Search PubMed⌕ Search

Biomedical subjects

M Zabel

Publications and source records attributed to M Zabel.

At least 127 records · Page 7Linked to original sources
PubMed1995

Immunocytochemical characterization of two thyroid medullary carcinoma cell lines in vitro.

The immunocytochemical characterization of cell lines originating from thyroid medullary carcinoma, i.e. human TT cells and rat rMTC 6-23 cells, was undertaken. The immunocytochemical studies were supplemented by ultrastructural studies, including ultrastructural immunocytochemistry, and by radioimmunological estimation of calcitonin secretion to the medium. In rMTC 6-23 cells (subcultures 24 to 30), no hormone presence was demonstrated immunocytochemically, which corresponded to the absence of secretory granules at the ultrastructural level. Of various proteins sought, only neuron-specific enolase could be demonstrated. Nevertheless, the cells secreted calcitonin into the medium. TT cells (passages 145 to 160) produced secretory granules. The granules contained calcitonin, calcitonin gene-related peptide, somatostatin, neurotensin, met-enkephalin, leu-enkephalin, gastrin releasing peptide, parathyroid hormone-related protein, functional proteins of the chromogranin group and synaptophysin. Other functional proteins found in the cytosol of TT cells included non-specific enolase, calbindin and tyrosine hydroxylase. Receptor for calcitriol was localized in the cell nucleus. Marker proteins were localized in the cytosol (carcinoembryonic antigen) and in the cell skeleton (alpha-tubulin, cytokeratin). Following changes in ionized calcium levels in the medium, changes in calcitonin secretion and in immunocytochemical detectability of some hormones and functional proteins were observed. TT cells demonstrated the expression of numerous hormones and functional proteins associated with calcitonin secretion. Further, the cells in their ultrastructure, immunocytochemical and secretory characteristics, resemble more closely normal parafollicular cells of the thyroid and, in our opinion, represent a more appropriate model for functional studies.

Animals↗
PubMed1994

Hybridocytochemical and immuno-ultrastructural study of calcitonin gene expression in cultured medullary carcinoma cells.

The study was aimed at a morphological demonstration of calcitonin (CT) gene expression in cultured TT cells, or, more specifically, hybridocytochemical detection of CT mRNA and calcitonin gene-related peptide (CGRP) mRNA and ultrastructural localization of the two hormones. The TT cells originated from medullary carcinoma of human thyroid gland. Ultrastructural studies of TT cells demonstrated a well-developed rough endoplasmic reticulum, large Golgi apparatus and low number of secretory granules. Hybridocytochemical studies showed the presence of mRNAs for CT and CGRP in all TT cells. At the ultrastructural level, double immunolabelling demonstrated that the two hormones were always expressed together in the same secretory granules. Our results provide a significant addition to the biochemical studies performed up to now and indicate that all TT cells produce both mRNAs and both hormones in parallel.

Calcitonin↗
PubMed1994

Changes in autonomic tone following thrombolytic therapy for acute myocardial infarction: assessment by analysis of heart rate variability.

INTRODUCTION: Little data are available on changes in autonomic tone during the first 24 hours of acute infarction in patients undergoing thrombolytic therapy. Particularly, the association of changes in autonomic tone to reperfusion of the infarct-related artery has not been evaluated in man. Heart rate variability (HRV) is a noninvasive tool to assess cardiac autonomic tone, which carries prognostic information in postinfarction patients. METHODS AND RESULTS: To assess changes in autonomic tone with angiographically assessed success of thrombolysis in patients with acute infarction, the proportion of adjacent RR intervals different by greater than 50 msec (pNN50) was analyzed from 24-hour Holter monitoring initiated before the start of thrombolytic therapy in 103 consecutive patients. Mean heart rate (HR) and pNN50 were available in 95 of 103 patients and were separately analyzed for the first hour after initiation of thrombolysis (reperfusion phase) and the first 24 hours. As assessed by coronary angiography 90 minutes after start of thrombolysis, 74 patients (78%) had successful coronary artery reperfusion. HR averaged 72 +/- 13/min for the first hour in all 95 patients and 74 +/- 13/min for the first 24 hours. The respective values for pNN50 were 11.2% +/- 11.7% for the first hour and 9.7% +/- 9.2% for the first 24 hours. Patients with inferior myocardial infarction (MI) had a lower mean HR of 72 +/- 12/min versus 76 +/- 13/min (P = 0.11) and a higher pNN50 (11.2% +/- 9.8% versus 7.6% +/- 8.3%, P = 0.01) compared to patients with anterior MI. The mean HR correlated weakly with pNN50 (r = -0.33, P < 0.01). For patients with coronary artery patency after 90 minutes, mean HR was 70 +/- 12/min for the first hour compared to 80 +/- 13/min for patients without (P = 0.003). For the first 24 hours, these values were 72 +/- 12/min compared to 80 +/- 14/min (P = 0.02). For the first hour, pNN50 averaged 12.6% +/- 12.4% for patients with successful reperfusion compared to 6.6% +/- 7.3% for patients without (P = 0.024). For the first 24 hours, these values were 9.2% +/- 8.5% compared to 11.5% +/- 11.3% (P = NS). Patients with in-hospital ventricular fibrillation (n = 8) had a higher mean HR throughout the first 24 hours (88 +/- 16/min vs 73 +/- 12/min, P = 0.008) compared to patients with an uneventful course. Additionally, there was a trend toward a lower HRV in patients with ventricular fibrillation. CONCLUSION: Thrombolysis-induced reperfusion of the infarct-related artery results in a higher vagal tone during the early hours of MI as compared to failed reperfusion. This finding is independent from infarct location and associated with a trend toward a lower incidence of ventricular fibrillation during the acute phase of infarction.

