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Biomedical subjects

U Mayer

Publications and source records attributed to U Mayer.

At least 91 records · Page 5Linked to original sources

Chemical ablation by subendocardial injection of ethanol via catheter--preliminary results in the pig heart.

This study was set up to discover how a subendocardial application of ethanol administered via a catheter would affect an animal model. A 7 F bipolar catheter with a lumen, through which a 2 mm needle was inserted, was placed in the left ventricle of 11 pigs. Altogether, 33 subendocardial injections into the left ventricular myocardium were performed under fluoroscopic control using a mixture of 0.5-1.5 ml ethanol and 0.5-1 ml iopamidol as contrast medium. The mixtures were injected into the apical, lateral and septal walls of the left ventricle. After 25 days, the hearts were removed and the lesions examined pathologically. The calculated volume of the lesions was about 60 mm3, the area in projection to the endocardium about 35 mm2, the depth relative to the endocardium about 1.5 mm and the maximum diameter about 8 mm. Perforation of the myocardial wall by pericardial injection occurred twice without further complications. Subendocardial application of concentrated ethanol by catheter caused a controlled local necrosis. This technique may become a new approach with which to treat ventricular tachycardia by chemical ablation.

Animals↗

Mosaic structure of globular domains in the human type VI collagen alpha 3 chain: similarity to von Willebrand factor, fibronectin, actin, salivary proteins and aprotinin type protease inhibitors.

Human collagen alpha 3(VI) chain mRNA (approximately 10 kb) was cloned and shown by sequence analysis to encode a 25 residue signal peptide, a large N-terminal globule (1804 residues), a central triple helical segment (336 residues) and a C-terminal globule (803 residues). Some of the sequence was confirmed by Edman degradation of peptides. The N-terminal globular segment consists of nine consecutive 200 residue repeats (N1 to N9) showing internal homology and also significant identity (17-25%) to the A domains of von Willebrand Factor and similar domains present in some other proteins. Deletions were found in the N3 and N9 domains of several cDNA clones suggesting variation of these structures by alternative splicing. The C-terminal globule starts immediately after the triple helical segment with two domains C1 (184 residues) and C2 (248 residues) being similar to the N domains. They are followed by a proline rich, repetitive segment C3 of 122 residues, with similarity to some salivary proteins, and domain C4 (89 residues), which is similar to the type III repeats present in fibronectin and tenascin. The most C-terminal domain C5 (70 residues) shows 40-50% identity to a variety of serine protease inhibitors of the Kunitz type. The whole sequence contains 29 cysteines which are mainly clustered in short segments connecting domains N1, C1, C2 and the triple helix, and in the inhibitor domain. Five putative Arg-Gly-Asp cell-binding sequences are exclusively localized in the triple helical segment.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗

Pharmacokinetics and metabolism of iodo-doxorubicin and doxorubicin in humans.

The pharmacokinetics of doxorubicin (DOX), iodo-doxorubicin (I-DOX) and their metabolites in plasma has been examined in five patients each receiving 50 mg/m2 of both anthracyclines as a bolus injection. Terminal half-life, mean residence time (MRT), peak plasma concentration Cmax, and area under the curve (AUC) appeared smaller for I-DOX, whereas its plasma clearance (CLP) and volume of distribution at steady state (Vss) were larger than for DOX. The major metabolite of I-DOX was iodo-doxorubicinol (I-AOL) followed by doxorubicinol aglycone (AOLON). The AUC of I-AOL was 6-times larger than that of its counterpart AOL, which is the major metabolite of DOX. AOLON generated after I-DOX administration is a further important metabolite, as its AUC was 10-times larger than that of AOLON generated from DOX. The other aglycones, such as doxorubicin aglycone (AON) and the 7-deoxy-aglycones were only minor metabolites after either I-DOX or DOX injection. The ratio AUCI-AOL/AOL/AUCI-DOX/DOX was 27 in the case of I-DOX and 0.4 after DOX. The terminal half-lives of the cytostatic metabolites I-AOL and AOL were similar, although a longer MRT for AOL was calculated. Both metabolites had much longer MRTs than their parent drugs. The MRTs of the aglycones AOLON and AON were greater than those of the 7-deoxy-aglycones after both I-DOX and DOX. Approximately 6% DOX and less than 1% I-DOX were excreted by the kidneys during the initial 48 h. About 5% of I-DOX was excreted via the kidneys as I-AOL. Aglycones were not detected in significant amounts.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Toxicity, pharmacokinetics and metabolism of iododoxorubicin in cancer patients.

