Improved robust T-wave alternans detectors.

New statistical and spectral detectors, the modified matched pairs t test, the extended spectral method and the modified spectral method, were proposed for T-wave alternans (TWA) detection gaining robustness according to trend and single-frequency interferences. They were compared to classic detectors such as matched pairs t test, unpaired t test, spectral method, generalized likelihood ratio test and estimated TWA amplitude within a simulation framework and applied to real data. The optimal detection threshold was selected by using a full Monte-Carlo simulation where signals, with and without alternans episodes, were corrupted by Gaussian noise with different power and single-frequency interferences with different tones. All the combinations of noise and frequency were selected and repeated 500 times in order to compute probability of detection ([Formula: see text]) and the false alarm probability ([Formula: see text]), providing ROC curves. The study group consisted of 50 patients with implantable cardioverter-defibrillator (age: [Formula: see text]; LVEF: [Formula: see text]), who were paced (ventricular pacing) at 100 bpm. Two-minute recordings were analyzed. The XYZ orthogonal lead system was used. The best performance was reached by using the modified matched pairs t test (in comparison with the spectral method and other reference methods).

Bleeding complications after pacemaker or cardioverter-defibrillator implantation in patients receiving dual antiplatelet therapy: Results of a prospective, two-centre registry.

Introduction. The aim of the study was to define the prevalence of bleeding events in patients treated with dual antiplatelet therapy (DAT) in comparison with patients receiving only acetylsalicylic acid (ASA).Methods. Prospective two-centre registry of all first implantations of pacemakers, cardioverter-defibrillators and cardiac resynchronisation therapy units in patients receiving ASA (n=194) or DAT (n=53).Results. Bleeding complications were detected in 27 (16.2%) patients in the ASA group and in 13 (24.5%) in the DAT group. There was no significant difference in the overall number of complications between the patients receiving ASA or DAT, although there was a trend towards a higher incidence of overall complication rates in the DAT group (p=0.0637). The incidence of major complications (requiring blood transfusion or surgical intervention or prolonging hospital stay) was low (3.6%), and similar in both groups (3.6 and 3.8% respectively, ns). The rate of minor complications (subcutaneous haematomas) was greater in the DAT group (p=0.015).Conclusions. Treatment with DAT does not increase the risk of major bleeding complications as a result of device implantation; however, minor complications are significantly more frequent. Our results suggest that DAT could be continued in patients undergoing device implantation with a moderate risk of bleeding complications. (Neth Heart J 2010;18:230-5.).

Resolution of an aortic mobile mass with anticoagulation without evidence of arterial embolism.

The prognostic significance of aortic mobile debris detected by transesophageal echocardiography (TEE) in patients without history of embolism has not been established. A mobile aortic arch mass was found by TEE in a 59-year-old man with coronary artery disease, and with rheumatic mitral valve disease, and with no embolic symptoms. The patient was anticoagulated for 6 weeks and the mass was no longer seen on repeated TEE. He had no embolic symptoms during 9 months of follow-up. Different therapeutic approaches to mobile aortic debris are discussed and anticoagulant treatment of asymptomatic cases is advocated.

[Treatment of 3 patients with arrhythmias using "radiofrequency" ablation]. / Leczenie 3 chorych z zaburzeniami rytmu serca metada "radiofrequency".

In 3 patients radiofrequency (RF) ablation of AV node (n = 2) and left sided accessory pathway (n = 1) was performed because of intractable tachyarrhythmias. RF ablation was made in the first patient (ablation of AV node) using 135 Watts during 72 sec., in the second patient (AV node ablation) 331 Watts during 185 sec., and in the last patient 883 Watts during 695 sec. In the last patient ablation of accessory pathway was unsuccessful and the patient has been successfully operated. AV conduction was interrupted in 2 cases. No complications were noted. General anesthesia was not required. All the patients were discharged in a good state.

Promotion of neuronal survival in vitro by thermal proteins and poly(dicarboxylic)amino acids.

