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Biomedical subjects

M Zabel

Publications and source records attributed to M Zabel.

At least 73 records · Page 4Linked to original sources

[Cardiac autonomic tone in risk stratification after myocardial infarct: results of a prospective long-term study of 411 consecutive patients].

Prognosis of patients surviving acute myocardial infarction has substantially improved over the last two decades. However, stratification of patients at risk for death due to arrhythmic events remains a clinical challenge. Due to the important role of the autonomic nervous system in the genesis of sudden death, autonomic markers such as heart rate variability and baroreflex sensitivity have recently gained attention as risk stratification parameters. The present study reports the results of noninvasive risk stratification in 411 consecutive postinfarction patients treated due to contemporary therapeutical guidelines with a high proportion of patients discharged with a patent infarct related artery. The diagnostic arsenal of risk parameters comprised heart rate variability, baroreflex sensitivity, and more traditional markers such as non-sustained ventricular tachycardia, left ventricular ejection fraction, and ventricular late potentials. Patients were followed for a mean of 33 +/- 21 months. Stepwise logistic regression analysis revealed that left ventricular function, both autonomic markers, and the patency of the infarct related artery were independent predictors of the prospectively defined primary study endpoint, i.e., all-cause mortality plus ventricular tachyarrhythmic events. With respect to the secondary endpoint (ventricular tachyarrhythmic events), left ventricular function, heart rate variability, and infarct vessel patency were independent predictors. Ventricular late potentials and nonsustained ventricular tachycardia had no predictive value with respect to ventricular tachyarrhythmic events. These findings from a large prospective long-term study demonstrate the value of markers of cardiac autonomic tone in identifying infarct survivors at risk for malignant ventricular tachyarrhythmias and sudden death.

Adult↗

[T-wave alternans in microwave frequency as a new indicator of disordered ventricular repolarization: pathophysiology, methodology, clinical results].

Primary prevention of sudden cardiac death is hampered by the inability to accurately identify high risk patients. Various noninvasive methods such as determination of left ventricular function or heart rate variability as well as invasive electrophysiologic testing are currently used for risk stratification. Noninvasive measurement of microvolt T wave alternans (TWA) is a promising new method to assess repolarization abnormalities; in experimental studies, TWA was associated with an increased incidence of ventricular tachyarrhythmias. Since the occurrence of TWA is heart rate-dependent, it is measured either during atrial pacing or during exercise stress testing. The first clinical validation of the method was performed in patients undergoing invasive EP testing to assess prediction of inducibility of ventricular tachyarrhythmias. A first prospective validation of the noninvasive method was performed in patients surviving out-of-hospital cardiac arrest fitted with an ICD. Further studies have shown a good concordance between invasive and noninvasive TWA determination. The occurrence of TWA in this population was of predictive value with respect to arrhythmia recurrence. Recently published data confirm the value of TWA assessment with respect to identification of patients with congestive heart failure at high risk of malignant ventricular tachyarrhythmias. The use of this method in post myocardial infarction risk stratification is currently under prospective evaluation.

Cardiac Pacing, Artificial↗

Polyhormonal aspect of the endocrine cells of the human fetal pancreas.

