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Biomedical subjects

R S Fritsch

Publications and source records attributed to R S Fritsch.

At least 19 recordsLinked to original sources

[Scintigraphy using 131I in oxyphilic carcinomas of the thyroid gland].

The aim of the study was to ascertain the role of 131I scintigraphy (RIS) in the follow-up of oxyphilic thyroid carcinomas (OTC). It is discussed that metastases (M) and local recurrencies (LR) are incapable of accumulating 131I sufficiently; therefore, the usual strategy of RIS cannot be used for follow-up. The re-examination of 91 patients suffering from OTC showed that 10/20 patients with M/LR did have a positive uptake of 131I, which could be used for therapy in 8 patients. An ablation of M using high-dose 131I therapy could be demonstrated in three younger patients who had cervical lymph node M 3 months after thyroidectomy as an early manifestation of their disease. In three patients RIS first led to the metastatic site. The clinical course of patients with distant M that developed at a later stage was unfavourable, even though they did accumulate 131I. Patients with positive uptake of 131I in M/LR were significantly younger (55a) than patients who had no uptake (67a) and belonged more often to stage I and II of UICC, namely 7/10 vs 2/10. RIS should be used especially in an early interval after thyroidectomy and individually for follow-up: as a diagnostic method and therapeutic instrument.

Adult↗

Histomorphometry in paraffin sections of thyroid tumors.

Planimetric features of cell nuclei in paraffin-embedded histological sections of benign and malignant thyroid tumors, as well as normal thyroid tissue as control, were determined by means of a semiautomatic system. The main aim was to objectify possible quantitative differences between adenomas and carcinomas of the thyroid gland, which had recently been reported by several authors. For each nuclear profile, the area, the maximum diameter as well as two form factors were calculated. Statistical analyses of morphometric differences between normal controls, oxyphilic adenomas and carcinomas, and between follicular adenomas and carcinomas were performed using the T-test, a multivariate test, and a discriminant analysis. The tests revealed significant differences between controls and all other groups. The most striking result, however, was the total discrimination between follicular adenomas and carcinomas, with no false reclassification. Carcinomas had a higher mean nuclear area and diameter and a lower form factor. A similar reliability of discrimination could be obtained by comparing these morphometric values in oxyphilic adenomas and carcinomas. When using a test set of 9 cases (4 adenomas, 5 carcinomas), only one adenoma was falsely reclassified as a carcinoma by the discriminant analysis. Our results thus allow the conclusion that planimetric nuclear measurements indeed seem to be useful for the objectivation of cytomorphologic differences between adenomas and carcinomas of the thyroid gland.

Adenoma↗

[The clinical course of oxyphilic carcinoma of the thyroid].

In a total of 1665 patients with malignant thyroid neoplasms 90 oxyphilic thyroid carcinomas (OTC) were found of whom 55 could be re-examined and newly classified. Morphological and clinical parameters influencing the clinical course were determined. During a mean follow-up period of 6.5 y metastases or local recurrent disease occurred in 12 patients (24%). Apart from 3 early manifestations of metastases, 9 patients developed recurrent disease within, on average, 4.7 y after thyroidectomy: local lymph node metastases and local recurrences occurred within an average of 5.4 y, distant metastases after only 2.7 y. Thyroglobulin proved to be reliable for follow-up with a sensitivity of 88% on levothyroxine and 75% on endogenous TSH-stimulation (specificity: 98%). The frequency of metastases and local recurrences correlated with age at the time of tumor diagnosis, the degree of invasiveness and the local tumor extension (pT4 vs. pT1-3), whereas other factors such as the absolute diameter of the tumor or patient's sex had no influence on the clinical course. The survival probability for 5 and 10 years was 95 and 75%, respectively. All OTC patients should be examined regularly at least once a year by cervical sonography and thyroglobulin measurement. Because 18% recurrences occurred within 4.7 y such examinations should be repeated beyond year 5 after thyroidectomy.

Aged↗

Megakaryocytes in chronic myeloproliferative disorders: numerical density correlated between different entities.

A morphometric evaluation of number and grouping of megakaryocytes (MK) in five different groups of chronic myeloproliferative disorders (CMPD) was performed by counting 60 high power fields equaling approximately 14.28 mm2 of haematopoiesis in each case. Twenty-one up to 29 cases were evaluated for each of five categories of CMPD and one control group; a total of 132 cases of CMPD and 33 control cases were used. The mean number of MK per square millimetre was 15.54 +/- 1.53 in chronic myeloid leukaemia of common or granulocytic type (CML.CT), 69.91 +/- 5.85 in CML with megakaryocytic increase (CML.MI), 59.59 +/- 3.27 in polycythaemia vera (P. vera), 59.85 +/- 4.59 in primary thrombocythaemia (PTH), 67.58 +/- 4.11 in chronic megakaryocytic granulocytic myelosis (CMGM), and 19.7 +/- 3.07 in controls. The distinction between free or isolated MK, and between clustered or grouped MK corresponds to the total cell counts of MK in the various groups of CMPD. Clustering of MK was significantly higher in CMGM and PTH compared to other groups, but the difference between them was not statistically significant. Significant differences in the mean number of MK were obtained between controls and CML.CT on the one hand and all other groups of CMPD on the other. The results further support the histological sub-classification of CMPD according to the primary disorders of the Hannover classification (not advanced by sclerosis, fibrosis or excess of blasts, respectively).

