In-hospital and mid-term adverse clinical outcomes of a direct stenting strategy versus stenting after predilatation for the treatment of coronary artery lesions

Background

Direct stenting without balloon dilatation may reduce procedural costs and duration, and hypothetically, the restenosis rate. This study was designed to compare the in-hospital and long-term outcomes of direct stenting (DS) versus stenting after pre-dilatation (PS) in our routine clinical practice.

Methods

The 1 603 patients treated with stenting for single coronary lesions were enrolled into a prospective registry. Patients with acute myocardial infarction (MI) within the preceding 48 hours, and those with highly calcified lesions, total occlusions, or a lesion in a saphenous graft were excluded. The baseline, angiographic and procedural data, inhospital outcomes and follow-up data were recorded in our database and analysed with appropriate statistical methods.

Results

Eight hundred and fifty-seven patients (53.5%) were treated with DS and 746 (46.5%) underwent PS. In the DS group, lesions were shorter in length, larger in diameter and had lower pre-procedural diameter stenosis. Type C and diffuse lesions and drug-eluting stents were found less often (p < 0.001). With univariate analysis, dissection and non-Q-wave MI occurred less frequently in this group (0.2 and 0.6% vs 3.9 and 2.1%, p < 0.001 and p = 0.01, respectively). However, the cumulative major adverse cardiac events (MACE) did not differ significantly (4.9 vs 4.6%, p = 0.79). With multivariate analysis, direct stenting reduced the risk of dissection (OR = 0.07, 95% CI: 0.01–0.33, but neither the cumulative endpoint of MACE (OR = 1.1, 95% CI = 0.58–2.11, p = 0.7) nor its constructing components were different between the groups.

Conclusions

Direct stenting in the real world has at least similar long-term outcomes in patients treated with stenting after pre-dilatation, and is associated with lower dissection rates.     

Kinetics of specific anti-influenza antibody production by cultured lymphocytes from patients with systemic lupus erythematosus following influenza immunization.

Specific antibody responses to influenza viral antigens produced by cultured peripheral blood mononuclear leucocytes stimulated with influenza virus or pokeweed mitogen (PWM) have been measured in seven patients with systemic lupus erythematosus (SLE) before and at time intervals after influenza immunization. Cells from two patients stimulated with influenza virus in vitro produced high levels of specific antibody 7 days after immunization. Cells from a third patient produced small amounts of specific antibody at day 14. No antibody was produced by cells from the remaining four patients. Responses were of short duration and were not detectable 1 month after immunization. Specific anti-influenza antibody was induced by PWM only from cells of those patients who responded to virus antigen although absolute levels of antibody produced were not as high. In six patients serum haemagglutination inhibiting antibody to influenza virus was measured, and all six had a greater than four-fold increase. The disparity between in vitro antibody production by peripheral blood mononuclear leucocytes and changes in serum antibody suggests that in patients with systemic lupus erythematosus, in vitro functions of peripheral blood lymphocytes do not reflect the immune system as a whole.     

The hippocampus in families with schizophrenia in relation to obstetric complications

BACKGROUND: Hippocampal volume reduction is a well replicated finding in schizophrenia. Evidence indicates a contribution of genetic and environmental factors, especially the influence of obstetric complications to this volume reduction. The aim of this study was to compare hippocampal volume of schizophrenic patients as well as and their relatives with control subjects and to quantify the additional contribution of obstetric complications. METHODS: T1 weighted MRI brain scans of 50 schizophrenic patients, 88 first-degree relatives and 53 healthy control subjects were used to perform volumetric measurements on the left and right hippocampus. A set of clinical measures including obstetric complications were recorded for all family members. RESULTS: Numerically our measurements revealed a hippocampal volume reduction in schizophrenic patients (left: - 14%, right: - 15%) and, although less pronounced, in their unaffected relatives (left: - 6%, right: - 10%). Noted differences in hippocampal volume between schizophrenic patients and controls were only significant for the left side. Hippocampal volumes of patients and their relatives with obstetric complications were reduced bilaterally. CONCLUSIONS: Hippocampal volume reduction is present in schizophrenic patients and their first-degree relatives, suggesting an influence of genetic factors.. In addition, however, obstetric complications have also been shown to play a major role.     

