Yves Frances

Gender differences in artery wall biomechanical properties throughout life

Elevated large artery stiffness and pulse pressure have emerged as important risk factors for cardiovascular disease. The genders differ in large artery biomechanical properties throughout the lifespan with females displaying higher stiffness than males during the prepubertal years and a dramatic increase after menopause. Males on the other hand experience an increase in arterial stiffness postpuberty and a linear increase thereafter, suggesting that females have intrinsically stiffer large arteries than males, but that such effects are mitigated by sex steroids during the reproductive years. This review discusses anthropometric and sex steroid influences on gender differences in large artery stiffness and pressure dynamics from childhood to senescence. In particular, the sex-specific effects of estrogen, progesterone and testosterone on vascular structure and function and how these influence arterial stiffness are explored. These factors may contribute in part to the observed gender differences in the pathophysiology and clinical manifestations of cardiovascular disease.

Respective Roles of Preterm Birth and Fetal Growth Restriction in Blood Pressure and Arterial Stiffness in Adolescence

PURPOSE Recent studies show that low birth weight infants are at a risk of increased arterial blood pressure (BP) in adulthood. This study aimed to distinguish the influence of low birth weight either as a result of fetal growth restriction or preterm birth on arterial properties in adolescents. METHODS The effect of low birth weight on BP and arterial stiffness was examined among 90 adolescents aged 14 years who were either born at term with an appropriate birth weight for gestational age (controls, n = 41); born preterm with an appropriate birth weight for gestational age (n = 25); or born at term and small for gestational age (SGA) (n = 24). The pulse wave velocity between the carotid and radial arteries was measured to assess arterial stiffness. RESULTS As compared with control subjects, adolescents born with low birth weight as a result of preterm birth were found to have increased systolic BP and carotid-radial pulse wave velocity (117 ± 11 mm Hg vs. 123 ± 11 mm Hg, p = .04 and 7.0 ± .9 m/s vs. 7.7 ± 1.0 m/s, p = .01, respectively), whereas those who were born at term and SGA exhibited values similar to the controls (114 ± 15 mm Hg and 6.8 ± .9 m/s). CONCLUSION Preterm birth, rather than being SGA at term, increases BP and arterial stiffness in adolescents.

Evaluation of interleukin 13 polymorphisms in systemic sclerosis

Systemic sclerosis (SSc) is a multisystem disease of unknown etiology. It is characterized by excessive cutaneous and visceral fibrosis, damage to small blood vessels, and production of autoantibodies. Interleukin-13 (IL-13) has been shown to be involved in abnormal fibrosis in other diseases. Therefore, we have evaluated its possible involvement in SSc. We analyzed four IL13 gene polymorphisms, rs1800925 (IL13-1055), rs20541 (Arg130Gln), rs847, and rs2243204 in 107 unrelated SSc patients (40 patients having diffuse cutaneous form and 67 patients having limited cutaneous form) and in 170 controls. All subjects were Caucasians. In the total patient population and in the diffuse cutaneous subset, we observed an association between two IL13 polymorphisms, IL13 rs1800925 (IL13-1055), and IL13 rs2243204, and disease (p=0.03–0.04). The IL13 rs2243204T allele was more common in SSc patients (p=0.01, OR=2.3 CI 1.21–4.38) and in the diffuse cutaneous form (p=0.01, OR=2.95, CI 1.35–6.49) than in control subjects. Our result supports the suggestion that polymorphisms in IL13 are associated to SSc and skin fibrosis process. However, further studies on larger and independent population and functional analyses are needed to confirm these findings.

