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Biomedical subjects

T Mattfeldt

Publications and source records attributed to T Mattfeldt.

At least 19 recordsLinked to original sources

Physiological growth of arteries in the rat heart parallels the growth of capillaries, but not of myocytes.

Maladaption to hemodynamic overload, especially to arterial hypertension, has important clinical implications, and it is necessary to obtain criteria in order to discriminate physiological and pathological growth processes. We investigated the physiological growth of intramyocardial arteries in the rat heart. A new stereological method was introduced to determine the length of intramyocardial arteries from counts on histological sections. Four groups of male Sprague-Dawley rats of different ages were investigated. The growth rate of arteries was characterized by the growth coefficient b according to the exponential function y = axb (allometric growth function). Analysis of left ventricular weights (LVW) and total lengths of left ventricular intramyocardial arteries (L) revealed Lv = constant.LVW0.71 (r = 0.77, P < 0.001). The growth coefficient b < 1 indicates that the arterial supply of the heart, i.e. the length density of arteries Lv (length per unit myocardial volume), decreases during normal growth. Empirically, we found L = constant.LVW-0.28 (r = 0.43, P < 0.01). Previously, we estimated growth rates of b = 0.33 for the total length of left ventricular myocytes and b = 0.71 for the total length of capillaries. Thus, growth of intramyocardial arteries considerably exceeds the length increase of myocytes, but is proportional to the length increase of capillaries. Growth analysis of total mitochondrial volume using historical data of our group revealed proportionality to arteries, as well (b = 0.76). This indicates that growth of arteries and capillaries may be determined by oxygen consumption.

Animals

Effects of nifedipine and moxonidine on cardiac structure in spontaneously hypertensive rats. Stereological studies on myocytes, capillaries, arteries, and cardiac interstitium.

Light and electron microscopic stereological studies were performed on the myocardium of spontaneously hypertensive rats (SHR-SP) before and after treatment with nifedipine (27 mg/kg body weight/day) and the antisympathotonic agent moxonidine (8 mg/kg body weight/day). The treated groups were compared with nontreated SHR-SP and normotensive WKY (n = 10 in each group). At the beginning of therapy (when the male SHR-SP were 6 months old), blood pressure was increased and left ventricular hypertrophy had developed whereas pathologic changes of myocardial structure were not observed. After 3 months, the nontreated hypertensive rats showed cardiac fibrosis, activation and proliferation of interstitial cells, wall thickening of intramyocardial arteries, reduced capillarization as well as focal degeneration of myocytes at the ultrastructural level. Both treatments showed similar effects on blood pressure, degree of hypertrophy, and cardiac structure. Blood pressure as well as the degree of hypertrophy were significantly reduced. As far as myocardial fibrosis, capillarization, and regressive changes of myocytes are concerned a complete normalization was observed. Furthermore, nifedipine enhanced capillary supply beyond the normal level by induction of capillary neoformation. Microarteriopathy and activation of nonvascular interstitial cells (first step in development of interstitial myocardial fibrosis) were significantly suppressed by therapy, but the level of the normotensive control could not be maintained. Additional experiments with a low dose combination therapy of nifedipine and moxonidine that did not reduce blood pressure provided evidence that hypertension is an important determinant of the alterations of intramyocardial arteries, but not of cardiac interstitial fibrosis.

Animals

Effect of early onset angiotensin converting enzyme inhibition on myocardial capillaries.

We investigated the preventive effects of long-term treatment with the angiotensin converting enzyme inhibitor ramipril on myocardial left ventricular hypertrophy and capillary length density in spontaneously hypertensive rats. Rats were treated in utero and subsequently up to 20 weeks of age with a high dose (1 mg/kg per day) or with a low dose (0.01 mg/kg per day) of ramipril. Animals given a high dose of ramipril remained normotensive, whereas those given a low dose developed hypertension in parallel to vehicle-treated controls. At the end of the treatment period, converting enzyme activity in heart tissue was inhibited dose-dependently in the treated groups. Both groups revealed an increase in myocardial capillary length density together with increased myocardial glycogen and reduced citric acid concentrations. Left ventricular mass was reduced only in high dose- but not in low dose-treated animals. Our results demonstrate that early onset treatment with a converting enzyme inhibitor can induce myocardial capillary proliferation, even at doses too low to antagonize the development of hypertension or left ventricular hypertrophy. We hypothesize that potentiation of kinins is responsible for this effect, probably by augmenting myocardial blood flow, which is a well-known trigger mechanism of angiogenesis in the heart.

Administration, Oral

Effects of nifedipine and moxonidine on cardiac structure in spontaneously hypertensive rats (SHR)--stereological studies on myocytes, capillaries, arteries, and cardiac interstitium.

