Biomedical subjects

Jacques Bonnet

Publications and source records attributed to Jacques Bonnet.

At least 19 recordsLinked to original sources

PubMed2026

Cryo-EM structure, enzymatic activity and genome targeting of canonical PRC1.

Canonical Polycomb repressive complex 1 (cPRC1) preserves cell fate decisions by repressing aberrant transcription of developmental regulator genes. We report the cryo-electron microscopy structure of the human cPRC1 holocomplex assembled from RING1B, BMI1, PHC2 and CBX7 bound to an H3K27me3-modified mononucleosome together with the ubiquitin-conjugating enzyme UBCH5C. cPRC1 adopts a compact, highly integrated architecture in which the subunits RING1B, BMI1 and PHC2 form an extended interface that positions UBCH5C on the nucleosome to enable efficient monoubiquitination of histone H2A at K119. This organization is conserved in Drosophila, where mutational analyses identify the PHC2 ortholog Polyhomeotic (Ph) as a central scaffold and targeting factor. The Ph HD domain is required for complex assembly, whereas the Ph SAM domain is dispensable for assembly but essential for cPRC1 recruitment to Polycomb target genes and productive H2A monoubiquitination at these loci.

Journal Article↗

PubMed2006

Site-specific reduction of oxidative and lipid metabolism in adipose tissue of 3'-azido-3'-deoxythymidine-treated rats.

Although it is well accepted that treatment with some nucleoside reverse transcriptase inhibitors modifies both fat metabolism and fat distribution in humans, the mechanisms underlying these modifications are not yet known. The present investigation examined whether a decrease in oxidative capacity, induced by a chronic oral administration of 3'-azido-3'-deoxythymidine (AZT) in rats, could be associated with an alteration of the lipogenic capacity of white adipose tissues. The impact of obesity as a factor was then evaluated. Results showed that AZT treatment induced differential effects depending on anatomical localization. Indeed, in the inguinal adipose tissue, the specific activities of cytochrome c oxidase and fatty acid synthase, two rate-controlling enzymes in energy and lipogenic metabolisms, respectively, both decreased under AZT treatment, thus leading to a lowered cell lipid accumulation. Moreover, the AMP-activated protein kinase phosphorylation level tended to increase, thus implying that AZT causes an energy imbalance. Furthermore, the inguinal tissue of obese rats presented a sensitivity to AZT treatment that was higher than that of lean rats. In contrast, for epididymal tissue, no significant change in all these parameters could be detected under AZT treatment, regardless of the nutritional status of the animals. Taken together, these data demonstrate differential effects of AZT on subcutaneous adipose tissue and visceral white adipose tissue. It could be considered that the chronic decreases in energy and lipogenic metabolism of inguinal adipocyte, consecutive to AZT treatment, may lead, in the long term, to adipose tissue atrophy.

Adipose Tissue↗

PubMed2006

Prevalence of metabolic syndrome after acute coronary syndrome and its prognostic significance.

Metabolic syndrome (MS) consists of a cluster of metabolic and hemodynamic disorders that promote the development of atherosclerosis and increase cardiovascular morbidity/mortality. We evaluated the prevalence and characteristics of MS after acute coronary syndrome (ACS) and the effect of intensive risk factor management on the morbidity/mortality associated with MS in a therapeutic cohort; 480 consecutive patients were summoned 3 months after an ACS for cardiovascular evaluation and management. Follow-up was carried out 16 months later. At 3 months after ACS, prevalence of MS was 20.8%, as assessed by criteria of the National Cholesterol Education Program Adult Treatment Panel III and 27.7% according to the definition of the International Diabetes Federation. The most common metabolic disorders were abdominal obesity, hypertriglyceridemia, and fasting hyperglycemia. Characteristics of the initial ACS showed no significant difference between the MS and non-MS groups. Atherosclerotic extent was greater in the MS group according to Adult Treatment Panel III. At follow-up, the MS and non-MS groups achieved optimal low-density lipoprotein cholesterol and blood pressure levels. During follow-up, there was an increase in total mortality in the MS group compared with the non-MS group (5.2% vs 1.4%, p <0.01) as assessed by International Diabetes Federation criteria; however, no difference in minor or major cardiovascular events was found between the 2 groups. In conclusion, MS was highly prevalent after an ACS, notably in young patients, and was not associated with a specific ACS presentation.

