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Biomedical subjects

R Meyer

Publications and source records attributed to R Meyer.

At least 127 records · Page 7Linked to original sources
PubMed1997

Weaning from mechanical cardiac support in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: Implantation of mechanical cardiac support systems (MCSS) in patients with idiopathic dilated cardiomyopathy (IDC) may improve cardiac function and allow explantation of the device. We report of long-term effects of ventricular unloading on cardiac function, humoral anti-beta1-adrenoceptor autoantibodies (A-beta1-AABs), and myocardial fibrosis. METHODS AND RESULTS: Seventeen patients in New York Heart Association functional class IV with nonischemic IDC received MCSS. All had a cardiac index of < 1.6 L x min(-1) x m(-2) of body surface area, a left ventricular ejection fraction (LVEF) of <16%, and a left ventricular internal diameter in diastole (LVIDd) of >68 mm and tested positive for A-beta1-AABs. Echocardiographic evaluation, serum tests for A-beta1-AABs, and histological assessment of myocardial fibrosis were performed before and after MCSS implantation. The mean support duration was 230+/-201 days. Six patients died, four were transplanted, and two are still on MCSS. Five patients with significant cardiac recovery (mean LVIDd, 54+/-2.3 mm; LVEF, 47+/-3.7%) were weaned after 160 to 794 days and are now device free for 51 to 592 days. A-beta1-AABs disappeared gradually during MCSS without increase after weaning; cardiac function and volume density of fibrosis remained normal. Nine patients' cardiac function hardly improved during ventricular unloading. CONCLUSIONS: Cardiac function can be normalized in selected patients with end-stage IDC by MCSS. The degree of preoperative myocardial fibrosis may be an indicator for outcome; A-beta1-AABs can be used to monitor myocyte recovery. Weaning from MCSS offers an alternative to cardiac transplantation in certain patients.

Adult↗
PubMed1997

Overexpression of human poly(ADP-ribose) polymerase in transfected hamster cells leads to increased poly(ADP-ribosyl)ation and cellular sensitization to gamma irradiation.

Poly(ADP-ribosyl)ation is a posttranslational modification of nuclear proteins catalyzed by poly(ADP-ribose) polymerase (PARP), an enzyme which uses NAD+ as substrate. Binding of PARP to DNA single-strand or double-strand breaks leads to enzyme activation. Inhibition of poly(ADP-ribose) formation impairs the cellular recovery from DNA damage. Here we describe stable transfectants of the Chinese hamster cell line CO60 that constitutively overexpress human PARP (COCF clones). Immunofluorescence analysis of gamma-irradiation-stimulated poly(ADP-ribose) synthesis revealed consistently larger fractions of cells positive for this polymer in the COCF clones than in control clones, which failed to express human PARP. HPLC-based quantitative determination of in vivo levels of poly(ADP-ribose) confirmed this result and revealed that the basal polymer levels of undamaged cells were significantly higher in the COCF clones. The COCF clones were sensitized to the cytotoxic effects of gamma irradiation compared with control transfectants and parental cells. This effect could not be explained by depletion of cellular NAD+ or ATP pools. Together with the well-known cellular sensitization by inhibition of poly(ADP-ribosyl)ation, our data lead us to hypothesize that an optimal level of cellular poly(ADP-ribose) accumulation exists for the cellular recovery from DNA damage.

Adenosine Diphosphate Ribose↗
PubMed1997

Millimeter-Wave Absorption Free Jet Spectrum, Barriers to Internal Rotation, and Torsional Relaxation in p-Anisaldehyde