Evaluating molecules for their ability to promote survival and growth of neurons, we tested thermal proteins on cultures of dissociated fetal rat forebrain neurons. (Thermal proteins are polyamino acids formed when mixtures of amino acids with minimal proportions of glutamic or aspartic acid are heated.) Thermal proteins, added to low-density cultures in serum-free medium, stimulated neurite outgrowth and induced the formation of neuronal networks which survived for 6-10 days. Neurons in control cultures failed to grow and degenerated completely within 2-4 days. Effective concentrations (EC50) of thermal proteins ranged from 3 to 100 micrograms/ml. They were equally effective when present in the medium during the culture time or after precoating of the culture dishes. A single preparation which contained only aspartic and glutamic acid was effective, and similar survival promoting actions were then found for polyglutamic acid and mixed polyamino acids containing glutamic or aspartic acid. Thermal proteins and polyglutamic acid acted in a specific manner since, under the same experimental conditions, many control peptides, proteins and growth hormones failed to promote survival of neurons. Furthermore, their effects were antagonized by heparin, but not heparan sulfate nor chondroitin sulfate. These findings suggest that sequences of successive dicarboxylic amino acid residues are able to promote survival and neurite elongation of cultured neurons and that such sequences are responsible for the survival promoting action of thermal proteins. They invite the speculation that sequences of successive dicarboxylic amino acids, while occur in many proteins and show a high degree of evolutionary conservation, may have functional role in molecular recognition processes during neuronal development.

[Preliminary experience with achieving immune tolerance in patients with hemophilia A and circulating factor VIII inhibitor]. / Wstepne doswiadczenia w uzyskiwaniu tolerancji immunologicznej u chorych na hemofilie A z krazacym antykoagulantem.

The appearance of antibodies to factor VIII is a serious complication in the treatment of haemophilia A. A protocol is presented aiming at suppression of the anticoagulant using continued treatment with factor VIII (25 u/kg b.w. twice weekly). Ten patients with previous maximal factor VIII antibody titre from 7 to 2900 Bethesda units were treated. So far the inhibitor was eradicated in 3 cases treated continuously for from 5 to 20 months. In two of these three cases successful surgical procedures were performed without anamnestic response.

Pharmacological activities in thermal proteins: relationships in molecular evolution.

The model of protobiological events that has been presented in these pages has increasing relevance to pharmacological research. The thermal proteins that function as key substances in the proteinoid theory have recently been found to prolong the survival of rat forebrain neurons in culture and to stimulate the growth of neurites. A search for such activity in thermal proteins added to cultures of modern neurons was suggested by the fact that some of the microspheres assembled from proteinoids rich in hydrophobic amino acids themselves generate fibrous outgrowths.

Thermal proteinoids as excitability-inducing materials.

The deposition of thermal copolyamino acids on planar lipid membranes causes oscillations and action potentials upon electrical stimulation. Results are reported for compositionally simple thermal copoly(asp,glu) and for a more heterotonic polyamino acid. The data conform to the interference that electrical activity of cellular membranes is due to the polypeptide components, not to the lipid components. Because of the ease and controllability of producing polypeptides by thermal copolymerization of amino acids, new possibilities in investigation of structure-excitability relationships are provided.

Excitable cell made of thermal proteinoids.

Such phenomena as electrical polarization across the membrane, electrical discharges, current-voltage characteristics, negative resistance and some light characteristics are described for synthetic cells made of thermal proteinoids. The thermal proteinoid cell is considered as a structural and functional model of the excitable natural cell.

Excitable artificial cells of proteinoid.

