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Biomedical subjects

S Seregard

Publications and source records attributed to S Seregard.

At least 37 records · Page 2Linked to original sources

Psychological reactions and quality of life in patients with posterior uveal melanoma treated with ruthenium plaque therapy or enucleation: a one year follow-up study.

PURPOSE: To investigate psychological reactions and quality of life among patients with posterior uveal melanoma. METHODS: Consecutive patients with uveal malignant melanoma (99/106), referred to St Erik's Eye Hospital 1995-1996, treated with rutheniuim plaque radiotherapy (n = 50) or enucleation (n = 49), were included in this non-randomised prospective comparative study. Questionnaires were completed before treatment (Hospital Anxiety and Depression Scale, HAD scale) and 2 and 12 months after diagnosis including the HAD scale, the Impact of Event Scale and the EORTC QLQ-C30. A disease-specific questionnaire was included 12 months after diagnosis. Between-group differences were analysed by chi-square, Student's t-test and ANOVA. RESULTS: A majority of the patients reported reduced 'Quality of Life' (72-85%), 'Emotional functioning' (60-74%) and 'Cognitive functioning' (51-61%). 'Fatigue' was the most frequently reported symptom (61-72%) followed by 'Insomnia' (43-58%). Anxiety and depressive symptoms were relatively frequent up to 1 year after treatment, but the levels of anxiety decreased during the first year after treatment. Disease and treatment-related problems were reported in both treatment groups 1 year after diagnosis. Enucleated patients had more problems with appearance and judging distances, whereas those treated with radiotherapy reported vision impairment to a higher extent. CONCLUSIONS: Enucleated patients reported high levels of emotional distress, problems with appearance and judging distances during the first year after treatment. Patients treated with radiotherapy reported similar levels of quality of life and emotional problems, but more problems with visual impairment. These differences in impact on disease-related functioning should be taken into account when treatment options are discussed.

Adult↗

Matrix metalloproteinase (MMP) expression in experimental choroidal neovascularization.

PURPOSE: Matrix metalloproteinases (MMP) are a family of proteolytic enzymes that degrade basement membrane and extracellular matrix proteins. To gain information on the possible role of MMPs in choroidal neovascularization (CNV), we have analyzed the mRNA expression of MMP-2 and MMP-9, two forms of MMPs implicated in ocular neovascularization, in a rat model. METHODS: Choroidal neovascularization was induced in pigmented rats by krypton laser photocoagulation of the fundus whereafter eyes were enucleated at 1, 3, 5, 7, 10 and 60 days. Antisense and sense riboprobes were generated using DNA complementary to MMP-2 and MMP-9, and mRNA expression was analyzed using in situ hybridization. RESULTS: In the untreated eyes MMP-2 mRNA expression was weakly detected in cells within the choroid. In laser-treated eyes MMP-2 mRNA expression was markedly increased and mainly localized to macrophage-like and retinal pigment epithelial (RPE)-like cells invading the choroid, subretinal space and inner retina. This increase in MMP-2 mRNA expression peaked at day 10 whereafter a decline was detected. MMP-9 mRNA expression was low in untreated eyes and did not increase following laser treatment. CONCLUSION: The results show that MMP-2 mRNA expression is increased in experimental CNV, and support of a role for MMP-2 in the development of CNV in age-related macular degeneration.

Animals↗

BK virus as the cause of meningoencephalitis, retinitis and nephritis in a patient with AIDS.

