Transradial Approach for Coronary Intervention: 25 Years for 25 Centimeters

The first series of transradial coronary angiograms was carried out by Lucien Campeau and published in 1989. The devices available at that time made the technique difficult to perform. Four years later, when stenting started being widely used with a significant rate of local complications induced by Coumadin treatment, F. Kiemeneij proposed the radial approach as a good alternative to the femoral approach to reduce the rate of local complications. Since then, the use of the radial approach has been increasing, though it remains limited. The first reason for this lies in the significant learning period that is all the longer as a low percentage of patients are treated via this approach. This is why we think it is preferable to perform at least 25% of all procedures, and especially coronary angiograms, through this approach before setting up a radial program. Patients with contraindications to the femoral approach (anticoagulation or GP IIb/IIIa inhibitors, obesity, aneurysm of the abdominal aorta, or vessel disease of the lower limbs, etc.) should be selected. The second reason is the small diameter of the radial artery that can generate a number of problems when large diameter guiding catheters are used (7Fr or 8Fr). However, the reduction in guiding‐catheter size, and the increasing use of 6Fr catheters should solve this problem. In our center, the femoral approach is usually selected when 7Fr or 8Fr catheters are used. It is to be noted that the radial approach is now widely used in some interventional cardiology centers where the learning period has been completed. With operator experience, puncture failure is extremely rare and the technical failure rate is around 1%, mainly due to the anatomic variations of the radial artery (antebrachial and humeral loops). Apart from the difficulties associated with the learning curve, the radial approach has few limitations. The procedure and x‐ray exposure times are slightly longer for coronary angiography but not for angioplasty. The risk of radial occlusion ranges from 2% to 5%, however, radial occlusion is asymptomatic in patients with a normal Allen's test. Conversely, the radial approach has many advantages. Patient comfort is significantly improved due to the ease of radial compression, ambulation is almost immediate, and the rate of local complications is almost nil. Same day discharge following coronary angiography and angioplasty can be considered. Finally, with the increasing use of GP IIb/IIIa inhibitors, sometimes in combination with thrombolysis in the treatment of myocardial infarction, the radial approach could become the preferred approach in this setting.     

Solid phase synthesis of the retro viral nucleocapsid protein NCp10 of Moloney Murine Leukaemia virus and related “zinc-fingers” in free SH forms

The core of retroviruses contains a highly conserved, low molecular weight, basic protein that binds nucleic acids and is essential for genomic RNA packaging. The 56 amino acid protein, NCp10, of Moloney Murine Leukaemia virus (MoMuLV) has the CysX₂CysX⁴HisX⁴Cys zinc finger-like motif shared by all retrovirus nucleocapsid proteins. The native protein and five modified peptides containing the zinc binding domain were synthesized by solid phase in order to investigate the structural and biochemical role of Zn²⁺ chelation in MoMuLV NCp10 activity. The purity of the synthetic molecules was verified by HPLC and their sequences were confirmed by amino acid analysis and sequencing in the case of NCp10. Thiol dosage agreed with the theoretical value of free cysteine for all these molecules. Fluorescence measurements performed on synthetic NCp10 and zinc finger fragments showed that the tryptophan quantum yield was Zn²⁺ -dependent allowing a 1:1 stoichiometry for the complex to be determined. The apparent affinity constant of NCp10 for the metal was estimated to be superior to 10⁶ M^-1. The synthetic protein, in the presence of Zn²⁺ ions, possesses all the biological properties of NCp10 isolated from virions. It catalyzes both the MoMuLV RNA dimerization and the annealing of the replication primer tRNA^Pro onto MoMuLV RNA.     

Comparison of conformational properties of linear and cyclic δ selective opioid ligands DTLET (Tyr-D-Thr-Gly-Phe-Leu-Thr) and DPLPE (Tyr-c[D-Pen-Gly-Phe-Pen]) by 1H n.m.r. spectroscopy

The preferential conformations of the δ selective opioid peptides DPLPE (Tyr-c[D-Pen-Gly-Phe-Pen]) and DTLET (Tyr-D-Thr-Gly-Phe-Leu-Thr) were studied by 400 MHz ¹H n.m.r. spectroscopy in DMSO-d₆ solution. In neutral conditions, the weak NH temperature coefficients of the C-terminal residue (Pen⁵ or Thr⁶), associated with interproton NH-NH and α-NH NOE's (ROESY experiments), indicated large analogies between the backbone folding tendency of both the linear and cyclic peptides. Various γ and/or β turns may account for these experimental data. A similar orientation of the N-terminal tyrosine related to the folded backbones is observed for the two agonists, with a probable γ turn around the amino acid in position 2. Finally, a short distance, about 10 Å, between Tyr and Phe side chains and identical structural roles for threonyl and penicillamino residues are proposed for both peptides. These results suggest the occurrence of similar conformers in solution for the constrained peptide DPLPE and the flexible hexapeptide DTLET. Therefore, it may be hypothesized that the enhanced δ selectivity of DPLPE is related to a very large conformational expense of energy needed to interact with the μ opioid receptor, a feature not encountered in the case of DTLET. These findings might allow peptides to be designed retaining a high affinity for δ opioid receptors associated with a very low cross-reactivity with μ binding sites.     