The rotational spectrum of p-anisaldehyde in a supersonic expansion has been investigated in the frequency range 60-78 GHz. Transitions up to J = 57 measured for the anti and syn conformers have been used to determine complete sets of fourth-order centrifugal distortion constants. Methyl group internal rotation splittings have also been observed for some of the lines and have yielded the respective barriers for both conformers. A vibrational satellite observed for each of the two conformers has been assigned to the respective first excited methoxy torsional state. The jet conditions, in particular the stagnation pressure of the carrier gas, can be adjusted to control the degree of cooling achieved in the expansion. This possibility has been exploited in the present work to enhance the intensities of the observed vibrational satellites. Applying a two-dimensional flexible model to the methoxyl and aldehydic groups torsions, the potential energy and structural deformation parameters transferred from anisole and benzaldehyde have been found to be suitable to describe these motions in p-anisaldehyde. Mixing of anti and syn conformations has been found to be insignificant within the first 82 calculated torsional eigenstates and therefore less likely to explain the intermediate bands observed in the low-resolution microwave spectrum than the internal vibrational relaxation suggested by R. K. Bohn, M. S. Farag, C. M. Ott, J. Radhakrishnan, S. A. Sorenson, and N. S. True (1992, J. Mol. Struct. 268, 107-121). A qualitative discussion of relaxation among the torsional states and its effect on the rotational spectrum is given. Copyright 1997 Academic Press. Copyright 1997Academic Press

Journal Article↗
PubMed1997

[Temporary mechanical left heart support. Recovery of heart function in patients with end-stage idiopathic dilated cardiomyopathy].

BACKGROUND: Implantation of a mechanical cardiac support system (MCSS) in patients with idiopathic dilated cardiomyopathy (IDC) may improve cardiac function and allow explantation of the device. Our experience now includes 13 patients who have been "weaned" from MCSS and we report about the overall results of this treatment as well as the effects of ventricular unloading on cardiac function, anti-beta 1-adrenoceptor-autoantibody (A-beta 1-AAB) level and the degree of myocardial fibrosis. METHODS: 13 patients with non-ischemic IDC who had been admitted here in cardiogenic shock (CI < 1.61.min-1.m2, left ventricular ejection fraction [LVEF] < 16% and left ventricular internal diameter in diastole [LVIDd] > 68 mm) and who all tested positive for A-beta 1-AABs were implanted with an uni-(12 patients) or a biventricular (1 patient) mechanical assist device. Echocardiographic evaluation and A-beta 1-AAB-level-monitoring was routinely performed after implantation and explantation of the MCSS and the degree of myocardial fibrosis was assessed at the time of implantation and after explantation. RESULTS: During a mean duration of mechanical support of 236 +/- 201 days (range: 30 to 794 days), LV-EF improved to a mean of 46% and LVIDd decreased to a mean value of 56 mm in these 13 patients. A-beta 1-AABs decreased and disappeared 11.7 weeks after implantation of the device and did not reincrease thereafter. The highly pathologic degree of fibrosis at the time of implantation diminished to normal values about 1 year after explantation. One patient died of anesthesiologic complications and another patient shortly presented with a new episode of cardiac insufficiency 6 months after explantation. He was implanted again with an univentricular assist device was successfully transplanted 3 weeks later. Mean observation period of the remaining 11 patients now amounts to 12.6 +/- 9.77 (range: 3 to 26) months after explantation of the device--as of May, 31, 1997--with a cumulative observation period of 139 patient months. CONCLUSION: Temporary implantation of a MCSS may normalize cardiac function in selected patients with IDC. The striking degree of myocardial fibrosis can reduce to normal values after explantation of the device. A-beta 1-AABs disappear during ventricular unloading and do not increase thereafter. "Weaning" from mechanical device may constitute an alternative treatment to cardiac transplantation in selected patients.

Adult↗
PubMed1997

Temperature and pressure dependence of Shaker K+ channel N- and C-type inactivation.

