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Biomedical subjects

B Hølund

Publications and source records attributed to B Hølund.

At least 19 recordsLinked to original sources

[Status of preventive examinations against uterine cervix cancer in Denmark].

In 1986, The Danish National Board of Health published guidelines for cervical cancer screening. These guidelines recommend organized screening with personal invitations every three years to women in the age group 23-59 years, and in the years to come also invitations to women aged 60-74 years. Five years have now elapsed since publication of these guidelines, and we have therefore studied the present organization of cervical cancer screening in Danish counties. Organized screening programmes are now, medio 1991, running in 11 out of the 16 "counties" (this includes the municipalities of Copenhagen and Frederiksberg). One county follows the national guidelines entirely. Six counties follow these guidelines in general, but they do not invite women over the age of 60 years. In all, 45% of women aged 25-74 years are at present invited for cervical cancer screening in Denmark. Two counties have decided to start organized screening programmes in 1992.

Adult

Malignant mixed müllerian tumors of the ovary. Report of 13 cases.

Thirteen patients with verified malignant mixed Müllerian tumor of the ovary treated in Denmark during the 7-year period 1981-87 were reviewed. Two patients had homologous and 11 patients had heterologous tumors. Four patients with early stage disease underwent radical surgery; 9 patients had stage III disease. Median survival for all 13 patients was 12 months. Six patients received platinum-containing cytotoxic therapy; 2 of these patients without measurable disease became long-term survivors (survival times 42+ and 92+ months, respectively) and 3 of the 4 remaining patients with evaluable disease obtained an objective remission.

Aged

Immunohistochemical study of possible changes in keratin expression during neoplastic transformation of the uterine mucosa.

The present study aimed to examine possible changes in keratin expression during neoplastic transformation of the uterine mucosa and possible differences in keratin expression between endocervical and endometrial adenocarcinomas. Routinely processed specimens with normal morphology or neoplastic changes were stained immunohistochemically using 5 commercial antibodies to keratin-filaments of molecular weight 39-58 kD: CAM 5.2, RCK 102, MCA 144, PKE and PRE. We generally found a change in keratin expression during the neoplastic transformation, consisting of pronounced heterogeneity compared with normal epithelia. In distinguishing koilocytic atypia from CIN, RCK 102 (52.5, 58 Kd) may prove helpful as it stains neoplastic cells strongly and shows no reaction in koilocytic. Staining with the antibody CAM 5.2 (reactive with 39, 43, 50 kD filaments) may aid in distinguishing between cervical and endometrial adenocarcinomas. The former is stained uniformly; the latter shows a more variable staining.

Adenocarcinoma

A randomized trial comparing two methods of cold knife conization with laser conization.

In a randomized study, 62 women were submitted to cold knife conization with application of Sturmdorf sutures, 60 to cold knife conization without sutures, and 61 to laser conization. Early hemorrhage occurred in 1.6, 13.3, and 6.6% of women, respectively (P less than .05), and late hemorrhage in 15.3, 3.6, and 11.7%, respectively. Considering early and late hemorrhage together, there was no significant difference among the three treatment groups. Dysmenorrhea tended to be more common after application of Sturmdorf sutures, as it was reported by 27.8, 13.2, and 14.3% of patients, respectively, but the difference was not statistically significant. Dysmenorrhea occurred in 13% of the cases with a cone height of 20 mm or less and in 26% of the cases with a cone height greater than 20 mm (P less than .05). Endocervical cells were present significantly more often after sampling with a cytobrush than with a cotton swab (P less than .0001), whereas the method of conization had no influence. In smears obtained with a cytobrush, endocervical cells were present in 88.0, 84.9, and 82.5% of the cases; in smears obtained with a cotton swab, endocervical cells were present in 46.6, 57.7, and 54.5%, respectively. We conclude that cold knife conization without Sturmdorf sutures is about equal to laser conization in overall complications, but the laser is preferable for outpatient treatment because of a lower frequency of early hemorrhage. Sturmdorf sutures should be avoided. Smears at follow-up should be taken with a cytobrush and a wooden spatula.

Adult

The efficiency of the cytobrush and cotton swab in obtaining endocervical cells in smears taken after conization of the cervix.

