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Steffen Heegaard

Publications and source records attributed to Steffen Heegaard.

At least 19 recordsLinked to original sources
PubMed2007

[Possible therapeutic intervention with inhibitors and promoters of phospholipase A2 subtypes].

Phospholipase A2 (PLA2) is a group of enzymes discovered more than a century ago in insect and snake poison. Not more than 20 years ago they were identified in vertebrates, and during the last five years, research has accelerated in relation to isolating and cloning several members of this super-family in humans. PLA2 inhibitors are in the process of being developed for pharmaceutical use. The purpose of this review is to outline the relevance and prospectives of PLA2 in a clinical perspective.

Brain Diseases↗
PubMed2007

Role of Helicobacter pylori in conjunctival mucosa-associated lymphoid tissue lymphoma.

OBJECTIVE: Conjunctiva-associated lymphoid tissue is the conjunctival equivalent to mucosa-associated lymphoid tissue (MALT). Mucosa-associated lymphoid tissue lymphoma has been shown to be associated with Helicobacter pylori. In this study, the prevalence and possible role of H. pylori infection in conjunctival MALT lymphoma were evaluated. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Thirteen cases of conjunctival MALT lymphoma were investigated. Five samples of conjunctival lymphoid hyperplasia and 20 biopsies of normal conjunctiva served as controls. METHODS: The specimens were investigated for the presence of H. pylori with immunohistochemistry (IHC) and nested polymerase chain reaction (PCR) techniques. For each case of conjunctival MALT lymphoma, information regarding gender, age at presentation, conjunctival localization, and information of generalized MALT lymphoma were collected. MAIN OUTCOME MEASURES: Detection of H. pylori and patient characteristics. RESULTS: The 13 conjunctival MALT lymphomas originated from 8 women and 5 men with an average age of 62 years (range, 25-87). Only 1 patient had evidence of systemic MALT lymphoma. H. pylori could not be identified in any of the conjunctival MALT lymphomas, in conjunctival lymphoid hyperplasia, or in normal conjunctival biopsies using IHC and PCR techniques. CONCLUSIONS: An association between H. pylori and localized conjunctival MALT lymphoma could not be verified. Antigens other than H. pylori may take part in the development of conjunctival MALT lymphoma.

Adult↗
PubMed2007

Optic nerve invasion of uveal melanoma.

The aim of the study was to identify the histopathological characteristics associated with the invasion of the optic nerve of uveal melanoma and to evaluate the association between invasion of the optic nerve and survival. In order to achieve this, all uveal melanomas with optic nerve invasion in Denmark between 1942 and 2001 were reviewed (n=157). Histopathological characteristics and depth of optic nerve invasion were recorded. The material was compared with a control material from the same period consisting of 85 cases randomly drawn from all choroidal/ciliary body melanomas without optic nerve invasion. Prelaminar/laminar optic nerve invasion was in multivariate analysis associated with focal retinal invasion, neovascularization of the chamber angle, and scleral invasion. Postlaminar invasion was further associated with non-spindle cell type and rupture of the inner limiting membrane of the retina. The optic nerve was invaded in four different ways: 1) by tumor extension from the neuroretina through the lamina cribrosa; 2) by direct extension into the optic nerve head between Bruch's membrane and the border tissue of Elschnig; 3) by direct invasion through the border tissue of Elschnig; and 4) in one case a tumor spread along the inner limiting membrane to the optic nerve through the lamina cribrosa. Invasion of the optic nerve had no impact on all-cause mortality or melanoma-related mortality in multivariate analyses. The majority of melanomas invading the optic nerve are large juxtapapillary tumors invading the optic nerve because of simple proximity to the nerve. A neurotropic subtype invades the optic nerve and retina in a diffuse fashion unrelated to tumor size or location.

Adult↗
PubMed2006

Human papillomavirus and pterygium. Is the virus a risk factor?