Acute Disease↗
PubMed1994

Open infarct artery, late potentials, and other prognostic factors in patients after acute myocardial infarction in the thrombolytic era. A prospective trial.

BACKGROUND: Successful reperfusion of the infarct-related artery in patients with acute myocardial infarction has been shown to reduce in-hospital as well as 1-year mortality. Besides the thrombolysis-induced myocardial salvage, there is increasing evidence that an open infarct-related artery results in increased electrical stability of the heart and that this effect is at least in part responsible for the favorable long-term outcome of these patients. The exact incidence of arrhythmic events during the first year after myocardial infarction and the predictive value of different risk factors for these complications, however, have not been determined in patients in the thrombolytic era. METHODS AND RESULTS: A total of 173 patients with acute myocardial infarction, 51% treated with thrombolysis, were prospectively entered into the study. At the time of hospital discharge, signal-averaged ECG, Holter monitoring, radionuclide angiography, coronary angiography, and levocardiography were performed in all patients. An open infarct-related artery was documented in 136 patients. The overall incidence of late potentials was 24% (41 patients). By multivariate analysis, an occluded infarct-related artery (P = .04) and the presence of regional wall motion abnormalities (P = .02) were the strongest independent predictors for the development of a late potential. Residual ischemia was treated by either percutaneous transluminal coronary angioplasty or surgery in 86 of 173 patients (50%). Seventy percent of the patients received beta-blocker therapy. During a mean follow-up of 12 +/- 5 months, 7 patients died suddenly or had ventricular fibrillation documented, while only 2 developed sustained monomorphic ventricular tachycardia. Overall 1-year mortality was 4.1%. Multivariate analysis revealed only an occluded infarct-related artery as an independent predictor of arrhythmic complications (P = .017). CONCLUSIONS: In patients with acute myocardial infarction treated according to contemporary therapeutic guidelines, with a large proportion of individuals undergoing coronary artery revascularization, a low incidence of arrhythmic events, particularly of ventricular tachycardia, was observed in the first year after the index infarction. The presence or absence of an open infarct-related artery was the strongest independent predictor of these events, whereas other traditional risk factors, such as late potentials, were less helpful in identifying patients prone to sudden death. These findings emphasize the importance of the open artery hypothesis in patients recovering from acute myocardial infarction.

Adult↗
PubMed1994

Immunocytochemical studies on pancreatic endocrine cells at early stages of development of the pig.

The studies were performed on pig embryos between 23rd and 31st day of intrauterine life. Immunocytochemical markers of neuroendocrine cells, i.e. neuron-specific enolase, chromogranin and synaptophysin as well as basal hormones, i.e. insulin, glucagon, somatostatin, pancreatic polypeptide and, additionally, serotonin and gastrin were detected in serial sections. Our studies indicate that differentiation of pancreatic endocrine cells does not take place unitemporally. At the first stage, the cells acquire the traits of neuroendocrine cells and secrete more than one hormone while final specialization toward cells secreting individual hormones take places at a later stage.

Animals↗
PubMed1993

Effect of sotalol on heart rate variability assessed by Holter monitoring in patients with ventricular arrhythmias.

