Search PubMed⌕ Search

Biomedical subjects

S Seregard

Publications and source records attributed to S Seregard.

At least 55 records · Page 3Linked to original sources
PubMed1997

Results following episcleral ruthenium plaque radiotherapy for posterior uveal melanoma. The Swedish experience.

The Swedish experience of ruthenium 106 plaque radiotherapy for posterior uveal melanoma includes 266 patients treated between 1979 and 1995. The median dose delivered at the tumour apex was 100 Gy and the median follow-up after radiotherapy was 3.6 years (range = 0.5 to 12.5 years) with no patient being lost to follow-up. Visual acuity deteriorated moderately following treatment but appeared to stabilize after 5 to 6 years. Treatment failure defined as enucleation following plaque treatment occurred in 46 of the 266 (17%) studied patients. The cumulative 5-year probability of retaining the eye after radiotherapy was 82% and by univariate analysis tumour height, tumour diameter and tumour stage each predicted subsequent treatment failure, whereas in multivariate analysis no single covariate retained a predictive value. Forty-five of the 266 patients died of any cause during follow-up; 27 of these deaths were melanoma-related. The cumulative 5-year survival proportion (based on melanoma-related deaths only) was 86%. Death in metastatic disease appeared to be more common among patients that failed ruthenium plaque radiotherapy, however these patients also tended to have large tumours.

Adult↗
PubMed1996

[A study of children with retinoblastoma. Diagnosis is often delayed].

Retinoblastoma is an uncommon but highly malignant ocular tumour of the early childhood. The delay in diagnosis following presentation at a health care facility was studied for 22 consecutive cases derived from the National Retinoblastoma Center in Sweden. Four of the children were regularly examined owing to a family history of retinoblastoma, but among the remaining 18 children the delay in diagnosis exceeded one month in five cases (including all children presenting with squint). However, there was no appreciable delay once appropriate fundus examination had been performed, thus stressing the need of early ophthalmological assessment in all cases of children manifesting signs consistent with retinoblastoma.

Child, Preschool↗
PubMed1996

Expression of vascular endothelial growth factor (VEGF) in retinoblastoma but not in posterior uveal melanoma.

All solid tumors must acquire a vascular stroma to grow beyond a minimal size. Vascular endothelial growth factor (VEGF) is a potent and specific angiogenic growth factor both in vitro and in vivo that may participate in the formation of the vascular tumor stroma. In the present study, we examined the expression of VEGF in the paraffin sections of 20 eyes harboring retinoblastoma or posterior uveal melanoma, but also in corresponding tumor cellines. By using in situ hybridization, we found that all but one of the retinoblastomas expressed VEGF mRNA. Particularly high expression was detected in areas of loosely packed tumor cells with prominent chromatin. By contrast, none of the posterior uveal melanomas expressed significant amounts of VEGF mRNA. Immunostaining with an antibody against VEGF confirmed that retinoblastomas, but not posterior uveal melanomas, also contained detectable VEGF protein. To further study the expression of VEGF in these tumor cells we performed Northern blotting on a retinoblastoma celline, Y79, and on an uveal melanoma celline, OM431. Both of these cellines expressed low levels of VEGF mRNA under normal culture conditions. However, when the cells were cultured under hypoxic conditions, a strong increase in VEGF mRNA could be seen in Y79 cells but not in OM431 cells. By using a bioassay, we also found that hypoxia stimulated the secretion of VEGF protein into the culture medium of Y79 cells. In conclusion, we have shown that VEGF mRNA and protein are expressed in retinoblastomas but not in posterior uveal melanomas. Moreover we have shown that VEGF is hypoxia-inducible in retinoblastoma cells. These results suggest that focal hypoxia may act as a stimulus for VEGF production in retinoblastomas, that in turn may contribute to tumor growth by stimulating the formation of a vascular stroma.

Blotting, Northern↗
PubMed1996

Posterior uveal melanoma. The Swedish perspective.

Posterior uveal melanoma is the most common primary intraocular malignant tumour and in Sweden some 70-80 new cases present each year. While uveal melanoma is more prevalent in the setting of ocular melanocytosis and neurofibromatosis, there is little conclusive data on the aetiology. Most patients experience a progressive visual field defect and present with a grey or greyish-brown mass of the posterior choroid. Diagnostic procedures include fluorescein angiography, ultrasound and magnetic resonance imaging. In some cases, intraocular biopsy may be required to make a correct diagnosis. Posterior uveal melanomas can usually be managed by any of a number of eye-preserving options like plaque radiotherapy and charged particle irradiation, but eyes containing large tumours are often enucleated. Nearly half of patients with posterior uveal melanoma, and in particular those with large tumours, ultimately succumb to metastatic disease. While most patients with tumour dissemination are treated with systemic chemotherapy possibly combined with interferon, metastatic spread confined to the liver may potentially be managed by intraarterial perfusion chemotherapy or liver resection. However, outcome of patients with systemic disease remains extremely poor with a median survival following detectable tumour dissemination of only two to five months. There are still insufficient data on the impact of various treatments on survival, but a large prospective trial addressing this issue is in progress. The present review summarizes the state-of-the-art knowledge and current management of posterior uveal melanoma from a Swedish perspective.