BACKGROUND: Pterygium is a disease of unknown origin and pathogenesis that might be vision threatening. It is characterised by a wing-like conjunctival overgrowth of the cornea. Several studies have investigated human papillomavirus (HPV) as a risk factor for the development of pterygia, but the results are inconclusive. AIM: To investigate a large sample of pterygia for the presence of HPV in order to clarify the putative association between pterygia and HPV. METHODS: 100 specimens of pterygium from Danish patients and 20 normal conjunctival biopsy specimens were investigated for the presence of HPV with PCR technique using beta-globin primers to access the quality of the extracted DNA and the HPV primers MY09/11 and GP5+/6+. HPV-positive specimens underwent subsequent HPV typing with type-specific HPV primers and further investigation with DNA in situ hybridisation (ISH). RESULTS: 90 of 100 investigated pterygia proved suitable for HPV analysis by PCR. As beta-globin could not be amplified, 10 specimens were excluded from the study. 4 of 90 pterygia harboured HPV. HPV type 6 was identified in all four HPV-positive pterygia. The 20 normal conjunctival biopsy specimens were beta-globin positive and HPV negative. All four pterygia that were HPV type 6 positive were DNA ISH negative. CONCLUSIONS: The low presence of HPV DNA in pterygia does not support the hypothesis that HPV is involved in the development of pterygia in Denmark.

Adult↗
PubMed2006

Human papillomavirus in normal conjunctival tissue and in conjunctival papilloma: types and frequencies in a large series.

AIM: To examine conjunctival papilloma and normal conjunctival tissue for the presence of human papillomavirus (HPV). METHODS: Archival paraffin wax-embedded tissue from 165 conjunctival papillomas and from 20 histological normal conjunctival biopsy specimens was analysed for the presence of HPV by PCR. Specimens considered HPV positive using consensus primers, but with a negative or uncertain PCR result using type-specific HPV probes, were analysed with DNA sequencing. RESULTS: HPV was present in 86 of 106 (81%) beta-globin-positive papillomas. HPV type 6 was positive in 80 cases, HPV type 11 was identified in 5 cases and HPV type 45 was present in a single papilloma. All the 20 normal conjunctival biopsy specimens were beta-globin positive and HPV negative. CONCLUSION: There is a strong association between HPV and conjunctival papilloma. The study presents the largest material of conjunctival papilloma investigated for HPV and the first investigation of HPV in normal conjunctival tissue. HPV types 6 and 11 are the most common HPV types in conjunctival papilloma. This also is the first report of HPV type 45 in conjunctival papilloma.

Adolescent↗
PubMed2006

Pleomorphic adenoma arising in an accessory lacrimal gland of Wolfring.

PURPOSE: To describe a patient with pleomorphic adenoma arising in an accessory lacrimal gland of Wolfring in the lower lid and to illustrate the immunohistochemical and molecular cytogenetics. DESIGN: Single interventional case report. METHODS: A 62-year-old man presented with a 20-year history of a painless slowly growing mass at the temporal part of the right lower eyelid. Histological, immunohistochemical, and fluorescence in situ hybridization studies of the excised tumor were performed. RESULTS: Histological evaluation showed many glandular elements embedded in a myxoid stroma. The tumor was situated beneath an area of a normal accessory lacrimal gland of Wolfring and in close association with normal meibomian glands. Myoepithelial tumor cells in the myxoid stroma reacted strongly with an antibody against glial fibrillary acidic protein, which did not bind to normal lacrimal gland tissue. Tumor cells with both epithelial and myoepithelial morphologies reacted positively for both pleomorphic adenoma gene-1 and high-mobility group A2 proteins. Fluorescence in situ hybridization analysis showed no evidence of clonal translocations or numerical abnormalities involving chromosome 8 or 12. CONCLUSIONS: Pleomorphic adenoma of the accessory lacrimal gland is an exceedingly rare tumor of the ocular adnexa. Glial fibrillary acidic protein seems to be a tumor-associated antigen. Genetically, this case of pleomorphic adenoma arising from an accessory lacrimal gland of Wolfring is identical with those originating from salivary glands.

Adenoma, Pleomorphic↗
PubMed2006

Intrastromal diathermal keratostomy: a new micropenetrating clear-cornea glaucoma procedure.