Histological studies were performed on 30 pancreases obtained from normal human fetuses aged between the 9th and 38th week. For immunocytochemistry, the avidin-biotin-peroxidase method was used to identify and colocalise insulin, glucagon, somatostatin, pancreatic polypeptide and proliferating cell nuclear antigen. In the 9th week, cells containing all investigated peptides were present. During the fetal period, two populations of endocrine cells have been distinguished, Langerhans islets and freely dispersed cells. The free cells were polyhormonal, containing insulin, glucagon, somatostatin and pancreatic polypeptide, and were localised in the walls of pancreatic ducts throughout the whole gland. During the development of the islets we have observed four stages: (1) the scattered polyhormonal cell stage (9th-10th week), (2) the immature polyhormonal islet stage (11th-15th week), (3) the insulin monohormonal core islet stage (16th-29th week), in which zonular and mantle islets are observed, and (4) the polymorphic islet stage (from the 30th week onwards), which is characterised by the presence of monohormonal cells expressing glucagon or somatostatin. Bigeminal and polar islets also appeared during this last stage. The islets consisted of an insulin core surrounded by a thick (in the part developing from the dorsal primordium) or thin rim (part of the pancreas concerned with the ventral primordium) of intermingled mono- or dihormonal glucagon-positive or somatostatin-positive cells. The most externally located polyhormonal cells exhibited a reaction for glucagon, somatostatin and pancreatic polypeptide. Apart from the above-mentioned types of islets, all arrangements observed in earlier stages were present. Proliferating cell nuclear antigen-positive cells (single in the large islets and more numerous in the smaller ones) were predominantly observed in the outermost layer. Taken together our data indicate that, during the human prenatal development of the islet, endocrine cells are able to synthesise several different hormones. Maturation of these cells involved or depended on a change from a polyhormonal to a monohormonal state and is concerned with decreasing proliferative capacity. This supports the concept of a common precursor stem cell for the hormone-producing cells of the fetal human pancreas.

Animals↗

Prevalence, characteristics and prognostic value during long-term follow-up of nonsustained ventricular tachycardia after myocardial infarction in the thrombolytic era.

OBJECTIVES: The purpose of this study was to determine the prevalence, characteristics and the predictive value of nonsustained ventricular tachycardia (VT) for subsequent death and arrhythmic events after acute myocardial infarction (AMI). BACKGROUND: Nonsustained VT has been linked to an increased risk for sudden death in coronary patients. It is unknown whether this parameter can be used for selection of high-risk patients to receive an implantable defibrillator for primary prevention of sudden death in patients shortly after AMI. METHODS: In 325 consecutive infarct survivors, 24-h Holter monitoring was performed 10+/-6 days after AMI. All patients underwent coronary angiography, determination of left ventricular function and assessment of heart rate variability (HRV). Mean follow-up was 30+/-22 months. RESULTS: There was a low prevalence (9%) of nonsustained VT shortly after AMI. Nonsustained VT together with depressed left ventricular ejection fraction (LVEF) was found in only 2.4% of patients. During follow-up, 25 patients reached one of the prospectively defined end points (primary composite end point of cardiac death, sustained VT or resuscitated ventricular fibrillation; secondary end point: arrhythmic events). Kaplan Meier event probability analyses revealed that only HRV, LVEF and status of the infarct-related artery were univariate predictors of death or arrhythmic events. The presence of nonsustained VT carried a relative risk of 2.6 for the primary study end point but was not a significant predictor if only arrhythmic events were considered. On multivariate analysis, only HRV, LVEF and the status of the infarct artery were found to be independently related to the primary study end point. CONCLUSIONS: There is a low prevalence of nonsustained VT shortly after AMI. Only 2% to 3% of all infarct survivors treated according to contemporary guidelines demonstrate both depressed LVEF and nonsustained VT. The predictive value of nonsustained VT for subsequent mortality and arrhythmic events is inferior to that of impaired autonomic tone, LVEF or infarct-related artery patency. Accordingly, the use of nonsustained VT to select patients for primary implantable cardioverter/defibrillator prevention trials shortly after AMI appears to be limited.

Adult↗

Immunocytochemical study of parafollicular (C) cells of the thyroid in some wild rodents.

