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Biomedical subjects

S Rex

Publications and source records attributed to S Rex.

At least 37 records · Page 2Linked to original sources

Initial United Kingdom experience with the use of permanent, biventricular pacemakers: implantation procedure and technical considerations.

AIMS: To describe the institution of a biventricular pacing programme with particular reference to the implantation procedure and new technological considerations. METHODS AND RESULTS: Analysis of outcomes of a consecutive series of 54 patients undergoing attempted biventricular pacemaker implantation between February 1998 and April 1999. Successful implantation was achieved in 49 of the 54 patients (91%). Five patients required lead repositioning after initial successful implantation. Left ventricular lead pacing thresholds were found to be satisfactory and stable in the long term, with pacing thresholds of 1.3 V, 1.9 V and 1.6 V at implantation, 1 and 3 months, respectively. Left-sided lead function was not dependent on lead position within the tributaries of the coronary sinus. The implantation procedure was found to be safe, although one patient died during long-term follow-up. CONCLUSION: With appropriate previous experience in complex and coronary sinus pacing and with access to up-to-date pacemaker and lead technology, a biventricular pacemaker implantation service can be instituted with good medium-term results.

Adult↗

Initial results with left ventricular pacemaker lead implantation using a preformed "peel-away" guiding sheath and "side-wire" left ventricular pacing lead.

We report our preliminary experience with the use of preformed "peel-away" guiding sheaths and "side-wire" pacing leads for permanent biventricular pacemaker insertion in 13 patients with heart failure. Three of these patients were undergoing an upgrade of a preexistent VVIR pacing system after prior His ablation for medically refractory atrial fibrillation. Six of the patients had undergone attempted biventricular pacemaker insertion, but required left ventricular lead repositioning after total implantation failure or late displacement of the lead. The remaining patients were undergoing new system implantation. Target vessel cannulation was achieved in all patients. However, in one patient, diaphragmatic pacing throughout the target vessel length prevented successful implantation. All other implants were ultimately successful (92% success rate). We conclude that device implantation using a preformed sheath and side-wire pacing lead is feasible and may offer significant benefits over implantation with currently available technology.

Adult↗

Preliminary results with the simultaneous use of implantable cardioverter defibrillators and permanent biventricular pacemakers: implications for device interaction and development.

We report our preliminary experience with the combined use of implantable cardioverter defibrillators (ICD) and biventricular pacemakers in six patients with heart failure and malignant ventricular arrhythmia. Two patients underwent ICD implantation for malignant ventricular arrhythmia after previous biventricular pacemaker implantation. One patient underwent biventricular pacemaker insertion for NYHA Class III heart failure after previous ICD implantation. Two patients underwent single device implantation. In the sixth patient, a combined implantation failed due to an inability to obtain a satisfactory left ventricular pacemaker lead position. The potential for device interaction was explored during implantation. In two patients a potentially serious interaction was discovered. Subsequent alterations in device configuration and programming prevented these interactions with long-term use. No complication of combined device use has been demonstrated during a mean follow-up of 2 months (range 1-4 months). Satisfactory ICD and pacemaker function has also been demonstrated. We conclude that combined device implantation may be feasible with currently available pacing technology and that further prospective studies are required in this area.

Adult↗

The use of a "side-wire" permanent transvenous pacing electrode for left ventricular pacing.

It has been reported that biventricular pacing can improve the symptomatic status of patients with heart failure. However, using currently available transvenous left ventricular pacemaker leads the implantation procedure is difficult and has a high failure rate. We report the successful use of a new type of left ventricular pacing lead, the 'side-wire' pacing lead. This lead is initially introduced through a specifically designed guiding sheath to aid coronary sinus cannulation and then over a pre-positioned guide wire to aid final positioning. The more widespread introduction of this type of left ventricular pacing lead may reduce the difficulty of left ventricular pacing via the coronary sinus and thus improve the overall success rate of this therapeutic approach.

Electrodes↗

Biventricular implantable cardioverter defibrillator use in a patient with heart failure and ventricular tachycardia secondary to Emery-Dreifuss syndrome.

