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M Oberholzer

Publications and source records attributed to M Oberholzer.

At least 19 recordsLinked to original sources

Densitometric and morphometric study of immunocytochemical estrogen receptors detection in breast carcinomas.

Immunohistochemical quantitative evaluation of estrogen receptors (ER) detected in tissue sections from 30 breast tumors by monoclonal antibody was performed using a densitometric method. In particular, ER concentration was calculated by nuclear mean optical density (nMOD), while heterogeneity in ER content was calculated by the coefficient of variation (CV) of the nuclear optical density histogram. Tumors which showed more than 60% of positive cells had a mean value of ER-nMOD of 0.116 +/- 0.002 a.u. and of ER-CV of 33.74 +/- 0.68. Tumors which showed 30% to 60% of positive cells had a mean value of ER-nMOD of 0.082 +/- 0.006 a.u. (arbitrary units) and of ER-CV of 36.25 +/- 3.44. Tumors showing less than 30% of positive cells had ER-nMOD of 0.052 +/- 0.009 a.u. and ER-CV of 48.49 +/- 5.61. These results indicate that the greater the concentration the lower the ER heterogeneity within the tumor sample. No significant differences between ER-ICA results, nuclear size and form factors were found.

Breast Neoplasms

Cytometry in histological sections of colon carcinoma.

A short description of a project of cytometry in histological sections of colon carcinoma is given with emphasis on the methodical aspects. Possible strategies of cytometric measurement and problems related to it (focus, overlap, segmentation of objects) are described. The main effort concerns interactive selection of tumor cells and the segmentation in cases of densely distributed and overlapping nuclei. All other succeeding processing steps are performed fully automatically. The resulting quantitative features are stored together with the original images on an optical disk for further examinations and reexaminations, allowing the direct relation of feature values to visual image content. The evaluation of the features as well as their interpretation is only at the beginning. Especially the problem of relating section information with true 3-dimensional information is not described here and necessitates further research. In a first investigation only a few tumors without and with metastases were analyzed. The preliminary results correspond with findings of Kunze et al.

Cell Nucleus

Age-related modification of average volume and anisotropy of vascular smooth muscle cells.

The aim of this study was to determine what changes in the arterial wall are related to age. In two groups of rabbits, one young and one adult, the aorta and carotid were studied using a morphometric approach based on stereological axioms and planimetric morphometry. The problem of anisotropy of smooth muscle cells is discussed in detail. Two forms of anisotropy must be distinguished, that of single cell and that due to the histological pattern of the smooth muscle cells in the arterial wall. Our results show in adult animals, as compared to the young ones, statistically significant decrease in anisotropy of the cell pattern which tends to become more regular. Moreover, in aorta and carotid of young and adult animals there is an increment of 95.39% and 80% of the absolute cell volume, respectively. We suggest that there may be a direct relationship between aging and phenotypical modulation of the smooth muscle cells and that the modification of the architectural cell pattern with age may represent an adaptive event related to the change in forces acting upon the arterial wall.

Aging

Morphological, immunohistochemical, stereological and nuclear shape characteristics of proliferative Leydig cell alterations in rats.

Proliferative Leydig cell (LC) alterations (hyperplasia, adenoma) of laboratory rats often pose diagnostic problems because the progression from normal to hyperplasia to neoplasia is continuous. The LC compartments of 130 Wistar rats (kfm: WIST strain) of approximately 2 years of age were examined. Ten typical cases conventionally classified as being normal or as showing diffuse or focal hyperplasia or small or large adenomata were investigated in more detail. In large adenomata, areas with large and small LC nuclei were identified. Immunohistochemical characterization, EM examination, as well as stereologic and planimetric investigations were performed. Hyperplastic and neoplastic LC essentially retained their normal appearance and immunohistochemical characteristics, but were found to contain more lipid droplets, fibroblast-like cells and patches of collagen than normal LC at the EM level. LC proliferation was accompanied by significant LC hypertrophy. LC nuclei of hyperplastic LC compartments were slightly larger while those of LC adenoma were markedly larger than nuclei of normal LC. The values for circle-related and ellipticity factors indicated that the nuclei of normal and hyperplastic LC were more markedly oval than nuclei of neoplastic LC. Concavity factor and bending energy measurements revealed that the small and oval nuclei of normal and hyperplastic LC had significantly more and deeper indentations than the larger and somewhat rounder nuclei of neoplastic LC. It is concluded that LC proliferations conventionally diagnosed as hyperplasia or adenoma on the basis of their size were composed of cytologically different LC populations.

