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Biomedical subjects

W Meyer

Publications and source records attributed to W Meyer.

At least 235 records · Page 13Linked to original sources

Histological grading of breast cancer. Interobserver, reproducibility and prognostic significance.

A study was conducted to assess the reproducibility and prognostic significance of the histopathological grading by using the criteria of Bloom and Richardson. 166 breast carcinomas of the invasive ductal type (NOS - not otherwise specified) according to the WHO criteria, selected from the biopsy material of the years 1980 to 1988 were investigated. 85 of the patients presented axillary lymph node metastases in the mastectomy specimens. A satisfactory correlation of histopathological grades assessed by three pathologists was found in 72.3% of all cases. Fifteen cases (9%) were over- and 31 cases (18.7%) were underestimated compared with an expert's grade. A disagreement of two grades occurred in one case only. In comparison of grade 1 and grade 3 tumours as well as of grade 2 and grade 3 tumours significant differences in the overall survival could be found. Irrespective of statistically significant differences between the three grades in actuarial survival, the histopathological grading is of rather low value for the prediction of prognosis of individual patients.

Breast Neoplasms↗

[Results of flow image analytic DNA determination in histologic preparations of malignant tumors].

The steadily increasing interest in DNA and ploidy determination of malignant tumours led to an increased application of flow image cytometric methods in tumour research and clinical pathology for some years. The investigations are mainly designed to explore the proliferative capacity and deviations in the characteristic DNA-content, finally to obtain clues about the actual malignancy grade and the prognostic outcome of a given malignant tumour therapy. The results of the study on 84 breast and 30 gastric cancers show the principal opportunity to use image cytometric techniques for DNA determination in histological sections. Apart from all disadvantages of these methods compared with flow cytometry, the image cytometry is capable of giving prognostic information with respect to survival as well as to the metastatic potential. Although several significant differences exist between the prognostic subgroups in seven and four DNA parameters, respectively, the case-related decision is not satisfying the clinical demands. Gastric cancers did not show any significant differences on the single-parameter level. Single distinct DNA parameters having the same diagnostic importance in both different tumour types and different prognostic problems could not be found.

Adenocarcinoma↗

[Cell nucleus analyses on the heterogenicity, proliferation and metastasis of malignant tumors].

The heterogeneity of primary and metastatic tumors was studied on the basis of their nuclear images. Feulgen-stained tissue sections of invasive ductal carcinomas of the breast (84 primaries, 15 lymph node metastases), adenocarcinomas of the stomach (30 primaries) and colorectal adenocarcinomas (30 primaries, 10 lymph node metastases) were investigated by high resolution image analysis. At least 150 tumour cell nuclei as well as 50 diploid reference cells were measured in each case. By means of multivariate statistical analysis significant differences could be found between primary tumors with and without lymph node involvement or distant metastases. In contrast, in a majority of the cases primary tumors and their metastases were largely identical with regard to the nuclear image and the DNA content. Features with high discriminant power for differentiation of metastasising tumors and malignant tumors without metastatic spread were the nuclear area, the number of coarse chromatin particles and other descriptors of the chromatin structure. The DNA content as a useful tool for the prediction of prognosis was of minor importance for the prediction of the metastatic phenotype.

Adenocarcinoma↗

[Grading, staging, DNA content and prognosis of invasive ductal breast cancer].

The importance to prognostication of grading, staging, and image cytometric DNA parameters was investigated in 84 cases of invasive ductal mammary carcinoma. Correlations between tumour size, lymph node condition, and five-year survival were shown to be statistically significant. Similar correlations were found to exist between the grade of histopathological malignancy and various DNA parameters derived from the DNA histogram. However, the relevance of all the above single factors has proved to be of limited value in the individual tumour case. Multivariate analysis of DNA parameters, 80.3 percent in probability, was found to enable the best prognostic prediction of an individual course. These results suggested nuclear DNA content to be an objective marker of biological behaviour of a given tumour.

Adult↗

Application of malignancy-associated changes of the cervical epithelium in a hierarchic classification concept.

For almost 10 years malignancy-associated changes (MAC) have been consistently found by means of high resolution image analysis of apparently normal uterine cervical cells. This study was performed on Feulgen-stained monolayer specimens from 55 healthy women and 19 patients suffering from various stages of cervical neoplasia. About 200 epithelial cells and 30 trout red blood cells in each case were measured by image cytometry at a spatial resolution of 0.27 micron. The philosophy of classification is based on the hierarchic stepwise definition of 'truly normal' specimens by removal of all suspicious specimens, characterized by the presence of atypical cells or subvisually altered cell populations. The suitability of MAC-sensitive classifiers, in combination with classifiers for the recognition of atypical cells, was demonstrated. The demands of automated prescreening were met by several decision tree procedures (95-100% sensitivity, 85-95% specificity). By focussing on the MAC evidence a new risk group from seemingly healthy women may be defined.