PURPOSE: The filtering intrastromal diathermal keratostomy (IDK) was developed to comply with the call for a low postoperative intraocular pressure (IOP) and a bleb morphology without a thin, cystic appearance. PATIENTS AND METHODS: A diathermal microkeratostomy (150 to 200 microm) was created into the anterior chamber, anterior to the Schwalbe line through the floor of a surgical corneoscleral tunnel incision into the subconjunctival space. A newly developed, bipolar diathermal microneedle was used to create the keratostomy, replacing the Holmium laser used previously. Subconjunctival injections of 3 microg mitomycin C were used in each eye 1 week before the IDK to obtain maximum antiproliferative effect at the time of the operation. Nine patients (10 eyes) with complicated, refractory primary and secondary open-angle glaucoma are discussed. RESULTS: Histologic examination of the IDK and clinical postoperative ultrasound biomicroscopy showed an optimal appearance of the diathermal microkeratostomy. After 34 months (range 24 to 42 mo) the mean IOP was 11 mm Hg (SD+/-3, range 6 to 16) without medication in all 10 eyes. IDK revision with internal needling of postoperative subconjunctival fibrosis through the tunnel incision was performed in 5 eyes after an average of 3 months (range 0.2 to 7 mo). After 33 months (range 19 to 38 mo), the postrevision mean IOP was 10 mm Hg (SD+/-2, range 8 to 14) without medication in all 5 eyes. All 10 eyes showed noncystic diffuse blebs with optimal spongy subepithelial morphology: in 2 eyes the blebs were totally avascular and in 8 eyes they were relatively avascular. CONCLUSIONS: The preliminary results of the new clear-cornea IDK seem promising because of postoperative IOP of about 10 mm Hg despite a low dose of mitomycin C and noncystic bleb morphology.

Adult↗
PubMed2006

Caruncular lesions in Denmark 1978-2002: a histopathological study with correlation to clinical referral diagnosis.

PURPOSE: To carry out a retrospective clinicopathological evaluation of caruncular lesions. METHODS: Data were collected from all surgically removed and histopathologically evaluated caruncular lesions registered by Danish pathology departments during the 25-year period 1978-2002. RESULTS: A total of 574 caruncular lesions were identified. The number of caruncular lesions increased significantly during the 25-year period. This was due to an increase in the number of benign lesions, whereas the number of premalignant and malignant lesions remained constant. A total of 550 (96%) of the lesions were benign. Naevus (n = 248, 43%) and papilloma (n = 131, 23%) were the most common neoplasms. Premalignant lesions (n = 10, 1.7%) were dominated by primary acquired melanosis (PAM) with atypia and epithelial dysplasia. Malignant lesions constituted a total of 14 neoplasms (2.4%), with basal cell carcinoma (n = 4, 0.7%) and lymphoma (n = 4, 0.7%) being the most frequent. The preoperative clinical diagnosis was correct in 286 (50%) of cases. CONCLUSION: Caruncular lesions are predominately benign but the lesions are rare and diverse, making clinical diagnosis difficult. Referral of excised lesions for pathological examination is recommended.

Adult↗
PubMed2006

Optic nerve invasion of uveal melanoma: clinical characteristics and metastatic pattern.

PURPOSE: To determine the frequency of optic nerve invasion in uveal melanoma, to identify clinical factors associated with optic nerve invasion, and to analyze the metastatic pattern and the association with survival. METHODS: All iris, ciliary body, and choroidal melanomas (N = 2758) examined between 1942 and 2001 at the Eye Pathology Institute, University of Copenhagen, Denmark, and the Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark, were reviewed. Cases with optic nerve invasion were identified and subdivided into prelaminar or laminar invasion and postlaminar invasion. Clinical characteristics were compared with those from 85 cases randomly drawn from all ciliary body and choroidal melanomas without optic nerve invasion from the same period. Survival data were obtained by the Kaplan-Meier method, and the Mantel-Cox log-rank test was used to test differences in survival among the three patient groups. RESULTS: Optic nerve invasion was found in 157 uveal melanomas (5.7%; 95% confidence interval [CI], 4.8%-6.6%). Frequency varied during the observation period between 5% and 7%. Only choroidal and ciliary body melanomas were found to invade the optic nerve. Eighty-five (54%) were confined to the prelaminar or laminar part, and 72 (46%) were confined to the postlaminar part. Increased intraocular pressure (IOP) and juxtapapillary location were associated with prelaminar or laminar invasion and postlaminar invasion. Age older than 70 years, reduced vision to light perception or worse, nonvisible fundus, and large (>15 mm) tumor size were associated with postlaminar spread. In univariate analysis, patients with postlaminar invasion had significantly higher all-cause and melanoma-related mortality than the other patients. CONCLUSIONS: Optic nerve invasion in uveal melanoma is found in 1 in 20 patients. Visible juxtapapillary melanoma or loss of light perception should make the clinician suspicious of melanoma with optic nerve invasion, and special awareness of postlaminar spread should be addressed when increased IOP is present independently of decreased visual acuity and tumor location.