BACKGROUND: The two widely spread human polyomaviruses, BK virus (BKV) and JC virus (JCV) establish latency in the urinary tract, and can be reactivated in AIDS. JCV might cause progressive multifocal leucoencephalopathy, but although up to 60% of AIDS patients excrete BKV in the urine there have been few reports of BKV-related renal and/or neurological disease in AIDS. OBJECTIVE: To report on an AIDS patient with progressive renal and neurological symptoms involving the retina. DESIGN: Case report. SETTING: Venhälsan, Söder Hospital, Stockholm, Sweden. METHODS: The brain, eye tissue, cerebrospinal fluid, urine and peripheral blood mononuclear cells were analysed by nested PCR for polyoma-virus DNA. Macroscopical and microscopical examination were performed of the kidney and brain post mortem. Immunohistochemical stainings for the two BKV proteins, the VP1 and the agnoprotein, were performed on autopsy material and virus infected tissue culture cells. RESULTS: BKV could be demonstrated in the brain, cerebrospinal fluid, eye tissues, kidneys and peripheral blood mononuclear cells. CONCLUSION: During 6 years, approximately 400 cerebrospinal fluid samples from immunosuppressed individuals with neurological symptoms have been investigated by PCR for the presence of polyomaviruses. BKV DNA has, so far, only been found in the case reported here. Although reports of BKV infections in the nervous system are rare, there is now evidence for its occurrence in immunocompromised patients and the diagnosis should be considered in such patients with neurological symptoms and signs of renal disease. The diagnosis is simple to verify and is important to establish.

AIDS-Related Opportunistic Infections↗

Compound-heterozygous mutations in the plasminogen gene predispose to the development of ligneous conjunctivitis.

Homozygous type I plasminogen deficiency has been identified as a cause of ligneous conjunctivitis. In this study, 5 additional patients with ligneous conjunctivitis are examined. Three unrelated patients (1 boy, 1 elderly woman, and 1 man) had plasminogen antigen levels of less than 0.4, less than 0.4, and 2.4 mg/dL, respectively, but had plasminogen functional residual activity of 17%, 18%, and 17%, respectively. These subjects were compound-heterozygotes for different missense mutations in the plasminogen gene: Lys19 --> Glu/Arg513 --> His, Lys19 --> Glu/Arg216 --> His, and Lys19 --> Glu/Leu128 --> Pro, respectively. The other 2 patients, a 14-year-old boy and his 19-year-old sister, who both presented with a severe course of the disease, exhibited plasminogen antigen and functional activity levels below the detection limit (<0.4 mg/dL and <5%, respectively). These subjects were compound-heterozygotes for a deletion mutation (del Lys212) and a splice site mutation in intron Q (Ex17 + 1del-g) in the plasminogen gene. These findings show that certain compound-heterozygous mutations in the plasminogen gene may be associated with ligneous conjunctivitis. Our findings also suggest that the severity of clinical symptoms of ligneous conjunctivitis and its associated complications may depend on the amount of plasminogen functional residual activity.

Adolescent↗

Differential expression of nm23 H-1 protein in conjunctival melanoma and potential precursor lesions.

Loss of nm23 gene expression is believed to enhance metastatic spread in diverse human tumors, including skin melanoma. The purpose of this work was to determine the pattern and prognostic relevance of nm23 protein immunoexpression in conjunctival melanoma and potential precursor lesion. Formaldehyde-fixed, paraffin-embedded conjunctival specimens comprising 85 melanocytic lesions (nevi, primary aquired melanosis with and without atypia and primary and locally recurrent malignant melanomas) from 73 patients were used. Sections from all specimens were examined by light microscopy to assess diverse prognostic parameters. Additional sections were then immunostained for nm23 H-1 protein and the immunoreactivity was assessed semi-quantitatively. Survival data for all patients were retrieved from the National Causes of Death Registry of Sweden.Nm23 H-1 protein was differentially expressed in conjunctival melanocytic lesions, however loss of immunoexpression was not more common in melanocytic lesions asociated with a high risk of malignant transformation. Also, primary and recurrent conjunctival melanomas showed an essentially similar nm23 expression pattern and we could not associate the pattern of nm23 immunoexpression with an increased risk for malignant transformation or locally recurrent disease. While there was a tentative separation between cause-specific survival curves after excision for low and high nm23 expression conjunctival melanoma, there was no statistically significant association with metastatic death of patients. However, loss of nm23 protein immunoexpression may still be of some importance as a marker for prognosis in conjunctival melanoma because the present study could only detect large differences in survival. Our results suggest that any potential prognostic value of nm23 immunoexpression would be independent of other markers, underlining the importance of further studies.

Biomarkers, Tumor↗

Identification of BK virus in a patient with acquired immune deficiency syndrome and bilateral atypical retinitis.