Cervix Uteri↗

[Laser therapy of colorectal tumors].

Between Jan. 1, 1986 and March 31, 1988 a total of 128 patients with tumours of the colon and rectum were treated by Nd-Yag laser at Nürnberg City Hospital. There were 36 benign and 92 malignant lesions. The indications for laser therapy were stenosis, bleeding, spasms of the pelvic floor and increased mucous production. Initial control of these problems could be achieved in 105 patients (82%), however, the symptoms recurred in 50% of the malignant and 47% of the benign tumours. Complications of laser treatment were encountered in 13 patients necessitating an operative intervention in 6. In all, 34 patients underwent additional surgery after laser treatment. Most frequently, a diverting colostomy had to be provided (n = 18) while 12 patients underwent anterior resection; in three an abdomino-perineal resection was performed and in one patient a Hartman procedure was necessary. The median observation time of patients with benign tumours is, at present, 16 months with 72% being free of disease. In malignant tumours the median survival time of patients with laser therapy only is 4.5 months; those with additional surgical treatment survived a median of 17.5 months.

Adult↗

Relation of positive inotropic and chronotropic effects of pimobendan, UD-CG 212 Cl, milrinone and other phosphodiesterase inhibitors to phosphodiesterase III inhibition in guinea-pig heart.

(1) This study was performed to elucidate the relation between positive inotropy and phosphodiesterase inhibition in the heart. Therefore, the influence on the activity of guinea-pig cardiac phosphodiesterase (PDE) I-III separated by DEAE-cellulose anion exchange chromatography was investigated for the new cardiotonic agents pimobendan, its metabolite UD-CG 212 Cl and milrinone. These effects were compared with those of various other PDE inhibitors such as IBMX, zaprinast, rolipram and AR-L 57 Cl. A selectivity factor (SF, mean of the IC50 values for PDE I and II inhibition divided by the IC50 for PDE III) was calculated for each drug. The greater this value the more selective was the PDE III inhibition. (2) UD-CG 212 Cl was the most potent (IC50 = 0.19 mumol/l) and most selective inhibitor of PDE III with a SF of 869. Also selective PDE III inhibitors were pimobendan (SF = 50.5) and milrinone (SF = 70.0) with slightly smaller potencies (IC50 = 2.40 and 1.52 mumol/l, respectively). Zaprinast and rolipram preferentially inhibited PDE I and II, respectively. IBMX and AR-L 57 Cl inhibited PDE I-III unselectively with similar potencies for all isoenzymes. (3) The PDE inhibitory effects of all substances were compared with their influence on force of contraction (electrically driven papillary muscles) and on frequency of beating (spontaneously beating right auricles) in guinea-pig hearts, thus in preparations of the same species. UD-CG 212 Cl and pimobendan resembled each other in their maximal positive inotropic effects with potencies (EC50) of 1.8 mumol/l and 6.0 mumol/l, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Grading and prognosis of invasive ductal mammary carcinoma by nuclear image analysis in tissue sections.

In primary tumours of 84 patients with invasive ductal carcinomas the prognostic significance of the nuclear image was assessed. Feulgen stained tissue sections were investigated by image cytometry. At least 150 tumour cell nuclei as well as 50 lymphocytes or trout erythrocytes for diploid reference were measured in each specimen. 35 morphological features, including those of the chromatin pattern, were derived from the digitized nuclear images. By means of multivariate discriminant analysis, significant differences could be found between tumours of 41 node-negative and 43 node-positive patients. The differences were sufficiently large to distinguish subgroups with low and high risk of lymph node involvement. Irrespective of lymph node status, 66 patients with an adequate 5 year follow-up were divided into two groups according to their survival time. The classification results revealed a clear relationship between characteristics of the nuclear image and prognosis. By image cytometry it is thus possible to separate both node-positive and node-negative patients into subgroups with increasing risk of recurrence. The results indicate that nuclear image analysis provides prognostic information in addition to established prognostic factors, such as histological grade and tumour stage.

Adult↗

Basal and isoprenaline-stimulated cAMP content in failing versus nonfailing human cardiac preparations.