Shaker B potassium channels undergo rapid N-type and slow C-type inactivation. While N-type inactivation is supposed to be mediated by occlusion of the pore by the N-terminal protein structure, the molecular mechanisms leading to C-type inactivation are less well understood. Considering N-type inactivation as a model for a protein conformational transition, we investigated inactivation of heterologously expressed Shaker B potassium channels and mutants thereof, showing various degrees of C-type inactivation, under high hydrostatic (oil) pressure. In addition to the derived apparent activation and reaction volumes (delta V), experiments at various temperatures yielded estimates for enthalpic (delta H) and entropic (T delta S) contributions. N-type inactivation was accelerated by increasing temperature and slowed by high hydrostatic pressure yielding at equilibrium delta H = 76 kJ/mole, T delta S = 82 kJ/mole, and delta V = 0.18 nm3 indicating that the transition to the N-type inactivated state is accompanied by an increase in volume and a decrease in order. N-terminally deleted Sh delta 6-46 constructs with additional mutations at either position 449 or 463 were used to investigate C-type inactivation. In particular at high temperatures, inactivation occurred in two phases indicating more than one process. At equilibrium the following values were estimated for the major inactivation component of mutant Sh delta 6-46 T449A: delta H = -64 kJ/mole, T delta S = -60 kJ/mole, and delta V = -0.25 nm3, indicating that the C-type inactivated state occupies a smaller volume and is more ordered than the noninactivated state. Thus, hydrostatic pressure affects N- and C-type inactivation in opposite ways.

Animals↗
PubMed1997

[Histologic specimen collection in pulmonary hypertension using percutaneous, transvascular biopsy--animal experiment and initial clinical data].

Pulmonary hypertension is a severe multietiological disease largely resistant to treatment. Biopsy is often necessary to establish differential diagnosis. In pulmonary hypertension transbronchial pulmonary biopsy is contraindicated and open lung biopsy is the method of choice. In our paper we report about experimental results in animals and first clinical data on a new biopsy technique (percutaneous transluminal biopsy, PTB) providing access to histology in pulmonary hypertension without the need of surgery. In a subset of animals pulmonary hypertension was produced experimentally. In addition, we carried out the PTB in patients with bronchial carcinoma. Our preliminary results demonstrate that sufficient material could be gained for the histologic evaluation of pulmonary parenchyma and in pulmonary vessels. No complications have been noted so far.

Animals↗
PubMed1997

Modulation of L-type calcium current by internal potassium in guinea pig ventricular myocytes.

OBJECTIVES: The early phase of myocardial ischemia is characterized by a considerable K+ efflux from cardiac myocytes, causing decreasing internal ([K+]i) and increasing external ([K+]o) K+ concentrations. The change in [K+]i and [K+]o is one of the factors thought to initiate the ischemia-induced changes in electrical activity. Nevertheless, little is known about the influence of [K+]i and [K+]o on the L-type calcium current. METHODS: The whole-cell patch-clamp technique combined with an internal perfusion system was used to test possible actions of altered [K+]i and [K+]o on L-type current carried by Ca2+ and Ba2+ in isolated guinea pig ventricular myocytes. RESULTS: Changing the [K+]i in the range of 110-170 mM revealed a sigmoidal concentration-response relationship between the L-type current and [K+]i. The maximum change in current amplitude was more than 40% with a half-saturation concentration of 136 mM which is near the physiological [K+]i. Ca2+ influx during action potential clamp increased by approximately 42% after raising [K+]i from 130 to 170 mM. Internal perfusion with Cs+ demonstrated that Cs+ is less effective than K+ in regulating the L-type current. By using ATP-analogues, [K+]i was shown to affect the L-type channel in a phosphorylation-independent way. Changes in [K+]o only modulated the L-type current via alterations in [K+]i. CONCLUSIONS: The decrease in [K+]i during early ischemia is, per se, sufficient to reduce the L-type current by up to 15%, thereby decreasing the action potential duration, and Ca2+ influx into the cells. This may act in addition to well-known mechanisms such as changes in internal pH and falling ATP levels, which influence the L-type current. Moreover, the phenomenon may complicate the interpretation of electrophysiological measurements of L-type current under conditions where [K+]i is not precisely controlled.

Animals↗
PubMed1997

Assessment of cerebrovascular reactivity by dynamic susceptibility contrast-enhanced MR imaging.

