Publications by authors named "Bjerregaard B"

84 Publications

Syncytin is involved in breast cancer-endothelial cell fusions.

Cell Mol Life Sci 2006 Aug;63(16):1906-11

Anatomy and Cell Biology, IBHV, KVL, Gronnegaardsvej 7, 1870 Frederiksberg C, Copenhagen, Denmark.

Cancer cells can fuse spontaneously with normal host cells, including endothelial cells, and such fusions may strongly modulate the biological behaviour of tumors. However, the underlying mechanisms are unknown. We now show that human breast cancer cell lines and 63 out of 165 (38%) breast cancer specimens express syncytin, an endogenous retroviral envelope protein, previously implicated in fusions between placental trophoblast cells. Additionally, endothelial and cancer cells are shown to express ASCT-2, a receptor for syncytin. Syncytin antisense treatment decreases syncytin expression and inhibits fusions between breast cancer cells and endothelial cells. Moreover, a syncytin inhibitory peptide also inhibits fusions between cancer and endothelial cells. These results are the first to show that syncytin is expressed by human cancer cells and is involved in cancer-endothelial cell fusions.
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http://dx.doi.org/10.1007/s00018-006-6201-9DOI Listing
August 2006

Automated identification of cancerous smears using various competitive intelligent techniques.

Oncol Rep 2006 ;15 Spec no.:1001-6

Department of Financial and Management Engineering, University of the Aegean, 31 Fostini Street, 82100 Chios, Greece.

In this study the performance of various intelligent methodologies is compared in the task of pap-smear diagnosis. The selected intelligent methodologies are briefly described and explained, and then, the acquired results are presented and discussed for their comprehensibility and usefulness to medical staff, either for fault diagnosis tasks, or for the construction of automated computer-assisted classification of smears. The intelligent methodologies used for the construction of pap-smear classifiers, are different clustering approaches, feature selection, neuro-fuzzy systems, inductive machine learning, genetic programming, and second order neural networks. Acquired results reveal the power of most intelligent techniques to obtain high quality solutions in this difficult problem of medical diagnosis. Some of the methods obtain almost perfect diagnostic accuracy in test data, but the outcome lacks comprehensibility. On the other hand, results scoring high in terms of comprehensibility are acquired from some methods, but with the drawback of achieving lower diagnostic accuracy. The experimental data used in this study were collected at a previous stage, for the purpose of combining intelligent diagnostic methodologies with other existing computer imaging technologies towards the construction of an automated smear cell classification device.
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http://dx.doi.org/10.3892/or.15.4.1001DOI Listing
April 2006

Analysis of 65 tuberous sclerosis complex (TSC) patients by TSC2 DGGE, TSC1/TSC2 MLPA, and TSC1 long-range PCR sequencing, and report of 28 novel mutations.

Hum Mutat 2005 Oct;26(4):374-83

Department of Medical Genetics, John F. Kennedy Institute, Glostrup, Denmark.

Tuberous sclerosis complex (TSC) is a severe autosomal-dominant disorder characterized by the development of benign tumors (hamartomas) in many organs. It can lead to intellectual handicap, epilepsy, autism, and renal or heart failure. An inactivating mutation in either of two tumor-suppressor genes-TSC1 and TSC2-is the cause of this syndrome, with TSC2 mutations accounting for 80-90% of all mutations. Molecular diagnosis of TSC is challenging, since TSC1 and TSC2 consist of 21 and 41 coding exons, respectively, and the mutation spectrum is very heterogeneous. Here we report a new approach for detecting mutations in TSC: a denaturing gradient gel electrophoresis (DGGE) analysis for small TSC2 mutations, a multiplex ligation-dependent probe amplification (MLPA) analysis for large deletions and duplications in TSC1 or TSC2, and a long-range PCR/sequencing-based analysis for small TSC1 mutations. When applied in this order, the three methods provide a new sensitive and time- and cost-efficient strategy for the molecular diagnosis of TSC. We analyzed 65 Danish patients who had been clinically diagnosed with TSC, and identified pathogenic mutations in 51 patients (78%). These included 36 small TSC2 mutations, four large deletions involving TSC2, and 11 small TSC1 mutations. Twenty-eight of the small mutations are novel. For the missense mutations, we established a functional assay to demonstrate that the mutations impair TSC2 protein function. In conclusion, the strategy presented may greatly help small- and medium-sized laboratories in the pre- and postnatal molecular diagnosis of TSC.
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http://dx.doi.org/10.1002/humu.20227DOI Listing
October 2005

[Pathology database. Danish Society of Pathologic Anatomy and Cytology].

Ugeskr Laeger 2005 Mar;167(12-13):1401

Patologisk Institut, Aalborg Sygehus Nord, DK-9100 Aalborg.

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March 2005

Meiosis and embryo technology: renaissance of the nucleolus.

Reprod Fertil Dev 2005 ;17(1-2):3-14

Department of Animal and Veterinary Basic Sciences, Royal Veterinary and Agricultural University, Groennegaardsvej 7, DK-1870 Frederiksberg C, Denmark.