In a randomised study of cervical smears after conization, the efficacy of the combined wooden spatula and cytobrush was compared with that of the combined wooden spatula and cotton swab. The conization technique involved a could knife and two Sturmdorf sutures. A total of 75 women participated, 57 had smears taken with both methods. Eighteen with only one of the methods. Out of 66 taken with a wooden spatula and a cytobrush. 48 (72.7%) contained endocervical cells and 53 (80.3%) contained either endocervical or metaplastic cells. Out of 66 smears taken with a wooden spatula and a cotton swab, only 25 (37.9%) contained endocervical cells and 40 (60.6%) contained endocervical or metaplastic cells. Both differences were significant (P less than 0.001 and P less than 0.05, respectively). The combined use of a wooden spatula and cytobrush is recommended for cytological smears after conization.

Cervix Uteri

Demonstration of fibronectin in normal and acutely inflamed appendix.

The presence and localization of fibronectin in normal and acutely inflamed appendices in man was studied using indirect immunoperoxidase technique on sections of formaldehyde fixed and paraffin embedded tissue, following pretreatment with pepsin and testicular hyaluronidase. In the normal appendix fibronectin was demonstrated in the region of the basement membrane of the surface epithelium, in the loose connective tissue, in the perimysium around the individual smooth muscle cells and in the vessel walls. In the acutely inflamed appendices, fibronectin was found in the luminal necrotic area, both intercellularly and in the cytoplasma of some inflammatory cells. In relation to the surface inflammation and in the tissue matrix corresponding to the acute inflammatory reaction fibronection was, compared to the normal appendix, found in increased amount. Furthermore, a comparison between the use of a primary antibody to fibronectin, produced in our collaborating laboratory and two different commercial primary antibodies showed that the staining results concerning the localization of fibronectin were equal for all three antibodies, whereas the commercial antibodies showed a weaker staining intensity and some unspecific staining compared to the antibody produced in our collaborating laboratory.

Acute Disease

Circulating monoclonal IgM lambda cryoglobulin with collagen type I affinity in vasculitis.

A previously fit 66-years-old male primarily presented symptoms compatible with Henock-Schönlein's purpura, from which he seemingly recovered. Shortly hereafter he relapsed with an IgM lambda essential monoclonal cryoglobulinemia type I, presenting a systemic, necrotizing vasculitis, with low titer of circulating immune complexes and complement consumption. Glucocorticoid treatment and plasmapheresis did not prevent an ultimately lethal course. An indirect immunoperoxidase technique showed that the cryo-IgM bound to the interstitial connective tissue corresponding to the localization of collagen type I. In addition it bound to affinity purified human procollagen type I. These results indicate, that the IgM lambda of the proband was an autoantibody with collagen type I specificity.

Aged

Differentiation between metaplastic carcinomas and sarcomas of the human female breast by fibronectin.

The distribution pattern of fibronectin in metaplastic carcinomas, stromal sarcomas, malignant cystosarcoma phyllodes tumours and histiocytic type lymphomas of the human female breast has been studied using the indirect immunoperoxidase technique on formalin fixed paraffin embedded tissue. Fibronectin was demonstrated as intensely stained strands between tumour cells forming an irregular network in metaplastic carcinomas and lymphomas. Stromal sarcomas and the malignant stromal component of the phyllodes tumours exhibited, in contrast, a uniform staining throughout tumour cells and stroma which was weaker than in adjacent normal-looking connective tissue. We suggest that the intense staining reaction of metaplastic carcinomas is due to the scirrhous reaction generally associated with invasive human breast carcinomas. The advantage of using fibronectin as a diagnostic tool in the differentiation of carcinoma/lymphoma versus sarcoma is the fact that the antigen is a stromal marker and its staining intensity is not influenced by the morphology or degree of differentiation of non-mesenchymal tumours.

Breast Neoplasms

In vivo demonstration of cytoplasmic fibronectin in human breast carcinomas.

The distribution pattern of fibronectin in 24 invasive human breast carcinomas has been studied using the indirect immunoperoxidase technique. A positive cytoplasmic staining reaction was observed in 16 tumours. Well-differentiated carcinomas showed weak or no staining, whereas all moderately or poorly differentiated carcinomas and one signet ring cell carcinoma contained fibronectin positive tumour cells with moderate or strong staining. The staining intensity was positively correlated to degree of anaplasia with the exception of two moderately differentiated duct carcinomas and the two medullary carcinomas, which were only slightly positive. Non-attached independently growing tumour cells stained more intensely than tumour cells in clusters. Pericellular fibronectin was found in only one carcinoma of medullary type. In normal ducts and glands it was seen at the stromal-epithelial junction corresponding to the basement membrane, around myoepithelial cells and along the luminal border. The results support the findings of several in vitro investigations that breast tumour cells synthesize fibronectin. It also suggests that cytoplasmic fibronectin expression might be an indicator of tissue differentiation in non-solidly growing invasive duct carcinomas of the human mammary gland.