OBJECTIVE: To report the clinical and histopathologic characteristics of BK virus (BKV) retinitis. DESIGN: Case report. TESTING: The clinical features of bilateral retinitis in a 29-year-old homosexual white male with the acquired immune deficiency syndrome (AIDS) included focal, mottled fundus pigmentation, and haloes, as documented by fundus photography. After death of the patient, the left eye was studied by light microscopic and immunohistochemical examination. The nested polymerase chain reaction (PCR) was used to detect viral deoxyribonucleic acid (DNA) in the right eye and other nonocular tissues. The specificity was then confirmed by restriction enzyme analysis. RESULTS: The retina of the left eye showed focal necrosis and contained cells with intranuclear staining for the BKV VP1 protein. In the right eye, BKV DNA was detected in the retina and other tissues by nested PCR. Autopsy showed that BKV infection was also present in the brain, kidneys, and peripheral blood mononuclear cells. CONCLUSIONS: A number of pathogens may cause retinitis in patients with AIDS. The authors have shown that BKV should be included among those pathogens and that some clinical features may suggest the presence of BKV retinitis.

AIDS-Related Opportunistic Infections↗

Panorama of orbital space-occupying lesions. The 24-year experience of a referral centre.

PURPOSE: The aim of this survey was to study the frequency and management of orbital lesions requiring incisional or excisional biopsy for diagnostic or therapeutic purposes. METHODS: A histopathological review of specimens from 300 consecutive patients with space-occupying orbital lesions managed over a period of 24 years at a tertiary referral centre. RESULTS: The lesions could be attributed to 73 different entities with low-grade, non-Hodgkin lymphoma being the most common. More than half (54.3%) of lesions were neoplastic and malignant disease was present in 29.0% of patients. The majority of lesions were biopsied using the anterior transseptal or transconjunctival approach. CONCLUSION: Most orbital space-occupying lesions requiring biopsy are benign and easily accessible. However, the diversity of these rare lesions and complexity of management suggest that patient care is best provided by a team of experienced subspecialists at a designated orbital centre.

Adult↗

Long-term outcome of RPE allografts to the subretinal space of rabbits.

PURPOSE: To determine the long-term RPE allograft survival in the subretinal space using suspensions of RPE cells and atraumatic transplantation surgery. METHODS: Nineteen albino rabbits were transplanted with suspensions of pigmented RPE cells from brown rabbits. Following pars plana vitrectomy, the RPE cell suspension was injected through a small retinotomy using a glass micropipette into the subretinal space under microscopic control. No immunosuppression was used. The eyes were monitored by biomicroscopy, color fundus photography, and fluorescein angiography. Rabbits were sacrificed at 1, 3 and 6 months, respectively, and the eyes processed for light and electron microscopy, using monoclonal antibodies for identifying macrophages. RESULTS: Transplanted RPE cells were present in the subretinal space in all eyes at 6 months. There was no fluorescein leakage. Generally, the RPE allograft formed a monolayer, but focal fragmentation and disruption with dispersion of melanin pigment occurred. Foci of multilayers of cells in the subretinal space, containing large macrophages, were associated with adjacent photoreceptor damage. There was no infiltration of lymphocytes but macrophages and glial cells were contiguous to the transplant. Cells harboring intracytoplasmatic melanin pigment were observed in the neural retina. CONCLUSION: Transplantation of RPE cell suspensions to the subretinal space generally forms a monolayer that persists at 6 months. However, in areas of multilayers of RPE cells and macrophages, graft failure occurs in combination with adjacent photoreceptor damage. Graft failure is not associated with the infiltration of lymphocytes, but other mechanisms seem to occur.

Animals↗

Phakomatous choristoma may be located in the eyelid or orbit or both.

PURPOSE: Phakomatous choristoma is a rare congenital tumour of lenticular origin. The exact location at clinical presentation is controversial, but herein we provide evidence that phakomatous choristoma may be located in the lower eyelid or orbit or both. METHODS: Case report of an infant presenting with a mass in the lower eyelid at birth, a systematic review of previous cases of phakomatous choristoma and an outline of the histopathological features in normal mid-facial embryonic development at different gestational ages. RESULTS: The histopathological features of the present case were consistent with those of a phakomatous choristoma. The preoperative imaging studies and clinical findings at surgery suggested that the tumour occupied parts of both the lower eyelid and anterior orbit. Histopathological sections of a normal human embryo showed that at the 26-mm stage of development the embryonic lens is formed but the bony walls defining the orbit are not yet present. CONCLUSION: Phakomatous choristoma arises in a setting of undifferentiated mesenchymal tissue which later may develop into the lower eyelid or orbit depending on the choristomatous elements being deposited superficial or deep to the embryonic surface.

