[Sirolimus-eluting stent displaced fracture: case report and review of the literature]. / Fracture déplacée d'un stent actif au sirolimus : à propos d'un cas et revue de la littérature.

Drug-eluting stents have greatly reduced the risk of in-stent restenosis compared to bare metal stents by inhibiting neointimal growth. However, they may carry some long-term risks, especially the risk of late stent thrombosis. Recently, several cases of drug-eluting stent fracture have been also reported. The mechanisms, the diagnosis, the clinical implications and the management of this new complication are not well-known. We report the observation of a new case of displaced, sirolimus drug-eluting stent fracture. To our knowledge, this is the first reported case in France.

Genomewide linkage scan of schizophrenia in a large multicenter pedigree sample using single nucleotide polymorphisms.

A genomewide linkage scan was carried out in eight clinical samples of informative schizophrenia families. After all quality control checks, the analysis of 707 European-ancestry families included 1615 affected and 1602 unaffected genotyped individuals, and the analysis of all 807 families included 1900 affected and 1839 unaffected individuals. Multipoint linkage analysis with correction for marker-marker linkage disequilibrium was carried out with 5861 single nucleotide polymorphisms (SNPs; Illumina version 4.0 linkage map). Suggestive evidence for linkage (European families) was observed on chromosomes 8p21, 8q24.1, 9q34 and 12q24.1 in nonparametric and/or parametric analyses. In a logistic regression allele-sharing analysis of linkage allowing for intersite heterogeneity, genomewide significant evidence for linkage was observed on chromosome 10p12. Significant heterogeneity was also observed on chromosome 22q11.1. Evidence for linkage across family sets and analyses was most consistent on chromosome 8p21, with a one-LOD support interval that does not include the candidate gene NRG1, suggesting that one or more other susceptibility loci might exist in the region. In this era of genomewide association and deep resequencing studies, consensus linkage regions deserve continued attention, given that linkage signals can be produced by many types of genomic variation, including any combination of multiple common or rare SNPs or copy number variants in a region.

Prognostic impact of diabetes mellitus in patients with heart failure and preserved ejection fraction: a prospective five-year study.

OBJECTIVE: To evaluate the prognostic impact of diabetes mellitus (DM) in patients with heart failure and preserved ejection fraction (HFPEF) DESIGN: A five-year prospective observational study SETTING: Population of 368 consecutive patients from 11 healthcare establishments PATIENTS: All patients hospitalised for a first episode of HFPEF in 2000 in the Somme department, France. INTERVENTIONS: Diagnosis of heart failure (HF) was validated during the index hospitalisation by two independent cardiologists. Diabetic and non-diabetic groups were compared. After discharge, patients were managed by the general practitioner or referring cardiologist. MAIN OUTCOME MEASURES: Overall and cardiovascular mortality. RESULTS: The 96 diabetic patients (26%) were younger and had a higher prevalence of clinical coronary artery disease (CAD) than non-diabetic patients. Patients with DM had higher discharge prescription rates of angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers, nitrates and statins. During the five-year follow-up, 208 patients died (43.5%). DM was a potent independent predictor of five-year overall mortality (HR 1.77, 95% CI 1.27 to 2.48, p = 0.001). Compared to the expected survival of the age-matched and gender-matched general population, the five-year survival of patients with DM was dramatically lower (32% vs 79%). The five-year relative survival (observed/expected survival) of diabetic patients was lower than that of the non-diabetic group (41% vs 68%). Cardiovascular causes were responsible for >60% of deaths in the DM group. DM was associated with an increased risk of death in patients with clinical CAD (HR 1.82, 95% CI 1.02 to 3.25, p = 0.04), as well as in patients without clinical CAD (HR 1.85, 95% CI 1.22 to 2.82, p = 0.004). CONCLUSION: In patients with HFPEF, DM is a strong predictor of poorer long-term survival.

[Coronary artery disease observed in general hospitals: ETTIC study. Comparison between trimetazidine and mononitrate isosorbide for patients receiving betablockers]. / L'insuffisance coronaire chronique dans les hôpitaux généraux: registre ETICC. Comparaison entre la Trimetazidine et le Mononitrate d'isosorbide en complément du traitement bêtabloquant.