The proteinoid cells are assembled of thermal polymers of amino acids. Typically, an appropriate mixture of amino acids containing aspartic or glutamic acid is heated at 190 degrees C for 6 h, stirred with water for 2 h, dialyzed during 2 d, and lyophilized. Spheroidal cells are made from such polymer by dissolving it in the water by boiling, and then cooling. Many of them can be made by sonication at room temperature. These artificial cells, ranging from microns to tens of microns in diameter (depending on composition and preparation), have double membranes and various internal compositions. The spherules can microencapsulate dyes, oxidant-reductant compounds or acceptor-donor substances, and can be packed together. Such spherules display electrical polarization and electrical discharges and respond to intra- and extracellular ionic and electric influence upon membrane and action potential. These properties arise from the double membrane structure, asymmetric membrane permeability, and channeling phenomena. Such features as exponential dependence of the steady-state conductance and capacitance as well as negative resistance of the membrane seem to be responsible for the flip-flop alternations of the membrane polarization, rhythmic electric oscillations, and all-or-none action potentials. The presence of such chromophores as pteridine and flavin in polymers constituting these cells is responsible for their photosensitivity.

Membrane, action, and oscillatory potentials in simulated protocells.

Electrical membrane potentials, oscillations, and action potentials are observed in proteinoid microspheres impaled with (3 M KC1) microelectrodes. Although effects are of greater magnitude when the vesicles contain glycerol and natural or synthetic lecithin, the results in the purely synthetic thermal protein structures are substantial, attaining 20 mV amplitude in some cases. The results add the property of electrical potential to the other known properties of proteinoid microspheres, in their role as models for protocells.

Electrical membrane phenomena in spherules from proteinoid and lecithin.

Spontaneous and induced electrical phenomena resembling membrane and action potentials in natural excitable cells have been observed in artificial cells. These artificial cells were made from thermal proteinoid and lecithin in a solution of potassium acid phosphate with glycerol.

Carbon monoxide effect on the membrane potential of cells in nervous tissue cultures.

The effects of carbon monoxide (CO) on the membrane potential of neurons and glial cells were investigated using organotropic cultures of the cerebellum of newborn rats in two experimental groups. Group I comprised cultures maintained during 2, 3 and 4 weeks and exposed only once to CO during 30 minutes. In group II 3-week cultures were exposed twice to CO with a 30-minute interval between exposures. The gaseous environment of the cultures contained air with 10% of CO. The results of measurements of membrane potentials carried out immediately after exposure and 24 hours later were subjected to conventional statistical analysis. After one exposure to CO the membrane potential of the neurons and glial cells decreased, and after 24 hours it rose, without, however, reaching the value observed in the cells kept in standard cultures. Immediately after two exposures of 30 minutes each a significant fall of the membrane potential was observed in the neurons and glial cells, while 24 hours later the measurements of the resting potential in all cells showed zero value. The experiments with two exposures to CO for 10 minutes each demonstrated a fall in the membrane potential of neurons and glia, and after 24 hours this potential rose only in glial cells. The results of these investigations are compared with those reported in the literature and the mechanism of disturbances of cell membrane polarization during cytotoxic hypoxia is discussed.

Discharge pattern of single neuronal units in cortical projection area of vagus nerve during successive episodes of hypoxia.

For an analysis of discharge pattern of single neuronal units in the cortical projection area of the vagus nerve during successive episodes of hypoxia their action potentials were recorded extracellularly. Changes in the discharge pattern were assessed by means of histograms of interimpulse intervals. It was found that the reaction of neurons to repeated exposure to hypoxia includes: a) increased frequency of discharges, b) decreased activity, or c) habituation, i.e. reduction in the degree of neuronal activity changes during successive exposures to hypoxia.

Anoxia-induced changes in the resting potential of the cerebellar cells in tissue culture.

Membrane potentials of Purkyne cells, granular cells, astrocyte cells and oligodendrocyte cells were measured in the cerebral tissue culture under normal conditions and after anoxia. An increment of the membrane potential value with age of culture was found. After anoxia the resting potential decreased with exception of 2-week Purkyne cells and granular cells. The highest anoxia-induced decrease of the membrane potential of all the cells studied was observed in 3-week tissue culture.