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S Holck

Publications and source records attributed to S Holck.

At least 37 records · Page 2Linked to original sources

DNA ploidy and S-phase fraction in medullary carcinoma of the breast--a flow cytometric analysis using archival material.

In a population of 110 primary breast cancers with medullary features, registered in the Danish Breast Cancer Cooperative Group (DBCG) from 1977-82, we have determined ploidy and S-phase fraction (SF) by flow cytometry (FCM) on paraffin embedded tumour tissue. The distribution of DNA ploidy is not different from the distribution described for breast cancers in general. No difference is found between the subgroups of medullary and non-medullary cancer when using a new simplified histopathological definition of medullary carcinoma of the breast, recently proposed by us. When using the definition proposed by Ridolfi et al. in 1977, we find significantly more tumours with aneuploidy and high SF in the groups of typical medullary carcinoma (TMC) and atypical medullary carcinoma (AMC) than in the small group of non-medullary carcinoma (NMC), which seems a paradox, as patients with NMC have the worst prognosis. However, the number of patients in the NMC group is very small, and the percentage of aneuploid tumours is very low. In 84 protocolled patients we found no statistically prognostic importance of ploidy or SF, either in the whole group assessed or when stratifying for the histopathological subgroups. However, a prognostic influence of SF can be traced for the non-medullary cancers, according to the new definition, but not for the medullary cancers of the breast. The result emphasizes the impression of MC as being biologically different from other histological types of breast cancer.

Breast Neoplasms↗

Medullary carcinoma of the breast, prognostic importance of characteristic histopathological features evaluated in a multivariate Cox analysis.

In this study of 136 breast cancers with medullary features (MC), registered in the Danish Breast Cancer Cooperative Group (DBCG) from 1982 to 1987, we confirmed the prognostic importance of a new definition of medullary carcinoma of the breast (MC newdef) which was recently proposed by us, deduced from a previous study of a corresponding tumour material (DBCG 77-82). However, the individual histological criteria did not have the same prognostic importance as in our previous study, although prognostic trends were the same. To further improve and validate the diagnostic criteria, we combined the two populations and performed a multivariate Cox regression analysis. In the final Cox model, four histological parameters retained positive prognostic importance: (1) predominantly syncytial growth pattern, (2) no tubular component, (3) diffuse stromal infiltration with mononuclear cells and (4) sparse necrosis. We propose that these criteria are emphasized in the histological diagnosis of medullary carcinoma of the breast.

Breast Neoplasms↗

Vimentin expression in 98 breast cancers with medullary features and its prognostic significance.

The expression of vimentin, as assessed by immunohistochemistry, has been evaluated in 69 medullary carcinomas of the breast: 28 typical medullary carcinomas (TMC), 41 atypical medullary carcinomas (AMC), and 29 invasive ductal carcinomas with subtle medullary features that, however, did not fulfill the strict criteria of TMC or AMC. Immunoreactivity of at least 10% of the component cells was found in 14 of the medullary carcinomas (5 out of 28 TMC, 9 out of 41 AMC whereas only 1 of the invasive ductal carcinomas was vimentin-positive. The patients were followed for 8-13 years. No difference in recurrence-free survival or overall survival could be documented between vimentin-positive and vimentin-negative carcinomas with medullary features. No biological significance could be established for vimentin labelling in these lesions.

Breast Neoplasms↗

Lipid and biochemical changes after low-dose oral contraception.

A randomized double-blind study of the metabolic effects of 2 low-dose combined oral contraceptives was carried out in Singaporean women. The subjects comprised 58 women randomly allocated to two treatment groups (29 each): norethisterone 1 mg/ethinyl estradiol 35 micrograms (NET/EE) or levonorgestrel 150 micrograms/ethinyl estradiol 30 micrograms (LNG/EE) and a control group of 23 women using intra-uterine devices (IUD). Blood samples were taken on admission and at 3 and 12 months after pills or insertion of IUDs. Fasting glucose levels were decreased while 2h glucose and triglyceride were increased throughout the treatment period in NET/EE group [corrected]. LNG/EE group only showed significant increase of 2h glucose at 12 months and decrease of LDL cholesterol at 3 months while total cholesterol was significantly suppressed at 3 and 12 months [corrected]. The atherogenic index, LDL/HDL cholesterol was significantly reduced by 12 months. Both groups had no change in hemoglobin, hematocrit and total protein levels but alkaline phosphatase, bilirubin and aspartate transaminase (SGOT) were suppressed. While NET/EE suppressed albumin significantly, this was not observed with LNG/EE group. However, these differences observed with use of each pill preparations, were not so obvious between treatment groups and control. Changes in total, HDL and LDL cholesterol and SGOT were not significantly different than the IUD group. Furthermore, except for 2h glucose, there was no increase in the number of abnormal parameters after treatment. On the contrary, there was a reduction of abnormal values in most liver function parameters. Thus, except for glucose intolerance, the observed changes in metabolic parameters may not constitute any clinical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Pituitary histology in Cushing's disease.

