Jean-Claude Wautrecht

Predominance of type 1 CD4+T cells in human abdominal aortic aneurysm

The functional repertoire of T cells in abdominal aortic aneurysm (AAA) and the exact nature of aortic wall adaptive cellular immune responses still remains a matter of debate. In this study, we sought to determine whether type 1 or type 2 responses occur predominantly in human aneurysmal aortic lesions. We first examined the phenotype and cytokine secretion profile of T lymphocytes freshly isolated from aneurysmal aortic wall for comparison with their circulating counterparts using flow cytometry. We found that both populations of infiltrating CD4+ and CD8+T cells displayed a unique activated memory phenotype. In addition, we identified the presence in human aneurysmal aortic lesion of CD4+T cells producing high levels of interferon (IFN)‐γ but not interleukin (IL)‐4, reflecting their type 1 nature. Quantitative analysis of cytokine gene expression confirmed increased IFN‐γ transcript levels in infiltrating cells compared to controls. We next analysed aortic wall responses using LightCycler‐based quantitative real‐time reverse transcription‐polymerase chain reaction. Compared to control non‐diseased aortic samples, we demonstrated that whole AAA tissues exhibited high mRNA levels of IFN‐γ but not IL‐4. Overexpression of the transcription factor T‐bet in the absence of significant GATA‐3 expression further assessed the type 1 polarization of aortic wall immune responses. These findings indicate that type 1 CD4+T cells predominate in human AAA lesions. This study has important implications for the pathogenesis of aneurysm disease. Through the production of IFN‐γ, T cells may indeed contribute to orchestrate extracellular matrix remodelling.

Accuracy and safety of pretest probability assessment of deep vein thrombosis by physicians in training using the explicit Wells clinical model.

1 Esemuede N, Lee T, Pierre-Paul D, Sumpio BE, Gahtan V. The role of thrombospondin-1 in human disease. J Surg Res 2004; 122: 135–42. 2 Lawler J, Sunday M, Thibert V, Duquette M, George EL, Rayburn H, Hynes RO. Thrombospondin-1 is required for normal murine pulmonary homeostasis and its absence causes pneumonia. J Clin Invest 1998; 101: 982–92. 3 Polverini PJ, DiPietro LA, Dixit VM, Hynes RO, Lawler J. Thrombospondin-1 knockout mice showed delayed organization and prolonged neovascularization of skin wounds. FASEB J 1995; 9: A272. 4 Olson BA, Day JR, Laping NJ. Age-related expression of renal thrombospondin 1 mRNA in F344 rats: resemblance to diabetes-induced expression in obese Zucker rats. Pharmacology 1999; 58: 200–8. 5 Ramis JM, Franssen-van Hal NL, Kramer E, Llado I, Bouillaud F, Palou A, Keijer J. Carboxypeptidase E and thrombospondin-1 are differently expressed in subcutaneous and visceral fat of obese subjects. Cell Mol Life Sci 2002; 59: 1960–71. 6 Shang CA, Thompson BJ, Teasdale R, Brown RJ, Waters MJ. Genes induced by growth hormone in a model of adipogenic differentiation. Mol Cell Endocrinol 2002; 189: 213–9. 7 Okuno M, Arimoto E, Nishizuka M, Nishihara T, Imagawa M. Isolation of upand down-regulated genes in PPARgamma-expressing NIH-3T3 cells during differentiation into adipocytes. FEBS Lett 2002; 519: 108–12. 8 Voros G, Maquoi E, Demeulemeester D, Clerx N, Collen D, Lijnen HR.Modulation of angiogenesis during adipose tissue development in murine models of obesity. Endocrinology 2005; 146: 4545–54. 9 Rupnick MA, Panigrahy D, Zhang CY, Dallabrida SM, Lowell BB, Langer R, Folkman MJ. Adipose tissue mass can be regulated through the vasculature. Proc Natl Acad Sci USA 2002; 99: 10730–5. 10 Lijnen HR, Maquoi E, Demeulemeester D, Van Hoef B, Collen D. Modulation of fibrinolytic and gelatinolytic activity during adipose tissue development in a mouse model of nutritionally induced obesity. Thromb Haemost 2002; 88: 345–53. 11 Laitinen L. Griffonia Simplicifolia lectins bind specifically to endothelial cells and some epithelial cells in mouse tissues. Histochem J 1987; 19: 225–34. 12 Demeulemeester D, Collen D, Lijnen HR. Effect of matrix metalloproteinase inhibition on adipose tissue development. Biochem Biophys Res Commun 2005; 329: 105–10. 13 Bornstein P. Diversity of function is inherent in matricellular proteins: an appraisal of thrombospondin 1. J Cell Biol 1995; 130: 503–6.