The nucleolus is the site of rRNA and ribosome production. This organelle presents an active fibrillogranular ultrastructure in the oocyte during the growth of the gamete but, at the end of the growth phase, the nucleolus is transformed into an inactive remnant that is dissolved when meiosis is resumed at germinal vesicle breakdown. Upon meiosis, structures resembling the nucleolar remnant, now referred to as nucleolus precursor bodies (NPBs), are established in the pronuclei. These entities harbour the development of fibrillogranular nucleoli and re-establishment of nucleolar function in conjunction with the major activation of the embryonic genome. This so-called nucleologenesis occurs at a species-specific time of development and can be classified into two different models: one where nucleolus development occurs inside the NPBs (e.g. cattle) and one where the nucleolus is formed on the surface of the NPBs (e.g. pigs). A panel of nucleolar proteins with functions during rDNA transcription (topoisomerase I, RNA polymerase I and upstream binding factor) and early (fibrillarin) or late rRNA processing (nucleolin and nucleophosmin) are localised to specific compartments of the oocyte nucleolus and those engaged in late processing are, to some degree, re-used for nucleologenesis in the embryo, whereas the others require de novo embryonic transcription in order to be allocated to the developing nucleolus. In the oocyte, inactivation of the nucleolus coincides with the acquisition of full meiotic competence, a parameter that may be of importance in relation to in vitro oocyte maturation. In embryo, nucleologenesis may be affected by technological manipulations: in vitro embryo production apparently has no impact on this process in cattle, whereas in the pig this technology results in impaired nucleologenesis. In cattle, reconstruction of embryos by nuclear transfer results in profound disturbances in nucleologenesis. In conclusion, the nucleolus is an organelle of great importance for the developmental competence of oocytes and embryos and may serve as a morphological marker for the completion of oocyte growth and normality of activation of the embryonic genome.
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http://dx.doi.org/10.1071/rd04108DOI Listing
April 2006

Evolving rule-based systems in two medical domains using genetic programming.

Artif Intell Med 2004 Nov;32(3):195-216

Department of Financial and Management Engineering, University of the Aegean, 31 Fostini St., 82100 Chios, Greece.

Objective: To demonstrate and compare the application of different genetic programming (GP) based intelligent methodologies for the construction of rule-based systems in two medical domains: the diagnosis of aphasia's subtypes and the classification of pap-smear examinations.

Material: Past data representing (a) successful diagnosis of aphasia's subtypes from collaborating medical experts through a free interview per patient, and (b) correctly classified smears (images of cells) by cyto-technologists, previously stained using the Papanicolaou method.

Methods: Initially a hybrid approach is proposed, which combines standard genetic programming and heuristic hierarchical crisp rule-base construction. Then, genetic programming for the production of crisp rule based systems is attempted. Finally, another hybrid intelligent model is composed by a grammar driven genetic programming system for the generation of fuzzy rule-based systems.

Results: Results denote the effectiveness of the proposed systems, while they are also compared for their efficiency, accuracy and comprehensibility, to those of an inductive machine learning approach as well as to those of a standard genetic programming symbolic expression approach.

Conclusion: The proposed GP-based intelligent methodologies are able to produce accurate and comprehensible results for medical experts performing competitive to other intelligent approaches. The aim of the authors was the production of accurate but also sensible decision rules that could potentially help medical doctors to extract conclusions, even at the expense of a higher classification score achievement.
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http://dx.doi.org/10.1016/j.artmed.2004.02.007DOI Listing
November 2004

Regulation of ribosomal RNA gene expression in porcine oocytes.

Anim Reprod Sci 2004 Jul;82-83:605-16

Department of Animal and Veterinary Basic Sciences, The Royal Veterinary and Agricultural University, Groennegaardsvej 7, DK-1870 Frederiksberg C, Denmark.

In vitro production (IVP) of porcine embryos including in vitro maturation (IVM) of oocytes followed by in vitro fertilization (IVF) and in vitro culture (IVC) of the resultant embryos may result in live offspring, but it is still associated with great inefficiencies probably due to incomplete cytoplasmic maturation of the oocytes in vitro. Therefore, fundamental knowledge on the regulation of transcription during the oocyte growth phase when the messengers and protein synthetic machinery necessary for oocyte developmental competence are formed, is of great importance. In mammals, synthesis of RNA, up to 60-70% of which is ribosomal (rRNA), increases during oocyte growth and reaches a peak at the beginning of follicular antrum formation. In oocytes at the end of the growth phase, acquisition of full meiotic competence coincides with a markedly decreased rRNA transcriptional activity in the gametes. Our recent studies on the porcine oocyte growth phase have revealed a deeper molecular and biological insight into the complex regulation of rRNA transcription at different stages of follicular development. The data indicate that the so-called pocket protein, p130, is involved in the down-regulation of rRNA transcription at the end of the oocyte growth phase through an inhibition of the action of upstream binding factor (UBF). The latter protein is necessary for the function of RNA polymerase I (RNA Pol I), which is the actual enzyme driving rRNA gene transcription. Moreover, rRNA transcription also appears to be down-regulated by a decrease in the expression of mRNA encoding PAF53, an RNA Pol I-associated factor also required for the polymerase to exert its action. At the ultrastructural level, these molecular changes are paralleled by marginalization of the fibrillar centres of the oocyte nucleolus followed by compaction of the nucleolus into an inactive sphere of fibrils.
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http://dx.doi.org/10.1016/j.anireprosci.2004.04.023DOI Listing
July 2004

The most common chromosome aberration detected by high-resolution comparative genomic hybridization in vulvar intraepithelial neoplasia is not seen in vulvar squamous cell carcinoma.