Humans↗
PubMed1996

Cell growth and p53 expression in primary acquired melanosis and conjunctival melanoma.

AIMS: To evaluate cell growth and the pattern of p53 suppressor gene expression in atypical primary acquired melanosis (PAM) and in recurrent conjunctival melanoma. METHODS: Eighteen specimens of PAM with atypia and 24 specimens, comprising early and late lesions, from 12 patients with conjunctival melanoma were stained for the proliferating cell nuclear antigen using the PC10 antibody, and for the p53 gene product using the BP53-12-1, 1801 and DO7 clones. The immunoreactive cells were counted manually and the data evaluated statistically. RESULTS: Seven of nine PAM specimens progressing to melanoma expressed PC10. None of these lesions expressed the p53 gene product. The number of proliferating cells was higher in the late than in the early lesions of conjunctival melanoma. Four of the 12 recurrent melanomas displayed focal, but minimal, p53 expression. The proliferating cell count in the p53 positive tumours was very similar to that of the p53 negative conjunctival melanomas. CONCLUSION: Examination of the expression of proliferating cells in atypical PAM may be used as an adjunct to predict which lesions will progress to melanoma. The increase in the number of proliferating cells over time in recurrent conjunctival melanomas probably reflects more aggressive behaviour and may be used to monitor recurrence. The absence of p53 expression in PAM and minimal staining of conjunctival melanomas did not correlate with cell growth, suggesting that alterations in the p53 tumour suppressor gene are uncommon and late events in conjunctival melanoma, and that p53 expression is unlikely to be a useful prognostic indicator.

Adult↗
PubMed1996

PC-10 as a predictor of prognosis after antigen retrieval in posterior uveal melanoma.

PURPOSE: The immunoexpression of the PC-10 monoclonal antibody for the proliferating cell nuclear antigen is claimed to have prognostic value in diverse tumors, but previous data on posterior uveal melanoma are conflicting. The aim of the current study was to investigate further the potential value of the PC-10 antibody in predicting tumor-related death after enucleation for posterior uveal melanoma. METHODS: One observer calculated the number of cells after antigen retrieval that showed immunoreactivity for PC-10 in the high expression areas of 212 specimens containing posterior uveal melanomas. Survival data for all patients were entered into stepwise multivariate Cox regressions that included other potential prognostic covariates. The prognostic accuracy was assessed by receiver operating characteristic curve analysis. RESULTS: The only covariates of statistically significant prognostic value were the number of cells featuring immunoreactivity for PC-10 and the largest tumor diameter. When using the median PC-10 count as the cutoff, the cumulative 10-year survival proportion was 84% for the low PC-10 count group and 40% for patients harboring tumors with high PC-10 counts. Those with tumors featuring high PC-10 counts had a 5.8 times greater risk to die of metastatic melanoma. However, the prognostic accuracy of the PC-10 count was not significantly better than that of the largest tumor diameter, presumably because of insufficient statistical power. CONCLUSIONS: The number of cells showing immunoreactivity for the PC-10 antibody may be used to assess prognosis in posterior uveal melanoma, provided that antigen retrieval is performed. Additional work using a larger sample size is warranted for better comparison of the predictive accuracy with that of other prognostic markers.

Adult↗
PubMed1996

Subfoveal fibrovascular membranes in age-related macular degeneration express vascular endothelial growth factor.

PURPOSE: Vascular endothelial growth factor (VEGF) is a potent and specific angiogenic growth factor, in vitro and in vivo, that may be associated with the development of intraocular neovascularization. In the current study, the authors analyze the expression of VEGF in subfoveal fibrovascular membranes from patients with age-related macular degeneration. METHODS: Surgically removed subfoveal fibrovascular membranes from 18 eyes were analyzed for the expression of VEGF mRNA and protein using in situ hybridization and immunohistochemistry, respectively. RESULTS: Most specimens expressed both VEGF mRNA and protein. The VEGF mRNA expression was particularly high in areas with a marked inflammatory response, in which the expression was concentrated to cells resembling fibroblasts and to surrounding inflammatory cells. VEGF protein expression was seen in fibrovascular parts of the membranes and was predominantly localized to the cytoplasm of fibroblastlike cells. In some of these membranes, strong VEGF protein immunoreactivity also was concentrated to extracellular matrix foci within the fibrovascular stroma. CONCLUSIONS: Results indicate that VEGF may be of pathogenetic importance for the development of the choroidal neovascularization (age-related macular degeneration) and also may implicate a role of fibroblasts of presumable choroidal origin in this process.