We report a case of fully transvenous single-unit biventricular implantable cardioverter defibrillator (ICD) use in a 43-year-old woman with a manifesting carrier form of muscular dystrophy (Emery-Dreifuss syndrome). The indication for biventricular ICD use was progressive heart failure with ventricular arrhythmia, permanent atrial fibrillation and previous VVIR pacemaker insertion. Single-unit transvenous biventricular ICD implantation was undertaken without complication. No potentially serious device malfunction was noted during subsequent follow-up. We conclude that single-unit biventricular ICD implantation is feasible for pacing and ventricular tachyarrhythmia control in patients with underlying atrial fibrillation.

Adult↗

Quantitative studies on the melittin-induced leakage mechanism of lipid vesicles.

We have investigated, both experimentally and theoretically, the efflux of carboxyfluorescein (a self-quenching fluorescent dye) from vesicles of different sizes and lipid species (POPC, DOPC) after having added the bee venom peptide melittin. This comprises quantitative analyses regarding the extent of lipid-associated peptide, the mode as well as the temporal progress of dye release and the possible leakage mechanism. Our results indicate a graded efflux characterized by a single-pore retention factor reflecting the formation of pores whose lifetimes are rather small (millisecond range). The observed fluorescence signal arising from the dequenching of effluent dye has been converted to the number of pore openings over the course of time. All the resulting curves exhibit a pronounced slowing down of the pore formation rate revealing two distinct relaxation steps at about 20 and 200 s, respectively, being largely independent of vesicle type and peptide to lipid ratio. The pore formation rate itself increases in proportion to the amount of membrane bound peptide. We give a quantitative account of our experimental findings based on a novel reaction scheme applicable to any of our various liposome systems. It implies that the pore formation rate is controlled by a passage through two intermediate monomeric peptide states. These states are thought to become well populated in the initial stage of lipid bilayer perturbation, but would practically die out after some time owing to a restabilization of the membrane system.

Binding Sites↗

Experimental and Monte Carlo simulation studies of the thermodynamics of polyethyleneglycol chains grafted to lipid bilayers.

Experimental measurements of the affinity of binding of fluorescent acylated polyethyleneglycol (PEG) conjugates to bilayers containing varying levels of phosphatidylethanolamine-PEGs (PE-PEGs) have been combined with Monte Carlo simulations to investigate the properties of the polymer chains at a PEG-grafted lipid interface. The affinity of binding of such conjugates to large unilamellar phosphatidylcholine/phosphatidylethanolamine (9:1) vesicles decreases 27-fold as the size of the coupled PEG chain increases from 1 to 114 monomer units. Incorporation of increasing amounts of PE-PEG2000 or PE-PEG5000 into the vesicles progressively reduces the affinity of binding of acylpeptide-PEG2000 or -PEG5000 conjugates. Monte Carlo simulations of surfaces with grafted PEG chains revealed no significant dependence of several characteristic properties of the polymer chains, including the average internal energy per polymer and the radii of gyration, on the grafting density in the range examined experimentally. The average conformation of a surface-grafted PEG2000 or PEG5000 chain was calculated to be fairly extended even at low grafting densities, and the projected cross-sectional areas of the grafted PEG chains are considerably smaller than those predicted on the basis of the estimated Flory radius. The experimental variation of the binding affinity of acylated conjugates for bilayers containing varying mole fractions of PE-PEG2000 or -PEG5000 is well explained by expressions treating the surface-grafted PEG polymers either as a van der Waals gas or as a system of rigid discs described by scaled particle theory. From the combined results of our experimental and simulation studies we conclude that the grafted PEG chains exist in a "mushroom" regime throughout the range of polymer densities examined experimentally and that the diminished affinity of binding of acylated-PEG conjugates to bilayers containing PE-PEGs results from occlusion of the surface area accessible for conjugate binding by the mobile PE-PEG polymer chains.

Animals↗

S-Acylation and plasma membrane targeting of the farnesylated carboxyl-terminal peptide of N-ras in mammalian fibroblasts.