Cytogenet Genome Res 2004 ;106(1):43-8

Fertility Clinic, Rigshospitalet, Denmark.

We analyzed genetic changes in condylomas (four cases), vulvar intraepithelial neoplasia I-III (VIN I-III, eleven cases), and primary vulvar squamous cell carcinomas (VSCC, ten cases) by high-resolution comparative genomic hybridization (HR-CGH) and flowcytometry. All samples were also human papilloma virus (HPV)-genotyped. Gain of chromosome 1, the aberration most often seen in VIN III (67%), was not seen in HPV-positive or -negative VSCCs (0%). Both VIN III and VSCC frequently showed gain of 3q (56 and 70%, respectively). The VIN III samples often demonstrated gain of 20q (56%) and 20p (44%), and the VSCC samples gain of 8q (60%), loss of 3p (50%), and 8p (40%). None of the four most frequent changes in the VSCC samples occurred exclusively in the HPV-positive or -negative samples. As expected, we did not find any cytogenetic changes in condylomas and nearly any changes in VIN I-II.
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http://dx.doi.org/10.1159/000078559DOI Listing
December 2004

Nucleolar ultrastructure and protein allocation in in vitro produced porcine embryos.

Mol Reprod Dev 2004 Jul;68(3):327-34

Constantin the Philosopher University, Nitra, Slovak Republic.

The nucleolus formation was studied as an indirect marker of the ribosomal RNA (rRNA) genes activation in porcine embryos following oocyte maturation, fertilization, and culture in vitro. Nucleologenesis was assessed by transmission electron microscopy (TEM), light microscopical autoradiography following 20 min of 3H-uridine incubation, and immunocytochemical localization of key nucleolar proteins involved in rRNA transcription (upstream binding factor (UBF), topoisomerase I, and RNA polymerase I) and processing (fibrillarin, nucleophosmin, nucleolin) by confocal laser scanning microscopy. During the first four post-fertilization cell cycles, TEM revealed spherical nucleolus precursor bodies (NPBs), consisting of densely packed fibrils, as the most prominent intra-nuclear entities of the blastomeres. Fibrillo-granular nucleoli were observed in some blastomeres in a single embryo during the 5th cell cycle, i.e., the tentative 16-cell stage, where formation of fibrillar centres (FC), a dense fibrillar component, and a granular component on the surface of the NPBs was seen. In this embryo, autoradiographic labeling was detected over the nucleoplasm and in particular over the nucleoli. Fibrillarin was immunocytochemically localized in the presumptive NPBs of the pronuclei. This protein was again localized to the presumptive NPBs together with nucleolin from late during the 3rd cell cycle, i.e., the four-cell stage in some embryos. UBF, RNA polymerase I, and nucleophosmin were localized to the presumptive NPBs in a proportion of the embryos at the 4th cell cycle, i.e., the tentative eight-cell stage and onwards. Toposiomerase I was not localized to intra-nuclear entities even during the 5th post-fertilization cell cycle. Moreover, a considerable proportion of the blastomere nuclei apparently did not show localization of other nucleolar proteins. In conclusion, porcine embryos produced in vitro display a substantial delay in or even lack of the development of functional nucleoli.
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http://dx.doi.org/10.1002/mrd.20088DOI Listing
July 2004

Regulation of ribosomal RNA synthesis during the final phases of porcine oocyte growth.

Biol Reprod 2004 Apr 19;70(4):925-35. Epub 2003 Nov 19.

Department of Anatomy and Physiology, Royal Veterinary and Agricultural University, 1870 Frederiksberg, Denmark.

In porcine oocytes, acquisition of meiotic competence coincides with a decrease of general transcriptional activity at the end of the oocyte growth phase and, specifically, of ribosomal RNA (rRNA) synthesis in the nucleolus. The present study investigated the regulation of rRNA synthesis during porcine oocyte growth. Localization and expression of components involved in regulation of the rRNA synthesis (the RNA polymerase I-associated factor PAF53, upstream binding factor [UBF], and the pocket proteins p130 and pRb) were assessed by immunocytochemistry and semiquantitative reverse transcription-polymerase chain reaction and correlated with ultrastructural analysis and autoradiography following [3H]uridine incubation in growing and fully grown porcine oocytes. In addition, meiotic resumption, ultrastructure, and expression of p130, UBF, and PAF53 were analyzed in growing and fully grown porcine oocytes cultured with 100 microM butyrolactone I (BL-I), a potent inhibitor of cyclin-dependent kinases, to gain insight concerning the regulation of rRNA transcription during meiotic arrest. Immunocytochemical analysis demonstrated that p130 became colocalized with UBF and PAF53 and that the intensity of the PAF53 labeling decreased toward the end of the oocyte growth phase. These data suggest that the decrease in rRNA synthesis is regulated through inhibition of UBF by p130 as well as by decreased availability of PAF53. Moreover, expression of mRNA encoding PAF53 was decreased at the end of the oocyte growth phase. At the morphological level, these events coincided with inactivation of the nucleolus, as visualized by the transformation of the fibrillogranular nucleolus to an electron-dense fibrillar sphere with remnants of the fibrillar centers at the surface. Meiotic inhibition with 100 microM BL-I had a detrimental effect on the ability of porcine oocytes to resume meiosis and on nucleolus morphology, resulting in a lack of RNA synthetic capability as the fibrillar components, where rRNA transcription and initial processing occur, condensed or even disintegrated.
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http://dx.doi.org/10.1095/biolreprod.103.020941DOI Listing
April 2004

Immunolocalization of upstream binding factor and pocket protein p130 during final stages of bovine oocyte growth.