Adenoma

The efficacy and tolerability of cyclosporine G in human kidney transplant recipients.

Twelve consecutive first cadaveric kidney transplant recipients received cyclosporine G (CsG)(initial dose 12 mg/kg per day) as basic immunosuppressive treatment along with prednisone (initial dose 0.5 mg/kg per day) for the first three months after transplantation. Thereafter CsG was replaced by Sandimmun (cyclosporine, CsA). Evaluation of the immunosuppressive efficacy and assessment of possible side effects of CsG was made and compared with the results in 38 historical control patients starting with the same dose of CsA as part of the same immunosuppressive dosage schedule. Statistically, there was no difference in patient survival at three (91% in CsG group versus 95% in CsA group) and twelve months (91% in CsG group versus 92% in CsA group), or in graft survival at three (75% in CsG group versus 89% in CsA group) and twelve months (75% in CsG group versus 84% in the CsA group). At equivalent oral doses of CsG and CsA significantly higher blood levels of CsG were observed (2P less than 0.05). Nephrotoxicity assessed by graft biopsy could be demonstrated to a similar extent in both groups, whereas hepatotoxicity was more pronounced during CsG treatment. Sequential measurements of bilirubin revealed a significant increase in all patients but median values were significantly higher in the CsG patients. A pronounced and concordant elevation of liver enzymes occurred during CsG treatment in three out of 12 patients. Liver biopsies performed in these patients revealed histological alterations consistent with toxic liver injury. Thus, in human kidney transplant recipients CsG and CsA appeared to be equally immunosuppressive and nephrotoxic but more hepatotoxic. On the basis of this limited experience we conclude that in human kidney transplant recipients CsG has no advantage over CsA.

Adult

Elevated proinsulin levels related to islet cell antibodies in first-degree relatives of IDDM patients.

OBJECTIVE: To assess whether proinsulin levels are elevated in first-degree relatives of insulin-dependent diabetes mellitus (IDDM) patients and whether there is a relationship between proinsulin levels and the occurrence of immunological markers. RESEARCH DESIGN AND METHODS: Fasting proinsulin concentrations were measured in 85 first-degree relatives (54 siblings, 20 parents, 11 children) of IDDM patients and in 90 age- and weight-matched control subjects with no family history of diabetes mellitus. RESULTS: Fasting proinsulin levels (median, 25th, and 75th percentiles) were 8 pM (range 3.2-14 pM) in first-degree relatives and 1.7 pM (range 1.7-4 pM) in control subjects (P less than 0.0001). Proinsulin was significantly elevated in siblings (7.2 pM, range 3.8-15 pM; P less than 0.0001), parents (9.8 pM, range 6.4-13 pM; P less than 0.0001), and children (6.6 pM, range 1.8-12 pM, P = 0.04) compared with control subjects but without differences between these groups. Islet cell antibody positive (ICA+) IDDM relatives had significantly higher proinsulin levels than ICA- (16 pM; range 7.2-25 vs. 6.9 pM, range 3.1-12 pM; P = 0.02). There was no difference between individuals with and without insulin autoantibodies. No difference in proinsulin levels was observed if the relatives were subdivided according to HLA-DR sharing with the diabetic proband. CONCLUSIONS: Fasting proinsulin concentrations were raised not only in siblings but also in parents and children of IDDM patients. Because proinsulin is more elevated in ICA+ than in ICA- subjects, increased proinsulin levels could reflect minor beta-cell damage due to previous immunological attack.

Adult

Long distance image transfer: first results of its use in histopathological diagnosis.

Histopathological images were transferred by use of normal telephone lines between three pathology institutes located in three different cities in the FRG. Images were digitized using a colour TV camera and stored in a special computerized image transmission system. The stored image was transferred and visualized on a (receiver) colour TV screen after dialing the telephone number connected to the receiver image transmission system. An additional telephone dialogue was activated by use of a normal acoustic telephone, and the diagnostic difficulties of the underlying image were discussed. Diagnostic assistance was possible in all transferred cases as well as histopathological diagnosis. Resolution of the images was set at 512 x 512 pixel x 8 bit. Image transfer time was 3.2 min on average. The differences between the original and transferred image were measured by "retransfer" of the original image and by subtracting the two images from each other. No major transfer errors could be measured.