Cell surface expression of the epithelial Na channel and a mutant causing Liddle syndrome: A quantitative approach

The epithelial amiloride-sensitive sodium channel (ENaC) controls transepithelial Na⁺ movement in Na⁺-transporting epithelia and is associated with Liddle syndrome, an autosomal dominant form of salt-sensitive hypertension. Detailed analysis of ENaC channel properties and the functional consequences of mutations causing Liddle syndrome has been, so far, limited by lack of a method allowing specific and quantitative detection of cell-surface-expressed ENaC. We have developed a quantitative assay based on the binding of ¹²⁵I-labeled M₂ anti-FLAG monoclonal antibody (M₂Ab*) directed against a FLAG reporter epitope introduced in the extracellular loop of each of the α, β, and γ ENaC subunits. Insertion of the FLAG epitope into ENaC sequences did not change its functional and pharmacological properties. The binding specificity and affinity (K_d = 3 nM) allowed us to correlate in individual Xenopus oocytes the macroscopic amiloride-sensitive sodium current (I_Na) with the number of ENaC wild-type and mutant subunits expressed at the cell surface. These experiments demonstrate that: (i) only heteromultimeric channels made of α, β, and γ ENaC subunits are maximally and efficiently expressed at the cell surface; (ii) the overall ENaC open probability is one order of magnitude lower than previously observed in single-channel recordings; (iii) the mutation causing Liddle syndrome (β R564stop) enhances channel activity by two mechanisms, i.e., by increasing ENaC cell surface expression and by changing channel open probability. This quantitative approach provides new insights on the molecular mechanisms underlying one form of salt-sensitive hypertension.     

Mast cells are crucial for early inflammation, migration of Langerhans cells, and CTL responses following topical application of TLR7 ligand in mice

Until recently, IgE-activated mast cells have been regarded merely as effector cells of adaptive immune responses, involved in allergic reactions and mucosal immunity to parasites. Herein, we report that murine dermal mast cells, activated by local administration of a cream containing the synthetic TLR7 ligand imiquimod, are essential to initiate an early inflammatory reaction. The mast-cell-derived cytokines TNF-alpha and IL-1beta play an important role in this process. Furthermore, TLR7-activated mast cells are also able to promote the emigration of Langerhans cells, which partly depends on the expression of mast-cell-derived IL-1beta. We have previously shown that TLR7 ligation enhances transcutaneous immunization evoked by topical application of vaccine antigens to the skin, a procedure that directly targets skin-resident antigen-presenting cells. Consequently, we now demonstrate here that the capacity to mount a peptide-specific cytotoxic T-lymphocyte response following transcutaneous immunization using imiquimod as adjuvant is severely impaired in mast-cell-deficient mice. Thus, these findings demonstrate the potent versatility of alternatively activated mast cells at the interface of innate and adaptive immunity.     

De novo duplication of MECP2 in a girl with mental retardation and no obvious dysmorphic features