Acute Disease↗

PubMed2006

Relationships between genetic polymorphisms and anticancer drug cytotoxicity vis-à-vis the NCI-60 panel.

INTRODUCTION: The National Cancer Institute (NCI)-60 panel consists of 60 human tumor cell lines initially established for screening thousands of molecules for antiproliferative activity. It has been powerful for deciphering the relationships between anticancer drug cytotoxicity and cell molecular characteristics. We tested its potential interest for establishing relationships between the polymorphism of genes involved in drug metabolism and transport or in DNA repair, and drug cytotoxicity extracted from NCI databases. METHODS: Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques, three frequent single nucleotide polymorphisms (SNPs) were analyzed: Lys751Gln in the Xeroderma pigmentosum complementation group D (XPD, ERCC2) gene, Asp1104His in the Xeroderma pigmentosum complementation group G (XPG, ERCC5) gene and Ile105Val in the glutathione S-transferase P1 (GSTP1) gene. RESULTS: The allelic frequencies of the variants were 33% for ERCC2, 23% for ERCC5 and 39% for GSTP1. The ERCC2 polymorphism appeared to be a strong determinant of the in vitro cytotoxicity of most anticancer agents, with lower half maximal inhibitory concentration (IC50) values in variant homozygous lines than in common homozygous or heterozygous cell lines. Unexpectedly, the cytotoxicity of taxanes appeared markedly dependent upon the ERCC2 genotype, with threefold lower mean IC50 values in variant homozygous cell lines. The ERCC5 genotype appeared to be important only for taxanes, with fourfold higher IC50 values in variant homozygous cell lines. The GSTP1 polymorphism was related to the cytotoxicity of several drug classes, especially topoisomerase inhibitors, antimetabolites and N7 alkylating agents. CONCLUSION: The NCI-60 panel is capable of providing clues and tracks for the establishment of clinically useful relationships between a given genotype and the cytotoxicity of an anticancer agent.

Antineoplastic Agents↗

PubMed2005

In vitro prevention of cyclosporin-induced cell contraction by mycophenolic acid.

Nephrotoxicity is a major side-effect of cyclosporin A (CsA), which induces a vasoconstrictive response in vascular smooth muscle and mesangial cells. Mycophenolic acid (MPA) is used in combination with low-dose CsA to reduce nephrotoxicity. We previously demonstrated that MPA affected mesangial cell contractile response to angiotensin II or KCl. Aims of the present study were to evaluate if MPA can prevent CsA-induced contraction of human mesangial and aortic smooth muscle cells (ASMC). Using a morphoquantitative approach, we evidenced that pretreatment with MPA (1 microM) prevented the reduction of cell area induced by CsA within 30 min in both cell types. We then compared the expression of three main cytoskeleton proteins: tubulin, alpha-smooth actin (SMA) and basic calponin, in ASMC and in mesangial cells treated with MPA and/or CsA. CsA alone did not significantly change the expression level of these proteins neither in mesangial cells nor in ASMC. MPA decreased the expression level of tubulin in both mesangial cells and ASMC. Surprisingly, MPA, which stimulated SMA and calponin expression in mesangial cells, exerted an inhibitory effect on both contractile protein expression in ASMC. In conclusion, our results evidenced opposite effects of MPA on calponin and SMA protein expression in ASMC and in mesangial cells, despite similar antiproliferative properties, suggesting that sarcomeric protein expression is controlled by different intracellular mechanisms in mesangial and smooth muscle cells. However, MPA interferes in both cell types with the constrictive properties CsA, which may partially explain the protective effects of MPA against CsA nephrotoxicity.