Reduced vagal activity has been demonstrated to be associated with an increased risk of sudden death. Assessing the heart rate variability as a measure of the autonomic control of the heart has been established as a useful tool for the risk stratification of patients after myocardial infarction. In the current study, heart rate variability assessed by time- and frequency-domain measures was determined from Holter recordings before and during treatment with sotalol in 28 patients with chronic ventricular arrhythmias. The heart rate variability at baseline was independent of the presence or absence of spontaneous arrhythmias and of left ventricular function. Therapy with sotalol produced a significant improvement over control values in indices of parasympathetic tone (root mean square of the difference in successive RR intervals, proportion of adjacent RR intervals different by > 50 msec, high-frequency power spectrum). This improvement was not related to drug-induced changes in the mean heart rate or the suppression of ventricular ectopic activity. These effects on heart rate variability may contribute significantly to the overall efficacy profile of sotalol.

Adult↗
PubMed1993

Usefulness of CKMB and troponin T determinations in patients with acute myocardial infarction complicated by ventricular fibrillation.

The usefulness of creatine kinase (CK) time activity curves for diagnosis of acute myocardial infarction in patients who have been defibrillated for ventricular fibrillation is limited due to the release of the enzyme as a result of the countershock. The present study of four patients with acute infarction complicated by primary ventricular fibrillation indicates that analysis of CKMB and even more so of troponin T, a specific cardiac antigen, permits reliable diagnosis of acute myocardial infarction in this particular setting. Furthermore, the data indicate that noninvasive assessment of coronary artery patency may be also possible in these patients by means of these two serum markers.

Acute Disease↗
PubMed1993

In vitro prediction of cytostatic drug resistance in primary cell cultures of solid malignant tumours.

The in vitro monolayer proliferation assay (MP-assay) described here enables predictive determination of the efficacy of anticancer drugs considered for clinical application. The assay was designed (1) to achieve a high plating efficiency, (2) to adapt in vitro growth as close as possible to in vivo conditions, and (3) to prove that the cells in vitro correspond with the in vivo tumour cells they were derived from. From 452 freshly explanted or biopsied tumours, 321 (71%) proliferating cultures could be established. To prove malignant origin of the incubated cells each strain was characterised by DNA-cytophotometry for aneuploidy and by immunocytochemistry for marker proteins. Drug potency was determined by comparing the number of living cells in drug-treated cultures with non-treated controls. Drug concentrations in vitro corresponded with those achievable in tumour tissue and thus represented clinically relevant levels. Growth inhibition in vitro was correlated with in vivo tumour response. Two hundred in vitro/in vivo correlations were performed (50 retrospective, 150 prospective). Overall predictive accuracy of the MP-assay was 86%, with correct indication of resistance in 94.5% and of sensitivity in 75.8% (P < 0.001). The results show that the proposed assay is capable of estimating the response probability of cytostatic drugs in individual tumours and thus can contribute to reducing the applications of non-effective drugs and, within limitations, to improving the basis of drug selection.

Antineoplastic Agents↗
PubMed1993

Endocrine markers in malignant tumor cells producing parathyroid hormone-related protein.

Humoral hypercalcemia of malignancy may reflect the synthesis and secretion of biologically active parathyroid hormone-related protein (PTHrP) by a given tumor. In the present study we investigated 25 human non-endocrine carcinomas which were clinically associated with hypercalcemia (Ca > 11 mg%). By applying PTHrP-specific immunocytochemistry, PTHrP could be detected in all tumors. The intra-tumorous distribution was heterogeneous with strong positivity in relatively few cells or weak positivity in the majority of cells. Surprisingly, in the PTHrP producing cells none of the marker proteins typical of endocrine cells (neuron-specific enolase, Leu-7 antigen, chromogranin, synaptophysin and endocrine granule constituent) was found. On the other hand, PTHrP producing cells of endocrine origin, such as medullary cancer, or normal and adenomatous parathyroid glands, all produce these endocrine markers. Thus for the first time, the existence of peptide hormone producing tumor cells is reported without expression of endocrine markers. This indicates a special mechanism of PTHrP secretion.

Adenoma↗
PubMed1993

Analysis of creatine kinase, CK-MB, myoglobin, and troponin T time-activity curves for early assessment of coronary artery reperfusion after intravenous thrombolysis.