Aged↗
PubMed1995

Prevalence of primary acquired melanosis and nevi of the conjunctiva and uvea in the dysplastic nevus syndrome. A case-control study.

PURPOSE: To investigate whether conjunctival and uveal nevi and primary acquired melanosis are more common in individuals with the dysplastic nevus syndrome than in control subjects derived from the general population. METHODS: Power calculations were used to determine the sample size. After invitation, 162 individuals with the dysplastic nevus syndrome and 119 control subjects, matched for sex and age but otherwise randomized from the Stockholm county census file, were entered into the study. All individuals were examined in a masked fashion by the same ophthalmologist, and the presence of conjunctival and uveal melanocytic lesions and the iris color, skin type, and hair color of each individual were recorded. Contingency tables and odds ratios were used for statistical evaluation. RESULTS: The proportions of individuals with the dysplastic nevus syndrome featuring primary acquired melanosis of the conjunctiva, or nevi of the iris and choroid were not significantly different from those of control subjects. However, individuals with the dysplastic nevus syndrome appeared to have a more sun-sensitive skin type and a reddish or blond hair color more often than control subjects. CONCLUSION: In contrast to previous reports, this study suggests that ocular melanocytic lesions are no more common in individuals with the dysplastic nevus syndrome than in the general population. Therefore, this work does not provide support that periodic ophthalmic surveillance of individuals with the dysplastic nevus syndrome for the purpose of detecting conjunctival or uveal melanomas, or their precursors, is meaningful.

Adult↗
PubMed1995

Prognostic indicators following enucleation for posterior uveal melanoma. A multivariate analysis of long-term survival with minimized loss to follow-up.

Most previous reports on survival following enucleation for uveal malignant melanoma do not contain cumulative survival rates, do not use a multivariate approach and are liable to a considerable loss to follow-up. In this study, the long-term survival and tumour-related mortality were studied in 340 patients. Archival specimens containing posterior uveal melanomas were initially examined and sectioned by one pathologist. There was no loss to follow-up 6 to 22 years after enucleation. At the end of study, 233 (68.5%) individuals were dead; 137 (40.3%) of melanoma-related causes and 96 (28.2%) of other causes. Melanoma-related deaths appeared from 24 to 6848 days (18 years 8 months) after enucleation. The cumulative 5-year survival proportion based on melanoma-related deaths was 70% and the corresponding 10-year proportion was 56%. Multivariate Cox regression indicated that the largest tumour dimension, cell type, and tumour location all had independent prognostic value, the associated hazard ratios ranged from 1.2 to 1.4, suggesting a moderate increase of the relative risk. Pair-wise comparisons of the parameters indicated that large tumours were more common in the anterior choroid or ciliary body than in the posterior choroid. Similarly, large tumours were more often necrotic, composed of epitheloid cells, or featured extrascleral extension. Tumours with significant scleral invasion or extrascleral extension were more common in elderly patients.

Adult↗
PubMed1995

Orbital presentation of ethmoid sinus adenocarcinoma.

Ethmoid sinus adenocarcinoma with orbital invasion is distinctly uncommon. This case presented with epiphora, whereas proptosis and decreased ocular motility were later signs. Treatment was delayed for 4 months, while misdiagnoses like dacryocystitis and thyroid eye disease were entertained. Even an incisional biopsy was not sufficient for a conclusive diagnosis and adenomatous differentiation was only present in a small proportion of tissue available after an excisional attempt. The aggressive behaviour including this patient's death of metastatic disease, underlines the importance of considering secondary invasion from a sino-nasal malignancy in uncharacteristic orbital disease.

Adenocarcinoma↗
PubMed1995

Squamous spindle cell carcinoma of the conjunctiva. Fatal outcome of a plerygium-like lesion.

Squamous spindle cell carcinoma of the conjunctiva is an infrequent entity that behaves distinctly different from "ordinary' squamous cell carcinoma. This case report reviews the clinical and histopathological features of a lesion, that despite an insidious clinical appearance caused the patient's death 14 months following the initial excision. Data from previous reports are outlined.