Biol Reprod 2004 Apr 12;70(4):877-86. Epub 2003 Nov 12.

Institute of Animal Physiology, Slovak Academy of Sciences, 040 01Kosice, Slovakia.

The aim of this study was to describe the dynamic changes in the localization of the key nucleolar protein markers, fibrillarin, B23/nucleophosmin, C23/nucleolin, protein Nopp140, during the final stages of bovine oocyte growth. All these proteins were present in the large reticulated nucleoli of oocytes from the small-size category follicles (<1 mm). The entire nucleolus exhibited strong positivity for UBF (upstream binding factor, RNA polymerase I-specific transcription initiation factor), which displayed a dotted staining pattern. In contrast, protein p130 was diffusely distributed throughout the nucleus and excluded from nucleoli. In oocytes approaching the late period of growth (2-3-mm follicles), UBF localization shifted to the nucleolar periphery. Double staining of UBF-p130 revealed a gradual accumulation of p130 at the periphery shell around the nucleolus. In fully grown oocytes (>3-mm follicles), all studied nucleolar proteins were detected in the small compact nucleoli. The cap structure, attached to the compact nucleolus surface, was positive for UBF and PAF53 (subunit of RNA polymerase I). The UBF-positive cap showed a close structural association with p130. It is concluded that, during the process of oocyte nucleolus compaction, UBF and PAF53, proteins involved in the rDNA transcription, are segregated from fibrillarin and Nopp140, proteins essential for early steps of pre-rRNA processing. The observed changes may reflect the transition from pre-rRNA synthesis to pre-rRNA processing as an analysis of the relative abundance of the developmentally important gene transcripts confirmed. In addition, discovered structural association between UBF and p130 suggests a role for pocket proteins in ribosomal gene silencing in mammalian oocytes.
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http://dx.doi.org/10.1095/biolreprod.103.018408DOI Listing
April 2004

Expression of nucleolar-related proteins in porcine preimplantation embryos produced in vivo and in vitro.

Biol Reprod 2004 Apr 29;70(4):867-76. Epub 2003 Oct 29.

Department of Anatomy and Physiology, Royal Veterinary and Agricultural University, 1870 Frederiksberg C, Denmark.

The expression of nucleolar-related proteins was studied as an indirect marker of the ribosomal RNA (rRNA) gene activation in porcine embryos up to the blastocyst stage produced in vivo and in vitro. A group of the in vivo-developed embryos were cultured with alpha-amanitin to block the de novo embryonic mRNA transcription. Localization of proteins involved in the rRNA transcription (upstream binding factor [UBF], topoisomerase I, RNA polymerase I [RNA Pol I], and the RNA Pol I-associated factor PAF53) and processing (fibrillarin, nucleophosmin, and nucleolin) was assessed by immunocytochemistry and confocal laser-scanning microscopy, and mRNA expression was determined by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). These findings were correlated with ultrastructural data and autoradiography following 20-min [3H]uridine incubation. Additionally, expression of the pocket proteins pRb and p130, which are involved in cell-cycle regulation, was assessed by semiquantitative RT-PCR up to the blastocyst stage. Toward the end of third cell cycle, the nuclei in non-alpha-amanitin-treated, in vivo-produced embryos displayed different stages of transformation of the nuclear precursor bodies (NPBs) into fibrillogranular nucleoli associated with autoradiographic labeling. However, on culture with alpha-amanitin, NPBs were not transformed into a fibrillogranular nucleolus during this cell cycle, demonstrating that embryonic nucleogenesis requires de novo mRNA transcription. Moreover, immunolocalization of RNA Pol I, but not of UBF, and the mRNA expression of PAF53 and UBF were significantly reduced or absent after culture with alpha-amanitin, indicating that RNA Pol I, PAF53, and presumably, UBF are derived from de novo embryonic transcription. Embryonic genomic activation was delayed in porcine embryos produced in vitro compared to the in vivo-derived counterparts with respect to mRNAs encoding PAF53 and UBF. Moreover, differences existed in the mRNA expression patterns of pRb between in vivo- and in vitro-developed embryos. These findings show, to our knowledge for the first time, a nucleolus-related gene expression in the preimplantation porcine embryo, and they highlight the differences in quality between in vivo and in vitro-produced embryos.
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http://dx.doi.org/10.1095/biolreprod.103.021683DOI Listing
April 2004

Accumulation of the proteolytic marker peptide ubiquitin in the trophoblast of mammalian blastocysts.

Cloning Stem Cells 2001 ;3(3):157-61

Windows to the Zygote 2000: UNESCO-ICRO International Training Course in Cell and Molecular Biology of Gametes, Fertilization, and Early Embryonic Development. The Faculty of Sciences, Charles University, Prague, Czech Republic.