Breast Neoplasms

[Morphology and function of macrophages in AIDS in broncho-alveolar lavages (BAL)].

HIV infects susceptible T-cell and mononuclear phagocyte targets. Unlike the dramatic changes that occur with T-cells during HIV disease, changes in monocyte and macrophage phenotype and function are qualitatively minimal. The aim of the study was to quantitatively analyze the morphology of macrophages in broncho-alveolar lavages in patients without AIDS, with AIDS, with AIDS complicated by Pneumocystis carinii and in carcinoma patients. In patients with AIDS, the nuclei of macrophages demonstrate a higher integrated optical density (2P less than 0.10), are bigger in size (2P less than 0.05) and have less notches (2P less than 0.02).

Acquired Immunodeficiency Syndrome

[What role does informatics play in pathology?].

Informatics can be understood as an element of management, dealing with structures of files, algorithms and hardware. The most important prerequisite to successful use of informatics is an optimal compatibility between these single elements. To realize this compatibility and to ascertain a permanent operability of informatics in pathology, the realization of the following two conditions are advisable: 1) The differentiation between a general administrative system of the whole department of pathology and systems of special units (e.g. laboratories); 2) the modularity of the laboratory systems.

Humans

Some fundamental aspects of morphometry in clinical pathology, demonstrated on a simple, multipurpose analysis system.

The aim of this study was (1) to investigate the value of morphometry, (2) to fix a set of parameters suitable for analyzing diagnostic problems, and (3) to create a general strategy for data storage and for user-friendly data management. The intrinsic value of morphometry lies in the fact that in contrast to other morphologic methods, it permits the presentation of findings in the form of numbers. The following set of morphometric parameters, in the broad sense of the term morphometry, is standard in our laboratory: planimetric parameters (shape descriptors), parameters of the gray value histogram (descriptors of the general gray value distribution), texture parameters (descriptors of the correlation between various image segments), invariant moments (descriptors of the size and localization of textural image segments) and densitometric parameters. The introduction of morphometric procedures into the daily routine is facilitated if data registration and evaluation are performed separately. Original data generated by direct measurement are primary or raw data, which are stored as such. In a separate, second step these raw data are used to compare more or less complex morphometric parameters, which are called "secondary data". A system designed for separate data registration and evaluation can easily be adapted to new methodologic developments. For instance, primary data on objects (gray values, coordinates of the contour) measured one time in the past can be reused at any other time for computing new features from these data. This procedure is comparable to the possibilities in immunohistochemical staining: new immunohistochemical stains can be applied to newly prepared sections of old tissue blocks.

Computer Communication Networks

[Prerequisites for the application of statical morphometry in diagnostics].

The aims of the present paper were: 1. to test a set of parameters suitable for quantifying morphological features; 2. to create a generally valuable strategy for data storage and for a user friendly data management; 3. to examine the parameter set and the conception for an optimal data management by the quantification of cytological specimens of pleural effusions. The significance of a distinction between "primary parameters" (data directly captured during the measurement) and "secondary data" (data calculated from the primary data) is explained. In the first step of classification of the cytological specimens 81.8% of the patients with reactive alterations of mesothelial cells (n = 11) and 100% of the patients with tumours (mesotheliomas and metastasis of adenocarcinomas) (n = 19) were correctly classified with the aid of a little "expert system". In the second step (discrimination between mesotheliomas (n = 6) and metastasis of adenocarcinomas (n = 13] all patients were correctly classified.

Cytodiagnosis

Electron microscopic stereological analysis of the normal human prostate and of benign prostatic hyperplasia.

Normal and benign hyperplastic prostatic tissue was studied by quantitative electron microscopic measurements. Quantitative morphological procedures provide values for volume, surface, number of tissue and cellular components within human prostatic tissue. When a comparison is made of the stereological data of the glandular cell of benign prostatic hyperplasia to that of the normal human prostate no statistically significant difference in the relative volumetric amount of the cell organelles is indicated. An attempt was made to characterize the fine structure of the smooth muscle cells of the stromal area (fibromuscular) in normal and benign hyperplastic prostatic tissue. In benign prostatic hyperplasia a significant increase in the relative amount of organelles in the smooth muscle cell was found, indicating an activation of these cells. Light microscopic analysis has revealed that benign prostatic hyperplasia is primarily a stromal disease.