Adult↗
PubMed2005

Predominant rod photoreceptor degeneration in Leber congenital amaurosis.

PURPOSE: An unusual retinal vascular morphology in an enucleated eye from a patient with Leber congenital amaurosis (LCA) has been associated with a mutation in AIPL1. The AIPL1 protein is expressed in the pineal gland and retinal photoreceptors. In the retina, AIPL1 is expressed in both developing cone and rod photoreceptors, but it is restricted to rod photoreceptors in the adult human retina. Therefore, this study was conducted to determine the photoreceptor phenotype in this LCA patient to determine if photoreceptors were differentially affected. METHODS: Additional genetic screening was performed and the consequences of the H82Y amino acid substitution characterized in an in vitro assay of NUB1 modulation. The morphology of the photoreceptors was examined by light and electron microscopy. Immunohistochemistry and immunofluorescent confocal microscopy was performed using a range of retinal photoreceptor markers. RESULTS: Transfection of the H82Y mutant AIPL1 in SK-N-SH cells revealed a normal subcellular localization and solubility but resulted in an increased ability of AIPL1 to redistribute GFP-NUB1 to the cytoplasm and resolve NUB1 fragment inclusion formation. Morphologically, the LCA retina appeared to be cone-dominant with a single layer of cone-like cells remaining in the central retina. Photoreceptor outer segments were absent and the surviving residual inner segments were severely shortened. Severe degeneration of the LCA retina was associated with upregulation of glial fibrillary acidic protein (GFAP). No signal was detected for AIPL1, rhodopsin, or L/M and S cone opsins in the LCA retina. Double labeling with peanut agglutinin (PNA) and wheat germ agglutinin (WGA) supported a cone-dominant phenotype for the surviving photoreceptors in the LCA retina, as did double labeling for cone arrestin, and rod and cone recoverin. The cone arrestin signal was restricted to the residual photoreceptor inner segments and was not detected in the cell bodies, axons, or axon terminals of the surviving photoreceptors. Recoverin immunoreactivity was most intense in the residual photoreceptor inner segments. CONCLUSIONS: The phenotype in this patient suggests that although AIPL1 is required for the development of normal rod and cone photoreceptor function, it might only be essential for rod and not cone survival in the adult.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Altered expression of CLC, DSG3, EMP3, S100A2, and SLPI in corneal epithelium from keratoconus patients.

PURPOSE: This investigation was designed to determine whether the five genes, CLC, DSG3, EMP3, S100A2 and SLPI, are differentially expressed in keratoconus, as indicated from another study. METHODS: Gene expression was monitored using quantitative real-time PCR on 14 keratoconus samples and 16 controls, and normalized to GAPDH and B2M. The DSG3, S100A2, and SLPI proteins were quantified by Western blotting, and the cellular localization was determined by immunohistochemistry. One of the genes, CLC, was reduced in gene expression and its four exons were sequenced. RESULTS: The five genes were all differentially expressed in keratoconus (P < 0.04) and so were at least three of the encoded proteins (P = 0.009). DSG3 was expressed in association with the cell membrane of the basal and suprabasal epithelial cells, and S100A2 was expressed in the nucleus and cytoplasm, often as intracellular granules. Two SNPs (rs374185 and rs384138) were observed in the CLC gene, each with an allele frequency of 68%. No other mutations were detected. CONCLUSIONS: The five genes, and three of the encoded proteins, were shown differentially expressed between a group of keratoconus patients and a reference group using different techniques. These alterations, in combination with earlier findings, strongly demonstrate the genes to be involved in the corneal disease. We suggest the unambiguously expressed DSG3 protein to be used as a marker for keratoconus.