Avidin↗

Long-term survival after ruthenium plaque radiotherapy for uveal melanoma. A meta-analysis of studies including 1,066 patients.

PURPOSE: Most case series of patients managed by brachytherapy for uveal melanoma are small and survival data show considerable inter-study variation. The aim of this study was to summarise similarly structured case series by meta-analysis. METHODS: A systematic review generated 5 similarly structured case series including survival data for 1,066 patients treated by ruthenium plaque radiotherapy for uveal melanoma. After assessing the inter-study clinical heterogeneity, data were weighed for study size and pooled. RESULTS: Patient and radiotherapy characteristics were largely homogenous, but tumour size varied considerably between studies. The 5-year melanoma-related mortality rate was 6% for small and medium tumours (T1/T2) and 26% for large (T3) tumours. The 5-year and 10-year melanoma-related mortality rates for a balanced set of tumours with small, medium and large tumours being present in similar proportions were 14% and 22%, respectively. CONCLUSION: Case series of patients with uveal melanoma managed by brachytherapy may be pooled to increase sample size and study power. The present estimate of survival following ruthenium plaque radiotherapy compares favourably with previously summarised data of survival after enucleation for similarly sized tumours.

Brachytherapy↗

Blue light induced apoptosis in rat retina.

PURPOSE: To explore cell death in blue light induced retinal damage. METHODS: Sprague-Dawley rats reared under cyclic light were exposed continuously to diffuse blue light (400-480 nm) at 0.64 W/m2 for 3 or 6 h after 22 h of dark adaptation. The rats were kept in darkness and killed immediately, 8, 16 and 24 h following light exposure. The retinal damage by the blue light was examined with a transmission electron microscope. The cell death was characterised by in situ terminal dUTP nick end labelling (TUNEL) and gel electrophoresis. RESULTS: During the 24 h following light exposure, photoreceptor cell death was characterised by progressive condensation and margination of the chromatin, shrinkage or convolution and fragmentation of the nucleus, condensation of the cytoplasm, and formation of apoptotic bodies along with rapid removal of dying cells from damaged areas in the absence of inflammatory response. The TUNEL-positive nuclei were scattered individually in the outer nuclear layer just after light exposure. A wave of massive TUNEL labelling of photoreceptor nuclei peaked at 8-16 h and dropped at 24 h following light exposure. The distribution of TUNEL-positive nuclei was located predominantly at the upper temporal region of the retina, which was the most sensitive area to the damage caused by blue light. Furthermore, the multiples of internucleosomal cleavage of 180-200 base pairs were demonstrated at corresponding time points. CONCLUSION: Photoreceptor cell apoptosis is seen early after the retina is damaged by blue light.

Animals↗

Prognostic accuracy of the mean of the largest nucleoli, vascular patterns, and PC-10 in posterior uveal melanoma.

OBJECTIVE: This study aimed to compare the prognostic value and the predictive accuracy of the PC-10 cell cycling marker with the largest tumor diameter, the mean of the largest nucleoli, and vascular patterns in posterior uveal melanoma. DESIGN: The study design was a case-control study. PARTICIPANTS: Eyes enucleated for posterior uveal melanoma from patients who either died of metastatic melanoma or survived without signs of metastatic disease 10 years or more after surgery were studied. INTERVENTION: Three observers assessed the above prognostic indicators and standard histopathologic characteristics from microslides without access to survival data. MAIN OUTCOME MEASURES: Univariate and multivariate Cox models for survival were constructed, and a multiparameter prognostic index was calculated for each patient, based on covariates obtained from the final Cox model. The prognostic accuracy was determined by receiver operating characteristic curve analysis. RESULTS: The log PC-10 count, vascular networks, mean of the largest nucleoli, largest tumor diameter, age of patient, and prognostic index were independently associated with outcome. However, each of these indicators had no more than a poor-to-moderate predictive accuracy, and only the prognostic index was significantly better than the largest tumor diameter. CONCLUSIONS: The PC-10 count retains a prognostic value in uveal melanoma when adjusting for the effect of the mean of the largest nucleoli and diverse vascular patterns. A prognostic index combining two or more indicators may improve the predictive precision.