BACKGROUND: Thrombolysis has become the standard therapeutic approach in patients with acute myocardial infarction. To identify patients who may benefit from early invasive procedures, reliable noninvasive assessment of success or failure of thrombolytic therapy is mandatory. METHODS AND RESULTS: In a prospective study in 63 consecutive patients undergoing thrombolysis for their first myocardial infarction, serial measurements of creatine kinase (CK), its isoenzyme CK-MB, myoglobin, and troponin T were done to determine their value for noninvasive prediction of coronary artery patency. Blood samples were drawn every 15 minutes during the first 90 minutes, every 30 minutes during the first 4 hours, every 4 hours during the first 24 hours, and every 8 hours during the first 72 hours. The perfusion status of the infarct-related artery was assessed angiographically 90 minutes after initiation of thrombolysis. For each marker, time to its peak concentration and its early initial slope (start of thrombolysis to 90 minutes thereafter) were determined. Areas under receiver operator characteristic (ROC) curves were 0.83, 0.76, 0.82, and 0.80 for maxima of CK, CK-MB, myoglobin, and troponin T, respectively (p = NS by univariate Z test). The corresponding values for early slopes of CK, CK-MB, myoglobin, and troponin T were 0.79, 0.82, 0.89, and 0.80 (p = 0.23 for comparison between myoglobin and CK-MB; p = 0.07 between myoglobin and CK). Sensitivity, specificity, and positive and negative predictive values regarding noninvasive prediction of coronary artery patency after 90 minutes were 80%, 82%, 95%, and 61% for time to CK maximum; 91%, 77%, 91%, and 77% for time to myoglobin maximum; 87%, 71%, 89%, and 67% for early CK slope; and 94%, 88%, 94%, and 82% for myoglobin slope, respectively. When myoglobin slope was assessed together with other clinical reperfusion markers (resolution of chest pain or ST segment elevation, occurrence of reperfusion arrhythmias) by logistic regression analysis, only the myoglobin slope was an independent predictor of coronary artery patency (p < 0.0001). CONCLUSIONS: With regard to noninvasive prediction of coronary artery patency after thrombolytic therapy, measurement of the early initial slopes of the serum markers within only 90 minutes after the initiation of therapy is as accurate as the determination of the time to their peak concentration. Compared with the other markers examined, myoglobin appears to have advantages because of its earlier rise, yielding a better negative predictive value and a higher area under the ROC curve for determination of its early initial slopes.

Adult↗
PubMed1993

[QT-dispersion in the surface ECG as a parameter of increased electrical vulnerability in acute myocardial ischemia].

QT-dispersion defined as the difference between QTmax and QTmin in the 12-lead surface ECG was determined in 33 patients with acute myocardial infarction treated by intravenous thrombolysis. In 11 patients, ventricular fibrillation ensured during the first 24 h after hospital admission. These patients were then compared with 22 matching infarction patients without malignant ventricular rhythm disturbances. QT-dispersion as evaluated in the first ECG taken after hospital admission was significantly higher in patients with (88 +/- 16 ms) compared to QT-dispersion in patients without ventricular fibrillation (66 +/- 19 ms; p < 0.001). When QT-dispersion was again assessed in ECG tracings recorded prior to hospital discharge, it was markedly reduced, with no significant difference between either patient group (53 +/- 16 ms versus 54 +/- 18 ms). These results indicate that QT-dispersion in the surface ECG represents a marker of inhomogeneous repolarization in patients with acute myocardial infarction prone to ventricular fibrillation. This may allow early identification of high-risk patients soon after hospital admission.

Adrenergic beta-Antagonists↗
PubMed1993

[Reproducibility of heart rate variability measurements in repeated 24-hour long-term ECG registration].

Heart rate variability (HRV) is considered to indicate cardiac autonomic reflex activity. The reproducibility of HRV determinations from repeated Holter recordings has not been vigorously evaluated. This represents, however, an important question since HRV determinations are increasingly used to examine disease-related changes in the autonomic tone or the effects of therapeutic interventions. Thus, the present study examined the reproducibility of 4 commonly used time-domain parameters (SDNN, SDANN, rMSSD, pNN50) and the spectral components of HRV in 17 healthy volunteers and in patients with coronary artery disease (n = 9) or hypertensive heart disease (n = 9). In all subjects, 2 Holter recordings were obtained 7 days apart. In both, healthy volunteers and in patients, overall reproducibility of HRV parameters was good exhibiting correlation coefficients between 0.60 and 0.98. However, in individual subjects particularly in those without heart disease a higher degree of variability of HRV measurements was observed. In those patients with markedly reduced HRV, reproducibility was best. It is concluded that repeated HRV determinations may be utilized to examine the effects of underlying disease progress or of therapeutic interventions on cardiac autonomic tone.

Adult↗
PubMed1993

[Anti-centriole antibodies and high neuron-specific enolase activity in a patient with Raynaud phenomenon, cerebrovascular lesions, and ischemic finger necrosis--a functional relationship?].