Air Samples from a Building with Asbestos-Containing Material: Asbestos Content and in Vitro Toxicity on Rat Pleural Mesothelial Cells

Buildings equipped with asbestos-containing material may releaseasbestos fibers, the toxicity of which remains uncertain becauseof the generally low dose level. In 22 air samples collectedin a building the asbestos level ranged between 0 and 0.027f/ml. Both chrysotile and amphiboles were found. There was noassociation between in vitro cytotoxicity on rat pleural mesothelialcells and asbestos content, but there was a significant correlationwith the total amount of particulate material. Four samplesexhibited an enhancement of DNA synthesis in cells arrestedin G₁ with 5 mM hydroxyurea. This is more likely related tothe particulate matter associated with asbestos fibers.     

Directional Variability of Stimulation Threshold Measurements in Isolated Guinea Pig Cardiomyocytes: Relationship with Orthogonal Sequential Defibrillating Pulses

BARDOU A.L., ET AL.: Directional Variability of Stimulation Threshold Measurements in Isolated Guinea Pig Cardiomyocytes: Relationship with Orthogonal Sequential Defibrillating Pulses. Reports on delivery of separated orthogonal pulses markedly improving cardiac defibrillation have suggested that the stimulation threshold of heart fibers varies in accordance with their orientation within the electric field. The present work was aimed at investigating the directional variability of stimulation thresholds in isolated guinea pig cardiomyocytes. This variability was measured in 48 single myocytes by rotating each one through a theta (θ) angle between two-fixed parallel electrodes 1.1 cm apart, thus making θ vary between the electric field and the myocyte axis. For θ= 0°, the mean longitudinal current stimulation threshold was 16.92 ± 4.20 mA (n = 48). When θ was increased by increments of 10° up to 90°, the stimulation threshold increased in an exponential way. For θ= 90°, the mean transverse stimulation threshold was 63.23 ± 13.30 mA. These results clearly demonstrate the dependence of isolated cardiomyocyte stimulation thresholds on their orientation within the electric field and may account for the improved efficacy of defibrillation previously observed after delivery of orthogonal pulses.     

The Emotional Experience of Hospitalization: Its Moderators and Its Role in Patient Satisfaction With Foodservices

Objectives To investigate the basic dimensions of patient emotional experience of hospitalization; to identify the moderators of emotional experience in terms of individual characteristics and contextual factors; and to investigate the contribution of the dimensions of the patient emotional experience to satisfaction with f oodservices.Design Survey questionnaire.Subjects/setting One hundred two hospitalized patients of a specialized, acute-care, urban hospital in Canada who required one or more overnight stays. Patients with notable physical, cognitive, or emotional limitations were excluded from the study. Patients admitted to the obstetrics department were also excluded because of the unique nature of their emotional experience of hospitalization.Statistical analyses performed Factor analysis followed by orthogonal rotation (varimax), analyses of variance, and multiple regression analyses.Results Five dimensions represented the emotional experience of hospitalization: positive emotions, arousal emotions, and three negative dimensions structured on the basis of their possible causes (situation-, other-, or self-attributed negative emotions). Individual characteristics (gender, age, marital status, perceived health status) and contextual factors (perceived control over the situation, complexity of medical diagnosis, and admission procedures) significantly influenced patient emotions. Satisfaction with foodservices was structured in technical and interpersonal dimensions; the largest part of the common variance was accounted for by interpersonal aspects. The relationship between emotions and satisfaction was direct for positive emotions and, surprisingly, for situation-attributed negative emotions and self-attributed negative emotions. Other-attributed negative emotions and arousal emotions were negatively associated with satisfaction with foodservices.Applications Results suggest that dietitians’ interventions should be adapted for subgroups of patients who experience different emotions. Results also provide insights on individual and contextual factors that can be used to identify or better understand the specific characteristics of these subgroups. The pattern of relationships between emotions and satisfaction demonstrates that the fine-tuning of dietitians’ interventions as a function of patients’ emotional states may be conducive to increased patient satisfaction with foodservices. J Am Diet Assoc. 1996; 96:354-360.     