Incidence, Risk Profile and Morphological Pattern of Lower Extremity Venous Thromboembolism After Urological Cancer Surgery

PURPOSE We examined the incidence of asymptomatic and symptomatic lower extremity venous thromboembolism in patients who underwent urological surgery for cancer, and identified preoperative and operative risk factors predictive of the thromboembolism. MATERIALS AND METHODS A cohort of 583 consecutive patients undergoing urological cancer surgery was prospectively assessed using complete lower limb ultrasound at postoperative day 7 from January 2005 to July 2009. In all patients heparin and mechanical thromboprophylaxis were prescribed until complete ambulation. Potential variables predictive of venous thrombosis were analyzed. RESULTS Complete data were available in 538 patients (463 male and 75 female), of whom 177 underwent nephrectomy, 86 radical cystectomy and 275 radical prostatectomy. A total of 40 deep venous thrombosis cases were found (7.4%), most of which were asymptomatic (92%) and limited to deep calf veins (80%). Of those asymptomatic deep venous thrombosis cases 86% were limited to deep calf veins. In all, 12 pulmonary embolisms were diagnosed, of which 4 were lethal. On multivariate analysis history of venous thromboembolism (OR 5.16, p = 0.02) and radical cystectomy (OR 3.47, p = 0.002) were independently associated with venous thromboembolism. CONCLUSIONS Lower extremity venous thromboembolism has a high rate of occurrence after urological surgery for cancer despite the recommended venous thromboembolism prophylaxis. Most cases are asymptomatic and limited to deep calf veins. Our results suggest that complete lower limb ultrasound should be performed early after radical cystectomy and in patients with a personal history of venous thromboembolism.

Association between a CTGF gene polymorphism and systemic sclerosis in a French population.

Objective. Systemic sclerosis (SSc) is a life-threatening autoimmune disease characterized by chronic fibrosis of the skin and internal organs. Connective tissue growth factor (CTGF) is believed to be a primary mediator of chronic fibrosis. We assessed the possible association between 7 single-nucleotide polymorphisms (SNP) in the CTGF gene and scleroderma in a French population (registration number 2006/0182). Methods. We conducted a case-control study with 241 scleroderma patients and 269 controls. Seven SNP were genotyped using the TaqMan system. Univariate and multivariate analyses were performed. In silico electrophoretic mobility shift assay (EMSA), and reverse transcriptase polymerase chain reaction analyses were done to assess the effect of the SNP on CTGF gene expression. Results. The frequency of the rs9399005TT genotype was significantly lower in SSc patients than in controls. This association remained significant after adjustment for gender. An association was detected between the rs9399005 and the diffuse and limited cutaneous forms. Multivariate analysis between SSc patients and controls taking into account all 7 SNP and sex revealed that only sex and the rs9399005 SNP were associated with disease. DNA analysis by EMSA indicated that the T allele bound nuclear factors that were also bound by the C allele. The binding affinity was higher for the T allele. Analysis of the human database and experiments with human hepatocyte cell line indicated the existence of an alternative transcript containing the rs9399005 polymorphism in its 3’UTR region. In silico analysis indicated that this polymorphism may alter the structure of CTGF messenger RNA. Conclusion. These findings suggest that CTGF gene polymorphisms may contribute to susceptibility to scleroderma.

Endothelial function and hemodynamics in systemic sclerosis.

Introduction:  Systemic sclerosis (SSc) is characterized by the development of fibrosis of skin and internal organs that is associated with vascular damage. However, its related parameters have not been fully explored. The aim of this study was to investigate endothelial function in SSc and its relationship with systolic pulmonary artery pressure and systemic arterial compliance (SAC).

Évaluation de l'exposition toxique professionnelle de patients atteints de sclérodermie systémique. Revue de la littérature et résultat d'un auto-questionnaire

Systemic sclerosis (scleroderma) is a rare auto immune disease. Its physiopathology, based on various mechanisms, involves a predisposing genetic background and some exogenous factors. Among them, the role of toxic products is highly suggested according to several case-control studies. The aim of this study is to review the literature concerning occupational exposure associated with scleroderma. This review is completed by the results of a self-reported questionnaire on occupational exposures sent to 82 scleroderma patients followed in Marseille. Scleroderma associated with silica exposure should be declared as occupational disease. Moreover, the role of other toxic agents such as solvents is highly suspected and scleroderma occurring in case of high exposure should also be declared. Our study performed in Marseilles showed a occupational exposure in 10% of cases (five patients having an occupational exposure that could be involved in the genesis of the disease). One had an occupational silica exposure and was declared as occupational silica disease. Other cases had various toxic exposures including solvents and two were declared as disease of occupational nature. Occupational exposure (labour and leisure) must be searched for when faced with a scleroderma patient for two reasons: the possible declaration of an occupational disease and a better knowledge on toxics involved in scleroderma.