Cytological Techniques

Light microscopic stereological analysis of the normal human prostate and of benign prostatic hyperplasia.

Normal prostate glands from 6 men less than 30 years old and enucleated tissue of benign prostatic hyperplasia were analyzed by stereological methods. Studies on the relative volumetric amount of fibromuscular (stromal) and glandular areas of the gland reveal no statistically significant difference between the inner and outer parts of the normal prostate and between the inner part of the normal prostate and benign prostatic hyperplasia. However, in benign prostatic hyperplasia there is a significant increase in the volumetric amount of the fibromuscular tissue and a decrease in the glandular area compared to the outer part of the normal prostate and the whole normal prostate (sum of the inner and the outer parts). These stereological data are discussed with respect to the pathogenesis of benign prostatic hyperplasia.

Adult

Morphologic findings in central bronchi correlated to lung function data in obstructive airways disease.

Quantitative analyses of morphologic findings are the condition of clinico-pathological correlation studies. These quantitative analyses are possible by morphometry. The present correlation study shows that morphometry may therefore contribute to understanding the pathogenesis of obstructive airways disease: decreasing bronchial lumen and increasing volume of grandular ducts are correlated to increasing airways resistances (clinical parameters: RAW, FEV1). Increasing volume of bronchial muscles is correlated with resistance of airways at quiet breathing (RAW) and less with increasing residual volume (RV). Increasing volume of bronchial glands and glandular ducts is correlated with increasing resistance at forced expiration which is clinically shown by decreasing FEV1. These findings can be interpreted as follows. Airway resistances are mainly influenced by airway narrowing. At quiet breathing, muscle constriction is an additional cause of increasing airflow resistance due to bronchial narrowing. At forced expiration, however, mucus plugs probably limit the airflow because thickening of bronchial glands points to increased secretory activity. Until now it is not possible to understand why bronchial muscle volume correlates with residual volume.

Adult

Lung biopsy: methods, value, complications, timing, and indications.

Six methods of lung biopsy are discussed on the basis of literature reports: 1. Aspiration biopsy by fine needle, 2. split needle biopsy (Vim-Silverman), 3. cutting needle biopsy (Travenol), 4. trephine biopsy by rotating needle, 5. transbronchial biopsy, 6. open biopsy. Because of the high risk, biopsies with thick needles (methods 2--4) should be abandoned. Transbronchial biopsy is renounced because reliable results are only achieved in sarcoidosis which can be clearly diagnosed in high percentage of cases by other less dangerous procedures. In solitary tumors which could not be diagnosed by any other means aspiration biopsy is indicated because of its low risk and its diagnostic accuracy of more than 80%. In disseminated pulmonary disorders which cannot be diagnosed by any other means open lung biopsy is the most reliable method. The lung specimens can be taken under eye control. They should contain tissue from the transitional zone between diseased and unchanged areas, however. The specimens are usually big enough for additional electron and fluorescence microscopic examinations as well as dust analyses. The pathologist must be aware of all clinical data including X-ray pictures, laboratory findings, case history, and history of occupational and nonoccupational dust exposure. If these conditions are fulfilled and adequate methods are applied, lung biopsy provides diagnosis and prognosis, makes causal therapy possible, and amplifies the medical knowledge of pulmonary diseases.

Biopsy

[Morphometry in central bronchi and tissue sections. A supplemental method in pneumopathology].

Comparative clinical-pathological studies of pneumopathology call for quantitative analyses of bronchi and pulmonary tissue. Quantification of pathological findings is possible by morphometry. The most important stereologic definitions and the laws of morphometry are briefly described. Methodologic problems are discussed. Baseline data of central bronchi of 5 autopsy cases are calculated (volume densities of the different tissue compartments and the surface density of bronchial basement membrane in three reference volumes). The five patients had normal lung function tests during life.--Further, the grading of emphysema by point-counting on papermounted macrosections is reported. Grading of emphysema on lung slices correlated very well with grading of emphysema by point-counting.

Autopsy