Ubiquitination is a universal protein degradation pathway in which the molecules of 8.5-kDa proteolytic peptide ubiquitin are covalently attached to the epsilon-amino group of the substrate's lysine residues. Little is known about the importance of this highly conserved mechanism for protein recycling in mammalian gametogenesis and fertilization. The data obtained by the students and faculty of the international training course Window to the Zygote 2000 demonstrate the accumulation of ubiquitin-cross-reactive structures in the trophoblast, but not in the inner cell mass of the expanding bovine and mouse blastocysts. This observation suggests that a major burst of ubiquitin-dependent proteolysis occurs in the trophoblast of mammalian peri-implantation embryos. This event may be important for the success of blastocyst hatching, differentiation of embryonic stem cells into soma and germ line, and/or implantation in both naturally conceived and reconstructed mammalian embryos.
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http://dx.doi.org/10.1089/153623001753205115DOI Listing
May 2002

An empirical study of stalking victimization.

Authors:
B Bjerregaard

Violence Vict 2000 ;15(4):389-406

Department of Criminal Justice, University of North Carolina at Charlotte, 28223, USA.

This article empirically studies the phenomenon of stalking and its victims by utilizing a random sample of college students at a large public University. The study found that 25% of the women and 11% of the men had been stalked at some point in their lives and that six percent were currently being stalked. Additionally, the study found that the majority of stalking victims are women who are stalked by male offenders. The sample reported being stalked for an average of 347 days and having engaged in a variety of actions in response. A substantial number of victims reported being threatened by their stalkers. This threat was associated with higher levels of fear among the victims and a greater chance of physical attack by the stalkers, particularly for the female victims.
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June 2001

Osteoclast-like giant cells in leiomyomatous tumors of the uterus. A case report and review of the literature.

Acta Obstet Gynecol Scand 2001 Apr;80(4):371-4

Department of Pathology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.

Osteoclast-like giant cells (OLGC) in leiomyomatous tumors of the uterus are rarely seen, and their significance is unknown. We present a case of a large leiomyomatous tumor in which OLGC were found in only few sections showing leiomyosarcoma whereas the majority of sections revealed a leiomyoma. Though radically operated, the patient died a few months later with recurrent tumor in the pelvis and metastases to the lungs.
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April 2001

Staging uterine cervical carcinoma with low-field MR imaging.

Acta Radiol 2000 Nov;41(6):647-52

Department of Diagnostic Radiology, Copenhagen University Hospital at Herlev, Denmark.

Purpose: To assess the validity of low-field MR in staging cervical cancer compared to clinical staging.

Material And Methods: A total of 95 women entered the study over a 3-year period. MR examinations with a 0.1 T resistive magnet using a body coil and clinical staging according to the FIGO recommendations (1988) were performed within 2 weeks from clinical diagnosis. T1- and T2-weighted sequences were obtained in transversal and sagittal acquisitions, and an additional T1 before and after contrast (randomisation to 0.1 or 0.3 mmol/kg b.w. gadodiamide). Treatment decisions on surgery or radiation therapy were made solely on the clinical staging.

Results: Sixty-one patients were found to be eligible for surgery. In 5 women, the pathological results revealed a more advanced stage of the disease than assessed by clinical staging. MR correctly staged 4 of the 5 but otherwise tended to overstate the disease. Contrast enhancement significantly reduced this trend (p<0.05) regardless of the contrast medium dose used. Divided into two groups, an operable (less than stage 2b) and an inoperable group (more than stage 2a), the clinical staging correctly classified 57 patients (accuracy 92%) compared to 52 patients with MR using contrast enhancement (accuracy 84%). The specificity was no higher than 31%, whereas the reproducibility of the MR assessment was fairly good with kappa values around 0.65 for both intra- and inter-observer variations.

Conclusion: In the present set-up, clinical assessment was superior to low-field MR in staging cervical cancer. When using contrast enhancement, the staging accuracies of low-field MR were comparable to the ones reported for techniques with higher tesla values, whereas the specificity and reproducibility errors were lower. The method, therefore, needs to be optimised.
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http://dx.doi.org/10.1080/028418500127346072DOI Listing
November 2000

Liposarcoma in association with total hip replacement.

Int Orthop 1999 ;23(3):187-9

Department of Orthopaedic Surgery, Tumor Section, Herlev University Hospital, DK-2730 Herlev, Denmark.

A possible relation between joint replacement and malignancy has previously been suggested in a few cases. In the majority of these cases, the authors found either malignant fibrous histiocytomas or osteosarcomas. We hereby report the first case of a liposarcoma in the vicinity of a joint prosthesis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3619831PMC
http://dx.doi.org/10.1007/s002640050344DOI Listing
November 1999

Observer variation in the assessment of the histopathologic diagnosis of acute appendicitis.

Scand J Gastroenterol 1999 Jan;34(1):46-9

Dept. of Surgical Gastroenterology, Herlev Hospital, University of Copenhagen, Denmark.

Background: The objectives of this study were to determine observer variation in the assessment of the histopathologic diagnosis of acute appendicitis.

Methods: Two consultant pathologists independently evaluated 415 appendectomy specimens (set I). After a consensus conference at which the observers unified the criteria of the diagnosis of acute appendicitis, another 396 appendectomy specimens (set II) were evaluated. To calculate the intra-observer variation, one observer evaluated set II once more. Finally, using the consensus diagnosis as the final diagnosis, the diagnostic accuracy of the surgeon, the primary pathology report, and the two observer evaluations was calculated.