Actins↗

PubMed2005

Surface potential mapping of dispersed proteins.

We describe a method for detecting proteins after transfer to PVDF membranes, based on the surface potential attributed to each protein. Proteins separated by classical two-dimensional polyacrylamide gel electrophoresis could be detected by scanning the membrane surface with a vibrating capacitor (also called a Kelvin probe) on the basis of differences between their surface potential and that of the membrane. Coupled to colloidal gold staining, the technique enables detection of proteins previously undetectable by classical staining methods. Plotting variations of the surface potential in two dimensions visualizes proteins which migrate close together. Finally, we demonstrate that the Kelvin probe detects proteins over a concentration range from micro to sub-nanogram with increased sensitivity at lower concentrations, and unlike other methods, appears to be similar for all proteins tested so far. The method described is fast, reliable, and it can be automated for high throughput.

Electrochemistry↗

PubMed2005

Predicting drug response and toxicity based on gene polymorphisms.

The sequencing of the human genome has allowed the identification of thousands of gene polymorphisms, most often single nucleotide polymorphims (SNP), which may play an important role in the expression level and activity of the corresponding proteins. When these polymorphisms occur at the level of drug metabolising enzymes or transporters, the disposition of the drug may be altered and, consequently, its efficacy may be compromised or its toxicity enhanced. Polymorphisms can also occur at the level of proteins directly involved in drug action, either when the protein is the target of the drug or when the protein is involved in the repair of drug-induced lesions. There again, these polymorphisms may lead to alterations in drug efficacy and/or toxicity. The identification of functional polymorphisms in patients undergoing chemotherapy may help the clinician prescribe the optimal drug combination or schedule and predict with more accuracy the response to these prescriptions. We have recorded in this review the polymorphisms that have been identified up till now in genes involved in anticancer drug activity. Some of them appear especially important in predicting drug toxicity and should be determined in routine before drug administration; this is the case of the most common variations of thiopurine methyltransferase for 6-mercaptopurine and of dihydropyrimidine dehydrogenase for fluorouracil. Other appear determinant for drug response, such as the common SNPs found in glutathione S-transferase P1 or xereoderma pigmentosum group D enzyme for the activity of oxaliplatin. However, confusion factors may exist between the role of gene polymorphisms in cancer risk or overall prognosis and their role in drug response.

Cytochrome P-450 Enzyme System↗

PubMed2004

Hsp70 and Hsp40 chaperones do not modulate retinal phenotype in SCA7 mice.

Nine neurodegenerative diseases, including spinocerebellar ataxia type 7 (SCA7), are caused by the expansion of polyglutamine stretches in the respective disease-causing proteins. A hallmark of these diseases is the aggregation of expanded polyglutamine-containing proteins in nuclear inclusions that also accumulate molecular chaperones and components of the ubiquitin-proteasome system. Manipulation of HSP70 and HSP40 chaperone levels has been shown to suppress aggregates in cellular models, prevent neuronal death in Drosophila, and improve to some extent neurological symptoms in mouse models. An important issue in mammals is the relative expression levels of toxic and putative rescuing proteins. Furthermore, overexpression of both HSP70 and its co-factor HSP40/HDJ2 has never been investigated in mice. We decided to address this question in a SCA7 transgenic mouse model that progressively develops retinopathy, similar to SCA7 patients. To co-express HSP70 and HDJ2 with the polyglutamine protein, in the same cell type, at comparable levels and with the same time course, we generated transgenic mice that express the heat shock proteins specifically in rod photoreceptors. While co-expression of HSP70 with its co-factor HDJ2 efficiently suppressed mutant ataxin-7 aggregation in transfected cells, they did not prevent either neuronal toxicity or aggregate formation in SCA7 mice. Furthermore, nuclear inclusions in SCA7 mice were composed of a cleaved mutant ataxin-7 fragment, whereas they contained the full-length protein in transfected cells. We propose that differences in the aggregation process might account for the different effects of chaperone overexpression in cellular and animal models of polyglutamine diseases.