The extended use of interventional surgery of revascularisation has modified the prognosis and the evolution of ischaemic heart diseases. However, both coronary artery bypass graft and percutaneous transluminal coronary angioplasty failed to make the symptomatic or subclinical ischaemic manifestations of chronic coronary insufficiency disappear. The interest of using betablockers as a first-line therapy was widely demonstrated. However, their combination with another efficient molecule is often necessary. The aim of this trial has been to appreciate the efficiency of the association of a betablocker with either trimetazidine or with isosorbide monoitrate. Hundred and eighty five patients retaining a positive effort test despite 100 mg of atenolol, received in addition, either 60 mg of trimetazidine (93 cases) of 60 mg of isosorbide mononitrate (92 cases) for a two-month period and are then re-evaluated at the end of this period. The ischaemic threshold is delayed in a significant way in both groups (p < 0.0001; trimetazidine +7%, isosorbide mononitrate +10.7%). Twenty-three percent of the exercise tests under trimetzidine and 19% under isosorbide mononitrate become negative after two months of the therapeutic combination. The clinical improvement is even clearer with the disappearance of the angina crisis during the week before the second exercise test in 63% of the cases under trimetazidine and 54% of the cases under isosorbide mononitrate, among the patients who had kept it under atenolol at the inclusion. In conclusion, the combination of a second efficient molecule, trimetazidine or isosorbide mononitrate, brings a functional and objective improvement to patients with insufficient chronic coronary disease not totally controlled using a betablocker, even with high dosage. One should notice two important advantages in favour of the trimetazidine: one is practical due to a better tolerance (lack of cephalalgia), the other is conceptual (use of the complementary metabolic approach of cellular oxygenation rather than the haemodynamic approach of nitrate compounds which are already in concurrency with all other anti-ischaemic molecules).

Mapping of 13 horse genes by fluorescence in-situ hybridization (FISH) and somatic cell hybrid analysis.

We report fluorescence in-situ hybridization (FISH) and somatic cell hybrid mapping data for 13 different horse genes (ANP, CD2, CLU, CRISP3, CYP17, FGG, IL1RN, IL10, MMP13, PRM1, PTGS2, TNFA and TP53). Primers for PCR amplification of intronic or untranslated regions were designed from horse-specific DNA or mRNA sequences in GenBank. Two different horse bacterial artificial chromosome (BAC) libraries were screened with PCR for clones containing these 13 Type I loci, nine of which were found in the libraries. BAC clones were used as probes in dual colour FISH to confirm their precise chromosomal origin. The remaining four genes were mapped in a somatic cell hybrid panel. All chromosomal assignments except one were in agreement with human-horse ZOO-FISH data and revealed new and more detailed information on the equine comparative map. CLU was mapped by synteny to ECA2 while human-horse ZOO-FISH data predicted that CLU would be located on ECA9. The assignment of IL1RN permitted analysis of gene order conservation between HSA2 and ECA15, which identified that an event of inversion had occurred during the evolution of these two homologous chromosomes.

Cytogenetic localization of 44 new coding sequences in the horse.

The purpose of this study was to increase the number of genes assigned by in situ hybridization to equine chromosomes and thus the number of links for comparative mapping with other species. Forty-four new sequences were added to the horse cytogenetic map by FISH mapping of BAC clones containing genes (35) or ESTs (9). Three approaches were developed: use of horse BAC clones screened with (i) horse EST primers, (ii) interspecific consensus intraexonic primers, and (iii) use of goat BAC containing genes previously localized on goat chromosomes. Present data suggest that the second approach is the most promising. A total of 46 segments containing one or several genes could be compared, among which 40 loci could be included in 16 synteny groups between human and horse, displaying one ordered segment and several breaking points along chromosomes. All single BAC localizations confirm the most recent mapping data. Twenty-six out of 31 chromosomes now contain a gene mapped by in situ hybridization, and 14 new arm-to-arm segment homologies were revealed.

[Legionella myopericarditis]. / Myopéricardite à Legionella.