Results: In set I no difference was found in the level of agreement on the diagnosis of acute appendicitis versus other diagnoses, and a kappa value of 0.85 was obtained. In set II a kappa value of 0.88 was obtained, which was not significantly different from the kappa value in set I. However, the consensus conference did increase the level of agreement on the diagnosis of acute appendicitis. The intra-observer variation was calculated, and a kappa value of 0.88 was obtained. The cases in which the observers disagreed on a positive diagnosis were cases of mild appendicitis. The question remains how many specimens would have shown these changes if all tissue had been developed for microscopy. The observers' diagnoses were the most reliable, and there was a significant decrease in the diagnostic accuracy compared with both the primary pathology report and the surgeon's opinion, the last one being the least accurate.

Conclusions: These observations stress how important it is for the pathologist to discuss the diagnostic criteria of the diagnosis of acute appendicitis and for the surgeon to go back to the patient's record and look up the histopathologic diagnosis.
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http://dx.doi.org/10.1080/00365529950172826DOI Listing
January 1999

Intramuscular myxoma and fibrous dysplasia of bone--Mazabraud's syndrome. A case report.

Acta Radiol 1997 May;38(3):368-71

Department of Ultrasound, Herlev Hospital, University of Copenhagen, Denmark.

We present a case of Mazabraud's syndrome, a rare benign disease, with multiple intramuscular myxomas of the thoracic wall associated with fibrous dysplasia of bone. CT, MR imaging and ultrasonography (US) of the thorax showed 2 well circumscribed homogeneous intramuscular tumors. A US-guided needle biopsy with a large-core needle (2.0 mm) and a fine needle (0.8 mm) showed that the tumors were intramuscular myxomas with no sign of malignancy. 99mTc bone scintigraphy showed a markedly increased uptake in the right lower skull, and multiple smaller foci. CT of the skull revealed a right-sided unilateral bone thickening of the orbit and the ethmoidal cells, and right-sided exophthalmia. This case history suggests that patients with multiple intramuscular myxomas should be preoperatively examined for osseous lesions. A postoperative follow-up should also be performed to detect other soft-tissue myxomas not as yet clinically detectable, or rare osseous complications.
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http://dx.doi.org/10.1080/02841859709172085DOI Listing
May 1997

[A model for estimation of productivity and costs at a deparment of histopathology].

Ugeskr Laeger 1997 Mar;159(13):1935-40

Patologisk-anatomisk institut, Amtssygehuset i Herlev.

Two cost calculation models were used. The "top down" model calculated an average cost of all investigations; this proved suitable for the calculation of the costs of autopsies and electron microscopical specimens. The "bottom up" model calculated the cost of an individual investigation, depending on the resources used in handling each particular specimen; it was necessary to adopt this model for specimens sent for microscopy. Information about the type of specimen and technical details were registered in a computer system. Production was registered in points and the costs were distributed between the clinical departments. The study showed that the cost of the histological specimens varied considerably depending on the material received from the clinical departments. A model using points for technical details in a department of cyto- and histopathology is suitable for calculating production and cost.
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March 1997

[A time study in a department of histopathology].

Ugeskr Laeger 1997 Mar;159(13):1929-34

Patologisk-anatomisk institut, Amtssygehuset i Herlev.

In the Department of Histo- and Cytopathology, Herlev University Hospital, Copenhagen, a time study was performed according to the principles known from work sampling. From 22.11-12.12.1993 laboratory technicians, pathologists and secretaries were interviewed and an activity form was filled in. Six thousand nine hundred and fifty interviews were performed and the time study showed that for all groups of personnel 40% of the time was used on specimens sent for microscopy, 5% on autopsies (excl. microscopy), 15% on teaching and research, 20% on scientific meetings, reading and administration and 20% on other activities e.g. lunch, holiday, absence owing to illness. There was little variation for the different groups of personnel. On the other hand the time used on specific laboratory procedures, e.g. serial cutting, special-, and immunostaining, varied considerably for laboratory technicians, pathologists and secretaries respectively. Time studies, especially "work sampling" yield important information for the planning of laboratory services and provide documentation also for the time not directly related to routine work.
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March 1997

[EDP registration of the types of tests, working procedures and diagnosis in a department of histopathology. Minimum dataset for assessment of the workload].

Ugeskr Laeger 1997 Mar;159(13):1924-8

Patologisk-anatomisk institut, Amtssygehuset i Herlev.

The aim of the study was to develop a computer-based system for measuring workload in a department of histo- and cytopathology using routine registration of a minimum dataset. A group with representatives from the laboratory technicians, the pathologists and the secretaries defined 18 types of specimens. By studying each step of specimen processing it was shown, that 14 items for technical details could cover all the work done in the department. This information was collected in a computer-based system connected to the hospital network. The measurement of workload is essential for the efficient management of laboratory services. The registration of specimen types and a minimum dataset for specimen processing describes the work done in a department of histo- and cytopathology.
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March 1997

Computer-assisted diagnosis in gastroenterology.

Scand J Gastroenterol Suppl 1996 ;216:225-33

Dept. of Medicine, Svendborg Hospital, Denmark.

