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Biomedical subjects

H Kuhn

Publications and source records attributed to H Kuhn.

At least 127 records · Page 7Linked to original sources

Effects of cilazapril on the cerebral circulation in spontaneously hypertensive rats.

Chronic hypertension is associated with a lower cerebral vascular reserve due to thickening of the media of cerebral vessels. The goal of the present study was to determine if long-term inhibition of angiotensin converting enzyme with cilazapril, a new long-acting angiotensin converting enzyme inhibitor, could improve cerebral vascular reserve. For this purpose, two groups of 12 spontaneously hypertensive rats were compared. One group was treated with 10 mg/kg/day cilazapril from 14 weeks to 33 weeks of age and was compared with a group treated with placebo. A third group of 12 Wistar-Kyoto rats treated with placebo was used as reference. At the end of the treatment period, cerebral vascular reserve was evaluated by measuring cerebral blood flow (radioactive microspheres) at rest and during maximal vasodilation induced by seizures provoked by bicuculline. Then, the rats were perfusion-fixed, and morphometry of the cerebral vasculature was performed. Cerebral vascular reserve was severely impaired in the spontaneously hypertensive rats since their maximal cerebral blood flow was decreased by 52% compared with the Wistar-Kyoto rats. Cilazapril normalized cerebral blood flow reserve. This normalization was associated with a decreased thickness of the medial layer in the carotid artery, the middle cerebral artery, and in the pial arteries larger than 100 microns. Further studies are required to determine whether this decreased medial thickness is due to the normalization of blood pressure induced by cilazapril or to the reduction of trophic factors such as angiotensin II.

Animals↗

Effects of chronic ACE inhibition on cardiac hypertrophy and coronary vascular reserve in spontaneously hypertensive rats with developed hypertension.

Left ventricular hypertrophy due to hypertension is associated with a decrease of coronary vascular reserve. We have previously shown that chronic angiotensin converting enzyme (ACE) inhibition prevents cardiac hypertrophy and improves coronary vascular reserve when the treatment is started before appearance of hypertension in spontaneously hypertensive rats (SHR). However, the effects of starting chronic ACE inhibition when hypertension was already developed is not known. The goal of the present study was to assess the effects of chronic ACE inhibition on coronary vascular reserve and on the morphology of the coronary microvasculature when treatment was started after hypertension had developed. For this purpose, one group of SHR was treated from 3-8 months of age with cilazapril, a new ACE inhibitor, and compared with a group treated by placebo. At the end of treatment, cardiac hypertrophy, coronary vascular reserve, density and cross-sectional surface area of the myocardial capillaries (normalized for the myocardial mass) and wall/lumen ratio of the coronary arterioles were determined. Chronic ACE inhibition with cilazapril reduced cardiac hypertrophy and improved by more than 50% coronary vascular reserve in the left and right ventricles. In the left ventricle, the improvement was more pronounced in the subendocardium than in the subepicardium. Cilazapril increased the density and the cross-sectional surface area of the myocardial capillaries and decreased the wall/lumen ratio of the arterioles of the left ventricle. We conclude that chronic ACE inhibition can improve coronary vascular reserve, increase capillary density and capillary cross-sectional surface area and decrease the thickness of the media of coronary arterioles in SHR even when treatment is started after development of hypertension.

Angiotensin-Converting Enzyme Inhibitors↗

Growth and stability of thrombi in flowing citrated blood: assessment of platelet-surface interactions with computer-assisted morphometry.

The differential quantitation of platelet deposition in perfusion studies is a major problem. We report on methods to prepare semithin sections of platelet deposits on collagen coated on glass and plastic cover slips, to study growth and stability of thrombi in three dimensions, and the development of a computer-assisted differential quantitation of platelet-collagen interactions. The interactions were quantified as percentage of the surface covered with platelets (platelet adhesion), thrombus height, thrombus density and thrombus area per unit sectional length, respectively. Cover slips coated with fibrillar equine collagen in parallel-plate perfusion chambers were exposed to flowing citrated blood at shear rates ranging from 200 to 2,600 s-1. Thrombi, partially enmeshed in the collagen meshwork, prevailed on the surface at all shear rates. Maximal platelet adhesion and thrombus density were seen at greater than 5 micrograms/cm2 collagen, while thrombus area and height were maximal at greater than 10 micrograms/cm2. The volume of the thrombi appeared correlated to the number of deposited platelets (r = 0.92). En face preparations showed deposits of platelet islands which grew in diameter with time, particularly in the direction of the blood flow, becoming progressively confluent. Sections cut parallel to the direction of the blood stream indicated that this growth pattern was at least partially caused by thrombi bent in the direction of the blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Citrates↗

Inhibition of cell migrations by the linoleic acid oxygenation product 9S-hydroxy 10E,12Z octadecadienoic acid (9-HODE).

