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.

[Extensive coronary dissection after percutaneous transluminal angioplasty. Apropos of a case]. / Dissection coronaire étendue après angioplastie transluminale percutanée. A propos d'un cas.

The authors report a rare case of very extensive dissection of the right coronary artery immediately after angioplasty; the lesion was totally asymptomatic. Coronary bypass was performed 4 months later without complications and with a satisfactory result at a 15-month follow-up. Coronary dissection during angioplasty is usually located at the site of dilatation: its incidence varies from 6 to 13 p. 100 depending on the series reported. Facilitating factors are analysed, and the management of this complication is discussed: repeat angioplasty and/or emergency or elective coronary bypass, depending on the presence or absence of coronary thrombosis and symptoms, on the importance of the territory threatened and on the quality of collateral circulation.

[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.

[Transmural myocardial infarction and Prinzmetal's syndrome in an allergic reaction to glafenine. Physiopathological discussion. Apropos of a case]. / Infarctus myocardique transmural et syndrome de Prinzmetal au cours d'une réaction allergique à la glafénine. Discussion physiopathologique. A propos d'un cas.

The authors report the case of a 38 year old man who experienced at two month' interval, hypersensitivity reactions to the ingestion of 200 mg tablets of glafenine, complicated on the first occasion by a transmural anterior wall myocardial infarction as the first manifestation of coronary artery disease and on the second occasion by Prinzmetal angina due to posterior wall ischaemia. Coronary angiography was more or less normal. The timing of the symptoms in the context of an anaphylactic reaction and their repetition when the same molecule was reintroduced are strong arguments in favour of the pathogenic role of glafenine, even in the absence of biological criteria which are always variable. The mechanism of the coronary problems is discussed with reference to mediators released during the anaphylactic reaction: coronary vasoconstriction due to histamine and leukotriene release; inhibition of prostaglandin synthesis causing potentiation of the effects of histamine; lowering of the vasodilatory and antiaggregant prostacyclin enhancing the vasoconstrictor and platelet aggregant action of thromboxane A2. All the conditions favouring the initiation of coronary spasm with eventual coronary thrombosis, the one aggravating the other, are therefore present.

[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.

[Tumor of the tricuspid valve operated on with success. Apropos of a case simulating cyanotic heart disease]. / Tumeur de la valve tricuspide opérée avec succès. A propos d'un cas simulant une cardiopathie cyanogène.

The case of a 36 year old woman with a calcified tumour of the tricuspid valve is reported. The clinical signs suggested tricuspid stenosis with a right to left shunt via a patent foramen ovale simulating a cyanotic heart lesion. Preoperative diagnostic investigations were discordant. Echocardiography showed a stenotic tumoural tricuspid valve. Catheterisation and selective right ventriculography were more suggestive of dominant tricuspid incompetence. The patient was referred for surgery because of the severity of her shortness of breath and cyanosis, and tumoral involvement of the three tricuspid leaflets was found. This was removed and replaced by a bioprosthesis with good results 27 months after surgery. 17 other cases of tricuspid tumours have been previously reported. Their clinical presentation was usually that of a right ventricular tumour with stenosis of the right failure, positional syncope and pericardial effusion in the malignant forms. Signs of tricuspid stenosis with cyanosis and polycythaemia are very rare. The relative diagnostic values of angiography and echocardiography are discussed.

[Return to work after myocardial infarction. Study of factors in return to work by the statistical method of analysis of correspondences]. / Reprise du travail après infarctus du myocarde. Etude des facteurs de retour au travail par la méthode statistique d'analyse des correspondances.

A retrospective study has examined the predictive factors of return to work in 184 males patients with myocardial infarction between 1975 and 1982. The statistical method used was that of correspondence analysis which enables to define correlations between variables, here 12 in number. The chances of returning to work are positively correlated to young age (48-52 years), school education and social standing. They were not increased by coronary by-pass surgery. Cardiac insufficiency, and a large area of infarction contribute to the non-return to work, while subsequent angor and arrhythmias do not demonstrate any significant relation. Finally, a patient who has not returned to work after one year seems to have few chances of becoming active again.

[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).

[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.

[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.

[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.

[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.

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.

Public-academic linkages: a "linchpin" model.

The "linchpin" model of collaboration between state mental health agencies and university training programs has been developed in two states. This paper describes the model, pointing out both strengths and weaknesses. Recommendations for institutions seeking this type of collaboration and persons who are in the collaborative role are provided.

Education and training in public psychiatry.

The Public Psychiatry Training Program offers an education in the unique knowledge, attitudes, and skills essential for working with persons with severe and chronic illness in both hospital and community settings.

The influence of the right to refuse treatment on precommitment patients.

The unplanned extension of the right to refuse treatment to the precommitment period is described in this paper. This extension of the right to refuse treatment has important public policy implications for the civil commitment process. These implications, as well as the pros and cons of the extension of the right to refuse treatment, are discussed.

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.

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.