European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition--Communication.

Multidisciplinary, evidence-based guidelines for quality assurance in colorectal cancer screening and diagnosis have been developed by experts in a project coordinated by the International Agency for Research on Cancer. The full guideline document covers the entire process of population-based screening. It consists of 10 chapters and over 250 recommendations, graded according to the strength of the recommendation and the supporting evidence. The 450-page guidelines and the extensive evidence base have been published by the European Commission. The chapter on communication includes 35 graded recommendations. The content of the chapter is presented here to promote international discussion and collaboration by making the principles and standards recommended in the new EU Guidelines known to a wider professional and scientific community. Following these recommendations has the potential to enhance the control of colorectal cancer through improvement in the quality and effectiveness of screening programmes and services.

[Antiplatelet therapy during coronary endoprosthesis placement]. / Prescription des antiplaquettaires lors de la pose d'endoprothèses coronaires.

Coronary stent implantation is today a catheterisation laboratory routine procedure for de novo lesions and less frequently for bail-out situations. Antithrombotic pharmacological regimens based upon coumadin have filed to prevent sub-acute stent thrombosis. The use of new antiplatelet therapy (ticlopidine alone or in association with aspirin) have reduced the sub-acute thrombosis rate to 1%. Routine combining heparin is not useful. The benefit of ultrasound guided stenting or high pressure balloon expansion is not demonstrated in the thrombosis prevention. New pharmacological approaches inducing fibrinogen platelet receptor antagonists (antii GP IIb-IIIa) may extend stent implementations more especially in acute coronary syndromes.

[Diagnostic value of exercise tomoscintigraphy with thallium 201 in patients with complete left branch block]. / Valeur diagnostique de la tomoscintigraphie d'effort au thallium 201 chez les patients porteurs d'un bloc de branche gauche complet.

Eighteen patients with rate-dependent (n = 5) or chronic (n = 13) left bundle branch block underwent thallium 201 exercise SPECT and selective coronary arteriography. 15 patients showed significant septal or anteroseptal perfusion defects on the exercise scintigrams, but in only 4 of them did the coronary disease involve the left anterior descending artery (LAD) (n = 3) or the left main coronary artery (n = 1). Among patients with normal scintigrams, one had right coronary artery stenosis. Test performance in detecting individual coronary artery stenosis greater than 70 p. 100 was: sensitivity 80 p. 100 (4/5) and specificity 15 p. 100. In patients with left bundle branch block, T1 201 SPECT was indeterminate for LAD disease due to reversible septal perfusion defect. We conclude that the usefulness of stress thallium 201 SPECT in patients with left bundle branch block is very limited.

[Prognosis of ventricular tachycardia]. / Pronostic des tachycardies ventriculaires.

The prognosis of monomorphous, sustained, non-iatrogenic ventricular tachycardia was studied in 86 patients followed up for a mean period of 42.8 months. The patients were divided into three groups as follows: group I, 46 patients with myocardial infarction beyond the acute phase; group II, 30 patients with non-ischaemic heart disease; group III, 10 patients without heart disease detectable at angiography and/or echotomography. Fifty patients died during the follow-up period. Forty (80 p. cent) of these deaths (26 in group I, 14 in group II) were due to cardiac causes: heart failure in 24 cases, sudden death in 15 cases, recurrent myocardial infarction in 1 case. The percentage of cardiac death was higher in patients with left ventricular dysfunction (66 p. 100 versus 15.2 p. 100) and when the ejection fraction was below 0.40 (52.9 p. 100 versus 11.8 p. 100). The proportion of sudden death was 66.7 p. 100 when Lown's grade IV ectopic rhythm persisted under treatment, and only 7.7 p. 100 when this was not the case (p less than 0.001). These results confirm that: ventricular tachycardia has a high mortality rate in patients with heart disease; ventricular tachycardia on a "healthy" heart is of good prognosis; left ventricular dysfunction and persistence of repetitive forms under treatment have a high predictive value for cardiac death.

[Has the prognosis of recent myocardial infarction changed?]. / Le pronostic de l'infarctus du myocarde récent a-t-il changé?