Breast Neoplasms

Sequential appearance of fibronectin and collagen fibres in experimental arthritis in rabbits.

The sequential changes in the presence of fibronectin in the synovial membrane during the development of antigen-induced arthritis in rabbits were studied using an indirect immunoperoxidase technique on the tissue specimens fixed in formaldehyde, embedded in paraffin and pre-treated with pepsin and testicular hyaluronidase. The relation to the distribution of fibronectin and connective tissue fibres, demonstrated as either argyrophilic or red by van Gieson method, was studied. Initial after the induction of the arthritis the synoviocytes became increased in size and number. The subsynoviocytial tissue was invaded by granulocytes and the number of vessels was increased. Fibronectin in increased amount was seen around the lining cells. After 2-4 weeks a markedly reduced amount of granulocytes were seen together with an increase in the number of macrophages. At this stage, fibronectin was also found together with argyrophilic fibres in the subsynoviocytial connective tissue. After 8-13 weeks the synovial membrane was found hypertrophic and folded. The lining layer was unchanged, but in the subsynoviocytial tissue lymphocytes and plasma cells were more focally arranged. At that time fine fibres, stained by the van Gieson method, were present together with fibronectin and argyrophilic fibres in the subsynoviocytial tissue. The morphological change and the distribution of fibronectin in experimentally induced arthritis correlated temporally to the morphological change and the presence of fibronectin found in experimentally induced granulation tissue.

Animals

Rheumatoid nodules. A lightmicroscopical study with special reference to fibrin and fibronectin.

The presence and localization of fibrin and fibronectin in rheumatoid nodules were studied using an indirect immunoperoxidase technique on tissue specimens fixed in formaldehyde, embedded in paraffin and pretreated with pepsin and testicular hyaluronidase. Three zones characteristic for rheumatoid nodules was recognized. Central area with necrosis, containing at least in part fibrinogen-antigenic material and fibronectin especially in the peripheral part of the necrotic area. Around the necrosis a layer of mesenchymal cells in a palisade arrangement was found. Especially in the external part of this layer fibronectin was demonstrated around and between the cells, where fibrin was absent. Peripherally, a zone of non-specific granulation tissue containing moderate amount of fibronectin decreasing towards the surround mature connective tissue, was seen. In the border of the cellular layer vessels were found in variable amount. In some of the vessels vasculitis was demonstrated with the presence of inflammatory cell infiltration, fibrin deposition and occasionally thrombosis. The pathogenesis of the inflammatory reaction in rheumatoid nodules is discussed.

Adult

Fibrin and fibronectin in rheumatoid synovial membrane and rheumatoid synovial fluid.

Normal synovial membranes and synovial membranes from patients with classic rheumatoid arthritis were investigated for the presence of fibrin and fibronectin by an indirect immunoperoxidase technique. In normal synovial membranes, fibronectin was found around the monolayer of the synovial lining cells. Staining was most intense on the surface and beneath the lining cells, but not detectable in the cytoplasm. Fibronectin was also found in the cytoplasm of the endothelial cells. No staining for fibrin was found in the normal synovial membrane. In synovial membranes from patients with rheumatoid arthritis, large amounts of fibronectin were found around the multilayer of synovial lining cells, in the cytoplasm of the endothelial cells, and in argyrophilic fiber-rich connective tissue. In superficial areas denuded of synovial lining cells, high amounts of fibronectin were found incorporated in fibrin. In some areas with noninjured synovial lining cells, fibrin was also found, but in this case no fibronectin was incorporated. No fibronectin was found in connective tissue in areas with infiltration of inflammatory cells. After treatment of normal and rheumatoid synovial membranes with hyaluronidase, fibronectin was still present around the lining cells but the staining was found to be more distinct. This study relates the presence of fibrin and fibronectin in the rheumatoid synovial membrane to the high amount of these proteins, recently described, in rheumatoid synovial fluid. It also suggests that fibronectin present in the synovial membrane is produced and secreted by the endothelial cells.

Arthritis, Rheumatoid

Demonstration of fibronectin in normal and injured aorta by an indirect immunoperoxidase technique.