Occluding aortic endoluminal stent graft combined with extra-anatomic axillofemoral bypass as alternative management of abdominal aortic aneurysms for patients at high risk with complex anatomic features: a preliminary report.

PURPOSE To describe an exclusion endoluminal technique for management of abdominal aortic aneurysms among high-risk patients with complex anatomic features. METHODS From January 1995 to December 1996, among 143 patients with infrarenal abdominal aortic aneurysm treated by means of endograft placement, 9 (6.3%) had complex aortic or aortoiliac morphologic features. For these patients, the endograft was delivered through a femoral cutdown in an occluding aortoiliac configuration. The contralateral iliac artery was occluded with an iliac endograft. Axillofemoral bypass grafting was performed. Computed tomographic scans were obtained regularly. RESULTS There was 1 postoperative death of severe arrhythmia. All aneurysms were found to be affected by thrombosis on immediately postoperative computed tomographic scans, except in 1 patient with a proximal leak, which was managed successfully with angiographic embolization. The mean follow-up time was 12 months. Aortic aneurysm diameter decreased from 2 mm at 6 months (2 patients) to 6 mm at 12 months (6 patients). All axillofemoral bypass grafts are patent. CONCLUSIONS Placement of an occluding endograft associated with axillofemoral bypass grafting is a good alternative for patients at high risk with complex anatomic features. Longer-term follow-up study is needed to evaluate this endoluminal technique.

Cerebral venous thrombosis and procoagulant factors: A case study

Cerebral venous thrombosis is a polymorphic clinical entity for which diagnosis has become more frequent with the advent of neuroradiology. The superior sagittal and trans verse sinuses are frequently involved, whereas cavernous sinus thrombosis is much less frequent. Inherited resistance to the anticoagulant action of activated protein C (APC resistance), antithrombin deficiency, protein C and S deficiencies, and hyperhomocys teinemia seem to represent major causes of thrombophilia when unusual thromboembolic events (ie, before the age of 45 years) are observed. The authors present the combined occurrence of protein C and protein S deficiencies in a 32-year-old woman, manifested by extensive cerebral venous thrombosis.

Evaluation of two D-Dimer assays in the diagnosis of venous thromboembolism.

A qualitative (Instantia) and a quantitative (VIDAS D-Dimer) D-Dimer test have been evaluated and compared with an ELISA method (Asserachrom D-D) in a population of 74 patients suspected of presenting a deep vein thrombosis. Among the thirty-two patients presenting a deep vein thrombosis on phlebography, there were 16 (50%) proximal vein thrombosis and 16 (50%) distal vein thrombosis. Sensitivity and negative predictive value for proximal thrombosis were 100% in all three tests. For distal vein thrombosis, sensitivity and negative predictive value were respectively 81% and 81% for Asserachrom D-DI 75% and 76% for VIDAS D-Dimer and 63% and 82% for Instantia. In conclusion, this study shows that these D-Di assays are a useful tool to exclude proximal vein thrombosis, at least for patients who are not under anticoagulant therapy.

Clinical Significance of Cryofibrinogenemia: Possible Pathophysiological Link with Raynaud's Phenomenon