In this retrospective study changes in the prognosis of recent myocardial infarction were evaluated by comparing 731 patients hospitalized in the 1970-1974 period (group I) with 755 patients hospitalized in the 1984-1986 period (group II). The possible factors responsible for the changes observed were investigated. A 34 percent decrease in hospital mortality was recorded (19.2% in group I versus 12.6% in group II; P less than 0.001). The decrease was present irrespective of the patients' sexes and ages; it was more pronounced in patients under 65 (-42%) and in elderly women (-43%). Compared with group I patients, group II patients showed a significant decrease in cardiogenic shock (P less than 0.02), atrial fibrillation (P less than 0.05) and, chiefly, atrioventricular block (P less than 0.001). The improvement in prognosis cannot be ascribed to a change of population since both groups were matched in male to female ratio, age distribution and presence of the main risk factors. Three factors may have contributed to a better prognosis: (1) more rapid admission to hospital; the proportion of patients admitted within 6 hours of the initial symptoms rose from 37.5% in group I to 49.8% in group II (P less than 0.001); (2) modification of the conventional treatment, with a reduced prescription of digitalis and a less frequent recourse to temporary electrical pacing; (3) introduction of new treatments aimed at limiting the size of the necrotic area; these include thrombolytic agents which were administered in 19.2% of patients under 65 and may well have played the principal role in the improvement of outcome.

[Pilot study of the efficacy of ticlopidine in early patency of coronary endoprostheses]. / Etude pilote de l'efficacité de la ticlopidine dans la perméabilité précoce des endoprothèses coronaires.

Subacute thrombosis of coronary stents is the main complication of this technique. The authors studied the outcome of 387 patients and 400 coronary arteries who underwent implantation of 427 stents between December 1989 and February 1994 and followed up one month after the procedure: all patients receive 500 mg of ticlopidine daily from three days before angioplasty throughout the hospital period and continued for at least one month. Anticoagulation with heparin was undertaken by the intravenous route after implantation and relayed with subcutaneous heparin for one week until control coronary angiography performed in the first 300 patients. At one month, 96.9% of patients were free of clinical coronary events. The following major complications were observed: 5 deaths (1.3%), 5 Q wave myocardial infarctions (1.3%); no emergency bypass surgery. The peripheral vascular complication rate was 3.6%. Univariate analysis three risk factors of subacute thrombosis: age (p = 0.0058), arterial diameter of less than 3 mm (p < 0.01) and implantation for occlusive dissection (p = 0.03). Multivariate analysis showed two independent risk factors: age (p = 0.001) and arterial diameter of less than 3 mm (p = 0.01). This pilot study shows a particularly low subacute thrombosis rate in unselected indications with an acceptable level of vascular complications.

[Double mitral valve orifice. Apropos of a case discovered by echocardiography]. / Orifice mitral double. A propos d'un cas de découverte échocardiographique.

The authors report a case of isolated double orifice mitral valve in a 20-year old pregnant woman. This exceptional and seldom isolated anomaly is usually discovered at autopsy or surgery. In this particular case it was diagnosed by pulsed doppler ultrasound combined with echocardiography. Data from the literature are reviewed on that occasion, and the echocardiographic images of the malformation are described. Despite its rarity, double orifice mitral valve deserves to be known and its presence should be looked for by echocardiography, notably in patients with complete or partial atrioventricular canal.

The mechanism of GT element-mediated cell type-specific transcriptional control.

Promoter studies have revealed that sequences related to the GT-1 binding site, known as GT elements, are conserved in plant nuclear genes of diverse functions. In this work, we addressed the issue of whether GT elements are involved in cell type-specific transcriptional regulation. We found that the inactivation of GT-1 site-mediated transcription in roots is correlated with the absence of the GT-1 binding activity in root extracts. In addition, the mutation of the related GT-1 (from the pea rbcs-3A) and the S1F (from the spinach rps1) sites resulted in an increase of their transcriptional activity in roots that contain a distinct GT element-binding factor, referred to as RGTF. Although specific to GT elements, RGTF has a different sequence requirement and a lower sequence specificity than GT-1. Interestingly, RGTF has a higher binding affinity to the mutant GT-1 and S1F sites than to the wild-type sequences. This correlation suggests that RGTF may have some role in transcriptional regulation in roots. Furthermore, root cellular protein extracts contain an inhibitory activity that prevents GT-1 from binding to DNA. This helps to explain the absence of the GT-1 binding activity in roots in which the gene of GT-1 is expressed. Together, these data suggest that the cell type-specific transcription modulation by GT elements is achieved by using two different strategies.