In patients with cerebrovascular disease the acetazolamide (ACZ) test is performed to evaluate the decrease in cerebral perfusion pressure (CPP) through the investigation of the vasomotor reactivity (VMR). This latter is currently assessed with ACZ with several methods. Recently, magnetic resonance imaging (MRI) techniques have been developed that are sensitive to stimulus-induced changes in blood flow. Dynamic susceptibility contrast material-enhanced gradient-echo MRI techniques (DSC-MRI) might be an attractive tool to assess VMR. We aimed to test the ability of DSC-MRI in the assessment of VMR. Relative hemodynamic parameters rCBV, MTT, and rCBF were evaluated at baseline after the first injection of gadopentetate dimeglumine and 10 min after the intravenous administration of ACZ (1 g) with a second bolus of contrast agent. Assessment of hemodynamic parameters was performed over the whole hemisphere and also within regions of interest. The significances of the mean differences, before and after ACZ, were assessed with repeated-measures ANOVA with two within factors: laterality (right-left) and ACZ. DSC-MRI with ACZ test was performed in ten healthy controls (aged 51.4+/-16.2 years). The cerebral hemispheric ratio for the three parameters (cerebral blood volume (CBV), mean transit time (MTT), and cerebral blood flow (CBF)) ranged between 1.01 and 1.03. The mean gray matter-to-white matter ratio for CBV, CBF and MTT were 2.44, 2.41 and 1.05, respectively. As the laterality effect was not significant, left and right hemispheric values were averaged. A significant increase of all hemodynamic parameters was observed after ACZ (P<0.01-0.001). The same changes for CBV, CBF and MTT were observed after ACZ according to the regions of interest (P<0.006-0.015). DSC-MRI is a non-invasive method which enables the assessment of VMR. This technique may be added to any conventional MRI in order to detect a hemodynamic impact of an ICA stenosis. Therefore, it might be useful in determining the appropriate management when the indication for surgical versus medical therapy is in question.

Acetazolamide↗
PubMed1997

Cardiodepressive mediators are released after ischemia from an isolated heart: role of coronary endothelial cells.

OBJECTIVES: This study was designed to ascertain whether cardiodepressive mediators released after ischemia originate from coronary endothelial cells. BACKGROUND: Endothelial cells modulate myocardial contractility under physiologic conditions. Few data are available describing the role of coronary endothelial cells on myocardial function after ischemia. METHODS: Using a model of sequential perfusion of two isolated rat hearts, the effect of the reoxygenated coronary effluent of heart I was investigated on myocardial contractility of heart II. After 40 min of separate perfusion at constant flow (10 ml/min), the two hearts were perfused sequentially with (group I) or without (control group) preceding ischemia (10 min) of heart I. In groups II and III, the coronary endothelium of heart I was functionally removed by Triton X-100 or hyperkalemic infusion before global ischemia. Endothelial damage was confirmed by functional tests and electron microscopy. RESULTS: Under control conditions no changes were observed in heart II during sequential perfusion. In contrast, after 10 min of ischemia in heart I, a marked reversible decrease in left ventricular pressure, left ventricular dP/dtmax and left ventricular dP/dtmin (-55%, -66% and -70%, respectively) was observed in heart II. Heart rate and coronary perfusion pressure did not change significantly. Selective endothelial damage of heart I before ischemia did not modify the negative inotropic effect observed in heart II. CONCLUSIONS: Cardiodepressive mediators are released after ischemia during reperfusion from an isolated heart and induce a reversible negative inotropic effect in a sequentially perfused heart. It is unlikely that these agents are derived from the coronary endothelium.

Animals↗
PubMed1997

The relaxosome protein MobC promotes conjugal plasmid mobilization by extending DNA strand separation to the nick site at the origin of transfer.