Cardiac involvement in legionella infection is rare but it is the most common extra-pulmonary complication. It usually takes the form of pericarditis, but a case of legionella myoparicarditis with global left ventricular hypokinesia on echocardiography has been described. The authors report a case of myopericarditis with massive pulmonary oedema and respiratory distress which regressed clinically and on echocardiography with reduction in chamber dilatation and complete recovery of left ventricular function. Legionellosis was confirmed on serology. The infection was probably contracted during a previous hospital admission, therefore, probably a nosocomial infection. Following the description of this case, a review of the literature is proposed.

A repetitive probe for FISH analysis of bovine interphase nuclei.

The purpose of this study was to generate repetitive DNA sequence probes for the analysis of interphase nuclei by fluorescent in situ hybridisation (FISH). Such probes are useful for the diagnosis of chromosomal abnormalities in bovine preimplanted embryos. Of the seven probes (E1A, E4A, Ba, H1A, W18, W22, W5) that were generated and partially sequenced, five corresponded to previously described Bos taurus repetitive DNA (E1A, E4A, Ba, W18, W5), one probe (W22) shared no homology with other DNA sequences and one (H1A) displayed a significant homology with Rattus norvegicus mRNA for secretin receptor transmembrane domain 3. Fluorescent in situ hybridisation was performed on metaphase bovine fibroblast cells and showed that five of the seven probes hybridised most centromeres (E1A, E4A, Ba, W18, W22), one labelled the arms of all chromosomes (W5) and the H1A probe was specific to three chromosomes (ch14, ch20, and ch25). Moreover, FISH with H1A resulted in interpretable signals on interphase nuclei in 88% of the cases, while the other probes yielded only dispersed overlapping signals.

Report of the International Equine Gene Mapping Workshop: male linkage map.

The goal of the First International Equine Gene Mapping Workshop, held in 1995, was the construction of a low density, male linkage map for the horse. For this purpose, the International Horse Reference Family Panel (IHRFP) was established, consisting of 12 paternal half-sib families with 448 half-sib offspring provided by 10 laboratories. Blood samples were collected and DNA extracted in each laboratory and sent to the Lexington laboratory (KY, USA) for dispatch in aliquots to 14 typing laboratories. In total, 161 markers (144 microsatellites, seven blood groups and 10 proteins) were tested for all families for which the sire was heterozygous. Genealogies and typing data were sent for analysis to the INRA laboratory (Jouy-en-Josas, France) according to a specific format and entered into a database with input verification and output processes. Linkage analysis was performed with the CRIMAP program. Significant linkage was detected for 124 loci, of which 95 were unambiguously ordered using a multipoint analysis with an average spacing of 14.2 CM. These loci were distributed among 29 linkage groups. A more comprehensive analysis including synteny group data and FISH data suggested that 26 autosomes out of 31 are covered. The complete map spans 936 CM.

Comparison of horse chromosome 3 with donkey and human chromosomes by cross-species painting and heterologous FISH mapping.

The melanocortin 1 receptor (MC1R), mast/stem cell growth factor receptor (KIT), and platelet-derived growth factor receptor alpha (PDGFRA) are loci that all belong to equine linkage group 2 (LG2). Of these, KIT was fluorescent in situ hybridization (FISH) mapped to ECA3q21 with equine cDNA and heterologous porcine BAC probes, while MC1R was localized to ECA3p12 and PDGFRA to ECA3q21 with heterologous porcine BAC probes. A three-step comparison between ECA3 and donkey chromosomes was carried out. First, microdissected ECA3 painting probe was used on donkey chromosomes, which showed disruption of the equine synteny. Next, human (HSA) Chromosomes (Chrs) 16q and 4 specific paints, known to be homologous to ECA3p and 3q, respectively, were applied to detect homologous chromosomal segment(s) in donkey. Finally, four genes (MC1R, ALB, PDGFRA, KIT) and two equine microsatellite markers (SGCV18 and SGCV33) located on ECA3 were FISH mapped to donkey chromosomes. The findings refined the cross species painting homology results and added six new markers to the nascent donkey gene map. The hypothesis that Tobiano coat color in horses may be associated with a chromosomal inversion involving genes within LG2 was tested by G-banding-based cytogenetic analysis and ordering of four loci-KIT, PDGFRA, albumin (ALB), and MC1R-in Tobiano and non-tobiano (homozygous as well as heterozygous) horses. However, no difference either in banding patterns or location/relative order of the genes was observed in the three classes. The study highlights successful FISH mapping of BAC probes across evolutionarily diverged species, viz., pig and horse/donkey, and represents the first use of large-sized individual clones across distantly related farm animals.