Blood Cell Count↗

Planimetric analysis of megakaryocytes in the four main groups of chronic myeloproliferative disorders.

Planimetry of megakaryocytes (MK) was performed in bone marrow biopsies (BMBs) from patients with chronic myeloproliferative disorders (CMPD) to substantiate cytomorphologic differences in this cell lineage between the four main groups of CMPD. The biopsy specimens were classified histologically prior to morphometry, according to the Hannover Classification of CMPD. Five histological groups were investigated, evaluating between 21 and 30 biopsies in each group. The five groups were as follows: (1) Chronic myelocytic leukemia (CML) of common type (CML.CT), (2) CML with megakaryocytic increase (CML.MI), (3) polycythemia vera (P. vera), (4) primary thrombocythemia (PTH), and (5) chronic megakaryocytic-granulocytic myelosis (CMGM). The results of five variables, i.e. the cellular and nuclear size, the cellular and nuclear form factor, and nuclear segmentation, were determined in at least 50 MK per BMB. The results reveal significant differences in MK nuclear and cellular size, as well as in nuclear segmentation between CML and the three other groups in that the nuclear and cellular size of the MK in CML are smaller than in P. vera, PTH, and CMGM. Moreover, the degree of nuclear segmentation or lobulation differs significantly between the three disorders characterized by large MK. Discriminant analysis permits 78-100% reliability of reclassification by morphometry compared with the histologic classification. A reduced reliability of the morphometric classification to around 80% was found between P. vera and PTH, as well as between P. vera and CMGM. In the design of this study, morphometry of MK lends added weight to the subjective classification of these disorders.

Biopsy↗

Quantitative cytomorphology of megakaryocytes in chronic myeloproliferative disorders--analysis of planimetric and numeric characteristics by means of a knowledge based system.

Numeric and planimetric parameters of megakaryocytes have been analyzed in 162 bone marrow biopsies of patients with chronic myeloproliferative disorders--CMPD--and controls by means of an inductive knowledge-based system in combination with a multivariate data analysis. To achieve a reliable differential diagnosis between the different entities of CMPD and controls, decision trees and the rank order of the best discriminating parameters have been calculated. The cases measured were defined by 3 histopathologists who were involved in the elaboration of the Hannover Classification of CMPD. The results demonstrate striking numeric and morphologic characteristics of the megakaryopoiesis in each separate primary category of CMPD, that is (1) chronic myeloid leukemia of the common type and (2) with megakaryocytic increase, (3) polycythemia vera, (4) primary or idiopathic thrombocythemia, and (5) chronic megakaryocytic-granulocytic myelosis. Thus, the morphometric measurements did confirm the validity of the Hannover Classification of CMPDs. In order to evaluate the information contained in large quantitative and semiquantitative data bases and diagnostic decisions, knowledge-based expert systems seem to represent a valuable addition to conventional statistics.

Cell Count↗

[Granulopoiesis in chronic myeloproliferative disorders (CMPD): electron microscopy/morphometric investigations].

This pilot study comprises quantitative ultrastructural investigations of the normal, non-leukemic granulopoiesis in the bone marrow of four patients suffering from heart diseases, compared with the granulopoiesis of four patients with different types of CMPD. By evaluation of the morphometric parameters it could be demonstrated that normal granulopoiesis is subject to a strong functional order of organelles in the course of maturation, aiming at the preparation of mitoses of immature cells and the production of functionally capable specific granules. Contrary to this, the studied cases of CMPD exhibited striking differences of morphometric parameters, which may be interpreted as functional deficiencies or defects of organelles involved in the production of specific granules, with the phenomenon of dissociation of nuclear and cytoplasmic maturation.

Adult↗

Epidemiology and treatment of gastric Campylobacter pylori infection: more questions than answers.