The presence and localization of fibronectin in normal and mechanically injured aorta in rabbits was studied using an indirect immunoperoxidase technique on tissue specimens fixed in formaldehyde, embedded in paraffin and pretreated with pepsin. The effect on staining quality of treatment with testicular hyaluronidase prior to immunoperoxidase staining was also examined. In the intima from normal aorta fibronectin was present in the subendothelial basal layer, along the internal and external elastic laminae, around and between the smooth muscle cells of the media and along the collagen and elastic fibres in the adventitia. Sixteen days after a single mechanical dilatation of the descending thoracic aorta all animals developed gross atherosclerotic-like changes. Microscopic examination revealed prominent neo-intimal hyperplasia with subendothelial, cushion-like thickenings but no medial or adventitial alterations. Fibronectin, in increased amounts, was found between and around the endothelial cells and in the subendothelial thickenings between the proliferating smooth muscle cells in relation to the fine, thin elastic and argyrophilic fibres. In the media and adventitia the amount and distribution of fibronectin was indistinguishable from uninjured control aortas. Treatment with testicular hyaluronidase before immunoperoxidase staining resulted in a higher staining resolution in normal and injured aorta. The conspicuous observation in the present study is that fibronectin exclusively accumulates in areas of tissue repair. The origins and functions of fibronectin during tissue injury and repair are discussed.

Animals

Liver biopsy in chronic aggressive hepatitis. Diagnostic reproducibility in relation to size of specimen.

For the purpose of evaluating the reproducibility of the main diagnosis in liver needle biopsies and estimating the size of the specimen for an acceptable accuracy, 100 liver specimens selected from the daily routine, all 25 mm or more in length, were investigated. The material consisted of specimens from 50 patients with chronic aggressive hepatitis (CAH; including 37 without and 13 with suspicion of cirrhosis), 6 with macronodular cirrhosis, 5 with micronodular cirrhosis, 10 with acute viral hepatitis (including 3 with suspicion of chronicity), 10 with primary biliary cirrhosis, 6 with chronic persistent hepatitis, and 13 with other diagnoses. The specimens were investigated without knowledge of clinical data in five sessions with an increasing amount of tissue made visible. The predictive value of a diagnosis present (diagnostic specificity) and a diagnosis absent (diagnostic sensitivity) was used in evaluating the efficiency of the diagnosis made on the visible part of the biopsy. For CAH (with and without suspicion of cirrhosis) the number of biopsies with the correct diagnosis increased significantly with increasing amounts of tissue visible (p less than 0.01), and the required length for an acceptable accuracy of CAH was 15 mm. The diagnostic sensitivity for CAH was very high (94%) with only 5 mm tissue available and constant through all sessions.

Biopsy, Needle

Serum ferritin and the assessment of iron deficiency in rheumatoid arthritis.

In order to evaluate the diagnostic and pathogenetic importance of s-ferritin and p-lactoferrin in the anemia of rheumatoid arthritis (RA), 38 patients were examined. Twenty-one out of 38 randomly selected anemic patients with classical or definite RA had iron deficiency, as estimated from the iron content in stained bone marrow aspiration. S-ferritin concentrations below 60 micrograms per litre had sensitivity and a specificity for iron deficiency of 86% and 88%, respectively, which was much better than such commonly used variables as s-iron, p-transferrin, MCV, and MCHC. Although this cut-off level is higher than in patients without inflammatory disease, s-ferritin was not correlated to disease activity. In 7 out of 8 patients, the s-ferritin level rose during iron therapy. P-lactoferrin values were within the normal range and did not vary with the anemia or with disease activity. Thus p-lactoferrin appears to be of no pathogenetic importance in the anemia of RA.

Adult

The value of hyaluronidase treatment of different tissues before demonstration of fibronectin by the indirect immunoperoxidase technique.

The influence of testicular hyaluronidase treatment on the immunohistochemical localization of fibronectin in different tissues (human articular cartilage, large intestine, synovial membrane and experimental granulation tissue) as well on frozen as on formaldehyde fixed, paraffin embedded tissue, has been studied using the indirect immunoperoxidase technique. Pretreatment with hyaluronidase is essential in demonstrating fibronectin in frozen sections of human articular cartilage. In the other tissues examined treatment with hyaluronidase was not essential, but gave a more optimal staining quality. The effect of hyaluronidase treatment was to some extent dependent on the duration of treatment. In formaldehyde fixed, paraffin processed tissue the improvement with hyaluronidase treatment was only seen when the hyaluronidase followed pepsin digestion of the deparaffinized tissue sections.

Cartilage