Biomarkers↗
PubMed2005

A comparison of colour micrographs obtained with a charged couple device (CCD) camera and a 35-mm camera.

PURPOSE: The purpose of this study was to determine if micrographs produced with a colour charged couple device (CCD) camera were comparable in quality to micrographs obtained with a 35-mm colour film camera. The Axiocam (Zeiss, Jena, Germany) CCD camera produced images of 3900 x 3090 pixels. METHODS: Each picture in a series of 50 pairs of film and digital micrographs was rated independently by each of three observers on the categories of colour, detail and overall impression. A total of 28 of the 50 pairs of micrographs were discarded due to colour differences. RESULTS: Digital micrographs were rated lower on colour and higher on detail compared to film micrographs. The film and digital micrographs were rated equally on overall impression. The difference in colour between film and digital micrographs can be compensated for using image processing software on the digital image. However, such manipulation was not carried out as part of the present study. The study originally included 50 digital micrographs and 50 film micrographs. The micrographs were paired and 22 of the 50 pairs of micrographs were assessed. Thus 28 pairs were not evaluated due to colour differences in the non-manipulated pictures. The interobserver difference on colour in the remaining 22 pairs given as mean square +/- standard error of the mean was - 0.27 +/- 0.10, 0.62 +/- 0.10 and 0.90 +/- 0.11. The interobserver difference on detail was - 0.48 +/- 0.10, 0.95 +/- 0.10 and 1.43 +/- 0.10. The interobserver difference on overall impression was - 0.70 +/- 0.10, 0.57 +/- 0.10 and 1.27 +/- 0.10. All the results differed significantly (p < 0.001). CONCLUSION: Digital micrographs are sufficient in detail, colour and overall impression to replace the traditional 35-mm film recordings for use in histopathology.

Choroid Neoplasms↗
PubMed2005

Occurrence of lacrimal gland tissue outside the lacrimal fossa: comparison of clinical and histopathological findings.

PURPOSE: To analyse clinical referral diagnoses and the location of lesions with histologically verified lacrimal gland tissue occurring outside the fossa of the lacrimal gland. METHODS: Sections of lesions excised from areas outside the fossa of the lacrimal gland containing lacrimal gland tissue on histological examination were collected from the files of the Eye Pathology Institute, Copenhagen, Denmark. Specimens spanned a period of 50 years. Sections were re-examined and referral data on location and clinical diagnosis were compared with histological findings. RESULTS: A total of 120 lesions were collected. Of these, 59 (49%) consisted of prolapsed lacrimal gland. The remaining 61 (51%) lesions contained ectopic lacrimal gland tissue, either as part of a complex choristoma in 38 (32%) cases, or as solitary ectopic lacrimal gland tissue in 23 (19%) cases. The majority (97; 81%) of lesions had been located at the temporal epibulbar conjunctiva and included mainly prolapsed lacrimal gland and complex choristoma. The clinical referral diagnoses covered a wide spectrum of lesions. The most frequent clinical diagnoses were non-specific tumour (35%), non-specific cyst (18%) and dermoid (11%). Of the 61 lesions containing ectopic lacrimal gland tissue, only two had been preoperatively diagnosed as such and only two of the 59 lesions with prolapsed lacrimal gland had been correctly diagnosed. CONCLUSIONS: Prolapsed palpebral lobe of the lacrimal gland was the most common lesion and, as expected, the prime location was the temporal conjunctiva. Despite this location, the referring clinical diagnosis was often wrong or non-specific. Surgeons seem to have been unaware of the various clinical manifestations of extrafossal glandular tissue, particularly when excising lesions in the upper temporal region of the conjunctiva. Surgical intervention in this location may jeopardize the excretory ducts of the lacrimal gland and may consequently lead to dry eye and thus should be avoided when the typical clinical appearance of prolapsed lacrimal gland is encountered.

Choristoma↗
PubMed2005

Lesions of the lacrimal drainage system: a clinicopathological study of 643 biopsy specimens of the lacrimal drainage system in Denmark 1910-1999.