A synteny map of the horse genome comprised of 240 microsatellite and RAPD markers.

To generate a domestic horse genome map we integrated synteny information for markers screened on a somatic cell hybrid (SCH) panel with published information for markers physically assigned to chromosomes. The mouse-horse SCH panel was established by fusing pSV2neo transformed primary horse fibroblasts to either RAG or LMTk mouse cells, followed by G418 antibiotic selection. For each of the 108 cell lines of the panel, we defined the presence or absence of 240 genetic markers by PCR, including 58 random amplified polymorphic DNA (RAPD) markers and 182 microsatellites. Thirty-three syntenic groups were defined, comprised of two to 26 markers with correlation coefficient (r) values ranging from 0.70 to 1.0. Based on significant correlation values with physically mapped microsatellite (type II) or gene (type I) markers, 22 syntenic groups were assigned to horse chromosomes (1, 2, 3, 4, 6, 9, 10, 11, 12, 13, 15, 18, 19, 20, 21, 22, 23, 24, 26, 30, X and Y). The other 11 syntenic groups were provisionally assigned to the remaining chromosomes based on information provided by heterologous species painting probes and work in progress with type I markers.

[Comparative study of the global left ventricular ejection fraction obtained by ECG gated perfusion MIBI and thallium scintigraphy]. / Etude comparative de la fraction d'éjection globale du ventricule gauche obtenue par l'analyse couplée à l'ECG de la tomoscintigraphie de perfusion au MIBI et au thallium.

The isotopic LVEF was measured by a planar method with injection of a product visualising the ventricular cavity. Perfusion was assessed by Thallium and sesta MIBI. The investigation of ischaemia and assessment of wall motion in the coronary patient, therefore, requires two isotopic methods. The Cedars Sinai group have developed a programme allowing acquisition of a perfusion tomoscintigraphy in the cardiac cycle after injection of MIBI. This programme automatically detects the endocardial borders and calculates the LVEF. This provides a study of function and perfusion in a single investigation. However, MIBI is not considered by all as a good marker of viability, contrary to Thallium. And the acquisition of Thallium tomography with ECG gating may pose problems because of the low counting statistic. Several authors have therefore studied the possibility of using it for assessing left ventricular function. The authors have then compared LVEF with MIBI and with Thallium in 72 patients. The Thallium LVEF was 33.62% +/- 15.79%; that of MIBI was 32.51% +/- 14.73%. ThalEF = MIBI EF x 1.02 + 0.34 (r = 0.955). The mean of the standard deviation was 1.09. In conclusion, the EF measured by Thallium tomography with ECG gating was closely correlated to that obtained with MIBI. These results suggest that myocardial viability, ischaemia and function may be studied in routine daily practice with a single injection, so improving patient comfort and reducing the costs of the procedures.

Construction of a horse BAC library and cytogenetical assignment of 20 type I and type II markers.

A horse BAC library was constructed with about 40,000 clones and mean insert size of 110 kb representing a 1.5 genome equivalent coverage and a probability of finding a single sequence of 0.75. It was characterized by PCR screening of about 130 sequences of horse microsatellites and exonic gene sequences retrieved from databases. BACs containing 8 microsatellites and 12 genes were subsequently localized by fluorescent in situ hybridization (FISH) on chromosomes. Two linkage groups were newly assigned to chromosomes: LG2 to ECA3 and LG5 to ECA24, and five linkage groups were also oriented--LG3, LG4, LG5, LG8, and LG12--leaving only three groups unassigned. This work showed how this library makes an integrated map a realistic objective for the near future and how it can make comparative mapping more efficient in a search for candidate genes of interest.