During the last 20 years, Danish gastroenterologists and biostatisticians have been involved in practical and theoretical research aimed at providing computer-assisted decision support in clinical practice. On the practical side, we summarize two clinical applications, one in the acute abdomen, the other in jaundice. The former project is part of a worldwide effort which appears able to reduce considerably the perforated appendix rate and the negative laparotomy rate. In the latter project, also entwined in international activities, three methods of early statistical discrimination of jaundice causes have been tested, and it has been shown how ultrasonographic data can be incorporated into the diagnostic assessment. On the theoretical side, a Dutch-Danish group has been looking into how one best designs a trial and analyses its data in the context of measuring the quality and impact of machine-made diagnostic advice. Having pointed out the international ramifications of these activities, we outline what may lie ahead: Gastroenterologists must be prepared to join large-scale field trials of clinical advice-giving software. In the future, however, such software will often become embedded in general hospital recordkeeping systems.
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http://dx.doi.org/10.3109/00365529609094577DOI Listing
November 1996

Diagnostic value of cerebrospinal fluid cytology in comparison with tumor marker activity in central nervous system metastases secondary to breast cancer.

Cancer 1993 Oct;72(8):2376-82

Department of Oncology, Herlev Hospital, University of Copenhagen, Denmark.

Background: Central nervous system (CNS) metastases occur in approximately 35% of patients with breast cancer. Parenchymal brain metastases (MET) remain undetected in a large proportion of patients, and only 50% of patients with leptomeningeal carcinomatosis (MC) are diagnosed in vivo.

Methods: Cytology and activity of the tumor markers tissue polypeptide antigen (TPA) and creatine kinase-BB isoenzyme (CK-BB) were evaluated in the cerebrospinal fluid (CSF) in 71 consecutive patients with breast cancer suspected for CNS metastases.

Results: Forty-three patients had no CNS metastases, 12 patients had MET, 5 patients had both MET and MC, and 11 patients had MC alone. Seven of the patients with MC had an intracerebroventricular (ICV) reservoir inserted, and an additional 70 ICV CSF samples from these patients were obtained. In CSF obtained by lumbar puncture, 11% of the samples were classified as "suspicious for malignancy," but a very limited interobserver variability was demonstrated (Kappa test value, 0.81; 95% confidence limits, 0.67-0.95%). Fifty-one percent of the ICV CSF samples were classified as "suspicious for malignancy" (Kappa test value, 0.58; 95% confidence limits, 0.34-0.82%). TPA and CK-BB were both measured in 101 CSF specimens (61 from lumbar puncture and 40 ICV samples). The differences between patients with and without CNS metastases were significantly different according to TPA (P < 0.00001) and CK-BB (P < 0.00003; Mann-Whitney test). The sensitivity and predictive value of a negative test for having any CNS metastases (in case of elevated values of either TPA or CK-BB or both) were 85% (95% confidence limits, 65-96%) and 90% (95% confidence limits, 76-97%), respectively. In addition, a significant correlation between TPA and CK-BB was demonstrated in CSF from lumbar puncture (Spearmans-Rho, 0.49; P < 0.0001) and ICV (Spearmans-Rho, 0.37; P < 0.02).

Conclusions: Cytologic evaluation of CSF obtained by lumbar punctures is a reliable procedure. In CSF from ICV reservoirs, cytologic evaluation is of limited use, but CK-BB and TPA is of potential value.
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http://dx.doi.org/10.1002/1097-0142(19931015)72:8<2376::aid-cncr2820720814>3.0.co;2-6DOI Listing
October 1993

The significance of histology and morphometry in predicting lymph node metastases in patients with squamous cell carcinoma of the vulva.

Gynecol Oncol 1993 Sep;50(3):323-9

Department of Pathology, Herlev Hospital, University of Copenhagen, Denmark.

The material consists of a series of 73 patients with squamous cell carcinoma of the vulva. The site and the size of the primary tumor and the histological status of the lymph nodes of the groin were known. Two pathologists evaluated nuclear hyperchromatism, nuclear polymorphism, histological differentiation, number of mitoses, inflammatory response, and vascular invasion and graded these parameters from one to three. The reliability of the histopathological grades evaluated by the kappa coefficient showed considerable interobserver variation. Despite this a model which included the subjective parameter nuclear hyperchromatism could predict patients without lymph node metastases. The model consisted of patients with tumors which were not situated on the clitoris, were less than 40 mm in diameter, and exhibited only slight hyperchromatism. The model fitted 19 (26%) and 14 (19%) of the patients with two different pathologists evaluating the nuclear hyperchromatism and none of these patients had lymph node metastases. The quantitative parameter--mean nuclear volume--determined by morphometry was of no diagnostic value for the prediction of patients without groin node metastases at the time of operation.
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http://dx.doi.org/10.1006/gyno.1993.1219DOI Listing
September 1993

Benign breast lesions in Kenya: a histological study.

East Afr Med J 1992 May;69(5):231-5

Department of Pathology, Herlev University Hospital, Denmark.