Two-hundred and ten consecutive patients undergoing routine gastroscopy were additionally investigated for evidence of Campylobacter pylori (C.p.). 106 patients were positive in one or more tests: 99.1% using a rapid urease detecting test (CLO-test), 80.2% histology, 78.3% cytology and 60% culture. We found no difference between the CLO-test results from biopsies taken from different parts of the stomach in individual patients. C.p. was found in 100% of patients with significant chronic antral gastritis, 67.7% with gastric ulcers, 65% with duodenal ulcers and in 12.1% of normal individuals. The C.p. infection was apparently eliminated in 50% of cases treated with bismuth subsalicylate (BSS) for four weeks. The combination of BSS with amoxicillin, tinidazole or an H2-receptor antagonist offered no advantage over BSS alone. Treatment with BSS led to improvement in symptoms and histological findings including healing of ulcers in patients with or without persistent C.p. infection. The recurrence of C.p. infection after apparently successful treatment was, however, 75% in 4 weeks. In conclusion, C.p. infection correlates strongly with the presence of chronic gastritis, and significantly with gastric and duodenal ulceration. The best diagnostic approach is the combination of a rapid urease detecting test and histology. C.p. infection is of long duration and difficult to eliminate. The most effective treatment for C.p. infection remains BSS as single agent.

Adolescent↗

[Cardiotoxic and myelosuppressive activity of various antitumor antibiotics of the anthracycline type in the rat].

The cardiotoxic and myelosuppressive effects of the potential antitumor antibiotics violamycin BI (VBI) and violamycin BII (VBII) were studied in rats in comparison with daunorubicin (DAU), doxorubicin (ADR) and carminomycin (CAR). Rats were intravenously given the compounds 10 times for three weeks at total doses of 0.4 to 3 times of the acute LD50. Cardiac toxicity was measured using ECG (widening of the QRS complex), and screening parameters for bone marrow suppression were white blood cell counts, hematocrit and hemoglobin values. Following the drug injections the myocardium and the bone marrow were additionally investigated by light microscopy. With the exception of ADR, all the anthracyclines tested showed a more or less strong dissociation of cardiotoxic and myelotoxic activities. VBI was found to be only toxic on the heart but not on the bone marrow, whereas DAU, VBII and CAR were predominantly toxic on the bone marrow. Only ADR showed strong cardiac toxicity as well as distinct myelosuppression. A final evaluation of VBI and VBII has to include both the antineoplastic and the toxic properties of the compounds.

Aminoglycosides↗

The effect of ZIMET 3164 and ZIMET 3393 on phagocytosis in Tetrahymena pyriformis GL.

Tetrahymena pyriformis GL is a suitable model to study the influence on phagocytotic activity of two membrane-stabilizing benzimidazole nitrogen mustard derivative, ZIMET 3164 and ZIMET 3393 (cytostasan). Treatment by both compounds causes a gradual inhibition of food vacuole formation dependent on the concentrations used. Complete cessation of phagocytosis is observed by 5 micrograms/ml ZIMET 3164 and 50 micrograms/ml ZIMET 3393. Additionally, disturbances of ciliary movement including immobilization and changes of cell shape are induced. The cells resume food vacuole formation and ciliary movement after being rinsed with control solution. The results correspond well with those described recently in mammalian mononuclear phagocytes.

Animals↗

Toxic effects of violamycin Bi, carminomycin and daunorubicin on the myocardium of rabbits.

Cardiac toxicity of the new anthracycline antitumour antibiotics violamycin BI (V) and carminomycin (C) was studied in comparison with daunorubicin (D). Rabbits were intravenously given total doses of 0.1-1.5 mg/kg V or C, and 0.64-18 mg/kg D, respectively, twice weekly for one month. When examined two to six days, two and four weeks, respectively, after the last drug administration the gross findings consisted of hydropericard, hydrothorax and ascites in some animals. Histologically, loss of striation and focal necrosis of cardiac muscle cells and subsequently chronic inflammatory reactions and/or proliferation of mesenchyma cells were mostly found. These alterations were somewhat more pronounced in rabbits treated with V than in animals received D or C. At equitoxic doses of the antibiotics tested the ultrastructural lesion in the myocardial cells were altogether less marked after treatment with D than with C or V.

Aminoglycosides↗

Effect of a membrane-stabilizing compound on calcium binding to the plasma membrane of Acanthamoeba castellanii.

Binding of calcium ions at the plasma membrane was studied in Acanthamoeba cells pretreated with ZIMET 3164, a benzimidazole nitrogen mustard derivative, which is known to show a potent immunosuppressive action combined with a membrane-stabilizing effect in mice. For reference, 2 compounds were applied: ZIMET 3393 (Cytostasan¿), another benzimidazole mustard derivative, which exerts only a moderate membrane effect and acts as a strong cytostatic, and ZIMET 176/68, a barbituric acid derivative, which acts as an inhibitor of humoral immune responses but without membrane-stabilizing effect. Application of any of the 3 compounds does not reduce the appearance of calcium binding sites, visualized by means of ultracytochemical reaction, notwithstanding their different action in the mammalian organism. On the contrary, it was estimated by morphometric analysis that the number of Ca-dependent deposits was augmented after treatment with low doses of any of the 3 compounds, what seems to be connected with the induced metabolic disturbances in low molecular phosphates level. High doses and/or prolongation of treatment of the cells resulted in diminution of the number of deposits and induces profound disturbances in cell ultrastructure, probably due to the toxic action of the applied doses. In these cases, band-like structures crosslinking the two leaflets of the plasma membrane may be observed; it is suggested that they represent integral membrane proteins.