The linoleic acid metabolite 9S-HODE was prepared by means of tomato fruit lipoxygenase and purified by high-performance liquid chromatography (HPLC) to a high steric purity as judged by chiral-phase HPLC. 9S-HODE caused in the concentration range between 0.01 and 1 microM a strong dose-dependent inhibition of the migration of both cultured porcine aortic endothelial cells and of phytohaemagglutinin-stimulated human mononuclear cells. The effect was not observed with another polyenoic fatty acid metabolite, 15S-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid (15-HPETE). The results are discussed in the light of other biological actions of 9-HODE recently described.

Animals↗

Complexes of DNA hairpins and a single-stranded oligonucleotide detected by affinity chromatography and mung bean nuclease cleavage.

The emergence of a simple translation device consisting of an assembler strand (primordial mRNA) and RNA hairpins (primordial tRNA) is presumed to be an important step leading to the origin of life. The assumption of a non-enzymatic interaction of primordial tRNA and mRNA is experimentally approached. DNA hairpins containing five or more adenosine residues in the loop are able to bind to complementary oligonucleotides covalently bound to cellulose. The exact number of base pairs formed between the hairpins and the assembler strand is determined by two methods applied to DNA hairpin/assembler complexes. The melting temperature of a complex is measured and the cleavage pattern by nuclease from mung bean is determined. The loop of the smallest hairpin able to bind consists of five adenosine residues and only three base pairs are formed. This supports the idea of a primordial recognition similar to the contemporary codon-anticodon interaction.

Biological Evolution↗

A semiautomatic image analyzing system based on an APPLE II or IIe personal computer.

A new semiautomatic image analyzing system based on an APPLE II or IIe personal computer is described. The configurations of the hardware and software are extensively explained. The possibilities of applying the system are demonstrated by different examples taken from various projects in biological research and clinical pathology. The system is designed to fulfil the following requirements: (1) stepwise realization as a unit-by-unit system according to individual needs and interests, (2) acquisition and calculation of morphometric parameters, (3) provision of solutions for the greatest possible number of given problems in clinical and experimental pathology, (4) direct connection of the system to host computers for on-line data transfer and evaluation, and (5) optimum cost-benefit ratio by manifold application possibilities for the individual hardware and software elements. The advantages of the unit-by-unit system with personal computers outweigh in many respects the disadvantages (for example, increased file handling and limited capacity) in comparison with the closed automatized image evaluation system, particularly with regard to costs, flexibility and compatibility. The system is being further developed in collaboration with Kontron Bildanalyse GmbH, Eching/Munich, FRG.

Animals↗

Diagnosis of hypertrophic cardiomyopathies by non-ECG-gated cardiac computed tomography (CCT).

In order to study the significance of non-ECG-gated cardiac computed tomography (CCT) for the diagnosis of hypertrophic cardiomyopathies, the method was applied in 55 consecutive patients and the data were correlated with the echocardiogram. In a subset of 18 patients left and right heart catheterization was additionally performed, and in a subset of 17 patients, endomyocardial biopsy was performed. The CCT turned out to be an easily applicable, non-time-consuming method for obtaining a sectional visualization of the left and right ventricle. Regarding the septal thickness, there was an unexpectedly high correlation between CCT and echocardiogram (r = 0.9). The left ventricular deformity observed by echocardiogram and angiography in patients with hypertrophic cardiomyopathies corresponded well to that visualized by CCT, leading to a good differentiation between HOCM and HNCM (diagnostic specificity: 92% and 80%, respectively). It is concluded that the non-ECG-gated CCT seems to be a very helpful non-invasive method for diagnosing hypertrophic cardiomyopathies and differentiating between the obstructive and nonobstructive forms. From a clinical point of view, this may be important, mainly in patients in whom no clear-cut diagnosis is possible using previously applied non-invasive methods, including echocardiography. It may also be useful for follow-up studies, providing a sectional insight into the distribution of left ventricular hypertrophy.

Adult↗

Cardiac amyloid deposits in endomyocardial biopsies. Light microscopic, ultrastructural, and immunohistochemical studies.

In four patients with unexplained, abnormal thickening of the interventricular septum as demonstrated by echocardiography, right ventricular endomyocardial biopsy revealed unexpected cardiac amyloid deposits that resulted in increased myocardial thickness and rapidly progressive heart failure. Light microscopically, amyloid was observed in the subendocardial layer, interstitium, and walls of the intramural arterioles. Electron-microscopically, the amyloid fibrils were adjacent to the basement membranes of the heart muscle cells and the vascular smooth muscle cells. Immunohistochemical typing with specific antibodies against different amyloid fibril proteins on glutaraldehyde-fixed paraffin sections revealed different amyloid types. In two patients with generalized idiopathic amyloidosis and in two others with amyloidosis in multiple myeloma, the A-lambda form was diagnosed. In a fifth patient, AA-amyloidosis was found in familial Mediterranean fever with cardiac manifestation without thickening of the interventricular septum. The amyloid deposits were located almost exclusively within the walls of the myocardial arterioles. The amount of amyloid as observed in the myocardial biopsies correlates with the rapidly progressive cardiac failure. It is suggested that in patients with abnormal thickening of the interventricular septum of unknown origin the diagnosis should be clarified by endomyocardial biopsy.