Animals↗

PubMed2004

Intra-left ventricular electromechanical asynchrony. A new independent predictor of severe cardiac events in heart failure patients.

OBJECTIVES: We sought to assess the electromechanical parameters, using tissue Doppler echocardiography, as potential independent predictors of heart failure (HF) worsening. BACKGROUND: Ventricular conduction disorders worsen the prognosis for HF patients. However, the relationships between the QRS width and morphology, hemodynamic parameters, and presence and magnitude of intra-left ventricular (LV) and inter-ventricular (V) asynchrony have not been well clarified. METHOD: A total of 104 patients with an LV ejection fraction (EF) </=45% and stabilized HF, without myocardial infarction (MI), underwent echocardiography coupled with tissue Doppler imaging and were followed for one year. The protocol analyzed the incidence of worsening HF (hospitalization for cardiac decompensation). Inter-V and regional electromechanical delays for the anterior, septal, inferior, and lateral LV walls were correlated with the QRS morphology and duration. The intra-LV and inter-V asynchrony values of these patients were compared with those of healthy subjects matched by gender and age criteria to determine the respective normal ranges. RESULTS: The presence of intra-LV (but not inter-V) asynchrony was identified as an independent predictor of severe cardiac events (hazard ratio 3.39, p < 0.0001), independent of the LVEF and QRS width. Of patients with a QRS width <120 ms (55%; n = 57), 56% presented with major intra-LV asynchrony and 12% with inter-V asynchrony. Intra-LV asynchrony was observed in 84% of left bundle branch block patients, but also in 83% of right bundle branch block patients (p = NS). There was a poor correlation between the QRS width and intra-LV or inter-V asynchrony (r = 0.36, p = NS and r = 0.43, p = 0.05, respectively). CONCLUSIONS: In HF patients without MI, patients with intra-LV asynchrony are those with a significantly higher risk of cardiac events, independent of the QRS width and LVEF. Accordingly, such patients should be more actively identified for early intensive treatment and survey.

Aged↗

PubMed2004

Molecular determinants of the cytotoxicity of platinum compounds: the contribution of in silico research.

Gene expression profiling of tumors allows the establishment of relationships between gene expression profiles and sensitivity to anticancer drugs. In an attempt to study the molecular determinants of the activity of platinum compounds, we explored the publicly available databases of the National Cancer Institute (NCI; http://dtp.nci.nih.gov), which allow access to the gene expression profiles of the 60 cell lines for which drug cytotoxicity patterns already existed. Using this database, we have conducted an in silico research to identify the genes the expression of which was positively or negatively correlated to the sensitivity to four platinum compounds (cisplatin, carboplatin, oxaliplatin and tetraplatin). Important similarities were noticed between cisplatin and carboplatin on one hand, and tetraplatin and oxaliplatin on the other hand. In the restricted panel of 1416 genes and molecular markers, we identified 204 markers, among which 120 corresponded to identified genes, that significantly correlated (P < 0.001) with the cytotoxicity of at least one platinum compound. For example, the functionality of the p53-activated pathway appeared positively correlated with the cytotoxicity of all platinum compounds. More specific are the positive correlations between RAS gene mutations and MYC expression and the cellular sensitivity to oxaliplatin. Among the parameters already known as related to the sensitivity to platinum compounds, we identified, in the complete set of 9400 genes, numerous significant relationships, such as the negative correlations between ERB-B2 and BCL-X(L) expressions and the cytotoxicity of the platinum compounds. Public databases mining, therefore, appears to be a valuable tool for the identification of determinants of anticancer drug activity in tumors.