We have used a series of fluorescent lipid-modified peptides, based on the farnesylated C-terminal sequence of mature N-ras [-GCMGLPC(farnesyl)-OCH3], to investigate the membrane-anchoring properties of this region of the protein and its reversible modification by S-acylation in cultured mammalian fibroblasts. The farnesylated peptide associates with lipid bilayers (large unilamellar phospholipid vesicles) with high affinity but in a rapidly reversible manner. Additional S-palmitoylation of the peptide suppresses its ability to desorb from, and hence to diffuse between, lipid bilayers on physiologically significant time scales. NBD-labeled derivatives of the farnesylated N-ras C-terminal heptapeptide, when incubated with CV-1 cells in culture, are taken up by the cells and reversibly S-acylated in a manner similar to that observed previously for the parent protein. The S-acylation process is highly specific for modification of a cysteine rather than a serine residue but tolerates replacement of the peptide-linked farnesyl moiety by other hydrophobic groups. Fluorescence microscopy reveals that in CV-1 cells the S-acylated form of the peptide is localized preferentially to the plasma membrane, as has been observed for N-ras itself. This plasma membrane localization is unaffected by either reduced temperature (15 degrees C) or exposure to brefeldin A, treatments which inhibit various trafficking steps within the secretory pathway. These results suggest that in mammalian cells the plasma membrane localization of mature N-ras is maintained by a 'kinetic trapping' mechanism based on S-acylation of the protein at the level of the plasma membrane itself.

4-Chloro-7-nitrobenzofurazan↗

Effects of interferon-gamma, interleukin-1 beta, and tumor necrosis factor-alpha on the serotonin metabolism in the nucleus raphe dorsalis of the rat.

The effects of the cytokines interferon (IFN)-gamma, interleukin (IL)-1, and tumor necrosis factor (TNF)-alpha on the serotoninergic transmission in the nucleus raphe dorsalis (NRD) were studied after peripheral and central application. The studies were performed in the freely moving rat using differential pulse voltammetry with multicarbon fibre electrodes to study the extracellular levels of the serotonin (5-HT) metabolite 5-hydroxyindoleacetic acid (5-HIAA). The extracellular 5-HIAA levels were not changed in the NRD after peripheral application of rat recombinant IFN-gamma, but elevated by the cytokines IL-1 beta and TNF-alpha. After intracerebroventricular (i.c.v.) application the cytokines IFN-gamma, IL-1 beta and TNF-alpha stimulated the serotoninergic transmission in the NRD. Our data suggest that the effect of peripherally elevated cytokine concentrations on the serotonin metabolism in the NRD of the rat is cytokine-dependent. In this respect the T-cell and NK-cell cytokine IFN-gamma acts clearly different when compared to the mainly macrophage-derived cytokines IL-1 beta and TNF-alpha, and plays a different role in the communication between immune and central nervous system.

Animals↗

Pore formation induced by the peptide melittin in different lipid vesicle membranes.

We investigated the interaction of the peptide melittin with differently sized vesicles consisting of various lipid compositions. This system was characterized by dynamic light scattering to estimate the size of vesicles. For SUV we obtained a radius of 12 nm, for LUV 53 nm. The pore forming process of melittin in vesicles was investigated by efflux of encapsulated fluorescent dyes at a self-quenching concentration. The influence of the following parameters on efflux and pore formation was estimated: lipid composition (POPC and DOPC), vesicle size (SUV and LUV) and size of the encapsulated dye (carboxyfluorescein and FITC-dextran). We found that under similar conditions vesicles of DOPC give always less leakage than vesicles of POPC independent of the fluorescent dye. For SUV and LUV we have obtained a different leakage behaviour at identical surface concentrations of melittin (if the same partition coefficient is assumed). From efflux measurements with different dyes we concluded that 6-20 molecules of melittin are necessary to form a pore. The possibility that not pore formation but fusion is the mechanism of melittin induced efflux was disproved by fusion experiments using a resonance energy transfer assay.

Amino Acid Sequence↗

The effect of human menopausal gonadotrophin and highly purified, urine-derived follicle stimulating hormone on the outcome of in-vitro fertilization in down-regulated normogonadotrophic women.

