosis up to half the tumor thickness.

Animals↗

Bacteriochlorin a, a new photosensitizer in photodynamic therapy. In vivo results.

The photosensitizing properties of bacteriochlorin a (BCA), a nontoxic derivative of bacteriochlorophyll a, were investigated in vivo. BCA has an absorption band at a wavelength at which tissue penetration is optimal (760 nm), and it shows preferential tumor retention in Greene melanoma implanted in the anterior chamber of rabbit eyes. A dose of 20 mg/kg BCA was administered IV at 4-7 mm tumor diameter; 24 hr later the tumor was irradiated with near-infrared light (30 min, 760 nm, 150-280 J/cm2). On the day after the irradiation it appeared that tumor growth had stopped: fluorescein angiography showed nonperfusion of the tumor. Histopathology after enucleation showed subtotal tumor necrosis with occasionally small clusters of viable cells around a blood vessel and at the tumor periphery. Neither BCA nor light alone had any effect on the eye or melanoma.

Animals↗

Optic glioma with intraocular tumor and seeding in a child with neurofibromatosis.

We treated a 3-year-old boy with neurofibromatosis who had an optic glioma, intraocular extension with seeding, and iris tumors. On the basis of results of ultrasonography, computed tomography, magnetic resonance imaging, and fine needle aspiration, other intraocular and orbital tumors were excluded. Because of the malignant intraocular aspect, the optic nerve glioma was extirpated. Histologic examination confirmed the diagnosis of an optic nerve glioma with intraocular extension, seeding, and iris nodules. In this juvenile pilocytic astrocytoma with secondary perineural fibrous hyperplasia, several mitoses were found in the orbital and intraocular parts. In the optic canal, three small islands were found that were compatible with the diagnosis of malignant astrocytoma, grade 3. The iris nevi appeared as iris pits and not like the Lisch nodules typical of neurofibromatosis. Café au lait spots were present on the skin. The family history was positive for neurofibromatosis. The results of this study demonstrate that optic gliomas are true astrocytomas and not hamartomas, and have a continuous scale from benign to malignant differentiation.

Child, Preschool↗

MRI in eye tumors.

Thirty patients with intraocular tumors were examined with MRI. A clear demarcation was seen between the melanomas and other intraocular structures such as sclera, vitreous and ciliary body. Retinal detachment, hemorrhage or choroidal-retinal layer could be seen separated from the tumor. In all our patients investigated with MRI the absence of extraocular melanoma tissue was confirmed by histopathology or by the findings during surgery. The demarcation between tumor and sclera seemed more sensitive in MRI than in ultrasonography in establishing extrascleral extension. Our study showed that MRI can be a valuable addition to ultrasonography in detecting intraocular tumors or tumor simulating lesions.

Evaluation Studies as Topic↗