We measured force of contraction and cAMP content in human isolated electrically driven right ventricular trabeculae carneae with and without the addition of isoprenaline (0.2 microM). Basal cAMP content was approximately 200% higher in preparations from nonfailing hearts than from hearts with end-stage myocardial failure. Isoprenaline was less effective in increasing force of contraction in failing (by approximately 100%) than in nonfailing cardiac preparations (by approximately 500%). With isoprenaline, cAMP content was approximately 50% lower in failing than in nonfailing preparations. We conclude that the reduced increase in force of contraction of failing human cardiac preparations with isoprenaline added may be causally related to an inadequately increased cAMP content.

Cyclic AMP↗

Phosphodiesterase inhibition and positive inotropic effects.

Many newly developed positive inotropic agents are phosphodiesterase inhibitors. In the heart at least four phosphodiesterases (PDE I-IV) have been isolated. Depending on the species investigated, the positive inotropic effects of the PDE inhibitors appear to be correlated to the inhibition of a soluble or particulate PDE III or to a particulate PDE bound to the sarcoplasmic reticulum. In human ventricular tissue isolated from hearts with end-stage heart failure due to idiopathic dilated cardiomyopathy the positive inotropic effect of phosphodiesterase inhibitors is greatly reduced compared to healthy controls. This cannot be explained by an impaired sensitivity of the PDEs because the PDEs were similarly inhibited by PDE inhibitors in both healthy and diseased hearts. However, because the reduced positive inotropic effect is accompanied by a reduced increase in cellular cAMP concentration, an impaired formation of cAMP by the adenylate cyclase is probably involved. The impaired adenylate cyclase activity can result from an increased inhibitory GTP-binding protein (Gi-protein) recently observed in failing hearts.

Animals↗

Histochemistry of glycoconjugates in the skin of the bovine muzzle, with special reference to glandular structures.

The distribution of glycoconjugates in the muzzle of young adult Holstein cows has been studied by means of selected light-microscopic histochemical methods, including lectin histochemistry. In the skin layers, strong reactions were confined to intercellular substances in between the cells of the vital epidermis, exhibiting neutral glycoconjugates mainly with alpha-D-galactosyl and N-acetyl-D-galactosaminyl residues. In the nasolabial glands, distinctly positive staining for neutral glycoproteins with various saccharide residues (alpha-D-galactose, alpha-N-acetylgalactosamine, D-galactose-beta(1----3)D-N-acetylgalactosamine, beta-D-galactose), and for smaller amounts of acidic glycoconjugates, was found in the secretory cells and the luminal secretion. The cells of the excretory duct system showed weak to moderate reactions (alpha-D-galactose, beta-D-galactose), only the collecting ducts reacted positively for acidic glycoproteins with sialyl residues. The results obtained are discussed in view of muzzle function, with special reference to the salivary nature of the secretion of bovine nasolabial glands.

Animals↗

Quantitative morphology of primary and metastatic tumors: comparative studies on tissue sections.

Feulgen-stained tissue sections of 84 invasive ductal carcinomas of the breast (IDC), 30 colorectal adenocarcinomas (ACC), 30 gastric adenocarcinomas (ACG), 10 lymph node metastases of squamous cell carcinomas (SCC) and 11 lymph node metastases of malignant melanomas (MM) were investigated by image cytometry at a spatial resolution of 0.25 micron. At least 150 tumor cell nuclei were measured in each case. By means of multivariate statistical analysis the specificity of the nuclear image for different histological tumor types could be demonstrated in lymph node metastases of SCC and MM. Nuclear image analysis therefore may be a useful tool for pathologists in making the differential diagnosis on metastases of unknown primary tumors. For IDC, ACG and ACC the metastatic phenotype could be identified by nuclear image analysis of the primary tumors. The prognostic significance of the nuclear image has been proved in adenocarcinomas of the stomach. Features of chromatin structure played an important role in both the diagnosis of doubtful histological tumor types and the prediction of lymph node involvement or prognostic outcome.

Cell Nucleus↗

Lectin histochemical aspects of vascular development in fetal mammalian skin.

The study describes lectin reactivity of the developing vascular network in fetal mammalian skin. Skin samples were taken from fetuses of different gestational age of the pig, the goat and the cat. Clearly positive, endothelial lectin staining of capillaries and smaller vessels could only be obtained during mid gestation. The sequence of lectin reactivity, demonstrating: 1st alpha-D-N-acetylglucosamine and N-acetyl-alpha-D-galactosamine, 2nd alpha-D-galactose and sialic acid, and 3rd alpha-L-fucose, sialic acid and probably alpha-D-mannose/alpha-D-glucose residues, emphasizes different stages of cell surface coat as well as of cell membrane development. Thus, the typical outgrowth period of developing integumental blood vessels is reflected histochemically.

Animals↗