In a 49-year-old patient with acute thrombangitis obliterans, several vascular risk factors and associated features of collagen vascular disease, we observed anti-centriole autoantibodies and a strongly elevated neuron-specific enolase (NSE). The latter could not be attributed to an underlying malignant or neuroendocrine disease. The recent identification of NSE as a centrosomal protein suggests a causal relationship between anti-centriole autoantibodies and elevated serum NSE levels.

Autoantibodies↗
PubMed1992

Short- and long-term efficacy and safety of flecainide acetate for supraventricular arrhythmias.

This report summarizes efficacy and safety data on the use of flecainide acetate for supraventricular arrhythmias. For this purpose, 60 original articles were identified by a literature search representing data from 1,835 treatment courses. In 18 trials, flecainide was administered intravenously; in 19, orally; and in 23, both forms of therapy were applied. There were 5 placebo-controlled and 12 comparative studies, whereas data from uncontrolled studies were represented in 43 articles. Short-term flecainide administration terminated atrial fibrillation in 65% of attempts and terminated atrial flutter in 28%. The drug was effective during long-term therapy for atrial fibrillation in 49% of patients, with similar efficacy rates in 11 comparative trials and in 16 uncontrolled studies. In randomized, placebo-controlled studies in patients with paroxysmal atrial fibrillation, flecainide was shown to reduce significantly the number of attacks, to prolong the time between attacks, and to improve quality of life. In patients with atrioventricular (AV) reciprocating tachycardias, acute drug administration was successful in 72%; 83% of patients with AV nodal reentrant tachycardias and 74% exhibiting arrhythmias associated with the Wolff-Parkinson-White syndrome responded acutely. During long-term therapy, efficacy rates were 70%, 78%, and 69%, respectively. Ectopic atrial tachycardia responded in 86% and 95% of patients treated with flecainide acutely or chronically. Data concerning drug-related side effects were available for 1,794 of 1,835 treatment courses (98%). Overall, 352 of 1,794 patients (20%) reported at least one non-cardiac or cardiac adverse experience.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗
PubMed1992

Arrhythmias during the acute phase of reperfusion therapy for acute myocardial infarction: effects of beta-adrenergic blockade.

In 107 patients with acute myocardial infarction, the incidence of ventricular arrhythmias during the acute phase of thrombolysis was examined by means of Holter monitoring. In patients with a patient infarct-related artery as assessed angiographically at 90 minutes, the occurrence of accelerated idioventricular rhythms was noted significantly more frequently than in patients with a permanent occluded vessel. This arrhythmia peaked in the first 180 minutes after the start of thrombolysis. In addition, single ventricular premature beats and runs of ventricular tachycardia were also more common in patients with successful reperfusion. The effects of acute intravenous administration of beta-blockers were examined in 66 patients without contraindications to this therapeutic approach. There were no differences in the occurrence of any type of rhythm disorders in patients with (n = 43) or without beta-blockade (n = 23). Thus ventricular arrhythmias particularly accelerated idioventricular rhythms, and single ventricular premature beats occur more frequently in patients with a patent infarct artery within the first 24 hours after thrombolysis. Acute intravenous beta-blockade does not appear to exert significant antiarrhythmic effects during this period.

Adrenergic beta-Antagonists↗
PubMed1992

Efficacy and safety of sotalol in patients with complex ventricular arrhythmias.

Sotalol is a unique beta-blocker that prolongs repolarization. Its use in 626 patients with complex ventricular ectopic activity, as reported in the literature, resulted in suppression of arrhythmia in 50 to 60% of treatment attempts. Detailed analysis of data on arrhythmias in 356 patients that were entered prospectively into a database revealed a median reduction in ventricular premature beats of 76%, compared to a median suppression of repetitive ventricular ectopic activity of 91% and of episodes of nonsustained ventricular tachycardia of 97% (p = 0.002 vs reduction of ventricular premature beats). This marked antiarrhythmic potency of sotalol in repetitive ventricular arrhythmias is thought to be due to its class III activity. Drug efficacy was independent of age, sex, the presence or absence of organic heart disease and the degree of sotalol-induced prolongation of corrected QT interval. Evaluation of left ventricular function in 215 patients treated with the drug demonstrated that depression of left ventricular ejection fraction occurred far less frequently than expected with conventional beta-blockers. Even patients with severely depressed pump function tolerated sotalol surprisingly well. There is a propensity of the drug to aggravate arrhythmia, which resulted in serious proarrhythmic events in 30 (3.5%) of 853 patients. These often consisted of torsades de pointes (9 of 30 patients). Proarrhythmia occurred primarily within the first 3 days of dosing, and exhibited a dose-dependence. In conclusion, sotalol is an effective and well-tolerated antiarrhythmic drug in patients with complex ventricular ectopic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