Aged↗
PubMed1995

Proliferating cell nuclear antigen colocalization with corneal epithelial stem cells and involvement in physiological cell turnover.

Corneal integrity is dependent on a constant turnover of epithelial cells. According to the current hypothesis essential contributors to this process, the so-called stem-cells, are localized in the limbal area of the cornea. However, histological identification of stem cells of the cornea is thus far not possible. In the present study we have used specific antibodies against proliferating cell nuclear antigen (PCNA). The nuclear protein is expressed in cells during replication. Prior to establishment of staining indices the optimal fixation procedure was found to be of major importance for the results and standardized for fixation in 4% formaldehyde. This procedure also gave the best preservation of the morphology. In the corneas of ten New Zealand rabbits the staining index for PCNA was found to be on average 23% (SD +/- 13%) for the basal layer of the limbal epithelium. In the mid-peripheral and central corneal epithelium only occasional staining of PCNA was detected with a 2% staining index (SD +/- 2%). The agglomeration of PCNA-positive cells in the basal layer of the limbal epithelium together with their colocalization with the known location of stem cells strongly suggests that PCNA could serve as a reliable indicator for the proximity of proliferating corneal epithelial stem cells in histological sections, which would be of significant clinical importance.

Animals↗
PubMed1995

Giant cell angiofibroma. A distinctive orbital tumor in adults.

A series of seven cases of a previously unrecognized potentially recurrent tumor occurring in the orbit of adult patients is reported. This lesion shows histologic appearances intermediate between, but distinct from, solitary fibrous tumor and giant cell fibroblastoma of soft tissue. Morphologically it is characterised by a richly vascularized, patternless spindle-cell proliferation containing pseudovascular spaces. Multinucleate giant cells (often of floret type) and cells with large, rounded nuclei are present both in the cellular areas and also lining the pseudovascular spaces. The stroma is variably collagenized or sometimes myxoid. Immunohistochemically, the tumor cells exhibit positivity for vimentin and CD34. Follow-up in five cases (median duration 24 months) revealed local recurrence in one patient and persistent tumor in another. The clinical and morphologic features enable distinction of this lesion from both solitary fibrous tumor and giant cell fibroblastoma, and we suggest the designation "giant cell angiofibroma of the orbit".

Adult↗
PubMed1994

Immunohistochemical characterization of surgically removed subfoveal fibrovascular membranes.

Eighteen patients with age-related macular degeneration developed subfoveal membranes that were surgically removed and submitted for histopathological examination. Immunohistochemical techniques were performed, using a panel of monoclonal antibodies recognizing retinal pigment epithelial (RPE) cells, myofibroblasts, pericytes, endothelial cells, glial cells, smooth muscle cells and various types of macrophages. The PC10 antibody to proliferating cell nuclear antigen (PCNA) was applied as a marker of proliferating cells. The specimens displayed a core of neovascular stroma surrounded by a rim of more fibrous tissue. All specimens contained abundant RPE cells that in some cases appeared to envelop part of the membrane. Most cases had basal laminar deposits and thickened basement membrane material adjacent to the RPE cells suggestive of parts of Bruch's membrane. Often this Bruchlike membrane appeared at the surgical margin, forming a surgical cleavage plane. Chronic inflammatory cells were abundant, but polymorphonuclear leukocytes were notably absent. Nearly all specimens contained myofibroblasts and various types of macrophages. The presence of myofibroblasts suggests subretinal membrane contraction, which may induce new breaks and other pathology in RPE layer and Bruch's membrane.

Aged↗
PubMed1994

Retinochoroiditis in the acquired immune deficiency syndrome. Findings in consecutive post-mortem examinations.

A number of opportunistic agents may cause retinitis or retinochoroiditis in patients with the acquired immunodeficiency syndrome. Minimal consecutive data is available on the histopathologically confirmed prevalence of these ocular infections. A total of 48 consecutive patients with acquired immunodeficiency syndrome-related death underwent autopsy and had their eyes submitted for histopathological examination. Conventional light microscopy combined with immunohistochemistry revealed cytomegalovirus retinitis in 15 patients, toxoplasma gonddi retinochoroiditis in 3 patients and mycobacterial choroiditis in one individual with some infections being coexistent. Clinical examination prior to death was highly accurate in detecting cytomegalovirus retinitis, but failed to determine all non-cytomegalovirus causes of retinochoroiditis. Ten of 15 patients with cytomegalovirus retinitis had associated non-cular cytomegalovirus infections, most often in the brain and adrenals. After clinical detection of cytomegalovirus retinitis the median survival time was 5.5 months, not adversely affected by additional non-ocular cytomegalovirus infection.

AIDS-Related Opportunistic Infections↗