OBJECTIVE: We assessed pituitary histology in patients with Cushing's disease. DESIGN: Systematic histological assessment of pituitary tissue removed at surgery. PATIENTS: Thirty-six consecutive patients cured from Cushing's disease by transsphenoidal neurosurgery. MEASUREMENTS: Microscopical examination of all available tissue removed at operation. RESULTS: After selective removal of tissue supposed to represent an adenoma in 25 patients this could be histologically verified in 18. In the 11 patients who had undergone a total hypophysectomy an adenoma could be demonstrated in three patients only, despite a systematic search of the entire pituitary gland. Only in 21 of the 36 cured patients (58%) could an adenoma be verified. CONCLUSIONS: Combining the present results with previous reports there is strong reason to believe that in some patients with Cushing's disease no histological lesion in the pituitary is verifiable.

Adenoma↗

Prevalence of antibodies against heat-stable antigens from Helicobacter pylori in patients with dyspeptic symptoms and normal persons.

Heat-stable antigens from Helicobacter pylori were investigated for the detection of serum IgG, IgA and IgM antibodies against H. pylori by an ELISA technique. Antibody titers against H. pylori were measured in 167 dyspeptic patients, of whom 96 were H. pylori positive confirmed by culture or microscopy, and in 482 controls (0-98 years). Increased IgG antibody titers were found significantly more often in dyspeptic patients with active chronic gastritis than in patients with normal morphology, as well as in H. pylori-positive patients as compared to H. pylori-negative patients, independent of the endoscopic findings. The heat-stable antigens were compared with acid glycine-extracted antigens and a high degree of concordance was found in the results obtained with the two antigen preparations. The differences in the IgA antibody titers against H. pylori between H. pylori-positive and H. pylori-negative dyspeptic patients were significant and may be useful to confirm a borderline IgG result. No differences were found in IgM antibody titer between H. pylori-positive and -negative patients. The greatest age-dependent increase in IgG and IgA antibody titers was found in children, and if a lower cut-off level is used for children than for adults, as has been proposed, the proportion of people with increased antibody titers against H. pylori would be almost constant from the age of between five and 10 years until the time between 61 and 80 years. Comparison of H. pylori IgG antibodies with IgG antibodies against Campylobacter jejuni and total antibodies against cytomegalovirus (CMV) showed a greater similarity between H. pylori and C. jejuni (R = 0.51) than between H. pylori and CMV (R = 0.22). This may possibly be caused by cross-reactions between H. pylori and C. jejuni. The H. pylori heat-stabile antigen seems not to be very different from other crude H. pylori antigens like acid glycine-extracted antigens, but purification and characterization of the antigens are needed to improve antibody assays.

Adolescent↗

Medullary carcinoma of the breast, proposal for a new simplified histopathological definition. Based on prognostic observations and observations on inter- and intraobserver variability of 11 histopathological characteristics in 131 breast carcinomas with medullary features.

In a previous study of 131 breast carcinomas with medullary features, we evaluated the diagnostic inter- and intraobserver variation and its prognostic implications using the criteria of typical (TMC) and atypical (AMC) medullary carcinoma of the breast put forward by Ridolfi et al. (1977). We found a considerable interobserver variation as well as intraobserver variation, with significant implication on prognosis, and concluded that the histopathological definition of MC must be sharpened and simplified in order to increase the diagnostic reproducibility. In the present study of the same population of 131 patients with breast carcinomas with medullary features we have examined inter- and intraobserver variation concerning 11 histopathological characteristics. Furthermore, we have analysed the prognostic importance of these 11 histopathological features, and the prognostic implications of the observed inter- and intraobserver variation. Based on the observations, we have eliminated criteria with poor inter-/intraobserver agreement as well as those implying no or minimal impact on the prognosis. We propose a new simplified histopathological definition of medullary carcinoma of the breast (MC), retaining reproducible, prognostically significant criteria (syncytial growth pattern and diffuse, moderate or marked mononuclear infiltration). The prognosis of MC, based on this definition, is significantly better than those of infiltrating ductal carcinomas grade II + III.