The frequency of conjugal mobilization of plasmid R1162 is decreased approximately 50-fold if donor cells lack MobC, one of the plasmid-encoded proteins making up the relaxosome at the origin of transfer (oriT). The absence of MobC has several different effects on oriT DNA. Site- and strand-specific nicking by MobA protein is severely reduced, accounting for the lower frequency of mobilization. The localized DNA strand separation required for this nicking is less affected, but becomes more sensitive to the level of active DNA gyrase in the cell. In addition, strand separation is not efficiently extended through the region containing the nick site. These effects suggest a model in which MobC acts as a molecular wedge for the relaxosome-induced melting of oriT DNA. The effect of MobC on strand separation may be partially complemented by the helical distortion induced by supercoiling. However, MobC extends the melted region through the nick site, thus providing the single-stranded substrate required for cleavage by MobA.

Bacterial Proteins↗
PubMed1997

Operational aspects of bednet impregnation for community-based malaria control in Nicaragua, Ecuador, Peru and Colombia.

Community intervention projects with pyrethroid (permethrin and lambdacyhalothrin) impregnated bednets and an accompanying community education programme were carried out in 6 malaria endemic areas on the Pacific coast of Nicaragua, Ecuador, Peru and Colombia as well as in the Peruvian Amazon basin. In this paper the operational aspects are analysed: bednet coverage, results of promotional activities for increased bednet use, the sale of low-cost bednets, techniques and difficulties with impregnation, acceptance of the programme (including washing of impregnated nets), side-effects, residual concentrations of the chemical in the nets, costs of the impregnation programme and insecticide resistance of the malaria vectors. We found that the local manufacture of bednets and their sale through village health workers, even in communities with low cash income, is a viable way of increasing bednet coverage; the impregnation of bednets is well accepted if villagers perceive a direct benefit; pretesting of the soaking capacity of different net materials should be done at central level; the instructions for the impregnation procedures of different net materials (cotton and synthetic) should be simple and unambiguous; very cheap thin net materials should be avoided, particularly in the case of lambdacyhalothrin impregnation; educational methods and/or promotion of dark-colour nets should be further tested in order to decrease the washing frequency of bednets at household level; in areas with early-biting mosquitoes further studies on the protective efficacy of bednets are necessary; careful monitoring of side-effects, particularly those of last-generation pyrethroids, is necessary; and the community-based impregnation programme is a powerful tool for strengthening community involvement in health actions.

Bedding and Linens↗
PubMed1997

Isolation of cDNA encoding full-length rat (Rattus norvegicus) poly (ADP-ribose) polymerase.

Poly(ADP-ribose) polymerase (EC 2.4.2.30) is a nuclear enzyme which binds to DNA breaks and then catalyzes the covalent modification of acceptor proteins with poly(ADP-ribose). Poly(ADP-ribose) polymerase activity contributes to the recovery of proliferating cells from DNA damage and to the maintenance of genomic stability, which may be mediated by effects on chromatin structure, DNA base-excision repair and cell cycle regulation. We established the complete cDNA sequence of rat poly(ADP-ribose) polymerase by RT-PCR and direct sequencing of amplification products and compared it with that of other mammalian species. The amino acid sequence homology is strikingly high. The best conserved regions are the known functional modules of poly(ADP-ribose) polymerase.

Amino Acid Sequence↗
PubMed1997

Action potential-generating cells in human glioblastomas.

We studied the electrophysiological properties of cells from human glioblastomas obtained after surgery. The membrane currents were compared in cells of acute tissue slices and primary cultures using the whole cell mode of the patch-clamp technique. Very strikingly, in about a third of the tumor cells in situ and in vitro, depolarizing voltage steps elicited large, tetrodotoxin-sensitive inward currents with a threshold of about -30 mV, indicating the presence of voltage-gated sodium channels. In addition, three types of potassium currents, a delayed rectifying, an A-type, and an inward rectifying, were observed. Such a set of voltage-gated channels is characteristic for neurons. Indeed, in these glioblastoma cells, depolarizing current pulses in the current clamp mode were able to generate action potentials with properties similar to those observed in neurons. We interpret this finding as the ability of glioblastoma cells to acquire neuronlike properties but retain some glial features, since they still express markers typical for astrocytes and their precursors. The role of sodium channels in glioblastoma cells is unclear at this moment and needs further investigation. Our findings, however, imply that the tumor tissue can be intrinsically excitable and that neoplastic glial cells themselves may be an etiologic factor for epileptic seizures.