During 1981-85, 1084 cases of benign breast lesions were seen at Kenyatta National Hospital, Nairobi, Kenya. In the same period, 417 cases of breast carcinoma were diagnosed. Amongst the benign lesions fibroadenoma was the most common diagnosis (531 cases) followed by mastopathy (177 cases). The incidence rate of fibroadenoma was 1.6 per 100,000 person-years. Classic tubular adenoma was seen in 26 cases and in 26 cases a mixture of fibroadenoma and tubular adenoma was seen. These findings suggest that breast adenoma is probably one tumour with different expressions of the glandular and fibrous areas. We found no specific gross or microscopical features by which it was possible with certainty to distinguish between fibroadenoma and giant fibroadenoma and therefore suggest that the term giant fibroadenoma be avoided. The histopathologic pattern of mastopathy showed great variation, but the lesions were without difficulty divided into three main categories, i.e. cystic, fibrous and hyperplastic mastopathy. This distinction is important as cases with marked epithelial hyperplasia have been shown to have an increased cancer risk. Except for low parity no similarities in risk factors for mastopathy and breast cancer have been shown so far.
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May 1992

Tumours of the nose and maxillary sinus. Ten year survey from Kenya.

J Laryngol Otol 1992 Apr;106(4):337-41

Department of Pathology, Herlev Hospital, University of Copenhagen, Denmark.

Between 1976-1985, 127 cases of malignant tumours of the nose and maxillary sinus were seen at the Department of Human Pathology, Kenyatta National Hospital, Nairobi, Kenya. Cancer of the nose and maxillary sinus was a common diagnosis accounting for 0.8 per cent of all malignancies. Despite this, the incidence was low probably because the rural Kenyans have difficulty in gaining access to the oncology facilities in Nairobi. Incidence rates standardized to world population per 100,000 persons-years were 0.16 for males and 0.12 for females. Clinical information showed that malignancy should be expected in patients with swelling of the cheek and involvement of the orbit. Compared with Denmark the proportion of undifferentiated carcinomas was significantly higher in Kenya. The well known fact that anaplastic carcinoma of the postnasal space is causally associated with the Epstein Barr virus makes it tempting to suggest that anaplastic carcinoma of the nose and maxillary sinus may also be of viral aetiology.
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http://dx.doi.org/10.1017/s0022215100119437DOI Listing
April 1992

AgNOR counts and histological grade in stage pTa bladder tumours: reproducibility and relation to recurrence pattern.

Histopathology 1992 Mar;20(3):257-62

Department of Pathology and Urology, Herlev Hospital, University of Copenhagen, Denmark.

Silver-stained nucleolar organizer regions (AgNORs) were studied in 90 patients with a single, primary, non-invasive papillary bladder tumour (stage pTa). All tumours were locally resected and patients were followed for 5 years (n = 68) or until the development of an invasive recurrence (n = 22). AgNOR counts showed wide overlaps between the different tumour grades. Furthermore, AgNOR counts were unable to predict the non-invasive recurrence pattern (none, single, multiple). Almost equivalent invasive recurrence rates were found among the following AgNOR counts and Bergkvist grades: AgNOR less than or equal to 5 (0%) and grade I (5%); AgNOR greater than 5, but less than or equal to 8 (20%); and AgNOR greater than 8 (77%) and grade III (67%). Combining the two parameters showed that an AgNOR count greater than 8 resulted in a 75 and 80% invasive recurrence rate in grade III and II tumours respectively. The reproducibility for AgNOR counting was moderate (kappa = 0.52) and no better than Bergkvist grading (kappa = 0.50).
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http://dx.doi.org/10.1111/j.1365-2559.1992.tb00965.xDOI Listing
March 1992

Breast cancer in Kenya: a histopathologic and epidemiologic study.

East Afr Med J 1992 Jan;69(1):22-6

Department of Pathology, Herlev University Hospital, Denmark.

During 1981-1985, 417 cases of breast cancer were seen at the Department of Human Pathology, Kenyatta National Hospital, Nairobi, Kenya. During this period, 8041 cases of cancer were reported. Cancer of the breast accounted for 5% of all malignancies in Kenya and only second in number to cancer of the cervix. The incidence rate in females was 1.08 per 100,000 person-years. The incidence was low because the rural Kenyans have difficult access to the oncology facilities in Nairobi. The age specific incidence rates decreased after menopause. This is also found in other African countries but is in contrast with North America and Europe, where there is a rise after menopause. Young age of the first pregnancy, many pregnancies and a low fat content of the diet may contribute to the low incidence in post menopausal women. The distribution of the histological types was the same in Kenya with predominance of premenopausal cases and in the western world with predominance of postmenopausal cases. Invasive ductal carcinoma was the most common cancer type. Poorly differentiated tumours were common. This is probably explained by the fact that most patients seek medical help at a late state with advanced cancer. Only two cases of non-invasive intraductal carcinoma were found and in cases where lymphnodes were removed 88% had metastases.
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January 1992

Cytomegalovirus infection in classic, endemic and epidemic Kaposi's sarcoma analyzed by in situ hybridization.

APMIS 1991 Oct;99(10):893-7

Department of Pathology, Herlev University Hospital, Denmark.

In order to evaluate the association between cytomegalovirus (CMV) infection and Kaposi's sarcoma (KS) at the cellular level, four classic KS, five endemic (African) KS and 55 epidemic KS from 12 patients with AIDS were analyzed by in situ hybridization with a biotinylated specific CMV-DNA probe. CMV-DNA was sparsely demonstrated in the sarcomas in 10 of the patients with AIDS but in none of the classic or endemic sarcomas. The distribution and localization of the CMV-infected cells did not suggest CMV as a major pathogenic stimulus for the development of KS but rather as an opportunistic infection in severely immunosuppressed patients.
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October 1991
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