Animals↗

PubMed2004

Effects of switching statins on achievement of lipid goals: Measuring Effective Reductions in Cholesterol Using Rosuvastatin Therapy (MERCURY I) study.

BACKGROUND: In a multinational trial (4522IL/0081), we assessed the effects of switching to low doses of rosuvastatin from commonly used doses of atorvastatin, simvastatin, and pravastatin on low-density lipoprotein cholesterol (LDL-C) goal achievement in high-risk patients. METHODS: Hypercholesterolemic patients (n = 3140) with coronary heart disease, atherosclerosis, or type 2 diabetes were randomized to open-label rosuvastatin 10 mg, atorvastatin 10 or 20 mg, simvastatin 20 mg, or pravastatin 40 mg for 8 weeks. Patients either remained on these treatments for another 8 weeks or switched treatments from atorvastatin 10 mg, simvastatin 20 mg, and pravastatin 40 mg to rosuvastatin 10 mg or from atorvastatin 20 mg to rosuvastatin 10 or 20 mg. The primary efficacy measure was the proportion of patients reaching the Joint European Societies' LDL-C goal (<116 mg/dL) at week 16. For measures of cholesterol goal achievement, treatment arms were compared using logistic-regression analysis. RESULTS: Significant improvement in LDL-C goal achievement was found for patients who switched to rosuvastatin 10 mg, compared with patients who remained on atorvastatin 10 mg (86% vs 80%, P <.05), simvastatin 20 mg (86% vs 72%, P <.0001), and pravastatin 40 mg (88% vs 66%, P <.0001), and between patients switched to rosuvastatin 20 mg and those who remained on atorvastatin 20 mg (90% vs 84%, P <.01). Similar results were found for achievement of the European combined LDL-C and total cholesterol goals and National Cholesterol Education Program Adult Treatment Panel III LDL-C goals. All statins were well tolerated over 16 weeks. CONCLUSIONS: We demonstrated that switching to a more efficacious statin is an effective strategy to improve lipid goal achievement in patients requiring lipid-lowering therapy.

Aged↗

PubMed2004

Predicting drug response based on gene expression.

Predicting drug response is a challenging problem in oncology. In the 1975-1985 decade, important efforts were devoted to the generation of cellular assays able to predict, on an individual basis, the in vitro response of tumour cells to chemotherapeutic agents, but such methods could not be adopted in routine. Numerous mechanisms of resistance to anticancer agents have been identified in cultured cell lines selected for growth in the presence of infratoxic, increasing doses of anticancer agents. They mainly concern drug transport, drug activation or detoxification, target quantitative or qualitative alterations, DNA repair efficiency, and alterations in signalling and/or execution of cell death programmes. New molecular biology techniques have been developed in order to identify the genes involved in drug resistance; they mainly involve differential expression techniques, but functional approaches may also prove informative. The availability of techniques of gene expression profiling has allowed to establish correlations between gene expression and drug sensitivity of tumour cells or human cancers. This type of approach has been initiated on in vitro systems by the National Cancer Institute (NCI) in the USA and is pursued by a growing number of public and private laboratories around the world. In the clinical setting, a number of genes or proteins have been identified as potential predictive markers of drug activity and their use could be progressively implemented for drug selection in patients receiving chemotherapy, allowing thus more rational and individualised treatments.

Animals↗

PubMed2004

Semicarbazide-sensitive amine oxidase in annulo-aortic ectasia disease: relation to elastic lamellae-associated proteins.