Amoeba↗

Ultrastructural quantitative stereology on 'mixed' cell populations: problems and possibilities.

Contrary to homogeneous tissues, "mixed" tissues or cell suspensions are composed of different cell individuals. They have been characterized as heterogeneous cell populations (composed of cells of different cytogenetical source) and heteromorphous or inhomogeneous cell populations (of cells of the same type but of different individual functional state). Certain problems may arise during ultrastructural morphometrical investigations of heteromorphous populations. Because of the different size of planes of sectioning of individual cells, morphometrical results should be treated by means of modifications of the t-test [4]. Furthermore, the unambiguous classification of individual cell profiles necessitates a conscious selection of cell profiles containing a nuclear profile. This non-random sampling approach leads to systematic errors of computed parameters for the whole cell as the nuclear volume fraction and the specific cell surface area which should be corrected. Besides correction procedures derived from regular geometrical models we have presented correction methods for cells with non-spherical nucleus and a cell surface with marked surface projections [13, 21]. On the other hand, on heteromorphous cell populations, more detailed information about functional events can be gained, in comparison the customary stereological mean values, by means of frequency distributions of morphometrical data of individual cell profiles as well as by correlation of data of different cell organelles.

Animals↗

[Correction of nuclear volume fraction and specific surface area from random nucleated sections of cells with structured surfaces].

Correction procedures are proposed for the nuclear volume fraction (Vvn) and the specific surface area (Svc) of single cell populations which allow to calculate true values of Vvn and Svc from biased samples of nucleated sections. The methods can be applied on the understanding that the cells have an approximately spherical basic shape and that cells of eventually existing different size classes are geometrically similar; any regular shape of the nucleus is not necessary. The correction formulas are especially suitable for cells with an extremely folded cell membrane surface. The procedures are tested on four populations of peritoneal cells and the results are compared with those of correction formulas derived from the sphere-in-sphere model.

Animals↗

[A graphical method for the correction of nuclear volume fraction and specific surface area of the cell membrane from random nucleated sections of cells].

An empirical graphical method is described for the correction of the nuclear volume fraction and the specific cell surface area after stereological estimations on nuclear-biased samples of cell profiles. The method is basing on the assumption that from equatioral sections of representative cells of a given population informations can be obtained about the volume relations and surface relations of tme fraction and the specific cell surface area after stereological estimations on nuclear-biased samples of cell profiles. The method is basing on the assumption that from equatioral sections of representative cells of a given population informations can be obtained about the volume relations and surface relations of tme fraction and the specific cell surface area after stereological estimations on nuclear-biased samples of cell profiles. The method is basing on the assumption that from equatioral sections of representative cells of a given population informations can be obtained about the volume relations and surface relations of the (analysed) "cell stumps" containing nuclear profiles and the "cell caps" lacking nuclear profiles (which were excluded from the stereological estimation). Prerequisites for the application of the method are an approximately spherical shape of the basic cell body and the geometrical similarity of eventually occuring size classes of the cells. The graphical method was checked on peritoneal macrophages and lymphocytes as well as on corresponding cell model systems. The results have been compared with mathematical methods derived from sphere-in-sphere geometrical models. The graphical methods gave results generally comparable to those from methematical methods. Provided that the shape and position of the nucleus inside the cell as well as the structure of the cell surface showed considerable differences to the geometrical models underlying the mathematical corrections, the graphical method was superior, and should be favoured in such cases. On ideal sphere-in-sphere models, the mathematical methods derived from those models should be applied.

Animals↗

[Effect of preparation procedures on the calculation of average cell volumes from stereological data].

The shrinkage of peritoneal cell during the electron microscopical preparation was investigated by means of a special device. Independently of the procedure of fixation after critical point drying the cells exhibit only 54 to 59% of the original diameter (residual volume about 18%). The reduction of cell diameter after Epon embedding is about 25%, corresponding to a residual volume of 40%.

Animals↗

[Problems of statistical evaluation of stereological data from single cells].

A definition of morphometrical parameters of single cell populations is given. Methods for estimating these quantities (confidence estimation included) are described. For the comparison of equivalent parameters of 2 cell populations 2 statistical test procedures replacing the common t-test, are discussed. In addition, a homogeneity test is proposed for comparing the distributions of morphometrical data.

Cell Nucleus↗