25 patients, mostly pretreated, received 55 courses of iododoxorubicin as a single intravenous bolus every 2 weeks. The starting dose was 2 mg/m2 with seven steps to reach the dose-limiting toxicity level. 3 patients treated with 90 mg/m2 had WHO grade 4 myelotoxicity; 2 of these patients had not had cytostatic chemotherapy. 3 of 7 patients treated with 75 mg/m2 had grade 3-4 myelotoxicity; 4 had grade 1-2. Non-haematological toxicities were minor. Acute cardiotoxicity and objective tumour responses were not observed. Plasma and urine levels of iododoxorubicin and five metabolites were assayed in 16 patients. Metabolism to iododoxorubicinol was rapid and plasma clearance was dose-dependent and rapid. Plasma levels and the area under the curve for iododoxorubicin increased with dose. The mean residence time was 3.9 h in patients without liver metastasis and 10.4 h in patients with liver metastasis. Renal excretion was minor. The maximally tolerated dose was 90 mg/m2.

Adult↗

[Localization of premature and ectopic ventricular depolarization using a new nuclear medicine tomographic technique].

In planar radionuclide ventriculography (RNV) identification of the site of initial contraction is possibly by the Fourier phase. First clinical experiences will be presented with a new integrated tomographic technique--ISPECT--in noninvasively assessing the site of ectopic or premature ventricular depolarization. In six patients Fourier phases of RNV and ISPECT were performed and compared in five with results from the corresponding electrophysiologic study. It was possible to exactly localize the beginning of mechanical contraction in the two orthogonal planes: during pacemaker stimulation at the apex of the right ventricle, at the lateral border of a large aneurysm during ventricular tachycardia, and at the site of three of five WPW bundles. In the other two bundles the site of first contraction was near the area found during invasive mapping procedure. Thus, this new ISPECT approach together with planar radionuclide imaging may help in noninvasively localizing the site of ectopic and premature depolarization in addition to surface ECG.

Adult↗

Efficacy and safety of intravenous amiodarone in acute refractory arrhythmias.

Few data are available on intravenous amiodarone therapy in refractory arrhythmias. This retrospective study in 50 patients (14 with supraventricular and 36 with ventricular tachyarrhythmias) revealed a favorable effect of intravenous amiodarone in the treatment of life-threatening arrhythmias with an overall success rate of 76%. In the subgroup of patients with ventricular fibrillation and concomitant severe congestive heart failure success rate was low (25%, 2/8), whereas effectiveness in patients with ventricular tachycardias was high (greater than 90%) and proved to be independent of left ventricular function. If patients with recurrent ventricular fibrillation were excluded from the analysis, successful treatment with intravenous amiodarone was achieved in 90%, even in those patients with severely compromised myocardium.

Acute Disease↗

Clastogen-induced fragility may differentiate pancytopenia of congenital dyskeratosis from Fanconi anaemia.

A male infant is reported with congenital dyskeratosis and pancytopenia Zinsser-Engman-Cole. The bone marrow pathology showed similarities to Fanconi anaemia. Ophthalmological complications were vitreous haemorrhage, haemorrhagic cataracta complicata and glaucoma. Spontaneous and diepoxybutane-induced chromosomal fragility was within the range of normal cells but was elevated through induction with 4-nitroquinoline-oxide. These findings are contrasted with those of Fanconi anaemia.

Anemia, Aplastic↗

Sympathoadrenergic regulation of metabolism and cardiocirculation during and following running exercises of different intensity and duration.

In three different field studies running loads of 2 X 200 m and 400 m, 3 X 1000 m and 3000 m, and finally 10,000 m were performed by respective groups of sprinters, middle-, and long-distance runners. We investigated the effects of exercise on the sympathoadrenal system by determining catecholamine (CA) concentrations in the venous blood and urine [free norepinephrine (NE), epinephrine (EPI)] and the respective sulfoconjugates in plasma and various hormonal, metabolic, and cardiocirculatory parameters. Endurance-trained athletes showed a lower heart rate (HR) and plasma renin activity (PRA) at rest in comparison with the sprinters. The concentrations of the plasma CA reflected the intensity more than the duration of exercise. At rest and following recovery the ratio of free NE/EPI in plasma was markedly higher in the group of sprinters in comparison with the long-distance runners. During exercise, however, an opposite movement occurred resulting in a higher ratio in the latter group. The pre-start ratios of NE/EPI in urine were similar to those in plasma. The sports disciplines' specific differences in NE/EPI both at rest and during exercise suggest that the overall sympathetic activity, reflected by NE and EPI, is regulated in a quite differentiated pattern. The sulfoconjugated CA, however, increased less clearly after the middle- and long-distance bouts than the respective free CA which caused the ratio sulfates/free CA to decline. There were strong relations between the levels of free plasma NE and EPI and that of blood lactate which, however, rather reflects a parallelism subsequent to the highly intensive stimulation.