Characterization, genetic and physical mapping analysis of 36 horse plasmid and cosmid-derived microsatellites.

Thirty-six new horse microsatellites (11 from plasmid libraries and 25 from a cosmid library) were isolated and characterized on a panel of four horse breeds. Thirty were found to be polymorphic with heterozygosity levels ranging between 0.20 and 0.87. Twenty-two of the cosmids were physically mapped to R-banded single horse Chromosomes (Chrs) 1, 3, 4, 9, 11, 12, 13, 15, 18, 19, 21, 22, 23 and three to pericentromeric regions. Furthermore, linkage analysis between a selection of 42 DNA markers, including those presented in this study, and 16 conventional markers of the horse hemotype was performed on six paternal half-sib horse families. Five linkage groups were detected, of which four were assigned to Chr 10, 11, 15, and 18. This work increased by one-third the number of published polymorphic DNA markers suitable for horse mapping and approximately doubled the number of known linkage groups. Our cosmids labeled 14 out of the 31 horse autosomes. Moreover, the physical anchoring of part of these markers will orient linkage and synteny groups on the chromosomes and will contribute to their assignment.

[Isolated congenital diverticulum of the left ventricle disclosed by ventricular tachycardia in a 72-year-old woman]. / Diverticule congénital isolé du ventricule gauche découvert par une tachycardie ventriculaire chez une femme de 72 ans.

A 72-year-old woman presented with poorly tolerated ventricular tachycardia reduced by intravenous amiodarone. The possibility of an ischaemic aetiology led us to perform coronary angiography. The coronary arteries were pathological. Left ventricular angiography revealed limited anterior hypokinesia and a large contractile apical pouch appended to the left ventricle by a long narrow neck. Despite the appearance suggestive of congenital left ventricular diverticulum (contractility, narrow neck) and because of the coexistence of ischaemic heart disease, we preferred to confirm the muscular nature of the diverticulum by myocardial thallium scintigraphy, which showed reversible decreased uptake in the anterior zone related to coronary artery disease, and confirmed the muscular nature of the diverticulum which showed normal thallium uptake. MRI clearly visualized the ventricular ectasia attached by a narrow neck to the rest the left ventricle. This long narrow neck indicated that this muscular diverticulum constituted a congenital diverticulum. The contribution of ultrasonography was limited by a poorly defined point during the examination. This congenital diverticulum, discover during adulthood, and previously asymptomatic, is a rare lesion, in the light of a review of the literature.

[Malignant non-Hodgkin lymphoma of cardiac localization. Apropos of a case]. / Lymphome malin non hodgkinien à localisation cardiaque. A propos d'une observation.

Malignant non-Hodgkin's lymphomas are rare in the absence of human immunodeficiency virus infection and it is exceptional for a cardiac site to be the prominent feature. In our case, the malignant lymphoma was revealed by pericardial effusion in a context of alteration of the general state. Echocardiography revealed a heterogeneous mass in the right atrium and an abundant circumferential pericardial effusion. Thoracic computed tomography allowed local staging and magnetic resonance imaging (MRI) allowed a better definition, than CT scan, of the extension of the tumour into the various cardiac structures. The histological diagnosis was established on biopsy of a mediastinal lymph node. The patient died 7 months after the diagnosis, despite chemotherapy. The authors emphasize the contribution of echocardiography in the diagnosis of cardiac tumours, computed tomography in local staging, and MRI in the analysis of the various cardiac structures.

[Anaphylactic reaction with coronary spasm following coronarography]. / Réaction anaphylactique avec spasme coronarien. Au décours d'une coronarographie.

The authors report a case of anaphylactic shock following the injection of iodinated contrast medium for coronary angiography and complicated by two spasms affecting segments II and III of the right coronary. Vasospasm was relieved by the injection of linsidomine, revealing an angiographically healthy segment III. Such complications associated with various substances, notably iodinated contrast media, are rare. They should nevertheless always be borne in mind when evaluating anaphylactic type reactions. Vasoactive mediators (histamine, serotonin, arachidonic acid metabolites) released by the allergic reaction appear to play a major role. Treatment based upon pathogenesis can be proposed.