Adult↗

Autoradiographic evidence for penetration of 3H-ceftriaxone (Rocephin) into cells of spleen, liver and kidney of mice.

Ceftriaxone (Rocephin), a broad-spectrum parenteral cephalosporin with an exceptionally long elimination half-life, has a marked activity against both Salmonella typhimurium infections in mice and typhoid fever in man. This study investigates autoradiographically the penetration of ceftriaxone into murine cells of liver, spleen and kidney, with emphasis on the cells of the reticuloendothelial system (RES). The RES is an important site of localization of the pathogenic agent of typhoid fever. An incorporation of ceftriaxone was found in several cell types of the three investigated organs, in particular the cells of the RES and in precursors, e.g. monocytes of the blood stream, Kupffer cells or reticular cells. Besides long biological half-life, satisfactory penetration into phagocytes and other tissue cells has been shown, which is essential to the good in vivo activity of ceftriaxone against systemic Salmonella infections.

Animals↗

[Light and electron microscopy findings in early and late stages of heart failure. Studies of endomyocardial biopsies of patients with latent (LCM) and dilated (DCM) cardiomyopathy].

Right-ventricular myocardial biopsies were obtained from 28 patients with LCM (EF 72 +/- 10.4%) and 36 patients with DCM of different degrees (EF 45 +/- 15%). Using paraffin sections and electron micrographs, 16 structural variables were semiquantitatively evaluated. Hypertrophy of myofibres, and nuclear and mitochondrial alterations were significantly more pronounced in patients with DCM. A score of 9 selected variables was found to be significantly higher in the DCM-group as compared with the LCM-group. The diameter of the myofibres was significantly thicker in DCM (17.5 +/- 2.2 microns) than in LCM (14.6 +/- 0.95 microns), but no significant difference of the volume density of myofibrils and of mitochondria could be determined. In the myocytes of DCM the mitochondria were significantly smaller than in LCM. The EF correlates with the myofibre thickness, with the semiquantitative score, and with the size of the mitochondria, but no significant correlation was seen with the volume density of myofibrils or mitochondria. The study has shown: At present no alterations in myocardial biopsies are known to be diagnostic for LCM or DCM. The findings support the concept of a diffuse myocardial disease in LCM. Only one patient out of 28 exhibited a myocardium without any pathologic changes. There is no evidence for small vessel disease in LCM. From the morphological point of view DCM and LCM are different only in quantity, but not in quality of their structural alterations.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗

[Reduction of patient dose with maximum assurance of image quality].

Four methods of reducing the patient dose are reviewed. Without doubt, the patient dose can be considerably reduced by relatively simple means: With rare-earth screens by a factor of 2-4 compared with a CaWO4 universal screen (1 mR) and in some cases by a factor of 1.5-2 with prefiltration. A more complicated and expensive method is the 100 mm spotfilm technique. This permits a dose rate reduction by a factor of 10 compared with a CaWO4 universal screen or by a factor of 5 compared with a universal system with rare-earth screens. In the wide-ranging field of digital radiography, the possibilities of dose reductions by means of digital processing of conventional film screen exposures are investigated.

Absorption↗

[Myocardial hypertrophy: regression in hypertrophic cardiomyopathies?].

In contrast to all commonly observed myocardial disorders presenting more or less pronounced hypertrophy in the sense of an adaptation to increased work load, the hypertrophic process in hypertrophic cardiomyopathies is characterized by the unknown etiology and pathogenesis (no adaptation), by the non homogeneous gross anatomic and microscopic picture, by the problems in measuring the muscle mass, by a non dilating ventricular cavity during follow-up, by the lack of experimental models in animals, and by concealed myocardial storage diseases. Methods for the investigation of the regression of hypertrophy include echocardiography, angiocardiography, ECG and myocardial biopsy. The studies are based on changes of hypertrophy in the natural course and after the application of propranolol, verapamil and surgical management respectively. According to previous available results regression of cardiac hypertrophy could not be proved either during the natural course nor after medical or surgical treatment. The data indicate that clinical and hemodynamic improvements observed after therapeutic interventions are not induced by global or regional decrease of myocardial mass. They may be a consequence of systolic and diastolic improvement of ventricular function, which apparently is independent of regression of cardiac hypertrophy.

Animals↗