Lysyl oxidases (Lox), which are members of the amine oxidase family, are involved in the maturation of elastic lamellae and collagen fibers. Modifications of amine oxidases in idiopathic annulo-aortic ectasia disease (IAAED) have never been investigated. Our aim was to examine the expression of several proteins that might interfere with elastic fiber organization in control (n=10) and IAAED (n=18) aortic tissues obtained at surgery. Expression of amine oxidases and semicarbazide-sensitive amine oxidase (SSAO), and cellular phenotypic markers were examined by immunohistopathology and confocal microscopy. The expression of these proteins was assessed in relation to clinical and histomorphological features of the arterial wall. In control aorta, SSAO staining was expressed along elastic lamellae, whereas in aneurysmal areas of IAAED, SSAO was markedly decreased, in association with severe disorganization of elastic lamellae. Smooth muscle myosin heavy chain was also decreased in IAAED compared with controls, indicating smooth muscle cell dedifferentiation. Multiple regression analysis showed that elastic lamellar thickness (ELT) was correlated positively with the SSAO:elastin ratio and negatively with the Lox:elastin ratio, and that the clinical features of IAAED (aneurysm, thoracic aorta diameter, and aortic insufficiency) were positively correlated with ELT but not with SSAO. The relationship between SSAO expression and ELT suggests that this amine oxidase may be involved in elastic fiber organization. However, in advanced IAAED, the deficit in SSAO expression could be secondary to the decrease and fragmentation of elastic fibers and/or to vascular smooth muscle cell dedifferentiation.

Amine Oxidase (Copper-Containing)↗

PubMed2004

[Recent advances in pharmacogenomics in oncology].

Progress in understanding the molecular mechanisms of oncogenesis, together with the sequencing of the human genome and the availability of huge databases, bring new tools for the discovery and the evaluation of new potential targets for cancer therapy and for the individualisation of cancer chemotherapy as a function of the molecular characteristics of tumours. Targeting the genetic alterations of cancer cells appears feasible and the first successes of this approach allow to remain optimistic about the renewal of our therapeutic armamentarium. In addition, seeking for correlations between gene expression profiles and chemosensitivity has been performed on the in vitro models of the National Cancer Institute and may allow crucial improvements in the identification of patients who world best take advantage of a specific chemotherapy. Clinical trials, first on a retrospective basis, then performed prospectively, are implemented to validate this approach.

Antibodies↗

PubMed2003

Inhibition of Rho pathways induces radiosensitization and oxygenation in human glioblastoma xenografts.

We previously demonstrated in vitro that inhibiting the biological pathways of the small GTPase Rho radiosensitizes the human glioma U87 cell line. The aim of this study was to determine if Rho might be involved in the control of in vivo radiosensitivity altogether by controlling cellular radioresistance and by modifying tumor microenvironment. We demonstrate here that the in vivo induction of the dominant negative of Rho, RhoBN19, in U87 xenografts induces a significant decrease of tumor cell survival after irradiation more important than the one we previously observed in vitro. This in vivo increased effect of RhoBN19 expression is due to the improvement of the tumor oxygenation associated with a significant decrease of the vessel density and of the metalloproteinase 2 (MMP2) expression. Moreover, in vitro RhoBN19 expression in U87 cells leads to the inhibition of MMP2 activity. Our results demonstrate for the first time that inhibiting Rho pathways modifies the in vivo radiosensitivity of human glioma cells by controlling intrinsic radioresistance, hypoxia and angiogenesis. These data strongly suggest that Rho should be a major determinant of cellular resistance to ionizing radiation.

Animals↗

PubMed2003

Elongation of oligonucleotide primers forming a triple helix on double-stranded DNA templates by purified DNA polymerases.