Light and electron microscopic stereological studies were performed on the myocardium of spontaneously hypertensive rats (SHR) before and after treatment with nifedipine (27 mg/kg b.w./day) and the sympatholytic agent moxonidine (8 mg/kg b.w./day). The treated groups were compared with nontreated SHR and normotensive WKY (n = 10 in each group). When the therapy was started in 6-month old male SHR, blood pressure was increased and left ventricular hypertrophy had developed. On the other hand, pathologic changes of myocardial structure were not observed. After 3 months, the nontreated hypertensive rats showed cardiac fibrosis (volume density of fibrosis + 45%), activation and proliferation of interstitial cells (volume density of nonvascular interstitium + 240%), media hypertrophy of small arteries (total volume of arterial media in the left ventricle + 180%), reduced capillarization (length density of capillaries--11%), as well as focal degeneration of myocytes at the ultrastructural level. Both treatments showed similar effects on blood pressure, degree of hypertrophy, and cardiac structure. Blood pressure as well as degree of hypertrophy were significantly reduced (relative left ventricular weights: --25% and --16%). As far as myocardial fibrosis, capillarization, and regressive changes of myocytes are concerned a complete normalization was observed. Microarteriopathy and activation of nonvascular interstitial cells (first step in development of interstitial myocardial fibrosis) were significantly suppressed by therapy (total media volume --40%, volume density of nonvascular interstitium --38%), but the normal level of the normotensive control could not be maintained (+ 70%, + 111% vs WKY). This may be due to the slightly elevated systolic blood pressure despite therapy (+ 25%, vs WKY) or to hormonal factors in SHR which are independent of blood pressure. Since nifedipine and moxonidine are pharmacologically different drugs with different effects on sympathetic activity, one may cautiously conclude that increase in blood pressure itself is an important determinant of arterial, interstitial as well as myocellular alterations which are related to the pathogenesis of hypertensive heart muscle disease.

Animals

Stereology, flow cytometry, and immunohistochemistry of follicular neoplasms of the thyroid gland.

A retrospective analysis of surgically resected thyroid cold solitary nodules was performed by stereology, DNA flow cytometry, and immunohistochemistry in 15 follicular adenomas and 15 well-differentiated follicular carcinomas to determine if a differential diagnosis of both follicular neoplasms can be done exclusively from cytologic criteria. Between 150 and 200 tumor cell nuclei (TCN) were studied per case for their TCN profile area, perimeter, and density, as well as for stereologic estimates, including the new parameter, volume-weighted mean particle volume (Vv). Flow-cytometric analyses included measurement of the DNA index and the percentage of cells in S phase and G2M phase. The same tumors were examined for the expression of thyroglobulin and the intermediate filaments vimentin and keratin. Follicular adenomas and follicular carcinomas did not show any significant differences in stereologic estimates related to TCN size. Both groups included similar proportions of diploid and aneuploid neoplasms. Aneuploid follicular neoplasms showed a significantly greater area, perimeter, and volume of TCN as compared with diploid tumors, regardless of their histologic diagnosis. Follicular adenomas and follicular carcinomas expressed a similar staining pattern for the tested immunoreagents, with a few cases coexpressing vimentin and keratin. From our results, a differential diagnosis of follicular neoplasms cannot be performed on the basis of cytologic aspirates exclusively. Infiltration of capsula or vessels remains the only safe indicator of malignancy in the absence of metastases. The lack of cytologic differences suggests that some follicular adenomas are preinvasive carcinomas, not yet showing infiltrative growth at the time of resection.

Adenocarcinoma

[Differential diagnosis of follicular neoplasm of the thyroid].

Fifteen resected follicular adenomas and 15 well-differentiated follicular carcinomas of the thyroid gland were analysed to determine whether a differential diagnosis of both "follicular neoplasms" can be performed by cytological criteria exclusively. 150-200 tumor cell nuclei (TCN) were studied per case for their TCN profile area, perimeter, density and for stereological estimates including the new parameter Vv, volume-weighted mean particle volume. Flow-cytometric analyses included measurement of the DNA index, the percentage of cells in S-phase and in G2/M phase. Follicular adenomas and follicular carcinomas did not show any significant differences in stereological estimates related to TCN size. Both groups included similar proportions of diploid and aneuploid neoplasms. Aneuploid follicular neoplasms showed a significantly greater area, perimeter and volume of TCN as compared to diploid tumors, regardless of their histological diagnosis. From our results a differential diagnosis of follicular neoplasms cannot be performed on the basis of cytological aspirates exclusively. Infiltration of capsula or vessels remain the only safe indicators of malignancy in the absence of metastases. The lack of cytological differences provides evidence that some follicular adenomas are preinvasive carcinomas, not yet showing infiltrative growth at the time of resection.

Adenocarcinoma

The popliteal artery entrapment syndrome: presentation, morphology and surgical treatment of 13 cases.