Makrythanasis P, Moix I, Gimelli S, Fluss J, Aliferis K, Antonarakis SE, Morris MA, Béna F, Bottani A. De novo duplication of MECP2 in a girl with mental retardation and no obvious dysmorphic features. Loss‐of‐function mutations of MECP2 are responsible for Rett syndrome (RTT), an X‐linked neurodevelopmental disorder affecting mainly girls. The availability of MECP2 testing has led to the identification of such mutations in girls with atypical RTT features and the recognition of milder forms. Furthermore, duplication of the entire gene has recently been described in boys with mental retardation and recurrent infections. We describe a girl with a heterozygous de novo MECP2 duplication. The patient, at the age of 19, has mental retardation with no autistic features. She is friendly but gets frequently anxious. She has neither dysmorphic features nor malformations. Her motor development was delayed with walking at 20 months. Speech is fluid with good pronunciation but is simple and repetitive. Diagnosis was made after single‐strand conformation analysis (SSCA) and multiplex ligation‐dependent probe amplification (MLPA) analysis of MECP2. Array comparative genomic hybridization (aCGH) analysis showed a duplication of 29 kb including MECP2 and part of IRAK1. Fluorescent in situ hybridization (FISH) has revealed that the duplicated region is inserted near the telomere of the short arm of chromosome 10. X‐chromosome inactivation in leukocyte DNA was not skewed. We conclude that it is likely that this MECP2 duplication is responsible for the mental retardation in this patient. This case broadens the phenotypic spectrum of MECP2 abnormalities with consequent implication in diagnosis and genetic counselling of girls with non‐syndromic mental retardation.     

Stem cell-coated titanium implants for the partial joint resurfacing of the knee

The goal of the present study was to evaluate the partial surface replacement of the knee with stem cell-coated titanium implants and to provide a basis for a successful treatment of large osteochondral defects. Mesenchymal stem cells (MSCs) were isolated from bone marrow aspirates of adult sheep. Round titanium implants with a diameter of 2 x 7.3 mm were seeded with autologous MSC and inserted into an osteochondral defect in the medial femoral condyle. As controls, defects received either an uncoated implant or were left untreated. Nine animals with 18 defects were sacrificed after 6 months. Histological evaluation was performed by intravital polychrome fluorescent labelling, intravital perfusion with Indian ink, microradiographs and differential staining with toluidine blue. The quality of regenerated cartilage was assessed by in situ hybridization of collagen type II and immunohistochemistry of collagen types I and II. In 50% of the cases, defects treated with MSC-coated implants showed a complete regeneration of the subchondral bone layer. In these cases collagen type II and only traces of collagen type I were detected. A high level of collagen type II mRNA expression compared to articular cartilage indicates regenerating hyaline-like cartilage. A total of 50% of MSC-coated and uncoated implants failed to osseointegrate and formation of fibrocartilage was observed. Untreated defects as well as defects treated with uncoated implants demonstrated incomplete healing of subchondral bone and formation of fibrous cartilage. A modified histological score according to Wakitani significantly demonstrated better results for cell-coated implants (8.8+/-6.4) than for uncoated implants (5.5+/-3.9) and for untreated defects (2.8+/-2.5). Our results demonstrate that, in a significant number of cases, a partial joint resurfacing of the knee with stem cell-coated titanium implants occur. A slow bone and cartilage regeneration and an incomplete healing in half of the MSC-coated implants are limitations of the presented method. To improve our approach and optimize the experimental parameters, further investigations are needed prior to clinical application.     

Herpes virus entry mediator synergizes with Toll-like receptor mediated neutrophil inflammatory responses

In microbial infections polymorphnuclear neutrophils (PMN) constitute a major part of the innate host defence, based upon their ability to rapidly accumulate in inflamed tissues and clear the site of infection from microbial pathogens by their potent effector mechanisms. The recently described transmembrane receptor herpes virus entry mediator (HVEM) is a member of the tumour necrosis factor receptor super family and is expressed on many haematopoietic cells, including T cells, B cells, natural killer cells, monocytes and PMN. Interaction of HVEM with the natural ligand LIGHT on T cells has a costimulatory effect, and increases the bactericidal activity of PMN. To further characterize the function of HVEM on PMN, we evaluated the effect of receptor ligation on human PMN effector functions using an agonistic monoclonal antibody. Here we demonstrate that activation of HVEM causes activation of neutrophil effector functions, including respiratory burst, degranulation and release of interleukin-8 in synergy with ligands for Toll-like receptors or GM-CSF. In addition, stimulation via HVEM enhanced neutrophil phagocytic activity of complement opsonized, but not of non-opsonized, particles. In conclusion, these results indicate a new, as yet unknown, participation of HVEM in the innate immune response and points to a new link between innate and adaptive immunity.