Current knowledge on the replication of DNA involves enzymatic steps of DNA strand separation upon helicase activity, thus enabling the exposed bases of the single-stranded DNA to direct the polymerization of complementary nucleotides through Watson-Crick base pairing rules by DNA-dependent DNA polymerases. Here, we report that oligonucleotide primers (9-11 nt long) bound to the double-stranded DNA, can be elongated by the T7 and by the Thermus thermophilus DNA polymerases and by the Escherichia coli Klenow fragment. A perfectly base-paired DNA cannot be used as a template, but a single A/A mismatch located even 5 bp upstream from the theoretical 3'-end of the oligonucleotide primer is sufficient for DNA elongation by these first two enzymes, while five are required for the Klenow fragment. Elongation products from templates containing A/A mismatches at different positions revealed similar patterns independently of the positions of the A/A mismatches. The sequencing of the elongated products revealed that both purine and pyrimidine are incorporated at the pyrimidine-purine-pyrimidine transitions of the template strands, probably because of a shift of the primers on the double helix template. These data confirm that prokaryotic DNA polymerases may accommodate transiently three DNA strands in their catalytic centre. They also show for the first time that replication can occur on double-stranded DNA in the absence of DNA helicase, when mismatches are present in the vicinity of the triple helix initiation complex.

Base Sequence↗

PubMed2003

Cytoskeletal reorganization by mycophenolic acid alters mesangial cell migration and contractility.

Cytoskeleton alterations are a hallmark of mesangial cell activation during glomerulosclerosis. The aim of this study was to investigate whether mycophenolic acid (MPA) affects cytoskeletal organization and motility of human mesangial cells. Using the IP15 cell line, we found that treatment with 1 micromol/L MPA inhibited both receptor-dependent (angiotensin II) and receptor-independent (KCl) contractile responses, as well as serum-induced migration activity, suggesting alterations in the intracellular mechanisms that control mesangial cell motility. Immunofluorescence studies of MPA-treated cells provided evidence for decreased membrane disassembly/reassembly of alpha-smooth muscle actin and F-actin fibers, which was correlated with sustained quantitative and qualitative modifications of actin-associated proteins: calponin was overexpressed and became associated with actin fibers, whereas phosphorylation levels of cofilin and myosin light chain increased, suggesting both an activation of the mechanisms responsible for actin polymerization and an inhibition of actin-depolymerizing processes. These observations support a stabilizing effect of MPA on the mesangial actin cytoskeleton, which constitutes an additive action by which MPA, beyond its anti-inflammatory, antiproliferative and antifibrotic properties, might protect against excessive mesangial activation in the context of various glomerulopathies and kidney transplantation.

Angiotensin II↗

PubMed2003

Clinical outcome after a negative spiral CT pulmonary angiographic finding in an inpatient population from cardiology and pneumology wards.

STUDY OBJECTIVES: The purpose of this study was to assess the clinical follow-up of a negative spiral CT (SCT) angiographic finding after a suspicion of acute pulmonary embolism (PE) in a population of inpatients with cardiac and/or respiratory disease. In this high-risk population, clinical findings suggestive of PE are frequently misleading. DESIGN: One hundred seventy-five consecutive patients hospitalized in cardiac and pneumology wards underwent SCT angiography for suspected PE over a 30-month period. Angiographic findings were positive in one third. For the 117 patients with negative SCT angiographic findings, a clinical follow-up during a minimum of 6 months was assessed, particularly in relation to recurrent thromboembolism, mortality, and cause of death. RESULTS: The mean +/- SD follow-up was 21 +/- 11.5 months, and five patients were unavailable for follow-up. Of the 117 patients with negative findings, 81 patients did not receive anticoagulant therapy and 46 patients received anticoagulation for cardiac disease or deep venous thrombosis. Twenty-two patients died during the follow-up period, 3 of them during the first 3 months following the initial event from an undetermined cause. In patients still alive, a new PE occurred in two cases. Patients with a poor cardiopulmonary reserve did not present any recurrent events. In this population, tests other than imaging (d-dimers, cardiac echocardiography, or venous ultrasound) contributed little to eliminate the diagnosis of PE. CONCLUSIONS: Whether or not early deaths are considered or not to be related to a recurrent PE, the rate of recurrence after a negative SCT angiographic finding varied between 1.8% and 4.9%. SCT angiography can be used confidently to rule out significant PE, and may prevent further investigations and unnecessary treatment in an inpatient population with cardiac and/or respiratory diseases.

Adult↗