Breast Neoplasms↗

The Helicobacter (Campylobacter) pylori-colonized duodenal mucosa and gastric metaplasia.

Biopsies were obtained from non-ulcerated sites of the duodenum from 100 dyspeptic patients. Helicobacter (Campylobacter) pylori was cultivated from 19 of these biopsies. Active chronic duodenitis (ACD) was found in 17 biopsies and more than 5% gastric metaplasia in 20 biopsies. H. pylori as well as ACD occurred with a significantly increased frequency when more than 5% gastric metaplasia was found in the duodenal biopsies. H. pylori on metaplastic tissue without ACD was, however, seen in two cases. H. pylori was cultivated from 9% and ACD was found in 5% of the biopsies with less than 5% gastric metaplasia. Gastric metaplasia in the duodenum was found significantly more frequently in patients with endoscopic duodenitis or duodenal ulceration than in patients with normal endoscopy. No association between gastric metaplasia in the duodenum and gastric pH or serum antibodies against H. pylori was seen. This study indicates that there is an established, but not exclusive, connection between gastric metaplasia and the colonization of the duodenum by H. pylori, the most important role being played by the antral gastric mucosa rather than the duodenum.

Biopsy↗

Possible evidence of invasiveness of Helicobacter (Campylobacter) pylori.

Gastric/duodenal biopsy material from 52 patients was examined immunohistochemically for Helicobacter (Campylobacter) pylori. Specimens from 34 of the patients harboured Helicobacter pylori along the mucosal surface and 13 of these featured, in addition, immunopositive material within the lamina propria. The remaining 18 biopsies were non-reactive. This observation suggests that Helicobacter pylori can penetrate the epithelium and its basement membrane, resulting in the production of specific systemic antibodies.

Antibodies, Bacterial↗

A comparative study of the effects of a monophasic and a triphasic oral contraceptive containing ethinyl estradiol and levonorgestrel on lipid and lipoprotein metabolism.

A comparative study of the effects of a monophasic and a triphasic oral contraceptive containing ethinylestradiol (EE) and levonorgestrel (LNG) on lipid and lipoprotein metabolism was conducted on 45 Singapore women under the WHO Special Programme of Research in Human Reproduction. The women were randomly allocated to one of the two pill groups--a triphasic preparation containing low doses of LNG and EE in various proportions and a monophasic preparation of 150 micrograms LNG and 30 micrograms EE, and an additional 18 women, choosing to use IUDs, were recruited as controls. Blood samples were taken at admission, 3 and 12 months thereafter. For both pill groups, total cholesterol decreased with duration of use, while HDL cholesterol decreased slightly at 3 months and thereafter increased. LDL cholesterol decreased slightly at 3 months, returning to baseline at 12 months for the monophasic group, while remaining unchanged at 12 months for the triphasic group. The monophasic preparation appeared to lower total, LDL and HDL cholesterols to a greater extent at 3 months than the triphasic preparation. Compared with IUD users, for the monophasic group, both total and HDL cholesterols were significantly lower at 3 months and HDL and LDL cholesterols were lower at 12 months. In addition, ratios of HDL cholesterol/LDL cholesterol and HDL cholesterol/total cholesterol were significantly lower at 12 months. Changes in triglycerides were minimal for both pill groups. However, at 3 months, triglycerides for the triphasic group were significantly higher than the IUD users, but this observation was not of any clinical importance since comparison of changes with their respective pretreatment values were not statistically significant. These results indicate that these changes are related to the dosage and estrogen-progestogen ratio of the preparation. Furthermore, the monophasic preparation may have a disadvantage over the triphasic preparation since it appears to cause more disturbance in lipid metabolism. However, it is noted that these changes in lipids and lipoproteins were minimal and did not appear to be of any clinical significance.

Adolescent↗

The prognostic importance of syncytial growth pattern in medullary carcinoma of the breast.

The histopathological criteria for medullary carcinoma of the breast (MC) used by most pathologists today were delineated by Ridolfi et al. in 1977. The prime criterion is: "A predominantly syncytial growth pattern", predominantly being defined as including 75% or more of the tumour. However, no indication has been given as to why this limit was set at 75%. The present study analyzes the prognostic importance of the extent of syncytial growth in a population of 102 breast cancers with medullary features. Generally, we find a positive prognostic influence of an extensive syncytial growth. The prognostic importance of setting the limit for predominantly syncytial growth at 90% and at 75%, respectively, is evaluated. This comparative study provides no basis for changing the definition of predominantly syncytial growth pattern.