Adult↗

Risk of acute suprachoroidal hemorrhage with phacoemulsification.

PURPOSE: To establish whether small incision cataract surgery with phacoemulsification decreases the risk of acute suprachoroidal hemorrhage (ASCH) compared with traditional nucleus expression by extracapsular cataract extraction (ECCE). SETTING: St. Erik Eye Hospital, Stockholm, Sweden. METHODS: A retrospective study was done on the incidence of ASCH in cataract surgery between July 1990 and July 1996. During this period, 37,565 cataract extractions (phacoemulsification and ECCE) were performed at St. Erik Eye Hospital, combined procedures excluded. The criteria for diagnosis were the suspicion of ASCH during surgery and a verified diagnosis via an expulsive hemorrhage into the wound (4 cases), postoperative ultrasonic examination (20 cases), or a choroidal mass on performing ophthalmoscopy together with a postoperative history alluding to the diagnosis (2 cases). RESULTS: Twenty-six eyes were identified with ASCH, including 7 during phacoemulsification and 19 during ECCE. The incidence of ASCH was 0.03% in the 23,213 phacoemulsification cases and 0.13% in the 14,352 ECCE cases. The difference was statistically significant (P = .0003; chi-square test). CONCLUSION: Small incision surgery with phacoemulsification decreased the risk of ASCH in cataract surgery compared with the traditional nucleus expression technique.

Acute Disease↗

Matrix metalloproteinases and metalloproteinase inhibitors in choroidal neovascular membranes.

PURPOSE: Matrix metalloproteinases (MMP) are a family of extracellular matrix degrading enzymes associated with the development of neovascularization. To investigate the possible role of these enzymes in choroidal neovascularization, the mRNA expression of MMPs and tissue inhibitors of metalloproteinases (TIMPs) were analyzed in subfoveal fibrovascular membranes from patients with age-related macular degeneration (AMD). METHODS: Surgically removed subfoveal fibrovascular membranes from five eyes were analyzed for the expression of MMP and TIMP mRNA. In situ hybridization anti-sense and sense riboprobes were generated using DNA complementary to human collagenase (MMP-1), 72 kDa gelatinase (MMP-2), stromelysin (MMP-3), 92-kDa gelatinase (MMP-9), TIMP-1, TIMP-2, and TIMP-3. Vascular endothelial cells were detected using immunostaining for von Willebrand factor. RESULTS: MMP-2 and MMP-9 mRNA were detected in all specimens. Most of the membranes also expressed TIMP-1 and TIMP-3 mRNA, and two of the membranes expressed TIMP-2 mRNA. MMP-2, TIMP-1, and TIMP-2 mRNA had a similar overall distribution that was relatively uniform within the vascularized membrane stroma. MMP-2 expression appeared to be localized mainly to the vascular endothelial cells, whereas TIMP-1 and TIMP-3 were detected in other cell types such as fibroblastlike cells. MMP-9 expression was distinctly expressed by cells at the margins of the membranes and often in proximity to a thickened Bruch's membrane-like layer under the retinal pigment epithelial cells. TIMP-3 mRNA was strongly expressed within the retinal pigment epithelial cell layer and also in the stroma of one membrane. None of the membranes showed detectable MMP-1 or MMP-3 expression. CONCLUSIONS: The results support a role for MMPs in the development of choroidal neovascularization in AMD. The localization of MMP-2 and MMP-9 to the areas of new vessel formation and to the enveloping Bruch's-like membrane, respectively, suggests that MMP-2 and MMP-9 may be cooperatively involved in the progressive growth of choroidal neovascular membranes in AMD.

Aged↗

Localization of adenosine receptor messenger RNAs in the rat eye.