The morphology, clinical parameters and treatment of the popliteal artery entrapment syndrome (PAES) are presented on the basis of 13 of our own cases and from the literature. PAES is based on a segmental vascular compression due to an anatomical anomaly of the popliteal region and a new classification is presented distinguishing three variants according to the different anatomical conditions. PAES is mostly found in young sportsmen with well-developed muscles. Clinical symptoms are acute or chronic, and the diagnosis is made by physical examination, angiography and Doppler ultrasound, both in neutral position and in plantar flexion. Although thromboendarterectomy in some cases leads to good results, the preferred surgical therapy is decompression of the entrapped artery and reconstruction of the arterial pathway by vein graft interposition. The results were excellent in nine of 13 cases. In two patients, a recurrent thrombosis necessitated a femoro-crural bypass and in two others the entrapment was only diagnosed during reoperation for aneurysms of the venous graft.

Adult

Estimation of surface area and length with the orientator.

The orientator is a new technique for the estimation of length and surface density and other stereological parameters using isotropic sections. It is an unbiased, design-based approach to the quantitative study of anisotropic structures such as muscle, myocardium, bone and cartilage. A simple method for the practical generation of such isotropic planes in biological specimens is described. No special technical equipment is necessary. Knowledge of an axis of anisotropy can be exploited to optimize the efficiency. To randomize directions in space, points are selected with uniform probability in a square using various combinations of simple random, stratified random, and systematic random sampling. The point patterns thus produced are mapped onto the surface of a hemisphere. The mapped points define directions of sectional planes in space. The mapping algorithm ensures that these planes are isotropic, hence unbiased estimates of surface and length density can be obtained via the classical stereological formulae. Various implementations of the orientator are outlined: the prototype version, the orientator-generated ortrip, two systematic versions, and the smooth version. Orientator sections can be generated without difficulty in large specimens; we investigated human skeletal muscle, myocardium, placenta, and gut tissue. Slight practical modifications extend the applicability of the method to smaller organs like rat hearts. At the ultrastructural level, a correction procedure for the loss of anisotropic mitochondrial membranes due to oblique orientation relative to the electron beam is suggested. Other potential applications of the orientator in anisotropic structures include the estimation of individual particle surface area with isotropic nucleators, the determination of the connectivity of branching networks with isotropic disectors, and generation of isotropic sections for second-order stereology (three-dimensional pattern analysis).

Animals

[New methods for the morphometric analysis of anisotropic tissues].

Some unbiased, design-based stereological methods that have recently been developed for the study of anisotropic tissues like muscle, myocardium, brain, cartilage, and skin, are briefly reviewed. Vertical sections permit the unbiased estimation of surface density and mean volume-weighted particle volume from microscopic sections. The available experience includes various studies on malignant melanomas. In addition, the surface area of total organs (e.g., the pleural surface area) can be determined with vertical sections, which was hitherto not feasible. The orientator is a simple method to generate isotropic sections in biological material. With the orientator method it is possible to determine not only the surface density, but also the length density of the objects. Thus the method is suitable for the study of fascicular systems (tubules etc.), and for the study of vascularisation in particular.

Animals

Expression of epidermal growth factor receptor in benign and malignant primary tumours of the breast.

Using the monoclonal antibody EGF-R1, normal mammary gland and a series of 213 unselected primary breast tumours were investigated immunohistochemically for expression of epidermal growth factor receptor (EGFR). In normal breast EGFR was expressed in variable patterns in lobular, ductal, and myoepithelial cells. In fibroadenoma, EGFR was detectable in variable numbers of ductal and myoepithelial cells and in stromal fibroblasts. The myoepithelial compartment of 2 cystosarcomas phyllodes also expressed EGFR. Among the 197 carcinomas tested only 20.3% contained EGFR expressing tumour cells which represented a minority in 12.2%, the majority in 2.1%, and the entire neoplastic population in 6.1% of the cases. Again, non-neoplastic ductal remnants often contained EGFR positive myoepithelial and ductal cells whereas stromal fibroblasts expressed EGFR only occasionally. We conclude that in contrast to the normal state, EGFR-expression is a rather rare phenomenon in breast carcinoma cells, positively correlated with a declining grade of differentiation (p less than 0.025) and at least occasionally associated with squamous metaplasia within the tumour, that EGFR expression is not exclusively restricted to cells of the epithelial lineage, and that EGFR may have other functions not related to proliferation, since it is commonly detectable in myoepithelial cells.

Breast

Reaction patterns of the myocardial interstitium in different models of cardiac hypertrophy--stereological investigations.