Adaptation, Physiological↗

A group of genes required for pattern formation in the ventral ectoderm of the Drosophila embryo.

Mutations in the genes spitz (spi), Star (S), single-minded (sim), pointed (pnt), rhomboid (rho) (all zygotic), and sichel (sic) (maternal), collectively called the spitz group, cause similar pattern alterations in ventral ectodermal derivatives of the Drosophila embryo. The cuticle structures lacking in mutant embryos normally derive from longitudinal strips of the ventro-lateral blastoderm. Defects were found in the median part of the central nervous system in whole-mount embryos stained with anti-HRP (horseradish peroxidase) antibodies. In addition, the nerve cells expressing the even-skipped protein appeared abnormally arranged. These results suggest that groups of cells from the same region, including both epidermal and neural precursor cells, require spitz-group gene activity for normal development. The members of the spitz group differ from one another: sim affects a more median strip of the ventral ectoderm than the other zygotic genes and pnt causes separation rather than deletion of pattern elements. As shown by pole cell transplantations, spi and S are also required for normal development of the female germ line, while sim, rho, and pnt appear to be exclusively zygotically expressed, and the maternal gene sic acts in the germ line autonomously. Some embryos produced by sic-homozygous females differentiate the spitz phenotype, others develop normally or die early. Of all the spitz-group genes, sim appears to have the most specific effect on the embryonic pattern. The significance of the spitz-group phenotypes for the dorso-ventral pattern formation is discussed.

Animals↗

[Short stature, mental retardation, type I preaxial polydactyly with colobomatous abnormalities: a new syndrome].

A syndrome which consists of growth retardation, mental deficiency, preaxial polydactyly and colobomatous anomalies was observed in two sibs and might have been transmitted by an autosomal recessive mutation. In the brother there is an incomplete coloboma of the optic nerve head, in the sister a coloboma of the iris, optic nerve head, choroid, and retina. Polydactyly is unilateral. Similar observations have been quoted but no identical case seems to have been published.

Adolescent↗

Increased hyaluronate synthesis is required for fibroblast detachment and mitosis.

Human-embryo fibroblasts were synchronized by means of colchicine and cytochalasin, and the production of hyaluronate was determined by [3H]glucosamine incorporation and ion-exchange chromatography. Cells arrested by colchicine synthesized small amounts of hyaluronate, whereas cells blocked by cytochalasin were stimulated in hyaluronate production. When the colchicine block was released, there was an increased synthesis of hyaluronate, which appeared first in the cellular fraction and was then shed into the culture medium. After release of the cytochalasin block, the hyaluronate production declined to that found with unsynchronized cells. A comparable increase of hyaluronate synthase activity was observed during mitosis. When hyaluronate synthesis was blocked by periodate-oxidized UDP-glucuronic acid, the cells were arrested in mitosis before rounding of cells. These results suggest that hyaluronate synthesis is required for detachment and rounding of cells during mitosis.

Cell Cycle↗

[Fatal poisoning by the retard form of verapamil. Therapeutic considerations].

A 60-year-old woman swallowed 2.4 g verapamil in a retard form (Isoptin retard). Depsite intensive efforts she died 44 hours later in a coma due to circulatory collapse. In contrast to other reported cases of poisoning, the verapamil concentration in plasma continued to rise. This atypical course with continuing absorption of verapamil was due to small-intestinal deposits of the drug, found at autopsy.

Coma↗

Extreme variant of septo-optic dysplasia.

A newborn female is demonstrated, the first child of healthy unrelated parents who was born after an uneventful pregnancy. Computerized tomography of the brain revealed gross malformations of the parietal and occipital lobes, of the cerebellum and of midline structures. The pictures are reminiscent of hydranencephaly. The association with bilateral coloboma of the papilla and diabetes insipidus is considered an extreme variant of septo-optico dysplasia.

Brain↗

[Involvement of the eye in polycythemia vera (Vaquez-Osler disease)].

An example of chocked disk of 3-4 diopters (right eye) and 4-5 diopters (left eye) in a patient with cerebral alteration (encephalomalacia respectively bleeding) suffering from polycythemia vera is discussed in the light of own observation, literature, differential diagnosis, pathogenesis, and therapy. An internal treatment by radioactive phosphorus and blood-letting gave restitutio fere ad integrum.

Adult↗