S1F binding site is related to but different from the light-responsive GT-1 binding site and differentially represses the spinach rps1 promoter in transgenic tobacco.

Nuclear genes encoding plastid ribosomal proteins are more highly expressed in leaves than in roots. This leaf-specific induction seems to be light-independent. We have previously characterized a spinach nuclear factor S1F binding to a cis-element within the rps1 promoter, which negatively regulates both the rps1 and the cauliflower mosaic virus 35S promoters in transient expression assays. Here, we show that the S1F binding site is related to but different from the light-responsive Box II of the pea rbcS-3A promoter, which is recognized by the nuclear factor GT-1. Transgenic plant analyses showed that the S1F site tissue-specifically represses the rps1 promoter in roots as well as in etiolated seedlings. We suggest that the GT-1-related S1F binding site is responsible, at least in part, for the transcriptional repression of rps1 in nonphotosynthetic tissues such as roots.

T-cell receptor-mediated anergy of a human immunodeficiency virus (HIV) gp120-specific CD4(+) cytotoxic T-cell clone, induced by a natural HIV type 1 variant peptide.

Human immunodeficiency virus type 1 (HIV-1) infection triggers a cytotoxic T-lymphocyte (CTL) response mediated by CD8(+) and perhaps CD4(+) CTLs. The mechanisms by which HIV-1 escapes from this CTL response are only beginning to be understood. However, it is already clear that the extreme genetic variability of the virus is a major contributing factor. Because of the well-known ability of altered peptide ligands (APL) to induce a T-cell receptor (TCR)-mediated anergic state in CD4(+) helper T cells, we investigated the effects of HIV-1 sequence variations on the proliferation and cytotoxic activation of a human CD4(+) CTL clone (Een217) specific for an epitope composed of amino acids 410 to 429 of HIV-1 gp120. We report that a natural variant of this epitope induced a functional anergic state rendering the T cells unable to respond to their antigenic ligand and preventing the proliferation and cytotoxic activation normally induced by the original antigenic peptide. Furthermore, the stimulation of Een217 cells with this APL generated altered TCR-proximal signaling events that have been associated with the induction of T-cell anergy in CD4(+) T cells. Importantly, the APL-induced anergic state of the Een217 T cells could be prevented by the addition of interleukin 2, which restored their ability to respond to their nominal antigen. Our data therefore suggest that HIV-1 variants can induce a state of anergy in HIV-specific CD4(+) CTLs. Such a mechanism may allow a viral variant to not only escape the CTL response but also facilitate the persistence of other viral strains that may otherwise be recognized and eliminated by HIV-specific CTLs.

Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction.

BACKGROUND: When administered in conjunction with primary coronary stenting for the treatment of acute myocardial infarction, a platelet glycoprotein IIb/IIIa inhibitor may provide additional clinical benefit, but data on this combination therapy are limited. METHODS: We randomly assigned 300 patients with acute myocardial infarction in a double-blind fashion either to abciximab plus stenting (149 patients) or placebo plus stenting (151 patients) before they underwent coronary angiography. Clinical outcomes were evaluated 30 days and 6 months after the procedure. The angiographic patency of the infarct-related vessel and the left ventricular ejection fraction were evaluated at 24 hours and 6 months. RESULTS: At 30 days, the primary end point--a composite of death, reinfarction, or urgent revascularization of the target vessel--had occurred in 6.0 percent of the patients in the abciximab group, as compared with 14.6 percent of those in the placebo group (P=0.01); at 6 months, the corresponding figures were 7.4 percent and 15.9 percent (P=0.02). The better clinical outcomes in the abciximab group were related to the greater frequency of grade 3 coronary flow (according to the classification of the Thrombolysis in Myocardial Infarction trial) in this group than in the placebo group before the procedure (16.8 percent vs. 5.4 percent, P=0.01), immediately afterward (95.1 percent vs. 86.7 percent, P=0.04), and six months afterward (94.3 percent vs. 82.8 percent, P=0.04). One major bleeding event occurred in the abciximab group (0.7 percent); none occurred in the placebo group. CONCLUSIONS: As compared with placebo, early administration of abciximab in patients with acute myocardial infarction improves coronary patency before stenting, the success rate of the stenting procedure, the rate of coronary patency at six months, left ventricular function, and clinical outcomes.