Action Potentials↗
PubMed1997

Total external and internal construction in arhinia.

This case report relates to the surgical treatment of arhinia in a 6-year-old child. The external nose was constructed during the first stage with a forehead flap and a triangular rib graft. The nasal cavities were drilled out and lined during the second stage. In a third stage, the cavities were amplified, and silicone tubes were introduced for at least 1 year.

Humans↗
PubMed1997

[Stent implantation in severe tracheal and bronchial compression caused by aortic aneurysm].

A space-occupying growth in the left upper area of the lung was confirmed in a female patient of 75 years of age suffering from progressive cough and intermittent dyspnoea. Fibre bronchoscopy revealed distal stenosis of the trachea, the total findings being interpreted as pointing to the existence of a mediastinal tumour. A few hours after bronchoscopy the patient suffered from respiratory insufficiency, and the patient was referred to us with continuously increasing positive airway pressure breathing, for further clarification. We performed as an emergency measure bilaterally an endobronchial stent implantation. After airway pressure breathing had returned to normal, and subsequent extubation, compression of a stent occurred followed by renewed compulsory breathing. Ventilation could be optimised by an additional implantation of a stent. Cause of the compression was later identified as a monstrous aneurysm of the thoracic and abdominal aorta. During further conservative treatment there was a progressive bronchopneumonia and renal insufficiency requiring dialysis. The patient died on the 8th day after stent implantation. Autopsy showed that the stents were properly in position.

Aged↗
PubMed1997

[Reconstruction of lip isocele].

The surgical treatment of labial carcinoma must allow the complete excision of the tumor. This must be performed by using an immediate reconstruction procedure with respect of the lip function and with a satisfying aesthetic result. To achieve this goal, we choose the isosceles lip reconstruction, according with Meyer's advancement flap technique, described in 1965. By using this method we can restore up to the 2/3 of the lower or upper lip and also the lip commissure, after malignant tumor surgery. For total lip reconstruction, we have to combine this method with an Abbe-Estlander flap. Our paper presents this original lip reconstruction technique and analyses the results obtained. We especially base our conclusions on functional tests, but also on aesthetical considerations. We underline the interest of this choice of surgical procedure, permitting its adaptation to all cases of lip reconstruction, with immediate possibility of reconstruction, usually in one stage, without compromising either the function or the aesthetic aspect of the reconstructed lip.

Humans↗
PubMed1996

Expression of the plasma membrane Ca2+-ATPase in myogenic cells.

To study the physiological function of the plasma membrane calmodulin-dependent calcium ATPase (PMCA) in intact cells, L6 myogenic cell lines stably overexpressing the human PMCA isoform 4CI (= human PMCA isoform 4b) were generated. Several independent L6 clones and controls stably transfected with the empty expression vector were analyzed in detail. The resting cytosolic calcium level in hPMCA4CI-overexpressing muscle cells (measured by the Fura-2 method) was significantly reduced by 20-30% compared with controls. This was shown in a cytosolic window of 1322 single cells (p < 0.01). Furthermore, the differentiation process of these cells was remarkably accelerated compared with control myoblasts and parental nontransfected L6 cells as assessed by multinucleated myotube formation and creatine phosphokinase activity elevation. After 4 and 6 days of differentiation, PMCA-overexpressing L6 cells from four independent clones displayed a 3- and 4-fold higher creatine phosphokinase activity compared with controls (n = 5, p < 0.02). These results may extend the concept of the function of the PMCA from simple prevention of calcium overload to an active involvement in intracellular calcium regulation with potentially important consequences for cellular functions.

Animals↗