Breast Neoplasms↗

Inter- and intraobserver variability in the histopathological diagnosis of medullary carcinoma of the breast, and its prognostic implications.

One hundred thirty-one breast carcinomas with medullary features, registered in the Danish Breast Cancer Cooperative Group from 1977-1982, have been histopathologically reviewed by two senior pathologists and classified as typical medullary carcinoma (TMC), atypical medullary carcinoma (AMC), and non-medullary carcinoma (NMC). Diagnostic criteria were based on those put forward by Ridolfi et al. and Fisher et al. The procedure was repeated with an interval of about one year by both pathologists. The diagnostic interobserver agreement was 72% with a Kappa of 0.55. The intraobserver agreement was 77% and 63% with Kappa values of 0.64 and 0.44, respectively. To see whether the observed inter- and intraobserver variability had any prognostic implications, diagnostic subgroups for both pathologists were analyzed with Kaplan Meier plots for recurrence-free survival (RFS) and with log rank tests. In the first evaluation pathologist 1 segregated a group of TMC with a significantly better RFS than for the NMC group, and pathologist 2 segregated a group of TMC with a corresponding strong trend. These findings could not, however, be reproduced in the second evaluation. The study indicates that the criteria of TMC and AMC as proposed by Ridolfi et al. need to be sharpened and simplified in order to reduce inter- and intraobserver variability. Larger studies with a control group of infiltrating ductal carcinomas are mandatory to elucidate the clinical importance of the diagnoses of Typical and Atypical Medullary Carcinoma of the breast.

Actuarial Analysis↗

Campylobacter pylori detected by indirect immunohistochemical technique.

An immunohistochemical assay for staining C. pylori is described. The method is compared with cultivation of C. pylori and observation of campylobacter-like organisms (CLOs) in hematoxyline-eosine (HE) stained sections. Eighteen biopsies from which C. pylori was cultivated but not seen in HE stained sections and three culture negative biopsies with CLOs seen in HE stained sections were selected from 331 biopsies including 113 culture positive biopsies. There were agreements between cultivation of C. pylori and CLOs seen in HE stained sections in the remaining 310 biopsies. Fourteen of the 18 and one of the three biopsies were found positive by the immunohistochemical assay. In addition 21 culture-positive control biopsies and one of 18 culture-negative control biopsies were also found positive. When the immunohistochemical assay was compared with cultivation the predictive value of positive result is 93% and of negative result 89%. By this method we were able to detect single organisms and no cross-reactions to other curved bacteria on the gastric epithelium were observed.

Bacteriological Techniques↗

Heterogeneity of secretory granules of silent pituitary adenomas.

Silent pituitary adenomas were compared with hormonally active tumors taking into account the size, number, and ultrastructural characteristics of secretory granules (SG). The study group (a total of 79 primary pituitary adenomas) comprised 27 silent, 21 growth hormone (GH)-producing-, 16 prolactin (PRL)-producing-, 5 GH-PRL-producing- and 10 adrenocorticotropic hormone (ACTH)-producing adenomas. The SG of silent adenomas were significantly smaller than SG in endocrine active adenomas. All hormonally inactive tumors also contained small (mean, 94 nm) specific cytoplasmic granules, designated "silent adenoma granules" (SIG). The fine structural features of the SIG included: a flocculent, granular material occupying an eccentric position in a larger vesicle limited by a double membrane. In the silent adenomas this particular granule was present in up to 90% of the adenoma cells and constituted approximately 10 to 50% of the granules in each cell. These granules were not seen in hormonally active tumors and considered therefore diagnostic of silent pituitary adenomas.

Adenoma↗

Light bodies in human pituitary adenomas.

Light bodies are large cytoplasmic granules originally described in the gonadotrophic cells of the rat pituitary gland. In order to determine whether similar bodies occur in the human anterior pituitary gland, 89 pituitary adenomas and periadenomatous tissue from 20 cases were examined by transmission electron microscopy. Double membrane bound bodies with filamentous internal structure identical to rodent light bodies were identified in 10 hormone-producing adenomas: 5 PRL, 1 PRL-GH, 2 GH, and 2 ACTH-producing tumours. No light bodies were found in the remaining 79 tumours nor in the pituitary cells in periadenomatous tissue from 20 cases. These results show that some human pituitary adenomas may contain light bodies identical to those seen in gonadotrophs of rat pituitary.

Adenoma↗