99mTc DPD is the preferential bone tracer for diagnosis of cardiac transthyretin amyloidosis.

We emphasize the role of Tc-99m-3,3-diphosphono-1,2-propanodicarboxylicacid (DPD) scintigraphy as a noninvasive tool to distinguish transthyretin (TTR)-related cardiac amyloidosis from other forms of cardiac amyloidosis. We report the case of a 76-year-old male patient suffering from congestive heart failure in whom imaging investigation by DPD scintigraphy showed a strong cardiac uptake highly suggestive of TTR amyloidosis variant. TTR-related cardiac amyloidosis was confirmed on myocardial biopsies by immunohistochemistry analysis. This case supports the growing interest in DPD scintigraphy for typing cardiac amyloidosis and for its contribution in the place of invasive myocardial biopsy.

Low prevalence of anti-RNA polymerase III antibodies in a French scleroderma population: Anti-RNA polymerase III scleroderma

BACKGROUND Anti-RNA polymerase III antibodies (anti-RNAP III) have been reported as potential immune markers of Systemic Sclerosis (SSc). Until now, their clinical use was disregarded because of technical difficulties to perform immunoprecipitation. Recently, ELISA kits became commercially available allowing an easy detection of anti-RNAP III. We intended to clarify the relevance of these antibodies in the diagnosis of SSc by ELISA detection. METHODS The prevalence of anti-RNAP III was analyzed using two ELISA kits in 50 consecutive SSc patients from Marseilles in South of France. Controls included 66 patients with other systemic autoimmune diseases, 34 viral diseases and 50 healthy subjects. Positive results with at least one ELISA kit were controlled by immunoprecipitation which is the reference assay. RESULTS In this study, positivity for anti-centromere and/or anti-topoisomerase I antibodies was observed in 84% of SSc patients. The prevalence of anti-RNAP III in SSc patients was 0% to 6% (3/50) depending on the ELISA kit and only 2% by immunoprecipitation. Concerning controls, two rheumatoid arthritis patients were positive using ELISA (6%), including one with immunoprecipitation confirmation. No anti-RNAP III was detected in systemic lupus erythematosus patients. Three blood donors and one viral disease control were positive using ELISA, but all were negative by immunoprecipitation. CONCLUSIONS Anti-RNAP III was rarely detected in a French population of SSc patients. Their prevalence was even lower than the one observed in rheumatoid arthritis controls. Therefore local immunologic profiles should be established before deciding a change in clinical practice for SSc immune screening.

Bone marrow necrosis and sickle cell crisis associated with double heterozygosity for HbS and HbOARAB

A 39-year-old male from Maghreb, professional wrestler, with no family medical history, had been in perfect health until he developed muscular, back, and joints pain with fever and fatigue. The conjunctiva and the skin exhibited icterus; lumbar spine and knees were painful, and muscles were markedly tender. No other abnormalities were found during the examination. He had a regenerative anaemia (haemoglobin, 79 g/L; reticulocytes, 145 giga/L) with microcytosis (mean corpuscular volume, 72 fL), and mild thrombocytopenia (platelets, 110 3 109/L). The white blood cell count was 30,280/mm with 21,500/ mm3 neutrophils and myelemia. The peripheral blood smear showed anisopoikilocytosis and target cells; schistocytes or sickle cells were absent. Total bilirubin was 56 Image 1. Whole body MRI using ‘‘fluid sensitive’’ STIR sequences (Short Tau Inversion Reconvery) without gadolinium showing diffuse hyperintense involvement of the bone marrow spine (a and c) (even spinous process, c) and pelvic lesions (sacrum, ilium, ischium) with sharp margins and serpentine borders in favor of bone infarcts. There is also vertebral body endplate collapse.