Adenosine is present in all cells and body fluids and has been suggested to play several roles in the physiology of ocular tissues. The present study was undertaken to determine which types of adenosine receptor mRNAs are present in the rat eye, and where they are expressed. RNA or deoxyoligodeoxynucleotides complementary to rat adenosine receptor subtypes A1, A2A, A2B and A3 were used to generate 35S labeled antisense and sense probes. The probes were then used for in situ hybridization on 10 microm cryosections of the rat eye including the cornea, iris, ciliary body, lens, retina, choroid and sclera. A1, A2A and A2B receptor mRNAs were demonstrated in the ciliary processes. A1 receptor mRNA was also expressed in the ganglion cell layer of the retina. The retina also showed A2A receptor mRNA expression, which was most prominent in the inner nuclear layer and less prominent in the ganglion cell layer and outer nuclear layer. Weak A2A expression was found in the retinal pigment epithelium and choriocapillaris. No significant expression of A3 receptor mRNA was found in the rat eye. In conclusion, using in situ hybridization, we have demonstrated expression of mRNA for A1, A2A and A2B adenosine receptors in the rat eye. The expression patterns support specific roles for adenosine in the ciliary process and retina.

Animals↗

Photoreceptor decay over time and apoptosis in experimental retinal detachment.

BACKGROUND: Data are scarce on the actual rate and mode of outer nuclear layer decay in retinal detachment (RD). We used an experimental rabbit model to assess the presence of apoptosis and rate of photoreceptor death following RD. This model included the creation of localized and stable retinal blebs, while controlling for any decline of retinal elevation over time. METHODS: RD was produced in New Zealand white rabbits by injecting 0.05 ml of 15% sodium hyaluronate (Healon GV) under the neural retina using a microsurgical technique. Animals were killed at 1, 2, 4, 7, 14 and 29 days. Retinal tissue was processed for light and electron microscopy and for in situ end labeling of fragmented DNA using a modification of the TUNEL technique. Photoreceptor cell nuclei were counted in the RD areas of maximum retinal elevation of 28 eyes, and an additional 4 eyes were used for nick end labeling. RESULTS: Positive DNA nick end labeling, ultrastructural features and absence of necrotic cells indicated apoptotic photoreceptor cell death. Also, there was a rapid, almost linear elimination of photoreceptor nuclei over time. At 14 days only half of the number of nuclei were discernible, while approximately one tenth remained after 29 days. There was a statistically significant, but minimal decline in RD height over the 4 weeks of study. CONCLUSION: Following experimental RD in rabbits, apoptotic cell death is associated with an almost linear elimination of photoreceptor cells over time. The use of highly viscous sodium hyaluronate in separating the neural retina from the retinal pigment epithelium allows the RD to maintain a nearly constant height over a period of 4 weeks.

Animals↗

Tumour cell proliferation after failed ruthenium plaque radiotherapy for posterior uveal melanoma.

Enucleation following ruthenium plaque radiotherapy for posterior uveal melanoma indicates failure of treatment. This study focused on the histopathological findings and remaining tumour cell growth fraction in 42 of 46 patients with failed ruthenium plaque treatment (of 266 patients treated) for melanoma of the choroid or ciliary body. The cause for enucleation was clinically detected tumour regrowth in 27 (64%) patients, treatment-related ocular side effects in 12 (29%) cases and the patient's personal preference in three (7%) cases. The median time elapsing from plaque radiotherapy to enucleation was not significantly different for patients with recurrent tumour growth (23 months) compared to those enucleated without clinical signs of regrowth (19 months). While all tumours showed some regressive features by histopathological examination, only five melanomas were completely necrotic and viable-appearing tumours cells were present in all of the remaining 37 (88%) irradiated tumours. Microwave processed PC-10 immunostainings increased the sensitivity to detect cycling cells compared to the sole use of mitotic cell counts. By the former technique, proliferating tumour cells were detected in 17 of 23 (74%) studied melanomas of eyes enucleated for tumour regrowth following brachytherapy. Also, the number of cycling melanoma cells was similar to that of non-irradiated controls managed solely by enucleation. In contrast, the proliferative compartments of irradiated, but non-recurrent, posterior uveal melanomas were significantly reduced compared to those of matched controls. Still, cycling tumour cells were present in four of 13 (31%) irradiated melanomas, clinically assumed to be successfully treated.

Adult↗