Studies were done on 3 wild species of rodents: field voles (Microtus agrestis, Linnaeus 1761), bank voles (Clethrionomys glareolus, Schreber 1780), and forest mice (Apodemus flavicollis, Melchior 1834). Immunocytochemical reactions were used to detect calcitonin (CT), calcitonin gene-related peptide (CGRP), neuron-specific enolase (NSE), chromogranin A (CgA) in the thyroid parafollicular (C) cells in all species examined. Antisera to human CT, rat CGRP, bovine CgA, rat NSE and human NSE give probably a positive reaction in all C cells in the rodents examined. However, in the NSE determining reaction, much feebler positive C cells were observed. Individual variation in respect of shape and distribution of C cells was observed in all species. In forest mice the C cells resembled in shape the C cells previously described in mouse and rat. In field voles and bank voles the C cells were assembled into small groups more often than in forest mice. Antibodies (anti-human CT, anti-rat CGRP, anti-bovine CgA, anti-rat NSE and anti-human NSE) used by us were good markers of C cells in the thyroids of the 3 species of free-living rodents examined.

Animals↗

Effect of follicular cells on calcitonin gene expression in thyroid parafollicular cells in cell culture.

Expression of calcitonin (CT) gene in thyroid parafollicular cells involves alternate formation of CT mRNA or CGRP mRNA. High amounts of CT mRNA are formed only in thyroid gland and formation of CGRP mRNA dominates in the remaining organs. Apart from paracrine and endocrine factors, mRNA formation on the CT gene seems to be affected also by direct contacts with other cells present in the thyroid gland, in which parafollicular cells are located next to follicular cells. The present study aimed at examining whether thyroid follicular cells affect formation of mRNAs for CT and CGRP in parafollicular cells. The studies were performed in cell cultures. A parafollicular cell line (TT cells) and a follicular cell line (F6BTY cells) served as the experimental model. For comparison, co-cultures with fibroblasts, 3T3 cells, and malignant melanoma, MM cells, were also examined. CT gene expression was examined at the level of mRNAs (in situ hybridization and morphometric studies) and at the level of hormones (immunocytochemistry, morphometric studies and radioimmunological estimation of hormone levels in the medium). The immunocytochemical and hybridocytochemical studies, in line with morphometry studies, demonstrated that F6BTY and 3T3 cells were capable of affecting mRNA production for CT and CGRP and that they changed the ratio of CGRP/CT secretion by TT cells, as a sequel of contact between the two cell types and due to mediation of secreted substances. On the other hand, the malignant melanoma MM cells showed no effect on the secretion ratio. Our study seems to indicate that control of mRNA formation from CT gene may involve not only humoral factors but also direct contacts with other cells, which may explain differences in expression of the gene between cells localized in different organs.

Calcitonin↗

Strumal carcinoid of ovary. A case report with immunohistochemical investigations.

Clinical, histological and immunohistochemical findings in a rare ovarian tumor--strumal carcinoid--are presented. Neuropeptides detected by immunoreactions revealed the origin of tumor cells from the midgut. Immunohistochemical reaction revealed parathyroid hormone-related protein (PTHrp) in the carcinoid cells. After surgical resection of the tumor a decrease in serum calcium level was observed.

Carcinoid Tumor↗

Immunocytochemical localisation of PTHrP (parathormone-related peptide) in myoepithelial cells of human sweat and parotid glands.

PTHrP is a HHM-inducing peptide. It exhibits certain structural similarity to PTH and the two hormones may act through the same receptors. PTHrP is known to be produced in various tissues as well as during development. In this study we decided to immunocytochemically demonstrate PTHrP in normal skin and squamous cell carcinomas as well as in parotid glands (normal, inflamed and neoplastic). In the skin, PTHrP expression was demonstrated in epidermis and in smooth muscle cell layer of blood vessels. In squamous cell carcinomas, the expression was noted in foci of keratinization. In parotid glands, the peptide was localised in excretory ducts and in blood vessels, while inflammation of the gland and its tumours resulted most frequently in the less intense immunoreaction. The results are consistent with those of other authors. The novel observations include demonstration of PTHrP expression in myoepithelial cells of sweat glands and in parotid glands, where it may be involved in the control of their contractile activity.

Carcinoma, Squamous Cell↗