Early released lipid-soluble cardiodepressant factor and elevated oestrogenic substances in human septic shock

A cardiodepressant factor (CDF) able to decrease contractile activity of cultured rat heart cells was determined to be located in the lipid-soluble fraction of sera from men in septic shock. This heat-stable CDF has a molecular weight under 1000. Repeated fractionations of sera gave evidence of an oestrone-like chromatographic behaviour. Oestrone, oestradiol and cortisol were immunologically quantified in two groups (recovery and death) of men in septic shock. All of them were elevated in sera from patients with shock. Highest levels of oestrone 4330 pmol 1(-1), (SEM +/- 851, n = 15), oestradiol 1030 pmol 1(-1), (SEM +/- 220, n = 15) and cortisol 1096 pmol 1(-1), (SEM +/- 94, n = 15), were found in patients who failed to recover from shock. However, oestrone levels were the most striking, especially in the male. This study gives evidence for a polarity relationship between the CDF and oestrone, but natural oestrone does not appear to be a direct CDF. Moreover, this study shows that radioimmunoassay of oestrone could be an important index evaluating the severeness of septic shock.     

Choice of DES: A European Clinician's Perspective

The introduction of the first generation of drug-eluting stents (DES) in 2002 revolutionized interventional cardiology by minimizing restenosis. Reports of increased late stent thrombosis with these stents compared with bare metal stents, probably due to delayed endothelialization, emerged late in 2006. These studies contained serious methodological flaws, however. Subsequent meta-analyses clearly showed only a small incremental risk of late stent thrombosis across all patient groups. Importantly, a significant and sustained benefit of DES due to reduced restenosis and thus repeat revascularization was also shown. Several "real-world" registries have confirmed these results, as well as suggesting that use in more complex situations is not associated with adverse outcomes. Stent thrombosis is a multifactorial problem, in which the stent is only one element. Further research is required to determine optimal procedural technique and antiplatelet regimes.
Second-generation DES, with different antiproliferative drugs and more biocompatible polymers, have shown promising results in comparative studies with the first generation. Current follow-up data for these stents is only up to 3 years, however.
DES are safe and effective in the long term, though intensive research continues into ways to reduce the risk of stent thrombosis in the next generation.     

Immunosuppressive effects of 1,2 5-dihydroxyvitamin D3 and its analogue calcipotriol on epidermal cells

1,25-Dihydroxyvitamin D₃ (1,25(OH)₂D₃: calcitriol) is the biologically active form of vitamin D. This hormone is a potent immunoregulatory agent. Calcipotriol is a synthetic analogue of 1,25(OH)₂D₃, with similar receptor binding, and comparable effects on cell proliferation and differentiation, but less potent effects on calcium metabolism. As a step towards understanding the mechanisms by which vitamin D compounds affect T-cell activation by epidermal cells (EC), we assessed the effects of 1,25(OH)₂D₃ and calcipotriol on the human allogeneic mixed epidermal cell-lymphocyte reaction. All experiments were performed both with 1,25(OH)₂D₃, and calcipotriol, with similar results. Both compounds had potent immunoinhibitory properties on this model, and enhanced the immunosuppressive effects of cyclosporin A. Using preincubation experiments, we found that pretreatment of EC with 1,25(OH)₂D₃ resulted in a more pronounced inhibition than preincubation of lymphoid cells. The epidermal targets of this inhibitory effect have been further investigated, using cultures with freshly isolated Langerhans cells (LC) or LC-depleted keratinocytes, separated by an immunomagnetic particle technique. Pretreatment of LC induced a 30% decrease of proliferation, compared with vehicle-treated LC. These calcitriol-pulsed LC did not decrease the proliferation induced by unmodified autologous EC. As expected. LC-depleted keratinocytes failed to stimulate allogeneic lymphocytes. When added to autologous unmodified EC, however, calcitriol-pulsed keratinocytes induced an 85% decrease of proliferation, compared with vehicle-treated keratinocytes. The phenotypic expression of HLA-DR, -DQ, and -DP antigens on EC, assessed by immunoalkaline phosphatase staining, was not modified after a 2-h or 24-h pulse with 1,25(OH)₂D₃ or calcipotriol. The inhibitory effect of vitamin D compounds on EC was not modified by indomethacin, but was partially reversed by the addition of anti-TGF-β neutralizing antibodies. In conclusion, 1,25(OH)₂D₃ and calcipotriol may limit the immune response in human skin through decreased antigen presentation, mediated both by a direct effect on LC and indirectly through modulation of the production of cytokines by keratinocytes.