It has been suggested that the luteinizing hormone (LH) activity of human menopausal gonadotrophin (HMG) preparations used for ovarian stimulation in in-vitro fertilization (IVF) may have adverse effects on reproductive outcome. In the present prospective, randomized trial of 218 infertile couples this notion was investigated. A total of 114 women were treated with Pergonal (HMG group) and 104 with Fertinorm HP (HP-FSH group). The two groups were comparable with regard to duration of infertility, cause of infertility, age and number of previous IVF attempts and all had normal basal gonadotrophin concentrations before treatment was started. A standard hormonal treatment consisting of pituitary down-regulation with gonadotrophin-releasing hormone analogue (GnRHa) for 14 days starting on cycle day 21, followed by either HMG or highly purified follicle stimulating hormone (HP-FSH), three ampoules (225 IU) per day for 7 days, was used in all cases. The daily hormone dose was thereafter individualized according to the ovarian response. A maximum of two pre-embryos were transferred after 3 days of culture. Luteal support with progesterone (300 mg per day intravaginally) was used in all cases. Serum concentrations of oestradiol, FSH and LH were measured on days 1 and 8 of stimulation and on the day of oocyte retrieval. The mean number of days of stimulation, mean number of ampoules of HMG or HP-FSH used, mean total motile sperm count on the day of oocyte retrieval and mean numbers of oocytes retrieved (13.4 versus 13.7) or pre-embryos transferred (1.8 versus 1.8) were similar for both groups. Significantly (P < 0.05) more cycles in the HP-FSH group (17 = 16%) were cancelled due to complete failure of fertilization than in the HMG group (7 = 6%). The mean fertilization rate was significantly (P < 0.05) higher in the HMG group (56%) than in the HP-FSH group (50%), and significantly more transferable pre-embryos were obtained in the HMG than in the HP-FSH group (mean: 4.0 versus 3.2; P < 0.01). Serum hormone concentrations were similar to the two groups on stimulation day 1, but differed significantly with regard to FSH, LH and oestradiol on stimulation day 8. The clinical outcome was similar in the two groups, with an ongoing pregnancy rate (> 12 weeks of gestation) per started cycle of 33% in the HMG group and 29% in the HP-FSH group. The clinical abortion rates were similar (10 and 14%), and the implantation rate was 30% in each group. In conclusion, no detrimental effect of the LH activity of HMG on the clinical outcome of IVF in GnRHa down-regulated normogonadotrophic women was found. To the contrary, some beneficial effects of HMG on fertilization rates and pre-embryo development as compared with HP-FSH were demonstrated. These effects, as well as the differences in serum hormone concentrations during ovarian stimulation, may be caused by differences in LH content and/or in the composition of FSH isoforms of the HMG and HP-FSH preparations.

Adult↗

Comparison of self reported and observed length, width, and colour of scar tissue.

To evaluate the reliability of self assessment as a substitute for follow up, 30 self reported assessments of length, width, and colour of abdominal scars were compared with those of clinicians. The degree of disagreement between patients and medical observers was not significant. We conclude that as long as instructions to patients are unambiguous, reliable information may be obtained by postal inquiry. Self reported measurements may thus replace time-consuming follow up visits in studies on the influence of various factors on scar tissue.

Abdomen↗

Malignant mixed müllerian tumors of the ovary. Report of 13 cases.

Thirteen patients with verified malignant mixed Müllerian tumor of the ovary treated in Denmark during the 7-year period 1981-87 were reviewed. Two patients had homologous and 11 patients had heterologous tumors. Four patients with early stage disease underwent radical surgery; 9 patients had stage III disease. Median survival for all 13 patients was 12 months. Six patients received platinum-containing cytotoxic therapy; 2 of these patients without measurable disease became long-term survivors (survival times 42+ and 92+ months, respectively) and 3 of the 4 remaining patients with evaluable disease obtained an objective remission.

Aged↗

The effect of cigarette smoking on wound healing.

To see if there was any difference in the skin healing of smokers as opposed to non-smokers we studied 120 women admitted consecutively for laparotomy sterilisation. The method of skin suture was standardised. We compared width, length, and colour of the scars, and assessed the overall cosmetic result using a scoring system in 69 smokers and 51 non-smokers. When the incision was in the midline the scars in the smokers measured 7.4 mm averagely as compared with 2.7 mm in non-smokers (p less than 0.02). There was a corresponding tendency in transverse incisions. When the colour was compared, 26% of smokers had light coloured scars compared with 12% of non-smokers (p less than 0.05). There were no differences between the groups when dark coloured scars were assessed. Overall, using the scoring system, smokers had significantly worse cosmetic results than non-smokers.

Abdomen↗