PURPOSE: To determine the frequency of histologically verified lesions of the lacrimal drainage system in Denmark between the years 1910 and 1999. Furthermore, to correlate the clinical diagnosis with the pathology diagnosis. METHODS: Retrospective review of all pathology reports from 1910 to 1999 in the files of the Eye Pathology Institute, University of Copenhagen, describing a lesion of the lacrimal drainage system. In addition, a retrospective review of all reports describing a lesion of the lacrimal drainage system from the Danish Pathology Database. All specimens were re-evaluated, except in cases with a primary diagnosis of dacryocystitis. In these cases a sample of 25% was re-evaluated. RESULTS: A total of 643 lesions were collected. Dacryocystitis was the most frequent lesion, constituting 508 cases (79%). The remaining cases were diagnosed as dacryolithiasis (62 cases; 7.9%), tumour (29 cases; 4.5%), trauma (19 cases; 3.0%), congenital malformation (nine cases; 1.4%), canaliculitis (eight cases; 1.2%) and granulomatous inflammation (eight cases; 1.2%). Seventeen tumours were malignant, of which B-cell lymphoma was the most common (six cases). In 0.6% of cases with a clinical diagnosis of dacryocystitis/lithiasis a non-suspected malignant tumour was diagnosed. Micro-organisms were uncommon in dacryocystitis (9%) but frequent in cases of dacryolithiasis (87%). CONCLUSION: Dacryocystitis was by far the most frequent lesion of the lacrimal drainage system referred for histopathological evaluation. Dacryolithiasis was often associated with micro-organisms, especially Gram positive rods. Histopathology is necessary to confirm suspected tumours, more than half of which were inflammatory lesions, and to detect tumours that sometimes masquerade as inflammation.

Adolescent↗
PubMed2005

Exfoliation syndrome in Nordic countries: a comparative histopathological study of Danish and Finnish eyes with absolute glaucoma and uveal melanoma.

PURPOSE: To compare the frequency of exfoliation syndrome (EXS) in Denmark and Finland in eyes enucleated for absolute glaucoma and uveal melanoma and to correlate these results to reported clinical prevalence rates. METHODS: The material consisted of 304 and 39 eyes consecutively removed because of absolute glaucoma and of 240 and 149 eyes enucleated because of uveal melanoma in Denmark and Finland, respectively. Histological sections of all eyes were stained with haematoxylin-eosin and periodic acid-Schiff and examined under a light microscope for EXS. Diagnosis of EXS was made by the consensus of the investigators. RESULTS: In absolute glaucoma eyes, EXS was observed in 12 out of 304 eyes (3.9%, 95% CI 2.1-6.8) in Denmark, and in 16 out of 39 eyes (41%, 95% CI 26-58) in Finland (p < 0.0001). In the melanoma eyes, EXS was noted in two out of 240 eyes (0.8%, 95% CI 0.1-3.0) in Denmark and in nine out of 149 eyes (6.0%, 95% CI 2.8-11) (p < 0.0037) in Finland. CONCLUSIONS: The frequency of EXS was significantly higher in eyes removed for absolute glaucoma and malignant melanoma in Finland than in Denmark. This supports the clinical impression that EXS is rare in Denmark compared to other Nordic countries.

Adolescent↗
PubMed2004

Primary basal cell carcinoma of the caruncle with seeding to the conjunctiva.

BACKGROUND: To report the clinical and histopathological characteristics of a patient with a primary basal cell carcinoma (BCC) of the caruncle with seeding of the tumour to the conjunctiva. METHODS: Surgical excision and histological examination. RESULTS: A 60-year-old female presented with a lesion of the caruncle. Clinical examination revealed a pale lobulated tumour without skin involvement. Computer tomography scans showed orbital invasion. The tumour was excised. Three years later a small polypoid tumour developed in the inferior fornix of the same eye. Two and a half years later, the patient developed an orbital recurrence. Microscopically, both neoplasms were composed of infiltrative islands of basaloid tumour cells, scattered mitoses and peripheral palisading consistent with the diagnosis of BCC. CONCLUSION: This case describes a primary BCC of the caruncle with seeding to the conjunctiva.

Basal Cell Carcinoma↗