Objective. To describe the clinical findings and prevalence of patients with cryofibrinogenemia (CF) and to determine whether CF is associated with primary Raynaud’s phenomenon. Methods. Between June 2006 and December 2009, 227 patients were tested for CF in a single university hospital. Forty-five patients with primary Raynaud’s phenomenon were tested for CF. Results. A total of 117 patients with CF without cryoglobulinemia were included. The main clinical manifestations included skin manifestations (50%) and arthralgia (35%). There were 67 patients with primary CF and 50 patients with secondary CF. There was no significant difference in the mean concentration of the cryoprecipitate in primary CF as compared to the secondary form (172 ± 18.6 vs 192 ± 20.9 mg/dl, respectively; p = 0.41). Highest concentrations of cryoprecipitate were observed in those containing fibrinogen only as compared to cryoprecipitates containing fibrinogen and fibronectin (301 ± 43.5 vs 125 ± 10.6 mg/dl; p < 0.001). Patients having skin necrosis (n = 3) had significantly higher values of cryofibrinogen compared to those without necrosis (638 ± 105 vs 160 ± 10.2 mg/dl; p = 0.0046). Among the 45 patients with primary Raynaud’s phenomenon, 36 had associated CF. There was no significant difference in the mean concentration of the cryoprecipitate in these patients compared to those with primary CF. Conclusion. There seems to be a significant correlation between cryofibrinogen concentration and the severity of the clinical signs, particularly when cryoprecipitate is composed of fibrinogen alone. CF might have a possible pathophysiological role in primary Raynaud’s phenomenon.

Reference Intervals for Plasma Homocysteine by the AxSYM Immunoassay after Collection in Fluoride Tubes

Homocysteine (HCy) is an intermediate amino acid formed during the metabolism of methionine to cysteine. In the recent years, it has emerged as a risk factor for cardiovascular disease independent of known other factors (1)(2)(3). The first methods developed for total plasma HCy measurements were HPLC, with or without derivatization, and gas chromatography. Later, immunoassays were developed, allowing automation and widespread use of the marker in the medical world. Plasma HCy is influenced by various factors: genetics, diet, sex, age, ethnic group, drugs, and diseases. EDTA-, citrate-, or heparin-anticoagulated blood may be used, but plasma should be immediately separated from blood cells to avoid spurious increases (4). Addition of different substances has been suggested to reduce these spurious increases in HCy concentrations. Acidic citrate has been shown to be effective in some studies (5) but not in others (6). A specific inhibitor of S -adenosylhomocysteine hydrolase (3-deaza-adenosine) was successfully used, but unfortunately, it is not compatible with immunoassays (7). Fluoride appears to be the most interesting additive. Ubbink et al. (8) showed that it prevents in vitro increases for 2 h. Several studies have confirmed this effect (9), although others have not (10). In most studies, plasma HCy from blood collected in fluoride tubes has been lower than in EDTA tubes (10)(11)(12). Our aim was to evaluate the protective effect of fluoride against spurious increases of in vitro HCy and to establish reference intervals for the AxSYM immunoassay (Abbott) for plasma HCy from blood collected into fluoride tubes. The …

Vertebral arteriovenous fistula following central venous cannulation: a case report.

The authors report a case of vertebral arteriovenous fistula that has been disclosed three years after central venous cannulation (CVC). The real inci dence of this complication is discussed and various clinical presentations are enumerated. From a review of the literature, some recommendations are made to prevent the diagnosis from being missed and chiefly to reduce the risk of arterial puncture that results in fistula formation.

ESVM guidelines – the diagnosis and management of Raynaud’s phenomenon

Regarding the clinical diagnosis of Raynauds phenomenon and its associated conditions, investigations and treatment are substantial, and yet no international consensus has been published regarding the medical management of patients presenting with this condition. Most knowledge on this topic derives from epidemiological surveys and observational studies; few randomized studies are available, almost all relating to drug treatment, and thus these guidelines were developed as an expert consensus document to aid in the diagnosis and management of Raynauds phenomenon. This consensus document starts with a clarification about the definition and terminology of Raynauds phenomenon and covers the differential and aetiological diagnoses as well as the symptomatic treatment.

Focus on echovascular imaging assessment of arterial disease: complement to the ESC guidelines (PARTIM 1) in collaboration with the Working Group on Aorta and Peripheral Vascular Diseases

The main goal of the present document is to provide a set of practical recommendations for ultrasound imagers who are interested in artery diseases or for physicians who intend to undertake vascular procedures. This is the first part of the work. It is dedicated to general principles of ultrasonography, cervicoencephalic, subclavian, aortoiliac and lower extremity arteries, abdominal aorta, and popliteal aneurysms. It also discusses miscellaneous items such as medial arterial calcinosis, arterial embolism, arteritis, arterial stents and bypasses, false aneurysms, aortic dissection, popliteal entrapment syndrome, and iliac endofibrosis.