Several experimental models of cardiac hypertrophy were investigated in rats: 1. mild hypertrophy induced by physical exercise (18 weeks), 2. mild hypertrophy induced by renovascular hypertension (24 weeks), 3. moderate hypertrophy induced by renovascular hypertension in diabetic and non-diabetic animals (8 weeks), 4. moderate hypertrophy induced by renovascular hypertension in diabetic and non-diabetic animals (12 weeks), 5. moderate hypertrophy induced by thyroxin application (4 weeks), 6. mild hypertrophy in chronic uremia (5/6 nephrectomy, 3 weeks). It is concluded from quantitative stereological parameters of the left ventricular papillary muscles that 1. in hypertrophic hearts myocardial blood flow and oxygen consumption, respectively, rather than the size of muscle fibres determine the capillary supply of the myocardium, 2. interstitial fibrosis occurs in hypertrophy induced by chronic pressure overload and depends on degree and duration of hypertension, 3. the extent of interstitial fibrosis in hypertension is magnified by diabetes mellitus, and 4. the interstitial fibrosis which occurs in chronic uremia is not caused by hypertension.

Animals

Expression of HLA-A, -B, -C, -DR, -DP, -DQ, and of HLA-D-associated invariant chain (Ii) in non-neoplastic mammary epithelium, fibroadenoma, adenoma, and carcinoma of the breast.

Non-neoplastic mammary gland, 20 benign tumors and 206 carcinomas of the breast were immunohistochemically examined for expression of HLA-A, -B, -C, HLA-DR, -DP, and -DQ molecules and the HLA-D associated invariant chain (Ii). In contrast to cells from benign lesions, tumor cells of 51.2% of carcinomas had an abnormally low content of HLA-A, -B, and -C determinants ranging from reduction of antigenic density per cell (28.8%) over an incomplete (15.6%) to complete loss of antigens (6.8%). Associated with lymphohistiocytic stromal infiltrates, HLA-D/Ii determinants were found to be induced in benign duct and acinar epithelium after the order Ii greater than or equal to HLA-DR greater than or equal to HLA-DP greater than or equal to HLA-DQ. These antigens were also expressed, mostly noncoordinately, in 55.5% of carcinomas, and in 98 cases according to the above order. In 28.6%, Ii expression clearly exceeded HLA-D antigen expression; conversely, 6.2% contained HLA-DR+/Ii- tumor cell subsets. In breast carcinoma, the association of reduced HLA-A, -B, and -C expression and a noninduction of HLA-DR was highly significant (P less than 0.0009), suggesting an abnormal signal acting down-regulating on the expression of both classes of antigens. Because the modality of HLA-A, -B, and -C and HLA-D/Ii expression correlated with neither tumor type nor grade, it might be an independent parameter.

Adenofibroma

[The radiologic diagnosis of inflammatory aneurysms].

An inflammatory aneurysm is defined as a nonbacterial special type of atherosclerotic aneurysm. The macroscopic characteristics are: a porcelaneous appearance, excessive thickening of the aortic wall, and perianeurysmal adhesions. Chronic inflammatory infiltrations, which are localized in the adventitia, can be found via microscopy. Six of forty-three patients with abdominal aortic aneurysms were found to have an inflammatory aneurysm at operation. In a retrospective study, we examined the sonographic, computed tomographic and angiographic appearance of inflammatory aneurysms. Only with computed tomography can thickening of the aneurysmal wall be demonstrated; angiography does not have this capacity and can only find an inflammatory aneurysm in particular cases.

Angiography, Digital Subtraction

Volume estimation of biological objects by systematic sections.

The absolute volume of biological objects is often estimated stereologically from an exhaustive set of systematic sections. The usual volume estimator V is the sum of the section contents times the distance between sections. For systematic sectioning with a random start, it has been recently shown that V is unbiased when m, the ratio between projected object length and section distance, is an integer number (Cruz-Orive 1985). As this quantity is no integer in the real world, we have explored the properties of V in the general and realistic situation m epsilon R. The unbiasedness of V under appropriate sampling conditions is demonstrated for the arbitrary compact set in 3 dimensions by a rigorous proof. Exploration of further properties of V for the general triaxial ellipsoid leads to a new class of non-elementary real functions with common formal structure which we denote as np-functions. The relative mean square error (CE2) of V in ellipsoids is an oscillating differentiable np-function, which reduces to the known result CE2 = 1/(5m4) for integer m. As a biological example the absolute volumes of 10 left cardiac ventricles and their internal cavities were estimated from systematic sections. Monte Carlo simulation of replicated systematic sectioning is shown to be improved by using m epsilon R instead of m epsilon N. In agreement with the geometric model of ellipsoids with some added shape irregularities, mean empirical CE was proportional to m-1.36 and m-1.73 in the cardiac ventricle and its cavity. The considerable variance reduction by systematic sectioning is shown to be a geometric realization of the principle of antithetic variates.

Animals